tbuckley/cabot-search huggingface dataset:
Multiple Nervous System Involvement of Erdheim-Chester Disease With Responsive Perinephritic Hypermetabolism
Authors: Zehra Pinar Koç, Pinar Pelin Özcan, Anil Tombak, Kerim Sönmezoğlu
Journal: Clinical Nuclear Medicine (2024)

Abstract A 36-year-old man who was at follow-up for histiocytosis had sudden-onset symptoms of unilateral ophthalmic increased pressure. The patient was referred to the FDG PET/CT for determination of involvement with suspicion of Erdheim-Chester disease. The reduction of the FDG uptake in all of the lesions (medial temporal lobes, nasal septum, medulla spinalis in sacral region, as well as perinephritic infiltrations), which were determined by the first PET/CT, was achieved at second imaging.
The role of NMR in advancing small molecule drug discovery
Authors: Leszek Poppe
Journal: Trends in Pharmacological Sciences (2024)

Navigating the ever-evolving landscape of nuclear magnetic resonance (NMR) poses challenges for the industry. This work explores promising approaches that illuminate protein–ligand interactions in the context of structural dynamics, facilitating targeted drug discovery. I acknowledge existing limitations and highlight future opportunities, which may pave the way for broader NMR integration and faster therapeutic development.
Correction: Migraine and risk of premature myocardial infarction and stroke among men and women: A Danish population-based cohort study
Authors: Cecilia Hvitfeldt Fuglsang, Lars Pedersen, Morten Schmidt, Jan P. Vandenbroucke, Hans Erik Bøtker, Henrik Toft Sørensen
Journal: PLoS Medicine (2024)

[This corrects the article DOI: 10.1371/journal.pmed.1004238.].
Improved Disease-Free Survival With Adjuvant Chemotherapy After Nephroureterectomy for Upper Tract Urothelial Cancer: Final Results of the POUT Trial
Authors: Alison Jane Birtle, Robert Jones, John Chester, Rebecca Lewis, Katie Biscombe, Mark Johnson, Anthony Blacker, Richard T. Bryan, James W.F. Catto, Ananya Choudhury, Prantik Das, Satinder Jagdev, Thomas Powles, John Wagstaff, Ka Ching Cheung, Fay Cafferty, Emma Hall
Journal: Journal of Clinical Oncology (2024)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. POUT was a phase III, randomized, open-label trial, including 261 patients with muscle-invasive or lymph node–positive, nonmetastatic upper tract urothelial cancer (UTUC) randomly assigned after radical nephroureterectomy to platinum-based chemotherapy (132) or surveillance (129). Primary outcome analysis demonstrated that chemotherapy improved disease-free survival (DFS). At that time, the planned secondary outcome analysis of overall survival (OS) was immature. By February 2022, 50 and 67 DFS events had occurred in the chemotherapy and surveillance groups, respectively, at a median follow-up of 65 months. The 5-year DFS was 62% versus 45%, univariable hazard ratio (HR), 0.55 (95% CI, 0.38 to 0.80, P = .001). The restricted mean survival time (RMST) was 18 months longer (95% CI, 6 to 30) in the chemotherapy arm. There were 46 and 60 deaths in the chemotherapy and control arms, respectively. The 5-year OS was 66% versus 57%, with univariable HR, 0.68 (95% CI, 0.46 to 1.00, P = .049) and RMST difference 11 months (95% CI, 1 to 21). Treatment effects were consistent across chemotherapy regimens (carboplatin or cisplatin) and disease stage. Toxicities were similar to those previously reported, and there were no clinically relevant differences in quality of life between arms. In summary, although OS was not the primary outcome measure, the updated results add further support for the use of adjuvant chemotherapy in patients with UTUC, suggesting long-term benefits.
Differential Responses to Immune Checkpoint Inhibitors are Governed by Diverse Mismatch Repair Gene Alterations
Authors: Moh'd M. Khushman, Michael D. Toboni, Joanne Xiu, Upender Manne, Alex Farrell, Emil Lou, Anthony F. Shields, Philip A. Philip, Mohamed E. Salem, Jim Abraham, David Spetzler, John Marshall, Priya Jayachandran, Michael J. Hall, Heinz-Josef Lenz, Ibrahim Halil Sahin, Andreas Seeber, Mathew A. Powell
Journal: Clinical Cancer Research (2024)

