Wisdom is a multi-component trait that is important for mental health and well-being. In this study, we sought to understand gender differences in relative strengths in wisdom. A total of 659 individuals aged 27–103 years completed surveys including the 3-Dimensional Wisdom Scale (3D-WS) and the San Diego Wisdom Scale (SD-WISE). Analyses assessed gender differences in wisdom and gender’s moderating effect on the relationship between wisdom and associated constructs including depression, loneliness, well-being, optimism, and resilience. Women scored higher on average on the 3D-WS but not on the SD-WISE. Women scored higher on compassion-related domains and on SD-WISE Self-Reflection. Men scored higher on cognitive-related domains and on SD-WISE Emotion Regulation. There was no impact of gender on the relationships between wisdom and associated constructs. Women and men have different relative strengths in wisdom, likely driven by sociocultural and biological factors. Tailoring wisdom interventions to individuals based on their profiles is an important next step. Wisdom is one of six core virtues shared across cultures , and an The burgeoning positive psychiatry subfield focuses on improving outcomes like quality of life and well-being , so wisdIn this article, we examine the association between gender and wisdom. Some reviews and theoretical work have pronounced wisdom should be “androgynous”  and emphThe direction of the differences identified were mixed. In three studies of the nine studies where gender differences were found, women scored higher on overall wisdom . The resExamination of related psychological constructs yields support for gender differences in a subset of wisdom components. A meta-analysis of the 24 character traits making up the six virtues, including wisdom, found differences between women and men in 17 traits, although 13 of these were very small in size . There wGender norms, differential approaches to upbringing and socialization, and other sociocultural factors may support increased development of some areas of wisdom in women compared to men and vice versa. Related work finds that women and men report some variance in terms of how they conceptualize wisdom, where women are somewhat more likely to endorse a “integrative” model while men are somewhat more likely to endorse a “cognitive” model . This vaThus, the existing work in this area argues for a gender-neutral wisdom construct, but the empirical studies show mixed findings regarding the current gender-based differences in wisdom, which may exist for sociocultural and biological reasons. Identifying and characterizing gender differences is important because it will better illuminate the current wisdom construct as it is being commonly measured today, and whether it differs from the gender-neutral goal originally sought. It also allows for the consideration of individualized pathways to wisdom. The existence of wisdom subdomains, alongside previous discussion regarding individual development and pursuit of wisdom e.g., , suggestTherefore, in this study, we examined gender differences in a relatively large community-based sample across the adult lifespan using two validated rating scales . We inclBased on the existing literature, our first hypothesis was that compassion-related domains such as the Affective or Compassionate dimension of the 3-Dimensional Wisdom Scale (3D-WS), and Pro-Social Behaviors and Acceptance of Diverse Perspectives on the San Diego Wisdom Scale would be higher among women. The second hypothesis was that men would score higher on cognitive-related domains like the Cognitive dimension of the 3D-WS and Decisiveness on the San Diego Wisdom Scale. The third hypothesis was that women would score higher on wisdom total scores. Given significant differences between women and men in this same sample in age, income, education, and marital status, these variables were also included in the model. We conducted two sets of exploratory analyses: first, to test whether the magnitude of gender differences in wisdom would vary between more wise and less wise individuals, as posited by This study was approved by the University of California, San Diego Human Research Protections Program (#171635).The participants in this study were recruited from the UCSD Successful Aging Evaluation (SAGE) study, an ongoing project which has been described in previous work . BrieflyTwo measures of wisdom with good to excellent psychometric properties including reliability, convergent validity, and divergent validity were included in this study. The first was the 39-item 3D-WS, which has three subscales capturing the Cognitive, Reflective, and Affective (Compassionate) dimensions of wisdom . The secGender was self-reported with two categorical options: “male” or “female.” This approach allowed for examining differences between people identifying as men and women, the two most frequently reported genders , but hasAdditional measures were included to examine associated constructs: the Center for Epidemiologic Studies Depression Scale (CES-D) , UCLA Lod was calculated for each gender effect. For the first set of exploratory analyses, a median split was calculated for 3D-WS total score, SD-WISE total score, and subscale scores for each measure. Separate linear models were performed to identify how the interaction between gender and the median split dummy coded variable impacted the relationship between gender and each wisdom variable. For the second set of exploratory analyses, separate linear models were performed to identify how the interaction between gender and each wisdom total score and subscale score impacted CES-D (Depression), the UCLA-3 Loneliness, SF-36 Mental Well-being, LOT-R Optimism, and CD-RISC Resilience scores. These analyses were adjusted for family-wise error by using the false discovery rate (FDR) correction.Linear models were performed to examine the relationship between wisdom (the dependent variable) and gender (independent variable). Income, education, age, and marital status were also included as covariates because there were significant differences between women and men in this sample on those demographic areas. One model was calculated for 3D-WS total score, SD-WISE total score, and subscale scores for each measure. Cohen’s Detailed demographic comparison of men and women in the sample is presented in p = 0.008 with a medium effect size (Cohen’s d = 0.481). Men scored significantly higher on the Cognitive Dimension, p = 0.019, with a small effect size (Cohen’s d = 0.184). Women also had higher 3D-WS total score, p = 0.01, with a small effect size (Cohen’s d = 0.292). Please see On the 3D-WS, the mean score among women was significantly higher on the Affective or Compassionate Dimension subscale score relative to men, p < 0.05, d = 0.110–0.331), with the Emotion Regulation effect being the largest. There was no significant difference between women and men in the overall SD-WISE score, indicating that the relative strengths and weaknesses of each group balanced out in the overall score.There were significant differences between women and men in all six subscales of the SD-WISE . There was no significant difference between women and men in the “high wisdom” group for 3D-WS Reflective Dimension, p = 0.17. There were no other differences between “high wisdom” and “low wisdom” in any other categories.Median splits created “high wisdom” and “low wisdom” categories for each wisdom measure and subdomain to identify whether there was variability in size of gender effects by group. For 3D-WS Reflective Dimension, people in the “low wisdom” category had a larger gender difference such that women scored higher in wisdom than men, Exploratory analyses examined how gender may moderate the relationship between wisdom and measures of well-being. Main effects supported the relationship between these variables and wisdom regardless of gender; however, gender did not moderate the relationship between wisdom and any of the measures of well-being including depression, loneliness, mental well-being, optimism, and resilience –5.This study on gender differences in wisdom found evidence that women and men differed on some components of wisdom. However, these differences were not uniform, but rather varied based on subdomains of wisdom as hypothesized. Women scored higher on several subdomains associated with social connection and compassion, including 3D-WS Affective or Compassionate Dimension, and SD-WISE Acceptance of Diverse Perspectives, Pro-Social Behavior and Social Advising subscales. We did not hypothesize differences in the reflection subdomains; women also scored higher on SD-WISE Insight subscale, and women in the lower half of the median split scored higher than men in the 3D-WS Reflective Dimension. On the other hand, men scored higher on SD-WISE and Emotional Regulation and Decisiveness subscales, and the Cognitive Dimension of the 3D-WS. Our third hypothesis was only confirmed by one of the wisdom measures: total wisdom scores were higher among women on the 3D-WS but not on the SD-WISE total score. SD-WISE has 6 components and offers a more detailed examination of wisdom, with relative strengths in each gender being neutralized by relative weaknesses in others. Only one measure, the 3D-WS Reflective, supported theory and evidence that there are larger gender differences among people with less wisdom. We also did not find any evidence that the gender moderated the relationship between wisdom and measures of well-being including depression, loneliness, mental well-being, optimism, and resilience.Although some of these findings were unanticipated, others were well-aligned with past research in this and related areas. Acceptance of Diverse Perspectives and Social Advising both require perspective-taking and interest in the well-being and values of others even when they are misaligned with one’s own. It seems likely that both of these domains are related to compassion, a domain that women reliably score higher . PreviouThere are two potential causes for the gender differences we identified. One is biological. In this regard, it is important