tbuckley/cabot-search huggingface dataset:
Effectiveness of sulfadoxine–pyrimethamine plus amodiaquine and dihydroartemisinin–piperaquine for seasonal malaria chemoprevention in Uganda: a three-arm, open-label, non-inferiority and superiority, cluster-randomised, controlled trial
Authors: Anthony Nuwa, Kevin Baker, Richard Kajubi, Chukwudi A Nnaji, Katherine Theiss-Nyland, Musa Odongo, Tonny Kyagulanyi, Jane Nabakooza, David Salandini, Victor Asua, Maureen Nakirunda, Christian Rassi, Damian Rutazaana, Richard Achuma, Patrick Sagaki, John Baptist Bwanika, Godfrey Magumba, Adoke Yeka, Sam Nsobya, Moses R Kamya, James Tibenderana, Jimmy Opigo
Journal: The Lancet Infectious Diseases (2025)
Pembrolizumab with or without bevacizumab in platinum-resistant recurrent or metastatic nasopharyngeal carcinoma: a randomised, open-label, phase 2 trial
Authors: Wan-Qin Chong, Jia-Li Low, Joshua K Tay, Thi Bich Uyen Le, Grace Shi-Qing Goh, Kenneth Sooi, Hui-Lin Teo, Seng-Wee Cheo, Regina Tong-Xin Wong, Jens Samol, Ming-Yann Lim, Hao Li, Niranjan Shirgaonkar, Shumei Chia, Lingzhi Wang, Anil Gopinathan, Donovan Kum-Chuen Eu, Raymond King-Yin Tsang, Kwok-Seng Loh, Han-Chong Toh, Nicholas Syn, Li-Ren Kong, Ramanuj Dasgupta, Bee-Choo Tai, Yaw-Chyn Lim, Boon-Cher Goh
Journal: The Lancet Oncology (2025)
Efficacy of dolutegravir plus lamivudine in treatment-naive people living with HIV without baseline drug-resistance testing available (D2ARLING): 48-week results of a phase 4, randomised, open-label, non-inferiority trial
Authors: Ezequiel Cordova, Jeniffer Hernandez Rendon, Veronica Mingrone, Patricio Martin, Gisela Arevalo Calderon, Soledad Seleme, Jamile Ballivian, Norma Porteiro
Journal: The Lancet HIV (2025)
UK needs national strategy to tackle alcohol related harms
Authors: Julia M A Sinclair, Melinda King, Steven Masson, Ian Gilmore
Journal: BMJ (2025)

Alcohol is widely available and drunk by around 80% of adults in the UK.No safe level of alcohol consumption has been established, 1 and the physical and mental health harms increase (at different rates) with the amount consumed. 2Alcohol is well recognised as a leading preventable cause of cancer.
Improving maternity provision for incarcerated women in the UK
Authors: Laura Abbott, Kirsty Kitchen, Tanya Capper, Miranda Davies, Lucy Baldwin
Journal: BMJ (2025)

Two newborn babies died in UK prisons in 2019-20 and another died in transit to hospital in 2017. 1 2 The unique challenges faced by women in detained settings were highlighted in the Corston report in 2007, 3 but these deaths drew widespread attention to the serious shortcomings and substandard care for perinatal women in prison. 4The systemic problems need tackling urgently to protect the health of pregnant women, new mothers, and babies while in criminal justice settings.Women constitute about 4% of the overall prison population in England and Wales and tend to receive shorter sentences than men, usually for non-violent crimes. 3The decision to incarcerate pregnant women is a political one, with 11 countries, including Spain, Mexico, and Italy, prohibiting or severely limiting it.Research on care of pregnant women in prison in the UK is sparse, despite evident similarities in the underuse of mother and baby placements in prisons across the world.
Water, sanitation, and hygiene among transgender population living in urban informal settlements: a qualitative study in Odisha, India
Authors: Krushna Chandra Sahoo, S. Shradha Suman, Milinda Mishra, Abhinav Sinha, Dasarathi Das, Sanghamitra Pati
Journal: International Journal of Transgender Health (2025)

