tbuckley/cabot-search huggingface dataset:
Incidence of self-reported tuberculosis treatment with community-wide universal testing and treatment for HIV and tuberculosis screening in Zambia and South Africa: A planned analysis of the HPTN 071 (PopART) cluster-randomised trial
Authors: L. Telisinghe, S. Floyd, D. MacLeod, A. Schaap, R. Dunbar, J. Bwalya, N. Bell-Mandla, E. Piwowar-Manning, D. Donnell, K. Shaunaube, P. Bock, S. Fidler, R. J. Hayes, H. M. Ayles
Journal: PLoS Medicine (2024)

HIV is a potent risk factor for tuberculosis (TB). Therefore, community-wide universal testing and treatment for HIV (UTT) could contribute to TB control, but evidence for this is limited. Community-wide TB screening can decrease population-level TB prevalence. Combining UTT with TB screening could therefore significantly impact TB control in sub-Saharan Africa, but to our knowledge there is no evidence for this combined approach.
Leveraging zebrafish to investigate pancreatic development, regeneration, and diabetes
Authors: Jiarui Mi, Lipeng Ren, Olov Andersson
Journal: Trends in Molecular Medicine (2024)

The zebrafish has become an outstanding model for studying organ development and tissue regeneration, which is prominently leveraged for studies of pancreatic development, insulin-producing β-cells, and diabetes. Although studied for more than two decades, many aspects remain elusive and it has only recently been possible to investigate these due to technical advances in transcriptomics, chemical-genetics, genome editing, drug screening, and in vivo imaging. Here, we review recent findings on zebrafish pancreas development, β-cell regeneration, and how zebrafish can be used to provide novel insights into gene functions, disease mechanisms, and therapeutic targets in diabetes, inspiring further use of zebrafish for the development of novel therapies for diabetes.
The effect of dose, frequency, and timing of protein supplementation on muscle mass in older adults: A systematic review and meta-analysis
Authors: Jeewanadee Hettiarachchi, Esmee M. Reijnierse, Natalie Kew, Kate Fetterplace, Sze-Yen Tan, Andrea B. Maier
Journal: Ageing Research Reviews (2024)

Protein supplementation has shown to improve muscle mass in older adults. However, its effect may be influenced by supplementation dose, frequency and timing. This systematic review aimed to assess the effect of dose, frequency and timing of protein supplementation on muscle mass in older adults. Five databases were systematically searched from inception to 14 March 2023, for randomised controlled trials investigating the effect of protein supplementation on muscle mass in adults aged ≥65 years. Random effects meta-analyses were performed, stratified by population. Subgroups were created for dose (≥30 g, <30 g/day), frequency (once, twice, three times/day) and timing of supplementation (at breakfast, breakfast and lunch, breakfast and dinner, all meals, between meals). Heterogeneity within and between subgroups was assessed using I2 and Cochran Q statistics respectively. Thirty-eight articles were included describing community-dwelling (28 articles, n=3204, 74.6±3.4 years, 62.8% female), hospitalised (8 articles, n=590, 77.0±3.7 years, 50.3% female) and institutionalised populations (2 articles, n=156, 85.7±1.2 years, 71.2% female). Protein supplementation showed a positive effect on muscle mass in community-dwelling older adults (standardized mean difference 0.116; 95% confidence interval 0.032-0.200 kg, p=0.007, I2=15.3%) but the effect did not differ between subgroups of dose, frequency and timing (Q=0.056, 0.569 and 3.084 respectively, p>0.05). Data including hospitalised and institutionalised populations were limited. Protein supplementation improves muscle mass in community-dwelling older adults, but its dose, frequency or timing does not significantly influence the effect.
Urinary eicosanoid levels in early life and risk of atopic disease in childhood
Authors: Liang Chen, Nicklas Brustad, Min Kim, Yang Luo, Tingting Wang, Mina Ali, Nicole Prince, Yulu Chen, Su Chu, Sofina Begum, Kevin Mendez, Rachel S Kelly, Ann-Marie Schoos, Morten A Rasmussen, Javier Zurita, Johan Kolmert, Jakob Stokholm, Augusto Litonjua, Scott T Weiss, Klaus Bønnelykke, Craig E Wheelock, Jessica Lasky-Su, Bo Chawes
Journal: Journal of Allergy and Clinical Immunology (2024)