not to conflate sex and gender, but rather to discuss the potential impact of biological processes including sex on differences in wisdom. The finding of greater empathy and compassion toward others in women has been reported across time periods and across cultures. Sex-based differences in oxytocin receptor gene polymorphism may lead to increased empathy in women . In a diThese sociocultural processes mentioned are the second, and likely to be the most influential cause for the observed gender difference in wisdom, including social expectations, gender norms and how wisdom-relevant behaviors are differentially reinforced between boys/men and girls/women by parents, teachers, peers, and society at large. Boys and men tend to be socialized toward behaviors including toughness and leadership, which may translate into being more decisive and in control of emotions, whereas girls and women tend to be socialized toward behaviors including warmth and caretaking, which may translate into pro-social behaviors including being compassionate and accepting of diverse people and ideas . Male adIt has been argued that wisdom should be a broadly gender-neutral construct  so that Therefore, it seems to us that variance by subgroup in strengths and weaknesses at the wisdom subdomain level is not a flaw. It may not indicate gender bias as much as it does allowing for a diversity of paths toward wisdom. However, given the alignment between our findings and what has been previously noted to be valued as wise behavior by women and men, we wonder whether these differences might lessen as the divide in societal expectations of women and men fades. We would also note that these effects were small, indicating that although differences existed, women and men still had meaningful overlap as groups in their wisdom scores.Finally, it seems that, at the macro level, the SD-WISE measure does not show evidence of an overall gender difference, unlike 3D-WS. The subcomponents included in a measure of wisdom will of course impact gender and other group differences. These two measures of wisdom measures were developed conceptually and tested psychometrically, using theoretical and empirical findings on layperson and expert definitions of wisdom without focusing on gender balance c.f., ,c. Variacis women and men. We did not collect any biomarkers relevant to gender or sex, so assessment of the potential impact of hormones or other factors was not possible. The study sample was predominantly white and came from an urban county in the United States; thus, the findings may not apply to other race/ethnic groups and different cultural regions, and study of other groups is important. We should point out, however, that in a recent study using SD-WISE and ULS scale for loneliness, we found that the constructs of wisdom and loneliness seemed to be largely similar in a San Diego sample of middle-aged and older adults and an age-comparable sample from rural Italy (The cross-sectional design prevents assessment of differences in how wisdom develops and evolves over the lifespan. Future longitudinal work will be able to fully describe this development by gender, and the influence of other important factors including those associated with mental health and wellbeing. Longitudinal work may also be able to examine some of the hypotheses we and others have considered in regards to why and how gender differences occur. Participants self-identified their genders, and only binary options were offered so there were no options for people who are non-binary or other genders. Understanding wisdom profiles of non-binary people in future studies would be particularly enlightening in understanding how wisdom develops among people who may be less bound to traditional gender norms. We did not collect data to identify how many participants were transgender, which would aid in understanding whether transgender women and men have unique wisdom profiles relative to al Italy .On average, both women and men have strengths in wisdom subdomains that can be capitalized upon to promote their well-being. Helping people identify and lean on these strengths may promote related aspects of well-being including social connection and happiness. We also find that both groups have relative weaknesses that may benefit from individual and societal intervention to improve well-being and promote healthy living, including the growing set of positive psychiatry interventions. Consistent with past literature, we find a difference in compassion between women and men. There are a number of compassion interventions including compassion-focused therapy . We alsoThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the University of California, San Diego Human Research Protections Program. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.ET, BP, EL, and DJ conceptualized the study. ET completed the initial analyses with conceptual support from DJ and conceptual and pragmatic support from T-CW, MT, and XT, wrote the first draft of the manuscript, and made the first draft of the tables and figures. RD provided database management and analytic support. All authors contributed to revisions of the manuscript, tables, and figures.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The health workforce is a vital aspect of health systems, both essential in improving patient and population health outcomes and in addressing contemporary challenges such as universal health coverage (UHC) and sustainable development goals (SDGs). There is an increasing body of research that indicates that if the health workforce were to be redesigned from the ground up—based on population needs—we would see a very different configuration of the health workforce. This makes us wonder how one could design or develop innovative health workforce solution(s) for the future in order to make the health workforce more responsive to population needs.The 21st century presents several challenges to the health workforce and the health professions that require thoughtful consideration and analysis. Health inequalities continue to exist both within and across countries, especially affecting vulnerable and disadvantaged groups. Disease patterns are changing, with a rise in chronic conditions and non-communicable diseases, the COVID-19 pandemic notwithstanding. Increased life expectancies also present us with the challenge of meeting care provisions for an ageing population. Workforce shortages, geographic maldistribution, and international migration are omnipresent.Health workforce solutions have been diverse and generally dependent on condition, context, or country-specific scenarios. New health occupations, as well as reforming the scopes of practice of existing occupations, have been widely debated as solutions. Of importance has been how different health personnel groups can work collaboratively as a team, and at different levels of care—primary, secondary, and tertiary. Models of care specific to population groups  as well as health conditions , and health strategies  are emerging, with varied success.In this special issue of the International Journal of Environmental Research and Public Health, we have brought together research that debates and provides innovative health workforce solutions directed towards meeting population needs, mainly through integrated solutions or models of care. We have also included papers that cover challenges at an education or regulatory level. This special issue, entitled “The Future Health Workforce: Integrated Solutions and Models of Care”, features a compelling range of research that spreads across the health professions, including medicine, nursing, dentistry, and allied health. This edition embraces quantitative as well as qualitative research approaches, as well as methodological pluralism and a rapid review. A hallmark of each article is methodological rigor, and we are particularly pleased to have included research conducted with health workforce groups dealing with different conditions in a range of contexts and countries including the USA, the UK, Canada, Australia, Sweden, South Korea, Japan, China, and Brazil. This special issue features 13 papers.The first research paper, from a multidisciplinary team of researchers based in the Rural Clinical School in the Faculty of Medicine at the University of Queensland in Australia, provides a theory that assists us to understand factors that affect doctors in choosing a generalist or specialist medical career . Belindan = 295) in three categories of hospitals. The survey revealed that the informal and formal education received by medical leaders in these Chinese hospitals has not been effective in developing the required medical and leadership management competencies. This provides a basis for recommendations regarding health system and higher education strategies to improve the management competencies of clinical leaders in China. The second article reports research conducted with the health services management workforce in China . The staWe then turn to a thematic analysis of Twitter data and newspapers extracted through a search for new forms of team work in the health and social care of older people in response to the COVID-19 pandemic . The stuCatherine Cosgrave’s study addresses chronic workforce shortages and unmet health care needs in rural and remote communities in Australia . The finThe next paper in this special issue reports a national cross-sectional study of faculties supporting general medical practitioners (GPs) . Matthewn = 965) showed a sustainable return on investment, covering workers with heart disease and diabetes. The study concludes that this model of workers’ healthcare assistants is capable of enhancing workers’ health in companies, while reducing costs for employers and improving workers’ quality of life within the organisation.The following paper takes us to research conducted on an innovative model of workers’ healthcare assistants by a group of Portuguese researchers in Brazil . This stLuis Miguel Dos Santos has investigated reasons behind the shortage of public health, social work, and psychological counselling professionals who can provide multilingual services to minority groups and foreign residents in South Korea . This faThe next paper in this special issue investigated the future of careers for public-health professionals with training in climate change based on analysis of 16 years’ worth of job postings and a survey with prospective employers . HeatherInnovative health workforce solutions were needed for the Swedish mental health workforce due to the recent refugee crisis. Sandra Gupta and colleagues from Uppsala University Sweden explored the experiences of mental health workers towards new training solutions to effectively manage unaccompanied refugee minors . They suThe next paper from Sierras-Davo and colleagues based in Spain and Greece discusses how you can transform the future healthcare workforce across Europe through improvement science . They evYuki Ohara and colleagues based in Japan discuss an interesting paper on job attractiveness and job satisfaction of dental hygienists based on the 2019 Japanese dental hygienists survey . Using aA very interesting commentary is featured as the penultimate article, titled Broken Promises to the People of Newark. Franklin et al  discuss We round out this special issue with a rapid review of contemporary techniques and practices in oral health workforce modelling, conducted by a team of researchers from England and Australia . Workfor


