tbuckley/cabot-search huggingface dataset:
Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer—Cyclin-Dependent Kinase 4 and 6 Inhibitors: ASCO Guideline Rapid Recommendation Update
Authors: Rachel A. Freedman, Jennifer L. Caswell-Jin, Michael Hassett, Mark R. Somerfield, Sharon H. Giordano, Mariana Chavez-MacGregor, Amy H. Comander, Zoneddy Dayao, Andrea Eisen, Rachel A. Freedman, Ragisha Gopalakrishnan, Stephanie L. Graff, Michael J. Hassett, Tari A. King, Gary H. Lyman, Gillian Rice Maupin, Cheryl L. Perkins, Melinda L. Telli, Maureen E. Trudeau, Antonio C. Wolff, Sharon H. Giordano
Journal: Journal of Clinical Oncology (2024)

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In This Issue of <i>Diabetes Care</i>
Authors: Max Bingham
Journal: Diabetes Care (2024)

Continued Use of SGLT2 Inhibitors in Hospital Settings Reduces Mortality in DiabetesThe continued use of previously prescribed sodium-glucose cotransporter 2 (SGLT2) inhibitors in the inpatient setting appears to be associated with 45% lower hospital mortality rate, according to Singh et al. (p.933).When they compared these rates with those of patients who discontinued the diabetes drugs, they also found no overall difference in rates of acute kidney injury and a modestly shorter length of hospital stay.Based on the findings, the authors suggest that there may be a role for noninsulin-based pharmacotherapy in inpatient settings.Current recommendations indicate insulin for the management of hyperglycemia in nearly all hospitalized patients with diabetes, as abnormal glucose control in the hospital setting has been associated with poor clinical outcomes.The findings come from a nationwide cohort study that used data on acute care hospitalizations, over ~8 years between 2013 and 2021.After a series of exclusions, the authors identified ~36,500 admissions of individuals with diabetes, just under 6,000 of whom were continued on SGLT2 inhibitors after admission, with the balance discontinuing the therapy.The authors found there were 9.2 in-hospital deaths per 1,000 admissions in the group that continued SGLT2 inhibitors compared with 16.8 deaths per 1,000 admissions in the group that discontinued their use.This translated to 45% lower relative mortality, which remained following adjustment for confounders and across multiple sensitivity analyses."With our retrospective study design, we cannot identify causality or reasons that led to continuation or discontinuation of SGLT2 inhibitors," said author Elias K. Spanakis."However, we provide important evidence to support the continued use of SGLT2 inhibitors in the hospital setting in those patients who are receiving them in the ambulatory setting."Despite the limitations, the authors propose several mechanisms that could be behind the observations."Most importantly, we show that the reason for using SGLT2 inhibitors in the hospital environment is not for achieving better glycemic control, but because they have other, possibly cardiorenal, protective effects leading to reduced mortality."
111In-Pentetreotide–Guided Radiosurgery for Intraoperative Localization of Retroperitoneal Nodal Metastasis in a Patient With Ileal Neuroendocrine Tumor
Authors: Michael J. Demeure, Peter Giuliano, Jared Forester, Nazila Zakry, Gary A. Ulaner
Journal: Clinical Nuclear Medicine (2024)

64 Cu-DOTATATE PET/CT of a 44-year-old man with an ileal neuroendocrine tumor demonstrated the primary tumor, local nodal metastases, and a pericaval nodal metastasis. Localization of the pericaval node during surgery may be difficult, thus 4.4 mCi of 111 In-pentetreotide was administered before surgery to assist with localization and resection. At surgery, the pericaval nodal metastasis was readily detected by gamma probe, which could then be resected and pathologically proven to be a metastasis. This demonstrates the use of somatostatin receptor-targeted imaging for intraoperative localization of an otherwise difficult to surgically localize metastasis. Without intraoperative somatostatin receptor-targeted radiosurgery, disease may have been incompletely resected.
Wiring between close nodes in molecular networks evolves more quickly than between distant nodes
Authors: Alejandro Gil-Gomez, Joshua S Rest
Journal: Molecular Biology and Evolution (2024)

