Prevalence of Occult Ovarian Cancer and Metastatic Breast Cancer in Ovarian Ablation Specimens of Patients With Hormone Receptor-Positive Breast Cancer: Implications for Tissue Sampling Strategies, Early Ovarian Cancer Detection and Resource Utilization.

Bilateral oophorectomy is one method of hormone suppression for premenopausal patients with hormone receptor-positive breast cancer. Such specimens could, in theory, harbor occult early ovarian cancer and/or metastatic breast cancer but guidelines for tissue sampling for pathologic examination remain to be addressed. Therefore, we evaluated oophorectomy specimens from 166 patients who underwent ovarian ablation for hormone receptor-positive breast cancer. Results of germline genetic testing were documented by the surgeon in only 31.3% of the pathology specimen requisition forms, whereas that information was available for 81.3% of patients elsewhere in the electronic medical records. All but 5.2% tested negative for a hereditary ovarian cancer gene pathogenic variant before oophorectomy. Complete tissue sampling was performed in 77.1% of the cases and representative sampling in the remainder. No cases of ovarian cancer were observed. Ovarian metastasis of breast cancer was identified in 9.6% of patients, all of whom were already known to have advanced-stage disease. The number of tissue cassettes per ovary required for complete tissue submission was on average three times higher than that for representative tissue sampling (P < 0.01) and ranged up to 20 cassettes per ovary when multiple follicle cysts were present. We propose that guidelines for tissue sampling in this context be defined by a combination of hereditary risk and macroscopic examination; representative sampling is reasonable for macroscopically normal ovaries in hormone receptor-positive breast cancer patients whose germline genetic testing is negative. Positive genetic test results merit complete tissue submission even if macroscopically normal. This strategy balances the goals of early ovarian cancer detection and optimal resource utilization. However, it depends on clear documentation of genetic test results. Our study demonstrates that many opportunities remain to close gaps in the communication of genetic test results by clinicians submitting oophorectomy specimens for pathologic evaluation.

Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry.

INTRODUCTION: Despite a two-fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts. METHODS: Genome-wide association studies (GWAS) of 2,903 AD cases and 6,265 controls of African ancestry. Within-dataset results were meta-analyzed, followed by functional genomics analyses. RESULTS: A novel AD-risk locus was identified in MPDZ on chromosome (chr) 9p23 (rs141610415, MAF = 0.002, P = 3.68×10-9). Two additional novel common and nine rare loci were identified with suggestive associations (P < 9×10-7). Comparison of association and linkage disequilibrium (LD) patterns between datasets with higher and lower degrees of African ancestry showed differential association patterns at chr12q23.2 (ASCL1), suggesting that this association is modulated by regional origin of local African ancestry. DISCUSSION: These analyses identified novel AD-associated loci in individuals of African ancestry and suggest that degree of African ancestry modulates some associations. Increased sample sets covering as much African genetic diversity as possible will be critical to identify additional loci and deconvolute local genetic ancestry effects. HIGHLIGHTS: Genetic ancestry significantly impacts risk of Alzheimer's Disease (AD). Although individuals of African ancestry are twice as likely to develop AD, they are vastly underrepresented in AD genomics studies. The Alzheimer's Disease Genetics Consortium has previously identified 16 common and rare genetic loci associated with AD in African American individuals. The current analyses significantly expand this effort by increasing the sample size and extending ancestral diversity by including populations from continental Africa. Single variant meta-analysis identified a novel genome-wide significant AD-risk locus in individuals of African ancestry at the MPDZ gene, and 11 additional novel loci with suggestive genome-wide significance at P < 9×10-7. Comparison of African American datasets with samples of higher degree of African ancestry demonstrated differing patterns of association and linkage disequilibrium at one of these loci, suggesting that degree and/or geographic origin of African ancestry modulates the effect at this locus. These findings illustrate the importance of increasing number and ancestral diversity of African ancestry samples in AD genomics studies to fully disentangle the genetic architecture underlying AD, and yield more effective ancestry-informed genetic screening tools and therapeutic interventions.

Mixture and Non-mixture Cure Models for Health Technology Assessment: What You Need to Know.

