Fins are major functional appendages of fish that have been repeatedly modified in different lineages. To search for genomic changes underlying natural fin diversity, we compared the genomes of 36 percomorph fish species that span over 100 million years of evolution and either have complete or reduced pelvic and caudal fins. We identify 1,614 genomic regions that are well-conserved in fin-complete species but missing from multiple fin-reduced lineages. Recurrent deletions of conserved sequences in wild fin-reduced species are enriched for functions related to appendage development, suggesting that convergent fin reduction at the organismal level is associated with repeated genomic deletions near fin-appendage development genes. We used sequencing and functional enhancer assays to confirm that PelA, a Pitx1 enhancer previously linked to recurrent pelvic loss in sticklebacks, has also been independently deleted and may have contributed to the fin morphology in distantly related pelvic-reduced species. We also identify a novel enhancer that is conserved in the majority of percomorphs, drives caudal fin expression in transgenic stickleback, is missing in tetraodontiform, syngnathid, and synbranchid species with caudal fin reduction, and alters caudal fin development when targeted by genome editing. Our study illustrates a broadly applicable strategy for mapping phenotypes to genotypes across a tree of vertebrate species and highlights notable new examples of regulatory genomic hotspots that have been used to evolve recurrent phenotypes across 100 million years of fish evolution.

Importance

The nasal base view is often overlooked in rhinoplasty analysis and, unlike lateral and frontal views, lacks detailed quantitative analysis and descriptors. While shape-category analysis of the nasal base is well established, these descriptive methods remain subjective and do not facilitate quantitative analysis.

Objective

To establish a simple and quantitative classification scheme using a multiple-parameter numerical model for analyzing and describing the shape of the nasal base.

Design, setting, and participants

Deidentified photographs of the nasal base view were analyzed without knowledge of patients' pathology or medical history. Each nose was classified into 1 of 6 categories derived from literature (equilateral, narrow, flat, cloverleaf, boxy, and round). Finite parametric modeling was performed on each nose, and the correlations between the resulting parameters and the 6 categories were analyzed. Photographs for this study were acquired from the practice of a single facial plastic surgeon (B.J.F.W.) at a tertiary care academic medical center. One hundred twenty-one consecutive patients who had nasal base view photographs taken were included in the study.

Main outcomes and measures

All of the 121 images were classified into 1 of the 6 categories by 1 reviewer (C.H.B.). The contour of each nasal base was curve fit to a 5-parameter numerical model. The 5 parameters controlled base size, deviation from the midline, projection-to-width ratio, degree of nasal alar recurvature, and anterior-posterior positioning of nasal base bulk. A numerical value for each nasal base shape type was predicted by the parametric model.

Results

In 121 patient photographs, the parametric model generated shapes that accurately matched the tracing of the actual nasal base contours with an average correlation coefficient of greater than 0.98. This finding indicates close approximation of the nasal base shape with the curve fit constructed by the PM. Parameters b (projection-to-width ratio) and e (roundedness) were shown to have significant differences among the groups (F statistic, 8.88; P < .001 and F statistic, 13.05; P < .001, respectively). These two curve-fit parameters alone could be used to classify nasal shape into 1 of the 6 clinically determined base geometries.

Conclusions and relevance

A numerical approach to classify nasal base shape was developed using a 5-parameter model and tested against subjective analysis. This model may aid in the advancement of algorithm-driven objective nasal analysis techniques, preoperative modeling, intraoperative guidance, and surgical outcome measures beyond using Likert scales.

Level of evidence

NA.

Objective

To characterize associations between exposures within and outside the medical workplace with healthcare personnel (HCP) SARS-CoV-2 infection, including the effect of various forms of respiratory protection.

Design

Case-control study.

Setting

We collected data from international participants via an online survey.

Participants

In total, 1,130 HCP (244 cases with laboratory-confirmed COVID-19, and 886 controls healthy throughout the pandemic) from 67 countries not meeting prespecified exclusion (ie, healthy but not working, missing workplace exposure data, COVID symptoms without lab confirmation) were included in this study.