As species diverge, a wide range of evolutionary processes lead to changes in protein-protein interaction (PPI) networks and metabolic networks. The rate at which molecular networks evolve is an important question in evolutionary biology. Previous empirical work has focused on interactomes from model organisms to calculate rewiring rates, but this is limited by the relatively small number of species and sparse nature of network data across species. We present a proxy for variation in network topology: variation in drug-drug interactions (DDIs), obtained by studying drug combinations (DCs) across taxa. Here, we propose the rate at which DDIs change across species as an estimate of the rate at which the underlying molecular network changes as species diverge. We computed the evolutionary rates of DDIs using previously published data from a high-throughput study in gram-negative bacteria. Using phylogenetic comparative methods, we found that DDIs diverge rapidly over short evolutionary time periods, but that divergence saturates over longer time periods. In parallel, we mapped drugs with known targets in PPI and cofunctional networks. We found that the targets of synergistic DDIs are closer in these networks than other types of DCs and that synergistic interactions have a higher evolutionary rate, meaning that nodes that are closer evolve at a faster rate. Future studies of network evolution may use DC data to gain larger-scale perspectives on the details of network evolution within and between species.
Impact of single round of low dose CT lung cancer screening on cause of mortality in different socio-economic groups: a post-hoc analysis of long-term follow-up of the UKLS trial
Authors: Michael P A Davies, Daniel Vulkan, Rhian Gabe, Stephen W Duffy, John K Field
Journal: The Lancet Regional Health - Europe (2024)

Lower socioeconomic status, as measured by the Index of Multiple Deprivation (IMD), is associated with higher rates of smoking-related disease mortality, and with poor uptake of cancer screening. Here we explore whether socioeconomic status impacts the effectiveness of a single round of low-dose-CT screening, or impacts other causes of death, in the UKLS LDCT screening trial.
Maternal Urinary Fluoride and Child Neurobehavior at Age 36 Months
Authors: Ashley J. Malin, Sandrah P. Eckel, Howard Hu, E. Angeles Martinez-Mier, Ixel Hernandez-Castro, Tingyu Yang, Shohreh F. Farzan, Rima Habre, Carrie V. Breton, Theresa M. Bastain
Journal: JAMA Network Open (2024)

Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown.
Symptomatic Hemorrhage Risks in Stroke Thrombolysis
Authors: Shyam Prabhakaran, Jose G. Romano
Journal: JAMA Neurology (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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Neurology journal
Tapinarof cream 1% once daily: Significant efficacy in the treatment of moderate to severe atopic dermatitis in adults and children down to 2 years of age in the pivotal phase 3 ADORING trials
Authors: Jonathan I. Silverberg, Lawrence F. Eichenfield, Adelaide A. Hebert, Eric L. Simpson, Linda Stein Gold, Robert Bissonnette, Kim A. Papp, John Browning, Pearl Kwong, Neil J. Korman, Philip M. Brown, David S. Rubenstein, Stephen C. Piscitelli, Matthew C. Somerville, Anna M. Tallman, Leon Kircik
Journal: Journal of the American Academy of Dermatology (2024)