There is increasing interest in the use of cure modelling to inform health technology assessment (HTA) due to the development of new treatments that appear to offer the potential for cure in some patients. However, cure models are often not included in evidence dossiers submitted to HTA agencies, and they are relatively rarely relied upon to inform decision-making. This is likely due to a lack of understanding of how cure models work, what they assume, and how reliable they are. In this tutorial we explain why and when cure models may be useful for HTA, describe the key characteristics of mixture and non-mixture cure models, and demonstrate their use in a range of scenarios, providing Stata code. We highlight key issues that must be taken into account by analysts when fitting these models and by reviewers and decision-makers when interpreting their predictions. In particular, we note that flexible parametric non-mixture cure models have not been used in HTA, but they offer advantages that make them well suited to an HTA context when a cure assumption is valid but follow-up is limited.

Long-term Outcomes of Poly-4-Hydroxybutyrate (P4HB) in Aesthetic Breast Surgery.

BACKGROUND: Over the past decade, the use of poly-4-hydroxybutyrate (P4HB) in aesthetic breast surgery has grown in popularity. Published data on long-term outcomes, however, is scarce. OBJECTIVES: The purpose of this study was to assess long-term outcomes when using P4HB in various aesthetic breast procedures. METHODS: A retrospective review of all patients undergoing breast procedures with P4HB performed by the senior author (WPA) between July 2012 and March 2022. All patients with greater than one year of follow-up were evaluated, including demographics, surgical indications, complications, secondary procedures, and patient satisfaction. A Kruskal-Wallis test was performed to assess the stability of satisfaction over time. RESULTS: A total of 248 patients were evaluated. The mean follow-up length was 2.9 years (range, 1-9.3y). The most common surgical indication was breast ptosis, which comprised 68 percent (n=167) of patients. The overall complication rate was 8.0 percent (n=20), with an unplanned reoperation rate of 2.8 percent (n=7). Across the entire study population, the mean satisfaction score was 3.42 out of 4. When satisfaction scores were compared to follow-up length, Kruskal-Wallis test demonstrated no statistical differences (H = 18.2, p = 0.89, df = 2), suggesting stability of satisfaction over time. CONCLUSIONS: This study presents the senior author's entire experience with P4HB across a wide range of aesthetic breast procedures. With an average follow-up length of almost 3 years, P4HB appears to be both a safe and effective tool to support soft tissue in aesthetic breast surgery. Further, high patient satisfaction appears stable.

Evolution and host-specific adaptation of Pseudomonas aeruginosa.

The major human bacterial pathogen Pseudomonas aeruginosa causes multidrug-resistant infections in people with underlying immunodeficiencies or structural lung diseases such as cystic fibrosis (CF). We show that a few environmental isolates, driven by horizontal gene acquisition, have become dominant epidemic clones that have sequentially emerged and spread through global transmission networks over the past 200 years. These clones demonstrate varying intrinsic propensities for infecting CF or non-CF individuals (linked to specific transcriptional changes enabling survival within macrophages); have undergone multiple rounds of convergent, host-specific adaptation; and have eventually lost their ability to transmit between different patient groups. Our findings thus explain the pathogenic evolution of P. aeruginosa and highlight the importance of global surveillance and cross-infection prevention in averting the emergence of future epidemic clones.

Differing worldviews: The politics of happiness, meaning, and psychological richness.

OBJECTIVE/BACKGROUND: Conservative ideology, broadly speaking, has been widely linked to greater happiness and meaning in life. Is that true of all forms of a good life? We examined whether a psychologically rich life is associated with political orientation, system justification, and Protestant work ethic, independent of two other traditional forms of a good life: a happy life and a meaningful life. METHOD: Participants completed a questionnaire that assessed conservative worldviews and three aspects of well-being (N = 583 in Study 1; N = 348 in Study 2; N = 436 in Study 3; N = 1,217 in Study 4; N = 2,176 in Study 5; N = 516 in Study 6). RESULTS: Happiness was associated with political conservatism and system justification, and meaning in life was associated with Protestant work ethic. In contrast, zero-order correlations showed that psychological richness was not associated with conservative worldviews. However, when happiness and meaning in life were included in multiple regression models, the nature of the association shifted: Psychological richness was consistently inversely associated with system justification and on average less political conservatism, suggesting that happiness and meaning in life were suppressor variables. CONCLUSIONS: These findings suggest that happiness and meaning in life are associated with conservative ideology, whereas psychological richness is not.