Background Access to safe drinking water, sanitation, and hygiene (WASH) is recognized as a fundamental human right. However, transgender people residing in low-resource settings such as urban slums encounter unique challenges in accessing WASH facilities.
Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans
Authors: Quentin Riller, Boris Sorin, Charline Courteille, Duong Ho-Nhat, Tom Le Voyer, Jean-Christophe Debray, Marie-Claude Stolzenberg, Muriel Schmutz, Olivier Pellé, Thomas Becquard, María Rodrigo Riestra, Laureline Berteloot, Mélanie Migaud, Laure Delage, Marie Jeanpierre, Charlotte Boussard, Camille Brunaud, Aude Magérus, Charles Bretot, Victor Michel, Camille Roux, Capucine Picard, Cécile Masson, Christine Bole-Feysot, Nicolas Cagnard, Aurélien Corneau, Isabelle Meyts, Véronique Baud, Jean-Laurent Casanova, Alain Fischer, Emmanuel Dejardin, Anne Puel, Cécile Boulanger, Bénédicte Neven, Frédéric Rieux-Laucat
Journal: The Journal of Experimental Medicine (2025)

IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay–Wells syndrome-like features. We showed that both variants were loss-of-function. Non-canonical NF-κB activation was profoundly diminished in stromal and immune cells while the canonical pathway was unexpectedly partially impaired. Reintroducing wt CHUK restored non-canonical NF-κB activation. The patient had neutralizing autoantibodies against type I IFN, akin to non-canonical NF-κB pathway deficiencies. Thus, this is the first case of biallelic CHUK mutations disrupting IKKα kinase function, broadening non-canonical NF-κB defect understanding, and suggesting IKKα’s role in canonical NF-κB target gene expression in humans.
Tackling drug shortages must be an urgent priority for the NHS
Authors: Mohammad S Razai, Hina Azille, Simon Griffin, Azeem Majeed
Journal: BMJ (2025)

In recent years, the NHS has faced numerous drug shortages, with serious consequences for both patients and healthcare professionals. 1 2 These ongoing shortages have affected a wide range of drugs, including antibiotics, diabetes medicines, ADHD medications and hormone replacement therapy. 3 4As the NHS grapples with drug scarcity, it is necessary to understand the causes and prioritise solutions to tackle this recurrent problem.Medicine shortages doubled between 2022 and 2024, with 101 drug supply disruption notifications in February 2024 compared to 52 in the same month in 2022. 5 -7 In 2023, healthcare providers received an average of 137 monthly notifications about supply disruptions, signalling a worsening crisis which is affecting patient care.
NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2025
Authors: Douglas E. Wood, Ella A. Kazerooni, Denise R. Aberle, Christine Argento, Jonathan Baines, Brian Boer, Lisa M. Brown, Jessica Donington, Georgie A. Eapen, J. Scott Ferguson, Lifang Hou, Donald Klippenstein, Ana S. Kolansky, Rohit Kumar, Lorriana E. Leard, Ann N.C. Leung, Peter Mazzone, Robert E. Merritt, Kim Norris, Mark Onaitis, Sudhakar Pipavath, Varun Puri, Dan Raz, Chakravarthy Reddy, Mary E. Reid, Kim L. Sandler, Jacob Sands, Matthew B. Schabath, Catherine R. Sears, Jamie L. Studts, Lynn Tanoue, Amber L. Thacker, Betty C. Tong, William D. Travis, Benjamin Wei, Kenneth Westover, Beth McCullough, Swathi Ramakrishnan
Journal: Journal of the National Comprehensive Cancer Network (2025)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide criteria for selecting individuals for screening and offer recommendations for evaluating and managing lung nodules detected during initial and subsequent annual screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.
A policy framework for leveraging generative AI to address enduring challenges in clinical trials
Authors: Johnathon Edward Liddicoat, Gabriela Lenarczyk, Mateo Aboy, Timo Minssen, Sebastian Porsdam Mann
Journal: npj Digital Medicine (2025)

Can artificial intelligence improve clinical trial design? Despite their importance in medicine, over 40% of trials involve flawed protocols. We introduce and propose the development of application-specific language models (ASLMs) for clinical trial design across three phases: ASLM development by regulatory agencies, customization by Health Technology Assessment bodies, and deployment to stakeholders. This strategy could enhance trial efficiency, inclusivity, and safety, leading to more representative, cost-effective clinical trials.
Dermatofibrosarcoma Protuberans, Version 1.2025, NCCN Clinical Practice Guidelines In Oncology
Authors: Jeremy Bordeaux, Rachel Blitzblau, Sumaira Z. Aasi, Murad Alam, Arya Amini, Kristin Bibee, Diana Bolotin, Pei-Ling Chen, Carlo M. Contreras, Dominick DiMaio, Jessica M. Donigan, Jeffrey M. Farma, Karthik Ghosh, Kelly Harms, Nicole LeBoeuf, John Nicholas Lukens, Susan Manber, Lawrence Mark, Theresa Medina, Kishwer S. Nehal, Paul Nghiem, Kelly Olino, Gyorgy Paragh, Soo Park, Tejesh Patel, Jason Rich, Ashok R. Shaha, Bhavina Sharma, Yemi Sokumbi, Divya Srivastava, Valencia Thomas, Courtney Tomblinson, Puja Venkat, Yaohui Gloria Xu, Siegrid Yu, Mehran Yusuf, Beth McCullough, Sara Espinosa
Journal: Journal of the National Comprehensive Cancer Network (2025)

