tbuckley/cabot-search huggingface dataset:
Unveiling the Resistance to Therapies in Pancreatic Ductal Adenocarcinoma
Authors: Ashu Shah, Koelina Ganguly, Sanchita Rauth, Shamema S Sheree, Imran Khan, Apar K Ganti, Moorthy P Ponnusamy, Sushil Kumar, Maneesh Jain, Surinder K Batra
Journal: Drug Resistance Updates (2024)
PPARα affects hepatic lipid homeostasis by perturbing necroptosis signals in the intestinal epithelium
Authors: Shufang Na, Yanjie Fan, HongLei Chen, Ling Li, Guolin Li, Furong Zhang, Rongyan Wang, Yafei Yang, Zixia Shen, Zhuang Peng, Yafei Wu, Yong Zhu, Zheqiong Yang, Guicheng Dong, Qifa Ye, Jiang Yue
Journal: Acta Pharmaceutica Sinica B (2024)

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut–liver axis.
A randomized phase 3b study evaluating the safety and efficacy of risankizumab in adult patients with moderate-to-severe plaque psoriasis with non-pustular palmoplantar involvement
Authors: Mark Lebwohl, Michael Bukhalo, Linda Stein Gold, Brad Glick, Mar Llamas-Velasco, Samuel Sanchez-Rivera, Anqi Pan, Tianyu Zhan, Leonidas Drogaris, Kevin Douglas, Greg St. John, Ramon Espaillat, Robert Bissonnette
Journal: Journal of the American Academy of Dermatology (2024)

In plaque psoriasis, palmoplantar areas are more difficult to treat.
A quantitative computational framework for allopolyploid single-cell data integration and core gene ranking in development
Authors: Meiyue Wang, Zijuan Li, Haoyu Wang, Kande Lin, Shusong Zheng, Yilong Feng, Wan Teng, Yiping Tong, Wenli Zhang, Chenghong Liu, Hong-Qing Ling, Yue-Qing Hu, Yijing Zhang
Journal: Molecular Biology and Evolution (2024)

Polyploidization drives regulatory and phenotypic innovation. How the merger of different genomes contributes to polyploid development is a fundamental issue in evolutionary developmental biology and breeding research. Clarifying this issue is challenging because of genome complexity and the difficulty in tracking stochastic subgenome divergence during development. Recent single-cell sequencing techniques enabled probing subgenome divergent regulation in the context of cellular differentiation. However, analyzing single-cell data suffers from high error rates due to high-dimensionality, noise, and sparsity, and the errors stack up in polyploid analysis due to the increased dimensionality of comparisons between subgenomes of each cell, hindering deeper mechanistic understandings. Here, we developed a quantitative computational framework, pseudo-genome divergence quantification (pgDQ), for quantifying and tracking subgenome divergence directly at the cellular level. Further comparing with cellular differentiation trajectories derived from scRNA-seq data allowed for an examination of the relationship between subgenome divergence and the progression of development. pgDQ produces robust results and is insensitive to data dropout and noise, avoiding high error rates due to multiple comparisons of genes, cells, and subgenomes. A statistical diagonostic approach is proposed to identify genes that are central to subgenome divergence during development, which facilitates the integration of different data modalities, enabling the identification of factors and pathways that mediate subgenome-divergent activity during development. Case studies demonstrated that applying pgDQ to single cell and bulk tissue transcriptome data promotes a systematic and deeper understanding of how dynamic subgenome divergence contributes to developmental trajectories in polyploid evolution.
Reference Values of Strain-derived Myocardial Work Indices in Heart Transplant Patients
Authors: G E Mandoli, F Landra, L Tanzi, L Martini, C Fusi, C Sciaccaluga, E E Diviggiano, M Barilli, M C Pastore, M Focardi, S Bernazzali, M Maccherini, M Cameli, M Y Henein
Journal:  (2024)