Genetic diversity, determinants, and dissemination of Burkholderia pseudomallei lineages implicated in melioidosis in Northeast Thailand.

Melioidosis is an often-fatal neglected tropical disease caused by an environmental bacterium Burkholderia pseudomallei. However, our understanding of the disease-causing bacterial lineages, their dissemination, and adaptive mechanisms remains limited. To address this, we conduct a comprehensive genomic analysis of 1,391 B. pseudomallei isolates collected from nine hospitals in northeast Thailand between 2015 and 2018, and contemporaneous isolates from neighbouring countries, representing the most densely sampled collection to date. Our study identifies three dominant lineages, each with unique gene sets potentially enhancing bacterial fitness in the environment. We find that recombination drives lineage-specific gene flow. Transcriptome analyses of representative clinical isolates from each dominant lineage reveal increased expression of lineage-specific genes under environmental conditions in two out of three lineages. This underscores the potential importance of environmental persistence for these dominant lineages. The study also highlights the influence of environmental factors such as terrain slope, altitude, and river direction on the geographical dispersal of B. pseudomallei. Collectively, our findings suggest that environmental persistence may play a role in facilitating the spread of B. pseudomallei, and as a prerequisite for exposure and infection, thereby providing useful insights for informing melioidosis prevention and control strategies.

Protocol for a feasibility randomized controlled trial of gentle yoga in older patients discharged from phase II cardiac rehabilitation.

Background: Physical activity (PA) is essential following an acute cardiac event. Cardiac rehabilitation (CR) is commonly prescribed, and PA after CR is recommended. Because of age-related changes in functional ability and multi-comorbidity, many older cardiac patients struggle to continue performing PA at home after CR. Depressive symptoms and anxiety are prevalent in cardiac patients and associated with poor self-care, including lack of daily PA. Yoga has been demonstrated to improve psychological and physical health outcomes in cardiac patients, but it is unknown whether yoga, modified for older CR patients - Gentle Yoga - is beneficial in managing psychological distress and maintaining PA following phase II CR. Our specific aims are to:1) determine the feasibility and acceptability of a modified gentle yoga intervention delivered via video conferencing for older cardiac patients; 2) compare, at 3-month follow-up, the effects and determine effect sizes of a gentle yoga intervention versus control on psychological health and physical health. Methods: We are conducting a 2-group (intervention versus control) randomized controlled pilot study. The intervention is a 12-week gentle yoga program delivered via video conference. Short-term effects will be evaluated at 3-month. Conclusion: This study is designed to be suited for older cardiac patients who would not have access to supervised PA opportunities after facility-based CR to enhance PA. This study will provide data about the feasibility and acceptability of the protocol for older cardiac patients and will offer effect sizes to determine sample size for a fully powered randomized controlled trial.

Investigating Snake-Venom-Induced Dermonecrosis and Inflammation Using an Ex Vivo Human Skin Model.

Snakebite envenoming is a neglected tropical disease that causes >100,000 deaths and >400,000 cases of morbidity annually. Despite the use of mouse models, severe local envenoming, defined by morbidity-causing local tissue necrosis, remains poorly understood, and human-tissue responses are ill-defined. Here, for the first time, an ex vivo, non-perfused human skin model was used to investigate temporal histopathological and immunological changes following subcutaneous injections of venoms from medically important African vipers (Echis ocellatus and Bitis arietans) and cobras (Naja nigricollis and N. haje). Histological analysis of venom-injected ex vivo human skin biopsies revealed morphological changes in the epidermis (ballooning degeneration, erosion, and ulceration) comparable to clinical signs of local envenoming. Immunostaining of these biopsies confirmed cell apoptosis consistent with the onset of necrosis. RNA sequencing, multiplex bead arrays, and ELISAs demonstrated that venom-injected human skin biopsies exhibited higher rates of transcription and expression of chemokines (CXCL5, MIP1-ALPHA, RANTES, MCP-1, and MIG), cytokines (IL-1ß, IL-1RA, G-CSF/CSF-3, and GM-CSF), and growth factors (VEGF-A, FGF, and HGF) in comparison to non-injected biopsies. To investigate the efficacy of antivenom, SAIMR Echis monovalent or SAIMR polyvalent antivenom was injected one hour following E. ocellatus or N. nigricollis venom treatment, respectively, and although antivenom did not prevent venom-induced dermal tissue damage, it did reduce all pro-inflammatory chemokines, cytokines, and growth factors to normal levels after 48 h. This ex vivo skin model could be useful for studies evaluating the progression of local envenoming and the efficacy of snakebite treatments.