These factors induce angiogenesis and recruit various cells into the tumor niche, including neutrophils and monocytes which, in the tumor, are transformed into tumor-associated neutrophils (TAN) and tumor-associated macrophages (TAM) that participate in tumorigenesis.Chronic  hypoxia and cycling  hypoxia are two types of hypoxia occurring in malignant tumors. They are both associated with the activation of hypoxia-inducible factor-1 (HIF-1) and nuclear factor κB (NF-κB), which induce changes in gene expression. This paper discusses in detail the mechanisms of activation of these two transcription factors in chronic and cycling hypoxia and the crosstalk between both signaling pathways. In particular, it focuses on the importance of reactive oxygen species (ROS), reactive nitrogen species (RNS) together with nitric oxide synthase, acetylation of HIF-1, and the action of MAPK cascades. The paper also discusses the importance of hypoxia in the formation of chronic low-grade inflammation in cancerous tumors. Finally, we discuss the effects of cycling hypoxia on the tumor microenvironment, in particular on the expression of VEGF-A, CCL2/MCP-1, CXCL1/GRO-α, CXCL8/IL-8, and COX-2 together with PGE The growing knowledge of tumors indicates the significance of the tumor microenvironment, a collection of factors that act on cancer cells in the tumor. These factors include tumor-associated cells ,2 along An important aspect of hypoxia in the tumor microenvironment is chronic low-grade inflammation. The role of inflammation supports the fight of the immune system against pathogens and is an element strengthening the anti-tumor response . HoweverThis review expands on the mechanisms of the activation of hypoxia-inducible factors (HIFs) and nuclear factor κB (NF-κB) presented in our previous reviews on the effects of hypoxia on the CC  and CXC The intense division of cancer cells results in the proliferation of tumor tissue. This process does not go hand in hand with angiogenesis, i.e., the formation of new blood vessels. In this way, due to the low availability of blood vessels, the tumor has areas with chronically reduced oxygen concentration. This microenvironment is called chronic  hypoxia.The most important and best-known proteins activated in hypoxia are three hypoxia-inducible factors . The first two, HIF-1 and HIF-2, are responsible for the transcription of genes induced by hypoxia, while HIF-3, in addition to inducing gene expression, also decreases the activity of HIF-1 and HIF-2 ,13,14.All three HIFs are composed of two subunits, alpha and beta. The HIF-β subunits, also known as aryl hydrocarbon nuclear translocators (ARNT), are not regulated by any changes in oxygen, although a study on high-risk multiple myeloma cells shows that chronic hypoxia increases HIF-1β expression via NF-κB . The higIn contrast to HIF-β subunits, the expression levels of HIF-1α, HIF-2α, and HIF-3α subunits are tightly regulated by changes in oxygen concentration through proteolytic degradation and transcriptional regulation. In addition, HIF-3α expression is upregulated by HIF-1 and HIF-2 . This reIn normoxia, HIF-α undergoes hydroxylation on the proline residue in the N-terminal oxygen-dependent degradation domain (NODD) and C-terminal oxygen-dependent degradation domain (CODD) by three isoforms of prolyl hydroxylase (PHD) ,21—oxyge402 HIF-1α, Pro564 HIF-1α, Pro405 HIF-2α, and Pro531 HIF-2α . N. N122]. tination . This letination . The MAPinocytes ,107. In inocytes  and lunginocytes , the p38inocytes . This painocytes . Additioinocytes . Akt/PKBinocytes . Akt/PKB634 IKKβ . This in634 IKKβ , althougAfter activation, NF-κB forms a complex with its coactivators. These complexes include PHD2  and PHD3HIF-1 and HIF-2 also increase the expression of p65/RelA NF-κB in macrophages . HIF-1 cHypoxia is associated with a decrease in PHD1 activity, which leads to a decrease in the hydroxylation of IKKβ ,118 and Thanks to the aforementioned mechanisms, there is no simultaneous response of the cell to hypoxia and to pro-inflammatory factors. Nevertheless, NF-κB is activated in chronic hypoxia, leading to an increase in the expression of some inflammatory genes .The signaling pathways activated during chronic hypoxia are very well understood. Hydroxylation of HIF-α is reduced, which results in an accumulation of these subunits in the cell. Phosphorylation by MAPK kinase, change in acetylation, or influence of ROS are also responsible for the increase in HIF-α stability during chronic hypoxia. There is also an activation of NF-κB, which increases the expression of HIF-1α. Ultimately, chronic hypoxia occurs in 23 to 54% of the tumor area, depending on the tumor model and the adoption of threshold oxygen levels from which hypoxia is defined ,145. In In the initial stages of tumor growth, the intense proliferation of tumor cells is not matched by the development of blood vessels that supply cells inside the tumor with nutrients and oxygen. Therefore, chronic  hypoxia occurs inside the tumor . This caL) expression in cancer cells . T. T185].  subunit . The mec subunit . The incIn cycling hypoxia, ROS activates nuclear factor erythroid 2-related factor (Nrf2) , which rCycling hypoxia also causes changes in HIF-1α acetylation. Cycling hypoxia results in decreased expression of HDAC3 and HDAC5 proteins, but not the other HDACs , as demo63 TAK1 and activation of the entire NF-κB activation pathway.In cycling hypoxia, ROS activates NF-κB ,175,191.Chronic hypoxia is accompanied by an activation of NF-κB, which increases the expression of HIF-1α and some pro-inflammatory genes . HoweverBoth types of hypoxia also increase vascular endothelial growth factor (VEGF)-A expression. This effect depends on the cancer cell line. VEGF-A expression in the tumor cell is increased much more under chronic hypoxic conditions than in cycling hypoxia. This has been shown in melanoma WM793B cells and prostate cancer PC-3 cells , as well2 (PGE2)—the product of COX-2 activity. The main mechanism of the proangiogenic properties of CCL2/MCP-1 is the recruitment of monocytes into the tumor niche, which are transformed into TAM [2 [VEGF-A is one of the best described pro-angiogenic factors in a tumor  204,205205. Howeinto TAM ,207, whio TAM [2 . CCL2/MCo TAM [2 . CXCL1/Go TAM [2 ,211, reso TAM [2 ,213,214.o TAM [2 ,217,218—o TAM [2 ,220; MMPo TAM [2 .2 is also a pro-angiogenic factor, although not directly. It participates in angiogenesis and lymphangiogenesis by increasing the expression of various angiogenic and lymphangiogenic factors such as VEGF-A, VEGF-C, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), endothelin-1 [PGEthelin-1 ,225,226 thelin-1 .2, through its action on anti-tumor cells, is one of the mechanisms of cancer immunoevasion. It inhibits the anticancer function of NK cells and dendritic cells and enhances the pro-cancer function of M2 macrophages and regulatory T cells (Treg) [The aforementioned pro-inflammatory factors induced by cycling hypoxia also act on tumor-associated cells. For example, they recruit various cells into the tumor niche. CCL2/MCP-1 is a TAM recruiting factor ,228,229,s (Treg) ,233,234.Cycling hypoxia is a feature of all solid tumors ,154,155.2 production [Cycling hypoxia is associated with elevated COX-2 expression and consequently an increase in PGEoduction ,169,197.oduction , especiaoduction , colorecoduction , oesophaoduction , and prooduction . Neverthoduction ,239,240.Additionally, cycling hypoxia increases CCL2/MCP-1 production in the tumor ,198,199.In addition to CCL2/MCP-1, cycling hypoxia increases in the expression of CXCL1/GRO-α  and CXCL2 production. As already mentioned, PGE2 has no direct angiogenic effect, but it increases the expression of pro-angiogenic factors [2 production results in decreased expression of other pro-angiogenic factors. Another possibility is to combine bevacizumab with a CXCR1/CXCR2 dual inhibitor [Another option is to improve the anti-cancer anti-angiogenic therapy, e.g., by using bevacizumab—an anti-VEGF-A monoclonal antibody . However factors ,225,226.nhibitor . It is anhibitor . NF-κB anhibitor ,192,196.The vast majority of published in vitro experiments on hypoxia in cancer relate to chronic hypoxia. Most of the available work has not investigated the effect of cyclic changes in oxygen concentration on tumor cells. For this reason, this type of research model does not reflect the actual state of the cancerous tumor, with cycling hypoxia affecting a considerable part of the tumor. In this way, the results of studies showing the effect of chronic hypoxia only reflect the situation in one area in a tumor. For this reason, it is advisable that each study on hypoxia in a tumor should use an in vitro model that includes cycling hypoxia.