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous soft tissue sarcoma and affects an estimated 1,500 people annually in the United States. DFSP frequently exhibits extensive local infiltration. Initial treatment is through surgical excision, and care should be taken to ensure that negative margins are achieved to minimize recurrence. Although DFSP has a reported high rate of recurrence, metastasis is more uncommon. Fibrosarcomatous DFSP is an aggressive variant with an increased risk for local recurrence and metastasis. If achieving negative margins or resection is not feasible, radiation therapy or systemic treatment are options that may be considered by a multidisciplinary team. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline recommended treatment options available for DFSP.
Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder — recommendations from ECTRIMS and the EBMT
Authors: Paolo A. Muraro, Alice Mariottini, Raffaella Greco, Joachim Burman, Ellen Iacobaeus, Matilde Inglese, John A. Snowden, Tobias Alexander, Maria Pia Amato, Lars Bø, Giacomo Boffa, Olga Ciccarelli, Jeffrey A. Cohen, Tobias Derfuss, Dominique Farge, Mark S. Freedman, Maria Gaughan, Christoph Heesen, Majid Kazmi, Kirill Kirzigov, Per Ljungman, Gianluigi Mancardi, Roland Martin, Varun Mehra, Lucia Moiola, Riccardo Saccardi, Mar Tintoré, Bruno Stankoff, Basil Sharrack, Yolanda Blanco, Franziska Di Pauli, Gavin Giovannoni, Cheryl Hemingway, Azza Izmail, Iljias Jelcic, Ludwig Kappos, Luisa Klotz, Anne Kristine Lehmann, Marcin Mycko, Albert Saiz, Joost Smolders, Sandra Vukusic, Barbara Willekens, Helene Zephir
Journal: Nature Reviews Neurology (2025)
Challenges in determining the global burden of non-malignant central nervous system tumors: an analysis of international incidence and mortality data sources
Authors: Frances Dean, Hannah Henrikson, Rixing Xu, Hodo Farah, Dan Lu, James Harvey, Weijia Fu, Natalie Pritchett, Nickhill Bhakta, Daniel C Moreira, Ibrahim Qaddoumi, Fabio Girardi, Theo Vos, Mohsen Naghavi, Jonathan L Finlay, Lisa M Force
Journal: Neuro-Oncology (2025)

Abstract Background Non-malignant tumors of the CNS contribute substantially to the morbidity and mortality from CNS tumors. It is critical to understand the epidemiology of non-malignant CNS tumors separately from CNS malignancies to inform resource allocation and policy since treatment and prognosis can differ. High quality international data on non-malignant CNS tumor burden are needed to accomplish this goal. Methods We assessed cancer registry and vital registration data available to the Global Burden of Disease study by its inclusion of non-malignant CNS tumors, reporting on the availability of data over time and by World Bank income group. We analyzed preliminary age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and proportions of CNS tumors by behavior for adults, children, and all ages. Results Non-malignant CNS tumors were reported separately in 17·2% (N=66) of registry reports and in aggregate with malignant CNS tumors in 18·0% (N=69) of reports. Only seven low- and middle-income countries (LMICs) had data reporting CNS tumors separately by behavior. Across all ages combined, the median ASIR of non-malignant CNS tumor data was 0·31 (interquartile range: 0·15-0·50) and ASMR was 0·24 (0·10-0·44) per 100,000 in LMICs compared to median ASIR of 3·62 (2·62-4·97) and ASMR of 0·32 (0·16-0·65) in high-income countries (HICs). A larger proportion of incident CNS tumors across were reported as non-malignant in HIC data than LMIC data (p&amp;lt;0.0001). Conclusions Our study alludes to current challenges in understanding global non-malignant CNS tumor burden and a need for increased international data collection. Further research is needed to comprehensively investigate opportunities for future data inclusion.
Echocardiography of the right heart in pulmonary arterial hypertension: insights from the ULTRA RIGHT VALUE study
Authors: Francesco Lo Giudice, Pilar Escribano-Subias, Khodr Tello, Grzegorz Kopec, Stefano Ghio, George Giannakoulas, Michele D’Alto, Domenico Filomena, Giovanna Manzi, Antonio Orlando, Alessandra Greco, Tommaso Recchioni, Selin Yildiz, Carmen Jiménez López-Guarch, Alejandro Cruz-Utrilla, Polykarpos Psochias, Vasiliki Patsiou, Jakub Stępniewski, Kamil Jonas, Laura Scelsi, Nils Kremer, Andrea Vergara, Carmine Dario Vizza, Robert Naeije, Roberto Badagliacca
Journal:  (2025)

