tbuckley/cabot-search huggingface dataset:
Congenital hydrocephalus: a review of recent advances in genetic etiology and molecular mechanisms
Authors: Xiu-Yun Liu, Xin Song, Marek Czosnyka, Chiara Robba, Zofia Czosnyka, Jennifer Lee Summers, Hui-Jie Yu, Guo-Yi Gao, Peter Smielewski, Fang Guo, Mei-Jun Pang, Dong Ming
Journal: Military Medical Research (2024)

Abstract The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up to 40% of all cases observed globally. Knowledge about an individual’s genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise genetic etiology has only been pinpointed in fewer than 5% of human instances. More occurrences of CH cases are required for comprehensive gene sequencing aimed at uncovering additional potential genetic loci. A deeper comprehension of its underlying genetics may offer invaluable insights into the molecular and cellular basis of this brain disorder. This review provides a summary of pertinent genes identified through gene sequencing technologies in humans, in addition to the 4 genes currently associated with CH (two X-linked genes L1CAM and AP1S2 , two autosomal recessive MPDZ and CCDC88C ). Others predominantly participate in aqueduct abnormalities, ciliary movement, and nervous system development. The prospective CH-related genes revealed through animal model gene-editing techniques are further outlined, focusing mainly on 4 pathways, namely cilia synthesis and movement, ion channels and transportation, Reissner’s fiber (RF) synthesis, cell apoptosis, and neurogenesis. Notably, the proper functioning of motile cilia provides significant impulsion for cerebrospinal fluid (CSF) circulation within the brain ventricles while mutations in cilia-related genes constitute a primary cause underlying this condition. So far, only a limited number of CH-associated genes have been identified in humans. The integration of genotype and phenotype for disease diagnosis represents a new trend in the medical field. Animal models provide insights into the pathogenesis of CH and contribute to our understanding of its association with related complications, such as renal cysts, scoliosis, and cardiomyopathy, as these genes may also play a role in the development of these diseases. Genes discovered in animals present potential targets for new treatments but require further validation through future human studies.
Invasive fungal disease in the immunocompromised host: changing epidemiology, new antifungal therapies and management challenges
Authors: Maddalena Giannella, Fanny Lanternier, Sarah Dellière, Andreas H. Groll, Nicolas J. Mueller, Ana Alastruey-Izquierdo, Monica A. Slavin
Journal: Clinical Microbiology and Infection (2024)
Immune surveillance of cytomegalovirus in tissues
Authors: Andrea Mihalić, Jelena Železnjak, Berislav Lisnić, Stipan Jonjić, Vanda Juranić Lisnić, Ilija Brizić
Journal: Cellular and Molecular Immunology (2024)

Abstract Cytomegalovirus (CMV), a representative member of the Betaherpesvirinae subfamily of herpesviruses, is common in the human population, but immunocompetent individuals are generally asymptomatic when infected with this virus. However, in immunocompromised individuals and immunologically immature fetuses and newborns, CMV can cause a wide range of often long-lasting morbidities and even death. CMV is not only widespread throughout the population but it is also widespread in its hosts, infecting and establishing latency in nearly all tissues and organs. Thus, understanding the pathogenesis of and immune responses to this virus is a prerequisite for developing effective prevention and treatment strategies. Multiple arms of the immune system are engaged to contain the infection, and general concepts of immune control of CMV are now reasonably well understood. Nonetheless, in recent years, tissue-specific immune responses have emerged as an essential factor for resolving CMV infection. As tissues differ in biology and function, so do immune responses to CMV and pathological processes during infection. This review discusses state-of-the-art knowledge of the immune response to CMV infection in tissues, with particular emphasis on several well-studied and most commonly affected organs.
High-Throughput Deep Learning Detection of Mitral Regurgitation
Authors: Amey Vrudhula, Grant Duffy, Milos Vukadinovic, David Liang, Susan Cheng, David Ouyang
Journal: Circulation (2024)

