tbuckley/cabot-search huggingface dataset:
Impact of immunotherapy time-of-day infusion on survival and immunologic correlates in patients with metastatic renal cell carcinoma: a multicenter cohort analysis
Authors: Jimmy S Patel, Yena Woo, Amber Draper, Caroline S Jansen, Jennifer W Carlisle, Pasquale F Innominato, Francis A Lévi, Layla Dhabaan, Viraj A Master, Mehmet A Bilen, Mohammad K Khan, Michael C Lowe, Haydn Kissick, Zachary S Buchwald, David C Qian
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Recent studies have demonstrated that earlier time-of-day infusion of immune checkpoint inhibitors (ICIs) is associated with longer progression-free survival (PFS) and overall survival (OS) among patients with metastatic melanoma and non-small cell lung cancer. These data are in line with growing preclinical evidence that the adaptive immune response may be more effectively stimulated earlier in the day. We sought to determine the impact of time-of-day ICI infusions on outcomes among patients with metastatic renal cell carcinoma (mRCC). Methods The treatment records of all patients with stage IV RCC who began ICI therapy within a multicenter academic hospital system between 2015 and 2020 were reviewed. The associations between the proportion of ICI infusions administered prior to noon (denoting morning infusions) and PFS and OS were evaluated using univariate and multivariable Cox proportional hazards regression. Results In this study, 201 patients with mRCC (28% women) received ICIs and were followed over a median of 18 months (IQR 5–30). The median age at the time of ICI initiation was 63 years (IQR 56–70). 101 patients (50%) received ≥20% of their ICI infusions prior to noon (Group A) and 100 patients (50%) received &lt;20% of infusions prior to noon (Group B). Across the two comparison groups, initial ICI agents consisted of nivolumab (58%), nivolumab plus ipilimumab (34%), and pembrolizumab (8%). On univariate analysis, patients in Group A had longer PFS and OS compared with those in Group B (PFS HR 0.67, 95% CI 0.48 to 0.94, P univar =0.020; OS HR 0.57, 95% CI 0.34 to 0.95, P univar =0.033). These significant findings persisted following multivariable adjustment for age, sex, performance status, International Metastatic RCC Database Consortium risk score, pretreatment lactate dehydrogenase, histology, and presence of bone, brain, and liver metastases (PFS HR 0.70, 95% CI 0.50 to 0.98, P multivar =0.040; OS HR 0.57, 95% CI 0.33 to 0.98, P multivar =0.043). Conclusions Patients with mRCC may benefit from earlier time-of-day receipt of ICIs. Our findings are consistent with established mechanisms of chrono-immunology, as well as with preceding analogous studies in melanoma and lung cancer. Additional prospective randomized trials are warranted.
Benzopyrone, a privileged scaffold in drug discovery: An overview of FDA‐approved drugs and clinical candidates
Authors: Venu Sharma, Ankita Sharma, Bhagyashri N. Wadje, Sandip B. Bharate
Journal: Medicinal Research Reviews (2024)

Abstract Natural products have always served as an important source of drugs for treating various diseases. Among various privileged natural product scaffolds, the benzopyrone class of compounds has a substantial presence among biologically active compounds. One of the pioneering anticoagulant drugs, warfarin approved in 1954 bears a benzo‐α‐pyrone (coumarin) nucleus. The widely investigated psoriasis drugs, methoxsalen, and trioxsalen, also contain a benzo‐α‐pyrone nucleus. Benzo‐γ‐pyrone (chromone) containing drugs, cromoglic acid, and pranlukast were approved as treatments for asthma in 1982 and 2007, respectively. Numerous other small molecules with a benzopyrone core are under clinical investigation. The present review discusses the discovery, absorption, distribution, metabolism, excretion properties, and synthetic approaches for the Food and Drug Administration‐approved and clinical‐stage benzopyrone class of compounds. The role of the pyrone core in biological activity has also been discussed. The present review unravels the potential of benzopyrone core in medicinal chemistry and drug development.
Infection Microenvironment‐Responsive Coating on Titanium Surfaces for On‐Demand Release of Therapeutic Gas and Antibiotic
Authors: Kun Wang, Fan Rong, Haowei Peng, Zhang Yuan, Jingjing Huo, Pengxiang Liu, Rui Ding, Cuiping Yan, Guming Liu, Tengjiao Wang, Peng Li
Journal: Advanced Healthcare Materials (2024)

