tbuckley/cabot-search huggingface dataset:
Efficacy of typhoid vaccines against culture-confirmed Salmonella Typhi in typhoid endemic countries: a systematic review and meta-analysis
Authors: Rabab Batool, Zoya Haq Qamar, Rehana Abdus Salam, Mohammad Tahir Yousafzai, Per Ashorn, Farah Naz Qamar
Journal: The Lancet Global Health (2024)

<h2>Summary</h2><h3>Background</h3> Typhoid is a serious public health threat in many low-income and middle-income countries. Several vaccines for typhoid have been recommended by WHO for typhoid prevention in endemic countries. This study aimed to review the efficacy of typhoid vaccines against culture-confirmed <i>Salmonella enterica</i> serovar Typhi. <h3>Methods</h3> We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for studies published in English between Jan 1, 1986 and Nov 2, 2023. We included randomised controlled trials (RCTs) comparing typhoid vaccines with a placebo or another vaccine. This meta-analysis evaluated the efficacy and safety of several typhoid vaccines, including live attenuated oral Ty21a vaccine, Vi capsular polysaccharide (Vi-PS), Vi polysaccharide conjugated to recombinant Pseudomonas aeruginosa exotoxin A vaccine (Vi-rEPA), and Vi-tetanus toxoid conjugate vaccine (TCV). The certainty of evidence for key outcomes was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations methodology. The outcome of interest was typhoid fever confirmed by the isolation of <i>Salmonella enterica</i> serovar Typhi in blood and adverse events following immunisation. This study is registered with PROSPERO (CRD42021241043). <h3>Findings</h3> We included 14 RCTs assessing four different vaccines (Ty21a: four trials; Vi-PS: five trials; Vi-rEPA: one trial; TCV: four trials) involving 585 253 participants. All trials were conducted in typhoid endemic countries and the age of participants ranged from 6 months to 50 years. The pooled efficacy against typhoid fever was 45% (95% CI 33–55%; four trials; 247 649 participants; <i>I</i><sup>2</sup> 59%; moderate certainty) for Ty21a and 58% (44–69%; five trials; 214 456 participants; <i>I</i><sup>2</sup> 34%; moderate certainty) for polysaccharide Vi-PS. The cumulative efficacy of two doses of Vi-rEPA vaccine at 2 years was 91% (88–96%; one trial; 12 008 participants; moderate certainty). The pooled efficacy of a single shot of TCV at 2 years post-immunisation was 83% (77–87%; four trials; 111 130 participants; <i>I</i><sup>2</sup> 0%; moderate certainty). All vaccines were safe, with no serious adverse effects reported in the trials. <h3>Interpretation</h3> The existing data from included trials provide promising results regarding the efficacy and safety of the four recommended typhoid vaccines. TCV and Vi-rEPA were found to have the highest efficacy at 2 years post-immunisation. However, follow-up data for Vi-rEPA are scarce and only TCV is pre-qualified by WHO. Therefore, roll-out of TCV into routine immunisation programmes in typhoid endemic settings is highly recommended. <h3>Funding</h3> There was no funding source for this study.
Is intimate partner violence declining? It's still an open question – Authors' reply
Authors: Ning Ma, Yi Song, Zhihui Li
Journal: The Lancet Global Health (2024)

