tbuckley/cabot-search huggingface dataset:
Targeting oxidative phosphorylation to increase the efficacy of immune-combination therapy in renal cell carcinoma
Authors: Jihua Tian, Jing Luo, Xing Zeng, Chunjin Ke, Yanan Wang, Zhenghao Liu, Le Li, Yangjun Zhang, Zhiquan Hu, Chunguang Yang
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Immune checkpoint inhibitors (ICIs) are the standard of care for metastatic renal cell carcinoma (RCC); however, most patients develop de novo or acquired resistance to ICIs. Oxidative phosphorylation (OXPHOS) has been rarely explored as a potential target for correcting ICI resistance. Methods We systematically analyzed RNA sequencing and clinical data from CheckMate, JAVELIN Renal 101, and NCT01358721 clinical trials, and clinicopathological data of 25 patients from Tongji Hospital to investigate the relationship between OXPHOS and ICI resistance. The Ndufb8 -knockdown Renca cell line was derived to determine the effect of OXPHOS on RCC immunotherapy in vivo. Results An analysis of the CheckMate series data revealed that high OXPHOS levels are risk factors for ICI in patients with RCC, but are affected by thevon Hippel-Lindau protein (VHL) and hypoxia-inducible factor-1α status. This result is consistent with correlation between clinicopathological characteristics and prognostic observations at our institute. Knockdown of the mitochondrial complex I subunit Ndufb8 of the Renca cell line had no effect on cell growth and migration in vitro, but slowed down cell growth in vivo. Among anti-programmed death ligand 1 (PD-L1)-treated BALB/c mice, sh Ndufb8 Renca tumors grew slower than shControl Renca tumors and the corresponding mice survived longer. Flow cytometry revealed that CD8 + T cells in sh Ndufb8 Renca tumors, which were exposed to a lower degree of hypoxia and expressed less programmed death-1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3), secreted more interferon-γ after stimulation. Immunofluorescence demonstrated that the sh Ndufb8 Renca tumors had a higher proportion of CD8 + T cells and the proportion of these cells was lower in the hypoxic area. Conclusions OXPHOS is a reliable predictor of immunotherapy response in RCC and is more pronounced in metastatic lesions. RCC cells generate a hypoxic tumor microenvironment and inhibit T-cell function through oxidative metabolism, thereby leading to immunotherapy resistance.
Recording Quality Is Systematically Related to Electrode Impedance
Authors: Christopher M. Lewis, Christian Boehler, Rickard Liljemalm, Pascal Fries, Thomas Stieglitz, Maria Asplund
Journal: Advanced Healthcare Materials (2024)

Extracellular recordings with planar microelectrodes are the gold standard technique for recording the fast action potentials of neurons in the intact brain. The introduction of microfabrication techniques has revolutionized the in vivo recording of neuronal activity and introduced high-density, multi-electrode arrays that increase the spatial resolution of recordings and the number of neurons that can be simultaneously recorded. Despite these innovations, there is still debate about the ideal electrical transfer characteristics of extracellular electrodes. This uncertainty is partly due to the lack of systematic studies comparing electrodes with different characteristics, particularly for chronically implanted arrays over extended time periods. Here a high-density, flexible, and thin-film array is fabricated and tested, containing four distinct electrode types differing in surface material and surface topology and, thus, impedance. It is found that recording quality is strongly related to electrode impedance with signal amplitude and unit yield negatively correlated to impedance. Electrode impedances are stable for the duration of the experiment (up to 12 weeks) and recording quality does not deteriorate. The findings support the expectation from the theory that recording quality will increase as impedance decreases.
Zinpentraxin Alfa for Idiopathic Pulmonary Fibrosis: The Randomized Phase III STARSCAPE Trial
Authors: Luca Richeldi, Courtney Schiffman, Juergen Behr, Yoshikazu Inoue, Tamera Corte, Vincent Cottin, R. Gisli Jenkins, Steven D Nathan, Ganesh Raghu, Simon L. F. Walsh, Parminderjit K. Jayia, Nikhil Kamath, Fernando J. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: A phase II trial reported clinical benefit over 28 weeks in patients with idiopathic pulmonary fibrosis who received zinpentraxin alfa. Objectives: To investigate the efficacy and safety of zinpentraxin alfa in patients with idiopathic pulmonary fibrosis in a phase III trial. Methods: This 52-week phase III, double-blind, placebo-controlled, pivotal trial was conducted at 275 sites in 29 countries. Patients with idiopathic pulmonary fibrosis were randomized 1:1 to intravenous placebo or zinpentraxin alfa 10 mg/kg every four weeks. The primary endpoint was absolute change from baseline to Week 52 in forced vital capacity. Secondary endpoints included absolute change from baseline to Week 52 in percent predicted forced vital capacity and six-minute walking distance. Safety was monitored via adverse events. Post-hoc analysis of the phase II and phase III data explored changes in forced vital capacity and their impact on the efficacy results. Measurements and Main Results: Of 664 randomized patients, 333 were assigned to placebo and 331 to zinpentraxin alfa. Four of the 664 randomized patients were never administered study drug. The trial was terminated early following a pre-specified futility analysis that demonstrated no treatment benefit of zinpentraxin alfa over placebo. In the final analysis, absolute change from baseline to Week 52 in forced vital capacity was similar between placebo and zinpentraxin alfa (‒214.89 mL and ‒235.72 mL; P = 0.5420); there were no apparent treatment effects on secondary endpoints. Overall, 72.3% and 74.6% of patients receiving placebo and zinpentraxin alfa, respectively, experienced ≥1 adverse event. Post-hoc analysis revealed that extreme forced vital capacity decline in two placebo-treated patients resulted in the clinical benefit of zinpentraxin alfa reported by phase II. Conclusions: Zinpentraxin alfa treatment did not benefit patients with idiopathic pulmonary fibrosis over placebo. Learnings from this program may help improve decision-making around trials in idiopathic pulmonary fibrosis. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). Clinical trial registration available at www.clinicaltrials.gov, ID: NCT04552899
Hospital volume-mortality association after esophagectomy for cancer: a systematic review and meta-analysis
Authors: Jie Di, Xiao-Shi Lu, Min Sun, Zhe-Ming Zhao, Chun-Dong Zhang
Journal: International Journal of Surgery (2024)