BackgroundTapinarof cream 1% once daily (QD), a topical aryl hydrocarbon receptor agonist, downregulates pro-inflammatory Th2 cytokines, upregulates skin-barrier components, and reduces oxidative stress.ObjectiveTo assess tapinarof efficacy and safety in adults and children down to 2 years of age with atopic dermatitis (AD).MethodsEight hundred and thirteen patients were randomized to tapinarof or vehicle QD in two 8-week phase 3 trials.ResultsThe primary efficacy endpoint, Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and ≥2-grade improvement from baseline at Week 8, was met with statistical significance in both trials: 45.4% versus 13.9% and 46.4% versus 18.0% (tapinarof vs vehicle; both P < .0001). Significantly superior Eczema Area and Severity Index 75 (EASI75) responses were also observed with tapinarof versus vehicle at Week 8: 55.8% versus 22.9% and 59.1% versus 21.2% (both P < .0001). Rapid improvements in patient-reported pruritus were also significant with tapinarof versus vehicle. Common adverse events (≥5%) of folliculitis, headache, and nasopharyngitis were mostly mild or moderate, with lower discontinuations due to adverse events in the tapinarof groups than with vehicle.LimitationsLong-term efficacy was not assessed.ConclusionTapinarof demonstrated highly significant efficacy and favorable safety and tolerability in a diverse population of patients with AD down to 2 years of age.
Metabolic regulator LKB1 controls adipose tissue ILC2 PD-1 expression and mitochondrial homeostasis to prevent insulin resistance
Authors: Jiping Sun, Youqin Zhang, Qingbing Zhang, Lin Hu, Linfeng Zhao, Hongdong Wang, Yue Yuan, Hongshen Niu, Dongdi Wang, Huasheng Zhang, Jianyue Liu, Xujiao Feng, Xiaohui Su, Ju Qiu, Jing Sun, Heping Xu, Catherine Zhang, Kathleen Wang, Yan Bi, Edgar G Engleman, Lei Shen
Journal: Immunity (2024)
Plasmablastic lymphoma: 2024 update on diagnosis, risk stratification, and management
Authors: Andres Ramirez‐Gamero, Humberto Martínez‐Cordero, Brady E. Beltrán, Jorge Florindez, Luis Malpica, Jorge J. Castillo
Journal: American Journal of Hematology (2024)

Abstract Disease Overview Plasmablastic lymphoma (PBL) is a rare CD20‐negative aggressive lymphoma with a poor prognosis under standard treatment options. Though PBL is associated with human immunodeficiency virus infection and other immunosuppressed states, it can also affect immunocompetent individuals. Diagnosis The diagnosis requires a high clinical suspicion and pathological confirmation. EBER expression and MYC gene rearrangements are frequently detected. The differential diagnosis includes EBV+ diffuse large B‐cell lymphoma, extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B‐cell lymphoma, among others. Risk Stratification Age ≥60 years, advanced clinical stage, and high intermediate and high International Prognostic Index scores are associated with worse survival. Management Combination chemotherapy regimens, such as EPOCH, are recommended. The addition of bortezomib, lenalidomide, or daratumumab might improve outcomes. Including PBL patients and their participation in prospective clinical trials is warranted.
Corrigendum to “Are biomarkers in acute kidney injury ready for prime time? The time is right for a second look.” Kidney Int. 2024;105:675–678
Authors: Chirag R. Parikh, Steven G. Coca
Journal: Kidney International (2024)

DOI of original article: https://doi.org/10.1016/j.kint.2024.01.018 The authors regret that "safety" was misspelled in Figure 1. This has been corrected in the article online. The authors would like to apologize for any inconvenience caused. Are biomarkers in acute kidney injury ready for prime time? The time is right for a second lookKidney InternationalVol. 105Issue 4PreviewSince the early 2000s, the definition of acute kidney injury (AKI) has become sensitive and refined, but the current definition of AKI still has many flaws. Serum creatinine is affected by factors that have no relationship to changes in glomerular filtration rate, for example, changes in creatinine kinetics or muscle mass due to inflammation, medications affecting secretion of creatinine, and hydration. Because of analytic and biological variability, serum creatinine can fluctuate enough to meet the 0.3-mg/dl criterion for AKI without any actual injury. Full-Text PDF
Chimeric autoantibody receptor cell therapy for the treatment of membranous nephropathy
Authors: Jordi Rovira, Carolt Arana, Ainhoa Garcia-Busquets, Ilse Gille, Luís F. Quintana, Mirjam H.M. Heemskerk, Sebastiaan Heidt, Eduard Palou, Fritz Diekmann
Journal: Kidney International (2024)
Issue at a Glance
Authors: Sandeep Ravindran
Journal: Ophthalmology (2024)

