tbuckley/cabot-search huggingface dataset:
Hypotension during intensive care stay and mortality and morbidity: a systematic review and meta-analysis
Authors: Jaap Schuurmans, Benthe T. B. van Rossem, Santino R. Rellum, Johan T. M. Tol, Vincent C. Kurucz, Niels van Mourik, Ward H. van der Ven, Denise P. Veelo, Jimmy Schenk, Alexander P. J. Vlaar
Journal: Intensive Care Medicine (2024)

The aim of this study is to provide a summary of the existing literature on the association between hypotension during intensive care unit (ICU) stay and mortality and morbidity, and to assess whether there is an exposure-severity relationship between hypotension exposure and patient outcomes. CENTRAL, Embase, and PubMed were searched up to October 2022 for articles that reported an association between hypotension during ICU stay and at least one of the 11 predefined outcomes. Two independent reviewers extracted the data and assessed the risk of bias. Results were gathered in a summary table and studies designed to investigate the hypotension-outcome relationship were included in the meta-analyses. A total of 122 studies (176,329 patients) were included, with the number of studies varying per outcome between 0 and 82. The majority of articles reported associations in favor of 'no hypotension' for the outcomes mortality and acute kidney injury (AKI), and the strength of the association was related to the severity of hypotension in the majority of studies. Using meta-analysis, a significant association was found between hypotension and mortality (odds ratio: 1.45; 95% confidence interval (CI) 1.12–1.88; based on 13 studies and 34,829 patients), but not for AKI. Exposure to hypotension during ICU stay was associated with increased mortality and AKI in the majority of included studies, and associations for both outcomes increased with increasing hypotension severity. The meta-analysis reinforced the descriptive findings regarding mortality but did not yield similar support for AKI.
Prospective prenatal cell-free DNA screening for genetic conditions of heterogenous etiologies
Authors: Jinglan Zhang, Yanting Wu, Songchang Chen, Qiong Luo, Hui Xi, Jianli Li, Xiaomei Qin, Ying Peng, Na Ma, Bingxin Yang, Xiang Qiu, Weiliang Lu, Yuan Chen, Ying Jiang, Panpan Chen, Yifeng Liu, Chen Zhang, Zhiwei Zhang, Yu Xiong, Jie Shen, Huan Liang, Yunyun Ren, Chunmei Ying, Minyue Dong, Xiaotian Li, Congjian Xu, Hua Wang, Dan Zhang, Chenming Xu, Hefeng Huang
Journal: Nature Medicine (2024)
Hydroxyurea is associated with later onset of acute splenic sequestration crisis in sickle cell disease: Lessons from the European Sickle Cell Disease Cohort—Hydroxyurea (<scp>ESCORT‐HU</scp>) study
Authors: Slimane Allali, Frédéric Galactéros, Lena Oevermann, Giovanna Cannas, Laure Joseph, Gylna Loko, Narcisse Elenga, Malika Benkerrou, Maryse Etienne‐Julan, Marie‐Pierre Castex, Valentine Brousse, Mariane de Montalembert
Journal: American Journal of Hematology (2024)

Abstract Acute splenic sequestration crisis (ASSC) is a potentially life‐threatening complication of sickle cell disease (SCD), typically occurring in young patients under 5 years of age, with a median age at first episode of less than 2 years. Because a beneficial effect of hydroxyurea (HU) on spleen perfusion and splenic function has been suspected, we hypothesized that HU treatment might be associated with later onset of ASSC in patients with SCD. To investigate this hypothesis, we analyzed data from the ESCORT‐HU study on a large cohort of patients with SCD receiving HU, enrolled between January 2009 and June 2017 with a follow‐up of 7309 patient‐years of observation. The median age at ASSC of the 14 patients who experienced a first episode of ASSC during the study period was 8.0 [IQR: 5.0–24.1] years. The median age at HU initiation was significantly lower in these 14 patients (4.8 [IQR: 3.3–18.7] years) compared to the 1664 patients without ASSC (19.9 [8.8–33.4] years, p = .0008). These findings suggest that ASSC may occur at an unusually late age in patients receiving HU, possibly reflecting longer preservation of spleen perfusion and function secondary to early initiation of HU. Further studies are needed to better characterize the effects of HU on spleen perfusion/function and on the occurrence of ASSC in patients with SCD ( ClinicalTrials.gov identifier: NCT02516579; European registry ENCEPP/SDPP/10565).
Unselected donor‐derived hematopoietic stem cells boost for Chimeric Antigen Receptor T‐cell associated hematotoxicity
Authors: Eugenio Galli, Maria Assunta Limongiello, Elisabetta Metafuni, Sabrina Giammarco, Alberto Fresa, Nicola Piccirillo, Maria Bianchi, Luca Laurenti, Federica Sorà, Patrizia Chiusolo, Simona Sica
Journal: American Journal of Hematology (2024)

