tbuckley/cabot-search huggingface dataset:
Molecular heterogeneity in urothelial carcinoma and determinants of clinical benefit to PD-L1 blockade
Authors: Habib Hamidi, Yasin Senbabaoglu, Niha Beig, Juliette Roels, Cyrus Manuel, Xiangnan Guan, Hartmut Koeppen, Zoe June Assaf, Barzin Y Nabet, Adrian Waddell, Kobe Yuen, Sophia Maund, Ethan Sokol, Jennifer M Giltnane, Amber Schedlbauer, Eloisa Fuentes, James D Cowan, Edward E Kadel, Viraj Degaonkar, Alexander Andreev-Drakhlin, Patrick Williams, Corey Carter, Suyasha Gupta, Elizabeth Steinberg, Yohann Loriot, Joaquim Bellmunt, Petros Grivas, Jonathan Rosenberg, Michiel S van der Heijden, Matthew D Galsky, Thomas Powles, Sanjeev Mariathasan, Romain Banchereau
Journal: Cancer Cell (2024)
Personalized phosphoproteomics of skeletal muscle insulin resistance and exercise links MINDY1 to insulin action
Authors: Elise J Needham, Janne R Hingst, Johan D Onslev, Alexis Diaz-Vegas, Magnus R Leandersson, Hannah Huckstep, Jonas M Kristensen, Kohei Kido, Erik A Richter, Kurt Højlund, Benjamin L Parker, Kristen Cooke, Guang Yang, Christian Pehmøller, Sean J Humphrey, David E James, Jørgen F P Wojtaszewski
Journal: Cell Metabolism (2024)

Type 2 diabetes is preceded by a defective insulin response, yet our knowledge of the precise mechanisms is incomplete. Here, we investigate how insulin resistance alters skeletal muscle signaling and how exercise partially counteracts this effect. We measured parallel phenotypes and phosphoproteomes of insulin-resistant (IR) and insulin-sensitive (IS) men as they responded to exercise and insulin (n = 19, 114 biopsies), quantifying over 12,000 phosphopeptides in each biopsy. Insulin resistance involves selective and time-dependent alterations to signaling, including reduced insulin-stimulated mTORC1 and non-canonical signaling responses. Prior exercise promotes insulin sensitivity even in IR individuals by "priming" a portion of insulin signaling prior to insulin infusion. This includes MINDY1 S441, which we show is an AKT substrate. We found that MINDY1 knockdown enhances insulin-stimulated glucose uptake in rat myotubes. This work delineates the signaling alterations in IR skeletal muscle and identifies MINDY1 as a regulator of insulin action.
A tale of two algorithms: Structured slots explain prefrontal sequence memory and are unified with hippocampal cognitive maps
Authors: James C R Whittington, William Dorrell, Timothy E J Behrens, Surya Ganguli, Mohamady El-Gaby
Journal: Neuron (2024)

Remembering events is crucial to intelligent behavior. Flexible memory retrieval requires a cognitive map and is supported by two key brain systems: hippocampal episodic memory (EM) and prefrontal working memory (WM). Although an understanding of EM is emerging, little is understood of WM beyond simple memory retrieval. We develop a mathematical theory relating the algorithms and representations of EM and WM by unveiling a duality between storing memories in synapses versus neural activity. This results in a formalism of prefrontal WM as structured, controllable neural subspaces (activity slots) representing dynamic cognitive maps without synaptic plasticity. Using neural networks, we elucidate differences, similarities, and trade-offs between the hippocampal and prefrontal algorithms. Lastly, we show that prefrontal representations in tasks from list learning to cue-dependent recall are unified as controllable activity slots. Our results unify frontal and temporal representations of memory and offer a new understanding for dynamic prefrontal representations of WM.