Myocardial work (MW) is a relatively novel non-invasive echocardiographic method with increasing fields of application. Normal reference ranges of MW indices in patients who have undergone a heart transplant (HTx) have not been determined yet. The aim of this study was to obtain the reference ranges for 2D echocardiographic indices of MW for adult HTx patients and to compare them with the results of the European Association of Cardiovascular Imaging (EACVI) Normal Reference Ranges for Echocardiography (NORRE) study.
Endpoint Surrogacy in First-Line Chronic Lymphocytic Leukemia
Authors: Florian Simon, Rudy Ligtvoet, Sandra Robrecht, Paula Cramer, Nadine Kutsch, Moritz Fürstenau, Valentin Goede, Julia von Tresckow, Petra Langerbeins, Anna-Maria Fink, Henriette Huber, Eugen Tausch, Christof Schneider, Clemens M. Wendtner, Matthias Ritgen, Martin Dreyling, Lothar Müller, Lutz Jacobasch, Werner J. Heinz, Ursula Vehling-Kaiser, Liliya Sivcheva, Sebastian Böttcher, Peter Dreger, Thomas Illmer, Michael Gregor, Philipp B. Staber, Stephan Stilgenbauer, Carsten U. Niemann, Arnon P. Kater, Kirsten Fischer, Barbara Eichhorst, Michael Hallek, Othman Al-Sawaf
Journal: Journal of Clinical Oncology (2024)

PURPOSE Surrogate end points are commonly used to estimate treatment efficacy in clinical studies of chronic lymphocytic leukemia (CLL). This patient- and trial-level analysis describes the correlation between progression-free survival (PFS) and minimal residual disease (MRD) with overall survival (OS) in first-line trials for CLL. PATIENTS AND METHODS First, patient-level correlation was confirmed using source data from 12 frontline German CLL Study Group (GCLLSG)-trials. Additionally, a joint-frailty copula model was fitted to validate correlation in the setting of targeted therapies (TT). Second, a meta-analysis of first-line phase III trials in CLL from 2008 to 2024 was performed. Treatment effect correlation was quantified from seven GCLLSG and nine published trials, using hazard ratios (HRs) for time-to-event and odds ratios for binary end points. RESULTS The GCLLSG analysis set comprised 4,237 patients. Patient-level correlation for PFS/OS was strong with Spearman Rho &gt;0.9. The joint-frailty copula indicated a weak correlation for chemotherapy/chemoimmunotherapy (C/CIT) with a tau of 0.52 (95% CI, 0.49 to 0.55) while the correlation was strong for TT (tau, 0.91 [95% CI, 0.89 to 0.93). The meta-analysis set contained a total of 8,065 patients including 5,198 (64%) patients treated with C/CIT and 2,867 (36%) treated with TT. Treatment-effect correlation of the HRs for PFS and OS was R = 0.75 (95% CI, 0.74 to 0.76, R 2 = 0.56) while correlation of end-of-treatment MRD with PFS and OS was R = 0.88 (95% CI, –0.87 to 0.89; R 2 = 0.78) and 0.71 (95% CI, 0.69 to 0.73; R 2 = 0.5), respectively. CONCLUSION Patient-level correlation was confirmed in the setting of TTs while treatment-effect correlation between PFS and OS remains uncertain. MRD response status showed a high treatment-effect correlation with PFS but not OS, with the caveat of a limited number of randomized trials with available MRD data.
Life course financial mobility and later-life memory function and decline by gender, and race and ethnicity: an intersectional analysis of the US KHANDLE and STAR cohort studies
Authors: Lindsay C Kobayashi, Rachel L Peterson, Xuexin Yu, Justina Avila-Rieger, Priscilla A Amofa-Ho, Clara Vila-Castelar, Erika Meza, C Elizabeth Shaaban, Rachel A Whitmer, Paola Gilsanz, Elizabeth Rose Mayeda
Journal: The Lancet Healthy Longevity (2024)
Injectable dual thermoreversible hydrogel for sustained intramuscular drug delivery
Authors: Fakhar Ud Din, Jung Suk Kim, Ho Cheol Lee, Seunghyun Cheon, Mi Ran Woo, Sanghyun Woo, Sae Kwang Ku, Hye Hyun Yoo, Jong Oh Kim, Sung Giu Jin, Han-Gon Choi
Journal: Journal of Controlled Release (2024)
Real-time placental vessel segmentation in fetoscopic laser surgery for Twin-to-Twin Transfusion Syndrome
Authors: Szymon Płotka, Tomasz Szczepański, Paula Szenejko, Przemysław Korzeniowski, Jesús Rodriguez Calvo, Asma Khalil, Alireza Shamshirsaz, Robert Brawura-Biskupski-Samaha, Ivana Išgum, Clara I Sánchez, Arkadiusz Sitek
Journal: Medical Image Analysis (2024)

