tbuckley/cabot-search huggingface dataset:
Effectiveness and duration of protection of primary and booster immunisation against meningococcal serogroup C disease with meningococcal conjugate C and ACWY vaccines: Systematic review
Authors: Matas Griskaitis, Iris Thielemann, Viktoria Schönfeld, Annika Falman, Stefan Scholz, Ulrich Reinacher, Laura Haas, Ole Wichmann, Thomas Harder
Journal: Journal of Infection (2024)

To estimate vaccine effectiveness (VE) and duration of protection of single primary and booster immunisation with meningococcal C (MenC) and ACWY (MenACWY) conjugate vaccines in preventing MenC invasive meningococcal disease (IMD).
Chromothripsis is a novel biomarker for prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms
Authors: Ming‐Yi Zhang, Du He, Yi Zhang, Ke Cheng, Hong‐Shuai Li, Yu‐Wen Zhou, Qiong‐Xian Long, Rui‐Zhi Liu, Ji‐Yan Liu
Journal: MedComm (2024)

Abstract This study aimed to identify the role of chromothripsis as a novel biomarker in the prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms (pNENs). We conducted next‐generation gene sequencing in a cohort of 30 patients with high‐grade (G3) pNENs. As a reference, a similar analysis was also performed on 25 patients with low‐grade (G1/G2) pancreatic neuroendocrine tumors (pNETs). Chromothripsis and its relationship with clinicopathological features and prognosis were investigated. The results showed that DNA damage response and repair gene alteration and TP53 mutation were found in 29 and 11 patients, respectively. A total of 14 out of 55 patients had chromothripsis involving different chromosomes. Chromothripsis had a close relationship with TP53 alteration and higher grade. In the entire cohort, chromothripsis was associated with a higher risk of distant metastasis; both chromothripsis and metastasis (ENETS Stage IV) suggested a significantly shorter overall survival (OS). Importantly, in the high‐grade pNENs group, chromothripsis was the only independent prognostic indicator significantly associated with a shorter OS, other than TP53 alteration or pathological pancreatic neuroendocrine carcinomas (pNECs) diagnosis. Chromothripsis can guide worse prognosis in pNENs, and help differentiate pNECs from high‐grade (G3) pNETs.
Skeletal muscle: molecular structure, myogenesis, biological functions, and diseases
Authors: Lan‐Ting Feng, Zhi‐Nan Chen, Huijie Bian
Journal: MedComm (2024)

Skeletal muscle is an important motor organ with multinucleated myofibers as its smallest cellular units. Myofibers are formed after undergoing cell differentiation, cell-cell fusion, myonuclei migration, and myofibril crosslinking among other processes and undergo morphological and functional changes or lesions after being stimulated by internal or external factors. The above processes are collectively referred to as myogenesis. After myofibers mature, the function and behavior of skeletal muscle are closely related to the voluntary movement of the body. In this review, we systematically and comprehensively discuss the physiological and pathological processes associated with skeletal muscles from five perspectives: molecule basis, myogenesis, biological function, adaptive changes, and myopathy. In the molecular structure and myogenesis sections, we gave a brief overview, focusing on skeletal muscle-specific fusogens and nuclei-related behaviors including cell-cell fusion and myonuclei localization. Subsequently, we discussed the three biological functions of skeletal muscle (muscle contraction, thermogenesis, and myokines secretion) and its response to stimulation (atrophy, hypertrophy, and regeneration), and finally settled on myopathy. In general, the integration of these contents provides a holistic perspective, which helps to further elucidate the structure, characteristics, and functions of skeletal muscle.
The ischemia‐enhanced myocardial infarction protection‐related lncRNA protects against acute myocardial infarction
Authors: Rongzhou Wu, Tingting Wu, Qiaoyu Wang, Youyang Shi, Qianqian Dong, Xing Rong, Meiting Chen, Zhiyu He, Yu Fu, Lei Liu, Shuai Shao, Xueqiang Guan, Chunxiang Zhang
Journal: MedComm (2024)

