bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic effect of lipoprotein(a) and high-sensitivity C-reactive protein on the risk of all-cause and cardiovascular death in patients with acute myocardial infarction: a large prospective cohort study
Authors: Wang Zhenwei , Tang Junnan , Shi Qian , Fang Lijuan , Liu Naifeng , Zhang Jinying 
Published: May 2024

ObjectiveAlthough lipoprotein(a) [Lp(a)] and high-sensitivity C-reactive protein (Hs-CRP) are closely associated with the mortality of acute myocardial infarction (AMI), their synergistic effect on the risk of death remains unknown. Therefore, this study aimed to explore the combined effect of Lp(a) and Hs-CRP on the incidence of all-cause and cardiovascular death in AMI patients.MethodsA comprehensive cohort study enrolled 912 AMI patients, categorizing them into four groups based on Lp(a) and Hs-CRP levels: Group 1 [Lp(a) &lt; 30 mg/dL &amp; Hs-CRP &lt; 2 mg/L], Group 2 [Lp(a) &lt; 30 mg/dL &amp; Hs-CRP ≥ 2 mg/L], Group 3 [Lp(a) ≥ 30 mg/dL &amp; Hs-CRP &lt; 2 mg/L], and Group 4 [Lp(a) ≥ 30 mg/dL &amp; Hs-CRP ≥ 2 mg/L]. Cox regression analysis, Kaplan-Meier survival analysis and sensitivity analysis were employed to determine the combined effects of Lp(a) and Hs-CRP on the risk of all-cause and cardiovascular death.ResultsOver a median observation period of 38.98 months, 217 patients passed away, with 137 deaths attributed to cardiovascular causes. The multivariate Cox regression analysis revealed that in the comprehensively adjusted Model 3, only Lp(a) and the combination of Lp(a) and Hs-CRP exhibited a strong association with cardiovascular death risk. Specifically, for Lp(a) levels ≥ 30 mg/dL compared to &lt; 30 mg/dL, the hazard ratio (HR) was 2.434 with a 95% confidence interval (CI) of 1.653–3.583 (P &lt; 0.001); for log10(Lp(a)), the HR was 2.630 with a 95% CI of 1.530–4.523 (P &lt; 0.001); for Group 4 versus Group 1, the HR was 2.346 with a 95% CI of 1.054–5.220 (P = 0.037); and for Group 4 versus Groups 1 + 2 + 3, the HR was 1.878 with a 95% CI of 1.284–2.748 (P = 0.001). Sensitivity analysis indicated that the synergy between Lp(a) and Hs-CRP continued to be independently associated with the risk of cardiovascular death. For Group 3 versus Group 1, the HR was 3.353 with a 95% CI of 1.133–9.917 (P = 0.029); for Group 4 versus Group 1, the HR was 3.710 with a 95% CI of 1.466–9.392 (P = 0.006); and for Group 4 versus Groups 1 + 2 + 3, the HR was 2.433 with a 95% CI of 1.620–3.656 (P &lt; 0.001).ConclusionsCompared to elevated levels of either Lp(a) or Hs-CRP alone, the concurrent high levels of both significantly increased the risk of cardiovascular death in patients with AMI, underscoring the importance of considering their combined effects in the prognostic management of AMI patients.
Application of whole exome sequencing in the diagnosis of muscular disorders: a study of Taiwanese pediatric patients
Authors: Lee Chung-Lin , Chuang Chih-Kuang , Chiu Huei-Ching , Chang Ya-Hui , Tu Yuan-Rong , Lo Yun-Ting , Lin Hsiang-Yu , Lin Shuan-Pei 
Published: May 2024