Graphical Abstract Hematological toxicity following Chimeric Antigen Receptor-T therapy in a patient with a prior allogeneic stem cell transplantation was resolved by the infusion of unselected donor-derived stem cell boost. Due to the donor's lymphocytes, the patient experienced a well-controlled flare-up of acute graft versus host disease.
A Modular Microfluidic Organoid Platform Using LEGO‐Like Bricks
Authors: Daniel J. Carvalho, Anna M. Kip, Andreas Tegel, Matthias Stich, Christian Krause, Mírian Romitti, Carlotta Branca, Bart Verhoeven, Sabine Costagliola, Lorenzo Moroni, Stefan Giselbrecht
Journal: Advanced Healthcare Materials (2024)

The convergence of organoid and organ-on-a-chip (OoC) technologies is urgently needed to overcome limitations of current 3D in vitro models. However, integrating organoids in standard OoCs faces several technical challenges, as it is typically laborious, lacks flexibility, and often results in even more complex and less-efficient cell culture protocols. Therefore, specifically adapted and more flexible microfluidic platforms need to be developed to facilitate the incorporation of complex 3D in vitro models. Here, a modular, tubeless fluidic circuit board (FCB) coupled with reversibly sealed cell culture bricks for dynamic culture of embryonic stem cell-derived thyroid follicles is developed. The FCB is fabricated by milling channels in a polycarbonate (PC) plate followed by thermal bonding against another PC plate. LEGO-like fluidic interconnectors allow plug-and-play connection between a variety of cell culture bricks and the FCB. Lock-and-play clamps are integrated in the organoid brick to enable easy (un)loading of organoids. A multiplexed perfusion experiment is conducted with six FCBs, where thyroid organoids are transferred on-chip within minutes and cultured up to 10 d without losing their structure and functionality, thus validating this system as a flexible, easy-to-use platform, capable of synergistically combining organoids with advanced microfluidic platforms.
Myocardial sodium–glucose cotransporter <scp>2</scp> expression and cardiac remodelling in patients with severe aortic stenosis: The <scp>BIO‐AS</scp> study
Authors: Lucia Scisciola, Pasquale Paolisso, Marta Belmonte, Emanuele Gallinoro, Leen Delrue, Fatemeh Taktaz, Rosaria Anna Fontanella, Ivan Degrieck, Ada Pesapane, Filip Casselman, Armando Puocci, Martina Franzese, Frank Van Praet, Michele Torella, Raffaele Marfella, Marisa De Feo, Jozef Bartunek, Giuseppe Paolisso, Emanuele Barbato, Michelangela Barbieri, Marc Vanderheyden
Journal: European Journal of Heart Failure (2024)