Radiofrequency echographic multi spectrometry (REMS) in the diagnosis and management of osteoporosis: state of the art.

Radiofrequency Echographic Multi Spectrometry (REMS) is a radiation-free, portable technology, which can be used for the assessment and monitoring of osteoporosis at the lumbar spine and femoral neck and may facilitate wider access to axial BMD measurement compared with standard dual-energy x-ray absorptiometry (DXA).There is a growing literature demonstrating a strong correlation between DXA and REMS measures of BMD and further work supporting 5-year prediction of fracture using the REMS Fragility Score, which provides a measure of bone quality (in addition to the quantitative measure of BMD).The non-ionising radiation emitted by REMS allows it to be used in previously underserved populations including pregnant women and children and may facilitate more frequent measurement of BMD.The portability of the device means that it can be deployed to measure BMD for frail patients at the bedside (avoiding the complications in transfer and positioning which can occur with DXA), in primary care, the emergency department, low-resource settings and even at home.The current evidence base supports the technology as a useful tool in the management of osteoporosis as an alternative to DXA.

Host tracheal and intestinal microbiomes inhibit Coccidioides growth in vitro.

Coccidioidomycosis, also known as Valley fever, is a disease caused by the fungal pathogen Coccidioides. Unfortunately, patients are often misdiagnosed with bacterial pneumonia, leading to inappropriate antibiotic treatment. The soil Bacillus subtilis-like species exhibits antagonistic properties against Coccidioides in vitro; however, the antagonistic capabilities of host microbiota against Coccidioides are unexplored. We sought to examine the potential of the tracheal and intestinal microbiomes to inhibit the growth of Coccidioides in vitro. We hypothesized that an uninterrupted lawn of microbiota obtained from antibiotic-free mice would inhibit the growth of Coccidioides, while partial in vitro depletion through antibiotic disk diffusion assays would allow a niche for fungal growth. We observed that the microbiota grown on 2×GYE (GYE) and Columbia colistin and nalidixic acid with 5% sheep's blood agar inhibited the growth of Coccidioides, but microbiota grown on chocolate agar did not. Partial depletion of the microbiota through antibiotic disk diffusion revealed diminished inhibition and comparable growth of Coccidioides to controls. To characterize the bacteria grown and identify potential candidates contributing to the inhibition of Coccidioides, 16S rRNA sequencing was performed on tracheal and intestinal agar cultures and murine lung extracts. We found that the host bacteria likely responsible for this inhibition primarily included Lactobacillus and Staphylococcus. The results of this study demonstrate the potential of the host microbiota to inhibit the growth of Coccidioides in vitro and suggest that an altered microbiome through antibiotic treatment could negatively impact effective fungal clearance and allow a niche for fungal growth in vivo. IMPORTANCE: Coccidioidomycosis is caused by a fungal pathogen that invades the host lungs, causing respiratory distress. In 2019, 20,003 cases of Valley fever were reported to the CDC. However, this number likely vastly underrepresents the true number of Valley fever cases, as many go undetected due to poor testing strategies and a lack of diagnostic models. Valley fever is also often misdiagnosed as bacterial pneumonia, resulting in 60%-80% of patients being treated with antibiotics prior to an accurate diagnosis. Misdiagnosis contributes to a growing problem of antibiotic resistance and antibiotic-induced microbiome dysbiosis; the implications for disease outcomes are currently unknown. About 5%-10% of symptomatic Valley fever patients develop chronic pulmonary disease. Valley fever causes a significant financial burden and a reduced quality of life. Little is known regarding what factors contribute to the development of chronic infections and treatments for the disease are limited.

