tbuckley/cabot-search huggingface dataset:
Surgical Repair vs Splenectomy in Patients With Severe Traumatic Spleen Injuries
Authors: Dominik A. Jakob, Martin Müller, Apostolos Kolitsas, Aristomenis K. Exadaktylos, Demetrios Demetriades
Journal: JAMA Network Open (2024)

Importance The spleen is often removed in laparotomy after traumatic abdominal injury, with little effort made to preserve the spleen. Objective To explore the association of surgical management (splenic repair vs splenectomy) with outcomes in patients with traumatic splenic injuries undergoing laparotomy and to determine whether splenic repair is associated with lower mortality compared with splenectomy. Design, Setting, and Participants This is a trauma registry–based cohort study using the American College of Surgeons Trauma Quality Improvement Program database from January 2013 to December 2019. Participants included adult patients with severe splenic injuries (Abbreviated Injury Scale [AIS] grades 3-5) undergoing laparotomy after traumatic injury within 6 hours of admission. Data analysis was performed from April to August 2023. Exposures Splenic repair vs splenectomy in patients with severe traumatic splenic injury. Main Outcomes and Measures The primary outcome was in-hospital mortality. Outcomes were compared using different statistical approaches, including 1:1 exact matching with consecutive conditional logistic regression analysis as the primary analysis and multivariable logistic regression, propensity score matching, and inverse-probability weighting as sensitivity analyses. Results A total of 11 247 patients (median [IQR] age, 35 [24-52] years; 8179 men [72.7%]) with a severe traumatic splenic injury undergoing laparotomy were identified. Of these, 10 820 patients (96.2%) underwent splenectomy, and 427 (3.8%) underwent splenic repair. Among patients who underwent an initial splenic salvage procedure, 23 (5.3%) required a splenectomy during the subsequent hospital stay; 400 patients with splenic preservation were matched with 400 patients who underwent splenectomy (matched for age, sex, hypotension, trauma mechanism, AIS spleen grade, and AIS groups [0-2, 3, and 4-5] for head, face, neck, thorax, spine, and lower and upper extremity). Mortality was significantly lower in the splenic repair group vs the splenectomy group (26 patients [6.5%] vs 51 patients [12.8%]). The association of splenic repair with lower mortality was subsequently verified by conditional regression analysis (adjusted odds ratio, 0.4; 95% CI, 0.2-0.9; P = .03). Multivariable logistic regression, propensity score matching, and inverse-probability weighting confirmed this association. Conclusions and Relevance In this retrospective cohort study, splenic repair was independently associated with lower mortality compared with splenectomy during laparotomy after traumatic splenic injury. These findings suggest that efforts to preserve the spleen might be indicated in selected cases of severe splenic injuries.
Safety and Risk Assessment of No-Prescription Online Semaglutide Purchases
Authors: Amir Reza Ashraf, Tim K. Mackey, János Schmidt, Győző Kulcsár, Róbert György Vida, Jiawei Li, András Fittler
Journal: JAMA Network Open (2024)

This qualitative study assesses the quality, amount of active ingredient, and characteristics associated with counterfeiting of semaglutide purchased from illegal online pharmacies without a prescription.
Glycated Hemoglobin A<sub>1c</sub> Time in Range and Dementia in Older Adults With Diabetes
Authors: Patricia C. Underwood, Libin Zhang, David C. Mohr, Julia C. Prentice, Richard E. Nelson, Andrew E. Budson, Paul R. Conlin
Journal: JAMA Network Open (2024)

