tbuckley/cabot-search huggingface dataset:
The role of desmoglein-2 in kidney disease
Authors: Tong Xu, Lea Herkens, Ting Jia, Barbara M Klinkhammer, Sebastian Kant, Claudia A Krusche, Eva M Buhl, Sikander Hayat, Jürgen Floege, Pavel Strnad, Rafael Kramann, Sonja Djudjaj, Peter Boor
Journal: Kidney International (2024)

Desmosomes are multi-protein cell-cell adhesion structures supporting cell stability and mechanical stress resilience of tissues, best described in skin and heart. The kidney is exposed to various mechanical stimuli and stress, yet little is known about kidney desmosomes. In healthy kidneys, we found desmosomal proteins located at the apical-junctional complex in tubular epithelial cells. In four different animal models and patient biopsies with various kidney diseases, desmosomal components were significantly upregulated and partly miss-localized outside of the apical-junctional complexes along the whole lateral tubular epithelial cell membrane. The most upregulated component was desmoglein-2 (Dsg2). Mice with constitutive tubular epithelial cell-specific deletion of Dsg2 developed normally, and other desmosomal components were not altered in these mice. When challenged with different types of tubular epithelial cell injury (unilateral ureteral obstruction, ischemia-reperfusion, and 2,8-dihydroxyadenine crystal nephropathy), we found increased tubular epithelial cell apoptosis, proliferation, tubular atrophy, and inflammation compared to wild-type mice in all models and time points. In vitro, silencing DSG2 via siRNA weakened cell-cell adhesion in HK-2 cells and increased cell death. Thus, our data show a prominent upregulation of desmosomal components in tubular cells across species and diseases and suggest a protective role of Dsg2 against various injurious stimuli.
Tislelizumab versus Sorafenib in First-Line Treatment of Unresectable Hepatocellular Carcinoma: Impact on Health-Related Quality of Life in RATIONALE-301 Study
Authors: Richard S Finn, Masatoshi Kudo, Gisoo Barnes, Tim Meyer, Frederic Boisserie, Ramil Abdrashitov, Yaxi Chen, Songzi Li, Andrew X Zhu, Shukui Qin, Arndt Vogel
Journal: Liver Cancer (2024)

RATIONALE-301 (NCT03412773) was a global, phase 3 study comparing the efficacy and safety of tislelizumab with sorafenib as first-line (1L) treatment in adult patients with unresectable hepatocellular carcinoma (HCC) that met its primary endpoint of noninferiority in overall survival (OS). This analysis compared health-related quality-of-life (HRQOL) outcomes between the arms.
Feasibility of Continuous Noninvasive Pulmonary Artery Pressure Monitoring via the Cordella Implantable Pulmonary Artery Sensor
Authors: Wilfried Mullens, Stephen Rosenkranz, Faisal Sharif, Birgit Aßmus, Niall G Mahon, Tibor Kempf, Lynne W Stevenson, Jozef Bartunek
Journal: JACC Heart Failure (2024)
Differentiated mesenchymal stem cells-derived exosomes immobilized in decellularized sciatic nerve hydrogels for peripheral nerve repair
Authors: Bo Liu, Olawale A. Alimi, Yanfei Wang, Yunfan Kong, Mitchell Kuss, Mena Asha Krishnan, Guoku Hu, Yi Xiao, Jixin Dong, Dominick J. DiMaio, Bin Duan
Journal: Journal of Controlled Release (2024)
US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative, <i>ESR1</i>-Mutated Advanced or Metastatic Breast Cancer
Authors: Mirat Shah, Hima Lingam, Xin Gao, Haley Gittleman, Mallorie H. Fiero, Danielle Krol, Nikolett Biel, Tiffany K. Ricks, Wentao Fu, Salaheldin Hamed, Fang Li, Jillian (Jielin) Sun, Jianghong Fan, Robert Schuck, Manuela Grimstein, Liuya Tang, Shyam Kalavar, Abdelrahmman Abukhdeir, Anand Pathak, Soma Ghosh, Ilynn Bulatao, Amy Tilley, William F. Pierce, Bronwyn D. Mixter, Shenghui Tang, Richard Pazdur, Paul Kluetz, Laleh Amiri-Kordestani
Journal: Journal of Clinical Oncology (2024)