We appreciate Kathryn M Yount and colleagues for these insightful comments on our Article.1 First, following established practices in multicountry studies, we performed trend analysis and presented results at overall, regional, income, and country levels for a more comprehensive and multiperspective assessment.2,3 Considering the same concerns as Yount and colleagues, we applied the average annual rate of change using Poisson regression with robust error variance for countries with at least two surveys, mitigating the effect of different survey timepoints.
Lung-function trajectories: relevance and implementation in clinical practice
Authors: Erik Melén, Rosa Faner, James P Allinson, Dinh Bui, Andrew Bush, Adnan Custovic, Judith Garcia-Aymerich, Stefano Guerra, Robab Breyer-Kohansal, Jenny Hallberg, Lies Lahousse, Fernando D Martinez, Simon Kebede Merid, Pippa Powell, Hilary Pinnock, Sanja Stanojevic, Lowie E G W Vanfleteren, Gang Wang, Shyamali C Dharmage, Jadwiga Wedzicha, Alvar Agusti, Alicia Abellan, Ian Adcock, Shoaib Afzal, Peter Alter, Helena Backman, Xander Bertels, Chloe Bloom, Klaus Bønnelykke, Marie-Kathrin Breyer, Sandra Casas, Fan (Kian) Chung, Yunus Colak, Borja G. Cosio, Liesbeth Duijts, Leonardo Fabbri, Sara Fontanella, Elaine Fuertes, Juan Ramón Gonzalez, Raquel Granell, Sylvia Hartl, Natalia Hernandez-Pacheco, John Holloway, Deborah Jarvis, Hans Jacob Koefoed, Tessa Kole, Ashish Kumar, Arnulf Langhammer, Anne Lindberg, Maria Llopis, Anke-Hilse Maitland van der Zee, Howraman Meteran, Cosetta Minelli, Bright Nwaru, Nuria Olvera, Gabriela Peralta, Andrew Ritchie, Eva Rönmark, James Ross Chapman, Júlia Sangüesa Boix, Tamara Schikowski, Vivi Schlünssen, Seif Shaheen, Torben Sigsgaard, Marie Standl, Mohammad Talaei, Anhar Ullah, Anders Ullman, Carlos Valencia-Hernandez, Maarten van den Berge, Yoni van Dijk, Jørgen Vestbo, Susanne Vijverberg, Sigrid Anna Vikjord, Claus Volgelmeier, Judith Vonk, Nazanin Zounemat Kermani
Journal: The Lancet (2024)
Impact with equity: EDCTP and equitable research partnerships
Authors: Michael Makanga, Pauline Beattie, Dominika Jajkowicz, Thomas Nyirenda, Marcel Tanner, Catherine Hankins
Journal: The Lancet Global Health (2024)

In November, 2023, 1118 delegates from 64 countries converged in Paris, France, for the 11th European & Developing Countries Clinical Trials Partnership (EDCTP) forum. Commemorating EDCTP's 20th anniversary, the forum showcased findings from EDCTP-funded projects and highlighted results of years of investment in the conduct of clinical research, networks, and capacity strengthening, including the advancement of women in science.
No health without brain health
Authors: None The Lancet Global Health
Journal: The Lancet Global Health (2024)

The human brain is perhaps the most complex, fascinating, and poorly understood biological entity in the known universe. It has been referred to as the body's command centre, influencing every aspect of human existence from respiration to religious belief. Neuroscientists have, for some time, recognised that integration of the many scattered regional and subspecialty initiatives to advance brain research will be necessary to have a real impact in advancing our understanding at a molecular level.
Is intimate partner violence declining? It's still an open question
Authors: Kathryn M Yount, Lu Gram, Amber Peterman
Journal: The Lancet Global Health (2024)

Sustainable Development Goal 5.2 urges countries to "eliminate all forms of violence against all women and girls". Indicator 5.2.1—the proportion of partnered women and girls subjected to intimate partner violence (IPV) in the previous 12 months—is recommended to monitor this goal. In their Article,1 Ning Ma and colleagues leverage data for 21 countries with two or more Demographic and Health Surveys to assess trends during 2000–21 in IPV for women aged 15–49 years.1 We support this objective; however, our reading of their analysis and interpretations persuades us that a reliable, representative, and rigorous trend analysis of IPV against women is still needed.
National plans and awareness campaigns as priorities for achieving global brain health
Authors: Sebastian F Winter, Donna Walsh, Coriene Catsman-Berrevoets, Valery Feigin, Frédéric Destrebecq, Suzanne L Dickson, Matilde Leonardi, Volker Hoemberg, Cristina Tassorelli, Maria Teresa Ferretti, Anna Dé, Antonella Santuccione Chadha, Chris Lynch, Sophia Bakhtadze, Deanna Saylor, Soonmyung Hwang, Kevin Rostasy, Benzi M Kluger, Claire Wright, Phyllis C Zee, David W Dodick, Joke Jaarsma, Mayowa O Owolabi, Jelka Zaletel, Tit Albreht, Rajinder K Dhamija, Anne Helme, Joanna Laurson-Doube, Action Amos, Florence K Baingana, Gus A Baker, Francesca Sofia, Orla Galvin, Tadeusz Hawrot
Journal: The Lancet Global Health (2024)