Diagnosis of mitral regurgitation (MR) requires careful evaluation by echocardiography with Doppler imaging. This study presents the development and validation of a fully automated deep learning pipeline for identifying apical 4-chamber view videos with color Doppler echocardiography and detecting clinically significant (moderate or severe) MR from transthoracic echocardiograms.
Mineralocorticoid Receptor Antagonism Prevents Aortic Plaque Progression and Reduces Left Ventricular Mass and Fibrosis in Patients With Type 2 Diabetes and Chronic Kidney Disease: The MAGMA Trial
Authors: Sanjay Rajagopalan, Mirela Dobre, Jean-Eudes Dazard, Armando Vergara-Martel, Kim Connelly, Michael E. Farkouh, Juan Gaztanaga, Heather Conger, Ann Dever, Laleh Razavi-Nematollahi, Anas Fares, Gabriel Pereira, Jonnelle Edwards-Glenn, Mark Cameron, Cheryl Cameron, Sadeer Al-Kindi, Robert D. Brook, Bertram Pitt, Matthew Weir
Journal: Circulation (2024)

Persistent mineralocorticoid receptor activation is a pathologic response in type 2 diabetes and chronic kidney disease. Whereas mineralocorticoid receptor antagonists are beneficial in reducing cardiovascular complications, direct mechanistic pathways for these effects in humans are lacking.
Current Use of Echocardiography in Cardio-Oncology: Nationwide Real-World Data From an ANMCO/SIECVI Joint Survey
Authors: Andrea Barbieri, Massimiliano Camilli, Irma Bisceglia, Francesca Mantovani, Quirino Ciampi, Concetta Zito, Maria Laura Canale, Georgette Khoury, Francesco Antonini-Canterin, Scipione Carerj, Marco Campana, Carmine Riccio, Michele Massimo Gulizia, Massimo Grimaldi, Domenico Gabrielli, Furio Colivicchi, Mauro Pepi, Fabrizio Oliva
Journal:  (2024)

The need for cardio-oncology competencies is constantly growing, and with the establishment of cardio-oncology services, cardiovascular imaging, particularly transthoracic echocardiography (TTE), has become pivotal in patients' management. However, care pathways for oncologic patients largely depend on local health structures' resources. This survey from Associazione Italiana Medici Cardiologi Ospedalieri and the Italian Society of Echocardiography and Cardiovascular Imaging aimed at investigating the use of echocardiography in cardio-oncology services and knowledge levels on cancer patients' care.
Immune landscape of isocitrate dehydrogenase-stratified primary and recurrent human gliomas
Authors: Pravesh Gupta, Minghao Dang, Shivangi Oberai, Simona Migliozzi, Rakesh Trivedi, Gayatri Kumar, Mekenzie Peshoff, Nancy Milam, Aml Ahmed, Krishna Bojja, Tuan M Tran, Joy Gumin, Carlos Kamiya-Matsuoka, Jason Huse, Kathryn Cox, Jianzhuo Li, Huma Shehwana, Sameer A Sheth, Rodriguez Saxon, Sun Baohua, Brittany Parker Kerrigan, Atul Maheshwari, Edwin Roger Parra Cuentas, Nicholas E Navin, Amy B Heimberger, Frederick F Lang, Antonio Iavarone, Karen Clise-Dwyer, Linghua Wang, Krishna P Bhat
Journal: Neuro-Oncology (2024)

Human gliomas are classified using isocitrate dehydrogenase (IDH) status as a prognosticator; however, the influence of genetic differences and treatment effects on ensuing immunity remains unclear.
Machine learning of Raman spectra predicts drug release from polysaccharide coatings for targeted colonic delivery
Authors: Youssef Abdalla, Laura E McCoubrey, Fabiana Ferraro, Lisa Maria Sonnleitner, Yannick Guinet, Florence Siepmann, Alain Hédoux, Juergen Siepmann, Abdul W Basit, Mine Orlu, David Shorthouse
Journal: Journal of Controlled Release (2024)

