tbuckley/cabot-search huggingface dataset:
Maintenance Pembrolizumab Therapy in Patients with Metastatic HER2-negative Breast Cancer with Prior Response to Chemotherapy
Authors: Toshiaki Iwase, Evan N. Cohen, Hui Gao, Angela Alexander, Megumi Kai, Vivian Chiv, Xiaoping Wang, Savitri Krishnamurthy, Diane Liu, Yu Shen, Kumiko Kida, Alexandre Reuben, Rachel M. Layman, David L. Ramirez, Debasish Tripathy, Stacy L. Moulder, Clinton Yam, Vicente Valero, Bora Lim, James M. Reuben, Naoto T. Ueno
Journal: Clinical Cancer Research (2024)

Accumulating toxicities hinder indefinite chemotherapy for many patients with metastatic/recurrent HER2-negative breast cancer. We conducted a phase II trial of pembrolizumab monotherapy following induction chemotherapy to determine the efficacy of maintenance immunotherapy in patients with metastatic HER2-negative inflammatory breast cancer (IBC) and non-IBC triple-negative breast cancer (TNBC) and a biomarker study.
Acute Appendicitis—What’s Old Is New Again
Authors: Frederick Thurston Drake, Sabrina E. Sanchez
Journal: JAMA Surgery (2024)

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Long‐term efficacy and safety of tailored immunosuppressive therapy in immune‐mediated biopsy‐proven myocarditis: A propensity‐weighted study
Authors: Alida Linda Patrizia Caforio, Andrea Silvio Giordani, Anna Baritussio, Davide Marcolongo, Cristina Vicenzetto, Giuseppe Tarantini, Massimo Napodano, Giuseppe Toscano, Dario Gregori, Gloria Brigiari, Patrizia Bartolotta, Elisa Carturan, Monica De Gaspari, Stefania Rizzo, Cristina Basso, Sabino Iliceto, Renzo Marcolongo
Journal: European Journal of Heart Failure (2024)
Clinician Burnout and Effectiveness of Guideline-Recommended Psychotherapies
Authors: Nina A. Sayer, Adam Kaplan, David B. Nelson, Shannon Wiltsey Stirman, Craig S. Rosen
Journal: JAMA Network Open (2024)

Importance Clinician burnout has been associated with clinician outcomes, but the association with patient outcomes remains unclear. Objective To evaluate the association between clinician burnout and the outcomes of patients receiving of guideline-recommended trauma-focused psychotherapies for posttraumatic stress disorder (PTSD). Design, Setting, and Participants This cohort study was set at the US Veterans Affairs Health Care System and included licensed therapists who provided trauma-focused psychotherapies and responded to an online survey between May 2 and October 8, 2019, and their patients who initiated a trauma-focused therapy during the following year. Patient data were collected through December 31, 2020. Data were analyzed from May to September 2023. Exposures Therapists completing the survey reported burnout with a 5-point validated measure taken from the Physician Worklife Study. Burnout was defined as scores of 3 or more. Main Outcomes and Measures The primary outcome was patients’ clinically meaningful improvement in PTSD symptoms according to the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders ( Fifth Edition ). Patient dropout, therapist adherence, and session spacing was assessed through electronic health records. Multivariable random-effects logistic regression examined the association of therapist burnout and clinically meaningful improvement, adjusted for case-mix. Results In this study, 165 of 180 (91.7%) therapists (89 [53.9%] female) completed the burnout measure and provided trauma-focused psychotherapies to 1268 patients (961 [75.8%] male) with outcome data. Fifty-eight (35.2%) therapists endorsed burnout. One third of patients (431 [34.0%]) met criterion for clinically meaningful improvement. Clinically meaningful improvement in PTSD symptoms was experienced by 120 (28.3%) of the 424 patients seen by therapists who reported burnout and 311 (36.8%) of the 844 patients seen by therapists without burnout. Burnout was associated with lower odds of clinically meaningful improvement (adjusted odds ratio [OR],0.63; 95% CI, 0.48-0.85). The odds of clinically meaningful improvement were reduced for patients who dropped out (OR, 0.15; 95% CI, 0.11-0.20) and had greater session spacing (OR, 0.80; 95% CI, 0.70-0.92). Therapist adherence was not associated with therapy effectiveness. Adjusting for dropout or session spacing did not meaningfully alter the magnitude of the association between burnout and clinically meaningful improvement. Conclusions and Relevance In this prospective cohort study, therapist burnout was associated with reduced effectiveness of trauma-focused psychotherapies. Studying when and how burnout affects patient outcomes may inform workplace interventions.
Machine-learning–based plasma metabolomic profiles for predicting long-term complications of cirrhosis
Authors: Chengnan Guo, Zhenqiu Liu, Hong Fan, Haili Wang, Xin Zhang, Shuzhen Zhao, Yi Li, Xinyu Han, Tianye Wang, Xingdong Chen, Tiejun Zhang
Journal: Hepatology (2024)