The US Food and Drug Administration (FDA) approved elacestrant for the treatment of postmenopausal women or adult men with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 (
DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Mengjia Song, Chaoqi Zhang, Shaoyan Cheng, Dijun Ouyang, Yu Ping, Jieying Yang, YaoJun Zhang, Yan Tang, Hao Chen, Qi-jing Wang, Yong-qiang Li, Jia He, Tong Xiang, Yizhuo Zhang, Jian-Chuan Xia
Journal: Cancer Research (2024)

Abstract Neutrophil extracellular traps (NET), formed by the extracellular release of decondensed chromatin and granules, have been shown to promote tumor progression and metastasis. Tumor-associated neutrophils in hepatocellular carcinoma (HCC) are prone to NET formation, highlighting the need for a more comprehensive understanding of the mechanisms of action of NETs in liver cancer. Here, we showed that DNA of NETs (NET-DNA) binds transmembrane and coiled-coil domains 6 (TMCO6) on CD8+ T cells to impair antitumor immunity and thereby promote HCC progression. TGFβ1 induced NET formation, which recruited CD8+ T cells. Binding to NET-DNA inhibited CD8+ T cells function while increasing apoptosis and TGFβ1 secretion, forming a positive feedback loop to further stimulate NET formation and immunosuppression. Mechanistically, the N-terminus of TMCO6 interacted with NET-DNA and suppressed T-cell receptor signaling and NFκB p65 nuclear translocation. Blocking NET formation by inhibiting PAD4 induced potent antitumor effects in wild-type mice but not TMCO6−/− mice. In clinical samples, CD8+ T cells expressing TMCO6 had an exhausted phenotype. TGFβ1 signaling inhibition or TMCO6 deficiency combined with anti-PD-1 abolished NET-driven HCC progression in vivo. Collectively, this study unveils the role of NET-DNA in impairing CD8+ T-cell immunity by binding TMCO6 and identifies targeting this axis as an immunotherapeutic strategy for blocking HCC progression. Significance: TMCO6 is a receptor for DNA of NETs that mediates CD8+ T-cell dysfunction in HCC, indicating that the NET-TMCO6 axis is a promising target for overcoming immunosuppression in liver cancer.
Honeycomb-inspired ZIF-sealed interface enhances osseointegration via anti-infection and osteoimmunomodulation
Authors: Jiale Dong, Wei Zhou, Xianli Hu, Jiaxiang Bai, Siming Zhang, Xianzuo Zhang, Lei Yu, Peng Yang, Lingtong Kong, Mingkai Liu, Xifu Shang, Zheng Su, Dechun Geng, Chen Zhu
Journal: Biomaterials (2024)
Keeping Your Brain in Balance: Homeostatic Regulation of Network Function
Authors: Wei Wen, Gina G. Turrigiano
Journal: Annual Review of Neuroscience (2024)

To perform computations with the efficiency necessary for animal survival, neocortical microcircuits must be capable of reconfiguring in response to experience, while carefully regulating excitatory and inhibitory connectivity to maintain stable function. This dynamic fine-tuning is accomplished through a rich array of cellular homeostatic plasticity mechanisms that stabilize important cellular and network features such as firing rates, information flow, and sensory tuning properties. Further, these functional network properties can be stabilized by different forms of homeostatic plasticity, including mechanisms that target excitatory or inhibitory synapses, or that regulate intrinsic neuronal excitability. Here we discuss which aspects of neocortical circuit function are under homeostatic control, how this homeostasis is realized on the cellular and molecular levels, and the pathological consequences when circuit homeostasis is impaired. A remaining challenge is to elucidate how these diverse homeostatic mechanisms cooperate within complex circuits to enable them to be both flexible and stable.
An anti-mycobacterial conjugated oligoelectrolyte effective against <i>Mycobacterium abscessus</i>
Authors: Kaixi Zhang, Jakkarin Limwongyut, Alex S. Moreland, Samuel Chan Jun Wei, Tania Jim Jia Min, Yan Sun, Sung Jae Shin, Su-Young Kim, Byung Woo Jhun, Kevin Pethe, Guillermo C. Bazan
Journal: Science Translational Medicine (2024)