Individuals with diabetes commonly experience Alzheimer disease and related dementias (ADRD). Factors such as hypoglycemia, hyperglycemia, and glycemic variability have been associated with increased risk of ADRD. Traditional glycemic measures, such as mean glycated hemoglobin A1c (HbA1c), may not identify the dynamic and complex pathophysiologic factors in the association between diabetes and ADRD. The HbA1c time in range (TIR) is a previously developed measure of glycemic control that expresses HbA1c stability over time within specific ranges. This measure may inform the current understanding of the association between glucose levels over time and ADRD incidence.
A shared model-based linguistic space for transmitting our thoughts from brain to brain in natural conversations
Authors: Zaid Zada, Ariel Goldstein, Sebastian Michelmann, Erez Simony, Amy Price, Liat Hasenfratz, Emily Barham, Asieh Zadbood, Werner Doyle, Daniel Friedman, Patricia Dugan, Lucia Melloni, Sasha Devore, Adeen Flinker, Orrin Devinsky, Samuel A. Nastase, Uri Hasson
Journal: Neuron (2024)
ERCC2 mutations alter the genomic distribution pattern of somatic mutations and are independently prognostic in bladder cancer
Authors: Jayne A. Barbour, Tong Ou, Haocheng Yang, Hu Fang, Noel C. Yue, Xiaoqiang Zhu, Michelle W. Wong-Brown, Yuen T. Wong, Nikola A. Bowden, Song Wu, Jason W.H. Wong
Journal: Cell Genomics (2024)

Excision repair cross-complementation group 2 (ERCC2) encodes the DNA helicase xeroderma pigmentosum group D, which functions in transcription and nucleotide excision repair. Point mutations in ERCC2 are putative drivers in around 10% of bladder cancers (BLCAs) and a potential positive biomarker for cisplatin therapy response. Nevertheless, the prognostic significance directly attributed to ERCC2 mutations and its pathogenic role in genome instability remain poorly understood. We first demonstrated that mutant ERCC2 is an independent predictor of prognosis in BLCA. We then examined its impact on the somatic mutational landscape using a cohort of ERCC2 wild-type (n = 343) and mutant (n = 39) BLCA whole genomes. The genome-wide distribution of somatic mutations is significantly altered in ERCC2 mutants, including T[C>T]N enrichment, altered replication time correlations, and CTCF-cohesin binding site mutation hotspots. We leverage these alterations to develop a machine learning model for predicting pathogenic ERCC2 mutations, which may be useful to inform treatment of patients with BLCA.
Comment on “Prognostic Value of Baseline Tumor Burden and Tumor Dissemination Extracted From 18F-FDG PET/CT in a Cohort of Adult Patients With Early or Advanced Hodgkin Lymphoma”
Authors: Wenjue Tang, Yinlin Tang
Journal: Clinical Nuclear Medicine (2024)

Department of Pediatric Hematology & Oncology, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China. Department of Clinical Laboratory, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China [email protected] Conflicts of interest and sources of funding: none declared.
β-resorcylic acid released by Limosilactobacillus reuteri protects against cisplatin-induced ovarian toxicity and infertility
Authors: Yinglin Feng, Huimin Zheng, Chunhua Yin, Dong Liang, Siyou Zhang, Jingrui Chen, Feihong Mai, Zixin Lan, Menglin Zhu, Zhensheng Mai, Sj Shen, Thisun Jayawardana, Rong Wu, Wenli Tang, Renfang Zhang, Xiaoyun He, Shanshan Zheng, Qian Hu, Yubin Han, Yuanhao Yang, Shenhai Gong, Zhang Wang, Emad M. El-Omar, Wei Luo, Xueqin Chen, Guoqiang Chen, Pan Li, Xia Chen
Journal: Cell Reports Medicine (2024)