Aim Cardiac remodelling plays a major role in the prognosis of patients with aortic stenosis (AS) and could impact the benefits of aortic valve replacement. Our study aimed to evaluate the expression of sodium–glucose cotransporter 2 (SGLT2) gene and protein in patients with severe AS stratified in high gradient (HG) and low flow‐low gradient (LF‐LG) AS and its association with cardiac functional impairments. Methods and results Gene expression and protein levels of main biomarkers of cardiac fibrosis (galectin‐3, sST2, serpin‐4, procollagen type I amino‐terminal peptide, procollagen type I carboxy‐terminal propeptide, collagen, transforming growth factor [TGF]‐β), inflammation (growth differentiation factor‐15, interleukin‐6, nuclear factor‐κB [NF‐κB]), oxidative stress (superoxide dismutase 1 [SOD1] and 2 [SOD2]), and cardiac metabolism (sodium–hydrogen exchanger, peroxisome proliferator‐activated receptor [PPAR]‐α, PPAR‐γ, glucose transporter 1 [GLUT1] and 4 [GLUT4]) were evaluated in blood samples and heart biopsies of 45 patients with AS. Our study showed SGLT2 gene and protein hyper‐expression in patients with LF‐LG AS, compared to controls and HG AS ( p &lt; 0.05). These differences remained significant even after adjusting for age, gender, body mass index, history of diabetes mellitus, arterial hypertension, and coronary artery disease. SGLT2 gene expression was positively correlated with: (i) TGF‐β ( r = 0.72, p &lt; 0.001) and collagen ( r = 0.73, p &lt; 0.001) as markers of fibrosis; (ii) NF‐κB ( r = 0.36, p &lt; 0.01) and myocardial interleukin‐6 ( r = 0.68, p &lt; 0.001) as markers of inflammation: (iii) SOD2 ( r = −0.38, p &lt; 0.006) as a marker of oxidative stress; (iv) GLUT4 ( r = 0.33, p &lt; 0.02) and PPAR‐α ( r = 0.36, p &lt; 0.01) as markers of cardiac metabolism. Conclusion In patients with LF‐LG AS, SGLT2 gene and protein were hyper‐expressed in cardiomyocytes and associated with myocardial fibrosis, inflammation, and oxidative stress.
The effectiveness of pollen allergen immunotherapy on allergic rhinitis over 18 years: A national cohort study in Denmark
Authors: Peter Bager, Gry Poulsen, Jan Wohlfahrt, Mads Melbye
Journal: Allergy (2024)

Abstract Background Because long‐term effectiveness of pollen allergen immune therapy (AIT) for allergic rhinitis (AR) is not well‐described, we studied effectiveness over 18 years in Denmark. Methods A register‐based cohort study using data on filled prescriptions, 1995–2016, Denmark. In a cohort of 1.1 million intranasal corticosteroid inhaler users (proxy for AR), we matched users treated with grass, birch or mugwort AIT 1:2 with non‐treated users on baseline year and 24 characteristics in the 3 years prior to baseline. The primary outcome was the odds ratio (OR) of using anti‐allergic nasal inhaler during the pollen season in the treated versus non‐treated group by years since baseline. Results Among 7760 AR patients treated with pollen AIT, the OR of using nasal inhaler 0–5 years after baseline was reduced when compared with 15,520 non‐treated AR individuals (0–2 years, OR 0.84 (0.81–0.88); 3–5 years, OR 0.88 (0.84–0.92)), but was close to unity or higher thereafter (6–9 years, OR 1.03 (0.97–1.08); 10–18 years, OR 1.18 (1.11–1.26)). In post hoc analyses, results were more consistent for those who already had 3 of 3 baseline years of use, and in patients using nasal inhaler in the latest pollen season (0–2 years, OR 0.76 (0.72–0.79); 3–5 years OR 0.86 (0.81–0.93); 6–9 years, OR 0.94 (0.87–1.02); 10–18 years, OR 0.94 (0.86–1.04)) as opposed to no such use. Conclusions Patients treated with pollen AIT in routine care to a higher degree stopped using anti‐allergic nasal inhaler 0–5 years after starting the standard 3 years of therapy, and not beyond 5 years. Post hoc analyses suggested effectiveness was more consistent among patients with persistent AR.
RNPS1 stabilizes NAT10 protein to facilitate translation in cancer via tRNA ac4C modification
Authors: Xiaochen Wang, Rongsong Ling, Yurong Peng, Weiqiong Qiu, Demeng Chen
Journal: International Journal of Oral Science (2024)

Abstract Existing studies have underscored the pivotal role of N-acetyltransferase 10 (NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma (HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1 (RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6 (ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac 4 C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel tRNA-ac 4 C modification sites, thereby providing a potent sequencing tool for tRNA-ac 4 C research. Our findings expand the repertoire of tRNA ac 4 C modifications and identify a role of tRNA ac 4 C in the regulation of mRNA translation in HNSCC.
Predicting plant–pollinator interactions: concepts, methods, and challenges
Authors: Guadalupe Peralta, Paul J. CaraDonna, Demetra Rakosy, Jochen Fründ, María P. Pascual Tudanca, Carsten F. Dormann, Laura A. Burkle, Christopher N. Kaiser-Bunbury, Tiffany M. Knight, Julian Resasco, Rachael Winfree, Nico Blüthgen, William J. Castillo, Diego P. Vázquez
Journal: Trends in Ecology & Evolution (2024)
WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling
Authors: Qingling Huang, Yi Xiao, Ting Lan, Youguang Lu, Li Huang, Dali Zheng
Journal: International Journal of Oral Science (2024)