Interleukin-1α release during necrotic-like cell death generates myeloid-driven immunosuppression that restricts anti-tumor immunity
Authors: Kay Hänggi, Jie Li, Achintyan Gangadharan, Xiaoxian Liu, Daiana P Celias, Olabisi Osunmakinde, Aysenur Keske, Joshua Davis, Faiz Ahmad, Auriane Giron, Carmen M Anadon, Alycia Gardner, David G DeNardo, Timothy I Shaw, Amer A Beg, Xiaoqing Yu, Brian Ruffell
Journal: Cancer Cell (2024)
Arousal threshold modifies the effect of CPAP on executive function among individuals with obstructive sleep apnea
Authors: Andrey V. Zinchuk, Clete A. Kushida, Alexander Walker, Andrew Wellman, Ali Azarbarzin, Raichel M. Alex, Andrew W. Varga, Scott A. Sands, H. Klar Yaggi
Journal: European Respiratory Journal (2024)

Arousal Threshold Modifies the Effect of CPAP on Executive Function Among Individuals with Obstructive Sleep Apnea. Background Obstructive Sleep Apnea (OSA) is associated with neurocognitive dysfunction. However, randomized trials evaluating the effects of continuous positive airway pressure (CPAP) on neurocognition in those without dementia do not show a benefit. We thus aimed to assess whether arousal threshold (ArTH) modifies the effect of CPAP on neurocognitive function. Methods We performed a secondary analysis of a randomized, sham-controlled trial, Apnea Positive Pressure Long-term Efficacy Study. ArTH was estimated from polysomnography using a translatable method (Sands et al ., SLEEP 2018). Neurocognitive outcomes included the Sustained Working Memory Test-Overall-Mid-Day score (SWMT-OMD, executive function, primary outcome), with the Pathfinder Number Test – total time (attention) and Buschke Selective Reminding Test – sum recall (learning and memory) as secondary outcomes. Generalized linear modeling assessed whether the effect of CPAP was modified by baseline ArTH (treatment-by-ArTH interaction). 833 participants with OSA, [apnea-hypopnea index (AHI) ≥10 events/h], available ArTH, and outcomes were analyzed (CPAP n=437, Sham n=396). Results For executive function, the effect of CPAP treatment was modified by ArTH (p-interaction=0.042). Specifically, for every 1 sd increase in ArTH, the SWMT-OMD score improved by 0.10 95% CI (0.01, 0.18) in active compared to sham CPAP at 6 months; At ArTH 1 sd above the mean SWMT-OMD improvements were nearly three times that in those with average ArTH (0.139 [0.018, 0.261] versus 0.053 [-0.034, 0.140] respectively. No effect modification was observed for attention (p=0.311) or learning and memory (p=0.744). Conclusion In OSA, a higher ArTH is associated with greater improvements in executive function following CPAP therapy.
Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy in High-Grade Epithelial Ovarian Cancer
Authors: J. Alejandro Rauh-Hain, Alexander Melamed, René Pareja, Taymaa May, Abdulrahman Sinno, Leah McNally, Neil S. Horowitz, Pierandrea De Iaco, Chad M. Michener, Luc Van Lonkhuijzen, Maria D. Iniesta, Ying Yuan, Pedro T. Ramirez, Anna Fagotti
Journal: JAMA Network Open (2024)

Importance Despite the absence of high-quality evidence of its safety and effectiveness, minimally invasive surgery (MIS) is increasingly used to treat advanced epithelial ovarian cancer (EOC). Objective To assess the feasibility of conducting a full-scale randomized clinical trial (RCT) designed to compare the efficacy of MIS vs laparotomy in patients with advanced-stage EOC and a complete or partial response to neoadjuvant chemotherapy (NACT). Design, Setting, and Participants This lead-in pilot phase of LANCE (Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy), an international, open-label, noninferiority RCT, opened to enrollment in September 2020 and enrolled the 100th eligible patient in February 2023. It was conducted at 11 academic cancer centers in North America and Europe. Participants were adults with stage IIIC or IV epithelial ovarian, fallopian, or primary peritoneal carcinoma who had normal cancer antigen 125 levels and at least a partial radiologic response after 3 to 4 cycles of NACT. Patients were randomly assigned to receive either interval