Operating Room Extubation for Patients Undergoing Cardiac Surgery: A National Society of Thoracic Surgeons Database Analysis.

BACKGROUND: The utility of operating room extubation (ORE) after cardiac surgery over fast-track extubation (FTE) within 6 hours remains contested. We hypothesized ORE would be associated with equivalent rates of morbidity and mortality, relative to FTE. METHODS: Patients undergoing nonemergent cardiac surgery were identified in The Society of Thoracic Surgeons Adult Cardiac Surgery Database between July 2017 and December 2022. Only procedures with The Society of Thoracic Surgeons risk models were included. Risk-adjusted outcomes of ORE and FTE were compared by observed-to-expected ratios with 95% CIs aggregated over all procedure types, and ORE vs FTE adjusted odds ratios (ORs) specific to each procedure type using multivariable logistic regression. Analyzed outcomes were operative mortality, prolonged length of stay, composite reoperation for bleeding and reintubation, and composite morbidity and mortality. RESULTS: The study population of 669,099 patients across 1069 hospitals included 36,298 ORE patients in 296 hospitals. Risk-adjusted analyses found that ORE was associated with statistically similar or better results across each of the 4 outcomes and procedure subtypes. Notably, rates of postoperative mortality were significantly lower in ORE patients undergoing coronary artery bypass grafting (OR, 0.54; 95% CI, 0.46-0.65), aortic valve replacement (OR, 0.43; 95% CI, 0.24-0.77), and mitral valve replacement (OR, 0.48; 95% CI, 0.26-0.89). CONCLUSIONS: Extubation in the OR was safe and effective in a selected patient population and may be associated with superior outcomes in coronary artery bypass, aortic valve replacement, and mitral valve replacement. These national data appear to confirm institutional experiences regarding the potential benefit of OR extubation. Further refinement of optimal populations may justify randomized investigation.

Exogenous photocatalyst-free aryl radical generation from diaryliodonium salts and use in metal-catalyzed C-H arylation.

We demonstrate (1) detectable halogen bonding is not critical for enabling light-driven radical generation from diaryliodonium salts and (2) radicals generated by this route can be captured by transition-metals for C-H arylation reactions. These results are the first step toward developing new metal-catalyzed aryl radical couplings without exogenous photocatalysts.

Deciphering spatial domains from spatial multi-omics with SpatialGlue.

Advances in spatial omics technologies now allow multiple types of data to be acquired from the same tissue slice. To realize the full potential of such data, we need spatially informed methods for data integration. Here, we introduce SpatialGlue, a graph neural network model with a dual-attention mechanism that deciphers spatial domains by intra-omics integration of spatial location and omics measurement followed by cross-omics integration. We demonstrated SpatialGlue on data acquired from different tissue types using different technologies, including spatial epigenome-transcriptome and transcriptome-proteome modalities. Compared to other methods, SpatialGlue captured more anatomical details and more accurately resolved spatial domains such as the cortex layers of the brain. Our method also identified cell types like spleen macrophage subsets located at three different zones that were not available in the original data annotations. SpatialGlue scales well with data size and can be used to integrate three modalities. Our spatial multi-omics analysis tool combines the information from complementary omics modalities to obtain a holistic view of cellular and tissue properties.

Mitral valve repair in a regional quality collaborative: Respect or resect?