Long non-coding RNA RP11-64B16.4 (
Localization of protoporphyrin IX during glioma-resection surgery via paired stimulated Raman histology and fluorescence microscopy
Authors: Mustafa Nasir-Moin, Lisa Irina Wadiura, Vlad Sacalean, Devin Juros, Misha Movahed-Ezazi, Emily K Lock, Andrew Smith, Matthew Lee, Hannah Weiss, Michael Müther, Daniel Alber, Sujay Ratna, Camila Fang, Eric Suero-Molina, Sönke Hellwig, Walter Stummer, Karl Rössler, Johannes A Hainfellner, Georg Widhalm, Barbara Kiesel, David Reichert, Mario Mischkulnig, Rajan Jain, Jakob Straehle, Nicolas Neidert, Oliver Schnell, Jürgen Beck, Jay Trautman, Steve Pastore, Donato Pacione, Dimitris Placantonakis, Eric Karl Oermann, John G Golfinos, Todd C Hollon, Matija Snuderl, Christian W Freudiger, Dieter Henrik Heiland, Daniel A Orringer
Journal: Nature Biomedical Engineering (2024)
Immune dysfunction prior to and during vaccination in multiple myeloma: a case study based on COVID-19
Authors: Esperanza Martín-Sánchez, Luis-Esteban Tamariz-Amador, Camila Guerrero, Anastasiia Zherniakova, Aintzane Zabaleta, Catarina Maia, Laura Blanco, Diego Alignani, Maria-Antonia Fortuño, Carlos Grande, Andrea Manubens, Jose-Maria Arguiñano, Clara Gomez, Ernesto Perez-Persona, Iñigo Olazabal, Itziar Oiartzabal, Carlos Panizo, Felipe Prosper, Jesus F. San-Miguel, Paula Rodriguez-Otero, Bruno Paiva, Jesus F. San Miguel
Journal: Blood Cancer Journal (2024)

Abstract Infection is the leading cause of death in multiple myeloma (MM). However, the cellular composition associated with immune dysfunction is not defined. We analyzed immune profiles in the peripheral blood of patients with MM ( n = 28) and B-cell chronic lymphoproliferative disorders ( n = 53) vs. health care practitioners ( n = 96), using multidimensional and computational flow cytometry. MM patients displayed altered distribution of most cell types (41/56, 73%), particularly within the B-cell (17/17) and T-cell (20/30) compartments. Using COVID-19 as a case study, we compared the immune response to vaccination based on 64,304 data points generated from the analysis of 1099 longitudinal samples. MM patients showed limited B-cell expansion linked to lower anti-RBD and anti-S antibody titers after the first two doses and booster. The percentages of B cells and CD4 + T cells in the blood, as well as the absolute counts of B cells and dendritic cells, predicted vaccine immunogenicity at different time points. In contrast with the humoral response, the percentage and antigen-dependent differentiation of SARS-CoV-2-specific CD8 + T cells was not altered in MM patients. Taken together, this study defined the cellular composition associated with immune dysfunction in MM and provided biomarkers such as the B-cell percentage and absolute count to individualize vaccination calendars.
Investigating the impact of poverty on mental illness in the UK Biobank using Mendelian randomization
Authors: Mattia Marchi, Anne Alkema, Charley Xia, Chris H. L. Thio, Li-Yu Chen, Winni Schalkwijk, Gian M. Galeazzi, Silvia Ferrari, Luca Pingani, Hyeokmoon Kweon, Sara Evans-Lacko, W. David Hill, Marco P. Boks
Journal: Nature Human Behaviour (2024)