Abstract Purpose: The response to immune checkpoint inhibitors (ICI) in deficient mismatch repair (dMMR) colorectal cancer and endometrial cancer is variable. Here, we explored the differential response to ICIs according to different mismatch repair alterations Experimental Design: Colorectal cancer (N = 13,701) and endometrial cancer (N = 3,315) specimens were tested at Caris Life Sciences. Median overall survival (mOS) was estimated using Kaplan–Meier. The prediction of high-, intermediate-, and low-affinity epitopes by tumor mutation burden (TMB) values was conducted using R-squared (R2). Results: Compared with mutL (MLH1 and PMS2) co-loss, the mOS was longer in mutS (MSH2 and MSH6) co-loss in all colorectal cancer (54.6 vs. 36 months; P = 0.0.025) and endometrial cancer (81.5 vs. 48.2 months; P &amp;lt; 0.001) patients. In ICI-treated patients, the mOS was longer in mutS co-loss in colorectal cancer [not reached (NR) vs. 36 months; P = 0.011). In endometrial cancer, the mOS was NR vs. 42.2 months; P = 0.711]. The neoantigen load (NAL) in mutS co-loss compared with mutL co-loss was higher in colorectal cancer (high-affinity epitopes: 25.5 vs. 19; q = 0.017, intermediate: 39 vs. 32; q = 0.004, low: 87.5 vs. 73; q &amp;lt; 0.001) and endometrial cancer (high-affinity epitopes: 15 vs. 11; q = 0.002, intermediate: 27.5 vs. 19; q &amp;lt; 0.001, low: 59 vs. 41; q &amp;lt; 0.001), respectively. R2 ranged from 0.25 in mutS co-loss colorectal cancer to 0.95 in mutL co-loss endometrial cancer. Conclusions: Patients with mutS co-loss experienced longer mOS in colorectal cancer and endometrial cancer and better response to ICIs in colorectal cancer. Among all explored biomarkers, NAL was higher in mutS co-loss and may be a potential driving factor for the observed better outcomes. TMB did not reliably predict NAL.
Germline Mutations of Holliday Junction Resolvase Genes in Multiple Primary Malignancies Involving Lung Cancer Lead to PARP Inhibitor Sensitization
Authors: Haoran Wang, Yuping Chen, Xinshu Wang, Binhao Huang, Juntao Xie, Hui Yin, Jie Yang, Jinhuan Wu, Jian Yuan, Jie Zhang
Journal: Clinical Cancer Research (2024)

Abstract Purpose: The incidence of multiple primary malignancies (MPM) involving lung cancer has increased in recent decades. There is an urgent need to clarify the genetic profile of such patients and explore more efficacious therapy for them. Experimental Design: Peripheral blood samples from MPM involving patients with lung cancer were assessed by whole-exome sequencing (WES), and the identified variants were referenced for pathogenicity using the public available database. Pathway enrichment analysis of mutated genes was performed to identify the most relevant pathway. Next, the effects of mutations in relevant pathway on function and response to targeted drugs were verified by in vitro and in vivo experiments. Results: Germline exomes of 71 patients diagnosed with MPM involving lung cancer were sequenced. Pathway enrichment analysis shows that the homologous recombination repair (HRR) pathway has the strongest correlation. Moreover, HRR genes, especially key Holliday junction resolvases (HJR) genes (GEN1, BLM, SXL4, and RMI1), were most frequently mutated, unlike the status in the samples from patients with lung cancer only. Next, we identified a total of seven mutations in HJR genes led to homologous recombination DNA repair deficiency and rendered lung cancer cells sensitive to PARP inhibitor treatment, both in vitro and in vivo. Conclusions: This is the first study to map the profile of germline mutations in patients with MPM involving lung cancer. This study may shed light on early prevention and novel targeted therapies for MPM involving patients with lung cancer with HJR mutations.
Optimizing Cervical Target Volume in Patients with Nasopharyngeal Cancer Based On Nodal Drainage Distance
Authors: Yang Liu, Wenbin Yan, Chaosu Hu, Xiaodong Huang, Kai Wang, Yuan Qu, Xuesong Chen, Runye Wu, Ye Zhang, Jianghu Zhang, Jingwei Luo, Ye-Xiong Li, Jingbo Wang, Junlin Yi
Journal: Clinical Cancer Research (2024)

