搜索结果：Francisco

Professional society patient education materials frequently exceed recommended literacy levels, limiting equitable health information access. This study aimed to compare the readability, information quality, understandability, and actionability of artificial intelligence (AI)-generated patient education materials versus professional society materials across gastroenterology, surgery, ophthalmology, and anesthesiology. We conducted a cross-sectional comparative analysis of 100 paired topics (25 per specialty), comparing professional society materials with the responses generated by ChatGPT (OpenAI, San Francisco, California, United States) under standardized conditions. Readability was assessed using the Flesch-Kincaid grade level, information quality with DISCERN, and understandability and actionability with the Patient Education Materials Assessment Tool (PEMAT). Paired two-sided t-tests assessed within-specialty differences. In surgery, AI-generated materials had lower reading levels and higher quality, understandability, and actionability (all p<0.001). In anesthesiology, AI materials were more readable (p<0.001) with no differences in other measures. In ophthalmology, AI improved readability (p<0.001), while professional society materials had higher quality and understandability (p<0.01) with no difference in actionability. In gastroenterology, AI materials had higher reading levels (p<0.001) with no differences in quality or usability. The performance of AI-generated patient education materials varied by specialty and appeared to depend on the structure and complexity of clinical content. AI improved readability in several domains, but these gains were not uniform across specialties, particularly in areas requiring more complex or longitudinal explanations.

&#xa0;Artificial intelligence (AI) tools like ChatGPT (OpenAI, San Francisco, USA) are increasingly influencing medical education, yet their use among undergraduate students in Western India remains underexplored. This study aimed to assess students' acceptance, usage patterns, and key factors influencing AI adoption to support effective curriculum integration. This cross-sectional, questionnaire-based study evaluated attitudes toward and use of AI&#xa0;among undergraduate medical students from first year to final year. A structured 37-item English questionnaire was developed via Google Forms (Google LLC, Mountain View,&#xa0;USA) and distributed online using electronic channels, with informed consent obtained. Data were managed in Microsoft Excel 2013 (Microsoft Corp., Redmond, USA) and analyzed using GraphPad Prism version 10.6 (GraphPad Software, Boston, USA; www.graphpad.com), yielding key insights into perceptions and use of AI. This study was conducted among 791 medical students, with a mean age of 19.92 &#xb1; 1.64 years. Of these,&#xa0;701 (88.62%) participants engaged with AI, relying predominantly on social media (425 (53.72%)) and faculty lectures (199 (25.15%)) for information. Moreover, 784 (99.11%) participants showed high AI awareness. Multivariable logistic regression demonstrated that AI use was strongly associated with behavior (odds ratio (OR)=356.9; 95% confidence interval (CI): 77.83-6329), perceived usefulness (OR=18.5; 95% CI: 40.68-327), and inversely with perceived risk (OR=0.06; 95% CI: 0.003-0.31). Students more than 20 years of age, male participants, and consistent AI users showed significantly higher usefulness and strong positive attitudes. Notably, first-year students reported a higher perception of risk compared to their peers, underscoring significant variations in AI adoption and perception. &#xa0;The use of AI models among Western Indian undergraduate medical students and their attitudes were investigated in this study. Although there was variation in students' comprehension of AI-related concepts, the majority of students reported being aware of and having previously used AI tools, mostly through social media platforms. The use of AI and opinions of AI models were correlated with age, gender, academic year, perceived utility, and behavior. The results demonstrate the potential value of responsible and ethical AI guidance in medical education and may offer initial institutional-level insights for future multicentric research and curriculum development.