Twin-to-Twin Transfusion Syndrome (TTTS) is a rare condition that affects about 15% of monochorionic pregnancies, in which identical twins share a single placenta. Fetoscopic laser photocoagulation (FLP) is the standard treatment for TTTS, which significantly improves the survival of fetuses. The aim of FLP is to identify abnormal connections between blood vessels and to laser ablate them in order to equalize blood supply to both fetuses. However, performing fetoscopic surgery is challenging due to limited visibility, a narrow field of view, and significant variability among patients and domains. In order to enhance the visualization of placental vessels during surgery, we propose TTTSNet, a network architecture designed for real-time and accurate placental vessel segmentation. Our network architecture incorporates a novel channel attention module and multi-scale feature fusion module to precisely segment tiny placental vessels. To address the challenges posed by FLP-specific fiberscope and amniotic sac-based artifacts, we employed novel data augmentation techniques. These techniques simulate various artifacts, including laser pointer, amniotic sac particles, and structural and optical fiber artifacts. By incorporating these simulated artifacts during training, our network architecture demonstrated robust generalizability. We trained TTTSNet on a publicly available dataset of 2060 video frames from 18 independent fetoscopic procedures and evaluated it on a multi-center external dataset of 24 in-vivo procedures with a total of 2348 video frames. Our method achieved significant performance improvements compared to state-of-the-art methods, with a mean Intersection over Union of 78.26% for all placental vessels and 73.35% for a subset of tiny placental vessels. Moreover, our method achieved 172 and 152 frames per second on an A100 GPU, and Clara AGX, respectively. This potentially opens the door to real-time application during surgical procedures. The code is publicly available at https://github.com/SanoScience/TTTSNet.
Variability in performance of genetic-enhanced DXA-BMD prediction models across diverse ethnic and geographic populations: A risk prediction study
Authors: Yong Liu, Xiang-He Meng, Chong Wu, Kuan-Jui Su, Anqi Liu, Qing Tian, Lan-Juan Zhao, Chuan Qiu, Zhe Luo, Martha I Gonzalez-Ramirez, Hui Shen, Hong-Mei Xiao, Hong-Wen Deng
Journal: PLoS Medicine (2024)

Osteoporosis is a major global health issue, weakening bones and increasing fracture risk. Dual-energy X-ray absorptiometry (DXA) is the standard for measuring bone mineral density (BMD) and diagnosing osteoporosis, but its costliness and complexity impede widespread screening adoption. Predictive modeling using genetic and clinical data offers a cost-effective alternative for assessing osteoporosis and fracture risk. This study aims to develop BMD prediction models using data from the UK Biobank (UKBB) and test their performance across different ethnic and geographical populations.
IFNL4 Genotype and Other Personal Characteristics to Predict Response to 8-Week Sofosbuvir-Based Treatment for Chronic Hepatitis C
Authors: Thomas R O'Brien, David J Witt, Varun Saxena, Kerry Grace Morrissey, Sabrina Chen, Francine S Baker, Ludmila Prokunina-Olsson, Ruth M Pfeiffer, Jennifer B Lai
Journal: Journal of Infection (2024)

