tbuckley/cabot-search huggingface dataset:
The associations of socioeconomic status, social activities, and loneliness with depressive symptoms in adults aged 50 years and older across 24 countries: findings from five prospective cohort studies
Authors: Yaping Wang, Min Liu, Fude Yang, Hongguang Chen, Yaogang Wang, Jue Liu
Journal: The Lancet Healthy Longevity (2024)

Depression is the leading cause of mortality among mental health disorders. Evidence about the associations of socioeconomic status, social activities, and loneliness with depression is scarce. We aimed to identify whether social activities and loneliness mediate the association between socioeconomic status and depression, and the extent of interactive or joint relationships between social activities, loneliness, and socioeconomic status on depression.
Therapeutic drug monitoring of antibiotics for methicillin-resistant Staphylococcus aureus infections: an updated narrative review for clinicians
Authors: Valentina Galfo, Giusy Tiseo, Niccolò Riccardi, Marco Falcone
Journal: Clinical Microbiology and Infection (2024)

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are associated with high mortality rates. Optimal antibiotic dosage plays a crucial role in reducing MRSA burden; thus, the use of therapeutic drug monitoring (TDM) in the clinical practice, especially of new drugs such as ceftobiprole, ceftaroline, dalbavancin, and oritavancin, should be implemented.
Revisiting diagnostics: erythrocyte sedimentation rate and C-reactive protein: it is time to stop the zombie tests
Authors: Brad Spellberg, Travis B. Nielsen, Matthew C. Phillips, Bassam Ghanem, Tom Boyles, Boris Jegorović, Brent Footer, Jordan K. Mah, Anthony Lieu, Jake Scott, Noah Wald-Dickler, Todd C. Lee, Emily G. McDonald
Journal: Clinical Microbiology and Infection (2024)
Single-cell analysis reveals the implication of vascular endothelial cell-intrinsic ANGPT2 in human intracranial aneurysm
Authors: Guo Yu, Jia Li, Hongfei Zhang, Huaxing Zi, Mingjian Liu, Qingzhu An, Tianming Qiu, Peiliang Li, Jianping Song, Peixi Liu, Kai Quan, Sichen Li, Yingjun Liu, Wei Zhu, Jiulin Du
Journal: Cardiovascular Research (2024)

While previous single-cell RNA sequencing (scRNA-seq) studies have attempted to dissect intracranial aneurysm (IA), the primary molecular mechanism for IA pathogenesis remains unknown. Here, we uncovered the alterations of cellular compositions, especially the transcriptome changes of vascular endothelial cells (ECs), in human IA.
Increased risk of subsequent neoplasm after hematopoietic stem cell transplantation in 5-year survivors of childhood acute lymphoblastic leukemia
Authors: Aimée S. R. Westerveld, Pien Roesthuis, Helena J. H. van der Pal, Dorine Bresters, Marc Bierings, Jacqueline Loonen, Andrica C. H. de Vries, Marloes Louwerens, Maria M. W. Koopman, Marry M. van den Heuvel-Eibrink, Margriet van der Heiden-van der Loo, Peter Hoogerbrugge, Geert O. Janssens, Ronald R. de Krijger, Cecile M. Ronckers, Rob Pieters, Leontien C. M. Kremer, Jop C. Teepen
Journal: Blood Cancer Journal (2024)

Acute lymphoblastic leukemia (ALL) survivors are at risk for developing subsequent neoplasms, but there is limited information on long-term risks and risk factors for both subsequent malignant neoplasms (SMNs) and subsequent non-malignant neoplasms (SNMNs). We analyzed long-term risk and risk factors for SMNs and SNMNs among 3291 5-year ALL survivors from the Dutch Childhood Cancer Survivor Study-LATER cohort (1963–2014). We calculated standardized incidence ratios (SIRs) and cumulative incidences and used multivariable Cox proportional hazard regression analyses for analyzing risk factors. A total of 97 survivors developed SMNs and 266 SNMNs. The 30-year cumulative incidence was 4.1% (95%CI: 3.5–5.3) for SMNs and 10.4%(95%CI: 8.9–12.1) for SNMNs. Risk of SMNs was elevated compared to the general population (SIR: 2.6, 95%CI: 2.1–3.1). Survivors treated with hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI) (HR:4.2, 95%CI: 2.3–7.9), and without TBI (HR:4.0,95%CI: 1.2–13.7) showed increased SMN risk versus non-transplanted survivors. Cranial radiotherapy (CRT) was also a risk factor for SMNs (HR:2.1, 95%CI: 1.4–4.0). In conclusion, childhood ALL survivors have an increased SMN risk, especially after HSCT and CRT. A key finding is that even HSCT-treated survivors without TBI treatment showed an increased SMN risk, possibly due to accompanied chemotherapy treatment. This emphasizes the need for careful follow-up of HSCT and/or CRT-treated survivors.
Burden of risk factors in women and men with unrecognised myocardial infarction: a systematic review and meta-analysis
Authors: Julie A E van Oortmerssen, Noluthando Ntlapo, Martijn J Tilly, Wichor M Bramer, Hester M den Ruijter, Eric Boersma, Maryam Kavousi, Jeanine E Roeters van Lennep
Journal: Cardiovascular Research (2024)