Background: Postoperative mortality plays an important role in evaluating the surgical safety of esophagectomy. Although postoperative mortality after esophagectomy is partly influenced by the yearly hospital surgical case volume (hospital volume), this association remains unclear. Methods: Studies assessing the association between hospital volume and postoperative mortality in patients who underwent esophagectomy for esophageal cancer were searched for eligibility. Odds ratios (ORs) were pooled for the highest versus lowest categories of hospital volume using a random effects model. The dose-response association between hospital volume and the risk of postoperative mortality was analyzed. The study protocol was registered with PROSPERO. Results: Fifty-six studies including 385,469 participants were included. A higher-volume hospital significantly reduced the risk of post-esophagectomy mortality by 53% compared with their lower-volume counterparts (odds ratio, 0.47; 95% confidence interval, 0.41–0.54). Similar results were found in subgroup analyses. Volume-outcome analysis suggested that post-esophagectomy mortality rates remained roughly stable after the hospital volume reached a plateau of 45 esophagectomies per year. Conclusions: Higher-volume hospitals had significantly lower post-esophagectomy mortality rates in patients with esophageal cancer, with a threshold of 45 esophagectomies per year for a high-volume hospital. This remarkable negative correlation showed the benefit of a better safety in centralization of esophagectomy to a high volume hospital.
Treatment for behavioral insomnia in young children with neurotypical development under 6 years of age: A systematic review
Authors: Florian Lecuelle, Wendy Leslie, Marie-Paule Gustin, Patricia Franco, Benjamin Putois
Journal: Sleep Medicine Reviews (2024)

This literature review examines all treatments for behavioral insomnia in children under 6 years of age to determine which treatments have empirically demonstrated efficacy. Following PRISMA guidelines, three databases were investigated (Pubmed, Cochrane and Psychinfo) to select randomized controlled trials (RCTs) which assess treatments for behavioral insomnia in children under 6 years of age, all with neurotypical development. A total of 908 articles met the search criteria. 21 articles were selected and analyzed in their entirety for a total of 2363 children (ranging from 2 months to 6 years of age). Based on these studies, treatment of behavioral insomnia in young children under 6 years of age is primarily based on behavioral therapy. There is no evidence that pharmacological treatments are effective in the long term for neurotypical children. This review highlights the lack of RCTs in this field: new RCTs should be carried out among young children to refine and optimize the therapeutic approach and to address the risk of therapeutic abuse through the use of non-scientifically validated methods.
Sensing Dying Cells in Health and Disease
Authors: Elena Tutunea-Fatan, Shabitha Arumugarajah, Rita S. Suri, Cassandra R. Edgar, Ingrid Hon, Jimmy D. Dikeakos, Lakshman Gunaratnam
Journal: Journal of the American Society of Nephrology (2024)

