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PSH40 is the number of patient scheduled hours that result in 40 h of work per week as captured by EHR event log data. PSH40 represents the upper end of PSH of patient scheduled hours that will result in a 40-h work week because: (1) activities that occur outside of the EHR (such as phone calls and staff conversations) are not captured in EHR event log data; and (2) Epic’s Signal platform stops counting “active time” after 5 s of mouse or keyboard inactivity.

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Median PSH40 (h) by academic status and safety net status and by specialty group. PSH40: The number of patient scheduled hours per week that result in a 40-h work week as captured through EHR event log data in Epic’s Signal platform. Specialty group mappings are built to match the National Electronic Health Records Survey specialty categorization methodology, modified to include only those specialties with an ambulatory clinic practice and with over 500 physicians. See the footnotes of Table 1 for specific specialties included in each specialty group.

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(A, B) Non-scarring annular patches of hair loss (alopecia areata) at time of initial presentation.

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(A, B) Significant improvement of alopecia areata with belimumab.

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(A–D) Significant worsening of alopecia areata while on belimumab.

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(A–D) Progression of alopecia areata into alopecia totalis and alopecia universalis (only the progression is shown here).

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(A, B) Significant improvement in alopecia, with complete hair growth with baricitinib.

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Same as other existing methods, as a two-step TWAS fine-mapping approach, FABIO requires predicted GReX of the study cohort generated using the standard method like PrediXcan or BSLMM. Shown under the “GReX Modeling” and “Input Data” section, SNP weights are first estimated from the eQTL mapping cohort (sample size = n) with known genotypes and gene expression levels, then the predicted GReX will be generated in the study cohort (sample size = N, usually N > n), using known genotypes and estimated SNP weights. Shown under the “FABIO” section, FABIO explicitly models the binary nature of the outcome trait through a latent variable z with a sparsity inducing prior on each element of the gene effect sizes α. It also simultaneously models all genes on a single chromosome to account for the GReX correlation both within and between LD blocks, through the input of individual-level GReX matrix. We apply MCMC method to estimate the model parameters and obtain test statistic for each gene effect size αi, and use the posterior inclusion probability (PIP) as the evidence for the gene’s association with the binary outcome trait (“TWAS Fine-mapping” section). * Icons used in this figure are from BioRender.com.

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The red dashed line indicates a true FDR of 0.05. (a) Under different case/control ratios. (b) Under different percentages of PVE1.

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(a) Average number of genes in 95% credible set (CS) defined by FABIO or FOCUS and the number of true signal genes in 95% CS under different case/control ratios. (b) Power comparison for different methods based on a true false discovery rate (FDR) of 0.05 under different case/control ratios. (c) ROC curves of different methods with AUCs recorded under different case/control ratios. (d) Average number of genes in 95% credible set (CS) defined by FABIO or FOCUS and the number of true signal genes in 95% CS under different PVE1. (e) Power comparison for different methods based on a true false discovery rate (FDR) of 0.05 under different PVE1. (f) ROC curves of different methods with AUCs recorded under different PVE1.

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(a) Proportion of identified signal genes that locate in risk regions for the six diseases. Highlighted genes identified in TWAS fine-mapping analysis are labeled in black boxes in (b) and (d). Each gene is represented as a dot with x-axis indicating its genomic location and y-axis indicating its -log10 of p-value in the marginal TWAS association test. The dot of each gene is then colored based on different categories: (1) only identified by FABIO; (2) only identified by FOCUS; (3) only identified by FOGS; (4) identified by both FABIO and FOCUS; (5) identified by both FABIO and FOGS; (6) identified by both FOCUS and FOGS; (7) identified by all three methods; (8) located in a known risk region but missed by all three methods (uncaptured signal); (9) a gene shown no significance in both TWAS and GWAS analyses (non-signal). (b) TWAS Manhattan plot of gout. (c) LocusZoom plot of the corresponding LD block with the GWAS p-value of the SNP rs2231142 in ABCG2 for gout. (d) TWAS Manhattan plot of hypertension. (e) LocusZoom plot of the corresponding LD block with the GWAS p-value of the SNP rs3184504 in SH2B3 for hypertension.

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Natural edible ingredients improve epidermal permeability barrier via multiple mechanisms.