Unrecognized myocardial infarction (MI) is an MI that remains undetected in the acute phase and is associated with an unfavourable prognosis. With this systematic review and meta-analysis, we evaluated the burden of cardiovascular risk factors in individuals with unrecognized MI. We searched general population-based cohort studies diagnosing unrecognized MI by electrocardiogram or myocardial imaging up to 24 November 2023. Pooled mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs) were determined, and random-effects meta-analyses were performed. Fourteen cohort studies were included involving 200 450 individuals (mean age 62.8 ± 9.9 years, 56.0% women), among which 4322 (2.2%) experienced unrecognized MI (mean age 66.3 ± 8.2 years, 47.8% women) and 4653 (2.1%) recognized MI (mean age 68.5 ± 7.3 years, 33.8% women). Compared to individuals without MI, those with unrecognized MI had higher body mass index (MD 0.27, 95% CI 0.16-0.39) and systolic blood pressure (MD 4.48, 95% CI 2.81-6.15) levels, and higher prevalence of hypertension (RR 1.27, 95% CI 1.06-1.51) and diabetes mellitus (RR 1.67, 95% CI 1.36-2.06). Furthermore, individuals with unrecognized MI had lower prevalence of hypertension (RR 0.92, 95% CI 0.88-0.97) and diabetes mellitus (RR 0.80, 95% CI 0.70-0.92). Individuals with unrecognized MI are characterized by a substantial burden of metabolic risk factors. Our findings suggest insufficient recognition and management of cardiovascular risk factors among individuals with unrecognized MI.
Physiological and pathological ventricular hypertrophy: a role for Cavin-2 mediated Akt regulation
Authors: Raffaele Coppini, Lucrezia Giammarino, Elisabetta Cerbai
Journal: Cardiovascular Research (2024)

Ventricular cardiomyocytes are well tuned to meet the increased mechanical requirements caused by longlasting pathological stress or hemodynamically challenging conditions, through increase of their volume and myofilament content.Although ventricular hypertrophy is the result of both chronic myocardial diseases and intense exercise training, the long-term outcomes of the two hypertrophying pathways are In the manuscript "Loss of Cavin-2 destabilizes PTEN and enhances Akt signaling pathway in
Antibiotic-free ocular sterilization while suppressing immune response to protect corneal transparency in infectious keratitis treatment
Authors: Yaou Peng, Shuaiyue Pang, Yanlin Zeng, Jiayi Wei, Jinda Lu, Yangfan Ruan, Xinyu Hong, Xiuhui He, Xiaoying Chu, Yishun Guo, Hanwen Guo, Siyuan Qian, Zipei Jiang, Zhengxuan Jiang, Bailiang Wang
Journal: Journal of Controlled Release (2024)
Toll-like receptor agonists promote the formation of tertiary lymphoid structure and improve anti-glioma immunity
Authors: Shaoping Shen, Yong Cui, Mingxiao Li, Kefu Yu, Qinghui Zhu, Xiaokang Zhang, Weicheng Shen, Haoyi Li, Haihui Jiang, Ming Li, Xijie Wang, Xuzhe Zhao, Xiaohui Ren, Song Lin
Journal: Neuro-Oncology (2024)