<h2>Summary</h2> Neurological conditions are the leading cause of death and disability combined. This public health crisis has become a global priority with the introduction of WHO's <i>Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022–2031</i> (IGAP). 18 months after this plan was adopted, global neurology stakeholders, including representatives of the OneNeurology Partnership (a consortium uniting global neurology organisations), take stock and advocate for urgent acceleration of IGAP implementation. Drawing on lessons from relevant global health contexts, this Health Policy identifies two priority IGAP targets to expedite national delivery of the entire 10-year plan: namely, to update national policies and plans, and to create awareness campaigns and advocacy programmes for neurological conditions and brain health. To ensure rapid attainment of the identified priority targets, six strategic drivers are proposed: universal community awareness, integrated neurology approaches, intersectoral governance, regionally coordinated IGAP domestication, lived experience-informed policy making, and neurological mainstreaming (advocating to embed brain health into broader policy agendas). Contextualised with globally emerging IGAP-directed efforts and key considerations for intersectoral policy design, this novel framework provides actionable recommendations for policy makers and IGAP implementation partners. Timely, synergistic pursuit of the six drivers might aid WHO member states in cultivating public awareness and policy structures required for successful intersectoral roll-out of IGAP by 2031, paving the way towards brain health for all.
RNase P: Beyond Precursor tRNA Processing
Authors: Peipei Wang, Juntao Lin, Xiangyang Zheng, Xingzhi Xu
Journal: Genomics Proteomics & Bioinformatics (2024)

Abstract Ribonuclease P (RNase P) was first described in the 1970’s as an endoribonuclease acting in the maturation of precursor transfer RNAs (tRNAs). More recent studies, however, have uncovered non-canonical roles for RNase P and its components. Here, we review the recent progress of its involvement in chromatin assembly, DNA damage response, and maintenance of genome stability with implications in tumorigenesis. The possibility of RNase P as a therapeutic target in cancer is also discussed.
ADP-dependent glucokinase: the ancient, archaeal key to prostate cancer
Authors: Marcin M. Kamiński
Journal: Military Medical Research (2024)