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The Autologous Regeneration of Tissue (ART®) Skin Harvesting System shows (A) donor site harvesting using the ART® Handheld Device and (B) collection of the full‐thickness autologous microcolumn (FTAM) using a 316 needle cartridge within a donor site collection area of 6.4 cm2 (approximately 10% of the donor site area is collected with a single harvest). (C) Dispensing of the FTAM from the ART® Handheld Device at the recipient site and (D) scattering of a single FTAM donor site harvest from the 316 needle cartridge at the recipient site.

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Time to wound closure for split‐thickness skin graft (STSG), full‐thickness autologous microcolumn (FTAM) and Untreated control recipient sites. Data are presented as the mean ± SEM and was 4.1 weeks (Untreated control), 2.4 weeks (STSG) and 3.3 weeks (FTAM). Individual wound closure data points are represented as triangles on the graphs. A significant difference was observed for FTAM and STSG sites compared to Untreated control sites (*p < 0.05). A significant difference was also observed for FTAM sites compared to STSG (# p < 0.05). Statistical evaluation was done by one‐way analysis of variance with Tukey's multiple comparison post‐test. Note those wounds that were not completely closed by each terminal time‐point are excluded from the graph.

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Re‐epithelization of recipient sites was scored by macroscopic evaluation and is presented as the percentage of wounds with complete (100%) re‐epithelialization at Week 1 to Week 6. Intergroup comparisons within the same time point were performed using proportion z‐tests where *p < 0.05 compared to Untreated control and # p < 0.05 was compared to split‐thickness skin graft (STSG) recipient sites (n = 11–36 per group).

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Recipient wound histology. Representative images of haematoxylin & eosin‐stained sections from full‐thickness autologous microcolumn (FTAM) (A–C), split‐thickness skin graft (STSG) (G–I) and Untreated (M–O) recipient wounds and Masson's trichrome‐stained sections from FTAM (D–F), STSG (J–L) and Untreated (P–R) wounds and at 1, 3 and 6‐weeks post‐treatment. Wound margins are indicated by arrowheads. Boxes indicate areas shown at 5× magnification. One week post‐wounding, FTAM‐recipients were partially re‐epithelialized with pronounced epithelial islands throughout the wound bed (A, D indicated by stars). By week 6, complete re‐epithelialization was seen in all groups. Both FTAM and STSG‐recipient wounds developed rete ridges by Week 1 (arrows) that persisted to Week 6 when untreated sites were characterized by effacement of rete ridges. The characteristic uneven surface of meshed STSGs was evident as prominent folds in the epidermal and upper dermal layers, remaining through Week 6 (I, L, indicated with ovals). The scale bar corresponds to 2.5 mm (1× magnification, top panels) and 500 μm (5× magnification, bottom panels).

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Recipient wound site fluid was observed beginning on Day 4 and then weekly (Weeks 1–4). No fluid was observed after 4 weeks. Exudate was scored as N (negative), serous (S), serosanguinous (SS), blood (B), purulent (P) or fibrinous (F). Data are shown as the percentage of full‐thickness autologous microcolumn (FTAM), split‐thickness skin graft (STSG) and Untreated recipient sites with each exudate characteristic.

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Schematic representation of wound site locations on the pig dorsum. The full‐thickness autologous microcolumn (FTAM) and split‐thickness skin graft (STSG) donor sites are shown in blue. The FTAM, STSG and Untreated recipient wound sites were randomized and are shown in red.

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Representative images from Day 0 through Week 6 of split‐thickness skin graft (STSG) (top row) and full‐thickness autologous microcolumn (FTAM) (bottom row) donor sites. Compared to FTAM harvest sites, STSG had more serocellular crust, erythema, exudate and eschar at early time points and took longer to close. At Week 6, STSG donor skin appearance remains visually distinct from surrounding healthy tissue due to abnormalities in texture and colouration, a cosmetic outcome commonly observed with STSG donor sites in humans.

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Histological evaluation of the full‐thickness autologous microcolumn (FTAM) and split‐thickness skin graft (STSG) donor sites. Representative images of FTAM (A–C) and STSG (D–F) donor site sections stained with haematoxylin & eosin at 1, 3 and 6 weeks post‐harvest. FTAM harvest sites are indicated by arrowheads. Boxes indicate areas shown at higher magnification (5×) in lower panels. One week post‐harvest, FTAM harvest sites appear light pink compared to dark pink adjacent non‐wounded tissue (A). By Week 3, FTAM harvest sites appear closer to surrounding skin in colouration (B). By Week 6, FTAM columns are indistinguishable from surrounding tissue, with all tissue appearing universally dark pink (C). Adnexa (hair follicles and/or glandular tissue) are observed at Week 1 within FTAM harvest columns and increased in prevalence through Week 6 (indicated with stars). Conversely, the entire epidermis/top superficial dermal layer is removed during STSG harvest, as shown by light pink staining in sections from Weeks 1 and 3 (indicated by brackets, 5× magnification, panels D and E). By Week 6, the difference in pigmentation becomes less apparent (I). Scale bars correspond with 2.5 mm and 500 μm at 1× and 5× magnification, respectively.