Abstract It is unclear whether poverty and mental illness are causally related. Using UK Biobank and Psychiatric Genomic Consortium data, we examined evidence of causal links between poverty and nine mental illnesses (attention deficit and hyperactivity disorder (ADHD), anorexia nervosa, anxiety disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder and schizophrenia). We applied genomic structural equation modelling to derive a poverty common factor from household income, occupational income and social deprivation. Then, using Mendelian randomization, we found evidence that schizophrenia and ADHD causally contribute to poverty, while poverty contributes to major depressive disorder and schizophrenia but decreases the risk of anorexia nervosa. Poverty may also contribute to ADHD, albeit with uncertainty due to unbalanced pleiotropy. The effects of poverty were reduced by approximately 30% when we adjusted for cognitive ability. Further investigations of the bidirectional relationships between poverty and mental illness are warranted, as they may inform efforts to improve mental health for all.
Multiplex cerebrospinal fluid proteomics identifies biomarkers for diagnosis and prediction of Alzheimer’s disease
Authors: Yu Guo, Shi-Dong Chen, Jia You, Shu-Yi Huang, Yi-Lin Chen, Yi Zhang, Lin-Bo Wang, Xiao-Yu He, Yue-Ting Deng, Ya-Ru Zhang, Yu-Yuan Huang, Qiang Dong, Jian-Feng Feng, Wei Cheng, Jin-Tai Yu
Journal: Nature Human Behaviour (2024)
Systematic optimization of prime editing for the efficient functional correction of CFTR F508del in human airway epithelial cells
Authors: Alexander A. Sousa, Colin Hemez, Lei Lei, Soumba Traore, Katarina Kulhankova, Gregory A. Newby, Jordan L. Doman, Keyede Oye, Smriti Pandey, Philip H. Karp, Paul B. McCray, David R. Liu
Journal: Nature Biomedical Engineering (2024)

Abstract Prime editing (PE) enables precise and versatile genome editing without requiring double-stranded DNA breaks. Here we describe the systematic optimization of PE systems to efficiently correct human cystic fibrosis (CF) transmembrane conductance regulator ( CFTR ) F508del, a three-nucleotide deletion that is the predominant cause of CF. By combining six efficiency optimizations for PE—engineered PE guide RNAs, the PEmax architecture, the transient expression of a dominant-negative mismatch repair protein, strategic silent edits, PE6 variants and proximal ‘dead’ single-guide RNAs—we increased correction efficiencies for CFTR F508del from less than 0.5% in HEK293T cells to 58% in immortalized bronchial epithelial cells (a 140-fold improvement) and to 25% in patient-derived airway epithelial cells. The optimizations also resulted in minimal off-target editing, in edit-to-indel ratios 3.5-fold greater than those achieved by nuclease-mediated homology-directed repair, and in the functional restoration of CFTR ion channels to over 50% of wild-type levels (similar to those achieved via combination treatment with elexacaftor, tezacaftor and ivacaftor) in primary airway cells. Our findings support the feasibility of a durable one-time treatment for CF.
TFscope: systematic analysis of the sequence features involved in the binding preferences of transcription factors
Authors: Raphaël Romero, Christophe Menichelli, Christophe Vroland, Jean-Michel Marin, Sophie Lèbre, Charles-Henri Lecellier, Laurent Bréhélin
Journal: Genome biology (2024)

Characterizing the binding preferences of transcription factors (TFs) in different cell types and conditions is key to understand how they orchestrate gene expression. Here, we develop TFscope, a machine learning approach that identifies sequence features explaining the binding differences observed between two ChIP-seq experiments targeting either the same TF in two conditions or two TFs with similar motifs (paralogous TFs). TFscope systematically investigates differences in the core motif, nucleotide environment and co-factor motifs, and provides the contribution of each key feature in the two experiments. TFscope was applied to > 305 ChIP-seq pairs, and several examples are discussed.
sciMET-cap: high-throughput single-cell methylation analysis with a reduced sequencing burden
Authors: Sonia N Acharya, Ruth V Nichols, Lauren E Rylaarsdam, Brendan L O'Connell, Theodore P Braun, Andrew C Adey
Journal: Genome biology (2024)