Infections caused by nontuberculous mycobacteria have increased more than 50% in the past two decades and more than doubled in the elderly population.
Exploiting Tertiary Lymphoid Structures to Stimulate Antitumor Immunity and Improve Immunotherapy Efficacy
Authors: Giulia Petroni, Serena Pillozzi, Lorenzo Antonuzzo
Journal: Cancer Research (2024)

Abstract Tumor-associated tertiary lymphoid structures (TLS) have been associated with favorable clinical outcomes and response to immune checkpoint inhibitors in many cancer types, including non–small cell lung cancer. Although the detailed cellular and molecular mechanisms underlying these clinical associations have not been fully elucidated, growing preclinical and clinical studies are helping to elucidate the mechanisms at the basis of TLS formation, composition, and regulation of immune responses. However, a major challenge remains how to exploit TLS to enhance naïve and treatment-mediated antitumor immune responses. Here, we discuss the current understanding of tumor-associated TLS, preclinical models that can be used to study them, and potential therapeutic interventions to boost TLS formation, with a particular focus on lung cancer research.
An Updated Evaluation of Atrazine-Cancer Incidence Associations among Pesticide Applicators in the Agricultural Health Study Cohort
Authors: Richard V. Remigio, Gabriella Andreotti, Dale P. Sandler, Patricia A. Erickson, Stella Koutros, Paul S. Albert, Lauren M. Hurwitz, Christine G. Parks, Jay H. Lubin, Jonathan N. Hofmann, Laura E. Beane Freeman
Journal: Environmental Health Perspectives (2024)

Atrazine is a common agricultural herbicide in the United States. Few epidemiologic studies have evaluated cancer risks. Previous analyses within the Agricultural Health Study (AHS) have found some evidence of associations with cancer at some sites.
Selenomethionine in gelatin methacryloyl hydrogels: Modulating ferroptosis to attenuate skin aging
Authors: Jiachen Sun, Xiaoye Xie, Yaoyao Song, Tianjun Sun, Xinzhu Liu, Huageng Yuan, Chuanan Shen
Journal: Bioactive Materials (2024)

During skin aging, the degeneration of epidermal stem cells (EpiSCs) leads to diminished wound healing capabilities and epidermal disintegration. This study tackles this issue through a comprehensive analysis combining transcriptomics and untargeted metabolomics, revealing age-dependent alterations in the
Increased type 1 inflammation in gynecologic cervicovaginal samples in patients with APS-1
Authors: Iivo Hetemäki, Viivi Saari, Dawit A. Yohannes, Elina Holopainen, Tiina Holster, Suvi Jokiranta, Mikko I. Mäyränpää, Seppo Virtanen, Outi Mäkitie, Eliisa Kekäläinen, Saila Laakso
Journal: Journal of Allergy and Clinical Immunology (2024)

Inborn errors of immunity offer important insights into mucosal immunity. In autoimmune polyendocrine syndrome type-1 (APS-1), chronic mucocutaneous candidiasis has been ascribed to neutralizing IL-17 autoantibodies. Recent evidence implicates excessive T-cell IFN-γ secretion and ensuing epithelial barrier disruption in predisposition to candidiasis, but these results remain to be replicated. Whether IL-17 paucity, increased type I inflammation, or their combination underlies susceptibility to chronic mucocutaneus candidiasis in APS-1 is debated.
Fabrication of fully aligned self-assembled cell-laden collagen filaments for tissue engineering via a hybrid bioprinting process
Authors: JuYeon Kim, Hyeongjin Lee, Gyudo Lee, Dongryeol Ryu, GeunHyung Kim
Journal: Bioactive Materials (2024)