Objective: Mitral valve repair is the gold standard for treatment of mitral regurgitation, but the optimal technique remains debated. By using a regional collaborative, we sought to determine the change in repair technique over time. Methods: We identified all patients undergoing isolated mitral valve repair from 2012 to 2022 for degenerative mitral disease. Those with endocarditis, transcatheter repair, or tricuspid intervention were excluded. Continuous variables were analyzed via Wilcoxon rank sum, and categorical variables were analyzed via chi-square testing. Results: We identified 1653 patients who underwent mitral valve repair, with 875 (59.2%) undergoing a no resection repair. Over the last decade, there was no significant trend in the proportion of repair techniques across the region (P = .96). Those undergoing no resection repairs were more likely to have undergone prior cardiac surgery (5.0% vs 2.2%, P = .002) or minimally invasive approaches (61.4% vs 24.7%, P < .001) with similar predicted risk of mortality (median 0.6% vs 0.6%, P = .75). Intraoperatively, no resection repairs were associated with longer bypass times (140 [117-167] minutes vs 122 [91-159] minutes, P < .001). Operative mortality was similar between both groups (1.1% vs 1.0%, P = .82), as were other postoperative outcomes. Anterior leaflet prolapse (odds ratio, 11.16 [6.34-19.65], P < .001) and minimally invasive approach (odds ratio, 6.40 [5.06-8.10], P < .001) were most predictive of no resection repair. Conclusions: Despite minor differences in operative times, statewide over the past decade there remains a diverse mix of both classic "resect" and newer "respect" strategies with comparable short-term outcomes and no major timewise trends. These data may suggest that both approaches are equivocal.

Evaluating the risk of return to the operating room across all elective orthopaedic procedures.

BACKGROUND: Although elective procedures have life-changing potential, all surgeries come with an inherent risk of reoperation. There is a gap in knowledge investigating the risk of reoperation across orthopaedics. We aimed to identify the elective orthopaedic procedures with the highest rate of unplanned reoperation and the reasons for these procedures having such high reoperation rates. METHODS: Patients in the NSQIP database were identified using CPT and ICD-10 codes. We isolated 612,815 orthopaedics procedures from 2018 to 2020 and identified the 10 CPT codes with the greatest rate of unplanned return to the operating room. For each index procedure, we identified the ICD-10 codes for the reoperation procedure and categorized them into infection, mechanical failure, fracture, wound disruption, hematoma or seroma, nerve pathology, other, and unspecified. RESULTS: Below knee amputation (BKA) (CPT 27880) had the highest reoperation rate of 6.92% (37 of 535 patients). Posterior-approach thoracic (5.86%) or cervical (4.14%) arthrodesis and cervical laminectomy (3.85%), revision total hip arthroplasty (5.23%), conversion to total hip arthroplasty (4.33%), and revision shoulder arthroplasty (4.22%) were among the remaining highest reoperation rates. The overall leading causes of reoperation were infection (30.1%), mechanical failure (21.1%), and hematoma or seroma (9.4%) for the 10 procedures with the highest reoperation rates. CONCLUSIONS: This study successfully identified the elective orthopaedic procedures with the highest 30-day return to OR rates. These include BKA, posterior thoracic and cervical spinal arthrodesis, revision hip arthroplasty, revision total shoulder arthroplasty, and cervical laminectomy. With this data, we can identify areas across orthopaedics in which revising protocols may improve patient outcomes and limit the burden of reoperations on patients and the healthcare system. Future studies should focus on the long-term physical and financial impact that these reoperations may have on patients and hospital systems. LEVEL OF CLINICAL EVIDENCE: IV.

Investigating the association between self-reported physical function, temporo-spatial parameters, walking kinematics and community-based ambulatory activity: Analysis of post-operative hip preservation patients.