Eicosanoids are lipid mediators including thromboxanes (TXs), prostaglandins (PGs), and leukotrienes with a pathophysiological role in established atopic disease. However, their role in the inception of disease is unclear. This study aimed to investigate the association between urinary eicosanoids in early life and development of atopic disease.
Inhibition of lysine acetyltransferase KAT6 in ER+HER2− metastatic breast cancer: a phase 1 trial
Authors: Toru Mukohara, Yeon Hee Park, David Sommerhalder, Kan Yonemori, Erika Hamilton, Sung-Bae Kim, Jee Hyun Kim, Hiroji Iwata, Toshinari Yamashita, Rachel M. Layman, Monica Mita, Timothy Clay, Yee Soo Chae, Catherine Oakman, Fengting Yan, Gun Min Kim, Seock-Ah Im, Geoffrey J. Lindeman, Hope S. Rugo, Marlon Liyanage, Michelle Saul, Christophe Le Corre, Athanasia Skoura, Li Liu, Meng Li, Patricia M. LoRusso
Journal: Nature Medicine (2024)

Inhibition of histone lysine acetyltransferases (KATs) KAT6A and KAT6B has shown antitumor activity in estrogen receptor-positive (ER
Chromatin as an old and new anticancer target
Authors: Jacques Neefjes, Katerina Gurova, Jay Sarthy, Gábor Szabó, Steven Henikoff
Journal: Trends in cancer (2024)

Recent genome-wide analyses identified chromatin modifiers as one of the most frequently mutated classes of genes across all cancers. However, chemotherapies developed for cancers involving DNA damage remain the standard of care for chromatin-deranged malignancies. In this review we address this conundrum by establishing the concept of 'chromatin damage': the non-genetic damage to protein-DNA interactions induced by certain small molecules. We highlight anthracyclines, a class of chemotherapeutic agents ubiquitously applied in oncology, as an example of overlooked chromatin-targeting agents. We discuss our current understanding of this phenomenon and explore emerging chromatin-damaging agents as a basis for further studies to maximize their impact in modern cancer treatment.
Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal Hyperplasia
Authors: Richard J Auchus, Oksana Hamidi, Rosario Pivonello, Irina Bancos, Gianni Russo, Selma F Witchel, Andrea M Isidori, Patrice Rodien, Umasuthan Srirangalingam, Florian W Kiefer, Henrik Falhammar, Deborah P Merke, Nicole Reisch, Kyriakie Sarafoglou, Gordon B Cutler, Julia Sturgeon, Eiry Roberts, Vivian H Lin, Jean L Chan, Robert H Farber
Journal: New England Journal of Medicine (2024)

Adrenal insufficiency in patients with classic 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) is treated with glucocorticoid replacement therapy. Control of adrenal-derived androgen excess usually requires supraphysiologic glucocorticoid dosing, which predisposes patients to glucocorticoid-related complications. Crinecerfont, an oral corticotropin-releasing factor type 1 receptor antagonist, lowered androstenedione levels in phase 2 trials involving patients with CAH.
Combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (OPTIMIZE-1): a single-arm, multicentre phase 1b/2 study
Authors: Jean-Luc Van Laethem, Ivan Borbath, Hans Prenen, Karen Paula Geboes, Aurélien Lambert, Emmanuel Mitry, Philippe Alexandre Cassier, Jean-Frédéric Blanc, Lorenzo Pilla, Jaime Feliu Batlle, Mercedes Rodriguez Garrote, Roberto Antonio Pazo-Cid, Inmaculada Gallego, Karin Enell Smith, Peter Ellmark, Yago Pico de Coaña, Sumeet Vijay Ambarkhane, Teresa Macarulla
Journal: The Lancet Oncology (2024)
Towards automatic home-based sleep apnea estimation using deep learning
Authors: Gabriela Retamales, Marino E. Gavidia, Ben Bausch, Arthur N. Montanari, Andreas Husch, Jorge Goncalves
Journal: npj Digital Medicine (2024)