Patients navigating a fragmented health care system may feel increasingly tempted to turn to publicly available large language models for quick answers to clinical questions; however, these tools were not built with patient safety, risk stratification, or escalation pathways in mind. In this case study, the authors describe how Included Health designed, piloted, and clinically governed a risk-stratified artificial intelligence (AI) digital assistant that offered generalized health guidance while reliably routing higher-risk situations to human clinicians. Building on OpenAI's generative pretrained transformer 4 (GPT-4) model, the team created a multitier risk classification engine that separated emergency, high-risk, and standard-risk patient inquiries; developed conservative safety guardrails that blocked AI advice and triggered escalation for concerning symptoms; and ran a continuous human-in-the-loop audit program that reviewed 100% of clinical interactions during the pilot. Using a randomized rollout to half of the patient population, the authors found that the risk-stratified assistant maintained a high level of clinical safety (96% accurate guidance, 0% critical safety events, and no AI-generated diagnoses) while reducing standard-risk queries routed to human support by 65%, shortening average human response times from 9.6 to 3.6 minutes, and improving resolution of health inquiries without additional visits. This blueprint illustrates how health care organizations can pair proactive risk analysis, adversarial testing, and ongoing governance to deploy patient-facing generative AI that is explicitly designed to put safety ahead of convenience and still meet patients' expectations for timely, trustworthy guidance.

The ability of varespladib (VPL), a phospholipase A2 (PLA2) inhibitor, to attenuate several activities of the Amazon coral snake (Micrurus spixii) venom was assessed. The neutralization by VPL was compared to that of coral snake antivenom and, in some cases, neostigmine. The venom showed anticoagulant activity in human plasma (assessed using in vitro thromboelastometry), and was myotoxic (based on the increase in serum creatine kinase activity) and lethal to mice, in addition to causing neuromuscular blockade in chick isolated biventer cervicis preparations. Antivenom fully protected against lethality but only partially neutralized the other activities at the doses tested. VPL attenuated PLA2-dependent effects, including anticoagulant activity and myotoxicity, but did not abrogate lethality. A combination of VPL and antivenom was also effective against anticoagulant activity and myotoxicity. Antivenom and VPL were partially effective for inhibiting the neuromuscular blockade induced by the venom, suggesting that toxins other than PLA2s might be also involved. Antivenom and Varespladib combined have a higher inhibition than each of them alone against anticoagulant, myotoxic and neuromuscular blocking effects. Neostigmine, an anticholinesterase drug, showed only modest protection against lethality and neuromuscular blockade. These findings suggest that VPL could be a potential adjunct to conventional antivenom therapy in treating envenomation by M. spixii.

Access to audiological services and support for individuals with hearing loss varies widely across low- and middle- income countries (LMICs) and high-income countries (HICs). This study examines disparities in the availability of audiological services across World Bank income groups. An international cross-sectional survey was developed and distributed by the Global Otolaryngology Head and Neck Surgery Initiative. The survey evaluated the availability of audiology and support services across countries. Multiple responses from one country were combined into one entry. Statistical significance between groups was assessed using chi-squared tests.Study Sample: A total of 135 responses were received from 47 countries (30 LMICs and 17 HICs). Significant disparities were identified across most service categories. HICs reported greater availability of newborn hearing screening, diagnostic tests, paediatric and adult hearing assessments, vestibular services, and hearing technologies compared to LMICs. Advanced diagnostic tools and hearing devices such as cochlear implants were significantly more accessible in HICs. Substantial differences were observed in audiological and rehabilitative services across HICs and LMICs. Efforts to bridge significant gaps are essential for achieving equitable hearing health care worldwide.

Olverembatinib (HQP1351) is a potent third-generation (3G) tyrosine kinase inhibitor (TKI) that binds to both the active and inactive conformations of native ABL1 and mutant BCR::ABL1. It was developed as a potent inhibitor with activity against wild-type and mutated BCR::ABL1 for chronic myeloid leukemia (CML) patients. It is effective against the T315I mutation, which confers resistance to first and second generation TKIs. The results of clinical trials in China have led to olverembatinib approval by China's regulatory authority, National Medical Products Administration (NMPA), for adult patients with TKIresistant chronic phase (CP) or accelerated phase (AP) CML harboring the T315I mutation and for adult CP CML patients with resistance or intolerance to imatinib or 2G TKIs. Olverembatinib has also received breakthrough therapy designation by the NMPA in combination with low intensity chemotherapy for the first-line treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Global studies of olverembatinib are underway in CML and Ph +ALL, with the results of the US phase 1b study published in 2025. This review will summarize the safety, tolerability, and efficacy of olverembatinib in CML and Ph+ ALL in China and globally and discuss the role of olverembatinib among existing therapeutics and its future development.