BackgroundMuscular dystrophies and congenital myopathies encompass various inherited muscular disorders that present diagnostic challenges due to clinical complexity and genetic heterogeneity.MethodsThis study aimed to investigate the use of whole exome sequencing (WES) in diagnosing muscular disorders in pediatric patients in Taiwan. Out of 161 pediatric patients suspected to have genetic/inherited myopathies, 115 received a molecular diagnosis through conventional tests, single gene testing, and gene panels. The remaining 46 patients were divided into three groups: Group 1 (multiplex ligation-dependent probe amplification–negative Duchenne muscular dystrophy) with three patients (6.5%), Group 2 (various forms of muscular dystrophies) with 21 patients (45.7%), and Group 3 (congenital myopathies) with 22 patients (47.8%).ResultsWES analysis of these groups found pathogenic variants in 100.0% (3/3), 57.1% (12/21), and 68.2% (15/22) of patients in Groups 1 to 3, respectively. WES had a diagnostic yield of 65.2% (30 patients out of 46), detecting 30 pathogenic or potentially pathogenic variants across 28 genes.ConclusionWES enables the diagnosis of rare diseases with symptoms and characteristics similar to congenital myopathies and muscular dystrophies, such as muscle weakness. Consequently, this approach facilitates targeted therapy implementation and appropriate genetic counseling.
Pathogenic role of different phenotypes of immune cells in airway allergic diseases: a study based on Mendelian randomization
Authors: Xu Zhihan , Li Ren , Wang Leigang , Wu Yisha , Tian Yuhe , Su Yilin , Ma Yuqiang , Li Ruiying , Wei Yao , Zhang Chen , Han Shikai , Duan Siyu , Peng Haiyi , Xue Jinmei 
Published: May 2024

BackgroundAirway allergic disease (AAD) is a class of autoimmune diseases with predominantly Th2-type inflammation, mainly including allergic rhinitis (AR), allergic asthma (AS), and chronic sinusitis (CRS). There are very complex regulatory mechanisms between immune cells and AAD; however, previous reports found that the functions of the same immune cells in AAD are not identical.ObjectiveThe aim of this study was to explore the causal relationship between different phenotypic immune cells and their association with AAD.MethodUtilizing the publicly available Genome-Wide Association Studies (GWAS) database, this study conducted a bidirectional Mendelian randomization (MR) to assess the causal relationship between immune cells of 731 different immunophenotypes and AAD. The primary assessment methods included inverse variance weighting, weighted median, and MR Egger. Additionally, sensitivity analyses such as MR-PRESSO, leave-one-out, and scatter plots were employed to eliminate the interference of heterogeneity and pleiotropy, ensuring the stability of the causal inference.ResultA total of 38 immune cells with different immunophenotypes were found to be positively and causally associated with AR, of which 26 were protective factors and 12 were risk factors. Positive associations were found between 33 immune cells and AS, of which 14 were protective factors and 19 were risk factors, as well as between 39 immune cells and CRS, of which 22 were protective factors and 17 were risk factors. Finally, the results of all relevant immune cells for the three diseases were taken and intersected, and it was found that CD3 on CD39+-activated Treg (IVWAR = 0.001, IVWCRS = 0.043, IVWAS = 0.027) may be the key immune cell that inhibits the development of AAD (ORAR = 0.940, ORAS = 0.967, ORCRS = 0.976).ConclusionThis study reveals that different immune phenotypes of immune cells are closely related to AAD at the genetic level, which provides a theoretical basis for future clinical studies.
Motivational strategies used by health care professionals in stroke survivors in rehabilitation: a scoping review of experimental studies
Authors: Fernandes Júlio Belo , Fernandes Sónia , Domingos Josefa , Castro Cidália , Romão Ana , Graúdo Susana , Rosa Gonçalo , Franco Tânia , Ferreira Ana Patrícia , Chambino Claudine , Ferreira Bruno , Courela Susana , Ferreira Maria José , Silva Isabel , Tiago Vera , Morais Maria João , Casal Joana , Pereira Silvia , Godinho Catarina 
Published: May 2024

IntroductionCognitive and motor impairments are common among stroke survivors. Physical therapy is often used to improve the functional capacity of stroke survivors. However, limited adherence to rehabilitation programs is a challenge. Motivation plays a crucial role in the success of rehabilitation programs as it influences individual adherence to treatment and overall health outcomes. This review aims to identify current trends in motivational strategies used by healthcare professionals for stroke survivor rehabilitation.MethodsFollowing the framework developed by Arksey and O’Malley, a scoping review was conducted. We performed a literature search using MEDLINE, CINAHL, the Cochrane Central Register of Controlled Trials, Nursing &amp; Allied Health, and MedicLatina databases.ResultsA total of 906 papers were identified. After selecting and analyzing the articles, 17 papers were included in this review. Health professionals use various strategies to motivate stroke survivors. These approaches include establishing a therapeutic alliance, improving patients’ health literacy, defining realistic goals, fostering problem-solving skills, personalizing the rehabilitation program, showcasing success stories, utilizing persuasive techniques, offering encouragement and compliments, providing emotional support, and effectively managing symptoms.ConclusionThe knowledge gathered in this review can guide healthcare professionals in helping patients overcome barriers to rehabilitation, improve their motivation, and ultimately enhance their recovery outcomes.
Effect of folA gene in human breast milk-derived Limosilactobacillus reuteri on its folate biosynthesis
Authors: Jiang Yu , Li Xianping , Zhang Wei , Ji Yadong , Yang Kai , Liu Lu , Zhang Minghui , Qiao Weicang , Zhao Junying , Du Mengjing , Fan Xiaofei , Dang Xingfen , Chen Huo , Jiang Tiemin , Chen Lijun 
Published: May 2024