Chemotherapy-induced premature ovarian insufficiency (CIPOI) triggers gonadotoxicity in women undergoing cancer treatment, leading to loss of ovarian reserves and subfertility, with no effective therapies available. In our study, fecal microbiota transplantation in a cisplatin-induced POI mouse model reveals that a dysbiotic gut microbiome negatively impacts ovarian health in CIPOI. Multi-omics analyses show a significant decrease in Limosilactobacillus reuteri and its catabolite, β-resorcylic acid , in the CIPOI group in comparison to healthy controls. Supplementation with L. reuteri or β-RA mitigates cisplatin-induced hormonal disruptions, morphological damages, and reductions in follicular reserve. Most importantly, β-RA pre-treatment effectively preserves oocyte function, embryonic development, and fetus health, thereby protecting against chemotherapy-induced subfertility. Our results provide evidence that β-RA suppresses the nuclear accumulation of sex-determining region Y-box 7, which in turn reduces Bcl-2-associated X activation and inhibits granulosa cell apoptosis. These findings highlight the therapeutic potential of targeting the gut-ovary axis for fertility preservation in CIPOI.
The amalgam of naive CD4+ T cell transcriptional states is reconfigured by helminth infection to dampen the amplitude of the immune response
Authors: Zachary Even, Alexandre P. Meli, Antariksh Tyagi, Aurobind Vidyarthi, Neima Briggs, Dimitri A. de Kouchkovsky, Yong Kong, Yaqiu Wang, Daniel A. Waizman, Tyler A. Rice, Bony De Kumar, Xusheng Wang, Noah W. Palm, Joe Craft, Malay K. Basu, Sourav Ghosh, Carla V. Rothlin
Journal: Immunity (2024)

Naive CD4
Oncogenic Enhancers in Leukemia
Authors: Roger Mulet-Lazaro, Ruud Delwel
Journal: Blood Cancer Discovery (2024)

Although the study of leukemogenesis has traditionally focused on protein-coding genes, the role of enhancer dysregulation is becoming increasingly recognized. The advent of high-throughput sequencing, together with a better understanding of enhancer biology, has revealed how various genetic and epigenetic lesions produce oncogenic enhancers that drive transformation. These aberrations include translocations that lead to enhancer hijacking, point mutations that modulate enhancer activity, and copy number alterations that modify enhancer dosage. In this review, we describe these mechanisms in the context of leukemia and discuss potential therapeutic avenues to target these regulatory elements. Significance: Large-scale sequencing projects have uncovered recurrent gene mutations in leukemia, but the picture remains incomplete: some patients harbor no such aberrations, whereas others carry only a few that are insufficient to bring about transformation on their own. One of the missing pieces is enhancer dysfunction, which only recently has emerged as a critical driver of leukemogenesis. Knowledge of the various mechanisms of enhancer dysregulation is thus key for a complete understanding of leukemia and its causes, as well as the development of targeted therapies in the era of precision medicine.
Early detection of malignant and pre-malignant peripheral nerve tumors using cell-free DNA fragmentomics
Authors: R. Taylor Sundby, Jeffrey J. Szymanski, Alexander C. Pan, Paul A. Jones, Sana Z. Mahmood, Olivia H. Reid, Divya Srihari, Amy E. Armstrong, Stacey Chamberlain, Sanita Burgic, Kara Weekley, Béga Murray, Sneh Patel, Faridi Qaium, Andrea N. Lucas, Margaret Fagan, Anne Dufek, Christian F. Meyer, Natalie B. Collins, Christine A. Pratilas, Eva Dombi, Andrea M. Gross, AeRang Kim, John S.A. Chrisinger, Carina A. Dehner, Brigitte C. Widemann, Angela C. Hirbe, Aadel A. Chaudhuri, Jack F. Shern
Journal: Clinical Cancer Research (2024)

Early detection of neurofibromatosis type 1 (NF1)-associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1.
Echinocytes in pyruvate kinase deficiency, post‐splenectomy
Authors: Sarah A. Bassiony, Asad Luqmani, Barbara J. Bain
Journal: American Journal of Hematology (2024)

Mitapivat has been shown in a randomized clinical trial to significantly improve hemoglobin levels and reduce transfusion requirements,3 offering an improved quality of life, whilst also reducing the compounded risks associated with chronic transfusion in a young population. The authors declare no conflict of interest.
Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring
Authors: Elias Jabbour, Hagop Kantarjian
Journal: American Journal of Hematology (2024)

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an annual incidence of two cases/100 000. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults.
From foes to friends: rethinking the role of lymph nodes in prostate cancer
Authors: Raghav Gupta, Chandan K. Das, Sujit S. Nair, Adriana Marcela Pedraza-Bermeo, Ali H. Zahalka, Natasha Kyprianou, Nina Bhardwaj, Ashutosh K. Tewari
Journal: Nature Reviews Urology (2024)
A cohort study in family triads: impact of gut microbiota composition and early life exposures on intestinal resistome during the first two years of life
Authors: Roosa Jokela, Katariina MM Pärnänen, Alise J Ponsero, Leo Lahti, Kaija-Leena Kolho, Willem M de Vos, Anne Salonen
Journal: Gut Microbes (2024)