Heterozygous mutations of the gene encoding caspase-8 protease occur in 10% of human head and neck squamous cell carcinomas (HNSCCs). Cell line studies indicate that these mutations block apoptosis induced by death ligands. However, the in vivo role of caspase-8 mutations in the development of HNSCC and their impact on response to immune checkpoint blockade have not been determined. We generated mice with heterozygous, epithelium-specific knock-in of a representative, HNSCC-associated caspase-8 mutation (D305G). The impact of the caspase-8 mutation was assessed following treatment with the carcinogen 4-nitroquinoline-1-oxide (4NQO) in drinking water. Treatment of the D305G caspase-8 mutant mice with 4NQO resulted in a greater number of tongue tumors per mouse and a higher percentage of advanced-stage invasive carcinomas than was observed in 4NQO-treated mice with wild-type caspase-8, and tumors from the mutant mice were more resistant to anti-PD-1. We also engineered the murine oral cancer cell line MOC1 for heterozygous expression of caspase-8 mutations. Tumors generated from these engineered cells in syngeneic, immunocompetent mice demonstrated reduced responsiveness to anti-PD-1, relative to tumors with wild-type caspase-8. Further, the caspase-8 mutant tumors displayed reduced intratumoral and splenic CD8+ T cells and impaired recruitment of monocytes and dendritic cells during PD-1 blockade. Collectively, these findings demonstrate that caspase-8 mutation promotes carcinogen-induced HNSCC development and resistance to anti-PD-1. Investigation of caspase-8 mutations as potential biomarkers of poor response to immunotherapy in patients with HNSCC is warranted.

MORPHEUS-UC (NCT03869190) is a signal-seeking, global, phase Ib/II, open-label, multicenter, randomized, umbrella study in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC). Patients were randomly assigned to one of seven atezolizumab (anti-programmed death-ligand 1)-based treatment combinations or atezolizumab monotherapy. We report efficacy and safety results for atezolizumab + sacituzumab govitecan (trophoblast cell surface antigen-2-directed antibody conjugate) versus atezolizumab alone. Eligible patients were checkpoint inhibitor-na&#xef;ve and experienced disease progression or recurrence during or after &#x2264;1 platinum-containing regimen. Primary endpoints were investigator-assessed objective response rate (ORR) and safety. Secondary efficacy endpoints included investigator-assessed progression-free survival (PFS), duration of response, disease control rate, and overall survival (OS). Fifteen patients received atezolizumab + sacituzumab govitecan; 30 received atezolizumab alone. The best confirmed ORR was 6.7% with atezolizumab + sacituzumab govitecan and 27.6% with atezolizumab. No improvement in ORR, PFS, or OS was seen with the addition of sacituzumab govitecan to atezolizumab. Most frequent treatment-related adverse events (TRAEs) were anemia, neutropenia, pruritus, nausea, and alopecia with atezolizumab + sacituzumab govitecan, and pruritus, decreased appetite, rash, and fatigue with atezolizumab. No grade 5 TRAEs occurred. The atezolizumab + sacituzumab govitecan efficacy and safety results suggest limited rationale for further development of this combination in platinum-experienced patients with locally advanced or mUC.