Medeiros (p. 645) 等前瞻性地评估了通过功能性和结构性测试密集聚类以识别6个月内快速青光眼进展患眼的可行性和有效性。对 65 名原发性开角型青光眼受试者125 例患眼的分析显示,6个月的密集期内,125 例患眼中,19 例(15%)基于标准自动视野检查 (standard automated perimetry [SAP]) 24-2模式平均偏差 (mean deviation [MD])出现进展,14 例(11%)基于 SAP 10-2模式MD出现进展,16 例患眼(13%)基于视网膜神经纤维层厚度出现进展,125 例患眼中 30例(24%)在功能、结构或两者结合出现进展。 3 种测试的组合对于检测整个随访期间结构或功能进展的所有病例敏感性为 71%,同时保持 94% 的高特异性。 6 个月聚类方法还检测到快速进展者,敏感性为 93%,特异性为 85%。作者得出结论,密集、聚类的测试方法可以在 6 个月的短期随访期内检测出相当大比例的青光眼快速进展患眼。
A Simple Vista en Este Número
Authors: Sandeep Ravindran
Journal: Ophthalmology (2024)

Medeiros y otros (p. 645) realizaron una evaluación prospectiva de la viabilidad y eficacia de identificar ojos con progresión rápida del glaucoma durante 6 meses, por medio de la agrupación intensiva de pruebas funcionales y estructurales. El análisis de 125 ojos de 65 pacientes con glaucoma primario de ángulo abierto, mostró que 19 de 125 ojos (15%) progresaron según la desviación media (DM) 24-2 de la perimetría automatizada estándar (SAP) durante el período de agrupación de 6 meses, 14 ojos (11%) progresaron según la DM 10-2 de la SAP y 16 ojos (13%) progresaron según el grosor de la capa de fibras nerviosas de la retina, y 30 de 125 ojos (24%) progresaron según la función, la estructura o ambas.
This Issue at a Glance
Authors: Sandeep Ravindran
Journal: Ophthalmology (2024)

Medeiros et al (p. 645) prospectively evaluated the feasibility and efficacy of identifying eyes with rapid glaucoma progression over 6 months by intensive clustering of functional and structural testing. Analysis of 125 eyes from 65 primary open-angle glaucoma subjects showed that 19 of 125 eyes (15%) progressed based on standard automated perimetry (SAP) 24-2 mean deviation (MD) over the 6-month clustering period, 14 eyes (11%) progressed on SAP 10-2 MD, and 16 eyes (13%) progressed by retinal nerve fiber layer thickness, with 30 of 125 eyes (24%) progressing by function, structure, or both.
KDM5 family as therapeutic targets in breast cancer: Pathogenesis and therapeutic opportunities and challenges
Authors: Chang-Yun Li, Wanhe Wang, Chung-Hang Leung, Guan-Jun Yang, Jiong Chen
Journal: Molecular Cancer (2024)

