tbuckley/cabot-search huggingface dataset:
One-year transplant-free survival following hospital discharge after ICU Admission for ACLF in the Netherlands
Authors: Jubi de Haan, Fabian Termorshuizen, Nicolette de Keizer, Diederik Gommers, Caroline den Hoed
Journal: Journal of Hepatology (2024)

Background & AimsPatients with acute decompensated (AD) liver cirrhosis or acute-on-chronic liver failure (ACLF) often require intensive care unit (ICU) admission for organ support. Existing research, mostly from specialized liver transplant centers, largely addresses short-term outcomes. Our aim was to evaluate in-hospital mortality and 1-year transplant-free survival after hospital discharge in the Netherlands.MethodsWe conducted a nationwide observational cohort study, including patients with an history of cirrhosis or first complications of cirrhotic portal hypertension admitted to ICUs in the Netherlands between 2012 and 2020. The influence of ACLF grade at ICU admission on 1-year transplant-free survival after hospital discharge among hospital survivors was evaluated using unadjusted Kaplan-Meier (KM) survival curve and adjusted Cox proportional hazard model.ResultsOut of the 3,035 patients, 1,819 (59.9%) had ACLF grade 3. 1420 patients (46.8%) survived hospitalization after ICU admission. The overall probability of 1-year transplant-free survival after hospital discharge was 0.61 (95% CI 0.59-0.64). This rate varied with ACLF grade at ICU admission, being highest in patients without ACLF (0.71 [95% CI 0.66-0.76]) and lowest in those with ACLF-3 (0.53 [95% CI 0.49-0.58]) (Logrank P < 0.0001). However, after adjusting for age, malignancy status and MELD-score, ACLF grade at ICU admission was not associated with an increased risk of liver transplantation or death within one year after hospital discharge.ConclusionIn this nationwide cohort study, ACLF grade at ICU admission did not independently affect 1-year transplant-free survival after hospital discharge. Instead, age, presence of malignancy and the severity of liver disease played a more prominent role in influencing transplant-free survival after hospital discharge.Impact and implicationsPatients with Acute-on-chronic liver failure (ACLF) often require intensive care unit (ICU) admission for organ support. In these patients' short-term mortality is high, but long-term outcomes of survivors remain unknown. Using a large nationwide cohort of ICU patients, we discovered that the severity of ACLF at ICU admission does not influence one-year transplant-free survival after hospital discharge. Instead, age, malignancy status and overall severity of liver disease are more critical factors in determining their long-term survival.
Telomeres in glioma: Maintenance mechanisms to therapeutic potential
Authors: Nicholas O Stevers, Joseph F Costello
Journal: Neuro-Oncology (2024)

Journal Article Corrected proof Telomeres in glioma: Maintenance mechanisms to therapeutic potential Get access Nicholas O Stevers, Nicholas O Stevers Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph F Costello Joseph F Costello Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA Corresponding Author: Joseph F. Costello, PhD, Department of Neurological Surgery, University of California, San Francisco, 1450 3rd Street, Room HD471, San Francisco, CA 94158, USA (joseph.costello@ucsf.edu). https://orcid.org/0000-0003-3189-584X Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noae052, https://doi.org/10.1093/neuonc/noae052 Published: 11 March 2024 Article history Published: 11 March 2024 Corrected and typeset: 28 March 2024
Tumor microenvironment reprogramming by nanomedicine to enhance the effect of tumor immunotherapy
Authors: Yu Huang, Hui Fan, Huihui Ti
Journal: Asian Journal of Pharmaceutical Sciences (2024)

With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors that do not respond to standard treatment options. Despite its advances, immunotherapy still has limitations, such as poor clinical response rates and differences in individual patient responses, largely because tumor tissues have strong immunosuppressive microenvironments. Many tumors have a tumor microenvironment (TME) that is characterized by hypoxia, low pH, and substantial numbers of immunosuppressive cells, and these are the main factors limiting the efficacy of antitumor immunotherapy. The TME is crucial to the occurrence, growth, and metastasis of tumors. Therefore, numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME. Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy. The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy. However, the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects. Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting. Importantly, they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells. Therefore, nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy. Therefore, this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.
A meta-analytic review of anger management activities that increase or decrease arousal: What fuels or douses rage?
Authors: Sophie L. Kjærvik, Brad J. Bushman
Journal: Clinical Psychology Review (2024)