Background and Aims: The complications of liver cirrhosis occur after long asymptomatic stages of progressive fibrosis and are generally diagnosed late. We aimed to develop a plasma metabolomic–based score tool to predict these events. Approach and Results: We enrolled 64,005 UK biobank participants with metabolomic profiles. Participants were randomly divided into the training (n=43,734) and validation cohorts (n=20,271). Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with HCC. An interpretable machine-learning framework was applied to learn the metabolomic states extracted from 168 circulating metabolites in the training cohort. An integrated nomogram was developed and compared to conventional and genetic risk scores. We created 3 groups: low-risk, middle-risk, and high-risk through selected cutoffs of the nomogram. The predictive performance was validated through the area under a time-dependent receiver operating characteristic curve (time-dependent AUC), calibration curves, and decision curve analysis. The metabolomic state model could accurately predict the 10-year risk of liver cirrhosis complications in the training cohort (time-dependent AUC: 0.84 [95% CI: 0.82–0.86]), and outperform the fibrosis-4 index (time-dependent AUC difference: 0.06 [0.03–0.10]) and polygenic risk score (0.25 [0.21–0.29]). The nomogram, integrating metabolomic state, aspartate aminotransferase, platelet count, waist/hip ratio, and smoking status showed a time-dependent AUC of 0.930 at 3 years, 0.889 at 5 years, and 0.861 at 10 years in the validation cohort, respectively. The HR in the high-risk group was 43.58 (95% CI: 27.08–70.12) compared with the low-risk group. Conclusions: We developed a metabolomic state–integrated nomogram, which enables risk stratification and personalized administration of liver-related events.
Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation
Authors: Wenqi Ma, Kangni Jia, Haomai Cheng, Hong Xu, Zhigang Li, Hang Zhang, Hongyang Xie, Hang Sun, Lei Yi, Zhiyong Chen, Shengzhong Duan, Motoaki Sano, Keiichi Fukuda, Lin Lu, Fei Gao, Ruiyan Zhang, Xiaoxiang Yan
Journal: Circulation Research (2024)

Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease, diabetes, and aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, is a key regulator in apo (apolipoprotein) A-IV-induced atherosclerosis progression; however, its role in vascular calcification is poorly understood.
Sialic acid-based probiotic intervention in lactating mothers improves the neonatal gut microbiota and immune responses by regulating sialylated milk oligosaccharide synthesis via the gut–breast axis
Authors: Yushuang Wang, Binqi Rui, Xiaolei Ze, Yujia Liu, Da Yu, Yinhui Liu, Zhi Li, Yu Xi, Xixi Ning, Zengjie Lei, Jieli Yuan, Liang Li, Xuguang Zhang, Wenzhe Li, Yanjie Deng, Jingyu Yan, Ming Li
Journal: Gut Microbes (2024)