Abstract Breast cancer (BC) is the most frequent malignant cancer diagnosis and is a primary factor for cancer deaths in women. The clinical subtypes of BC include estrogen receptor (ER) positive, progesterone receptor (PR) positive, human epidermal growth factor receptor 2 (HER2) positive, and triple-negative BC (TNBC). Based on the stages and subtypes of BC, various treatment methods are available with variations in the rates of progression-free disease and overall survival of patients. However, the treatment of BC still faces challenges, particularly in terms of drug resistance and recurrence. The study of epigenetics has provided new ideas for treating BC. Targeting aberrant epigenetic factors with inhibitors represents a promising anticancer strategy. The KDM5 family includes four members, KDM5A, KDM5B, KDM5C, and KDMD, all of which are Jumonji C domain-containing histone H3K4me2/3 demethylases. KDM5 proteins have been extensively studied in BC, where they are involved in suppressing or promoting BC depending on their specific upstream and downstream pathways. Several KDM5 inhibitors have shown potent BC inhibitory activity in vitro and in vivo, but challenges still exist in developing KDM5 inhibitors. In this review, we introduce the subtypes of BC and their current therapeutic options, summarize KDM5 family context-specific functions in the pathobiology of BC, and discuss the outlook and pitfalls of KDM5 inhibitors in this disease.
Comparative cofactor screens show the influence of transactivation domains and core promoters on the mechanisms of transcription
Authors: Charles C Bell, Jesse J Balic, Laure Talarmain, Andrea Gillespie, Laura Scolamiero, Enid Y N Lam, Ching-Seng Ang, Geoffrey J Faulkner, Omer Gilan, Mark A Dawson
Journal: Nature Genetics (2024)
The microbial metabolite agmatine acts as an FXR agonist to promote polycystic ovary syndrome in female mice
Authors: Chuyu Yun, Sen Yan, Baoying Liao, Yong Ding, Xinyu Qi, Min Zhao, Kai Wang, Yingying Zhuo, Qixing Nie, Chuan Ye, Pengyan Xia, Ming Ma, Rong Li, Changtao Jiang, Jie Qiao, Yanli Pang
Journal: Nature Metabolism (2024)
Cortico-cortical transfer of socially derived information gates emotion recognition
Authors: Daniel Dautan, Anna Monai, Federica Maltese, Xiao Chang, Cinzia Molent, Daniele Mauro, Alberto Galbusera, Dania Vecchia, Federica Antonelli, Arianna Benedetti, Filippo Drago, Gian Marco Leggio, Marco Pagani, Tommaso Fellin, Alessandro Gozzi, Gunter Schumann, Francesca Managò, Francesco Papaleo
Journal: Nature Neuroscience (2024)
Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality
Authors: Hang Yuan, Tatiana Plekhanova, Rosemary Walmsley, Amy C. Reynolds, Kathleen J. Maddison, Maja Bucan, Philip Gehrman, Alex Rowlands, David W. Ray, Derrick Bennett, Joanne McVeigh, Leon Straker, Peter Eastwood, Simon D. Kyle, Aiden Doherty
Journal: npj Digital Medicine (2024)

Abstract Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts. Thus, we aimed to establish the accuracy of wrist-worn accelerometers for sleep stage classification and subsequently describe the association between sleep duration and efficiency (proportion of total time asleep when in bed) with mortality outcomes. We developed a self-supervised deep neural network for sleep stage classification using concurrent laboratory-based polysomnography and accelerometry. After exclusion, 1113 participant nights of data were used for training. The difference between polysomnography and the model classifications on the external validation was 48.2 min (95% limits of agreement (LoA): −50.3 to 146.8 min) for total sleep duration, −17.1 min for REM duration (95% LoA: −56.7 to 91.0 min) and 31.1 min (95% LoA: −67.3 to 129.5 min) for NREM duration. The sleep classifier was deployed in the UK Biobank with ~100,000 participants to study the association of sleep duration and sleep efficiency with all-cause mortality. Among 66,262 UK Biobank participants, 1644 mortality events were observed. Short sleepers (&lt;6 h) had a higher risk of mortality compared to participants with normal sleep duration 6–7.9 h, regardless of whether they had low sleep efficiency (Hazard ratios (HRs): 1.36; 95% confidence intervals (CIs): 1.18 to 1.58) or high sleep efficiency (HRs: 1.29; 95% CIs: 1.04–1.61). Deep-learning-based sleep classification using accelerometers has a fair to moderate agreement with polysomnography. Our findings suggest that having short overnight sleep confers mortality risk irrespective of sleep continuity.
A bilingual speech neuroprosthesis driven by cortical articulatory representations shared between languages
Authors: Alexander B Silva, Jessie R Liu, Sean L Metzger, Ilina Bhaya-Grossman, Maximilian E Dougherty, Margaret P Seaton, Kaylo T Littlejohn, Adelyn Tu-Chan, Karunesh Ganguly, David A Moses, Edward F Chang
Journal: Nature Biomedical Engineering (2024)
Gastroretentive Raft Forming System for Enhancing Therapeutic Effect of Drug‐Loaded Hollow Mesoporous Silica on Gastric Ulcers
Authors: Huayuan Chen, Li Pan, Chengyu Zhang, Lin Liu, Bin Tu, Ergang Liu, Yongzhuo Huang
Journal: Advanced Healthcare Materials (2024)