Medulloblastoma (MB) is an aggressive malignant tumor of the posterior fossa of the CNS that mainly affects children younger than 15 years of age. It is uncommon in the adult population compared to children. Any adult patient presenting with cerebellar mass must be evaluated with brain tissue biopsy to rule out MB. Our patient is a 27-year-old female who presented with sudden onset of frontal headache and was diagnosed with MB. Medulloblastoma (MB) is an aggressive neoplasm of embryonal origin. It is most commonly located in the vermis of the cerebellum and commonly affects children . It accoA 27-year-old female with a past medical history of migraine headache presented to the ED with a complaint of sudden onset frontal headache, different from her usual migraine headache. Headache was frontal, worse in the night and morning, not relieved with over-the-counter acetaminophen. The physical exam was normal, and vitals were stable. CT scan of the head without intravenous contrast showed a large right cerebellar mass measuring 1.4 x 2.2 x 1.5 cm with a midline shift in the posterior fossa  analysis cytology was negative for malignant cells. According to National Comprehensive Cancer Network (NCCN) guidelines, treatment protocol included maximal safe resection, followed by adjuvant therapy involving chemotherapy and radiation. The plan was to start the patient on adjuvant craniospinal radiotherapy with concurrent vincristine for a period of eight weeks, followed by maintenance multiagent chemotherapy including cisplatin, lomustine, and vincristine for eight cycles.MB is most commonly located in the vermis of the cerebellum in children but can involve the lateral hemispheres of the cerebellum in adults. It occurs more frequently in men than women . MetastaPatients with MB classically present with clinical signs and symptoms of increased intracranial pressure like night and early morning headache, nausea, vomiting, confusion, and blurring of vision. Tumors located in the midline can manifest as gait ataxia or truncal instability, whereas those located in the lateral cerebellar hemisphere cause limb clumsiness or incoordination . It can Apart from physical exams, CT and MRI of the brain are needed to support the diagnosis. MRI shows iso- or hypointense on T1-weighted images and hyper to hypointense on T2-weighted images . HydroceMB is classified into several variants by the WHO classification of brain tumors which divides the tumor based upon histopathologic criteria. Different variants of MB are classic, desmoplastic/nodular, desmoplastic with extensive nodularity, large cell, or anaplastic. Among these variants, classic MB is the most common variant among both children and adults (70-80%) and extensive nodularity is the least common one (3%) . HistoloAs MB in adults is rare, there is no clear guideline for treatment in adults. Treatment is based on guidelines in children itself . The aimIn a high-risk patient, with positive CSF cytology, combination treatment with standard-dose craniospinal radiotherapy with posterior fossa boost followed by multiagent maintenance chemotherapy is considered effective . Those pWith the evolving treatment modalities of MB, the prognosis is variable in both adults and children. In patients who received postoperative cranioradiation therapy, the prognosis was favorable for adults compared to children. Adult patients who have group 4 tumors are found to have poor prognoses compared to children. A desmoplastic variant has a better prognosis compared to the classic variant. Those patients who have positive CSF cytology are found to have an increased rate of relapse and poor outcomes. Any patient with spinal seeding at presentation also has a poor prognosis .MB is the most common brain tumor in children but is rare in adults. Every patient with posterior fossa mass must undergo a biopsy of the mass with histopathological and immunohistochemical examination to confirm the diagnosis, as radiographic imaging alone could be inadequate.


Oryza species are the natural reservoir of favorable alleles that are useful for rice breeding. To systematically evaluate and utilize potentially valuable traits of new QTLs or genes for the Asian cultivated rice improvement from all AA genome Oryza species, 6,372 agronomic trait introgression lines (ILs) from BC2 to BC6 were screened and raised based on the variations in agronomic traits by crossing 170 accessions of 7 AA genome species and 160 upland rice accessions of O. sativa as the donor parents, with three elite cultivars of O. sativa, Dianjingyou 1 (a japonica variety), Yundao 1 (a japonica variety), and RD23 (an indica variety) as the recurrent parents, respectively. The agronomic traits, such as spreading panicle, erect panicle, dense panicle, lax panicle, awn, prostrate growth, plant height, pericarp color, kernel color, glabrous hull, grain size, 1,000-grain weight, drought resistance and aerobic adaption, and blast resistance, were derived from more than one species. Further, 1,401 agronomic trait ILs in the Dianjingyou 1 background were genotyped using 168 SSR markers distributed on the whole genome. A total of twenty-two novel allelic variations were identified to be highly related to the traits of grain length (GL) and grain width (GW), respectively. In addition, allelic variations for the same locus were detected from the different donor species, which suggest that these QTLs or genes were conserved and the different haplotypes of a QTL (gene) were valuable resources for broadening the genetic basis in Asian cultivated rice. Thus, this agronomic trait introgression library from multiple species and accessions provided a powerful resource for future rice improvement and genetic dissection of agronomic traits.Rice improvement depends on the availability of genetic variation, and AA genome  Rice is one of the most important staple crops for almost half of the world’s population. The Food and Agriculture Organization of the United Nations predicts that rice yield will have to be increased 50 to 70% by 2050 to meet human’s demands, which increases that rice yield is still central for maintaining global food security . WhereasOryza contains twenty-two wild species and two cultivated rice species that represent 11 genomes: AA, BB, CC, BBCC, CCDD, EE, FF, GG, HHJJ, HHKK, and KKLL  and two cultivated species (O. sativa and O. glaberrima) were classified into the AA genome. Asian cultivated rice (O. sativa L.) was domesticated from wild species O. rufipogon thousands of years ago  is represented by the different segments in the genetic background of elite varieties. Genetic background noise of ILs can be eliminated significantly, which can be evaluated for any traits’ improvement over the recurrent parents for rice breeding, also for QTL mapping and gene discovering as a single Mendelian factor; in addition, potential favorable genes hidden in the background of related species could be expressed in the genetic background of cultivated rice . Thus, Ia sativa , some liAA genome species distributed in the natural and wild environment, which contains amount of useful allelic genes for improving rice yield and resistance to biotic and abiotic stresses . DiffereO. longistaminata, O. barthii, O. glumaepatula, O. meridinalis, O. nivara, O. rufipogon, O. glaberrima, and upland rice of O. sativa) into three elite, highly productive O. sativa varieties . A total of six thousand three hundred and seventy-two agronomic ILs in three different backgrounds were screened and developed based on the repeated evaluation and selection of agronomic traits. One thousand four hundred and one of 6,372 agronomic ILs in the Dianjingyou 1 background were used to analyze genotype and discover novel alleles for grain size. Thus, this agronomic introgression library provided a powerful resource for future rice improvement and genetic dissection of agronomic traits.In this study, to explore and utilize wild relatives in rice improvement, we systematically introduced foreign segments from eight different AA genome species , Yundao 1 (a japonica variety), and RD23 (an indica variety), were used as the recurrent parents.The plant materials included 1 accession of . sativa . Three eO. longistaminata were crossed with Dianjingyou 1 as the recurrent parent. A total of two hundred and twenty-six accessions as the donor parents, except for O. longistaminata and O. glaberrima, were used to cross with the recurrent parent Yundao 1. All the F1 plants were used as female parents to backcross to their respective recurrent parents to produce BC1F1 generation. More than 200 BC1F1 seeds were generated for each of the combinations. The moderate heading date of individuals was selected to backcross with the recurrent parents, and about 200 BC2F1 seeds were obtained. From each of the BC2F1 progeny, individuals that showed a significant agronomic difference from the recurrent parents were selected for further backcrossing or selfing. After 2–6 times backcrossing and 2–7 times selfing, the progeny with stable and different target traits from their recurrent parents was developed as agronomic ILs.A total of three hundred and twenty-nine accessions of AA genome species as the donor parents except for 1 plants were obtained by embryo rescue technique from the cross between 1 accession of O. longistaminata as the donor parent and an indica variety RD23 as the recurrent parent, and crossing and selfing from BC1F1 generation were performed as above mentioned procedure.The FAll materials were grown at the Sanya Breeding Station, Sanya , Hainan province, China. Ten individuals per row were planted at a spacing of 20 cm × 25 cm. All materials were grown and managed according to the local protocol.A randomized complete block design was carried out with three replications for agronomic trait evaluation under two different environments , respectively. Each line was planted in three rows with 10 individuals per row. The five plants in the middle of each row were used for scoring traits. The recurrent parents, Dianjingyou 1, Yundao 1, and RD23, were used as controls in the experiment, respectively.Prostrate growth habit was observed for the tiller angle in three main stages, which includes booting stage, heading stage, and grain filling stage. That tiller angle in ILs was larger than that in recurrent parent, which was regarded as the prostrate growth.Primary branches at the base of panicle of the lines extend outward were regarded as the spreading panicle. Erect panicle or drooping panicle was evaluated according to the angle between the lines that connecting panicle pedestal with panicle tip and the elongation line of stem; spikelet numbers were measured as the