bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sacubitril/valsartan compared to ramipril in high‐risk post‐myocardial infarction patients stratified according to use of mineralocorticoid receptor antagonists: Insight from the PARADISE MI trial
Authors: Schou Morten , Claggett Brian , Miao Zi Michael , Fernandez Alberto , Filippatos Gerasimos , Granger Christopher , Jering Karola , Maggioni Aldo P. , McCausland Finnian , Villota Julio Nuñez , Rouleau Jean‐Lucien , Mody Freny Vaghaiwalla , van der Meer Peter , Vinereanu Dragos , McGrath Martina , Zhou Yinong , Mann Douglas L. , Solomon Scott D. , Steg Philippe Gabriel , Braunwald Eugene , McMurray John J.V. , Pfeffer Marc A. , Køber Lars 
Published: November 2023

AbstractAimIt is unknown whether safety and clinical endpoints by use of sacubitril/valsartan (an angiotensin receptor–neprilysin inhibitor [ARNI]) are affected by mineralocorticoid receptor antagonists (MRA) in high‐risk myocardial infarction (MI) patients. The aim of this study was to examine whether MRA modifies safety and clinical endpoints by use of sacubitril/valsartan in patients with a MI and left ventricular systolic dysfunction (LVSD) and/or pulmonary congestion.Methods and resultsPatients (n = 5661) included in the PARADISE MI trial (Prospective ARNI vs. ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI) were stratified according to MRA. Primary outcomes in this substudy were worsening heart failure or cardiovascular death. Safety was defined as symptomatic hypotension, hyperkalaemia >5.5 mmol/L, or permanent drug discontinuation. A total of 2338 patients (41%) were treated with MRA. Safety of ARNI compared to ramipril was not altered significantly by ± MRA, and both groups had similar increase in symptomatic hypotension with ARNI. In patients taking MRA, the risk of hyperkalaemia or permanent drug discontinuation was not significantly altered by ARNI (p > 0.05 for all comparisons). The effect of ARNI compared with ramipril was similar in those who were and were not taking MRA (hazard ratio [HR]MRA 0.96, 95% confidence interval [CI] 0.77–1.19 and HRMRA– 0.87, 95% CI 0.71–1.05, for the primary endpoint; p = 0.51 for interaction [Clinical Endpoint Committee adjudicated]); similar findings were observed if investigator‐reported endpoints were evaluated (p = 0.61 for interaction).ConclusionsUse of a MRA did not modify safety or clinical endpoints related to initiation of ARNI compared to ramipril in the post‐MI setting in patients with LVSD and/or congestion.
Anticonvulsant effect of equilibrative nucleoside transporters 1 inhibitor in a mouse model of Dravet syndrome
Authors: Ho Shih‐Yin , Chen I‐Chun , Tsai Che‐Wen , Chang Kai‐Chieh , Lin Chun‐Jung , Chern Yijuang , Liou Horng‐Huei 
Published: November 2023

AbstractThere are limited therapeutic options for patients with Dravet syndrome (DS). The equilibrative nucleoside transporters 1 (ENT1) mediate both the influx and efflux of adenosine across the cell membrane exerted beneficial effects in the treatment of epilepsy. This study aimed to evaluate the anticonvulsant effect of the ENT1 inhibitor in an animal model of DS (Scn1aE1099X/+ mice). J7 (5 mg/kg) treatment was efficacious in elevating seizure threshold in Scn1aE1099X/+ mice after hyperthermia exposure. Moreover, the J7 treatment significantly reduced the frequency of spontaneous excitatory post‐synaptic currents (sEPSCs, ~35% reduction) without affecting the amplitude in dentate gyrus (DG) granule cells. Pretreatment with the adenosine A1 receptor (A1R) antagonist, DPCPX, abolished the J7 effects on sEPSCs. These observations suggest that the J7 shows an anticonvulsant effect in hyperthermia‐induced seizures in Scn1aE1099X/+ mice. This effect possibly acts on presynaptic A1R‐mediated signaling modulation in granule cells.
Healthy kids vids: Development and acceptability of narrative healthy lifestyle videos and text messages for parents of young children from socioeconomically disadvantaged populations
Authors: Hammersley Megan L. , Norman Jennifer , Smithers Lisa G. , Furber Susan , Plumb Melinda , Jones Rachel A. 
Published: November 2023