Anger is an unpleasant emotion that most people want to get rid of. Some anger management activities focus on decreasing arousal (e.g., deep breathing, mindfulness, meditation), whereas others focus on increasing arousal (e.g., hitting a bag, jogging, cycling). This meta-analytic review, based on 154 studies including 184 independent samples involving 10,189 participants, tested the effectiveness of both types of activities. The results indicated that arousal-decreasing activities decreased anger and aggression (g = −0.63, [−0.82, −0.43]), and the results were robust. Effects were stable over time for participants of different genders, races, ages, and cultures. Arousal-decreasing activities were effective in students and non-students, in criminal offenders and non-offenders, and in individuals with and without intellectual disabilities. Arousal-decreasing activities were effective regardless of how delivered (e.g., digital platforms, researchers, therapists), in both group and individual sessions, and in both field and laboratory settings. In contrast, arousal-increasing activities were ineffective overall (g = −0.02, [−0.13, 0.09]) and were heterogenous and complex. These findings do not support the ideas that venting anger or going for a run are effective anger management activities. A more effective approach for managing anger is "turning down the heat" or calming down by engaging in activities that decrease arousal.
Vulnerabilities in social anxiety: Integrating intra- and interpersonal perspectives
Authors: Rivkah Ginat-Frolich, Eva Gilboa-Schechtman, Jonathan D. Huppert, Idan M. Aderka, Lynn E. Alden, Yair Bar-Haim, Eni S. Becker, Amit Bernstein, Ronny Geva, Richard G. Heimberg, Stefan G. Hofmann, Todd B. Kashdan, Ernst H.W. Koster, Joshua Lipsitz, Jon K. Maner, David A. Moscovitch, Pierre Philippot, Ronald M. Rapee, Karin Roelofs, Thomas L. Rodebaugh, Franklin R. Schneier, Oliver C. Schultheiss, Ben Shahar, Ulrich Stangier, Murray B. Stein, Lusia Stopa, Charles T. Taylor, Justin W. Weeks, Matthias J. Wieser
Journal: Clinical Psychology Review (2024)
Nuclear AGO2 promotes myocardial remodeling by activating ANKRD1 transcription in failing hearts
Authors: Rong Xie, Shuai Yuan, Guo Hu, Jiabing Zhan, Kunying Jin, Yuyan Tang, Jiahui Fan, Yanru Zhao, Feng Wang, Chen Chen, Dao Wen Wang, Huaping Li
Journal: Molecular Therapy (2024)
Gastric mechanosensitive channel Piezo1 regulates ghrelin production and food intake
Authors: Yawen Zhao, Yang Liu, Tian Tao, Jinshan Zhang, Wenying Guo, Handan Deng, Mengxue Han, Haocong Mo, Xiaohan Tong, Song Lin, Jie Yang, Hening Zhai, Qimeng Wang, Zhengfang Hu, Weizhen Zhang, Hui Chen, Geyang Xu
Journal: Nature Metabolism (2024)
Hematopoietic stem cell gene editing rescues B-cell development in X-linked agammaglobulinemia
Authors: Sameer Bahal, Marta Zinicola, Shefta E Moula, Thomas E. Whittaker, Andrea Schejtman, Asma Naseem, Elena Blanco, Winston Vetharoy, Yi-Ting Hu, Rajeev Rai, Eduardo Gomez-Castaneda, Catarina Cunha-Santos, Siobhan O. Burns, Emma C. Morris, Claire Booth, Giandomenico Turchiano, Alessia Cavazza, Adrian J. Thrasher, Giorgia Santilli
Journal: Journal of Allergy and Clinical Immunology (2024)