INTRODUCTION: Wearable sensors provide the ability to assess ambulatory activity in the community after hip preservation surgery (HPS). In combination with gait analysis and patient reported outcomes, more perspective on post-operative function is gained. The purpose of this study was to assess the relationship between self-reported function/activity, temporo-spatial parameters and walking kinematics to objectively measured ambulatory activity. METHODS: Forty-nine participants (38 Females; age range 16-38 years) who were five years or more post-surgery and the following diagnoses were included: Acetabular Dysplasia (n=34), Femoroacetabular Impingement (n=12) and Legg-Calvé Perthes disease (n=3). Participants underwent 3D gait analysis and gait deviations were quantified using the Gait Deviation Index (GDI) and Gait Profile Score (GPS). Temporo-spatial parameters were also calculated. Self-reported pain/function and activity level were assessed via the Harris Hip Score (HHS) and UCLA Activity Scale (UCLA). Participants wore a StepWatch Activity Monitor in their community and the Intensity/Duration of ambulatory bouts were analyzed. Spearman correlation coefficients were run to assess the following relationships: in-lab walking measures, self-reported function/activity vs.community ambulatory activity. RESULTS: There were no statistically significant correlations between HHS, UCLA or temporospatial parameters with ambulatory activity (p>0.05). Worsening gait deviations (GDI/GPS scores) correlated with daily total ambulatory time (ρ=0.284/-0.284, p<0.05), time spent in Short duration ambulatory bouts (ρ=-0.321/0.321, p<0.05) and the amount of time in Long duration ambulatory bouts (ρ=0.366/-0.366, p<0.05). The amount of time spent in Easy intensity/Short duration and Easy intensity/Long duration ambulatory bouts did have a weak correlation with the GDI and GPS (p<0.05). CONCLUSIONS: In HPS patients after long-term follow up, ambulatory activity in the community did not correlate with patient reported outcomes but there was a weak correlation with the presence of gait deviations. Incorporating wearable sensors to assess community ambulatory bout intensity/duration, provides additional quantifiable measures into the overall function of patients following HPS.

Combining machine learning with high-content imaging to infer ciprofloxacin susceptibility in isolates of Salmonella Typhimurium.

Antimicrobial resistance (AMR) is a growing public health crisis that requires innovative solutions. Current susceptibility testing approaches limit our ability to rapidly distinguish between antimicrobial-susceptible and -resistant organisms. Salmonella Typhimurium (S. Typhimurium) is an enteric pathogen responsible for severe gastrointestinal illness and invasive disease. Despite widespread resistance, ciprofloxacin remains a common treatment for Salmonella infections, particularly in lower-resource settings, where the drug is given empirically. Here, we exploit high-content imaging to generate deep phenotyping of S. Typhimurium isolates longitudinally exposed to increasing concentrations of ciprofloxacin. We apply machine learning algorithms to the imaging data and demonstrate that individual isolates display distinct growth and morphological characteristics that cluster by time point and susceptibility to ciprofloxacin, which occur independently of ciprofloxacin exposure. Using a further set of S. Typhimurium clinical isolates, we find that machine learning classifiers can accurately predict ciprofloxacin susceptibility without exposure to it or any prior knowledge of resistance phenotype. These results demonstrate the principle of using high-content imaging with machine learning algorithms to predict drug susceptibility of clinical bacterial isolates. This technique may be an important tool in understanding the morphological impact of antimicrobials on the bacterial cell to identify drugs with new modes of action.

Association of Medical School Gap Year Research and Degree Programs With Otolaryngology Interview and Match Outcomes.

OBJECTIVE: To investigate whether a gap year for either research or a master's degree is associated with interview offers or match outcomes among otolaryngology applicants. METHODS: Using the Texas Seeking Transparency in Application to Residency (Texas STAR) database, we conducted a cross-sectional analysis of otolaryngology applicants from 2018 to 2022. Applicants were stratified based on the presence and type of gap year during medical school. Applicant characteristics, signaling, research productivity, and application costs were analyzed, with primary outcomes including number of interview offers and match status. RESULTS: Among 564 otolaryngology applicant respondents to the Texas STAR survey, 160 (28%) reported a gap year, including 64 (40%) applicants participating in a research year, 65 (41%) completing a Master of Public Health or Science (MPH and MSc), and 31 (19%) completing a Master of Business Administration, Education, or other degree (MBA and MEd). Gap-year applicants who completed a research year or MPH/MSc degree received more interview offers (P < .01) than MBA, MEd applicants, or those without a gap year. Applicants with a research year had the most publications, oral presentations, abstracts, posters, and research experiences (all P < .01). When controlling for USMLE scores, clerkship honors, and applications submitted, applicants completing a research year or an MPH/MSc-degree received increased interview offers (P < .01). No significant differences were seen in expenditures or match rates. CONCLUSIONS: Research and MPH/MSc gap years were associated with increased residency interview offers but not increased match success. Further longitudinal studies are needed to assess how yearlong experiences affect long-term career outcomes.