Shorter duration therapy for hepatitis C virus (HCV) infection might reduce treatment costs and increase the number of patients treated and cured. We determined factors associated with treatment response after an 8-week sofosbuvir-based therapy and developed a simple model to predict an individual's likelihood of treatment success.
Cefepime–Taniborbactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination
Authors: George G. Zhanel, Celine Mansour, Stacey Mikolayanko, Courtney K. Lawrence, Sheryl Zelenitsky, Danyel Ramirez, Frank Schweizer, Denice Bay, Heather Adam, Philippe Lagacé-Wiens, Andrew Walkty, Neal Irfan, Nina Clark, David Nicolau, Carlo Tascini, James A. Karlowsky
Journal: Drugs (2024)
Children with hemoglobin C or S trait have low serologic responses to a subset of malaria variant surface antigens
Authors: Rachel D Bailey, Jonathan G Lawton, Amadou Niangaly, Emily M Stucke, Jason A Bailey, Andrea A Berry, Amed Ouattara, Drissa Coulibaly, Kirsten E Lyke, Matthew B Laurens, Albert E Zhou, Jozelyn Pablo, Algis Jasinskas, Rie Nakajima, Matthew Adams, Shannon Takala-Harrison, Bourema Kouriba, Abdoulaye K Kone, Aldiouma Guindo, J Alexandra Rowe, Dapa A Diallo, Ogobara K Doumbo, Philip L Felgner, Christopher V Plowe, Mahamadou A Thera, Mark A Travassos
Journal: Journal of Infection (2024)

Children with hemoglobin AC or AS have decreased susceptibility to clinical malaria. Parasite variant surface antigen (VSA) presentation on the surface of infected erythrocytes is altered in erythrocytes with hemoglobin C (Hb AC) or sickle trait (Hb AS) mutations in vitro. The protective role of incomplete or altered VSA presentation against clinical malaria in individuals with Hb AC or AS is unclear. Using a high-throughput protein microarray, we sought to use serological responses to VSAs as a measure of host exposure to VSAs among Malian children with Hb AC, Hb AS, or wildtype hemoglobin (Hb AA). In uncomplicated malaria, when compared to Hb AA children, Hb AC children had significantly lower serological responses to extracellular Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) domains but did not differ in responses to intracellular PfEMP1 domains and other VSAs, including members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family. Healthy children with Hb AC and Hb AS genotypes recognized fewer extracellular PfEMP1s compared to children with Hb AA, especially CD36-binding PfEMP1s. These reduced serologic responses may reflect reduced VSA presentation or lower parasite exposure in children with Hb AC or AS and provide insights into mechanisms of protection.
ABCA7-dependent induction of neuropeptide Y is required for synaptic resilience in Alzheimer’s disease through BDNF/NGFR signaling
Authors: Hüseyin Tayran, Elanur Yilmaz, Prabesh Bhattarai, Yuhao Min, Xue Wang, Yiyi Ma, Ni Wang, Inyoung Jeong, Nastasia Nelson, Nada Kassara, Mehmet Ilyas Cosacak, Ruya Merve Dogru, Dolly Reyes-Dumeyer, Jakob Mørkved Stenersen, Joseph S Reddy, Min Qiao, Delaney Flaherty, Tamil Iniyan Gunasekaran, Zikun Yang, Nathalie Jurisch-Yaksi, Andrew F Teich, Takahisa Kanekiyo, Giuseppe Tosto, Badri N Vardarajan, Özkan İş, Nilüfer Ertekin-Taner, Richard Mayeux, Caghan Kizil
Journal: Cell Genomics (2024)
An isoform-resolution transcriptomic atlas of colorectal cancer from long-read single-cell sequencing
Authors: Zhongxiao Li, Bin Zhang, Jia Jia Chan, Hossein Tabatabaeian, Qing Yun Tong, Xiao Hong Chew, Xiaonan Fan, Patrick Driguez, Charlene Chan, Faith Cheong, Shi Wang, Bei En Siew, Ian Jse-Wei Tan, Kai-Yin Lee, Bettina Lieske, Wai-Kit Cheong, Dennis Kappei, Ker-Kan Tan, Xin Gao, Yvonne Tay
Journal: Cell Genomics (2024)