Gastropleural fistulas (GPFs) are rare pathologic communications between the stomach and the pleural cavity and are associated with high morbidity and limited success with conventional surgical repair. We aimed to describe the successful management of a complex, refractory GPF using a multimodal endoscopic approach. A 27-year-old man with traumatic diaphragmatic rupture and multiple failed surgical repairs was referred to our tertiary endoscopy center. Endoscopic evaluation confirmed a gastric-to-pleural fistula. A sequential strategy was used: initial endoscopic negative pressure therapy using a modified nasogastric vacuum system, followed by closure with an over-the-scope (OTS) clip. Negative pressure therapy promoted granulation tissue formation and reduction of fistula output. Deployment of an OTS clip achieved complete sealing of the orifice, with no further thoracic drainage. Total endoscopic therapy lasted 28 days. The patient was discharged in good clinical condition. At 6-month follow-up, he remained asymptomatic, with endoscopy confirming a well-healed scar and no recurrence. Multimodal endoscopic therapy combining negative pressure therapy and OTS clip placement represents a safe and minimally invasive option for complex GPFs refractory to surgery. This case highlights the growing role of advanced endoscopic techniques in the management of challenging gastrointestinal fistulas.

Patients with psychiatric emergencies experience emergency department (ED) lengths of stay 3 times longer than those with nonpsychiatric complaints, contributing to crowding and inefficiency. We evaluated whether a novel staffing model, the Psychiatric Model of Care, reduced length of stay for these patients. This quality improvement study used an interrupted time series design at a tertiary, urban academic medical center to analyze deidentified ED encounters from January 1, 2023, to December 31, 2024, spanning preimplementation, roll-out, and postimplementation periods. The model embedded psychiatry-specialized nurse practitioners and support staff in the ED 24/7 for assessment, crisis stabilization, and disposition planning. Adults with a psychiatric chief complaint, psychiatry consultation, or an involuntary psychiatric hold were included. The primary outcome was ED length of stay (time from rooming to final disposition) analyzed using segmented quantile regression. Among 5,222 encounters, median ED length of stay decreased from 8.35 hours (IQR 3.76-18.35 hours) to 5.61 hours (IQR 3.00-10.24 hours), with an adjusted median difference of -1.64 hours (95% confidence interval [CI] -3.15 to -0.13). The largest reductions occurred for patients on 72-hour (-9.66 hours; 95% CI -12.92 to -6.40) and 14-day (-18.80 hours; 95% CI -52.76 to -10.67) involuntary holds, and those transferred to psychiatric facilities (-4.80 hours; 95% CI -10.46 to -1.88). Differences were not significant for patients without holds or those discharged or admitted. The Psychiatric Model of Care significantly reduced ED length of stay for patients with psychiatric emergencies, suggesting a promising approach to improve patient flow and care delivery.

Diet is a source of environmental toxicants; however, chemical exposures are not considered in the United States Dietary Guidelines for Americans (DGA). We tested whether higher DGA adherence was associated with gestational chemical exposures. Pregnant participants in the Environmental influences on Child Health Outcomes Cohort completed a food frequency questionnaire or 24-h recall at a median of 21 wk of gestation, which we used to calculate the Healthy Eating Index (HEI)-2015 total and individual component scores to assess DGA adherence. In spot urine samples collected at a median of 22 wk of gestation, we measured 113 analytes representing 10 chemical classes, including insecticides, fungicides/herbicides, organophosphate esters (OPEs), halogenated phenols, benzophenones, bisphenols, parabens, antimicrobials, phthalates/alternatives, and polycyclic aromatic hydrocarbons (PAHs). Using Bayesian generalized linear mixed-effects regression, we estimated covariate-adjusted percentage differences (&#x3b2;; biomarkers with &#x2265;70% detection) or detection risk ratios (biomarkers with 30%-69% detection) and 95% credible intervals (CrIs) in urinary chemical biomarker concentrations for each 10-point increase in HEI-2015 total score. We used quantile-based g-computation to identify the top HEI-2015 component contributors to associations. Most participants (n = 1492) self-identified as non-Hispanic White (40%) or Black (36%), and 50% had incomes &#x2265;$50,000. The median (25th, 75th percentile) HEI-2015 score was 61.9 points (53.6, 70.2; of 100). We detected 53 analytes, representing 45 chemical biomarkers, in >30% of participants. Higher HEI-2015 scores were associated with lower OPE, halogenated phenol, bisphenol, phthalate, and PAH biomarker concentrations, most notably monobenzyl phthalate (&#x3b2;: -13.5%; 95% CrI: -21.0%, -5.8%). However, higher HEI-2015 scores were also associated with higher insecticide, paraben, and benzophenone biomarker concentrations, most notably benzophenone-3 (&#x3b2;: 16.2%; 95% CrI: 5.9%, 26.8%). Lower added sugar and higher protein, vegetable, fruit, and whole-grain intake were consistent predictors of lower or higher chemical biomarker concentrations. Greater DGA adherence may minimize exposure to some, but not all, toxicants.