Aseptic loosening and bacterial infection pose significant challenges in the clinical application of titanium (Ti) orthopedic implants, which are primarily caused by insufficient osseointegration and bacterial contamination. To address these issues, a responsive coating on Ti surface is constructed, which achieves enhanced osseointegration and infection elimination by on-demand release of therapeutic gas hydrogen sulfide (H
Transplant of microbiota from Crohn’s disease patients to germ-free mice results in colitis
Authors: Irshad Ali Sheikh, Jared Bianchi-Smak, Daniel Laubitz, Gabriele Schiro, Monica T. Midura-Kiela, David G. Besselsen, Gayatri Vedantam, Sara Jarmakiewicz, Rafał Filip, Fayez K. Ghishan, Nan Gao, Pawel R. Kiela
Journal: Gut Microbes (2024)

Although the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in genetically susceptible mice or in chemically induced colitis. We aimed to further test the host response to fecal microbiome transplantation (FMT) from Crohn's disease patients on mucosal homeostasis in ex-germ-free (xGF) mice. We characterized and transferred fecal microbiota from healthy patients and patients with defined Crohn's ileocolitis (CD_L3) to germ-free mice and analyzed the resulting microbial and mucosal homeostasis by 16S profiling, shotgun metagenomics, histology, immunofluorescence (IF) and RNAseq analysis. We observed a markedly reduced engraftment of CD_L3 microbiome compared to healthy control microbiota. FMT from CD_L3 patients did not lead to ileitis but resulted in colitis with features consistent with CD: a discontinued pattern of colitis, more proximal colonic localization, enlarged isolated lymphoid follicles and/or tertiary lymphoid organ neogenesis, and a transcriptomic pattern consistent with epithelial reprograming and promotion of the Paneth cell-like signature in the proximal colon and immune dysregulation characteristic of CD. The observed inflammatory response was associated with persistently increased abundance of Ruminococcus gnavus, Erysipelatoclostridium ramosum, Faecalimonas umbilicate, Blautia hominis, Clostridium butyricum, and C. paraputrificum and unexpected growth of toxigenic C. difficile, which was below the detection level in the community used for inoculation. Our study provides the first evidence that the transfer of a dysbiotic community from CD patients can lead to spontaneous inflammatory changes in the colon of xGF mice and identifies a signature microbial community capable of promoting colonization of pathogenic and conditionally pathogenic bacteria.
Artificial Vascular with Pressure‐Responsive Property based on Deformable Microfluidic Channels
Authors: Zhenlin Chen, Lei Fan, Shuxun Chen, Han Zhao, Qiang Zhang, Yun Qu, Ya Huang, Xinge Yu, Dong Sun
Journal: Advanced Healthcare Materials (2024)

Abstract In vitro blood vessel models are significant for disease modeling, drug assays, and therapeutic development. Microfluidic technologies allow to create physiologically relevant culture models reproducing the features of the in vivo vascular microenvironment. However, current microfluidic technologies are limited by impractical rectangular cross‐sections and single or nonsynchronous compound mechanical stimuli. This study proposes a new strategy for creating round‐shaped deformable soft microfluidic channels to serve as artificial in vitro vasculature for developing in vitro models with vascular physio‐mechanical microenvironments. Endothelial cells seeded into vascular models are used to assess the effects of a remodeled in vivo mechanical environment. Furthermore, a 3D stenosis model is constructed to recapitulate the flow disturbances in atherosclerosis. Soft microchannels can also be integrated into traditional microfluidics to realize multifunctional composite systems. This technology provides new insights into applying microfluidic chips and a prospective approach for constructing in vitro blood vessel models.
Bayesian interim analysis for prospective randomized studies: reanalysis of the acute myeloid leukemia HOVON 132 clinical trial
Authors: Niek G. van der Maas, Jurjen Versluis, Kazem Nasserinejad, Joost van Rosmalen, Thomas Pabst, Johan Maertens, Dimitri Breems, Markus Manz, Jacqueline Cloos, Gert J. Ossenkoppele, Yngvar Floisand, Patrycja Gradowska, Bob Löwenberg, Gerwin Huls, Douwe Postmus, Francesco Pignatti, Jan J. Cornelissen
Journal: Blood Cancer Journal (2024)