Research brings out an astounding discovery by Xu et al.[1] demonstrating a key role of the mysterious enzyme ADP-dependent glucokinase (ADPGK) in the cellular metabolism of prostate cancer (PCa).The ADPGKs are enzymes typically found in thermophilic archaea where they mediate the indispensable, first step of glucose metabolism, i.e. phosphorylation of glucose to glucose-6-phosphate. Strikingly, ADPGKs utilize ADP as a phosphate donor instead of ATP typically used to initiate glycolysis by four "classical" eukaryotic hexokinases (HK I-III and glucokinase).Thus, the discovery made by Ronimus and Morgan [2] of the functional form of ADPGK in mice, opened an intriguing question of the specific role of this enzyme in the metabolism of eukaryotic cell.Now, the research of Xu et al. [1] showed that the unique mode of ADPGK metabolic activity is advantageous for the survival and homeostasis of PCa cells.Most importantly, ADPGK expression level could be used as a prognostic marker for the overall survival of prostate adenocarcinoma patients.Looking for a putative metabolic target for cancer treatment, the authors first analyzed the expression of all glucokinases in clinical tissue samples and correlated this data with predictions of clinical outcomes.Strikingly, ADPGK was not only overexpressed on protein and mRNA levels but also was the only glucokinase that predicted worse overall survival of PCa patients.Univariate analysis and multivariate Cox models showed that high ADPGK level was a risk factor predicting biochemical recurrence (BCR) for PCa patients.Next, the authors established the molecular mechanism underlying the role of ADPGK in carcinogenesis.Namely, modulation of ADPGK levels in PCa cell lines by overexpression or knock-down resulted in enhanced or decreased proliferation and migration, respectively.Moreover, using a subcutaneous xenograft model into BALB/c nude mice, the authors demonstrated that PCa cell line overexpressing ADPGK yielded tumors that grew larger and faster as well as had higher metastatic potential than control cells.Furthermore, through the utilization of metabolomics, proteomics and Seahorse respirometry, it was found that modulation of ADPGK level regulates the glycolytic phenotype of PCa cells, confirming the role of high ADPGK level for upregulation of proliferation rate in PCa cells.However, the most surprising findings were: 1) the identification that ADPGK regulates AMP-activated protein kinase (AMPK) activity, and 2) the molecular interaction of ADPGK with glycolytic enzyme aldolase C (ALDOC).Down-or up-regulation of ADPGK levels was sufficient to decrease or increase AMPK activity, respectively, while immunoprecipitation experiments showed that in PCa cells ADPGK binds ALDOC.In addition, ADPGK expression positively correlated with expression of ALDOC in PCa cell lines as well as in patient samples.Importantly, patients with concomitantly high levels of
Randomized trial of anakinra plus zinc vs. prednisone for severe alcohol-associated hepatitis
Authors: Samer Gawrieh, Srinivasan Dasarathy, Wanzhu Tu, Patrick S. Kamath, Naga P. Chalasani, Craig J. McClain, Ramon Bataller, Gyongyi Szabo, Qing Tang, Svetlana Radaeva, Bruce Barton, Laura E. Nagy, Vijay H. Shah, Arun J. Sanyal, Mack C. Mitchell, Naga Chalasani, Kavish R. Patidar, Raj Vuppalanchi, Niha Samala, Lindsey Yoder, Lauren Nephew, Vijay H. Shah, Douglas A. Simonetto, Patrick Kamath, Hugo E. Vargas, Liu Yang, Srinivasan Dasarathy, Nicole Welch, Annette Bellar, Amy Attaway, Jaividhya Dasarathy, Ashley Growley, David Streem, Laura E. Nagy, Mack C. Mitchell, H. Franklin Herlong, Thomas Kerr, Thomas Cotter, Arun Sanyal, Sara O'Connor, Velimir Luketic, Amon Asgharpour, Stephanie Taylor, Craig J. McClain, Vatsalya Vatsalya, Loretta Jophlin, Matt Cave, Suman Kumar Jha, Luis Marsano, Ashutosh Barve, Jane Frimodig, Ramon Bataller, Samhita Ravi, Jaideep Behari, Sharvari Shivanekar, Paula Novelli, Andres Duarte-Rojo, Naudia Jonassaint, Gyongyi Szabo, None Curry, Zhenghui G. Jiang, Ushma Agarwal, Mia Hazel, Bernd Schnabl
Journal: Journal of Hepatology (2024)
Benchmarking Algorithms for Gene Set Scoring of Single-cell ATAC-seq Data
Authors: Xi Wang, Qiwei Lian, Haoyu Dong, Shuo Xu, Yaru Su, Xiaohui Wu
Journal: Genomics Proteomics & Bioinformatics (2024)