Abstract Background Glioma, characterized by limited lymphocytic infiltration, constitutes an “immune-desert” tumor displaying insensitivity to various immunotherapies. This study aims to explore therapeutic strategies for inducing tertiary lymphoid structure (TLS) formation within the glioma microenvironment (GME) to transition it from an immune resistant to an activated state. Methods TLS formation in GME was successfully induced by intracranial administration of Toll-like receptor (TLR) agonists (OK-432, TLR2/4/9 agonist) and glioma antigens (i.c. αTLR-mix). We employed staining analysis, antibody neutralization, single-cell RNA sequencing (scRNA-Seq), and BCR/TCR sequencing to investigate the underlying mechanisms of TLS formation and its role in anti-glioma immunity. Additionally, a preliminary translational clinical study was conducted. Results TLS formation correlated with increased lymphocyte infiltration in GME and led to improved prognosis in glioma-bearing mice. In the study of TLS induction mechanisms, certain macrophages/microglia and Th17 displayed markers of “LTo” and “LTi” cells, respectively, interaction through LTα/β-LTβR promoted TLS induction. Post-TLS formation, CD4 + and CD8 + T cells but not CD19 + B cells contributed to anti-glioma immunity. Comparative analysis of B/T cells between brain and lymph node showed that brain B/T cells unveiled the switch from naïve to mature, some B cells highlighted an enrichment of class switch recombination (CSR)-associated genes, V gene usage, and clonotype bias were observed. In related clinical studies, i.c. αTLR-mix treatment exhibited tolerability, and chemokines/cytokines assay provided preliminary evidence supporting TLS formation in GME. Conclusions TLS induction in GME enhanced anti-glioma immunity, improved the immune microenvironment, and controlled glioma growth, suggesting potential therapeutic avenues for treating glioma in the future.
Prevalent fast evolution of genes involved in heterochromatin functions
Authors: Leila Lin, Yuheng Huang, Jennifer McIntyre, Ching-Ho Chang, Serafin Colmenares, Yuh Chwen G Lee
Journal: Molecular Biology and Evolution (2024)

Heterochromatin is a gene-poor and repeat-rich genomic compartment universally found in eukaryotes. Despite its low transcriptional activity, heterochromatin plays important roles in maintaining genome stability, organizing chromosomes, and suppressing transposable elements. Given the importance of these functions, it is expected that genes involved in heterochromatin regulation would be highly conserved. Yet, a handful of these genes were found to evolve rapidly. To investigate whether these previous findings are anecdotal or general to genes modulating heterochromatin, we compile an exhaustive list of 106 candidate genes involved in heterochromatin functions and investigate their evolution over short and long evolutionary time scales in Drosophila. Our analyses find that these genes exhibit significantly more frequent evolutionary changes, both in the forms of amino acid substitutions and gene copy number change, when compared to genes involved in Polycomb-based repressive chromatin. While positive selection drives amino acid changes within both structured domains with diverse functions and intrinsically disordered regions, purifying selection may have maintained the proportions of intrinsically disordered regions of these proteins. Together with the observed negative associations between the evolutionary rate of these genes and the genomic abundance of transposable elements, we propose an evolutionary model where the fast evolution of genes involved in heterochromatin functions is an inevitable outcome of the unique functional roles of heterochromatin, while the rapid evolution of transposable elements may be an effect rather than cause. Our study provides an important global view of the evolution of genes involved in this critical cellular domain and provides insights into the factors driving the distinctive evolution of heterochromatin.
Mechanistic Differences between Torsemide and Furosemide
Authors: Veena S. Rao, Zachary L. Cox, Juan B. Ivey-Miranda, Daniel Neville, Natasha Balkcom, Julieta Moreno-Villagomez, Daniela Ramos-Mastache, Christopher Maulion, Lavanya Bellumkonda, W.H. Wilson Tang, Sean P. Collins, Eric J. Velazquez, Robert J. Mentz, F. Perry Wilson, Jeffrey M. Turner, Christopher S. Wilcox, David H. Ellison, James C. Fang, Jeffrey M. Testani
Journal: Journal of the American Society of Nephrology (2024)