AbstractIssue AddressedDietary intake and physical activity behaviours of many Australian children are not meeting recommendations, particularly for those living in socioeconomically disadvantaged circumstances. This study aimed to design and assess the feasibility and acceptability of a suite of narrative videos and text messages focused on healthy eating and physical activity behaviours appropriate for parents of young children from socioeconomically disadvantaged backgrounds.MethodsParents of 1–5‐year‐old children (n = 6) were recruited to develop a suite of 12 narrative videos on healthy eating and physical activity behaviours, underpinned by theory. Twelve complementary text messages were subsequently developed. A different group of parents (n = 16) recruited from socioeconomically disadvantaged areas reviewed the videos and text messages over 6 weeks and provided feedback via surveys and qualitative interviews (n = 13).ResultsThere was a high level of engagement with and acceptability of the videos and text message content. Participants found the videos easy to access and they liked the narrative style. Screen time videos and text messages relating to screen time, play and physical activity, role modelling and fussy eating were most useful.ConclusionsNarrative style healthy eating, physical activity and screen time videos and complementary text messages were highly acceptable to the sample of parents of 1–5‐year‐old children from socioeconomically disadvantaged areas recruited from the Illawarra Shoalhaven region of NSW, Australia.So What?Short narrative style videos and text messages are an easy to process and acceptable method of delivering healthy lifestyle promotion content to parents.
Identification of a novel cuproptosis‐related gene signature for multiple myeloma diagnosis
Authors: Zhu Yidong , Chang Shuaikang , Liu Jun , Wang Bo 
Published: November 2023

AbstractBackgroundMultiple myeloma (MM) ranks second among the most prevalent hematological malignancies. Recent studies have unearthed the promise of cuproptosis as a novel therapeutic intervention for cancer. However, no research has unveiled the particular roles of cuproptosis‐related genes (CRGs) in the prediction of MM diagnosis.MethodsMicroarray data and clinical characteristics of MM patients were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed gene analysis, least absolute shrinkage and selection operator (LASSO) and support vector machine‐recursive feature elimination (SVM‐RFE) algorithms were applied to identify potential signature genes for MM diagnosis. Predictive performance was further assessed by receiver operating characteristic (ROC) curves, nomogram analysis, and external data sets. Functional enrichment analysis was performed to elucidate the involved mechanisms. Finally, the expression of the identified genes was validated by quantitative real‐time polymerase chain reaction (qRT‐PCR) in MM cell samples.ResultsThe optimal gene signature was identified using LASSO and SVM‐RFE algorithms based on the differentially expressed CRGs: ATP7A, FDX1, PDHA1, PDHB, MTF1, CDKN2A, and DLST. Our gene signature‐based nomogram revealed a high degree of accuracy in predicting MM diagnosis. ROC curves showed the signature had dependable predictive ability across all data sets, with area under the curve values exceeding 0.80. Additionally, functional enrichment analysis suggested significant associations between the signature genes and immune‐related pathways. The expression of the genes was validated in MM cells, indicating the robustness of these findings.ConclusionWe discovered and validated a novel CRG signature with strong predictive capability for diagnosing MM, potentially implicated in MM pathogenesis and progression through immune‐related pathways.
Crosslinking chitosan with glucose via the modified Maillard reaction promotes the osteoinduction of mouse MC3T3‐E1 pre‐osteoblasts
Authors: Huang Kuo‐Chin , Lee Ding‐Yu , Chuang Po‐Yao , Yang Tien‐Yu , Su Yu‐Ping , Chang Shun‐Fu 
Published: November 2023

AbstractBone defects are a common clinical issue, but therapeutic efficiency can be challenging in cases of more considerable traumas or elderly patients with degenerated physiological metabolism. To address this issue, a more suitable cell‐biomaterial construct promoting bone regeneration has been extensively investigated, with the chitosan scaffold being considered a potential candidate. In this study, chitosan was crosslinked with different doses of glucose (CTS‐10~50%Glc) using a modified Maillard reaction condition to develop a more appropriate cell‐biomaterial construct. Mouse MC3T3‐E1 pre‐osteoblasts were seeded onto the scaffolds to examine their osteoinductive capability. The results showed that CTS‐Glc scaffolds with higher glucose contents effectively improved the adhesion and survival of mouse MC3T3‐E1 pre‐osteoblasts and promoted their differentiation and mineralization. It was further demonstrated that the membrane integrin α5 subunit of pre‐osteoblasts is the primary adhesion molecule that communicates with CTS‐Glc scaffolds. After that, Akt signaling was activated, and then bone morphogenetic protein 4 was secreted to initiate the osteoinduction of pre‐osteoblasts. The prepared CTS‐Glc scaffold, with enhanced osteoinduction capability and detailed mechanism elucidations, offers a promising candidate material for advancing bone tissue engineering and clinical regenerative medicine. As a result, this study presents a potential tool for future clinical treatment of bone defects.
Predicting the effects of mutations on protein solubility using graph convolution network and protein language model representation
Authors: Wang Jing , Chen Sheng , Yuan Qianmu , Chen Jianwen , Li Danping , Wang Lei , Yang Yuedong 
Published: November 2023