Abstract Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
Sodium loading in ambulatory patients with heart failure with reduced ejection fraction: Mechanistic insights into sodium handling
Authors: Jeroen Dauw, Evelyne Meekers, Pieter Martens, Sébastien Deferm, Sebastiaan Dhont, Wouter Marchal, Liesbeth Mesotten, Matthias Dupont, Petra Nijst, W.H. Wilson Tang, Stefan P. Janssens, Wilfried Mullens
Journal: European Journal of Heart Failure (2024)
Role of Genetic Risk in the Association Between Screen Time and Child Development—Reply
Authors: Midori Yamamoto, Hidetoshi Mezawa, Kenichi Sakurai
Journal: JAMA Pediatrics (2024)

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Association of Glutamate Infusion With Risk of Acute Kidney Injury After Coronary Artery Bypass Surgery
Authors: Jonas Holm, Farkas Vanky, Rolf Svedjeholm
Journal: JAMA Network Open (2024)

Importance Acute kidney injury (AKI) after cardiac surgery is associated with increased morbidity and mortality, and measures to prevent AKI have had limited success. Glutamate has been reported to enhance natural postischemic recovery of the heart, but not among animals and humans with diabetes. Objective To summarize pooled results from the GLUTAMICS (Glutamate for Metabolic Intervention in Coronary Surgery) trials regarding the effect of glutamate on postoperative AKI among patients without diabetes undergoing coronary artery bypass graft (CABG) surgery. Design, Setting, and Participants Data on a total of 791 patients without diabetes from 2 prospective, randomized, double-blind multicenter trials performed at 5 cardiac surgery centers in Sweden between October 4, 2005, and November 12, 2009, and between November 15, 2015, and September 30, 2020, were pooled. Patients had acute coronary syndrome, left ventricular ejection fraction of 0.30 or less, or a European System for Cardiac Risk Evaluation II score of 3.0 or more and underwent CABG with or without additional valve procedure. Statistical analysis was performed from May to November 2023. Interventions Intravenous infusion of 0.125-M l -glutamic acid or saline at 1.65 mL/kg/h for 2 hours during reperfusion, after which the infusion rate was halved and an additional 50 mL was given. Main Outcomes and Measures The primary end point was AKI, defined as postoperative increase of plasma creatinine of 50% or more, corresponding to the Risk stage or higher in the Risk, Injury, Failure, Loss, and End-Stage kidney disease (RIFLE) criteria. Results A total of 791 patients without diabetes (391 who received glutamate [mean (SD) age, 69.3 (9.1) years; 62 women (15.9%)] and 400 controls [mean (SD) age, 69.6 (9.5) years; 73 women (18.3%)]) were randomized. Baseline data did not differ between groups. Glutamate was associated with a significantly lower risk of AKI (relative risk, 0.49 [95% CI, 0.29-0.83]). Dialysis was required for 2 patients in the glutamate group and 5 patients in the control group. In multivariable analysis, glutamate remained significantly associated with a protective effect against AKI (odds ratio, 0.47 [95% CI, 0.26-0.86]). In the glutamate and control groups, the rate of postoperative mortality at 30 days or less was 0.5% (2 of 391) vs 1.0% (4 of 400), and the rate of stroke at 24 hours or less was 0.8% (3 of 391) vs 1.8% (7 of 400). Conclusions and Relevance In this pooled analysis of 2 randomized clinical trials, infusion of glutamate was associated with a markedly lower risk of AKI after CABG among patients without diabetes. The findings are exploratory and need to be confirmed in prospective trials. Trial Registration ClinicalTrials.gov Identifiers: NCT00489827 and NCT02592824
Enhanced gene transfection and induction of apoptosis in melanoma cells by branched poly(β-amino ester)s with uniformly distributed branching units
Authors: Zhaowei Chu, Zhili Li, Haiyang Yong, Delu Che, Bingjie Li, Cong Yan, Tong Zhou, Xi Wang, Yuqing Feng, Kun Guo, Songmei Geng
Journal: Journal of Controlled Release (2024)
Development and validation of an individualized and weighted Myeloma Prognostic Score System (<scp>MPSS</scp>) in patients with newly diagnosed multiple myeloma
Authors: Xuehan Mao, Wenqiang Yan, David Mery, Jiahui Liu, Huishou Fan, Jingyu Xu, Yan Xu, Weiwei Sui, Shuhui Deng, Dehui Zou, Chenxing Du, Shuhua Yi, Frits van Rhee, Bart Barlogie, John D. Shaughnessy, Kenneth C. Anderson, Fenghuang Zhan, Lugui Qiu, Gang An
Journal: American Journal of Hematology (2024)