Abstract Purpose: To determine the potential nodal drainage distances of nasopharyngeal carcinoma (NPC) by investigating spatial distribution of metastatic lymph nodes (LN). Experimental Design: Patients with NPC harboring at least two ipsilateral metastatic LNs were enrolled. LN spreading distances were analyzed in nonrestricted direction, cranial-to-caudal direction, and between the two most caudal LNs. Euclidean distance (ED) and vertical distance (VD) between any two LNs were computed. The nearest-neighbor ED and VD covering 95% of LNs or patients (p95-ED and p95-VD) were considered drainage distances, and were further validated by independent internal and external cohorts with recurrent LNs. Results: In all, 5,836 metastatic LNs in 948 patients were contoured. Corresponding to the three scenarios, per-LN level, the p95-EDs were 2.83, 3.28, and 3.55 cm, and p95-VDs were 2.17, 2.32, and 2.63 cm, respectively. Per-patient level, the p95-EDs were 3.25, 3.95, and 3.81 cm, and p95-VDs were 2.67, 2.81, and 2.73 cm, respectively. In internal validation, over 95% of recurred LNs occurred within ED of 2.91 cm and VD of 0.82 cm to the neighbor LN, and the corresponding distances in external validation were 2.77 and 0.67 cm, respectively. Conclusions: In NPC, the maximum LN drainage distance was 3.95 cm without considering the direction. Specifically, in cranial-to-caudal direction, the sufficient vertical drainage distance was 2.81 cm, indicating that a 3-cm extension from the most inferior node may be rational as caudal border of the prophylactic clinical target volume (CTV). These findings promote in-depth understanding of nodal spreading patterns, uncovering paramount evidence for individualized CTV.
A 25-Year Journey as Author and Associate Editor of<i>Pharmacological Reviews</i>—Editorial
Authors: Martin C. Michel
Journal: Pharmacological Reviews (2024)

My first contact with Pharmacological Reviews as an author was in the late 1990s. My mentor at the time, the late Dr. Otto-Erich Brodde, approached me one day asking whether I would like to join him in preparing a manuscript on adrenergic and muscarinic receptors in the heart for Pharmacological
An indicator framework for the monitoring and evaluation of event-based surveillance systems
Authors: Adam W Crawley, Kyeng Mercy, Sabrina Shivji, Hannah Lofgren, Daniella Trowbridge, Christine Manthey, Yenew Kebede Tebeje, Alexey Wil Clara, Kimberly Landry, Stephanie J Salyer
Journal: The Lancet Global Health (2024)