Key Points Oral torsemide was not superior to furosemide in measures of renal tubular delivery or duration of action. A dose equivalence of approximately 40 mg oral furosemide:10 mg oral torsemide resulted in similar natriuresis. The two-fold higher doses of torsemide did not improve fluid status due to the kidney’s compensation. Background Torsemide is proposed to have clinically important pharmacokinetic and pharmacodynamic advantages over furosemide. However, clinical outcomes did not differ in the Torsemide Comparison with Furosemide for Management of Heart Failure (TRANSFORM) randomized trial. Methods We conducted a multicenter mechanistic substudy of patients with heart failure randomized to oral furosemide or torsemide (TRANSFORM-Mechanism trial). At baseline and 30 days, participants underwent detailed assessments of pharmacokinetic and pharmacodynamic parameters. Results The TRANSFORM-Mechanism trial enrolled 88 participants. Kidney bioavailability, or the proportion of dose delivered to the tubular site of action, was significantly less with torsemide compared with furosemide (median, 17.1% [interquartile range, 12.3%–23.5%] versus 24.8% [16.6%–34.1%], P &lt; 0.001). Furosemide had a longer duration of kidney drug delivery and natriuresis ( P ≤ 0.004 for both). Prescribed doses of furosemide and torsemide in the TRANSFORM-Mechanism trial were similar to the TRANSFORM trial, with clinicians on average using a 2:1 dose equivalence conversion between drugs. However, these doses resulted in a substantially greater natriuresis with torsemide ( P &lt; 0.001). A dose equivalence of approximately 4:1 resulted in similar natriuresis. Higher diuretic doses in the torsemide group resulted in mild perturbations in kidney function and significant increases in renin, aldosterone, and norepinephrine ( P &lt; 0.05 for all). Plasma volume ( P = 0.52) and body weight ( P = 0.89) did not improve with torsemide versus furosemide. Conclusions We observed no meaningful pharmacokinetic/pharmacodynamic advantages for torsemide versus furosemide. The greater natriuresis from higher diuretic doses in the torsemide group was offset by greater neurohormonal activation and kidney dysfunction. Clinical Trial registry name and registration number: TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure (TRANSFORM-HF), NCT03296813; Torsemide Comparison With Furosemide for Management of Patients With Stable Heart Failure (TFO), NCT05093621.
Unravelling the physicochemical and antimicrobial mechanisms of human serum albumin/tannic acid coatings for medical-grade polycaprolactone scaffolds
Authors: Silvia Cometta, Bogdan C. Donose, Alfredo Juárez-Saldivar, Akhilandeshwari Ravichandran, Yanan Xu, Nathalie Bock, Tim R. Dargaville, Aleksandar D. Rakić, Dietmar W. Hutmacher
Journal: Bioactive Materials (2024)

Biofilm-related biomaterial infections are notoriously challenging to treat and can lead to chronic infection and persisting inflammation. To date, a large body of research can be reviewed for coatings which potentially prevent bacterial infection while promoting implant integration. Yet only a very small number has been translated from bench to bedside. This study provides an in-depth analysis of the stability, antibacterial mechanism, and biocompatibility of medical grade polycaprolactone (mPCL), coated with human serum albumin (HSA), the most abundant protein in blood plasma, and tannic acid (TA), a natural polyphenol with antibacterial properties. Molecular docking studies demonstrated that HSA and TA interact mainly through hydrogen-bonding, ionic and hydrophobic interactions, leading to smooth and regular assemblies.
Vascular wall microenvironment: Endothelial cells original exosomes mediated melatonin-suppressed vascular calcification and vascular ageing in a m6A methylation dependent manner
Authors: Su-Kang Shan, Xiao Lin, Feng Wu, Chang-Chun Li, Bei Guo, Fu-Xing-Zi Li, Ming-Hui Zheng, Yi Wang, Qiu-Shuang Xu, Li-Min Lei, Ke-Xin Tang, Yun-Yun Wu, Jia-Yue Duan, Ye-Chi Cao, Yan-Lin Wu, Chang-Ming Tan, Zi-Han Liu, Zhi-Ang Zhou, Xiao-Bo Liao, Feng Xu, Ling-Qing Yuan
Journal: Bioactive Materials (2024)

Vascular calcification and vascular ageing are "silent" diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N
Fertility-sparing treatment and follow-up in patients with cervical cancer, ovarian cancer, and borderline ovarian tumours: guidelines from ESGO, ESHRE, and ESGE
Authors: Philippe Morice, Giovanni Scambia, Nadeem R Abu-Rustum, Maribel Acien, Alessandro Arena, Sara Brucker, Ying Cheong, Pierre Collinet, Francesco Fanfani, Francesca Filippi, Ane Gerda Zahl Eriksson, Sebastien Gouy, Philipp Harter, Xavier Matias-Guiu, George Pados, Maja Pakiz, Denis Querleu, Alexandros Rodolakis, Christine Rousset-Jablonski, Artem Stepanyan, Antonia Carla Testa, Kirsten Tryde Macklon, Dimitrios Tsolakidis, Michel De Vos, François Planchamp, Michaël Grynberg
Journal: The Lancet Oncology (2024)
Primary biliary cholangitis
Authors: Atsushi Tanaka, Xiong Ma, Atsushi Takahashi, John M Vierling
Journal: The Lancet (2024)