Precision medicine has revolutionized oncology; however, tumor biomarkers are not reflective of the heterogeneous cancer population. We evaluated NRG Oncology prostate cancer (PCa) clinical trials for demographic differences among patients with optional biospecimen collection (BC) consent and biospecimen submission (BSub). Data from 19 NRG PCa clinical trials closed before 2015 were analyzed. Patients who consented to BC and completed BSub were evaluated by race, ethnicity, median income, area deprivation index (ADI; categorized as highest v lowest three quartiles), age at enrollment, site, and year of enrollment. T/chi-square tests were used for continuous/categorical variables, respectively, followed by logistic regression. Of the 15,648 randomized patients eligible for BC, 11,796 (75%) had specimens submitted. In all, 4,598 (82.2%) of 5,597 eligible patients consented for optional BC in nine clinical trials with a separate BC consent process (consent rates by race/ethnicity: 74.1% Black, 72.8% Hispanic/Latino, 83.8% White). A smaller proportion of Black and Hispanic/Latino patients consented to optional BC compared with those who did not (12.1% v 19.5% Black, P < .0001; 3.5% v 5.8% Hispanic, P = .0006). In univariable logistic regression models, high ADI (more socioeconomic disadvantage) was associated with a decreased likelihood for optional BC consent (odds ratio [OR], 0.67 [95% CI, 0.55 to 0.82]; P = .02), but not a decreased likelihood for BSub (OR, 0.74 [95% CI, 0.53 to 1.04]; P = .08). Multivariable models demonstrated that Black/Hispanic/Latino patients were less likely to consent to optional BC, and Black patients were less likely to have BSub (P < .05 for all). White/non-Hispanic patients and those with less socioeconomic disadvantage were more likely to consent to optional BC, whereas Black patients were less likely to have BSub. Targeted solutions are needed to improve biorepository representation so that precision medicine approaches better reflect the cancer population.

To evaluate the incidence, timing, and clinical predictors of radiation-induced hematuria following robotic stereotactic body radiation therapy (SBRT) for localized prostate cancer. This retrospective single-center cohort study included 397 patients treated with robotic SBRT between 2013 and 2019 for localized prostate cancer. All patients received 36.25&#x2009;Gy in 5 fractions with the urethral sparing technique. Radiation-induced hematuria was defined as gross hematuria or clinically significant microscopic hematuria without alternative etiology. Incidence, time to first event, and related interventions were assessed. Severity was graded using CTCAE version 5.0. Candidate predictors were selected based on the literature. Cox proportional hazards modeling identified clinical predictors of radiation-induced hematuria. At a median follow-up of 56&#x2009;months (IQR 29-79), 48 patients (12.1%) developed radiation-induced hematuria, occurring at a median of 30&#x2009;months (IQR 19-49) after radiation treatment. Severe events (grade 3) were rare, affecting only 5 patients (1.3%). Diagnostic cystoscopy was performed in 35 patients (72.9%) and 6 patients (12.5%) required a total of 10 therapeutic interventions. Diabetes was the only independent predictor (HR 2.63, 95% CI 1.37-5.00, p&#x2009;=&#x2009;0.004), while age, anticoagulant use, prostate volume, and Charlson Comorbidity Index showed no significant association. Radiation-induced hematuria following robotic SBRT is predominantly low-grade and late-occurring, confirming the favorable genitourinary toxicity profile. These findings help clinicians better understand this SBRT-related toxicity and provide more accurate patient counseling regarding timing and severity of potential hematuria. Diabetes was identified as an independent risk factor and may have clinical implications; however, whether optimization of glycemic control reduces hematuria risk remains uncertain and requires further investigation.