Cell-laden structures play a pivotal role in various tissue engineering applications, particularly in tissue restoration. Interactions between cells within bioprinted structures are crucial for successful tissue development and regulation of stem cell fate through intricate cell-to-cell signaling pathways. In this study, we developed a new technique that combines polyethylene glycol (PEG)-infused submerged bioprinting with a stretching procedure. This approach facilitated the generation of fully aligned collagen structures consisting of myoblasts and a low concentration (2 wt%) of collagen to efficiently encourage muscle tissue regeneration. By adjusting several processing parameters, we obtained biologically safe and mechanically stable cell-laden collagen filaments with uniaxial alignment. Notably, the cell filaments exhibited markedly elevated cellular activities compared to those exhibited by conventional bioprinted filaments, even at similar cell densities. Moreover, when we implanted structures containing adipose stem cells into mice, we observed a significantly increased level of myogenesis compared to that in normally bioprinted struts. Thus, this promising approach has the potential to revolutionize tissue engineering by fostering enhanced cellular interactions and promoting improved outcomes in regenerative medicine.
Characterisation of digital therapeutic clinical trials: a systematic review with natural language processing
Authors: Brenda Y Miao, Madhumita Sushil, Ava Xu, Michelle Wang, Douglas Arneson, Ellen Berkley, Meera Subash, Rohit Vashisht, Vivek Rudrapatna, Atul J Butte
Journal: The Lancet Digital Health (2024)

Digital therapeutics (DTx) are a somewhat novel class of US Food and Drug Administration-regulated software that help patients prevent, manage, or treat disease. Here, we use natural language processing to characterise registered DTx clinical trials and provide insights into the clinical development landscape for these novel therapeutics. We identified 449 DTx clinical trials, initiated or expected to be initiated between 2010 and 2030, from ClinicalTrials.gov using 27 search terms, and available data were analysed, including trial durations, locations, MeSH categories, enrolment, and sponsor types. Topic modelling of eligibility criteria, done with BERTopic, showed that DTx trials frequently exclude patients on the basis of age, comorbidities, pregnancy, language barriers, and digital determinants of health, including smartphone or data plan access. Our comprehensive overview of the DTx development landscape highlights challenges in designing inclusive DTx clinical trials and presents opportunities for clinicians and researchers to address these challenges. Finally, we provide an interactive dashboard for readers to conduct their own analyses.
RE.GA.IN.: the Real-world Gastritis Initiative–updating the updates
Authors: Massimo Rugge, Robert M Genta, Peter Malfertheiner, Mario Dinis-Ribeiro, Hashem El-Serag, David Y Graham, Ernst J Kuipers, Wai Keung Leung, Jin Young Park, Theodore Rokkas, Christian Schulz, Emad M El-Omar
Journal: Gut (2024)

At the end of the last century, a far-sighted ‘working party’ held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle. The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.
High-performance lung-targeted bio-responsive platform for severe colistin-resistant bacterial pneumonia therapy
Authors: Decui Cheng, Rui Tian, Tingting Pan, Qiang Yu, Li Wei, Jiaozhi Liyin, Yunqi Dai, Xiaoli Wang, Ruoming Tan, Hongping Qu, Min Lu
Journal: Bioactive Materials (2024)

Polymyxins are the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections. However, this last resort has been threatened by the emergence of superbugs carrying the mobile colistin resistance gene-1
Lifetime Suicide Attempts in Otherwise Psychiatrically Healthy Individuals
Authors: Maria A. Oquendo, Melanie Wall, Shuai Wang, Mark Olfson, Carlos Blanco
Journal: JAMA Psychiatry (2024)

Not all people who die by suicide have a psychiatric diagnosis; yet, little is known about the percentage and demographics of individuals with lifetime suicide attempts who are apparently psychiatrically healthy. If such suicide attempts are common, there are implications for suicide risk screening, research, policy, and nosology.
Beyond the Barrier: Unraveling the Mechanisms of Immunotherapy Resistance
Authors: Hannah N. Bell, Weiping Zou
Journal: Annual Review of Immunology (2024)