Colonic drug delivery offers numerous pharmaceutical opportunities, including direct access to local therapeutic targets and drug bioavailability benefits arising from the colonic epithelium's reduced abundance of cytochrome P450 enzymes and particular efflux transporters. Current workflows for developing colonic drug delivery systems involve time-consuming, low throughput in vitro and in vivo screening methods, which hinder the identification of suitable enabling materials. Polysaccharides are useful materials for colonic targeting, as they can be utilised as dosage form coatings that are selectively digested by the colonic microbiota. However, polysaccharides are a heterogeneous family of molecules with varying suitability for this purpose. To address the need for high-throughput material selection tools for colonic drug delivery, we leveraged machine learning (ML) and publicly accessible experimental data to predict the release of the drug 5-aminosalicylic acid from polysaccharide-based coatings in simulated human, rat, and dog colonic environments. For the first time, Raman spectra alone were used to characterise polysaccharides for input as ML features. Models were validated on 8 unseen drug release profiles from new polysaccharide coatings, demonstrating the generalisability and reliability of the method. Further, model analysis facilitated an understanding of the chemical features that influence a polysaccharide's suitability for colonic drug delivery. This work represents a major step in employing spectral data for forecasting drug release from pharmaceutical formulations and marks a significant advancement in the field of colonic drug delivery. It offers a powerful tool for the efficient, sustainable, and successful development and pre-ranking of colon-targeted formulation coatings, paving the way for future more effective and targeted drug delivery strategies.
ZIF-8-modified hydrogel sequentially delivers angiogenic and osteogenic growth factors to accelerate vascularized bone regeneration
Authors: Xiaolian Niu, Shengzhao Xiao, Ruoyu Huang, Di Huang, Katerina E Aifantis, Han Yu, Chao Xue, Lan Yin, Nicholas Dunne, Xiaoming Li
Journal: Journal of Controlled Release (2024)
Effects of Glucagon-Like Peptide-1 Receptor Agonists on Upper Gastrointestinal Endoscopy: A Meta-Analysis
Authors: Antonio Facciorusso, Daryl Ramai, Jahnvi Dhar, Jayanta Samanta, Saurabh Chandan, Paraskevas Gkolfakis, Stefano Francesco Crinò, Marcello Maida, Andrea Anderloni, Ivo Boskoski, Konstantinos Triantafyllou, Mario Dinis-Ribeiro, Cesare Hassan, Lorenzo Fuccio, Marianna Arvanitakis
Journal: Clinical Gastroenterology and Hepatology (2024)

Background and AimsLimited evidence exists regarding the impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on upper endoscopy. Therefore, a meta-analysis was conducted to comprehensively review the available evidence on this subject.MethodsA systematic bibliographic search was carried out until May 2024. Pooled estimates were analyzed using a random-effects model, with results presented as odds ratio (OR) and 95% confidence interval (CI). The primary outcome assessed was the rate of retained gastric content (RGC), while secondary outcomes included rates of aborted and repeated procedures, adverse event rate, and rates of aspiration.ResultsThis analysis included 13 studies involving a total of 84,065 patients. Patients receiving GLP-1RA therapy exhibited significantly higher rates of RGC (OR, 5.56; 95% CI, 3.35 to 9.23), a trend that was consistent among patients with diabetes (OR, 2.60; 95% CI, 2.23 to 3.02). Adjusted analysis, accounting for variables such as sex, age, body mass index, diabetes, and other therapies, confirmed the elevated rates of RGC in the GLP-1RA user group (adjusted OR, 4.20; 95% CI, 3.42 to 5.15). Furthermore, rates of aborted and repeated procedures were higher in the GLP-1RA user group (OR, 5.13; 95% CI, 3.01 to 8.75; and OR, 2.19; 95% CI, 1.43 to 3.35; respectively). However, no significant differences were found in AE and aspiration rates between the 2 groups (OR, 4.04; 95% CI, 0.63 to 26.03; and OR, 1.75; 95% CI, 0.64 to 4.77; respectively).ConclusionUse of GLP-1RAs is associated with increased retention of gastric contents and more frequent aborted procedures during upper endoscopy. However, the adverse event and aspiration rates do not seem different; therefore, adjusting fasting time instead of routinely withholding GLP-1RAs could be reasonable in these patients.Graphical abstract
Anifrolumab in Recalcitrant Cutaneous Dermatomyositis: A Multicenter Retrospective Cohort Study
Authors: Katharina S. Shaw, Kimberly B. Hashemi, Rochelle L. Castillo, Elizabeth Rainone, Allen W. Ho, Philip J. Kahn, Vikash S. Oza, Alisa Femia, Ruth Ann Vleugels
Journal: Journal of the American Academy of Dermatology (2024)
Immunogenicity of concomitant SARS-CoV-2 and influenza vaccination in UK healthcare workers: a prospective longitudinal observational study
Authors: Joshua Nazareth, Christopher A. Martin, Daniel Pan, Ian G. Barr, Sheena G. Sullivan, Heidi Peck, Neyme Veli, Mrinal Das, Luke Bryant, Nisha George, Marjan Gohar, Laura J. Gray, Lucy Teece, Denny Vail, Val Renals, Aleesha Karia, Paul Renals, Paul Moss, Andrea Tattersall, Ashley D. Otter, Pranab Haldar, Andrea Cooper, Iain Stephenson, Martin J. Wiselka, Julian W. Tang, Laura Nellums, Manish Pareek
Journal: The Lancet Regional Health - Europe (2024)