Apnea and hypopnea are common sleep disorders characterized by the obstruction of the airways. Polysomnography (PSG) is a sleep study typically used to compute the Apnea-Hypopnea Index (AHI), the number of times a person has apnea or certain types of hypopnea per hour of sleep, and diagnose the severity of the sleep disorder. Early detection and treatment of apnea can significantly reduce morbidity and mortality. However, long-term PSG monitoring is unfeasible as it is costly and uncomfortable for patients. To address these issues, we propose a method, named DRIVEN, to estimate AHI at home from wearable devices and detect when apnea, hypopnea, and periods of wakefulness occur throughout the night. The method can therefore assist physicians in diagnosing the severity of apneas. Patients can wear a single sensor or a combination of sensors that can be easily measured at home: abdominal movement, thoracic movement, or pulse oximetry. For example, using only two sensors, DRIVEN correctly classifies 72.4% of all test patients into one of the four AHI classes, with 99.3% either correctly classified or placed one class away from the true one. This is a reasonable trade-off between the model's performance and the patient's comfort. We use publicly available data from three large sleep studies with a total of 14,370 recordings. DRIVEN consists of a combination of deep convolutional neural networks and a light-gradient-boost machine for classification. It can be implemented for automatic estimation of AHI in unsupervised long-term home monitoring systems, reducing costs to healthcare systems and improving patient care.
Fruquintinib plus paclitaxel versus placebo plus paclitaxel for gastric or gastroesophageal junction adenocarcinoma: the randomized phase 3 FRUTIGA trial
Authors: Feng Wang, Lin Shen, Weijian Guo, Tianshu Liu, Jin Li, Shukui Qin, Yuxian Bai, Zhendong Chen, Jufeng Wang, Yueyin Pan, Yongqian Shu, Fuyou Zhao, Ying Cheng, Feng Ye, Kangsheng Gu, Tao Zhang, Hongming Pan, Haijun Zhong, Fuxiang Zhou, Yanru Qin, Lei Yang, Weidong Mao, Qiu Li, Wenxiang Dai, Wei Li, Shubin Wang, Yong Tang, Dong Ma, Xianli Yin, Yanhong Deng, Ying Yuan, Man Li, Wenwei Hu, Donghui Chen, Guoxin Li, Qiqi Liu, Panfeng Tan, Songhua Fan, Michael Shi, Weiguo Su, Rui-Hua Xu
Journal: Nature Medicine (2024)
Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma
Authors: Vania Hungria, Pawel Robak, Marek Hus, Vera Zherebtsova, Christopher Ward, P Joy Ho, Ana Carolina Ribas de Almeida, Roman Hajek, Kihyun Kim, Sebastian Grosicki, Hanlon Sia, Adam Bryant, Marcelo Pitombeira de Lacerda, Gracia Aparecida Martinez, Anna Maria Sureda Balarí, Irwindeep Sandhu, Claudio Cerchione, Peter Ganly, Meletios Dimopoulos, Chengcheng Fu, Mamta Garg, Al-Ola Abdallah, Albert Oriol, Moshe E Gatt, Michele Cavo, Robert Rifkin, Tomoaki Fujisaki, Michał Mielnik, Nick Pirooz, Astrid McKeown, Simon McNamara, Xiangdong Zhou, Maureen Nichols, Eric Lewis, Rachel Rogers, Hena Baig, Lydia Eccersley, Sumita Roy-Ghanta, Joanna Opalinska, María-Victoria Mateos
Journal: New England Journal of Medicine (2024)

Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies.
Enhancing volumetric muscle loss (VML) recovery in a rat model using super durable hydrogels derived from bacteria
Authors: Seyyed Vahid Niknezhad, Mehdi Mehrali, Farinaz Riyahi Khorasgani, Reza Heidari, Firoz Babu Kadumudi, Nasim Golafshan, Miguel Castilho, Cristian Pablo Pennisi, Masoud Hasany, Mohammadjavad Jahanshahi, Mohammad Mehrali, Younes Ghasemi, Negar Azarpira, Thomas L. Andresen, Alireza Dolatshahi-Pirouz
Journal: Bioactive Materials (2024)

Bacteria can be programmed to deliver natural materials with defined biological and mechanical properties for controlling cell growth and differentiation. Here, we present an elastic, resilient and bioactive polysaccharide derived from the extracellular matrix of Pantoea sp. BCCS 001. Specifically, it was methacrylated to generate a new photo crosslinkable hydrogel that we coined Pantoan Methacrylate or put simply PAMA. We have used it for the first time as a tissue engineering hydrogel to treat VML injuries in rats. The crosslinked PAMA hydrogel was super elastic with a recovery nearing 100 %, while mimicking the mechanical stiffness of native muscle. After inclusion of thiolated gelatin via a Michaelis reaction with acrylate groups on PAMA we could also guide muscle progenitor cells into fused and aligned tubes – something reminiscent of mature muscle cells. These results were complemented by sarcomeric alpha-actinin immunostaining studies. Importantly, the implanted hydrogels exhibited almost 2-fold more muscle formation and 50 % less fibrous tissue formation compared to untreated rat groups. In vivo inflammation and toxicity assays likewise gave rise to positive results confirming the biocompatibility of this new biomaterial system. Overall, our results demonstrate that programmable polysaccharides derived from bacteria can be used to further advance the field of tissue engineering. In greater detail, they could in the foreseeable future be used in practical therapies against VML.
Novel clinical risk stratification and treatment strategies in relapsed/refractory peripheral T-cell lymphoma
Authors: Esther Wei Yin Chang, Ya Hwee Tan, Jason Yongsheng Chan
Journal: Journal of Hematology & Oncology (2024)

Abstract Peripheral T cell lymphoma (PTCL) represents a group of heterogeneous hematological malignancies, which are notoriously challenging to treat and outcomes are typically poor. Over the past two decades, clinical prognostic indices for patient risk stratification have evolved, while several targeted agents are now available to complement combination chemotherapy in the frontline setting or as a salvage strategy. With further understanding of the molecular pathobiology of PTCL, several innovative approaches incorporating immunomodulatory agents, epigenetic therapies, oncogenic kinase inhibitors and immunotherapeutics have come to the forefront. In this review, we provide a comprehensive overview of the progress in developing clinical prognostic indices for PTCL and describe the broad therapeutic landscape, emphasizing novel targetable pathways that have entered early phase clinical studies.
Neurodegenerative disorders: Mechanisms of degeneration and therapeutic approaches with their clinical relevance
Authors: Dnyandev G. Gadhave, Vrashabh V. Sugandhi, Saurav Kumar Jha, Sopan N. Nangare, Gaurav Gupta, Sachin Kumar Singh, Kamal Dua, Hyunah Cho, Philip M. Hansbro, Keshav Raj Paudel
Journal: Ageing Research Reviews (2024)