Abstract Randomized controlled trials (RCTs) are the gold standard to establish the benefit-risk ratio of novel drugs. However, the evaluation of mature results often takes many years. We hypothesized that the addition of Bayesian inference methods at interim analysis time points might accelerate and enforce the knowledge that such trials may generate. In order to test that hypothesis, we retrospectively applied a Bayesian approach to the HOVON 132 trial, in which 800 newly diagnosed AML patients aged 18 to 65 years were randomly assigned to a “7 + 3” induction with or without lenalidomide. Five years after the first patient was recruited, the trial was negative for its primary endpoint with no difference in event-free survival (EFS) between experimental and control groups (hazard ratio [HR] 0.99, p = 0.96) in the final conventional analysis. We retrospectively simulated interim analyses after the inclusion of 150, 300, 450, and 600 patients using a Bayesian methodology to detect early lack of efficacy signals. The HR for EFS comparing the lenalidomide arm with the control treatment arm was 1.21 (95% CI 0.81–1.69), 1.05 (95% CI 0.86–1.30), 1.00 (95% CI 0.84–1.19), and 1.02 (95% CI 0.87–1.19) at interim analysis 1, 2, 3 and 4, respectively. Complete remission rates were lower in the lenalidomide arm, and early deaths more frequent. A Bayesian approach identified that the probability of a clinically relevant benefit for EFS (HR &lt; 0.76, as assumed in the statistical analysis plan) was very low at the first interim analysis (1.2%, 0.6%, 0.4%, and 0.1%, respectively). Similar observations were made for low probabilities of any benefit regarding CR. Therefore, Bayesian analysis significantly adds to conventional methods applied for interim analysis and may thereby accelerate the performance and completion of phase III trials.
Cardiovascular Effects of Oral Ketone Ester Treatment in Patients With Heart Failure With Reduced Ejection Fraction: A Randomized, Controlled, Double-Blind Trial
Authors: Kristoffer Berg-Hansen, Nigopan Gopalasingam, Kristian Hylleberg Christensen, Bertil Ladefoged, Mads Jønsson Andersen, Steen Hvitfeldt Poulsen, Barry A. Borlaug, Roni Nielsen, Niels Møller, Henrik Wiggers
Journal: Circulation (2024)

Heart failure triggers a shift in myocardial metabolic substrate utilization, favoring the ketone body 3-hydroxybutyrate as energy source. We hypothesized that 14-day treatment with ketone ester (KE) would improve resting and exercise hemodynamics and exercise capacity in patients with heart failure with reduced ejection fraction.
HDGFL2 cryptic proteins report presence of TDP-43 pathology in neurodegenerative diseases
Authors: Anna Calliari, Lillian M. Daughrity, Ellen A. Albagli, Paula Castellanos Otero, Mei Yue, Karen Jansen-West, Naeyma N. Islam, Thomas Caulfield, Bailey Rawlinson, Michael DeTure, Casey Cook, Neill R. Graff-Radford, Gregory S. Day, Bradley F. Boeve, David S. Knopman, Ronald C. Petersen, Keith A. Josephs, Björn Oskarsson, Aaron D. Gitler, Dennis W. Dickson, Tania F. Gendron, Mercedes Prudencio, Michael E. Ward, Yong-Jie Zhang, Leonard Petrucelli
Journal: Molecular Neurodegeneration (2024)

This letter demonstrates the potential of novel cryptic proteins resulting from TAR DNA-binding protein 43 (TDP-43) dysfunction as markers of TDP-43 pathology in neurodegenerative diseases.
Bleeding self‐assessments by patients with immune thrombocytopenia (ITP): An agreement study
Authors: Bianca Clerici, Sahrish Masood, Ishac Nazy, Ngan Tang, Madison Cranstone, Yang Liu, Milena Hadzi‐Tosev, Joanne Nixon, Melanie St John, Maryam Shirinzadeh, Erin Jamula, John G. Kelton, Donald M. Arnold
Journal: American Journal of Hematology (2024)

We designed anagreement study to compare the results of bleeding assessments done in tandem by ITP patients and trained research staff. We used a modified version of the ITP Bleeding Scale, which captured the patients' worst bleeding event at any of nine anatomical sites since the time of the last assessment. Interrater agreement was determined using the 2-way kappa for the assessment of severe vs. non-severe bleeds. We analyzed 108 consecutive patients with ITP from the McMaster ITP Registry who had duplicate bleeding assessments. Two-way agreement was excellent for gynecological (k = 0.86, 95% CI 0.71-1.02), gastrointestinal (k = 1), genitourinary (k = 1), pulmonary (k = 1) and intracranial (k = 1) bleeds; good for skin (k = 0.68, 95% CI, 0.54-0.82), oral (k = 0.76, 95% CI, 0.53-0.98) and ocular (k = 0.66, 95% CI, 0.04-1-28) bleeds; and moderate for epistaxis (k = 0.58, 95% CI, 0.21-0.95). Bleeding self-assessments by ITP patients were similar to trained research staff, but disagreements in severity grades were more frequent with skin bleeds, oral bleeds and epistaxis. Bleeding self-assessments could simplify bleeding assessments in clinical trials.
Cracking the NLRP3 code: Pioneering precision medicine for inflammation
Authors: Alexander N.R. Weber, Maria Mateo Tortola, Jasmin B. Kuemmerle-Deschner
Journal: The Journal of Experimental Medicine (2024)