Event-based surveillance (EBS) systems have been implemented globally to support early warning surveillance across human, animal, and environmental health in diverse settings, including at the community level, within health facilities, at border points of entry, and through media monitoring of internet-based sources. EBS systems should be evaluated periodically to ensure that they meet the objectives related to the early detection of health threats and to identify areas for improvement in the quality, efficiency, and usefulness of the systems. However, to date, there has been no comprehensive framework to guide the monitoring and evaluation of EBS systems; this absence of standardisation has hindered progress in the field. The Africa Centres for Disease Control and Prevention and US Centers for Disease Control and Prevention have collaborated to develop an EBS monitoring and evaluation indicator framework, adaptable to specific country contexts, that uses measures relating to input, activity, output, outcome, and impact to map the processes and expected results of EBS systems. Through the implementation and continued refinement of these indicators, countries can ensure the early detection of health threats and improve their ability to measure and describe the impacts of EBS systems, thus filling the current evidence gap regarding their effectiveness.
Antibody agonists trigger immune receptor signaling through local exclusion of receptor-type protein tyrosine phosphatases
Authors: Anna H. Lippert, Christopher Paluch, Meike Gaglioni, Mai T. Vuong, James McColl, Edward Jenkins, Martin Fellermeyer, Joseph Clarke, Sumana Sharma, Sara Moreira da Silva, Billur Akkaya, Consuelo Anzilotti, Sara H. Morgan, Claire F. Jessup, Markus Körbel, Uzi Gileadi, Judith Leitner, Rachel Knox, Mami Chirifu, Jiandong Huo, Susan Yu, Nicole Ashman, Yuan Lui, Ian Wilkinson, Kathrine E. Attfield, Lars Fugger, Nathan J. Robertson, Christopher J. Lynch, Lynne Murray, Peter Steinberger, Ana Mafalda Santos, Steven F. Lee, Richard J. Cornall, David Klenerman, Simon J. Davis
Journal: Immunity (2024)

Antibodies can block immune receptor engagement or trigger the receptor machinery to initiate signaling. We hypothesized that antibody agonists trigger signaling by sterically excluding large receptor-type protein tyrosine phosphatases (RPTPs) such as CD45 from sites of receptor engagement. An agonist targeting the costimulatory receptor CD28 produced signals that depended on antibody immobilization and were sensitive to the sizes of the receptor, the RPTPs, and the antibody itself. Although both the agonist and a non-agonistic anti-CD28 antibody locally excluded CD45, the agonistic antibody was more effective. An anti-PD-1 antibody that bound membrane proximally excluded CD45, triggered Src homology 2 domain-containing phosphatase 2 recruitment, and suppressed systemic lupus erythematosus and delayed-type hypersensitivity in experimental models. Paradoxically, nivolumab and pembrolizumab, anti-PD-1-blocking antibodies used clinically, also excluded CD45 and were agonistic in certain settings. Reducing these agonistic effects using antibody engineering improved PD-1 blockade. These findings establish a framework for developing new and improved therapies for autoimmunity and cancer.
Signaling via a CD27-TRAF2-SHP-1 axis during naive T cell activation promotes memory-associated gene regulatory networks
Authors: Carla A. Jaeger-Ruckstuhl, Yun Lo, Elena Fulton, Olivia G. Waltner, Tamer B. Shabaneh, Sylvain Simon, Pranav V. Muthuraman, Colin E. Correnti, Oliver J. Newsom, Ian A. Engstrom, Sami B. Kanaan, Shruti S. Bhise, Jobelle M.C. Peralta, Raymond Ruff, Jason P. Price, Sylvia M. Stull, Andrew R. Stevens, Grace Bugos, Mitchell G. Kluesner, Valentin Voillet, Vishaka Muhunthan, Fionnuala Morrish, James M. Olson, Raphaël Gottardo, Jay F. Sarthy, Steven Henikoff, Lucas B. Sullivan, Scott N. Furlan, Stanley R. Riddell
Journal: Immunity (2024)

The interaction of the tumor necrosis factor receptor (TNFR) family member CD27 on naive CD8+ T (Tn) cells with homotrimeric CD70 on antigen-presenting cells (APCs) is necessary for T cell memory fate determination. Here, we examined CD27 signaling during Tn cell activation and differentiation. In conjunction with T cell receptor (TCR) stimulation, ligation of CD27 by a synthetic trimeric CD70 ligand triggered CD27 internalization and degradation, suggesting active regulation of this signaling axis. Internalized CD27 recruited the signaling adaptor TRAF2 and the phosphatase SHP-1, thereby modulating TCR and CD28 signals. CD27-mediated modulation of TCR signals promoted transcription factor circuits that induced memory rather than effector associated gene programs, which are induced by CD28 costimulation. CD27-costimulated chimeric antigen receptor (CAR)-engineered T cells exhibited improved tumor control compared with CD28-costimulated CAR-T cells. Thus, CD27 signaling during Tn cell activation promotes memory properties with relevance to T cell immunotherapy.
Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort
Authors: Laury Sellem, Bernard Srour, Guillaume Javaux, Eloi Chazelas, Benoit Chassaing, Emilie Viennois, Charlotte Debras, Nathalie Druesne-Pecollo, Younes Esseddik, Fabien Szabo de Edelenyi, Nathalie Arnault, Cédric Agaësse, Alexandre De Sa, Rebecca Lutchia, Inge Huybrechts, Augustin Scalbert, Fabrice Pierre, Xavier Coumoul, Chantal Julia, Emmanuelle Kesse-Guyot, Benjamin Allès, Pilar Galan, Serge Hercberg, Mélanie Deschasaux-Tanguy, Mathilde Touvier
Journal: PLoS Medicine (2024)