total number of spikelets of the whole plant divided by its total number of panicles. Dense panicle was scored by the ratio of spikelet numbers to panicle length.Tiller number was recorded from five random plants; plant height was measured from the ground level to the tip of the tallest panicle.To measure the grain size, grains were selected from primary panicle and stored at room temperature for at least 3 months before testing. Twenty grains were used to measure grain length (GL), grain width (GW), and the ratio of grain length to grain width (RLW) from each plant. Photographs of grains per individual were taken using stereomicroscope, and then, grain size was measured by software Image J. The average value of 20 grains was used as phenotypic data. The weight of one thousand grains was measured by weighting fertile, fully mature grains from five panicles.Aerobic adaptation was evaluated by biomass, yield, harvest index, heading date, and plant height in both aerobic and irrigated environments. Drought tolerance was assessed by the same traits as the aerobic adaptation in both upland and irrigated environments. For the aerobic and upland treatments, we used direct sowing with 4 seeds per hole and retained one seedling at the three-leaf stage. There is some difference in water management, and the rainfall provided the essential water for plant growth without the extra irrigation under aerobic treatment, whereas mobile sprinkler irrigation facilities were used to maintain a humid soil environment at the sow, tiller, and heading stage under upland treatment. For the irrigating treatment, sowing and transplanting single seedlings were done, and the field was managed according to the local standard practices.Magnaporthe oryzae for 3 weeks after sowing by spraying with conidial suspension. After 7 days, lesion types on rice leaves were observed and scored according to a standard reference scale based on a dominant lesion type . When the japonica varieties Dianjingyou 1 and Yundao 1 used as the recurrent parents were crossed with the accession of O. longistaminata, the crossing was failed despite many efforts. Only the cross using an indica variety RD23 as the recurrent parent and O. longistaminata as the donor was obtained by embryo rescue. Fortunately, the female gametes from the interspecific hybrids were partially fertile, and some hybridization seeds in the different combinations could be harvested by backcrossing F1 as the female parent with O. sativa as the male parent. Finally, agronomic IL library that contains 6,372 lines was developed based on the agronomic trait selection, and agronomic ILs showed a significant difference from the recurrent parents, which include spreading panicle, erect panicle, dense panicle, lax panicle, awn, prostrate growth, plant height, pericarp color, kernel color, glabrous hull, grain size, 1,000-grain weight, drought resistance and aerobic adaption, and blast resistance  in the two subspecies  Pid3 locus was analyzed based on the 3K RGP sequencing data, and different strategies were developed to apply the functional Pid3 alleles to indica and japonica rice breeding  an abundant genetic variations were introgressed into the cultivated rice genome; (2) target genes or QTLs for the same phenotype could be validated by the different donors, and it will provide the information that these target genes or QTLs could be the same haplotype; (3) the genes or QTLs responsible for the opposite phenotypes, for example, long-grain size and short-grain size, could also be confirmed using the different populations from multiple donors, and it could be the different haplotypes. Therefore, this agronomic IL library will help us to improve rice breeding and interesting gene discovery and utilization.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/YZ and DT draft the manuscript. DT designed the research. JZ, PX, WD, and XD developed the introgression lines. YZ, YYa, YYu, JL, and QP participated the genotype and phenotype evaluation. YZ performed the data analysis. All authors reviewed and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


CHRIS supported the Victorian ICU response during the COVID‐19 pandemicThe coronavirus disease 2019 (COVID‐19) pandemic put an unprecedented strain on intensive care resources throughout the world. Initially in Wuhan (China)In late March 2020, rising numbers of COVID‐19‐related admissions to ICUs were observed throughout Australia.A nationwide dashboard of ICU activity, the Critical Health Resources Information System (CHRIS), was rapidly developed as a collaboration between Telstra Purple, Ambulance Victoria, ANZICS and the Australian Government Department of Health. All adult and paediatric ICUs (public and private) in Australia were instructed to enter data twice daily. This manual data entry typically took 5 minutes. Each ICU was immediately able to see patient numbers and resources available within every ICU in their region and also see an aggregate summary of all ICUs in Australia. CHRIS was available to all state and territory health departments, to all patient transport and retrieval agencies, and also to ICUs in New Zealand. The system went live on 1 May 2020, after 26 days of development. Three weeks later, 184 out of 188 eligible ICUs (98%) in Australia were contributing data.After a decline in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections throughout Australia, notifications rose again in Melbourne at the end of June 2020.From the beginning of July to the end of September 2020, there were 237 ICU admissions with COVID‐19 pneumonitis, of which 210 (88%) occurred in July and August. Admissions were predominantly to public hospitals in north‐western Melbourne.Spare ventilators were available at all sites on all days. On six occasions in August, there were more than 140 ventilated patients (with or without COVID‐19) in Victoria. On each of these days, there were more than 500 spare ICU ventilators available .Box 1ACT = Australian Capital Territory; COVID‐19 = coronavirus disease 2019; ECMO = extracorporeal membrane oxygenation; HDU = high dependency unit; ICU = intensive care unit; NSW = New South Wales; NT = Northern Territory; NZ = New Zealand; QLD = Queensland; SA = South Australia; TAS = Tasmania; VIC = Victoria; WA = Western Australia.Box 2LOWESS = locally weighted scatterplot smoothing.CHRIS provided real‐time data on ICU activity and capacity. In addition to facilitating the transfer of critically ill patients, CHRIS also enabled early diversion of ambulance presentations to emergency departments at hospitals where ICUs had capacity. These approaches were integral to ensuring standards of care were maintained by clinicians, retrieval agencies and the Victorian health department. At the same time, there was visibility to the Australian Government Department of Health, which would, if required, coordinate a national response to overwhelmed ICU services.Although several individual ICUs came under strain, retrieval and critical care systems in metropolitan Melbourne were not overwhelmed. Strategies to redistribute critical care demand are likely to have contributed to high survival rates for ventilated patients with COVID‐19 in Victoria.The local application of a national tool (CHRIS) for real‐time display of ICU activity and resources was a key component of the response to the COVID‐19 pandemic in Victoria. CHRIS has the potential to augment existing ICU monitoring systems. The tool may also assist in the response to local and national public health emergencies, such as mass casualty events, bushfiresNo relevant disclosures.Not commissioned; externally peer reviewed.Video S1Click here for additional data file.


The continuous growth in energy demand requires researchers to find new solutions to enlarge and diversify the possible ways of exploiting renewable energy sources. Our idea is the development of a solar concentrator based on trapping the luminous radiation with a smart window. This system is able to direct light towards the photovoltaic cells placed on window borders and produce electricity, without any movable part and without changing its transparency. Herein, we report a detailed study of cellulose ethers, a class of materials of natural origin capable of changing their state, from transparent aqueous solution to scattering hydrogel, in response to a temperature change. Cellulose thermotropism can be used to produce a scattering spot in a window filled with the thermotropic fluid to create a new kind of self-tracking solar concentrator. We demonstrate that the properties of the thermotropic fluid can be finely tuned by selecting the cellulose functionalization, the co-dissolved salt, and by regulating their dosage. Lastly, the results of our investigation are tested in a proof-of-concept demonstration of solar concentration achieved by thermotropism-based light trapping. Thermotropic polymers are a class of materials able to switch their state, from clear to strongly scattering, in response to a temperature change. Thanks to the reversibility of this transparent/opaque transition, they are attractive for photonic applications, particularly in smart windows, where they can play a critical role in enhancing the energy efficiency and the comfort level of indoor spaces .The physical mechanism under thermotropism relies on a phase transition, occurring at the critical temperature, from polymer homogeneously dissolved in the solvent to the appearance of partially undissolved/aggregated polymer chains. Below the phase transition temperature, that in case of polymer gels or blends is often called “lower critical solution temperature” (LCST), the refractive indices of the polymer and the solvent are almost identical, so that the system exhibits a transparent state. When the temperature rises above the LCST, the refractive index of the aggregated polymer phase increases, generating an index mismatch with respect to the matrix, which causes light scattering .In addition to reflecting back part of the light passing through the material and therefore acting similarly to an automatic temperature-driven light protection, the scattering state of a thermotropic polymer opportunely confined in a transparent window can be exploited to trap light into waveguide modes. In fact, as light is backscattered by the thermotropic polymer in every direction, part of it will hit the outer surfaces of the cell windows with angles satisfying the conditions for total internal reflection. Consequently, light will be trapped inside the window.In our idea, sunlight passing through a smart window is conveyed by waveguide to the window edges, where small photovoltaic cells are positioned. The final