cytoreductive surgery performed using MIS or laparotomy. Data analysis was based on the evaluable population. Interventions The MIS arm underwent laparoscopic or robotic surgery, vs laparotomy for the control arm. Resection of all visible tumor was attempted, and conversion from MIS to laparotomy was performed when necessary to attain complete resection. Main Outcomes and Measures Trial feasibility was defined by 3 primary end points: patient accrual rate of at least 5.6 patients per month by the last month of the lead-in pilot phase, conversion from MIS to laparotomy in less than 25% of patients, and a difference in complete gross resection rates of fewer than 20 percentage points between study arms. Results One hundred women (median [IQR] age, 63 [39-82] years) were included, of whom 49 were randomly assigned to MIS and 51 to laparotomy; 95 were evaluable for surgical outcomes. Most patients (34 [67%] in the laparotomy arm, and 33 [67%] in the MIS arm) had stage IIIC cancer. The monthly accrual rate reached 5.9 patients per month in the final month of the study. Six of 48 evaluable patients (12.5%; 95% CI, 4.7%-25.2%) assigned to MIS underwent conversion to laparotomy. Surgeons achieved a complete gross resection rate in 42 of 48 evaluable patients (88%) assigned to MIS and in 39 of 47 patients (83%) assigned to laparotomy (difference, 4.5 [95% CI, −9.7 to 18.8] percentage points). Conclusions and Relevance Results of this lead-in pilot study indicated the feasibility of the LANCE RCT to compare the oncological outcomes of MIS vs laparotomy. Trial Registration ClinicalTrials.gov Identifier: NCT04575935
Integrated Studies on Male Reproductive Toxicity of Decabromodiphenyl Ethane in Zebrafish Spermatozoa <i>Ex Vivo</i> , Male Zebrafish <i>in Vivo</i> , and GC-1 Cells <i>in Vitro</i>
Authors: Lihua Yang, Yindan Zhang, Jianghuan Hua, Guili Song, Fan Li, Na Zheng, Taotao Zhang, Zhixiang Xu, Xinxin Ren, Biran Zhu, Yanna Han, Yongyong Guo, Jian Han, Bingsheng Zhou
Journal: Environmental Health Perspectives (2024)

Legacy brominated flame retardants have been recognized as risky factors leading to declined sperm quality. The widespread utilization of decabromodiphenyl ethane (DBDPE) as a replacement for decabromodiphenyl ether has given rise to considerable concern over its potential risks to reproductive health. The objectives were to quickly determine whether DBDPE affects sperm quality upon ex vivo exposure, to reveal the reproductive outcomes and underlying molecular mechanisms using an in vivo zebrafish model exposed to DBDPE, and to validate the potential impact on DNA damage and energy metabolism balance in vitro. Zebrafish spermatozoa were treated with DBDPE (0.01, 0.1, 1, 10μM) for 3 h, and the spermatozoa motility and fertilization ability with normal eggs were evaluated. Then adult male zebrafish were treated with DBDPE (0.1, 1, 10, and 100 nM) for 2 months, and their reproductive performance was examined. Four-dimensional label-free proteome and phosphoproteome were performed in zebrafish testes, and the findings were validated by multiple indicators. Finally, mouse spermatogonial GC-1 cells were treated with DBDPE (0.1, 1μM) for 72 h, and DNA damage was examined, as well as the energy production of glycolysis and oxidative phosphorylation. Ex vivo exposure to DBDPE caused lower motility and fertilization rates of zebrafish spermatozoa. In vivo exposure to DBDPE caused lower sperm motility and abnormal spermatogenesis in male zebrafish testes. Integrated whole-proteome and phosphoproteome analysis revealed DNA damage responses and energy metabolic disorders in zebrafish testes. A dosage window characterized by higher mitochondrial membrane potential (MMP) in combination with unchanged reactive oxygen species and apoptosis rates was observed in both zebrafish testes and GC-1 cells. This study suggests that in zebrafish, DBDPE exposure could impair sperm quality and spermatogenesis, and the underlying mechanism could be related to DNA damage and energy metabolic reprogramming in testicular germ cells. https://doi.org/10.1289/EHP14426.