Abstract DNA methylation is a key component of the mammalian epigenome, playing a regulatory role in development, disease, and other processes. Robust, high-throughput single-cell DNA methylation assays are now possible (sciMET); however, the genome-wide nature of DNA methylation results in a high sequencing burden per cell. Here, we leverage target enrichment with sciMET to capture sufficient information per cell for cell type assignment using substantially fewer sequence reads (sciMET-cap). Accumulated off-target coverage enables genome-wide differentially methylated region (DMR) calling for clusters with as few as 115 cells. We characterize sciMET-cap on human PBMCs and brain (middle frontal gyrus).
Joint impact of polygenic risk score and lifestyles on early- and late-onset cardiovascular diseases
Authors: Dong Sun, Yinqi Ding, Canqing Yu, Dianjianyi Sun, Yuanjie Pang, Pei Pei, Ling Yang, Iona Y. Millwood, Robin G. Walters, Huaidong Du, Xiaofang Chen, Dan Schmidt, Rebecca Stevens, Junshi Chen, Zhengming Chen, Liming Li, Jun Lv
Journal: Nature Human Behaviour (2024)
The cerebellum modulates thirst
Authors: Ila Mishra, Bing Feng, Bijoya Basu, Amanda M Brown, Linda H Kim, Tao Lin, Mir Abbas Raza, Amelia Moore, Abigayle Hahn, Samantha Bailey, Alaina Sharp, Juan C Bournat, Claire Poulton, Brian Kim, Amos Langsner, Aaron Sathyanesan, Roy V Sillitoe, Yanlin He, Atul R Chopra
Journal: Nature Neuroscience (2024)
Author Correction: Distinct developmental pathways generate functionally distinct populations of natural killer cells
Authors: Yi Ding, Marieke Lavaert, Simon Grassmann, Victor I Band, Liang Chi, Arundhoti Das, Sumit Das, Christelle Harly, Susannah C Shissler, Justin Malin, Dingkang Peng, Yongge Zhao, Jinfang Zhu, Yasmine Belkaid, Joseph C Sun, Avinash Bhandoola
Journal: Nature Immunology (2024)
Blood protein assessment of leading incident diseases and mortality in the UK Biobank
Authors: Danni A Gadd, Robert F Hillary, Zhana Kuncheva, Tasos Mangelis, Yipeng Cheng, Manju Dissanayake, Romi Admanit, Jake Gagnon, Tinchi Lin, Kyle L Ferber, Heiko Runz, Christopher N Foley, Riccardo E Marioni, Benjamin B Sun
Journal: Nature Aging (2024)

Abstract The circulating proteome offers insights into the biological pathways that underlie disease. Here, we test relationships between 1,468 Olink protein levels and the incidence of 23 age-related diseases and mortality in the UK Biobank ( n = 47,600). We report 3,209 associations between 963 protein levels and 21 incident outcomes. Next, protein-based scores (ProteinScores) are developed using penalized Cox regression. When applied to test sets, six ProteinScores improve the area under the curve estimates for the 10-year onset of incident outcomes beyond age, sex and a comprehensive set of 24 lifestyle factors, clinically relevant biomarkers and physical measures. Furthermore, the ProteinScore for type 2 diabetes outperforms a polygenic risk score and HbA1c—a clinical marker used to monitor and diagnose type 2 diabetes. The performance of scores using metabolomic and proteomic features is also compared. These data characterize early proteomic contributions to major age-related diseases, demonstrating the value of the plasma proteome for risk stratification.
Tracking cognitive trajectories in older survivors of COVID-19 up to 2.5 years post-infection
Authors: Yu-Hui Liu, Quan-Xin Wu, Qing-Hua Wang, Qiao-Feng Zhang, Yi Tang, Di Liu, Jing-Juan Wang, Xiao-Yu Liu, Ling-Ru Wang, Li Li, Cheng Xu, Jie Zhu, Yan-Jiang Wang
Journal: Nature Aging (2024)
Periprocedural Management and Multidisciplinary Care Pathways for Patients With Cardiac Implantable Electronic Devices: A Scientific Statement From the American Heart Association
Authors: Elaine Y. Wan, Albert J. Rogers, Michael Lavelle, Mason Marcus, Sarah A. Stone, Linda Ottoboni, Uma Srivatsa, Miguel A. Leal, Andrea M. Russo, Larry R. Jackson, George H. Crossley
Journal: Circulation (2024)