Antibiotic resistance genes (ARGs) are prevalent in the infant gut microbiota and make up the intestinal resistome, representing a community ARG reservoir. This study focuses on the dynamics and persistence of ARGs in the early gut microbiota, and the effect of early exposures therein. We leveraged 2,328 stool metagenomes from 475 children in the HELMi cohort and the available parental samples to study the diversity, dynamics, and intra-familial sharing of the resistome during the first two years of life. We found higher within-family similarity of the gut resistome composition and ARG load in infant-mother pairs, and between spouses, but not in father-infant pairs. Early gut microbiota composition and development correlated with the ARG load;
G‐quadruplex‐Based Artificial Transmembrane Channels Induce Cancer Cell Apoptosis by Perturbing Potassium Ion Homeostasis
Authors: Shuangna Liu, Wanyu Xu, Jing Zheng, Kleins Ngocho, Hui Chen, Kemin Wang, Siqi Xiong, Xiaoxiao He, Jianbo Liu
Journal: Advanced Healthcare Materials (2024)

Transmembrane ion transport modality has received a widespread attention due to its apoptotic activation toward anticancer cell activities. In this study, G-quadruplex-based potassium-specific transmembrane channels have been developed to facilitate the intracellular K
Incidence of laboratory-confirmed influenza and RSV and associated presenteeism and absenteeism among healthcare personnel, Israel, influenza seasons 2016 to 2019
Authors: Eduardo Azziz-Baumgartner, Avital Hirsch, Young M Yoo, Alon Peretz, David Greenberg, Yonat Shemer Avni, Aharona Glatman-Freedman, Michal Mandelboim, Adam MacNeil, Emily T Martin, Gabriella Newes-Adeyi, Mark Thompson, Arnold S Monto, Ran D Balicer, Min Z Levine, Mark A Katz
Journal: Eurosurveillance (2024)

BackgroundHealthcare personnel (HCP) are at high risk for respiratory infections through occupational exposure to respiratory viruses.AimWe used data from a prospective influenza vaccine effectiveness study in HCP to quantify the incidence of acute respiratory infections (ARI) and their associated presenteeism and absenteeism.MethodsAt the start and end of each season, HCP at two Israeli hospitals provided serum to screen for antibodies to influenza virus using the haemagglutination inhibition assay. During the season, active monitoring for the development of ARI symptoms was conducted twice a week by RT-PCR testing of nasal swabs for influenza and respiratory syncytial virus (RSV). Workplace presenteeism and absenteeism were documented. We calculated incidences of influenza- and RSV-associated ARI and applied sampling weights to make estimates representative of the source population.ResultsThe median age of 2,505 participating HCP was 41 years, and 70% were female. Incidence was 9.1 per 100 person-seasons (95% CI: 5.8-14.2) for RT-PCR-confirmed influenza and 2.5 per 100 person-seasons (95% CI: 0.9-7.1) for RSV illness. Each season, 18-23% of unvaccinated and influenza-negative HCP seroconverted. The incidence of seroconversion or RT-PCR-confirmed influenza was 27.5 per 100 person-seasons (95% CI: 17.8-42.5). Work during illness occurred in 92% (95% CI: 91-93) of ARI episodes, absence from work in 38% (95% CI: 36-40).ConclusionInfluenza virus and RSV infections and associated presenteeism and absenteeism were common among HCP. Improving vaccination uptake among HCP, infection control, and encouraging sick HCP to stay home are important strategies to reduce ARI incidence and decrease the risk of in-hospital transmission.
Resurgence of Bordetella pertussis, including one macrolide-resistant isolate, France, 2024
Authors: Carla Rodrigues, Valérie Bouchez, Anaïs Soares, Sabine Trombert-Paolantoni, Fatima Aït El Belghiti, Jérémie F Cohen, Nathalie Armatys, Annie Landier, Thomas Blanchot, Marie Hervo, Julie Toubiana, Sylvain Brisse
Journal: Eurosurveillance (2024)