Advances in the management of psoriatic arthritis in adults
Authors: Fadi Kharouf, Dafna D Gladman
Journal: BMJ (2024)

Abstract Psoriatic arthritis is an inflammatory arthritis that affects around 30% of patients with psoriasis. The disease spectrum includes peripheral arthritis, enthesitis, tenosynovitis, dactylitis, axial involvement, and skin and nail psoriasis in most patients. In addition to the cutaneous and musculoskeletal manifestations, several comorbidities can complicate the disease course, including cardiovascular disease, diabetes mellitus, metabolic syndrome, gout, anxiety, and depression. The management of patients with psoriatic arthritis begins with a careful assessment of the skin and joints and screening for comorbidities. This review describes the assessment tools and outcome measures used in the evaluation of patients with psoriatic arthritis. It summarizes the approach to therapy, including non-medicinal interventions such as education, lifestyle changes, physiotherapy, and occupational therapy. It discusses the evidence on pharmacologic treatments, including drugs used for symptomatic relief such as non-steroidal anti-inflammatory drugs, and those used to control the disease process; this last group comprises conventional synthetic disease modifying anti-rheumatic drugs (DMARDs), including methotrexate, leflunomide, and sulfasalazine, and biologic and targeted DMARDs, including anti-tumor necrosis factor (TNFα), anti-interleukin-17 (IL-17), anti-IL-12/23, and anti-IL-23 agents, as well as Janus kinase (JAK) inhibitors and phosphodiesterase 4 (PDE4) antagonists. Although these drugs are usually tailored to the clinical profile of the patient, biomarkers predictive of response to therapy are needed so that a more personalized approach can be followed.
Cancer cells restrict immunogenicity of retrotransposon expression via distinct mechanisms
Authors: Siyu Sun, Eunae You, Jungeui Hong, David Hoyos, Isabella Del Priore, Kaloyan M Tsanov, Om Mattagajasingh, Andrea Di Gioacchino, Sajid A Marhon, Jonathan Chacon-Barahona, Hao Li, Hua Jiang, Samira Hozeifi, Omar Rosas-Bringas, Katherine H Xu, Yuhui Song, Evan R Lang, Alexandra S Rojas, Linda T Nieman, Bidish K Patel, Rajmohan Murali, Pharto Chanda, Ali Karacay, Nicolas Vabret, Daniel D De Carvalho, Daniel Zenklusen, John LaCava, Scott W Lowe, David T Ting, Christine A Iacobuzio-Donahue, Alexander Solovyov, Benjamin D Greenbaum
Journal: Immunity (2024)
Obesity Prevention at an Early Age
Authors: Kevin G. Volpp
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Letting Go
Authors: David Haosen Xiang
Journal: JAMA Oncology (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Mapping of the T Cell Landscape of Biliary Tract Cancer Unravels Anatomical Subtype-Specific Heterogeneity
Authors: Jianhua Nie, Shuyuan Zhang, Ying Guo, Caiqi Liu, Jiaqi Shi, Haotian Wu, Ruisi Na, Yingjian Liang, Shan Yu, Fei Quan, Kun Liu, Mingwei Li, Meng Zhou, Ying Zhao, Xuehan Li, Shengnan Luo, Qian Zhang, Guangyu Wang, Yanqiao Zhang, Yuanfei Yao, Yun Xiao, Sheng Tai, Tongsen Zheng
Journal: Cancer Research (2024)

Abstract Biliary tract cancer (BTC), encompassing diseases such as intrahepatic (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC), is not only on the rise but also poses a significant and urgent health threat due to its high malignancy. Genomic differences point to the possibility that these subtypes represent distinct diseases. Elucidation of the specific distribution of T cell subsets, critical to cancer immunity, across these diseases could provide better insights into the unique biology of BTC subtypes and help identify potential precision medicine strategies. To address this, we conducted scRNA-seq and scTCR-seq on CD3+ T cells from 36 samples from 16 BTC patients across all subtypes and analyzed 355 pathological slides to examine the spatial distribution of T cells and tertiary lymphoid structures (TLS). Compared to ICC and GBC, ECC possessed a unique immune profile characterized by T cell exhaustion, elevated CXCL13 expression in CD4+ T helper-like and CD8+CXCL13+ exhausted T cells, more mature TLS, and fewer desert immunophenotypes. Conversely, ICC displayed an inflamed immunophenotype with an enrichment of interferon related pathways and high expression of LGALS1 in activated regulatory T cells, associated with immunosuppression. Inhibition of LGALS1 reduced tumor growth and Treg prevalence in ICC mouse models. Overall, this study unveils T cell diversity across BTC subtypes at the single-cell and spatial level that could open paths for tailored immunotherapies.