Primary biliary cholangitis is a chronic, autoimmune, cholestatic disease that mainly affects women aged 40-70 years. Recent epidemiological studies have shown an increasing incidence worldwide despite geographical heterogeneity and a decrease in the female-to-male ratio of those the disease affects. Similar to other autoimmune diseases, primary biliary cholangitis occurs in genetically predisposed individuals upon exposure to environmental triggers, specifically xenobiotics, smoking, and the gut microbiome. Notably, the diversity of the intestinal microbiome is diminished in individuals with primary biliary cholangitis. The intricate interplay among immune cells, cytokines, chemokines, and biliary epithelial cells is postulated as the underlying pathogenic mechanism involved in the development and progression of primary biliary cholangitis, and extensive research has been dedicated to comprehending these complex interactions. Following the official approval of obeticholic acid as second-line treatment for patients with an incomplete response or intolerance to ursodeoxycholic acid, clinical trials have indicated that peroxisome proliferator activator receptor agonists are promising additional second-line drugs. Future dual or triple drug regimens might reach a new treatment goal of normalisation of alkaline phosphatase levels, rather than a decrease to less than 1·67 times the upper limit of normal levels, and potentially improve long-term outcomes. Improvement of health-related quality of life with better recognition and care of subjective symptoms, such as pruritus and fatigue, is also an important treatment goal. Promising clinical investigations are underway to alleviate these symptoms. Efforts to facilitate better access to medical care and dissemination of current knowledge should enable diagnosis at an earlier stage of primary biliary cholangitis and ensure access to treatments based on risk stratification for all patients.
Respiratory syncytial virus infection among children younger than 2 years admitted to a paediatric intensive care unit with extended severe acute respiratory infection in ten Gavi-eligible countries: the RSV GOLD—ICU Network study
Authors: Dina N Abdelrahman, Fatima L Abdullahi, Fadlulai Abdu-Raheem, Lynda T Abicher, Hamdalla Adelaiye, Ansumana Badjie, Abdou Bah, Krishna P Bista, Louis J Bont, Trisja T Boom, W Chris Buck, Milka Amanda Cáceres Avila, Ram Hari Chapagain, Daniela Cianci, Alexandra Deroncelay, Vanessa Dor, Karen Ekotto, Khalid A Enan, Charlotte Eposse, Esquivel Fouobang, Abdou Gai, Abdoulie Garba, Maria A Garba, Jacqueline Gautier, Fatima J Giwa, Evance K Godfrey, Bamenla Quarm Goka, Musa Jaiteh, Mariama Jallow, Alasana Jallow, Sheikh Joof, Prakash Joshi, Bankole P Kuti, Yvette N Löwensteyn, Lamin Makalo, Henshaw Mandi, Yara Manjate, Elias Manjate, Izilda Matimbe, Natalie I Mazur, Safaa A Medani, Peter T Mendy, Valéria Muando, Tufária Mussá, Harish Nair, Ousman Nyan, Evangeline Obodai, Aira A Olorukooba, Kwabena Agyapong Osman, Khalid Osman, Daisy Luisa Fátima Peñarrieta Echenique, Jose Gareca Pérales, Neele Rave, Yasser Habresh Said, Farina L Shaaban, Arun K Sharma, Aika A Shoo, Rupesh Shrestha, Cristina Sinussene, Afshan Tahibo, Joukje E Willemsen, Job BM van Woensel, Farida Zavale, Hanneke JAA van Zoggel
Journal: The Lancet Global Health (2024)

Patient-level data on life-threatening respiratory syncytial virus (RSV) infection in children in low-income and lower-middle-income countries (LMICs) are scarce, and this scarcity might limit demand for RSV interventions in LMICs who rely on support from Gavi, the Vaccine Alliance. We aimed to describe the characteristics of RSV-positive children younger than 2 years who were admitted to paediatric intensive care units (PICUs) with extended severe acute respiratory infection (eSARI) in Gavi-eligible countries.
Interventions to reduce harms related to drug use among people who experience incarceration: systematic review and meta-analysis
Authors: Christel Macdonald, Georgina Macpherson, Oscar Leppan, Lucy Thi Tran, Evan B Cunningham, Behzad Hajarizadeh, Jason Grebely, Michael Farrell, Frederick L Altice, Louisa Degenhardt
Journal: The Lancet Public Health (2024)
The role of mental illness and neurodevelopmental conditions in human papillomavirus vaccination uptake within the Swedish school-based vaccination programme: a population-based cohort study
Authors: Kejia Hu, Mary M Barker, Eva Herweijer, Jiangrong Wang, Adina L Feldman, Donghao Lu, Unnur Valdimarsdóttir, Karin Sundström, Fang Fang
Journal: The Lancet Public Health (2024)

Despite documented mental illness-related disparities in cervical cancer screening and incidence, insufficient data exist on differences in cervical cancer prevention strategies, such as human papillomavirus (HPV) vaccination. We aimed to investigate the association of mental illness and neurodevelopmental conditions among girls and their parents with uptake of HPV vaccination in Sweden.