Human milk oligosaccharides (HMOs) are vital milk carbohydrates that help promote the microbiota-dependent growth and immunity of infants. Sialic acid (SA) is a crucial component of sialylated milk oligosaccharides (S-MOs); however, the effects of SA supplementation in lactating mothers on S-MO biosynthesis and their breastfed infants are unknown. Probiotic intervention during pregnancy or lactation demonstrates promise for modulating the milk glycobiome. Here, we evaluated whether SA and a probiotic (Pro) mixture could increase S-MO synthesis in lactating mothers and promote the microbiota development of their breastfed neonates. The results showed that SA+Pro intervention modulated the gut microbiota and 6'-SL contents in milk of maternal rats more than the SA intervention, which promoted Lactobacillus reuteri colonization in neonates and immune development. Deficient 6'-SL in the maternal rat milk of St6gal1 knockouts (St6gal1−/−) disturbed intestinal microbial structures in their offspring, thereby impeding immune tolerance development. SA+Pro intervention in lactating St6gal1± rats compromised the allergic responses of neonates by promoting 6′-SL synthesis and the neonatal gut microbiota. Our findings from human mammary epithelial cells (MCF-10A) indicated that the GPR41-PI3K-Akt-PPAR pathway helped regulate 6′-SL synthesis in mammary glands after SA+Pro intervention through the gut – breast axis. We further validated our findings using a human-cohort study, confirming that providing SA+Pro to lactating Chinese mothers increased S-MO contents in their breast milk and promoted gut Bifidobacterium spp. and Lactobacillus spp. colonization in infants, which may help enhance immune responses. Collectively, our findings may help alter the routine supplementation practices of lactating mothers to modulate milk HMOs and promote the development of early-life gut microbiota and immunity.
Chronic Progressive Pink-Yellow Papules and Nodules in a Middle-Aged Man
Authors: Jessica A. Kern, Brian R. Hinds, Veronica Shi
Journal: JAMA Dermatology (2024)

A 38-year-old man presented with numerous pink-yellow firm papules and nodules on the bilateral elbows for 10 years spreading to the hands and knees in the past year. What is your diagnosis?
Visual Impairment and Suicide Risk
Authors: Chung Young Kim, Ahnul Ha, Sung Ryul Shim, In Hwan Hong, In Boem Chang, Young Kook Kim
Journal: JAMA Network Open (2024)

Importance Suicide is a substantial public health concern that involves various recognized contributing factors. Sensory impairments, specifically visual impairment, are deemed potential risk factors. Nonetheless, comprehensive information about associated risk levels and underlying determinants remains limited. Objective To investigate the association between visual impairment and different aspects of suicide, including the assessment of risk levels and exploration of potential contributing factors. Data Sources An electronic search was performed in the PubMed, EMBASE, Scopus, and Cochrane Library databases from their inception to February 8, 2024. Study Selection All published studies were considered without restrictions on study design, publication date, or language. Data Extraction and Synthesis Two independent reviewers extracted the published data using a standardized procedure in accordance with the Meta-analysis of Observational Studies in Epidemiology ( MOOSE ) and Preferred Reporting Items for Systematic Reviews and Meta-analyses ( PRISMA ) reporting guidelines. Random-effects meta-analyses were used to estimate pooled effect sizes. Multiple meta-regression analyses were conducted to identify potential factors contributing to the association between visual impairment and the risk of suicide. Main Outcomes and Measures The primary outcome measure was the odds ratio (OR) of suicidal behavior (including suicide attempt and suicide death) for individuals with visual impairment compared with those without. The secondary outcome measures were the pooled ORs of suicidal ideation and suicide death, respectively. Results A total of 31 population-based studies with 5 692 769 unique individuals (mean [SD] age, 48.4 [8.5] years; 2 965 933 females [52%]) were included. For 17 studies (5 602 285 individuals) that evaluated suicidal behavior, the pooled OR was 2.49 (95% CI, 1.71-3.63). For 21 studies (611 899 individuals) that assessed suicidal ideation, the pooled OR was 2.01 (95% CI, 1.62-2.50). For 8 studies (5 067 113 individuals) investigating the association between visual impairment and suicide death, the pooled OR was 1.89 (95% CI, 1.32-2.71). The multiple meta-regression model identified age group as a predictive factor associated with suicidal behavior, with the studies included suggesting that adolescents were at the highest risk. While this analysis showed moderate heterogeneity for suicide death, high heterogeneity was observed for suicidal behavior and suicidal ideation. Conclusions and Relevance The findings of this systematic review and meta-analysis support the association between visual impairment and increased risk of suicidal tendencies. The risk differed by age group, with a pronounced risk observed among adolescents.
A Patient With Type 1 Diabetes and Acute Rhinosinusitis
Authors: Francisco J. Machiavello Roman, Marwan M. Azar, Paul A. Trubin
Journal: JAMA (2024)