TDP-43 proteinopathy is a hallmark of neurodegenerative disorders such as amyotrophic lateral sclerosis and frontotemporal dementia where mislocalization of TDP-43 has been observed in neurons and glial cells. However, the role of TDP-43 in microglia and the consequences of its loss of function remain unexplored. Combining magnetic resonance imaging, and confocal, and electron microscopy, we uncovered structural changes and myelin abnormalities in the early postnatal brain of mice lacking microglial TDP-43. Spatial transcriptomics further revealed an enriched interferon-responsive signature associated with oligodendrocyte dysfunction. Early depletion of microglial TDP-43 led to motor deficits in adult mice. Mechanistically, knocking out TDP-43 impaired microglial ability to engulf and degrade myelin. It also led to cryptic exon inclusion in the Tyrobp mRNA, resulting in truncated DAP12 protein, thus causing defective TREM2 signaling. Our findings reveal a role for TDP-43 in regulating the TREM2-DAP12 axis in mice, highlighting a previously unrecognized mechanism through which TDP-43 controls microglial function.

While studies outside general surgery (GS) have investigated applicant experiences with preference signaling, more data are needed regarding GS-specific applicant experiences. We aimed to describe, in the current 15-signal system, (1) how GS applicants allocate signals and (2) the applicant-perceived impact of signaling. An anonymous, voluntary survey was distributed electronically by the Association of American Medical Colleges to all applicants to GS residency in the 2024 to 2025 cycle (inclusive of applicants from allopathic, osteopathic, Caribbean, and international medical schools). Survey items were developed based on a previous qualitative study of applicant signaling experiences. Descriptive analysis was performed. Electronic survey was administered to US GS residency applicants. Overall, 249 applicants to categorical GS programs (58% female, 30% racially under-represented, 53% US MD) from the 2024 to 25 cycle responded to the survey (8.4% response rate). Program culture and location were applicants' most important considerations when allocating signals. Applicants spread signals out across program competitiveness, signaling a median of 5 target, 5 reach, and 2 safety programs. Of applicants with a home GS program (n&#x202f;=&#x202f;131), 26% were told to signal their home program to be considered for an interview with 33% actually allocating a signal. Of applicants who completed an away rotation (n&#x202f;=&#x202f;118), 79% signaled their away institution, but only 45% were instructed by their away program to signal for interview consideration. Applicants attended a median of 6 interviews at signaled programs and 4 interviews at nonsignaled programs. Of matched applicants (n&#x202f;=&#x202f;188), 68% matched at a signaled program. Although applicants saw signals as significantly more beneficial to programs (median&#x202f;=&#x202f;8/10, 10&#x202f;=&#x202f;high benefit) than applicants (median&#x202f;=&#x202f;6/10, p&#x202f;<&#x202f;0.001), 83% of applicants felt that signaling should continue. With respect to the future of signaling, applicants reported that a median of 0 programs provided transparency regarding their use of signals, but felt program transparency in the future would be useful (median&#x202f;=&#x202f;5/5, 5&#x202f;=&#x202f;extremely useful). While applicants feel that signaling is more beneficial for programs than applicants, the majority want signaling to continue. Applicants highlight the current lack of and need for transparency from programs regarding how signals are used when reviewing applications.