AbstractSolubility is one of the most important properties of protein. Protein solubility can be greatly changed by single amino acid mutations and the reduced protein solubility could lead to diseases. Since experimental methods to determine solubility are time‐consuming and expensive, in‐silico methods have been developed to predict the protein solubility changes caused by mutations mostly through protein evolution information. However, these methods are slow since it takes long time to obtain evolution information through multiple sequence alignment. In addition, these methods are of low performance because they do not fully utilize protein 3D structures due to a lack of experimental structures for most proteins. Here, we proposed a sequence‐based method DeepMutSol to predict solubility change from residual mutations based on the Graph Convolutional Neural Network (GCN), where the protein graph was initiated according to predicted protein structure from Alphafold2, and the nodes (residues) were represented by protein language embeddings. To circumvent the small data of solubility changes, we further pretrained the model over absolute protein solubility. DeepMutSol was shown to outperform state‐of‐the‐art methods in benchmark tests. In addition, we applied the method to clinically relevant genes from the ClinVar database and the predicted solubility changes were shown able to separate pathogenic mutations. All of the data sets and the source code are available at https://github.com/biomed-AI/DeepMutSol.
Impact of a hospital service for adults with chronic childhood‐onset disease: A propensity weighted analysis
Authors: Feeney Colby , Chandler Mark , Platt Alyssa , Sun Shifeng , Setji Noppon , Ming David Y. 
Published: November 2023

AbstractBackgroundYoung adults with chronic childhood‐onset diseases (CCOD) transitioning care from pediatrics to adult care are at high risk for readmission after hospital discharge. At our institution, we have implemented an inpatient service, the Med‐Peds (MP) line, to improve transitions to adult care and reduce hospital utilization by young adults with CCOD.ObjectiveThis study aimed to assess the effect of the MP line on length of stay (LOS) and 30‐day readmission rates compared to other inpatient services.MethodsThis was an observational, retrospective cohort analysis of patients admitted to the MP line compared to other hospital service lines over a 2‐year period. To avoid potential confounding by indication for admission to the MP line, propensity score weighting methods were used.ResultsThe MP line cared for 302 patients with CCOD from June 2019 to July 2021. Compared to other service lines, there was a 33% reduction in relative risk of 30‐day readmission (26.9% compared to 40.3%, risk ratio = 0.67, 95% confidence interval [CI] 0.55–0.81). LOS was 10% longer for the MP line (event time ratio (ETR): 1.10 95% CI 1.0–1.21) with median LOS 4.8 versus 4.5 days. Patients with sickle cell disease had less of a reduction in 30‐day readmissions and longer LOS.ConclusionHospitalization for young adults with CCOD on a MP service line was associated with lower 30‐day readmission rates and longer LOS than hospitalization on other services. Further research is needed to assess which components of the line most contribute to decreased utilization.
Metabolic characterization of neurogenetic disorders involving glutamatergic neurotransmission
Authors: Illescas Sofía , Diaz‐Osorio Yaiza , Serradell Anna , Toro‐Soria Lucía , Musokhranova Uliana , Juliá‐Palacios Natalia , Ribeiro‐Constante Juliana , Altafaj Xavier , Olivella Mireia , O'Callaghan Mar , Darling Alejandra , Armstrong Judith , Artuch Rafael , García‐Cazorla Àngels , Oyarzábal Alfonso 
Published: November 2023