BackgroundCo-administration of inactivated influenza vaccine (IIV) and SARS-CoV-2 vaccine may impact SARS-CoV-2 vaccine induced humoral immune responses. We aimed to compare IIV and SARS-CoV-2 vaccine induced cellular and humoral immune responses in those receiving concomitant vaccination to those receiving these vaccines separately.MethodsWe conducted a cohort study between 29th September 2021 and 5th August 2022 in healthcare workers who worked at the local NHS trust and in the surrounding area that were vaccinated with a mRNA SARS-CoV-2 booster and cell-based IIV. We measured haemagglutination inhibition assay (HAI) titres, SARS-CoV-2 anti-spike antibody and SARS-CoV-2 ELISpot count pre-vaccination, 1-month and 6-months post-vaccination and evaluated differences by vaccine strategy.FindingsWe recruited 420 participants, 234/420 (56%) were vaccinated concomitantly and 186/420 (44%) separately. The 1-month post-vaccination mean fold rise (MFR) in SARS-CoV-2 anti-spike antibodies was lower in those vaccinated concomitantly compared to separately (MFR [95% confidence interval (CI)] 9.7 [8.3, 11.4] vs 12.8 [10.3, 15.9], p = 0.04). After adjustment for age and sex, the adjusted geometric mean ratio (aGMR) remained lower for those vaccinated concomitantly compared to separately (aGMR [95% CI] 0.80 [0.70, 0.92], p = 0.001). At 6-months post-vaccination, we found no statistically significant difference in SARS-CoV-2 anti-spike antibody titres (aGMR [95% CI] 1.09 [0.87, 1.35], p = 0.45). We found no statistically significant correlation between vaccine strategy with SARS-CoV-2 ELISpot count and influenza HAI titres at 1-month and 6-months post-vaccination.InterpretationOur study found that concomitant vaccination with SARS-CoV-2 and IIV has no statistically significant impacts on long-term immunogenicity. Further research is required to understand the underlying mechanisms and assess the clinical significance of reduced anti-spike antibodies in those vaccinated concomitantly.FundingResearch and Innovation (UKRI) through the COVID-19 National Core Studies Immunity (NCSi) programme (MC_PC_20060).
CBX4 counteracts cellular senescence to desensitize gastric cancer cells to chemotherapy by inducing YAP1 SUMOylation
Authors: Yunru Gu, Tingting Xu, Yuan Fang, Jun Shao, Tong Hu, Xi Wu, Haoyang Shen, Yangyue Xu, Jingxin Zhang, Yu Song, Yang Xia, Yongqian Shu, Pei Ma
Journal: Drug Resistance Updates (2024)
Skin microdialysis detects distinct immunologic patterns in chronic inflammatory skin diseases
Authors: Moritz Maximilian Hollstein, Stephan Traidl, Anne Heetfeld, Susann Forkel, Andreas Leha, Natalia Alkon, Jannik Ruwisch, Christof Lenz, Michael Peter Schön, Martin Schmelz, Patrick Brunner, Martin Steinhoff, Timo Buhl
Journal: Journal of Allergy and Clinical Immunology (2024)