Background Emulsifiers are widely used food additives in industrially processed foods to improve texture and enhance shelf-life. Experimental research suggests deleterious effects of emulsifiers on the intestinal microbiota and the metabolome, leading to chronic inflammation and increasing susceptibility to carcinogenesis. However, human epidemiological evidence investigating their association with cancer is nonexistent. This study aimed to assess associations between food additive emulsifiers and cancer risk in a large population-based prospective cohort. Methods and findings This study included 92,000 adults of the French NutriNet-Santé cohort without prevalent cancer at enrolment (44.5 y [SD: 14.5], 78.8% female, 2009 to 2021). They were followed for an average of 6.7 years [SD: 2.2]. Food additive emulsifier intakes were estimated for participants who provided at least 3 repeated 24-h dietary records linked to comprehensive, brand-specific food composition databases on food additives. Multivariable Cox regressions were conducted to estimate associations between emulsifiers and cancer incidence. Overall, 2,604 incident cancer cases were diagnosed during follow-up (including 750 breast, 322 prostate, and 207 colorectal cancers). Higher intakes of mono- and diglycerides of fatty acids (FAs) (E471) were associated with higher risks of overall cancer (HR high vs. low category = 1.15; 95% CI [1.04, 1.27], p-trend = 0.01), breast cancer (HR = 1.24; 95% CI [1.03, 1.51], p-trend = 0.04), and prostate cancer (HR = 1.46; 95% CI [1.09, 1.97], p-trend = 0.02). In addition, associations with breast cancer risk were observed for higher intakes of total carrageenans (E407 and E407a) (HR = 1.32; 95% CI [1.09, 1.60], p-trend = 0.009) and carrageenan (E407) (HR = 1.28; 95% CI [1.06, 1.56], p-trend = 0.01). No association was detected between any of the emulsifiers and colorectal cancer risk. Several associations with other emulsifiers were observed but were not robust throughout sensitivity analyses. Main limitations include possible exposure measurement errors in emulsifiers intake and potential residual confounding linked to the observational design. Conclusions In this large prospective cohort, we observed associations between higher intakes of carrageenans and mono- and diglycerides of fatty acids with overall, breast and prostate cancer risk. These results need replication in other populations. They provide new epidemiological evidence on the role of emulsifiers in cancer risk. Trial registration ClinicalTrials.gov NCT03335644 .
Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): final results of a randomised phase 3 study
Authors: Thomas Yau, Ahmed Kaseb, Ann-Lii Cheng, Shukui Qin, Andrew X Zhu, Stephen L Chan, Tamar Melkadze, Wattana Sukeepaisarnjaroen, Valery Breder, Gontran Verset, Edward Gane, Ivan Borbath, Jose David Gomez Rangel, Baek-Yeol Ryoo, Tamta Makharadze, Philippe Merle, Fawzi Benzaghou, Steven Milwee, Zhong Wang, Dominic Curran, Robin Kate Kelley, Lorenza Rimassa
Journal: The Lancet. Gastroenterology & hepatology (2024)
Do pulmonary rehabilitation programmes improve outcomes in patients with COPD posthospital discharge for exacerbation: a systematic review and meta-analysis
Authors: Alex R Jenkins, Chris Burtin, Pat G Camp, Peter Lindenauer, Brian Carlin, Jennifer A Alison, Carolyn Rochester, Anne E Holland
Journal: Thorax (2024)