Precisely diagnosing and effectively treating cryopyrin-associated periodic syndrome (CAPS), an inflammatory condition linked to gain-of-function NLRP3 inflammasome mutations, poses challenges. A novel classification approach may help inform therapeutic decisions and offer valuable insights into broader inflammatory conditions (Cosson et al. J. Exp. Med. 2024. https://doi.org/10.1084/jem.20231200).
Estimated Sustainable Cost-Based Prices for Diabetes Medicines
Authors: Melissa J. Barber, Dzintars Gotham, Helen Bygrave, Christa Cepuch
Journal: JAMA Network Open (2024)

Importance The burden of diabetes is growing worldwide. The costs associated with diabetes put substantial pressure on patients and health budgets, especially in low- and middle-income countries. The prices of diabetes medicines are a key determinant for access, yet little is known about the association between manufacturing costs and current market prices. Objectives To estimate the cost of manufacturing insulins, sodium-glucose cotransporter 2 inhibitors (SGLT2Is), and glucagonlike peptide 1 agonists (GLP1As), derive sustainable cost-based prices (CBPs), and compare these with current market prices. Design, Setting, and Participants In this economic evaluation, the cost of manufacturing insulins, SGLT2Is, and GLP1As was modeled. Active pharmaceutical ingredient cost per unit (weighted least-squares regression model using data from a commercial database of trade shipments, data from January 1, 2016, to March 31, 2023) was combined with costs of formulation and other operating expenses, plus a profit margin with an allowance for tax, to estimate CBPs. Cost-based prices were compared with current prices in 12 countries, collected in January 2023 from public databases. Countries were selected to provide representation of different income levels and geographic regions based on the availability of public databases. Main Outcomes and Measures Estimated CBPs; lowest current market prices (2023 US dollars). Results In this economic evaluation of manufacturing costs, estimated CBPs for treatment with insulin in a reusable pen device could be as low as $96 (human insulin) or $111 (insulin analogues) per year for a basal-bolus regimen, $61 per year using twice-daily injections of mixed human insulin, and $50 (human insulin) or $72 (insulin analogues) per year for a once-daily basal insulin injection (for type 2 diabetes), including the cost of injection devices and needles. Cost-based prices ranged from $1.30 to $3.45 per month for SGLT2Is (except canagliflozin: $25.00-$46.79) and from $0.75 to $72.49 per month for GLP1As. These CBPs were substantially lower than current prices in the 12 countries surveyed. Conclusions and Relevance High prices limit access to newer diabetes medicines in many countries. The findings of this study suggest that robust generic and biosimilar competition could reduce prices to more affordable levels and enable expansion of diabetes treatment globally.
Conductive Peptide‐Based MXene Hydrogel as a Piezoresistive Sensor
Authors: Dana Cohen‐Gerassi, Or Messer, Gal Finkelstein‐Zuta, Moran Aviv, Bar Favelukis, Yosi Shacham‐Diamand, Maxim Sokol, Lihi Adler‐Abramovich
Journal: Advanced Healthcare Materials (2024)

Abstract Wearable pressure sensors have become increasingly popular for personal healthcare and motion detection applications due to recent advances in materials science and functional nanomaterials. In this study, a novel composite hydrogel is presented as a sensitive piezoresistive sensor that can be utilized for various biomedical applications, such as wearable skin patches and integrated artificial skin that can measure pulse and blood pressure, as well as monitor sound as a self‐powered microphone. The hydrogel is composed of self‐assembled short peptides containing aromatic, positively‐ or negatively charged amino acids combined with 2D Ti 3 C 2 T z MXene nanosheets. This material is low‐cost, facile, reliable, and scalable for large areas while maintaining high sensitivity, a wide detection range, durability, oxidation stability, and biocompatibility. The bioinspired nanostructure, strong mechanical stability, and ease of functionalization make the assembled peptide‐based composite MXene‐hydrogel a promising and widely applicable material for use in bio‐related wearable electronics.
In Memoriam—William H. Gaasch, MD, 1937-2022
Authors: Gerard P. Aurigemma, Theo E. Meyer, Michael R. Zile
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Improved Tool to Assess Complicated Appendicitis Probability
Authors: Jussi Haijanen, Paulina Salminen
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Radiation Recall Dermatitis With Bruton Tyrosine Kinase Inhibitor Therapy
Authors: Ahmad Rajeh, Sarah Ferree, Milan J. Anadkat
Journal: JAMA Dermatology (2024)

This case report describes a woman in her 70s with a history of breast cancer and chronic lymphocytic leukemia who presented with a painful rash of the bilateral chest extending onto the flanks.
Errors in Figure
Journal: JAMA Network Open (2024)

DNAemia and DNA Virus Seropositivity and Mortality in Pediatric Sepsis," 1 published February 26, 2024, the x-axis labels "Reactivated" and "Latent" were inadvertently transposed in Figure 4A-D, and the comparisons in footnotes a through e were incorrect.This article has been corrected.
Lepodisiran for Elevated Lipoprotein(a)
Authors: Michioki Endo, Masahiro Kami
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 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