goal is to feed the solar cells with more radiation than what they would normally capture, hence boosting electricity conversion.Several efforts have been made to maximize the efficiency of both organic and inorganic solar cells ,4, and tIn our system, depicted in Chemically, thermoresponsive polymers have both hydrophilic and hydrophobic subunits. The hydrophilic subunits can form hydrogen bonds with water and keep the polymer chains in a random coil-shaped, hydrated state. Thus, the polymer is dissolved in water leading to a single, homogenous, transparent phase. When the temperature increases beyond LCST, the conformation is changed from coil to globule form. The hydrophilic subunits become inaccessible to water molecules, causing the dehydration of polymer chains and, consequently, the formation of a biphasic, nonhomogeneous, scattering system. Given the requirement of hydrophilic and hydrophobic domains on their chain, LCST-type thermotropic polymers can belong to different chemical classes: ethers, alcohols, amides and polypeptides .Among thermotropic materials, one of the most widely studied is poly(N-isopropylacrylamide), which forms thick hydrogels with LCST around 30–32 °C in its homopolymer form ,13,14, aFor our application, the scattering medium should be chemically simple and economically affordable, with transition temperature within the range of 45–60 °C, high enough to be not reachable in standard sun conditions, and easily reachable by little sun concentration. For these reasons, a more suitable class of material to be considered for the scattering medium is represented by cellulose ethers.Cellulose is a natural polymer characterized by a high hydrophilicity on its chain structure. Because cellulose forms strong intermolecular hydrogen bonds, however, it is insoluble in water. When a certain fraction of hydroxyl groups is substituted by hydrophobic groups such as methoxide groups, intermolecular hydrogen bonds are weakened, resulting in water solubility . The resCellulose ethers, like native cellulose, are not digestible, not toxic, not allergenic, and they are extensively used as a thickener and emulsifier in various food and cosmetic products, in laxative drugs and in the manufacturing of drug capsules . More reTheir easy availability, directly connected to the extensive industrial usage, their LCST generally around 40 °C and above, and the possibility of different chemical substitution leading to tunable optical properties, make cellulose ethers the perfect candidate materials for our scattering-based solar concentrator, with respect to other synthetic and natural polymers with thermotropic properties. Furthermore, this material perfectly meets the requirements of sustainability such as low cost, easy availability, abundance, non-toxicity and does not present disposal problems, creating a virtuous combination of energy and sustainability. Even though the concept of a self-tracking solar concentrator based on a scattering medium was proposed a few years ago, to our knowledge, no practical demonstration/proof-of-concept has ever been published . FollowiFor our study, we initially considered six different cellulose derivatives that can be easily found on the market. In this series, cellulose ethers are characterized by either different viscosity while sharing the same kind of substitution (methyl celluloses) or by different substituting groups methyl), as summarized in In a preliminary screening aimed at testing the scattering capability of the selected materials, the diluted aqueous solutions were gradually heated with a hair-drier until we observed the formation of a scattering phase. The cuvette containing 1 wt % cellulose ether solutions quickly became opaque. By repeating the experiment in partially filled vials, we could verify by turning them upside-down that a liquid-gel transition accompanies the observed optical transition, increasing the viscosity of the mixture. By immersing the cuvette/vial in cold water, the temperature was quickly decreased, and the reversibility of the process could be visually confirmed .The visual comparison between the different cellulose derivatives before and after reaching the LCST revealed some differences. The scattering phase of methyl-celluloses sill maintained a minimum of transparency which allowed to glimpse the text underneath. HEC did not show any evident scattering phase upon heating; therefore, it was not considered anymore in this study. HPC produced a narrow scattering solid immersed in the transparent matrix. HPMC scattering phase was highly opaque and perfectly hid the text behind . In geneFollowing this preliminary assay, the next step was to determine the LCST of the different cellulose derivatives. To do so, we recorded the variation in light transmission through the cuvette filled with the cellulose solution by the microscope camera while varying their temperature from 30 to 95 °C. After reaching the highest temperature, the temperature scan was repeated back until it reached the initial cold point.As reported by the plot in This screening provided a first indication that cellulose ethers can be suitable for developing a self-tracking solar concentrator based on waveguiding, provided that the proper polymer functionalization and thus the right LCST is selected. However, the kind of functionalization is not the only parameter that must be taken into consideration. In fact, salts are known to influence the temperature-induced phase transitions in aqueous solutions of thermosensitive polymers . This isFor anions, a typical Hofmeister order is:− and SCN−, and one “salting-out” anion, namely Cl−, on the LCST of cellulose ethers. To better elucidate the effect of the anions, the counterion was always K+, and salt concentration was fixed at 0.5 M. As expected, in the presence of KI and KSCN all the cellulose ethers increased their LCST of 5–15 °C, while the addition of KCl lowered the LCST of the corresponding polymer of 5–10 °C  data are reported in The CS values were obtained by measuring with an integration sphere the light reaching the lateral side of the cell. For each wavelength AM 1.5 D ,37. The The average CS values in the investigated wavelength range were equal to 0.49 and 0.32 for the measurements at 3 cm and at 8 cm, respectively. These results indicate that the system in this non-optimized setup failed to concentrate the solar radiation. In fact, for CS values smaller than 1, the concentrated light reaching the window’s side is less than the non-concentrated light reaching the same area. Still, the amount of light trapped by our system and potentially usable to generate electricity is relevant, and the experiment demonstrated for the first time the potentiality of using thermotropic cellulose derivatives in self-tracking solar concentrators. The setup however demonstrated that a part of the light collected by the lens was deviated from its original direction through this optical device and in principle such behavior should happen for a certain range of incidence angles without the need of any mechanical tracking system.To achieve a real working system, the main parameters must be optimized. Specifically, by regulating the thickness of the thermotropic fluid , the size and efficiency of the scattering spot and the performance of the focusing optics, it would be possible, in principle, to maximize the amount of light reaching the window edges and to reach the goal of CS values exceeding unity.Cellulose ethers were purchased from TCI Europe N.V.  except for (hydroxypropyl)methyl cellulose batches, that were purchased from Merck KGaA .−1. The maximum temperature was maintained for 10 s before starting the return run. The same values of light intensity and exposition were used for all the experiments. The transparency data were extrapolated by measuring the average brightness of each micrograph with ImageJ [The transparency variation plots were obtained by using a Nikon Eclipse Te2000  inverted microscope equipped with a Linkam hot-stage system . Micrographs were taken every 2 s while the sample temperature was varied between 30 to 95 °C and then back to the 30 °C, at the rate of 1 °C × sh ImageJ . Since tThe solar concentration experiments were performed by focalizing the solar radiation on a glass cell of 160 × 160 × 4 mm filled with the thermotropic fluid, by using a PMMA Fresnel lens. The temperature of glass surface in correspondence of the concentrated light spot during a sunny day reached 50–55 °C. Data were acquired by positioning an integration sphere on the edge of the window and on the window’s face, towards the sun .In this study, we proposed to use the phenomenon of thermotropism to produce a scattering spot in a window filled with a thermotropic fluid, to create a new kind of self-tracking solar concentrator. By investigating different cellulose ethers in aqueous solution, we demonstrated that the properties of the thermotropic fluid can be finely tuned by selecting the cellulose functionalization, the co-dissolved salt, and by regulating their dosage. Then, we tested the results of our study in a proof-of-concept demonstration of solar concentration, showing that a part of the light collected by the lens is effectively trapped and deviated from its original direction by thermotropic effect without the need of any mechanical tracking, even though the system needs some optimization.It is worth noting that the perfectly sustainable thermotropic system developed here is highly tunable to respond to a certain temperature range; specifically, fluids with different LCST can be used in different geographical areas or can be easily replaced in the same window depending on the season, thanks to the low cost, low toxicity and easy availability of the chosen approach. A further advantage is that this kind of transparent photovoltaic window utilizes only the direct sun radiation, while the diffused skylight arising from the scattering of the direct solar beam by molecules or particulates in the atmosphere, which represents normally 10–15% of the total radiation, will be still available to illuminate the internal ambient. More importantly, conversely to what happens with luminescent solar concentrators, here the natural illumination is maintained without any chromatic modification. Therefore, this system, based only on a lens protruding from a transparent window, can possibly become a design element that, by preventing the entry of direct light, is able to create a more pleasant and soft illuminated ambient.In conclusion, after proper optimization, the solution proposed could be a viable alternative to enlarge and diversify the possible ways of exploiting renewable energy sources.