A 41-year-old with type 1 diabetes had generalized weakness, muffled voice, and slurred speech. Neck computed tomography showed soft-tissue gas in the nasopharynx and prevertebral fascia; examination of sinus mucosal samples identified numerous broad, nonseptate right-angled hyphae and fruiting bodies. What is the diagnosis and what would you do next?
Nociceptor spontaneous activity is responsible for fragmenting non–rapid eye movement sleep in mouse models of neuropathic pain
Authors: Chloe Alexandre, Giulia Miracca, Victor Duarte Holanda, Ashley Sharma, Kamila Kourbanova, Ashley Ferreira, Maíra A. Bicca, Xiangsunze Zeng, Victoria A. Nassar, Seungkyu Lee, Satvinder Kaur, Sridevi V. Sarma, Pierre Sacré, Thomas E. Scammell, Clifford J. Woolf, Alban Latremoliere
Journal: Science Translational Medicine (2024)

Spontaneous pain, a major complaint of patients with neuropathic pain, has eluded study because there is no reliable marker in either preclinical models or clinical studies. Here, we performed a comprehensive electroencephalogram/electromyogram analysis of sleep in several mouse models of chronic pain: neuropathic (spared nerve injury and chronic constriction injury), inflammatory (Freund’s complete adjuvant and carrageenan, plantar incision) and chemical pain (capsaicin). We find that peripheral axonal injury drives fragmentation of sleep by increasing brief arousals from non–rapid eye movement sleep (NREMS) without changing total sleep amount. In contrast to neuropathic pain, inflammatory or chemical pain did not increase brief arousals. NREMS fragmentation was reduced by the analgesics gabapentin and carbamazepine, and it resolved when pain sensitivity returned to normal in a transient neuropathic pain model (sciatic nerve crush). Genetic silencing of peripheral sensory neurons or ablation of CGRP + neurons in the parabrachial nucleus prevented sleep fragmentation, whereas pharmacological blockade of skin sensory fibers was ineffective, indicating that the neural activity driving the arousals originates ectopically in primary nociceptor neurons and is relayed through the lateral parabrachial nucleus. These findings identify NREMS fragmentation by brief arousals as an effective proxy to measure spontaneous neuropathic pain in mice.
Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub
Authors: Sung-mok Jung, Sara L. Loo, Emily Howerton, Lucie Contamin, Claire P. Smith, Erica C. Carcelén, Katie Yan, Samantha J. Bents, John Levander, Jessi Espino, Joseph C. Lemaitre, Koji Sato, Clifton D. McKee, Alison L. Hill, Matteo Chinazzi, Jessica T. Davis, Kunpeng Mu, Alessandro Vespignani, Erik T. Rosenstrom, Sebastian A. Rodriguez-Cartes, Julie S. Ivy, Maria E. Mayorga, Julie L. Swann, Guido España, Sean Cavany, Sean M. Moore, T. Alex Perkins, Shi Chen, Rajib Paul, Daniel Janies, Jean-Claude Thill, Ajitesh Srivastava, Majd Al Aawar, Kaiming Bi, Shraddha Ramdas Bandekar, Anass Bouchnita, Spencer J. Fox, Lauren Ancel Meyers, Przemyslaw Porebski, Srini Venkatramanan, Aniruddha Adiga, Benjamin Hurt, Brian Klahn, Joseph Outten, Jiangzhuo Chen, Henning Mortveit, Amanda Wilson, Stefan Hoops, Parantapa Bhattacharya, Dustin Machi, Anil Vullikanti, Bryan Lewis, Madhav Marathe, Harry Hochheiser, Michael C. Runge, Katriona Shea, Shaun Truelove, Cécile Viboud, Justin Lessler
Journal: PLoS Medicine (2024)

Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval).
Loneliness and Mortality Risk Among Cancer Survivors in the United States: A Retrospective, Longitudinal Study
Authors: Jingxuan Zhao, Jennifer B. Reese, Xuesong Han, K. Robin Yabroff
Journal: Journal of the National Comprehensive Cancer Network (2024)