Neurodegenerative disorders (NDs) are expected to pose a significant challenge for both medicine and public health in the upcoming years due to global demographic changes. NDs are mainly represented by degeneration/loss of neurons, which is primarily accountable for severe mental illness. This neuronal degeneration leads to many neuropsychiatric problems and permanent disability in an individual. Moreover, the tight junction of the brain, blood-brain barrier (BBB)has a protective feature, functioning as a biological barrier that can prevent medicines, toxins, and foreign substances from entering the brain. However, delivering any medicinal agent to the brain in NDs (i.e., Multiple sclerosis, Alzheimer's, Parkinson's, etc.) is enormously challenging. There are many approved therapies to address NDs, but most of them only help treat the associated manifestations. The available therapies have failed to control the progression of NDs due to certain factors, i.e., BBB and drug-associated undesirable effects. NDs have extremely complex pathology, with many pathogenic mechanisms involved in the initiation and progression; thereby, a limited survival rate has been observed in ND patients. Hence, understanding the exact mechanism behind NDs is crucial to developing alternative approaches for improving ND patients' survival rates. Thus, the present review sheds light on different cellular mechanisms involved in NDs and novel therapeutic approaches with their clinical relevance, which will assist researchers in developing alternate strategies to address the limitations of conventional ND therapies. The current work offers the scope into the near future to improve the therapeutic approach of NDs.
Donanemab, another anti-Alzheimer's drug with risk and uncertain benefit
Authors: Poul F. Høilund-Carlsen, Abass Alavi, Jorge R. Barrio, Rudolph J. Castellani, Tommaso Costa, Karl Herrup, Kasper P. Kepp, Rachael L. Neve, George Perry, Mona-Elisabeth Revheim, Nikolaos K. Robakis, Stefano L. Sensi, Bryce Vissel
Journal: Ageing Research Reviews (2024)
Crosslinking with UV-A and riboflavin in progressive keratoconus: From laboratory to clinical practice – Developments over 25 years
Authors: Frederik Raiskup, Robert Herber, Janine Lenk, Lutz E. Pillunat, Eberhard Spoerl
Journal: Progress in Retinal and Eye Research (2024)

Changes in the biomechanical and biochemical properties of the human cornea play an important role in the pathogenesis of ectatic diseases. A number of conditions in primarily acquired (keratoconus or pellucid marginal degeneration) or secondarily induced (iatrogenic keratectasia after refractive laser surgeries) ectatic disorders lead to decreased biomechanical stability. Corneal collagen cross-linking (CXL) represents a technique to slow or even halt the progression of ectatic pathologies. In this procedure, riboflavin is applied in combination with ultraviolet A radiation. This interaction induces the production of reactive oxygen species, which leads to the formation of additional covalent bonds between collagen molecules and subsequent biomechanical corneal strengthening. This procedure is so far the only method that partially interferes etiopathogenetically in the treatment of ectatic diseases that slows or stops the process of corneal destabilization, otherwise leading to the need for corneal transplantation. Besides, CXL process increases markedly resistance of collagenous matrix against digesting enzymes supporting its use in the treatment of corneal ulcers. Since the discovery of this therapeutic procedure and the first laboratory experiments, which confirmed the validity of this method, and the first clinical studies that proved the effectiveness and safety of the technique, it has been spread and adopted worldwide, even with further modifications. Making use of the Bunsen-Roscoe photochemical law it was possible to shorten the duration of this procedure in accelerated CXL and thus improve the clinical workflow and patient compliance while maintaining the efficacy and safety of the procedure. The indication spectrum of CXL can be further expanded by combining it with other vision-enhancing procedures such as individualized topographically-guided excimer ablation. Complementing both techniques will allow a patient with a biomechanically stable cornea to regularise it and improve visual acuity without the need for tissue transplantation, leading to a long-term improvement in quality of life.
Lowering Fecal Immunochemical Test Positivity Threshold vs Multitarget Stool RNA Testing for Colorectal Cancer Screening
Authors: Tobias Niedermaier, Teresa Seum, Michael Hoffmeister, Hermann Brenner
Journal: JAMA (2024)

This analysis uses data from 2 studies to explore whether lowering the threshold for fecal immunochemical test positivity can achieve comparable levels of sensitivity and specificity as multitarget stool RNA testing for colorectal cancer screening.
A review of uncertainty quantification in medical image analysis: Probabilistic and non-probabilistic methods
Authors: Ling Huang, Su Ruan, Yucheng Xing, Mengling Feng
Journal: Medical Image Analysis (2024)