Introduction Previous systematic reviews have provided heterogeneous and differing estimates for the efficacy of pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this review was to examine the efficacy of pulmonary rehabilitation programmes initiated within 3 weeks of hospital discharge following an exacerbation of COPD. Methods An update of a previous Cochrane review was undertaken using the Cochrane Airways Review Group Specialised Register. Searches were conducted from October 2015 to August 2023 for studies that initiated pulmonary rehabilitation within 3 weeks of hospital discharge. Studies assessing the impact of solely inpatient pulmonary rehabilitation were excluded. Forest plots were generated using a generic inverse variance random effects method. Results Seventeen studies were included. Posthospital discharge pulmonary rehabilitation reduced hospital re-admissions (OR 0.48, 95% CI 0.30 to 0.77, I 2 =67%), improved exercise capacity (6 min walk test, mean difference (MD) 57 m, 95% CI 29 to 86, I 2 =89%; incremental shuttle walk test, MD 43 m, 95% CI 6 to 79, I 2 =81%), health-related quality of life (St. George’s Respiratory Questionnaire, MD −8.7 points, 95% CI −12.5 to −4.9, I 2 =59%; Chronic Respiratory Disease Questionnaire (CRQ)-emotion, MD 1.0 points, 95% CI 0.4 to 1.6, I 2 =74%; CRQ-fatigue, MD 0.9 points, 95% CI 0.1 to 1.6, I 2 =91%), and dyspnoea (CRQ-dyspnoea, MD 1.0 points, 95% CI 0.3 to 1.7, I 2 =87%; modified Medical Research Council Dyspnoea Scale, MD −0.3 points, 95% CI −0.5 to −0.1, I 2 =60%). Significant effects were not observed for CRQ-mastery, COPD assessment test, EuroQol-5 Dimension-5 Level and mortality. No intervention-related adverse events were reported. Discussion Pulmonary rehabilitation delivered posthospital discharge for exacerbation of COPD results in a reduction in hospital re-admissions and improvements in exercise capacity, health-related quality of life and dyspnoea in the absence of any intervention-related adverse events. Trial registration number CRD42023406397.
Intensive care unit interventions to promote sleep and circadian biology in reducing incident delirium: a scoping review
Authors: M Elizabeth Wilcox, Lisa Burry, Marina Englesakis, Briar Coman, Marietou Daou, Frank MP van Haren, E Wes Ely, Karen J Bosma, Melissa P Knauert
Journal: Thorax (2024)

Despite plausible pathophysiological mechanisms, research is needed to confirm the relationship between sleep, circadian rhythm and delirium in patients admitted to the intensive care unit (ICU). The objective of this review is to summarise existing studies promoting, in whole or in part, the normalisation of sleep and circadian biology and their impact on the incidence, prevalence, duration and/or severity of delirium in ICU.
Barriers and facilitators for optimizing HIV screening target trans women in Taiwan: convergent mixed-method design
Authors: Piao-Yi Chiou, Ben Vincent, Ling-Xi Chen, Chia-Lin Li, Szu-Jui Chou, Wei-Wen Tsao, Jheng-Min Yu, Sen-Chieh Hsu
Journal: International Journal of Transgender Health (2024)

Background Trans women are a key global population affected by HIV infection. Although strategies have targeted to encourage trans women to complete HIV screening, frequency of testing in this population remains low.
Development and evaluation of a human CD47/HER2 bispecific antibody for Trastuzumab-resistant breast cancer immunotherapy
Authors: Binglei Zhang, Jianxiang Shi, Xiaojing Shi, Xiaolu Xu, Le Gao, Song Li, Mengmeng Liu, Mengya Gao, Shuiling Jin, Jian Zhou, Dandan Fan, Fang Wang, Zhenyu Ji, Zhilei Bian, Yongping Song, Wenzhi Tian, Yichao Zheng, Linping Xu, Wei Li
Journal: Drug Resistance Updates (2024)