Status epilepticus (SE) is a neurological emergency associated with high morbidity and mortality. Benzodiazepines (BZDs) are recommended as first-line treatment within minutes of seizure onset; however, treatment delays remain common, particularly in low- and middle-income countries, where data regarding determinants of refractory status epilepticus (RSE) are limited. We conducted a retrospective single-center cohort study including consecutive patients aged&#xa0;&#x2265;&#xa0;16&#xa0;years with SE. The primary objective was to identify factors associated with progression to RSE, with particular focus on latency to first BZD administration. Multivariable logistic regression analysis was performed. A total of 109 SE episodes were analyzed, of which 62 (56.9&#xa0;%) progressed to RSE. Early BZD administration (&#x2264;30&#xa0;min) occurred in 34.9&#xa0;% of cases, whereas latency was undocumented in 14.7&#xa0;%. Early treatment was more frequent in non-RSE than RSE episodes (48.9&#xa0;% vs 24.2&#xa0;%), while unknown latency was more common in RSE cases than non-RSE (22.6&#xa0;% vs 4.3&#xa0;%; p&#xa0;<&#xa0;0.01). Two multivariable models were built, differing in how time to BZD was coded. In Model 1 (three-level time-to-BZD variable), undocumented latency was associated with RSE (OR&#xa0;=&#xa0;9.3, 95&#xa0;%CI:1.77-49.0; p&#xa0;=&#xa0;0.01); administration beyond 60&#xa0;min (OR&#xa0;=&#xa0;2.4, 95&#xa0;% CI:0.91-6.63; p&#xa0;=&#xa0;0.09) and acute symptomatic etiology (OR&#xa0;=&#xa0;2.2, 95&#xa0;%CI:0.96-5.0; p&#xa0;=&#xa0;0.06) were not. In Model 2 (dichotomized time-to-BZD), acute symptomatic etiology was independently associated with RSE (OR&#xa0;=&#xa0;2.3, 95&#xa0;%CI:1.05-5.22; p&#xa0;=&#xa0;0.04). Undocumented latency to BZD administration and acute symptomatic etiology were independently associated with RSE, highlighting challenges of timely SE recognition and supporting efforts to standardize treatment pathways in resource-limited settings.

While scientific environments have been described as unwelcoming to the LGBTQ+ community, and fields such as physics have systematically documented these challenges, the climate in biology-specific workplaces has not exclusively been assessed. We conducted the largest survey to date of LGBTQ+ biologists to examine how their sense of belonging and perception of climate in the biology workplace and professional societies compare to that of their straight and cis peers. In 2023, we surveyed 1419 biologists across five professional societies, with 486 identifying as LGBTQ+. Trans and gender non-conforming (TGNC) biologists reported lower belonging and morale within the workplace, professional societies, and the biology community compared with cis, straight biologists. They also reported being less comfortable with the climate of various professional biology environments. While LGBTQ+ biologists report that their workplaces are moderately inclusive, over 20% of all LGBTQ+ biologists and nearly 40% of TGNC biologists experience exclusionary behavior at work. This landmark survey provides the first comprehensive analysis of the LGBTQ+ climate in biology, revealing specific challenges faced by TGNC scientists.

暂无摘要（点击查看详情）

Impaired mitochondrial proteostasis underlies a broad spectrum of diseases, yet effective therapies remain limited. Here we show that deficiency of HTRA2, a mitochondrial intermembrane space protease, can be rescued by hypoxia therapy. Using an Htra2 mutant mouse model that displays severe neurodegeneration and early lethality, we find that continuous hypoxia rescues striatal degeneration and extends lifespan. Mechanistically, we demonstrate that HTRA2 forms a functional complex with the disaggregase CLPB. Loss of function of either protein drives aggregation of intermembrane space-facing subunits of complex I of the electron transport chain, resulting in secondary complex I dysfunction. These changes impair tissue oxygen consumption and probably cause pathological hyperoxia, which is corrected by hypoxia. Together, these findings define a proteostasis pathway linking intermembrane space quality control to complex I function and expand the potential of hypoxia therapy to secondary complex I disease.