The comprehensive integration of machine learning healthcare models within clinical practice remains suboptimal, notwithstanding the proliferation of high-performing solutions reported in the literature. A predominant factor hindering widespread adoption pertains to an insufficiency of evidence affirming the reliability of the aforementioned models. Recently, uncertainty quantification methods have been proposed as a potential solution to quantify the reliability of machine learning models and thus increase the interpretability and acceptability of the results. In this review, we offer a comprehensive overview of the prevailing methods proposed to quantify the uncertainty inherent in machine learning models developed for various medical image tasks. Contrary to earlier reviews that exclusively focused on probabilistic methods, this review also explores non-probabilistic approaches, thereby furnishing a more holistic survey of research pertaining to uncertainty quantification for machine learning models. Analysis of medical images with the summary and discussion on medical applications and the corresponding uncertainty evaluation protocols are presented, which focus on the specific challenges of uncertainty in medical image analysis. We also highlight some potential future research work at the end. Generally, this review aims to allow researchers from both clinical and technical backgrounds to gain a quick and yet in-depth understanding of the research in uncertainty quantification for medical image analysis machine learning models.
Whole blood transcriptome in long-COVID patients reveals association with lung function and immune response
Authors: Jelle M. Blankestijn, Nadia Baalbaki, Somayeh Bazdar, Inés Beekers, Rosanne J.H.C.G. Beijers, Joop P. van den Bergh, Lizan D. Bloemsma, Merel E.B. Cornelissen, Tamara Dekker, Jan Willem Duitman, Laura Houweling, John J.L. Jacobs, Ivo van der Lee, Paulien M.A. Linders, Lieke C.E. Noij, Esther J. Nossent, Marianne A. van de Pol, Brigitte M. Sondermeijer, J.J. Miranda Geelhoed, Els J.M. Weersink, Korneliusz Golebski, Mahmoud I. Abdel-Aziz, Anke H. Maitland-van der Zee
Journal: Journal of Allergy and Clinical Immunology (2024)

Background Months after infection with SARS-CoV-2, at least 10% of patients still experience complaints. Long-COVID is a heterogeneous disease and clustering efforts revealed multiple phenotypes on a clinical level. However, the molecular pathways underlying long-COVID phenotypes are still poorly understood. Objectives This study aims to cluster patients according to their blood transcriptomes and uncover the pathways underlying their disease. Methods Blood was collected from 77 patients with long-COVID from the P4O2 COVID-19 study. Unsupervised hierarchical clustering was performed on the whole blood transcriptome. These clusters were analysed for differences in clinical features, pulmonary function tests and gene ontology (GO) term enrichment. Results Clustering revealed two distinct clusters on a transcriptome level. Compared to cluster 2 (n=65), patients in cluster 1 (n=12) showed a higher rate of pre-existing cardiovascular disease (58% vs 22%), higher prevalence of gastrointestinal symptoms (58% vs 29%), shorter hospital duration during SARS-CoV-2 infection (median: 3 vs 8 days), lower Tiffeneau index (72% vs 81%) and lower diffusion capacity of the lung for carbon monoxide (DLCO) (68% vs 85% predicted). GO-term enrichment analysis revealed upregulation of genes involved in the antiviral innate immune response in cluster 1, while genes involved with the adaptive immune response were upregulated in cluster 2. Conclusion This study provides a start in uncovering the pathophysiological mechanisms underlying long-COVID. Further research is required to unravel why the immune response is different in these clusters, and to identify potential therapeutic targets to create an optimized treatment or monitoring strategy for the individual long-COVID patient.
Emerging and re-emerging genotype 2c Porcine Epidemic Diarrhoea virus with high pathogenicity in China
Authors: Cheng Yang, Jiu-Ying Sun, Xin-Lei Li, Ning Cheng, Kai-Yue Wang, Li-Qin Li, Xue-Jiao Cheng, Ying-Feng Sun
Journal: Journal of Infection (2024)