Graphical abstractAbstractBackgroundX-linked agammaglobulinemia (XLA) is an inborn error of immunity that renders boys susceptible to life-threatening infections due to loss of mature B cells and circulating immunoglobulins. It is caused by defects in the gene encoding the Bruton tyrosine kinase (BTK) that mediates the maturation of B cells in the bone marrow and their activation in the periphery. This paper reports on a gene editing protocol to achieve "knock-in" of a therapeutic BTK cassette in hematopoietic stem and progenitor cells (HSPCs) as a treatment for XLA.MethodsTo rescue BTK expression, this study employed a clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 system that creates a DNA double-strand break in an early exon of the BTK locus and an adeno-associated virus 6 virus that carries the donor template for homology-directed repair. The investigators evaluated the efficacy of the gene editing approach in HSPCs from patients with XLA that were cultured in vitro under B-cell differentiation conditions or that were transplanted in immunodeficient mice to study B-cell output in vivo.ResultsA (feeder-free) B-cell differentiation protocol was successfully applied to blood-mobilized HSPCs to reproduce in vitro the defects in B-cell maturation observed in patients with XLA. Using this system, the investigators could show the rescue of B-cell maturation by gene editing. Transplantation of edited XLA HSPCs into immunodeficient mice led to restoration of the human B-cell lineage compartment in the bone marrow and immunoglobulin production in the periphery.ConclusionsGene editing efficiencies above 30% could be consistently achieved in human HSPCs. Given the potential selective advantage of corrected cells, as suggested by skewed X-linked inactivation in carrier females and by competitive repopulating experiments in mouse models, this work demonstrates the potential of this strategy as a future definitive therapy for XLA.
2D Is Better: Engineering Polydopamine into Cationic Nanosheets to Enhance Anti‐Inflammatory Capability
Authors: Lulu Liu, Chenxin Lu, Zhenchao Tao, Zhengbao Zha, Hua Wang, Zhaohua Miao
Journal: Advanced Healthcare Materials (2024)

Polydopamine nanomaterials have emerged as one of the most popular organic materials for the management of oxidative stress-mediated inflammatory diseases. However, their current anti-inflammatory ability is still unsatisfactory because of limited phenolic hydroxyl groups, and oxidation reaction-medicated reactive oxygen and nitrogen species (RONS) scavenging. Herein, via fusing dimension engineering and surface charge engineering, 2D cationic polydopamine nanosheets (PDA NSs) capable of scavenging multiple danger signals to enhance anti-inflammatory capability are reported. Compared with conventional spherical polydopamine nanoparticles, 2D PDA NSs exhibit three- to fourfold enhancement in RONS scavenging capability, which should be attributed to high specific surface area and abundant phenol groups of 2D ultrathin structure. To further enhance the anti-inflammatory ability, polylysine molecules are absorbed on the surface of PDA NSs to endow the scavenging capability of cell-free DNA (cfDNA), another typical inflammatory factor to exacerbate the pathogenesis of inflammation. Molecular mechanisms reveal that cationic PDA NSs can concurrently activate Keap1-Nrf2 and block TLR9 signaling pathway, achieving synergistical inflammation inhibition. As a proof of concept, cationic PDA NSs with RONS and cfDNA dual-scavenging capability effectively alleviate the inflammatory bowel disease in both delayed and prophylactic models, much better than the clinical drug 5-aminosalicylic acid.
Early onset of pathological polyploidization and cellular senescence in hepatocytes lacking RAD51 creates a pro-fibrotic and pro-tumorigenic inflammatory microenvironment
Authors: Wenqing Bu, Xue Sun, Xiaotong Xue, Shengmiao Geng, Tingting Yang, Jia Zhang, Yanan Li, Chao Feng, Qiao Liu, Xiyu Zhang, Peishan Li, Zhaojian Liu, Yufang Shi, Changshun Shao
Journal: Hepatology (2024)