As other European countries, France is experiencing a resurgence of pertussis in 2024. Between 1 January and 31 May 2024, 5,616 (24.9%) positive Bordetella pertussis qPCR tests were identified, following a 3-year period of almost null incidence. Of 67 cultured and whole genome sequenced B. pertussis isolates, 66 produced pertactin and 56 produced FIM2, in contrast to pre-COVID-19 years. One isolate of genotype Bp-AgST4 was resistant to macrolides. Pertussis resurgence may favour isolates that produce FIM2 and pertactin.
Antifungal heteroresistance causes prophylaxis failure and facilitates breakthrough Candida parapsilosis infections
Authors: Bing Zhai, Chen Liao, Siddharth Jaggavarapu, Yuanyuan Tang, Thierry Rolling, Yating Ning, Tianshu Sun, Sean A. Bergin, Mergim Gjonbalaj, Edwin Miranda, N. Esther Babady, Oliver Bader, Ying Taur, Geraldine Butler, Li Zhang, Joao B. Xavier, David S. Weiss, Tobias M. Hohl
Journal: Nature Medicine (2024)
The traditional Chinese medicine Qiliqiangxin in heart failure with reduced ejection fraction: a randomized, double-blind, placebo-controlled trial
Authors: Iokfai Cheang, Wenming Yao, Yanli Zhou, Xu Zhu, Gehui Ni, Xinyi Lu, Shengen Liao, Rongrong Gao, Fang Zhou, Jiangang Shen, Alice Yeuk Lan Leung, Meng Jiang, Hong Kong, Ling Bai, Ailiman Mahemuti, Haitao Yuan, Yu-Gang Dong, Chun-Ka Wong, Qinghua Xu, Gaoxing Zhang, Jianhua Wu, Qi Lu, Junhai Zhang, Chunxi Cha, Qian Ren, Lu Fu, Bing Wang, Yongshun Xu, Houxiang Hu, Jing Dong, Zhuo Shang, Chaoping Yu, Songsen Li, Chen Yao, Lingling Gao, Haifeng Zhang, Anthony Rosenzweig, Zhenhua Jia, Xinli Li
Journal: Nature Medicine (2024)

Previous findings have indicated the potential benefits of the Chinese traditional medicine Qiliqiangxin (QLQX) in heart failure. Here we performed a double-blind, randomized controlled trial to evaluate the efficacy and safety of QLQX in patients with heart failure and reduced ejection fraction (HFrEF). This multicenter trial, conducted in 133 hospitals in China, enrolled 3,110 patients with HFrEF with NT-proBNP levels of ≥450 pg ml
A GnRH neuronal population in the olfactory bulb translates socially relevant odors into reproductive behavior in male mice
Authors: Laurine Decoster, Sara Trova, Stefano Zucca, Janice Bulk, Ayden Gouveia, Gaetan Ternier, Tori Lhomme, Amandine Legrand, Sarah Gallet, Ulrich Boehm, Amanda Wyatt, Vanessa Wahl, Philipp Wartenberg, Erik Hrabovszky, Gergely Rácz, Federico Luzzati, Giulia Nato, Marco Fogli, Paolo Peretto, Sonja C. Schriever, Miriam Bernecker, Paul T. Pfluger, Sophie M. Steculorum, Serena Bovetti, Sowmyalakshmi Rasika, Vincent Prevot, Mauro S. B. Silva, Paolo Giacobini
Journal: Nature Neuroscience (2024)
Twenty-five years of sentinel laboratory-based surveillance of shigellosis in a high-income country endemic for the disease, Israel, 1998 to 2022
Authors: Dani Cohen, Orit Treygerman, Shifra Ken-Dror, Orli Sagi, Merav Strauss, Miriam Parizade, Sophy Goren, Analía V Ezernitchi, Assaf Rokney, Lital Keinan-Boker, Ravit Bassal
Journal: Eurosurveillance (2024)