Kidney injury molecule-1 (KIM-1), also known as T-cell Ig and mucin domain-1 (TIM-1), is a widely recognized biomarker for AKI, but its biological function is less appreciated. KIM-1/TIM-1 belongs to the T-cell Ig and mucin domain family of conserved transmembrane proteins, which bear the characteristic six-cysteine Ig-like variable domain. The latter enables binding of KIM-1/TIM-1 to its natural ligand, phosphatidylserine, expressed on the surface of apoptotic cells and necrotic cells. KIM-1/TIM-1 is expressed in a variety of tissues and plays fundamental roles in regulating sterile inflammation and adaptive immune responses. In the kidney, KIM-1 is upregulated on injured renal proximal tubule cells, which transforms them into phagocytes for clearance of dying cells and helps to dampen sterile inflammation. TIM-1, expressed in T cells, B cells, and natural killer T cells, is essential for cell activation and immune regulatory functions in the host. Functional polymorphisms in the gene for KIM-1/TIM-1, HAVCR1 , have been associated with susceptibility to immunoinflammatory conditions and hepatitis A virus-induced liver failure, which is thought to be due to a differential ability of KIM-1/TIM-1 variants to bind phosphatidylserine. This review will summarize the role of KIM-1/TIM-1 in health and disease and its potential clinical applications as a biomarker and therapeutic target in humans.
Genome sequencing as a generic diagnostic strategy for rare disease
Authors: Gaby Schobers, Ronny Derks, Amber den Ouden, Hilde Swinkels, Jeroen van Reeuwijk, Ermanno Bosgoed, Dorien Lugtenberg, Su Ming Sun, Jordi Corominas Galbany, Marjan Weiss, Marinus J. Blok, Richelle A. C. M. Olde Keizer, Tom Hofste, Debby Hellebrekers, Nicole de Leeuw, Alexander Stegmann, Erik-Jan Kamsteeg, Aimee D. C. Paulussen, Marjolijn J. L. Ligtenberg, Xiangqun Zheng Bradley, John Peden, Alejandra Gutierrez, Adam Pullen, Tom Payne, Christian Gilissen, Arthur van den Wijngaard, Han G. Brunner, Marcel Nelen, Helger G. Yntema, Lisenka E. L. M. Vissers
Journal: Genome Medicine (2024)

Abstract Background To diagnose the full spectrum of hereditary and congenital diseases, genetic laboratories use many different workflows, ranging from karyotyping to exome sequencing. A single generic high-throughput workflow would greatly increase efficiency. We assessed whether genome sequencing (GS) can replace these existing workflows aimed at germline genetic diagnosis for rare disease. Methods We performed short-read GS (NovaSeq™6000; 150 bp paired-end reads, 37 × mean coverage) on 1000 cases with 1271 known clinically relevant variants, identified across different workflows, representative of our tertiary diagnostic centers. Variants were categorized into small variants (single nucleotide variants and indels &lt; 50 bp), large variants (copy number variants and short tandem repeats) and other variants (structural variants and aneuploidies). Variant calling format files were queried per variant, from which workflow-specific true positive rates (TPRs) for detection were determined. A TPR of ≥ 98% was considered the threshold for transition to GS. A GS-first scenario was generated for our laboratory, using diagnostic efficacy and predicted false negative as primary outcome measures. As input, we modeled the diagnostic path for all 24,570 individuals referred in 2022, combining the clinical referral, the transition of the underlying workflow(s) to GS, and the variant type(s) to be detected. Results Overall, 95% (1206/1271) of variants were detected. Detection rates differed per variant category: small variants in 96% (826/860), large variants in 93% (341/366), and other variants in 87% (39/45). TPRs varied between workflows (79–100%), with 7/10 being replaceable by GS. Models for our laboratory indicate that a GS-first strategy would be feasible for 84.9% of clinical referrals (750/883), translating to 71% of all individuals (17,444/24,570) receiving GS as their primary test. An estimated false negative rate of 0.3% could be expected. Conclusions GS can capture clinically relevant germline variants in a ‘GS-first strategy’ for the majority of clinical indications in a genetics diagnostic lab.
Reanalysis Following Removal of Participants From 1 Site in Multicenter Trial of Upadacitinib vs Dupilumab for Atopic Dermatitis
Authors: Andrew Blauvelt
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Salpingectomy and Ovarian Cancer Prevention
Authors: Karen M. Tuesley, Penelope M. Webb, Susan J. Jordan
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
“Alarming Trend” Persists as Syphilis Cases Swelled in the US in 2022
Authors: Emily Harris
Journal: JAMA (2024)