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Histological evaluation of collagen and elastin at full‐thickness autologous microcolumn (FTAM) and split‐thickness skin graft (STSG) donor sites. Representative images of FTAM (A–F) and STSG (G–L) donor wound sections stained with Masson's trichrome (left panels) or Verhoeff (right panels) at 1, 3 and 6‐weeks post‐harvest. FTAM harvest sites are indicated by arrowheads. Boxes indicate areas shown at higher magnification (5× trichrome and 40× Verhoeff) in lower panels. In Masson's trichrome‐stained sections, collagen appears blue with a darker colour associated with thicker collagen fibres/increased maturation. One week post‐harvest, FTAM harvest sites appear light pink compared to blue adjacent non‐wounded tissue (A). By Week 3, FTAM harvest columns appear blue, indicating the presence of collagen (B). By Week 6, FTAM columns are indistinguishable from surrounding tissue, with all tissue appearing universally dark blue (C). Adnexa (hair follicles and/or glandular tissue) are observed at Week 1 within FTAM harvest columns and increased in prevalence through Week 6 (indicated with stars). Conversely, the entire epidermis/top superficial dermal layer is removed during STSG harvest, as shown by pink staining in sections from Weeks 1 and 3 (indicated by brackets, 5× magnification, panels G and H). By Week 6, wounds are not fully healed, as the collagen stain remains light blue (I, bracket). In Verhoeff‐stained tissues, thicker/mature collagen bundles appear dark pink; less mature collagen appears light pink. Elastin appears as fine dark lines (arrows). Positive elastin staining was observed beginning at Week 1 in FTAM harvest sites (D) and Week 3 in STSG harvest sites (K) and increased in prevalence over time. Scale bars correspond with 2.5 mm, 500 μm, and 50 μm at 1×, 5× and 40× magnification, respectively.

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Donor site collagen and elastin. Donor sites were stained with Masson's trichome and Verhoeff to grade collagen (A) and elastin (B) deposition and organization, respectively. The percentage of donor sites with majority of stroma having a similar appearance of native dermal collagen (Score 4) (A) and scanty and scattered elastin deposition (Score 1) (B) in the superficial dermis is shown. The percentage of sites with notable collagen content (Score 4) and positively staining for elastin was higher and occurred sooner in full‐thickness autologous microcolumn (FTAM) donors when compared to split‐thickness skin graft (STSG) donors. Intergroup comparisons within the same time point were performed using proportion z‐tests where *p < 0.05 was considered statistically significantly different (n = 13–39 per group per week).

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Donor wound site fluid was observed beginning on Day 4 and then weekly (Weeks 1–4). No fluid was observed after 4 weeks. Exudate was scored as N (negative), serous (S), serosanguinous (SS), blood (B) or fibrinous (F). Data are shown as the percentage of full‐thickness autologous microcolumn (FTAM) and split‐thickness skin graft (STSG) donor sites with each exudate characteristic. Note a few data points are missing from the analysis at Week 1 and Week 2 for the STSG donor sites.

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Representative photographs of two recipient wounds 2 days before (A), immediately following (B) and 6 days post‐full‐thickness autologous microcolumn (FTAM) deposition (C). Epithelial islands can be seen on Day 6 as the light‐coloured substance in the middle of the wound beds. On casual observation these may appear similar to wound sloughing or purulent material, but they consist of epidermal outgrowth derived from the FTAMs (see histologic images in Figure 10). These epithelial islands are not seen in Untreated controls (last row).

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Representative recipient sites from Day 0 (pre‐ and post‐grafting) until Week 6 for split‐thickness skin graft (STSG) recipient sites (top row), full‐thickness autologous microcolumn (FTAM) recipient sites (middle row) and Untreated control sites (bottom row). Tattoos were used to monitor changes in wound size due to animal growth and assess contracture. Note the presence of a linear scar and incomplete wound closure of Untreated sites at Week 6 compared to STSG and FTAM recipient sites, which healed by re‐epithelialization and are completely closed.