Gene set scoring (GSS) has been routinely conducted for gene expression analysis of bulk or single-cell RNA sequencing (RNA-seq) data, which helps to decipher single-cell heterogeneity and cell type-specific variability by incorporating prior knowledge from functional gene sets. Single-cell assay for transposase accessible chromatin using sequencing (scATAC-seq) is a powerful technique for interrogating single-cell chromatin-based gene regulation, and genes or gene sets with dynamic regulatory potentials can be regarded as cell type-specific markers as if in single-cell RNA-seq (scRNA-seq). However, there are few GSS tools specifically designed for scATAC-seq, and the applicability and performance of RNA-seq GSS tools on scATAC-seq data remain to be investigated. Here, we systematically benchmarked ten GSS tools, including four bulk RNA-seq tools, five scRNA-seq tools, and one scATAC-seq method. First, using matched scATAC-seq and scRNA-seq datasets, we found that the performance of GSS tools on scATAC-seq data was comparable to that on scRNA-seq, suggesting their applicability to scATAC-seq. Then, the performance of different GSS tools was extensively evaluated using up to ten scATAC-seq datasets. Moreover, we evaluated the impact of gene activity conversion, dropout imputation, and gene set collections on the results of GSS. Results show that dropout imputation can significantly promote the performance of almost all GSS tools, while the impact of gene activity conversion methods or gene set collections on GSS performance is more dependent on GSS tools or datasets. Finally, we provided practical guidelines for choosing appropriate preprocessing methods and GSS tools in different application scenarios.
IL-15-secreting CAR natural killer cells directed toward the pan-cancer target CD70 eliminate both cancer cells and cancer-associated fibroblasts
Authors: Astrid Van den Eynde, Laura Gehrcken, Tias Verhezen, Ho Wa Lau, Christophe Hermans, Hilde Lambrechts, Tal Flieswasser, Delphine Quatannens, Gils Roex, Karen Zwaenepoel, Elly Marcq, Philippe Joye, Edgar Cardenas De La Hoz, Christophe Deben, Alessia Gasparini, Pierre Montay-Gruel, Maxim Le Compte, Eva Lion, Filip Lardon, Steven Van Laere, Vasiliki Siozopoulou, Diana Campillo-Davo, Jorrit De Waele, Patrick Pauwels, Julie Jacobs, Evelien Smits, Jonas R. M. Van Audenaerde
Journal: Journal of Hematology & Oncology (2024)

Abstract Background It remains challenging to obtain positive outcomes with chimeric antigen receptor (CAR)-engineered cell therapies in solid malignancies, like colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). A major obstacle is the lack of targetable surface antigens that are not shared by healthy tissues. CD70 emerges as interesting target, due to its stringent expression pattern in healthy tissue and its apparent role in tumor progression in a considerable amount of malignancies. Moreover, CD70 is also expressed on cancer-associated fibroblasts (CAFs), another roadblock for treatment efficacy in CRC and PDAC. We explored the therapeutic potential of CD70 as target for CAR natural killer (NK) cell therapy in CRC, PDAC, focusing on tumor cells and CAFs, and lymphoma. Methods RNA-seq data and immunohistochemical analysis of patient samples were used to explore CD70 expression in CRC and PDAC patients. In addition, CD70-targeting CAR NK cells were developed to assess cytotoxic activity against CD70 + tumor cells and CAFs, and the effect of cytokine stimulation on their efficacy was evaluated. The in vitro functionality of CD70-CAR NK cells was investigated against a panel of tumor and CAF cell lines with varying CD70 expression. Lymphoma-bearing mice were used to validate in vivo potency of CD70-CAR NK cells. Lastly, to consider patient variability, CD70-CAR NK cells were tested on patient-derived organoids containing CAFs. Results In this study, we identified CD70 as a target for tumor cells and CAFs in CRC and PDAC patients. Functional evaluation of CD70-directed CAR NK cells indicated that IL-15 stimulation is essential to obtain effective elimination of CD70 + tumor cells and CAFs, and to improve tumor burden and survival of mice bearing CD70 + tumors. Mechanistically, IL-15 stimulation resulted in improved potency of CD70-CAR NK cells by upregulating CAR expression and increasing secretion of pro-inflammatory cytokines, in a mainly autocrine or intracellular manner. Conclusions We disclose CD70 as an attractive target both in hematological and solid tumors. IL-15 armored CAR NK cells act as potent effectors to eliminate these CD70 + cells. They can target both tumor cells and CAFs in patients with CRC and PDAC, and potentially other desmoplastic solid tumors.
TCRosetta: an integrated analysis and annotation platform for T-cell receptor sequences
Authors: Tao Yue, Si-Yi Chen, Wen-Kang Shen, Zhan-Ye Zhang, Liming Cheng, An-Yuan Guo
Journal: Genomics Proteomics & Bioinformatics (2024)