Background: Loneliness, a subjective feeling of being isolated, is a prevalent concern for elderly people and more so among cancer survivors because a cancer diagnosis and its subsequent treatment may result in long-term adverse health effects. This study aimed to examine the association of loneliness and mortality risk among cancer survivors in the United States. Methods: We identified a longitudinal cohort of cancer survivors aged ≥50 years from the nationally representative panel surveys of the 2008–2018 Health and Retirement Study. Follow-up for vital status was through 2020. Loneliness was measured using an 11-item abbreviated version of the UCLA Loneliness Scale (Version 3), including questions about lacking companionship and feeling isolated from others. A score was assigned according to the responses to each question, with 1 for least lonely, 2 for moderately lonely, and 3 for the loneliest option. Items were summed to create total loneliness scores for each individual, which were categorized into 4 levels: 11–12 (low/no loneliness), 13–15 (mild loneliness), 16–19 (moderate loneliness), and 20–33 (severe loneliness) based on the sample distribution. Time-varying Cox proportional hazard models with age as a time scale were used to examine the association of loneliness and survival among cancer survivors. Results: A total of 3,447 cancer survivors with 5,808 person-years of observation were included, with 1,402 (24.3%), 1,445 (24.5%), 1,418 (23.6%), and 1,543 (27.6%) reporting low/no, mild, moderate, and severe loneliness, respectively. Compared with survivors reporting low/no loneliness, survivors reporting greater loneliness had a higher mortality risk, with the highest adjusted hazard ratios (aHRs) among the loneliest group (aHR, 1.67 [95% CI, 1.25–2.23]; P =.004) following a dose–response association. Conclusions: Elevated loneliness was associated with a higher mortality risk among cancer survivors. Programs to screen for loneliness among cancer survivors and to provide resources and support are warranted, especially considering the widespread social distancing that occurred during the COVID-19 pandemic.
Diffuse Pleural Mesotheliomas with Genomic Near-Haploidization: A Newly Recognized Subset with Distinct Clinical, Histologic, and Molecular Features
Authors: Soo-Ryum Yang, Gowtham Jayakumaran, Jamal Benhamida, Christopher A. Febres Aldana, Rachel Fanaroff, Jason Chang, Erika Gedvilaite, Liliana B. Villafania, Jennifer L. Sauter, Michael Offin, Marjorie G. Zauderer, Marc Ladanyi
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Diffuse pleural mesotheliomas (DPM) with genomic near-haploidization (GNH) represent a novel subtype first recognized by The Cancer Genome Atlas project; however, its clinicopathologic and molecular features remain poorly defined. Experimental Design: We analyzed clinical genomic profiling data from 290 patients with DPM using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay. Allele-specific copy number analysis was performed using the Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) algorithm. Results: A total of 210 patients were evaluable for loss of heterozygosity (LOH) analysis using FACETS from MSK-IMPACT tumor:normal sequencing data. In this cohort, GNH, defined as LOH across &amp;gt;80% of the genome, was detected in 10 cases (4.8%). Compared with non-GNH tumors, GNH DPMs were associated with younger age and less frequent self-reported history of occupational asbestos exposure. Histologically, GNH DPMs were enriched in biphasic subtype (80% vs. 14.5%) and showed abundant tumor-infiltrating lymphocytes (TILs). Genomic analysis revealed a higher frequency of TP53 alterations, whereas SETDB1 mutations were present in nearly all and only in this subset. The clinicopathologic and molecular findings were further validated in a separate cohort. Despite the younger age, patients with GNH DPMs had a shorter overall survival (10.9 vs. 25.4 months, P = 0.004); the poor prognostic impact of GNH remained significant after controlling for biphasic histology. Of three patients with GNH DPMs who received immune checkpoint blockade, two achieved a clinician-assessed partial response. Conclusions: GNH defines an aggressive subtype of mainly biphasic DPMs in younger patients with recurrent alterations in SETDB1 and TP53. The enrichment in biphasic histology and TILs, together with our preliminary immune checkpoint blockade response data and anecdotal clinical trial data, suggests that further evaluation of immunotherapy may be warranted in this subset.
Mutations in the splicing factor SF3B1 are linked to frequent emergence of HLA-DRlow/neg monocytes in lower-risk myelodysplastic neoplasms
Authors: Susann Winter, Marie Schneider, Uta Oelschlaegel, Giulia Maggioni, Elena Riva, Marco Gabriele Raddi, Sara Bencini, Benedetta Peruzzi, Desmond Choy, Rita Antunes Dos Reis, Esther Güse, Christopher Lischer, Julio Vera, Jessica A. Timms, Nicolas Sompairac, Katja Sockel, Antonella Poloni, Antje Tunger, Matteo Giovanni Della Porta, Valeria Santini, Marc Schmitz, Uwe Platzbecker, Shahram Kordasti
Journal: Leukemia (2024)