Abstract Current standard predictive models of disease risk do not adequately account for the heterogeneity of survival outcomes in patients with new‐diagnosed multiple myeloma (NDMM). In this retrospective, multicohort study, we collected clinical and genetic data from 1792 NDMM patients and identified the prognostic impact of all features. Using the top‐ranked predictive features, a weighted Myeloma Prognostic Score System (MPSS) risk model was formulated and validated to predict overall survival (OS). In the training cohort, elevated lactate dehydrogenase level (LDH), International Staging System (ISS) Stage III, thrombocytopenia, and cumulative high‐risk cytogenetic aberration (HRA) numbers were found to have independent prognostic significance. Each risk factor was defined as its weighted value respectively according to their hazard ratio for OS (thrombocytopenia 2, elevated LDH 1, ISS III 2, one HRA 1, and ≥2 HRA 2, points). Patients were further stratified into four risk groups: MPSS I (22.5%, 0 points), II (17.6%, 1 points), III (38.6%, 2–3 points), and IV (21.3%, 4–7 points). MPSS risk stratification showed optimal discrimination, as well as calibration, of four risk groups with median OS of 91.0, 69.8, 45.0, and 28.0 months, for patients in MPSS I to IV groups ( p &lt; .001), respectively. Importantly, the MPSS model retained its prognostic value in the internal validation cohort and an independent external validation cohort, and exhibited significant risk distribution compared with conventional prognostic models (R‐ISS, R2‐ISS, and MASS). Utilization of the MPSS model in clinical practice could improve risk estimation in NDMM patients, thus prompting individualized treatment strategies.
Invasive cervical cancer incidence following bivalent human papillomavirus vaccination: a population-based observational study of age at immunization, dose, and deprivation
Authors: Tim J Palmer, Kimberley Kavanagh, Kate Cuschieri, Ross Cameron, Catriona Graham, Allan Wilson, Kirsty Roy
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background High-risk human papillomavirus causes cervical cancer. Vaccines have been developed that significantly reduce the incidence of preinvasive and invasive disease. This population-based observational study used linked screening, immunization, and cancer registry data from Scotland to assess the influence of age, number of doses, and deprivation on the incidence of invasive disease following administration of the bivalent vaccine. Methods Data for women born between January 1, 1988, and June 5, 1996, were extracted from the Scottish cervical cancer screening system in July 2020 and linked to cancer registry, immunization, and deprivation data. Incidence of invasive cervical cancer per 100 000 person-years and vaccine effectiveness were correlated with vaccination status, age at vaccination, and deprivation; Kaplan Meier curves were calculated. Results No cases of invasive cancer were recorded in women immunized at 12 or 13 years of age irrespective of the number of doses. Women vaccinated at 14 to 22 years of age and given 3 doses of the bivalent vaccine showed a significant reduction in incidence compared with all unvaccinated women (3.2/100 000 [95% confidence interval (CI) = 2.1 to 4.6] vs 8.4 [95% CI = 7.2 to 9.6]). Unadjusted incidence was significantly higher in women from most deprived (Scottish Index of Multiple Deprivation 1) than least deprived (Scottish Index of Multiple Deprivation 5) areas (10.1/100 000 [95% CI = 7.8 to 12.8] vs 3.9 [95% CI = 2.6 to 5.7]). Women from the most deprived areas showed a significant reduction in incidence following 3 doses of vaccine (13.1/100 000 [95% CI = 9.95 to 16.9] vs 2.29 [95% CI = 0.62 to 5.86]). Conclusion Our findings confirm that the bivalent vaccine prevents the development of invasive cervical cancer and that even 1 or 2 doses 1 month apart confer benefit if given at 12-13 years of age. At older ages, 3 doses are required for statistically significant vaccine effectiveness. Women from more deprived areas benefit more from vaccination than those from less deprived areas.