Borreliella to differentiate types and establish evolution over time. Investigating the ospC genetic types of Borreliella burgdorferi across multiple organ tissues of white-footed mice has the potential to contribute to our understanding of Lyme disease and the wide spectrum of clinical presentation associated with infection. In this study, five unique tissue types were sampled from 90 mice and screened for B. burgdorferi infections. This initial screening revealed a 63% overall B. burgdorferi infection rate in the mice collected (57/90). A total of 163 tissues (30.4%) tested positive for B. burgdorferi infections and when mapped to Borreliella types, 143,894 of the initial 322,480 reads mapped to 10 of the reference sequences in the ospC strain library constructed for this study at a 97% MOI. Two tissue types, the ear and the tongue, each accounted for 90% of the observed Borreliella sequence diversity in the tissue samples surveyed. The largest amount of variation was observed in an individual ear tissue sample with six ospC sequence types, which is equivalent to 60% of the observed variation seen across all tested specimens, with statistically significant associations observed between tissue type and detected Borreliella. There is strong evidence for genetic variability in B. burgdorferi within local white-footed mouse populations and even within individual hosts by tissue type. These findings may shed light on drivers of infection sequalae in specific tissues in humans and highlights the need for expanded surveillance on the epigenetics of B. burgdorferi across reservoirs, ticks, and infected patients.Outer surface protein C (OspC) is a commonly used marker in population studies of  Peromyscus leucopus) are the principle reservoir for Borreliella burgdorferi  in the eastern United States (Ixodes (Acari: Ixodidae) species ticks . However, once the tick initiates feeding, the dominant outer surface protein expression switches from OspA to OspC. OspC is required for productive mammalian infection to occur, with peak expression during tick-feeding at the 48-h mark  infections are commonly reported from the United States, Europe, and Asia. The strains responsible for Lyme disease infections in Europe  are primarily associated with neurological and dermal clinical manifestations respectively, while infections in the United States, originating from the B. burgdorferi sensu stricto strains, are most associated with skin lesions and arthritis , Goodwood (38.834570–77.358750), Huntley Meadows Park (38.756417–77.115347), Graves (38.771210–77.095720), Stoneybrooke (38.770943–77.096315).Collected mice were necropsied to separate spleen, liver, ear, tongue, tail, heart, and kidney tissues prior to storage in separate sterile microcentrifuge tubes at −80°C. DNA extraction was performed using the Qiagen DNeasy Blood & Tissue Kit according to the manufacturer’s instructions, diluted (1: 5 in DEPC water), and both the original DNA and dilutions were stored at −80°C for future use.B. burgdorferi ospC was performed on all mouse tissues using a semi-nested PCR protocol with the first round amplifying a 597 base pair fragment and the second amplifying a 314 base pair fragment. The first PCR was performed using extracted DNA as a template and a combination of two forward primers (WangEF) and (LinF) with a reverse primer (LinR). The second PCR was performed using template DNA from the first PCR, a M13 tagged forward primer (WangIF M13F), and a M13 reverse tagged primer (WangER M13R) found in . Nextgen sequencing was performed using the Ion Torrent Personal Genome Machine.via De Novo assembly, to conduct multiple alignments, develop a reference library, BLAST search, construct phylogenetic trees, and for reference mapping. The MBAC Galaxy Portal was then used to organize and rename sequence reads and with the program FigTree to customize phylogenetic trees. Several in-house Perl scripts were also used to create tables, sort reads, and rename sequences.The results obtained from the sequencing yielded 322,480 reads. The bioinformatics program Geneious, version 10.0, was used to analyze sequence data De Novo assembly in Geneious and the resulting contigs were then uploaded into BLAST. The 20 unique strain reference matches from the BLAST search were recorded by accession number along with 27 additional strain references from BorreliaBaseBorrelia spp. and different strains found worldwide. These matched references were imported into Geneious to build a reference library of 47 sequences. The strain references in the library were aligned to each other and trimmed to the ospC primers that were utilized for the PCR. References that were within 3% similarity to each other were removed from the library to eliminate redundancy, after which a neighbor-joining tree was built in Geneious to examine phylogenetic distance. The final number of reference strain sequences remaining in the library was reduced to 30 unique sequences and used for the remainder of the analysis.The 322,480 fasta read master files were put through a The 322,480 sample reads were mapped to the reference library, of which, 143,894 reads had a 97% minimum overlap identity (MOI) resulting in the production of 10 contigs that corresponded to 10 unique references from the reference library. The remaining unused reads were further examined and mapped back to the reference library at a lower MOI to determine if novel variations were being lost or if these unused reads contained errors that precluded them from being incorporated into the original 97% MOI mapping.p-value of <0.05 considered significant.All data were analyzed and cleaned using STATA v. 14.1 . Categorical data were coded in a binary fashion and analyzed using a simple logistic regression to determine the likelihood of other tissues testing positive, when compared to positive samples within the same mouse as well as the association between the number of detected types by mouse to determine if specific tissues were prone to more genetic diversity. An Analysis of Variance (ANOVA) was attempted, but the variance was not equal between groups, and thus an inappropriate test for this dataset. Z-scores and 95% confidence intervals for odds ratios were calculated to capture magnitude of association with a An IACUC was completed and approved by George Mason University under the Institutional Biosafety Committee (IBC) protocol# 12-28Mod1. Trapping was conducted under the Virginia Department of Game and Inland Fisheries (VADGIF) permit number 032199, 035522, 046610, and 050364.B. burgdorferi infections. When mapped to the Borreliella types in the reference library at a 97% MOI, 143,894 sample sequences mapped to 10 of the original 30 reference sequences in the reference library. The frequency and distribution of these tissues to the mapped reference sequences was tabulated  tested positive for abulated  and visuabulated , 2.Borreliella variation, 143,894 of the initial 322,480 reads mapped to 10 of the reference sequences in the ospC strain library constructed for this study at a 97% MOI  and JQ951096.1 were 3.58 and 2.94 times more likely to infect ear tissue than other tissue types (p < 0.01).A statistically significant association was observed between tissue and the type of the ue types , 5. The Borreliella types identified from the 537 tissues tested in this study are all endemic to North America and were mostly described from the northeastern states of New York and Massachusetts. The observed diversity of these types was different between trapping locations and between tissue types. Interestingly, several tissues tested positive for more than one type, which should be studied further in the future in terms of immune response and competition between types. Prior studies established the correlation between OspC types and the invasiveness of infections seen in humans, specifically OspC types A, B, C, D, H, K, and N , had fewer tissues infected per mouse (2), but had all 10 types observed for the entire study. It is important to note that the discrepancy between the total number of mice collected at each site was not evenly distributed, due to trap success rate. This lack of even distribution precluded statistical analysis of infection rate with respect to trapping location. The frequency distribution of the types was less evenly distributed than overall number of infected mice collected from trapping sites and therefore statistical significance of types was not reported.The observed diversity of ospC of B. burgdorferi and its pervasive spread through all trapping locations surveyed in Fairfax County suggests that Borreliella is actively transmitted and maintained within white-footed mice populations. Fragmentated and highly disturbed habitats, such as those in Fairfax County, Virginia, naturally lend themselves to increased non-mouse reservoir population and further increase the risk of creating infected tick vectors  and JQ951096.1 were only found in ear tissue. To further explore the relationship between OspC type and tissue specificity, a larger sample size of white-footed mice would be required. Regardless, pairing genetic testing and surveillance of Borreliella in mammalian hosts with active cases of Lyme disease in neighboring populations, may hold important insights to drivers of tissue specific infection and the overall clinical management of acute and chronic Lyme disease infection.The genetic diversity of All datasets presented in this study are included in the article/ The animal study was reviewed and approved by George Mason University, Institutional Biosafety Committee.SZ: conceptualization, methodology, formal analysis, lab analysis, sequencing, sample collection, investigation, and writing—original draft. MvF: methodology formal analysis, data visualization, and writing—original draft. TW: formal analysis, data visualization, and writing—editing and review. MS: methodology, lab analysis, sequencing, and writing—editing and review. PG: supervision, methodology, data curation, data visualization, and writing—editing and review. All authors contributed to the article and approved the submitted version.This project was supported using funds provided by George Mason University, Microbiome Analysis Center. Funding to cover publication costs was provided by George Mason University Libraries Open Access Publishing Fund.