Background and Aims: RAD51 recombinase (RAD51) is a highly conserved DNA repair protein and is indispensable for embryonic viability. As a result, the role of RAD51 in liver development and function is unknown. Our aim was to characterize the function of RAD51 in postnatal liver development. Approach and Results: RAD51 is highly expressed during liver development and during regeneration following hepatectomy and hepatic injury, and is also elevated in chronic liver diseases. We generated a hepatocyte-specific Rad51 deletion mouse model using Alb -Cre ( Rad51 -conditional knockout (CKO)) and Adeno-associated virus 8-thyroxine-binding globulin-cyclization recombination enzyme to evaluate the function of RAD51 in liver development and regeneration. The phenotype in Rad51 -CKO mice is dependent on CRE dosage, with Rad51 fl/fl ; Alb -Cre +/+ manifesting a more severe phenotype than the Rad51 fl/fl ; Alb -Cre +/− mice. RAD51 deletion in postnatal hepatocytes results in aborted mitosis and early onset of pathological polyploidization that is associated with oxidative stress and cellular senescence. Remarkable liver fibrosis occurs spontaneously as early as in 3-month-old Rad51 fl/fl ; Alb -Cre +/+ mice. While liver regeneration is compromised in Rad51 -CKO mice, they are more tolerant of carbon tetrachloride–induced hepatic injury and resistant to diethylnitrosamine/carbon tetrachloride–induced HCC. A chronic inflammatory microenvironment created by the senescent hepatocytes appears to activate ductular reaction the transdifferentiation of cholangiocytes to hepatocytes. The newly derived RAD51 functional immature hepatocytes proliferate vigorously, acquire increased malignancy, and eventually give rise to HCC. Conclusions: Our results demonstrate a novel function of RAD51 in liver development, homeostasis, and tumorigenesis. The Rad51 -CKO mice represent a unique genetic model for premature liver senescence, fibrosis, and hepatocellular carcinogenesis.
Hypoxia‐activated ADCC‐enhanced humanized anti‐CD147 antibody for liver cancer imaging and targeted therapy with improved selectivity
Authors: Fang‐Zheng Qi, Hui‐Shan Su, Bo Wang, Luo‐Meng Qian, Yang Wang, Chen‐Hui Wang, Ya‐Xin Hou, Ping Chen, Qing Zhang, Dong‐Mei Li, Hao Tang, Jian‐Li Jiang, Hui‐Jie Bian, Zhi‐Nan Chen, Si‐He Zhang
Journal: MedComm (2024)

Abstract Therapeutic antibodies (Abs) improve the clinical outcome of cancer patients. However, on‐target off‐tumor toxicity limits Ab‐based therapeutics. Cluster of differentiation 147 (CD147) is a tumor‐associated membrane antigen overexpressed in cancer cells. Ab‐based drugs targeting CD147 have achieved inadequate clinical benefits for liver cancer due to side effects. Here, by using glycoengineering and hypoxia‐activation strategies, we developed a conditional Ab‐dependent cellular cytotoxicity (ADCC)‐enhanced humanized anti‐CD147 Ab, HcHAb18‐azo‐PEG 5000 (HAP18). Afucosylated ADCC‐enhanced HcHAb18 Ab was produced by a fed‐batch cell culture system. Azobenzene (Azo)‐linked PEG 5000 conjugation endowed HAP18 Ab with features of hypoxia‐responsive delivery and selective targeting. HAP18 Ab potently inhibits the migration, invasion, and matrix metalloproteinase secretion, triggers the cytotoxicity and apoptosis of cancer cells, and induces ADCC, complement‐dependent cytotoxicity, and Ab‐dependent cellular phagocytosis under hypoxia. In xenograft mouse models, HAP18 Ab selectively targets hypoxic liver cancer tissues but not normal organs or tissues, and has potent tumor‐inhibiting effects. HAP18 Ab caused negligible side effects and exhibited superior pharmacokinetics compared to those of parent HcHAb18 Ab. The hypoxia‐activated ADCC‐enhanced humanized HAP18 Ab safely confers therapeutic efficacy against liver cancer with improved selectivity. This study highlights that hypoxia activation is a promising strategy for improving the tumor targeting potential of anti‐CD147 Ab drugs.
Enhancing Health Care Communication With Large Language Models—The Role, Challenges, and Future Directions
Authors: Charumathi Raghu Subramanian, Daniel A. Yang, Raman Khanna
Journal: JAMA Network Open (2024)