Methods

Respondents were queried regarding workplace exposures, respiratory protection, and extra-occupational activities. Odds ratios for HCP infection were calculated using multivariable logistic regression and sensitivity analyses controlling for confounders and known biases.

Results

HCP infection was associated with non-aerosol-generating contact with COVID-19 patients (adjusted OR, 1.4; 95% CI, 1.04-1.9; P = .03) and extra-occupational exposures including gatherings of ≥10 people, patronizing restaurants or bars, and public transportation (adjusted OR range, 3.1-16.2). Respirator use during aerosol-generating procedures (AGPs) was associated with lower odds of HCP infection (adjusted OR, 0.4; 95% CI, 0.2-0.8, P = .005), as was exposure to intensive care and dedicated COVID units, negative pressure rooms, and personal protective equipment (PPE) observers (adjusted OR range, 0.4-0.7).

Conclusions

COVID-19 transmission to HCP was associated with medical exposures currently considered lower-risk and multiple extra-occupational exposures, and exposures associated with proper use of appropriate PPE were protective. Closer scrutiny of infection control measures surrounding healthcare activities and medical settings considered lower risk, and continued awareness of the risks of public congregation, may reduce the incidence of HCP infection.

INTRODUCTION: Lung cancer is the deadliest cancer in the United States and worldwide, and lung adenocarcinoma (LUAD) is the most prevalent histologic subtype in the United States. LUAD exhibits a wide range of aggressiveness and risk of recurrence, but the biological underpinnings of this behavior are poorly understood. Past studies have focused on the biological characteristics of the tumor itself, but the ability of the immune response to contain tumor growth represents an alternative or complementary hypothesis. Emerging technologies enable us to investigate the spatial distribution of specific cell types within the tumor nest and characterize this immune response. This study aimed to investigate the association between immune cell density within the primary tumor and recurrence-free survival (RFS) in stage I and II LUAD. METHODS: This study is a prospective collection with retrospective evaluation. A total of 100 patients with surgically resected LUAD and at least 5-year follow-ups, including 69 stage I and 31 stages II tumors, were enrolled. Multiplexed immunohistochemistry panels for immune markers were used for measurement. RESULTS: Cox regression models adjusted for sex and EGFR mutation status revealed that the risk of recurrence was reduced by 50% for the unit of one interquartile range (IQR) change in the tumoral T-cell (adjusted hazard ratio per IQR increase = 0.50, 95% confidence interval: 0.27-0.93) and decreased by 64% in mast cell density (adjusted hazard ratio per IQR increase = 0.36, confidence interval: 0.15-0.84). The analyses were reported without the type I error correction for the multiple types of immune cell testing. CONCLUSIONS: Analysis of the density of immune cells within the tumor and surrounding stroma reveals an association between the density of T-cells and RFS and between mast cells and RFS in early-stage LUAD. This preliminary result is a limited study with a small sample size and a lack of an independent validation set.

Bcl-2 family proteins reorganize mitochondrial membranes during apoptosis, to form pores and rearrange cristae. In vitro and in vivo analysis integrated with human genetics reveals a novel homeostatic mitochondrial function for Bcl-2 family protein Bid. Loss of full-length Bid results in apoptosis-independent, irregular cristae with decreased respiration. Bid-/- mice display stress-induced myocardial dysfunction and damage. A gene-based approach applied to a biobank, validated in two independent GWAS studies, reveals that decreased genetically determined BID expression associates with myocardial infarction (MI) susceptibility. Patients in the bottom 5% of the expression distribution exhibit >4 fold increased MI risk. Carrier status with nonsynonymous variation in Bids membrane binding domain, BidM148T, associates with MI predisposition. Furthermore, Bid but not BidM148T associates with Mcl-1Matrix, previously implicated in cristae stability; decreased MCL-1 expression associates with MI. Our results identify a role for Bid in homeostatic mitochondrial cristae reorganization, that we link to human cardiac disease.