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Acinetobacter pittii strain, co-producing chromosomal NDM-1 and OXA-820 carbapenemases.To characterize one KL38-OCL6-ST220 carbapenem-resistant A. pittii TCM strain was isolated from a bloodstream infection (BSI). Antimicrobial susceptibility tests were conducted via disc diffusion and broth microdilution. Stability experiments of blaNDM-1 and blaOXA-820 carbapenemase genes were further performed. Whole-genome sequencing (WGS) was performed on the Illumina and Oxford Nanopore platforms. Multilocus sequence typing (MLST) was analyzed based on the Pasteur and Oxford schemes. Resistance genes, virulence factors, and insertion sequences (ISs) were identified with ABRicate based on ResFinder 4.0, virulence factor database (VFDB), and ISfinder. Capsular polysaccharide (KL), lipooligosaccharide outer core (OCL), and plasmid reconstruction were tested using Kaptive and PLACNETw. PHASTER was used to predict prophage regions. A comparative genomics analysis of all ST220 A. pittii strains from the public database was carried out. Point mutations, average nucleotide identity (ANI), DNA–DNA hybridization (DDH) distances, and pan-genome analysis were performed.A. pittii TCM was ST220Pas and ST1818Oxf with KL38 and OCL6, respectively. It was resistant to imipenem, meropenem, and ciprofloxacin but still susceptible to amikacin, colistin, and tigecycline. WGS revealed that A. pittii TCM contained one circular chromosome and four plasmids. The Tn125 composite transposon, including blaNDM-1, was located in the chromosome with 3-bp target site duplications (TSDs). Many virulence factors and the blaOXA-820 carbapenemase gene were also identified. The stability assays revealed that blaNDM-1 and blaOXA-820 were stabilized by passage in an antibiotic-free medium. Moreover, 12 prophage regions were identified in the chromosome. Phylogenetic analysis showed that there are 11 ST220 A. pittii strains, and one collected from Anhui, China was closely related. All ST220 A. pittii strains presented high ANI and DDH values; they ranged from 99.85% to 100% for ANI and from 97.4% to 99.9% for DDH. Pan-genome analysis revealed 3,200 core genes, 0 soft core genes, 1,571 shell genes, and 933 cloud genes among the 11 ST220 A. pittii strains.A. pittii presents a huge challenge in healthcare settings. Increased surveillance of this species in hospital and community settings is urgently needed.The coexistence of chromosomal NDM-1 and OXA-820 carbapenemases in  Acinetobacter is ubiquitous in diverse environments and clinical settings. The species belonging to the Acinetobacter calcoaceticus–Acinetobacter baumannii complex (ACB complex) including A. calcoaceticus, A. baumannii, A. dijkshoorniae, A. lactucae, A. nosocomialis, A. pittii, and A. seifertii are of great importance , pneumonia, and urinary tract infections (UTIs) (The genus portance . Among ts (UTIs) . One imps (UTIs) . These ds (UTIs) .Acinetobacter spp., including A. pittii , including the New Delhi metallo-β-lactamase (NDM)  . NDM couse (NDM) . NDM in A. baumannii is commonly considered to be a low virulent pathogen  in China. To the best of our knowledge, this is the first description of an ST220 A. pittii strain in which co-harboring blaNDM-1 and blaOXA-820 carbapenemase genes resided on the chromosome. A combination of Illumina and MinION whole-genome sequencing was conducted to provide comprehensive insight into the genomic and chromosome structure features.In this study, we investigate the characteristics of one sequence of type 220 Ahttps://cmap.ihmc.us)  . Based oihmc.us) .A. pittii TCM strain was isolated from a BSI during routine diagnostic analysis on 19 January 2018 in Hangzhou, China. Isolate identification to species level was conducted by matrix-assisted laser desorption ionization–time of flight mass spectrometry  and confirmed by 16S rRNA gene-based sequencing . The antibiotic disks used in this study included imipenem , meropenem , Amikacin , and ciprofloxacin  in a Mueller-Hinton agar (MHA) culture medium . In addition to the antibiotics mentioned above, colistin  and tigecycline  were also investigated using broth microdilution. Escherichia coli ATCC 25922 served as the quality control strain.Minimum inhibitory concentrations (MICs) for A. pittii TCM strain was grown overnight in three separate cultures at 37°C in 2 ml of Luria broth (LB) without antibiotics, followed by serial passage of 2 µl of overnight culture into 2 ml of LB daily, yielding 10 generations each lasting 7 days (blaNDM-1 and blaOXA-820 was confirmed via PCR. Primers were designed based on the full-length sequences of blaNDM-1 and blaOXA-820 on the A. pittii TCM chromosome (GenBank accession number: CP095407) using Snapgene  BLAST  2.3.2 and BLAST software. Primers are listed in g 7 days . On the A. pittii TCM strain using a Qiagen minikit  in accordance with the manufacturer’s recommendations. Whole-genome sequencing was performed using both the Illumina HiSeq platform  and the Oxford Nanopore MinION platform . De novo assembly of the reads of Illumina and MinION was constructed using Unicycler v0.4.8 (https://github.com/tseemann/abricate) based on ResFinder 4.0 updated in 2020 (http://genomicepidemiology.org/) (http://www.mgc.ac.cn/VFs/) (Kaptive v2.0.0 updated in 2021 (via the Center for Genomic Epidemiology (CGE) website updated in 2020 (https://cge.cbs.dtu.dk/services/MLST/). The Phage Search Tool (PHASTER) updated in 2016 was used for the prediction of bacteriophages  . The poigy.org/) . Bactericn/VFs/) . Inserticn/VFs/) . Capsula in 2021 . Multiloiophages .https://proksee.ca/) (A. pittii strains from the PubMLST database (https://pubmlst.org/) was further performed using the Bacterial Isolate Genome Sequence Database (BIGSdb) (https://itol.embl.de/) (Plasmid reconstruction was conducted using the PLACNETw tool . Plasmidsee.ca/) . Compara(BIGSdb) . The genmbl.de/) . DefaultA. pittii HUMV-6483 as the reference strain and species positive control (via the Roary software (https://jameshadfield.github.io/phandango/#/main).The taxonomic relationships among these isolates were further evaluated using the average nucleotide identity (ANI)  and DNA– control . Pan-gensoftware  and visuThe genome and protein-coding sequences (CDS) were annotated and predicted using PGAP and RAST. According to PGAP annotation, there are 4,330 genes, of which 4,102 are protein-coding genes, 131 are pseudogenes, and the remaining 97 are predicted RNA-coding genes, composed of 74 tRNAs, 18 rRNAs and 5 ncRNAs.In contrast to PGAP, 4,280 genes that belonged to 313 subsystems were annotated using RAST. The subsystem each CDS was classified into is shown in A. pittii TCM strain possessed a multidrug-resistant (MDR) profile when both CLSI and EUCAST breakpoints were used. The inhibition zone diameters of imipenem, meropenem, ciprofloxacin, and amikacin were 17 mm (R), 13 mm (R), 7 mm (R), and 21 mm (S), respectively. The broth microdilution results showed that the MICs of imipenem and meropenem were 8 and 16 mg/L, respectively. A. pittii TCM strain also exhibited a resistance to ciprofloxacin (32 mg/L). In our case, A. pittii TCM was still susceptible to amikacin (2 mg/L), colistin (1 mg/L), and tigecycline (0.5 mg/L). The susceptibility of the A. pittii TCM strain against the antimicrobial agents above was consistent when the isolate was classified as resistant or susceptible using CLSI and EUCAST breakpoints.The antimicrobial susceptibility testing results revealed the A. pittii TCM strain revealed that in addition to co-harboring blaNDM-1 and blaOXA-820, a series of genes conferring resistance to β-lactams (blaADC-43), bleomycin (ble-MBL), streptomycin [ant(2’’)-Ia], sulfonamides (sul2), and macrolide [msr(IE) and mph(E)] were also identified (gyrA (DNA gyrase) was found. However, no pmrAB and lpxACD mutations were identified in this strain. Based on these results, the genotype and the phenotype were consistent.Analysis of the genome of the A. pittii TCM strain. One was the outer membrane protein ompA gene pga operon (pgaABCD) encoding poly-β-1,6-N-acetyl-d-glucosamine (PNAG), which is important for biofilm development. Others were csu operon encoding Csu pili and pbpG encoding PbpG for serum resistance—a quite important two-component regulatory system bfmRS involved in Csu expression. Then, finally, there were lpxABC and lpxL encoding lipopolysaccharide (LPS) and many genes  encoding Acinetobactin for iron uptake.Many virulence factors were identified in the blaNDM-1 and blaOXA-820 were quite stable even after 70 samples under antibiotics-free condition. These results were confirmed with PCR . According to the Oxford MLST schemes, it belonged to ST1818 . The specific positions of all housekeeping genes are shown in Based on the Pasteur MLST scheme, the Kaptive showed that the A. pittii TCM strain contains OC locus 6 (OCL-6), matching the 98.98% coverage of reference sequence with 80.55% nucleotide identity. The K locus in the A. pittii TCM strain is KL38. It matches 100% of the locus with an overall nucleotide identity of 96.89%.A. pittii TCM strain had a 4,250,902-bp circular chromosome  possible target site duplications (TSDs). Moreover, the composite transposon structure of Tn125 with another 3-bp (AAA) TSD in the plasmid pDETAB2 (GenBank accession number: CP047975), which was isolated from a rectal swab sample in China, is identical to this Tn125 with a percentage of 99.99%  software family, Proksee, was utilized for generating high-quality, navigable maps of circular genomes. This tool is a Java program and originally intended for bacterial genomes. In our case, four plasmids were identified in the A. pittii TCM strain, namely pTCM-1 to pTCM-4, with sizes between 6,078 and 84,108 bp and GC contents ranging from 33.29% to 39.54%  disseminated predominantly within the ICU in China. However, limited data and knowledge concerning NDM-1-positive A. pittii-causing BSI have been acquired to date in China   could neutralize the activity of ß-lactam antibiotics ibiotics . In previn China . Authorsfunction . Consistfunction .A. pittii isolates, an outbreak of ST63 clone that carried a 45-kb blaNDM-1-bearing plasmid was reported in an ICU in China . However, no studies completely clarify the chromosome and plasmid structures of blaNDM-1-positive carbapenem-resistant A. pittii strain. Few studies highlight the importance of mobile genetic elements (MGEs) in A. pittii. MGEs, including insertion sequences (ISs), integrons, and transposons, play a particularly important role in the resistance gene transfer between plasmid and chromosomes  to a previously described blaNDM-1-blaOXA-58-harboring plasmid from an A. baumannii strain isolated from the rectal swab of a hospitalized patient in an ICU in Hangzhou, China  and a 28-bp recombination site dif, could play key roles in the resistance genes transfer of blaOXA-40-like, blaOXA-499, and blaOXA-58  of carbapenems resistance genes, such as blaNDM-1 and blaOXA-23  and the Natural Science Foundation of Zhejiang Province .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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