AbstractThe study of inborn errors of neurotransmission has been mostly focused on monoamine disorders, GABAergic and glycinergic defects. The study of the glutamatergic synapse using the same approach than classic neurotransmitter disorders is challenging due to the lack of biomarkers in the CSF. A metabolomic approach can provide both insight into their molecular basis and outline novel therapeutic alternatives. We have performed a semi‐targeted metabolomic analysis on CSF samples from 25 patients with neurogenetic disorders with an important expression in the glutamatergic synapse and 5 controls. Samples from patients diagnosed with MCP2, CDKL5‐, GRINpathies and STXBP1‐related encephalopathies were included. We have performed univariate (UVA) and multivariate statistical analysis (MVA), using Wilcoxon rank‐sum test, principal component analysis (PCA), and OPLS‐DA. By using the results of both analyses, we have identified the metabolites that were significantly altered and that were important in clustering the respective groups. On these, we performed pathway‐ and network‐based analyses to define which metabolic pathways were possibly altered in each pathology. We have observed alterations in the tryptophan and branched‐chain amino acid metabolism pathways, which interestingly converge on LAT1 transporter‐dependency to cross the blood–brain barrier (BBB). Analysis of the expression of LAT1 transporter in brain samples from a mouse model of Rett syndrome (MECP2) revealed a decrease in the transporter expression, that was already noticeable at pre‐symptomatic stages. The study of the glutamatergic synapse from this perspective advances the understanding of their pathophysiology, shining light on an understudied feature as is their metabolic signature.
Acute gastroenteritis outbreak associated with multiple and rare norovirus genotypes after storm events in Santa Catarina, Brazil
Authors: Fumian Tulio Machado , Malta Fábio Correia , Sarmento Sylvia Kahwage , Fernandes Sandra Bianchini , Negri Cynthia Maria , Belettini Senele Ana de Alcantara , Machado Mariza Hoffmann , Guimarães Maria Angelica Arpon Marandino , de Assis Rosane Maria Santos , Baduy Gabriel Assad , Fialho Alexandre Madi , Burlandy Fernanda Marcicano 
Published: November 2023

AbstractNorovirus is a major cause of acute diarrheal disease (ADD) outbreaks worldwide. In the present study, we investigated an ADD outbreak caused by norovirus in several municipalities of Santa Catarina state during the summer season, southern Brazil in 2023. As of the 10th epidemiological week of 2023, approximately 87 000 ADD cases were reported, with the capital, Florianópolis, recording the highest number of cases throughout the weeks. By using RT‐qPCR and sequencing, we detected 10 different genotypes, from both genogroups (G) I and II. Some rare genotypes were also identified. Additionally, rotavirus and human adenovirus were sporadically detected among the ADD cases. Several features of the outbreak suggest that sewage‐contaminated water could played a role in the surge of ADD cases. Storm events in Santa Catarina state that preceded the outbreak likely increased the discharge of contaminated wastewater and stormwater into water bodies, such as rivers and beaches during a high touristic season in the state. Climate change‐induced extreme weather events, including intensified rainfall and frequent floods, can disturb healthcare and sanitation systems. Implementing public policies for effective sanitation, particularly during peak times, is crucial to maintain environmental equilibrium and counter marine pollution.
An event‐driven model of fractional‐N CPPLLbasedFMCWsynthesizers
Authors: Li Hao , Mawuli Ernest Smith , Xing Zhao , Liu Huihua , Wu Yunqiu , Zhao Chenxi , Yu Yiming , Zhang Jingzhi , Kang Kai 
Published: November 2023

AbstractThis paper proposes an improved event‐driven (ED) model to improve the simulation efficiency of a mixed‐signal charge‐pump phase locked loop (CP‐PLL) design for a frequency‐modulated continuous‐wave (FMCW) chirp generation. The improvement mainly comes into three parts. First, we update the data only when it changes during the previous trigger. Second, we save the data at the triggering moment of the reference clock to achieve uniform sampling for better noise characterization. Furthermore, we propose a simplified model that is specifically optimized for the third‐order loop filter (LF). This article presents a detailed design flow of the improved ED model, and we apply it to the simulation of the FMCW chirp generation. Compared to the conventional transistor‐level simulation, our proposed model reduces the simulation time to less than 1 s, which leads to a reduction of the simulation time by five or six orders of magnitude.
Association between dietary total choline and abdominal aorta calcification among older US adults: A cross‐sectional study of the National Health and Nutrition Examination Survey
Authors: Zhang Kai , Han Yu , Gu Fangmin , Gu Zhaoxuan , Zhao JiaYu , Chen Jianguo , Chen Bowen , Gao Min , Hou Zhengyan , Yu Xiaoqi , Cai Tianyi , Gao Yafang , Xie Jinyu , Liu Tianzhou , Liu Kexiang 
Published: November 2023