Colorectal cancer (CRC) ranks as the second leading cause of cancer deaths globally. In recent years, short-read single-cell RNA sequencing (scRNA-seq) has been instrumental in deciphering tumor heterogeneities. However, these studies only enable gene-level quantification but neglect alterations in transcript structures arising from alternative end processing or splicing. In this study, we integrated short- and long-read scRNA-seq of CRC samples to build an isoform-resolution CRC transcriptomic atlas. We identified 394 dysregulated transcript structures in tumor epithelial cells, including 299 resulting from various combinations of splicing events. Second, we characterized genes and isoforms associated with epithelial lineages and subpopulations exhibiting distinct prognoses. Among 31,935 isoforms with novel junctions, 330 were supported by The Cancer Genome Atlas RNA-seq and mass spectrometry data. Finally, we built an algorithm that integrated novel peptides derived from open reading frames of recurrent tumor-specific transcripts with mass spectrometry data and identified recurring neoepitopes that may aid the development of cancer vaccines.
ONCOLINER: A new solution for monitoring, improving, and harmonizing somatic variant calling across genomic oncology centers
Authors: Rodrigo Martín, Nicolás Gaitán, Frédéric Jarlier, Lars Feuerbach, Henri de Soyres, Marc Arbonés, Tom Gutman, Montserrat Puiggròs, Alvaro Ferriz, Asier Gonzalez, Lucía Estelles, Ivo Gut, Salvador Capella-Gutierrez, Lincoln D Stein, Benedikt Brors, Romina Royo, Philippe Hupé, David Torrents
Journal: Cell Genomics (2024)
Human milk microbiota, oligosaccharide profiles, and infant gut microbiome in preterm infants diagnosed with necrotizing enterocolitis
Authors: Andrea C Masi, Lauren C Beck, John D Perry, Claire L Granger, Alice Hiorns, Gregory R Young, Lars Bode, Nicholas D Embleton, Janet E Berrington, Christopher J Stewart
Journal: Cell Reports Medicine (2024)

Necrotizing enterocolitis (NEC) is a severe intestinal disease of very preterm infants with mother's own milk (MOM) providing protection, but the contribution of the MOM microbiota to NEC risk has not been explored. Here, we analyze MOM of 110 preterm infants (48 NEC, 62 control) in a cross-sectional study. Breast milk contains viable bacteria, but there is no significant difference in MOM microbiota between NEC and controls. Integrative analysis between MOM microbiota, human milk oligosaccharides (HMOs), and the infant gut microbiota shows positive correlations only between Acinetobacter in the infant gut and Acinetobacter and Staphylococcus in MOM. This study suggests that NEC protection from MOM is not modulated through the MOM microbiota. Thus, "'restoring" the MOM microbiota in donor human milk is unlikely to reduce NEC, and emphasis should instead focus on increasing fresh maternal human milk intake and researching different therapies for NEC prevention.
Sex and gender bias in chronic coronary syndromes research: analysis of studies used to inform the 2019 European Society of Cardiology guidelines
Authors: Kathleen Bastian-Pétrel, Jessica L Rohmann, Sabine Oertelt-Prigione, Marco Piccininni, Katja Gayraud, Michelle Kelly-Irving, Nathalie Bajos
Journal: The Lancet Regional Health - Europe (2024)
Phase 1a study of ESG401, a Trop2 antibody-drug conjugate, in patients with locally advanced/metastatic solid tumors
Authors: Jiani Wang, Zhongsheng Tong, Yinuo Tan, Yehui Shi, Yun Wu, Qing Zhou, Xiaoyan Xing, Xiaomei Chen, Fuming Qiu, Fei Ma
Journal: Cell Reports Medicine (2024)
Decoupling HIV-1 antiretroviral drug inhibition from plasma antibody activity to evaluate broadly neutralizing antibody therapeutics and vaccines
Authors: Magdalena Schwarzmüller, Cristina Lozano, Merle Schanz, Irene A Abela, Silvan Grosse-Holz, Selina Epp, Martina Curcio, Jule Greshake, Peter Rusert, Michael Huber, Roger D Kouyos, Huldrych F Günthard, Alexandra Trkola
Journal: Cell Reports Medicine (2024)
Global wastewater surveillance for pathogens with pandemic potential: opportunities and challenges
Authors: Nicholas C Grassly, Alexander G Shaw, Michael Owusu
Journal: The Lancet Microbe (2024)