The rapid technological advancements in cardiac implantable electronic devices such as pacemakers, implantable cardioverter defibrillators, and loop recorders, coupled with a rise in the number of patients with these devices, necessitate an updated clinical framework for periprocedural management. The introduction of leadless pacemakers, subcutaneous and extravascular defibrillators, and novel device communication protocols underscores the imperative for clinical updates. This scientific statement provides an inclusive framework for the periprocedural management of patients with these devices, encompassing the planning phase, procedure, and subsequent care coordinated with the primary device managing clinic. Expert contributions from anesthesiologists, cardiac electrophysiologists, and cardiac nurses are consolidated to appraise current evidence, offer patient and health system management strategies, and highlight key areas for future research. The statement, pertinent to a wide range of health care professionals, underscores the importance of quality care pathways for patient safety, optimal device function, and minimization of hemodynamic disturbances or arrhythmias during procedures. Our primary objective is to deliver quality care to the expanding patient cohort with cardiac implanted electronic devices, offering direction in the era of evolving technologies and laying a foundation for sustained education and practice enhancement.
Unmutated RRAS2 emerges as a key oncogene in post-partum-associated triple negative breast cancer
Authors: Claudia Cifuentes, Clara L. Oeste, Isabel Fernández-Pisonero, Alejandro M. Hortal, Carmen García-Macías, Jeanne Hochart, Regina Rubira, Lydia Horndler, Carlos Horndler, Xosé R. Bustelo, Balbino Alarcón
Journal: Molecular Cancer (2024)

Abstract Background Breast cancer (BC) is the most common cancer in women, with triple negative BC (TNBC) accounting for 20% of cases. While early detection and targeted therapies have improved overall life expectancy, TNBC remains resistant to current treatments. Although parity reduces the lifetime risk of developing BC, pregnancy increases the risk of developing TNBC for years after childbirth. Although numerous gene mutations have been associated with BC, no single gene alteration has been identified as a universal driver. RRAS2 is a RAS-related GTPase rarely found mutated in cancer. Methods Conditional knock-in mice were generated to overexpress wild type human RRAS2 in mammary epithelial cells. A human sample cohort was analyzed by RT-qPCR to measure RRAS2 transcriptional expression and to determine the frequency of both a single-nucleotide polymorphism (SNP rs8570) in the 3’UTR region of RRAS2 and of genomic DNA amplification in tumoral and non-tumoral human BC samples. Results Here we show that overexpression of wild-type RRAS2 in mice is sufficient to develop TNBC in 100% of females in a pregnancy-dependent manner. In human BC, wild-type RRAS2 is overexpressed in 68% of tumors across grade, location, and molecular type, surpassing the prevalence of any previously implicated alteration. Still, RRAS2 overexpression is notably higher and more frequent in TNBC and young parous patients. The increased prevalence of the alternate C allele at the SNP position in tumor samples, along with frequent RRAS2 gene amplification in both tumors and blood of BC patients, suggests a cause-and-effect relationship between RRAS2 overexpression and breast cancer. Conclusions Higher than normal expression of RRAS2 not bearing activating mutations is a key driver in the majority of breast cancers, especially those of the triple-negative type and those linked to pregnancy.
Entactogen Effects of Ketamine: A Reverse-Translational Study
Authors: Evan M. Hess, Dede K. Greenstein, Olivia L. Hutchinson, Carlos A. Zarate, Todd D. Gould
Journal: American Journal of Psychiatry (2024)