Jonah Zaretsky, MD; Jeong Min Kim, MD; Samuel Baskharoun, MD; Yunan Zhao, MS; Jonathan Austrian, MD; Yindalon Aphinyanaphongs, MD, PhD; Ravi Gupta, MD; Saul B. Blecker, MD; Jonah Feldman, MD
Development of a Health Equity Framework for the US Preventive Services Task Force
Authors: Jennifer S. Lin, Elizabeth M. Webber, Sarah I. Bean, Corinne V. Evans
Journal: JAMA Network Open (2024)

Importance Clinical practice guidelines can play an important role in mitigating health inequities. The US Preventive Services Task Force (USPSTF) has prioritized addressing health equity and racism in its recommendations. Objective To develop a framework that would allow the USPSTF to incorporate a health equity lens that spans the entirety of its recommendation-making process. Evidence Review Key guidance, policy, and explanatory frameworks related to health equity were identified, and their recommendations and findings were mapped to current USPSTF methods. USPSTF members as well as staff from multiple entities supporting the USPSTF portfolio were consulted. Based on all the gathered information, a draft health equity framework and checklist were developed; they were then circulated to the USPSTF’s key partners for input and review. Findings An equity framework was developed that could be applied to all phases of the recommendation process: (1) topic nomination, selection, and prioritization; (2) development of the work plan; (3) evidence review; (4) evidence deliberation; (5) development of the recommendation statement; and (6) dissemination of recommendations. For each phase, several considerations and checklist items to address are presented. These items include using health equity as a prioritization criterion and engaging a diverse group of stakeholders at the earliest phases in identifying topics for recommendations; developing necessary equity-relevant questions (eg, beyond effectiveness and harms) to address during the protocol phase; using methods in synthesizing the evidence and contextual issues in the evidence review related to specific populations experiencing a disproportionate burden of disease; and examining the magnitude and certainty of net benefit, implementation considerations, risk assessment, and evidence gaps through an equity lens when developing evidence-based recommendations. Conclusions and Relevance Executing this entire framework and checklist as described will be challenging and will take additional time and resources. Nonetheless, whether adopted in its entirety or in parts, this framework offers guidance to the USPSTF, as well as other evidence-based guideline entities, in its mission to develop a more transparent, consistent, and intentional approach to addressing health equity in its recommendations.
Association between atopic dermatitis and eating disorders: a cross-sectional study in the All of Us Research Program
Authors: Gloria F Chen, Suzanne Xu, Marney A White, Jeffrey M Cohen
Journal: British Journal of Dermatology (2024)

We investigated the association between atopic dermatitis (AD) and eating disorders through a cross-sectional study of US adults in the All of Us Research Program, a diverse cohort of over 250 000 participants with a focus on populations traditionally under-represented in biomedical research. Using multivariable analysis, we found that AD was significantly associated with all eating disorders tested, with binge eating disorder having the greatest multivariable odds ratio of 3.58 (95% confidence interval 2.48–5.02, P &amp;lt; 0.001) when adjusted for age, sex, ethnicity and race.
Age and Probability of Spontaneous Umbilical Hernia Closure
Authors: Katherine He, Dionne A. Graham, Louis Vernacchio, Jonathan Hatoun, Laura Patane, Shannon L. Cramm, Shawn J. Rangel
Journal: JAMA Pediatrics (2024)

This cohort study of children younger than 6 years uses electronic health records to investigate whether a child’s age is associated with the probability of spontaneous umbilical hernia closure and to refine guidelines for surgical repair.
Microbleeds in Heterozygous <i>HTRA1</i>-Related Cerebral Small Vessel Disease
Authors: Yu Guo, Qing Peng, Chen Ling
Journal: JAMA Neurology (2024)

This case report describes the evaluation of a 44-year-old man with a history of headache, dizziness, and imbalance and imaging that showed lacunar infarctions and bilateral white matter hyperintensities.