Abstract Gastric ulcers are characterized by damage to the stomach lining and are often triggered by substances such as ethanol and non‐steroidal anti‐inflammatory drugs. Patchouli alcohol (PA) has demonstrated effectiveness in treating gastric ulcers through antioxidative and anti‐inflammatory effects. However, the water insolubility of PA and rapid gastric emptying cause low drug concentration and poor absorption in the stomach, resulting in limited treatment efficacy of PA. This study develops an oral gastroretentive raft forming system (GRFDDS) containing the aminated hollow mesoporous silica nanoparticles (NH 2 ‐HMSN) for PA delivery. The application of NH 2 ‐HMSN can enhance PA‐loading capacity and water dispersibility, promoting bio‐adhesion to the gastric mucosa and sustained drug release. The incorporation of PA‐loaded NH 2 ‐HMSN (NH 2 ‐HMSN‐PA) into GRFDDS can facilitate gastric drug retention and achieve long action, thereby improving therapeutic effects. The results reveal that NH 2 ‐HMSN‐PA protects the gastric mucosa damage by inhibiting NLRP3‐mediated pyroptosis. The GRFDDS, optimized through orthogonal design, demonstrates the gastric retention capacity and sustained drug release, exhibiting significant therapy efficacy in an ethanol‐induced acute gastric ulcers model and an aspirin‐induced chronic gastric ulcers model through antioxidation, anti‐pyroptosis, and anti‐inflammation. This study provides a potential strategy for enhancing druggability of insoluble natural compounds and therapeutic management of gastric ulcers.
Antibody-displaying extracellular vesicles for targeted cancer therapy
Authors: Oscar P B Wiklander, Doste R Mamand, Dara K Mohammad, Wenyi Zheng, Rim Jawad Wiklander, Taras Sych, Antje M Zickler, Xiuming Liang, Heena Sharma, Andrea Lavado, Jeremy Bost, Samantha Roudi, Giulia Corso, Angus J Lennaárd, Manuchehr Abedi-Valugerdi, Imre Mäger, Evren Alici, Erdinc Sezgin, Joel Z Nordin, Dhanu Gupta, André Görgens, Samir El Andaloussi
Journal: Nature Biomedical Engineering (2024)

Extracellular vesicles (EVs) function as natural delivery vectors and mediators of biological signals across tissues. Here, by leveraging these functionalities, we show that EVs decorated with an antibody-binding moiety specific for the fragment crystallizable (Fc) domain can be used as a modular delivery system for targeted cancer therapy. The Fc-EVs can be decorated with different types of immunoglobulin G antibody and thus be targeted to virtually any tissue of interest. Following optimization of the engineered EVs by screening Fc-binding and EV-sorting moieties, we show the targeting of EVs to cancer cells displaying the human epidermal receptor 2 or the programmed-death ligand 1, as well as lower tumour burden and extended survival of mice with subcutaneous melanoma tumours when systemically injected with EVs displaying an antibody for the programmed-death ligand 1 and loaded with the chemotherapeutic doxorubicin. EVs with Fc-binding domains may be adapted to display other Fc-fused proteins, bispecific antibodies and antibody-drug conjugates.