Abstract Aims Outcome in pulmonary arterial hypertension (PAH) is determined by right ventricular (RV) function adaptation to increased afterload. Echocardiography is easily available to assist bedside evaluation of the RV. However, no agreement exists about the feasibility and most relevant measurements. We therefore examined the feasibility, quality, and clinical correlations of standard echocardiographic variables in the evaluation of PAH. Methods and results The present multicentric study collected echocardiographic examinations with centralized reading in 401 patients with prevalent PAH. Clinical variables, as World Health Organization (WHO) functional class (FC), 6 min walk distance (6MWD), brain natriuretic peptide (BNP)/NT-proBNP, invasive haemodynamics, the European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines-derived four-strata score, and the United States Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) 2.0 score, were also collected. Echocardiographic measurements showed variable degrees of dilation of the right heart as assessed by right atrial and RV areas, altered indices of systolic function such as tricuspid annular plane systolic excursion (TAPSE), fractional area change, or 2D strain, and derived estimates of RV to pulmonary artery (PA) coupling by referring these measurements to systolic PA pressure (sPAP). All these measurements were feasible. All measurements of right heart dimensions and function, particularly TAPSE/sPAP, were correlated with WHO-FC, 6MWD, BNP/NT-proBNP, invasive haemodynamics, and ESC/ERS and REVEAL 2.0 scores. Conclusion The present quality-controlled data from a network of PAH referral centres offer the background needed for further evaluation of the added value of echocardiography to currently recommended risk assessments in PAH.
SIRT2 and ALDH1A1 as critical enzymes for astrocytic GABA production in Alzheimer’s disease
Authors: Mridula Bhalla, Jinhyeong Joo, Daeun Kim, Jeong Im Shin, Yongmin Mason Park, Yeon Ha Ju, Uiyeol Park, Seonguk Yoo, Seung Jae Hyeon, Hyunbeom Lee, Junghee Lee, Hoon Ryu, C. Justin Lee
Journal: Molecular Neurodegeneration (2025)

Abstract Background Alzheimer’s Disease (AD) is a neurodegenerative disease with drastically altered astrocytic metabolism. Astrocytic GABA and H 2 O 2 are associated with memory impairment in AD and synthesized through the Monoamine Oxidase B (MAOB)-mediated multi-step degradation of putrescine. However, the enzymes downstream to MAOB in this pathway remain unidentified. Methods Using transcriptomics analysis, we identified two candidate enzymes, Aldehyde Dehydrogenase 1 family member A1 (ALDH1A1) and Sirtuin 2 (SIRT2) for the steps following MAOB in the astrocytic GABA production pathway. We used immunostaining, metabolite analysis and electrophysiology, both in vitro and in vivo, to confirm the participation of these enzymes in astrocytic GABA production. We checked for the presence of SIRT2 in human AD patients as well as the mouse model APP/PS1 and finally, we selectively ablated SIRT2 in the astrocytes of APP/PS1 mice to observe its effects on pathology. Results Immunostaining, metabolite analysis, and electrophysiology recapitulated the participation of ALDH1A1 and SIRT2 in GABA production. Inhibition of SIRT2 reduced the production of astrocytic GABA but not H 2 O 2 , a key molecule in neurodegeneration. Elevated expression of these enzymes was found in hippocampal astrocytes of AD patients and APP/PS1 mice. Astrocyte-specific gene-silencing of SIRT2 in APP/PS1 mice restored GABA production and partially improved memory function. Conclusions Our study is the first to identify the specific role of SIRT2 in reactive astrogliosis and determine the specific pathway and metabolic step catalyzed by the enzyme. We determine the partial, yet significant role of ALDH1A1 in this process, thereby highlighting 2 new players the astrocytic GABA production pathway. Our findings therefore, offer SIRT2 as a new tool to segregate GABA from H 2 O 2 production, aiding future research in neurodegenerative diseases. Graphical Abstract
Microbial succinate promotes the response to metformin by upregulating secretory immunoglobulin a in intestinal immunity
Authors: Ying Zhang, Aiting Wang, Wei Zhao, Jia’an Qin, Yu Zhang, Bing Liu, Chengcheng Yao, Jianglan Long, Mingxia Yuan, Dan Yan
Journal: Gut Microbes (2025)

Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus; however, many patients respond poorly to this drug in clinical practice. The potential involvement of microbiota-mediated intestinal immunity and related signals in metformin responsiveness has not been previously investigated. In this study, we successfully constructed a humanized mouse model by fecal transplantation of the gut microbiota from clinical metformin-treated – responders and non-responders, and reproduced the difference in clinical phenotypes of responsiveness to metformin. The abundance of Bacteroides thetaiotaomicron, considered a representative differential bacterium of metformin responsiveness, and the level of secretory immunoglobulin A (SIgA) in intestinal immunity increased significantly in responder recipient mice following metformin treatment. In contrast, no significant alterations in B. thetaiotaomicron and SIgA were observed in non-responder recipient mice. The study of IgA˗/˗ mice confirmed that downregulated expression or deficiency of SIgA resulted in non-response to metformin, meaning that metformin was unable to improve dysfunctional glucose metabolism and reduce intestinal and adipose tissue inflammation, ultimately leading to systemic insulin resistance. Furthermore, supplementation with succinate, a microbial product of B. thetaiotaomicron, potentially reversed the non-response to metformin by inducing the production of SIgA. In conclusion, we demonstrated that upregulated SIgA, which could be regulated by succinate, was functionally involved in metformin response through its influence on immune cell-mediated inflammation and insulin resistance. Conversely, an inability to regulate SIgA may result in a lack of response to metformin.
Host-microbe multi-omics and succinotype profiling have prognostic value for future relapse in patients with inflammatory bowel disease
Authors: Jill O’Sullivan, Shriram Patel, Gabriel E. Leventhal, Rachel S. Fitzgerald, Emilio J. Laserna-Mendieta, Chloe E. Huseyin, Nina Konstantinidou, Erica Rutherford, Aonghus Lavelle, Karim Dabbagh, Todd Z. DeSantis, Fergus Shanahan, Andriy Temko, Shoko Iwai, Marcus J. Claesson
Journal: Gut Microbes (2025)

Crohn's disease (CD) and ulcerative colitis (UC) are chronic relapsing inflammatory bowel disorders (IBD), the pathogenesis of which is uncertain but includes genetic susceptibility factors, immune-mediated tissue injury and environmental influences, most of which appear to act via the gut microbiome. We hypothesized that host-microbe alterations could be used to prognostically stratify patients experiencing relapses up to four years after endoscopy. We therefore examined multiple omics data, including published and new datasets, generated from paired inflamed and non-inflamed mucosal biopsies from 142 patients with IBD (54 CD; 88 UC) and from 34 control (non-diseased) biopsies. The relapse-predictive potential of 16S rRNA gene and transcript amplicons (standing and active microbiota) were investigated along with host transcriptomics, epigenomics and genetics. While standard single-omics analysis could not distinguish between patients who relapsed and those that remained in remission within four years of colonoscopy, we did find an association between the number of flares and a patient's succinotype. Our multi-omics machine learning approach was also able to predict relapse when combining features from the microbiome and human host. Therefore multi-omics, rather than single omics, better predicts relapse within 4 years of colonoscopy, while a patient's succinotype is associated with a higher frequency of relapses.
Failure of colonization following gut microbiota transfer exacerbates DSS-induced colitis
Authors: Kevin L. Gustafson, Trevor R. Rodriguez, Zachary L. McAdams, Lyndon M. Coghill, Aaron C. Ericsson, Craig L. Franklin
Journal: Gut Microbes (2025)

To study the impact of differing specific pathogen-free gut microbiomes (GMs) on a murine model of inflammatory bowel disease, selected GMs were transferred using embryo transfer (ET), cross-fostering (CF), and co-housing (CH). Prior work showed that the GM transfer method and the microbial composition of donor and recipient GMs can influence microbial colonization and disease phenotypes in dextran sodium sulfate-induced colitis. When a low richness GM was transferred to a recipient with a high richness GM via CH, the donor GM failed to successfully colonize, and a more severe disease phenotype resulted when compared to ET or CF, where colonization was successful. By comparing CH and gastric gavage for fecal material transfer, we isolated the microbial component of this effect and determined that differences in disease severity and survival were associated with microbial factors rather than the transfer method itself. Mice receiving a low richness GM via CH and gastric gavage exhibited greater disease severity and higher expression of pro-inflammatory immune mediators compared to those receiving a high richness GM. This study provides valuable insights into the role of GM composition and colonization in disease modulation.