Background Shigella is a leading cause of moderate-to-severe diarrhoea worldwide and diarrhoeal deaths in children in low- and-middle-income countries. Aim We investigated trends and characteristics of shigellosis and antimicrobial resistance of Shigella sonnei in Israel. Methods We analysed data generated by the Sentinel Laboratory-Based Surveillance Network for Enteric Pathogens that systematically collects data on detection of Shigella at sentinel laboratories, along with the characterisation of the isolates at the Shigella National Reference Laboratory. Trends in the shigellosis incidence were assessed using Joinpoint regression and interrupted time-series analyses. Results The average incidence of culture-confirmed shigellosis in Israel declined from 114 per 100,000 population (95% confidence interval (CI): 112–115) 1998–2004 to 80 per 100,000 population (95% CI: 79–82) 2005–2011. This rate remained stable 2012–2019, being 18–32 times higher than that reported from the United States or European high-income countries. After decreasing to its lowest values during the COVID-19 pandemic years (19/100,000 in 2020 and 5/100,000 in 2021), the incidence of culture-confirmed shigellosis increased to 39 per 100,000 population in 2022. Shigella sonnei is the most common serogroup, responsible for a cyclic occurrence of propagated epidemics, and the proportion of Shigella flexneri has decreased. Simultaneous resistance of S. sonnei to ceftriaxone, ampicillin and sulphamethoxazole-trimethoprim increased from 8.5% (34/402) in 2020 to 92.0% (801/876) in 2022. Conclusions These findings reinforce the need for continuous laboratory-based surveillance and inform the primary and secondary prevention strategies for shigellosis in Israel and other endemic high-income countries or communities.
Longitudinal proteomics of leptin treatment in humans with acute and chronic energy deficiency-induced hypoleptinemia reveal novel, mainly immune-related, pleiotropic effects
Authors: Konstantinos Stefanakis, Martina Samiotaki, Vassiliki Papaevangelou, Laura Valenzuela-Vallejo, Nick Giannoukakis, Christos S. Mantzoros
Journal: Metabolism (2024)
Safety and reactogenicity of a controlled human infection model of sand fly-transmitted cutaneous leishmaniasis
Authors: Vivak Parkash, Helen Ashwin, Shoumit Dey, Jovana Sadlova, Barbora Vojtkova, Katrien Van Bocxlaer, Rebecca Wiggins, David Thompson, Nidhi Sharma Dey, Charles L Jaffe, Eli Schwartz, Petr Volf, Charles J N Lacey, Alison M Layton, Paul M Kaye
Journal: Nature Medicine (2024)

Abstract The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available. To facilitate vaccine development, we conducted an open-label observational study to establish a controlled human infection model (CHIM) of sand fly-transmitted cutaneous leishmaniasis (CL) caused by Leishmania major . Between 24 January and 12 August 2022, we exposed 14 participants to L. major -infected Phlebotomus duboscqi . The primary objective was to demonstrate effectiveness of lesion development (take rate) and safety (absence of CL lesion at 12 months). Secondary and exploratory objectives included rate of lesion development, parasite load and analysis of local immune responses by immunohistology and spatial transcriptomics. Lesion development was terminated by therapeutic biopsy (between days 14 and 42 after bite) in ten participants with clinically compatible lesions, one of which was not confirmed by parasite detection. We estimated an overall take rate for CL development of 64% (9/14). Two of ten participants had one and one of ten participants had two lesion recurrences 4–8 months after biopsy that were treated successfully with cryotherapy. No severe or serious adverse events were recorded, but as expected, scarring due to a combination of CL and the biopsy procedure was evident. All participants were lesion free at &gt;12-month follow-up. We provide the first comprehensive map of immune cell distribution and cytokine/chemokine expression in human CL lesions, revealing discrete immune niches. This CHIM offers opportunities for vaccine candidate selection based on human efficacy data and for a greater understanding of immune-mediated pathology. ClinicalTrials.gov identifier: NCT04512742 .