The syphilis epidemic continued in the US in 2022, the most recent year with sexually transmitted disease (STD) data available. The Centers for Disease Control and Prevention reported more than 207 000 syphilis cases that year, a nearly 80% increase from 2018.
Balancing Ertapenem Therapy in Recalcitrant Hidradenitis Suppurativa With Antibiotic Stewardship
Authors: Haley B. Naik
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Every repeat is unique: Exploring the genomic impact of human L1 retrotransposons at locus-specific resolution
Authors: Stephanie Workman, Sandra R. Richardson
Journal: Cell Genomics (2024)

Fully understanding the impact of the human retrotransposon L1 requires that each of ∼500,000 L1 copies be evaluated as a potentially unique genomic entity. In this issue of Cell Genomics, Lanciano et al.1 strive toward this goal, illuminating the reciprocal regulatory influence between individual L1s and their genomic integration sites.
Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant
Authors: Qiang Wang, Marta Martínez-Bonet, Taehyeung Kim, Jeffrey A. Sparks, Kazuyoshi Ishigaki, Xiaoting Chen, Marc Sudman, Vitor Aguiar, Sangwan Sim, Marcos Chiñas Hernandez, Darren J. Chiu, Alexandra Wactor, Brian Wauford, Miranda C. Marion, Maria Gutierrez-Arcelus, John Bowes, Stephen Eyre, Ellen Nordal, Sampath Prahalad, Marite Rygg, Vibeke Videm, Soumya Raychaudhuri, Matthew T. Weirauch, Carl D. Langefeld, Susan D. Thompson, Peter A. Nigrovic
Journal: Cell Genomics (2024)
Quantitative and qualitative mutational impact of ionizing radiation on normal cells
Authors: Jeonghwan Youk, Hyun Woo Kwon, Joonoh Lim, Eunji Kim, Taewoo Kim, Ryul Kim, Seongyeol Park, Kijong Yi, Chang Hyun Nam, Sara Jeon, Yohan An, Jinwook Choi, Hyelin Na, Eon-Seok Lee, Youngwon Cho, Dong-Wook Min, HyoJin Kim, Yeong-Rok Kang, Si Ho Choi, Min Ji Bae, Chang Geun Lee, Joon-Goon Kim, Young Seo Kim, Tosol Yu, Won-Chul Lee, Jong-Yeon Shin, Dong Soo Lee, Tae-You Kim, Taeyun Ku, Su Yeon Kim, Joo-Hyeon Lee, Bon-Kyoung Koo, Hyunsook Lee, On Vox Yi, Eon Chul Han, Ji Hyun Chang, Kyung Su Kim, Tae Gen Son, Young Seok Ju
Journal: Cell Genomics (2024)

The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 indels, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate or cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights a comprehensive and clear picture of IR effects on normal mammalian genomes.
Phylogenomic analyses unraveled the evolution of viral tolerance in bats
Authors: Yulong Xie, Guojie Zhang
Journal: Cell Genomics (2024)

Bats host a range of viruses, exhibiting a coevolution process with many virus genera and a special capacity for viral tolerance. Foley et al.1 performed phylogenomic analyses for 60 bat species, finding that swarming behavior might facilitate cross-species introgression and the spread of anti-virus immunity gene loci across species.
Episodic memory development: Bridging animal and human research
Authors: Juraj Bevandić, Loïc J. Chareyron, Jocelyne Bachevalier, Francesca Cacucci, Lisa Genzel, Nora S. Newcombe, Faraneh Vargha-Khadem, H. Freyja Ólafsdóttir
Journal: Neuron (2024)

Human episodic memory is not functionally evident until about 2 years of age and continues to develop into the school years. Behavioral studies have elucidated this developmental timeline and its constituent processes. In tandem, lesion and neurophysiological studies in non-human primates and rodents have identified key neural substrates and circuit mechanisms that may underlie episodic memory development. Despite this progress, collaborative efforts between psychologists and neuroscientists remain limited, hindering progress. Here, we seek to bridge human and non-human episodic memory development research by offering a comparative review of studies using humans, non-human primates, and rodents. We highlight critical theoretical and methodological issues that limit cross-fertilization and propose a common research framework, adaptable to different species, that may facilitate cross-species research endeavors.
Better translation via collaboration: The MRC National Mouse Genetics Network
Authors: Owen Sansom, Sara Wells, David Kent, Andrew Wood, Robert D.S. Pitceathly, Anthony Isles, Karen Liu, Stephen Twigg, Karen Blyth, Louis Chesler
Journal: Cell Genomics (2024)

The MRC National Mouse Genetics Network (NMGN) has been established in the UK to bring together researchers from academia and industry across the country from a wide range of disease areas and research backgrounds to rapidly facilitate clinical translation of mouse research findings and foster an environment of interdisciplinary learning.