Immune checkpoint blockade (ICB) induces a remarkable and durable response in a subset of cancer patients. However, most patients exhibit either primary or acquired resistance to ICB. This resistance arises from a complex interplay of diverse dynamic mechanisms within the tumor microenvironment (TME). These mechanisms include genetic, epigenetic, and metabolic alterations that prevent T cell trafficking to the tumor site, induce immune cell dysfunction, interfere with antigen presentation, drive heightened expression of coinhibitory molecules, and promote tumor survival after immune attack. The TME worsens ICB resistance through the formation of immunosuppressive networks via immune inhibition, regulatory metabolites, and abnormal resource consumption. Finally, patient lifestyle factors, including obesity and microbiome composition, influence ICB resistance. Understanding the heterogeneity of cellular, molecular, and environmental factors contributing to ICB resistance is crucial to develop targeted therapeutic interventions that enhance the clinical response. This comprehensive overview highlights key mechanisms of ICB resistance that may be clinically translatable.
Genome-wide association study identifies high-impact susceptibility loci for HCC in North America
Authors: Manal M. Hassan, Donghui Li, Younghun Han, Jinyoung Byun, Rikita I. Hatia, Erping Long, Jiyeon Choi, Robin Kate Kelley, Sean P. Cleary, Anna S. Lok, Paige Bracci, Jennifer B. Permuth, Roxana Bucur, Jian-Min Yuan, Amit G. Singal, Prasun K. Jalal, R. Mark Ghobrial, Regina M. Santella, Yuko Kono, Dimpy P. Shah, Mindie H. Nguyen, Geoffrey Liu, Neehar D. Parikh, Richard Kim, Hui-Chen Wu, Hashem El-Serag, Ping Chang, Yanan Li, Yun Shin Chun, Sunyoung S. Lee, Jian Gu, Ernest Hawk, Ryan Sun, Chad Huff, Asif Rashid, Hesham M. Amin, Laura Beretta, Robert A. Wolff, Samuel O. Antwi, Yehuda Patt, Lu-Yu Hwang, Alison P. Klein, Karen Zhang, Mikayla A. Schmidt, Donna L. White, John A. Goss, Saira A. Khaderi, Jorge A. Marrero, Francisco G. Cigarroa, Pankil K. Shah, Ahmed O. Kaseb, Lewis R. Roberts, Christopher I. Amos
Journal: Hepatology (2024)

Background and Aims: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). Approach and Results: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40–0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62–0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29–1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33–1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51–1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74–0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. Conclusions: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.
First evidence of a mother-to-child transmission of an HIV-1/MO intergroup recombinant form
Authors: Manon Vautrin, Fabienne Tombette, Vinca Icard, Marie Leoz, Mary-Anne Trabaud, Antoine Ouziel, Luc Panetta, Véronique Lemée, Jean-Christophe Plantier, Alice Moisan
Journal: Clinical Microbiology and Infection (2024)
Endothelial to mesenchymal transition: at the axis of cardiovascular health and disease
Authors: Ignacio Fernando Hall, Franceska Kishta, Yang Xu, Andrew H Baker, Jason C Kovacic
Journal: Cardiovascular Research (2024)

Abstract Endothelial cells (ECs) line the luminal surface of blood vessels and play a major role in vascular (patho)-physiology by acting as a barrier, sensing circulating factors and intrinsic/extrinsic signals. ECs have the capacity to undergo endothelial-to-mesenchymal transition (EndMT), a complex differentiation process with key roles both during embryonic development and in adulthood. EndMT can contribute to EC activation and dysfunctional alterations associated with maladaptive tissue responses in human disease. During EndMT, ECs progressively undergo changes leading to expression of mesenchymal markers while repressing EC lineage-specific traits. This phenotypic and functional switch is considered to largely exist in a continuum, being characterized by a gradation of transitioning stages. In this report, we discuss process plasticity and potential reversibility and the hypothesis that different EndMT-derived cell populations may play a different role in disease progression or resolution. In addition, we review advancements in the EndMT field, current technical challenges, as well as therapeutic options and opportunities in the context of cardiovascular biology.
Clinical consequences of infliximab immunogenicity and the effect of proactive therapeutic drug monitoring: exploratory analyses of the randomised, controlled NOR-DRUM trials
Authors: Marthe Kirkesæther Brun, Johanna E Gehin, Kristin Hammersbøen Bjørlykke, David John Warren, Rolf A Klaasen, Joseph Sexton, Øystein Sandanger, Tore K Kvien, Cato Mørk, Jørgen Jahnsen, Nils Bolstad, Kristin Kaasen Jørgensen, Espen A Haavardsholm, Guro Løvik Goll, Silje Watterdal Syversen
Journal: The Lancet Rheumatology (2024)