SummaryWastewater surveillance holds great promise as a sensitive method to detect spillover of zoonotic infections and early pandemic emergence, thereby informing risk mitigation and public health response. Known viruses with pandemic potential are shed in human stool or urine, or both, and the experiences with SARS-CoV-2, monkeypox virus, and Zika virus highlight the feasibility of community-based wastewater surveillance for pandemic viruses that have different transmission routes. We reviewed human shedding and wastewater surveillance data for prototype viruses representing viral families of concern to estimate the likely sensitivity of wastewater surveillance compared with that of clinical surveillance. We examined how data on wastewater surveillance detection, together with viral genetic sequences and animal faecal biomarkers, could be used to identify spillover infections or early human transmission and adaptation. The opportunities and challenges associated with global wastewater surveillance for the prevention of pandemics are described in this Personal View, focusing on low-income and middle-income countries, where the risk of pandemic emergence is the highest. We propose a research and public health agenda to ensure an equitable and sustainable solution to these challenges.
A bispecific antibody targeting EGFR and AXL delays resistance to osimertinib
Authors: Arturo Simoni-Nieves, Moshit Lindzen, Suvendu Giri, Nitin Gupta, Rishita Chatterjee, Boobash-Raj Selvadurai, Marieke Van Daele, Danielle Love, Yuya Haga, Donatella Romaniello, Tomer-Meir Salame, Mirie Zerbib, Roni Oren, Yasuo Tsutsumi, Mattia Lauriola, Ilaria Marrocco, Yosef Yarden
Journal: Cell Reports Medicine (2024)
International Union of Basic and Clinical Pharmacology. CXVII: Taste 2 receptors—Structures, functions, activators, and blockers
Authors: Maik Behrens
Journal: Pharmacological Reviews (2024)

Bitter perception plays a critical role for the detection of potentially harmful substances in food items for most vertebrates. The detection of bitter compounds is facilitated by specialized receptors located in taste buds of the oral cavity. This work focuses on the receptors, including their sensitivities, structure-function relationships, agonists and antagonists. Moreover, the existence of numerous bitter taste receptor variants in the human population and the fact that several of them affect individual bitter tasting profoundly, is discussed as well. The identification of bitter taste receptors in numerous tissues outside the oral cavity and their multiple proposed roles in these tissues is also described briefly. Although this work is mainly focused on human bitter taste receptors, it is imperative to compare human bitter taste with that of other animals to understand which evolutionary forces might have shaped bitter taste receptors and their functions and to distinguish apparent typical human from rather general features. For the readers who are not too familiar with the gustatory system short descriptions of taste anatomy, signal transduction and oral bitter taste receptor expression are included in the beginning of this article. <b>Significance Statement</b> Apart from their role as sensors for potentially harmful substances in the oral cavity, the numerous additional roles of bitter taste receptors in tissues outside the gustatory system have received much attention recently. For the careful assessment of functions inside and outside the taste system a solid knowledge about the specific and general pharmacological features of these receptors and the growing toolbox available for studying them is imperative and provided in this work.