The authors sought to assess the prosocial, entactogen effects of ketamine. Pleasure from social situations was assessed in a sample of participants with treatment-resistant depression from randomized, double-blind, placebo-controlled studies, using four items of the Snaith-Hamilton Pleasure Scale (SHAPS) at five time points over 1 week following treatment with ketamine (0.5 mg/kg intravenously) or placebo. The primary endpoint was postinfusion self-reported pleasure on the four SHAPS items pertaining to social situations, including the item on helping others, between the ketamine and placebo groups. In a rodent experiment, the impact of ketamine on helping behavior in rats was assessed using the harm aversion task. The primary endpoint was a reduction in lever response rate relative to baseline, which indicated the willingness of rats to forgo obtaining sucrose to help protect their cage mate from electric shock. Relative to placebo, ketamine increased ratings of feeling pleasure from being with family or close friends, seeing other people's smiling faces, helping others, and receiving praise, for 1 week following treatment. In the rodent experiment, during the harm aversion task, ketamine-treated rats maintained lower response rates relative to baseline to a greater extent than what was observed in vehicle-treated rats for 6 days posttreatment and delivered fewer shocks overall. In patients with treatment-resistant depression, ketamine treatment was associated with increased pleasure from social situations, such as feeling pleasure from helping others. Ketamine-treated rats were more likely to protect their cage mate from harm, at the cost of obtaining sucrose. These findings suggest that ketamine has entactogen effects.
Association Between Intrauterine System Hormone Dosage and Depression Risk
Authors: Søren Vinther Larsen, Anders Pretzmann Mikkelsen, Brice Ozenne, Trine Munk-Olsen, Øjvind Lidegaard, Vibe Gedso Frokjaer
Journal: American Journal of Psychiatry (2024)

The authors compared the associated risk of incident depression between first-time users of low-, medium-, and high-dose levonorgestrel-releasing intrauterine systems (LNG-IUSs).
Identification of an alternative ligand‐binding pocket in peroxisome proliferator‐activated receptor gamma and its correlated selective agonist for promoting beige adipocyte differentiation
Authors: Qiang Tian, Miaohua Wang, Xueting Wang, Zhenli Lei, Owais Ahmad, Dianhua Chen, Wei Zheng, Pingping Shen, Nanfei Yang
Journal: MedComm (2024)

ABSTRACT The pharmacological activation of peroxisome proliferator‐activated receptor gamma (PPARγ) is a convenient and promising strategy for promoting beige adipocyte biogenesis to combat obesity‐related metabolic disorders. However, thiazolidinediones (TZDs), the full agonists of PPARγ exhibit severe side effects in animal models and in clinical settings. Therefore, the development of efficient and safe PPARγ modulators for the treatment of metabolic diseases is emerging. In this study, using comprehensive methods, we report a previously unidentified ligand‐binding pocket (LBP) in PPARγ and link it to beige adipocyte differentiation. Further virtual screening of 4097 natural compounds based on this novel LBP revealed that saikosaponin A (NJT‐2), a terpenoid compound, can bind to PPARγ to induce coactivator recruitment and effectively activate PPARγ‐mediated transcription of the beige adipocyte program. In a mouse model, NJT‐2 administration efficiently promoted beige adipocyte biogenesis and improved obesity‐associated metabolic dysfunction, with significantly fewer adverse effects than those observed with TZD. Our results not only provide an advanced molecular insight into the structural ligand‐binding details in PPARγ, but also develop a linked selective and safe agonist for obesity treatment.
Air Pollution, Genetic Susceptibility, and Risk of Incident Systemic Lupus Erythematosus: A Prospective Cohort Study
Authors: Meiqi Xing, Yudiyang Ma, Feipeng Cui, Dankang Li, Jianing Wang, Linxi Tang, Lei Zheng, Jian Yang, Yaohua Tian
Journal: Arthritis & Rheumatology (2024)

There are few existing studies that investigate the risk of systemic lupus erythematosus (SLE) associated with long-term exposure to air pollutants. This study aimed to explore associations between long-term exposure to air pollutants and incident SLE and further evaluate interactions and joint effects of genetic risk and air pollutants.