Physical Activity and All-Cause Mortality by Age in 4 Multinational Megacohorts
Authors: David Martinez-Gomez, Mengyun Luo, Yu Huang, Fernando Rodríguez-Artalejo, Ulf Ekelund, Mercedes Sotos-Prieto, Ding Ding, Xiang-Quian Lao, Verónica Cabanas-Sánchez
Journal: JAMA Network Open (2024)

Importance Physical activity (PA) guidelines recommend the same amount of PA through adulthood to live longer. Objective To explore whether there is an age-dependent association between PA and all-cause mortality and to investigate the age-dependent associations between other modifiable health factors (high educational level, not smoking, not regularly consuming alcohol, healthy body weight, and living without hypertension and diabetes) and mortality. Design, Setting, and Participants This cohort study used a pooled analysis of 4 population-based prospective cohorts (National Health Interview Survey, 1997-2018; UK Biobank, 2006-2010; China Kadoorie Biobank, 2004-2008; and Mei Jau, 1997-2016). Data were analyzed from June 2022 to September 2024. Exposures Self-reported leisure-time PA. Main Outcomes and Measures The primary outcome was deaths identified through follow-up linkage to national death registries. Analyses were performed for the total sample and by age groups (20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥80 years). Cox proportional hazards regression models with stratification by study were used to calculate mortality hazard ratios and their 95% CIs for the pooled dataset and by age group. Results A heterogeneous sample of 2 011 186 individuals (mean [SD] age, 49.1 [14.3] years; age range, 20-97 years; 1 105 581 women [55.0%]) were included. After a median (IQR) follow-up of 11.5 (9.3-13.5) years, 177 436 deaths occurred. The association between PA and mortality in the total sample showed a nonlinear dose-response pattern, but age modified this association ( P for interaction &amp;amp;lt;.001); PA was consistently associated with a lower risk of mortality across all age groups, but the reduction in risk was greater in older vs younger age groups, especially at high levels of PA. The hazard ratio for mortality associated with meeting the recommended PA in the total sample was 0.78 (95% CI, 0.77-0.79). This inverse association between meeting PA recommendations and mortality was somewhat greater as age increased ( P for interaction &amp;amp;lt;.001). Age also modified the associations of the other modifiable health factors with mortality (all P for interaction &amp;amp;lt;.001), but the magnitude of associations was greater in younger vs older age groups. Conclusions and Relevance In this pooled analysis of cohort studies, the association between PA and mortality risk remained consistent across the adult lifespan, which contrasts with other modifiable health factors, for which associations with mortality risk diminished with age. Given these findings, the promotion of regular PA is essential at all stages of adult life.
More on Waterpipe Tobacco Smoking and Cancer Mortality Content —Reply
Authors: Ngoan Tran Le, Jian-Min Yuan, Hung N. Luu
Journal: JAMA Oncology (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Dual impacts of serine/glycine-free diet in enhancing antitumor immunity and promoting evasion via PD-L1 lactylation
Authors: Huan Tong, Zedong Jiang, Linlin Song, Keqin Tan, Xiaomeng Yin, Chengyuan He, Juan Huang, Xiaoyue Li, Xiaofan Jing, Hong Yun, Guangqi Li, Yunuo Zhao, Qianlong Kang, Yuhao Wei, Renwei Li, Zhiwen Long, Jun Yin, Qiang Luo, Xiao Liang, Yanzhi Wan, Aiping Zheng, Nan Lin, Tao Zhang, Jiayi Xu, Xinggang Yang, Yuting Jiang, Yueyi Li, Yu Xiang, Yu Zhang, Lusi Feng, Zhen Lei, Hubing Shi, Xuelei Ma
Journal: Cell Metabolism (2024)