AbstractBackgroundNumerous studies indicate a potential bidirectional association between dietary choline intake and its derivative, betaine, and subclinical atherosclerosis. However, little research has been conducted on the relationship between dietary choline and severe abdominal aortic calcification (SAAC).MethodsThis cross‐sectional study analyzed population‐based data from the National Health and Nutrition Examination Survey (2013–2014). Choline intake and food sources were measured using two 24‐h dietary‐recall interviews. The abdominal aortic calcification score was measured using a dual‐emission x‐ray absorptiometry scan. To assess the relationship between choline intake and SAAC, the study utilized restricted cubic spline and a multivariable logistic regression model.ResultsAmong the 2640 individuals included in the study, 10.9% had SAAC. After adjusting for all selected covariates, compared with the lowest quartile of dietary choline, the odds ratios of SAAC for the second‐quartile, third‐quartile, and fourth‐quartile dietary choline intake were 0.63 (95% confidence interval [CI], 0.43–0.93), 0.63 (95% CI, 0.42–0.94), and 0.77 (95% CI, 0.5–1.16), respectively. The study found an L‐shaped relationship between dietary choline and SAAC in the dose‐response analysis. Subgroup analyses did not demonstrate any statistically significant interaction effects for any subgroup.ConclusionThe study found that a higher intake of dietary choline is associated with a lower prevalence of SAAC. The dose‐response analysis revealed an L‐shaped relationship between dietary choline and SAAC. However, further studies are warranted to investigate the direct role of choline in the development of SAAC.
Extracellular adenosine triphosphate regulates inflammatory responses of periodontal ligament cells
Authors: Kyawsoewin Maythwe , Manokawinchoke Jeeranan , Termkwanchareon Chutimon , Egusa Hiroshi , Osathanon Thanaphum , Limraksasin Phoonsuk 
Published: November 2023

AbstractBackgroundVarious stimuli, that is, mechanical stresses or inflammation, induce the release of adenosine triphosphate (ATP) by human periodontal ligament cells (HPDLCs). Extracellular adenosine triphosphate (eATP) affects HPDLCs’ functions such as immunosuppressive action and inflammatory responses. Lipopolysaccharide (LPS) is the key factor involved in periodontal inflammation. However, the possible correlation and detailed mechanism of inflammation‐mediated eATP by LPS and inflammatory cascade formation in HPDLCs is unclarified. This study aims to examine the role of eATP on the HPDLCs’ responses concerning inflammatory actions after LPS treatment.MethodsHPDLCs were stimulated with Porphyromonas gingivalis LPS and polyinosinic:polycytidylic acid (poly I:C). The amount of ATP release was measured at different time points using a bioluminescence assay. HPDLCs were treated with eATP. The expression of pro‐inflammatory and anti‐inflammatory genes was determined. Specific P2X purinoreceptor 7 (P2X7) inhibitors (brilliant blue G [BBG] and KN62), a specific P2Y purinoreceptor 1 (P2Y1) inhibitors (MRS2179), calcium chelator (EGTA), protein kinase C (PKC) inhibitors, nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF𝜅B) activation inhibitors, and cyclic adenosine monophosphate (cAMP)‐dependent protein kinase A (PKA) inhibitors (H89 dihydrochloride) and activators (forskolin) were used to dissect the mechanism of eATP‐induced HPDLCs’ inflammatory responses.ResultsLPS and poly I:C induced ATP release. A low concentration of eATP (50 µM) increased pro‐inflammatory genes (COX2, IL1B, IL6, IL8, IL12, and TNFA), while a high concentration (500 µM) enhanced anti‐inflammatory genes (IL4 and IL10). BBG, KN62, and NF𝜅B activation inhibitors impeded eATP‐induced pro‐inflammatory genes. MRS2179 and H89 markedly suppressed eATP‐induced anti‐inflammatory genes. Forskolin induced IL4 and IL10.ConclusionHPDLCs respond to LPS by releasing ATP. eATP has dose‐dependent dual functions on HPDLCs’ inflammatory responses via different pathways. As regulation of inflammation is important in regeneration, eATP may help to limit inflammation and trigger periodontal regeneration.