Abstract T cells and T-cell receptors (TCRs) are essential components of the adaptive immune system. Characterization of the TCR repertoire offers a promising and highly informative source for understanding the functions of T cells in the immune response and immunotherapy. Although TCR repertoire studies have attracted much attention, there are few online servers available for TCR repertoire analysis, especially for TCR sequence annotation or advanced analyses. Therefore, we developed TCRosetta, a comprehensive online server that integrates analytical methods for TCR repertoire analysis and visualization. TCRosetta combines general feature analysis, large-scale sequence clustering, network construction, peptide–TCR binding prediction, generation probability calculation, and k-mer motif analysis for TCR sequences, making TCR data analysis as simple as possible. The TCRosetta server accepts multiple input data formats and can analyze ∼ 20,000 TCR sequences in less than 3 min. TCRosetta is the most comprehensive web server available for TCR repertoire analysis and is freely available at https://guolab.wchscu.cn/TCRosetta/.
Risk of a post-colonoscopy colorectal cancer in patients with diverticular disease: a population-based cohort study
Authors: Frederikke S. Troelsen, Henrik T. Sørensen, Rune Erichsen
Journal: Endoscopy (2024)

Abstract Background Post-colonoscopy colorectal cancers (PCCRCs) may account for up to 30% of all colorectal cancers (CRCs) diagnosed in patients with diverticular disease; however, absolute and relative risks of PCCRC among these patients undergoing colonoscopy remain unknown. Methods We performed a cohort study (1995–2015) including patients with and without diverticular disease who underwent colonoscopy. We calculated 7–36-month cumulative incidence proportions (CIPs) of PCCRC. We used Cox proportional hazards regression models to compute hazard ratios (HRs) of PCCRC, comparing patients with and without diverticular disease, as a measure of relative risk. We calculated 3-year PCCRC rates, as per World Endoscopy Organization recommendations, to estimate the proportion of CRC patients with and without diverticular disease who were considered to have PCCRC. We stratified all analyses by PCCRC location. Results We observed 373 PCCRCs among 56 642 patients with diverticular disease and 1536 PCCRCs among 306 800 patients without diverticular disease. The PCCRC CIP after first-time colonoscopy was 0.45% (95%CI 0.40%–0.51%) for patients with and 0.36% (95%CI 0.34%–0.38%) for patients without diverticular disease. Comparing patients with and without diverticular disease undergoing first-time colonoscopy, the adjusted HR was 0.84 (95%CI 0.73–0.97) for PCCRC and 1.23 (95%CI 1.01–1.50) for proximal PCCRCs. The 3-year PCCRC rate was 19.0% (22.3% for proximal PCCRCs) for patients with and 6.5% for patients without diverticular disease. Conclusions Although the absolute risk was low, the relative risk of proximal PCCRCs may be elevated in patients with diverticular disease undergoing colonoscopy compared with patients without the disease.
Deciphering the molecular interplay and tumorigenesis in hepatocellular carcinoma through insights into FBXL6 and KRASG12D
Authors: Qiang Cai, Quazi T. H. Shubhra
Journal: Military Medical Research (2024)

Hepatocellular carcinoma, F-box and leucine-rich repeat 6 (FBXL6) activation, Kirsten rat sarcoma (KRAS) G12D mutation, Mitogen-activated protein kinase (MEK)/mammalian
Colorectal submucosal dissection using a novel traction method with a threaded clip attached to the outside of the lesion
Authors: Keisaku Yamada, Masahiro Tajika, Tsutomu Tanaka, Nobuhito Ito, Akihiro Takagi, Yasumasa Niwa
Journal: Endoscopy (2024)

Colorectal endoscopic submucosal dissection (ESD) continues to present technical challenges. However, several reports indicate that traction devices can effectively reduce procedure times and complications associated with colorectal ESD [1] [2].