Graphical abstractAbstractBackgroundInsight into the pathophysiology of inflammatory skin diseases, especially at the proteomic level, is severely hampered by the lack of adequate in situ data.ObjectiveWe characterized lesional and nonlesional skin of inflammatory skin diseases using skin microdialysis.MethodsSkin microdialysis samples from patients with atopic dermatitis (AD, n = 6), psoriasis vulgaris (PSO, n = 7), or prurigo nodularis (PN, n = 6), as well as healthy controls (n = 7), were subjected to proteomic and multiplex cytokine analysis. Single-cell RNA sequencing of skin biopsy specimens was used to identify the cellular origin of cytokines.ResultsAmong the top 20 enriched Gene Ontology (GO; geneontology.org) annotations, nicotinamide adenine dinucleotide metabolic process, regulation of secretion by cell, and pyruvate metabolic process were elevated in microdialysates from lesional AD skin compared with both nonlesional skin and controls. The top 20 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG; genome.jp/kegg) pathways in these 3 groups overlapped almost completely. In contrast, nonlesional skin from patients with PSO or PN and control skin showed no overlap with lesional skin in this KEGG pathway analysis. Lesional skin from patients with PSO, but not AD or PN, showed significantly elevated protein levels of MCP-1 compared with nonlesional skin. IL-8 was elevated in lesional versus nonlesional AD and PSO skin, whereas IL-12p40 and IL-22 were higher only in lesional PSO skin. Integrated single-cell RNA sequencing data revealed identical cellular sources of these cytokines in AD, PSO, and PN.ConclusionOn the basis of microdialysates, the proteomic data of lesional PSO and PN skin, but not lesional AD skin, differed significantly from those of nonlesional skin. IL-8, IL-22, MCP-1, and IL-12p40 might be suitable markers for minimally invasive molecular profiling.
Physiological presentation and risk factors of long COVID in the UK using smartphones and wearable devices: a longitudinal, citizen science, case–control study
Authors: Callum Stewart, Yatharth Ranjan, Pauline Conde, Shaoxiong Sun, Yuezhou Zhang, Zulqarnain Rashid, Heet Sankesara, Nicholas Cummins, Petroula Laiou, Xi Bai, Richard J B Dobson, Amos A Folarin
Journal: The Lancet Digital Health (2024)
High-dose hyperfractionated simultaneous integrated boost radiotherapy versus standard-dose radiotherapy for limited-stage small-cell lung cancer in China: a multicentre, open-label, randomised, phase 3 trial
Authors: Jiayi Yu, Leilei Jiang, Lina Zhao, Xue Yang, Xiaomin Wang, Dan Yang, Minglei Zhuo, Hanxiao Chen, Wei Huang, Zhengfei Zhu, Min Zhang, Yipeng Song, Quanfu Li, Zhanshu Ma, Qifeng Wang, Yanli Qu, Rong Yu, Huiming Yu, Jun Zhao, Anhui Shi
Journal: The Lancet Respiratory Medicine (2024)
Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): long-term, health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial
Authors: Emanuel Bührer, Michal Kicinski, Mario Mandala, Madeline Pe, Georgina V Long, Victoria Atkinson, Christian U Blank, Andrew Haydon, Stéphane Dalle, Adnan Khattak, Matteo S Carlino, Andrey Meshcheryakov, Shahneen Sandhu, Susana Puig, Dirk Schadendorf, Rahima Jamal, Piotr Rutkowski, Alfonsus J M van den Eertwegh, Corneel Coens, Dmitri Grebennik, Clemens Krepler, Caroline Robert, Alexander M M Eggermont
Journal: The Lancet Oncology (2024)
The burden and contemporary epidemiology of sepsis in children
Authors: R Scott Watson, Enitan D Carrol, Michael J Carter, Niranjan Kissoon, Suchitra Ranjit, Luregn J Schlapbach
Journal: The Lancet Child & Adolescent Health (2024)

Sepsis is a dysregulated host response to infection that leads to life-threatening organ dysfunction. Half of the 50 million people affected by sepsis globally every year are neonates and children younger than 19 years. This burden on the paediatric population translates into a disproportionate impact on global child health in terms of years of life lost, morbidity, and lost opportunities for children to reach their developmental potential. This Series on paediatric sepsis presents the current state of diagnosis and treatment of sepsis in children, and maps the challenges in alleviating the burden on children, their families, and society. Drawing on diverse experience and multidisciplinary expertise, we offer a roadmap to improving outcomes for children with sepsis. This first paper of the Series is a narrative review of the burden of paediatric sepsis from low-income to high-income settings. Advances towards improved operationalisation of paediatric sepsis across all age groups have facilitated more standardised assessment of the Global Burden of Disease estimates of the impact of sepsis on child health, and these estimates are expected to gain further precision with the roll out of the new Phoenix criteria for sepsis. Sepsis remains one of the leading causes of childhood morbidity and mortality, with immense direct and indirect societal costs. Although substantial regional differences persist in relation to incidence, microbiological epidemiology, and outcomes, these cannot be explained by differences in income level alone. Recent insights into post-discharge sequelae after paediatric sepsis, ranging from late mortality and persistent neurodevelopmental impairment to reduced health-related quality of life, show how common post-sepsis syndrome is in children. Targeting sepsis as a key contributor to poor health outcomes in children is therefore an essential component of efforts to meet the Sustainable Development Goals.