IntroductionFolate supplementation is crucial for the human body, and the chemically synthesized folic acid might have undesirable side effects. The use of molecular breeding methods to modify the genes related to the biosynthesis of folate by probiotics to increase folate production is currently a focus of research.MethodsIn this study, the folate-producing strain of Limosilactobacillus reuteri B1-28 was isolated from human breast milk, and the difference between B1-28 and folA gene deletion strain ΔFolA was investigated by phenotyping, in vitro probiotic evaluation, metabolism and transcriptome analysis.ResultsThe results showed that the folate producted by the ΔFolA was 2–3 folds that of the B1-28. Scanning electron microscope showed that ΔFolA had rougher surface, and the acid-producing capacity (p = 0.0008) and adhesion properties (p = 0.0096) were significantly enhanced than B1-28. Transcriptomic analysis revealed that differentially expressed genes were mainly involved in three pathways, among which the biosynthesis of ribosome and aminoacyl-tRNA occurred in the key metabolic pathways. Metabolomics analysis showed that folA affected 5 metabolic pathways, involving 89 different metabolites.DiscussionIn conclusion, the editing of a key gene of folA in folate biosynthesis pathway provides a feasible pathway to improve folate biosynthesis in breast milk-derived probiotics.
Pineal gland volume loss in females with multiple sclerosis
Authors: Vuković Miloš , Nosek Igor , Boban Jasmina , Kozić Duško 
Published: May 2024

IntroductionMultiple sclerosis has a complex pathophysiology, and numerous risk factors can contribute to its development, like exposure to sunlight that is associated with serum levels of melatonin. The aim of this study was to determine whether the volume of the pineal gland, assessed by magnetic resonance imaging (MRI), correlated with the presence of multiple sclerosis.MethodsThis retrospective study included a total of 394 patients. Subjects were divided into two groups: the first group consisted of 188 patients with a definite diagnosis of multiple sclerosis (based on revised McDonald criteria) and the second group consisted of 206 healthy controls. To examine the influence of age on pineal gland volume, we stratified the whole sample into three age groups: first involved patients under 20 years, second patients between 20 and 40 years, and third group included patients over 40 years. The maximum length (L) and height (H) of the pineal gland were measured on the T1-weighted sagittal images, and the width (W) was measured on the T2-weighted coronal or axial images. The volume of the gland was calculated as an approximation to an ellipse, according to the formula V = (L × H × W)/2.ResultsPineal gland volume of female multiple sclerosis (MS) patients (N = 129) was significantly lower than in healthy females (N = 123) (p = 0.013; p &lt; 0.05), unlike in males where there is not such difference. Also, pineal gland volume is not age-dependent, and the observed smaller pineal gland in MS patients can reliably be attributed to the disease itself. Additionally, large pineal gland size, especially over 62.83 mm3 when compared to pineal gland volume below 31.85 mm3 is associated with more than double reduced risk of multiple sclerosis (OR 0.42; p = 0.003).DiscussionOur results suggest that women with multiple sclerosis have smaller pineal glands that can theoretically be explained by a lack of input stimuli and the resultant decrease in gland volume. Additionally, the risk of multiple sclerosis is reduced in larger pineal gland volumes.
A novel PSMB8 isoform associated with multiple sclerosis lesions induces P-body formation
Authors: Shaw Benjamin C. , Williams Jessica L. 
Published: May 2024

IntroductionMultiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). Current therapies primarily target the inflammatory component of the disease and are highly effective in early stages of MS while limited therapies have an effect in the more chronic progressive stages of MS where resident glia have a larger role. MS lesions tend to be inflammatory even after the initial peripheral immune cell invasion has subsided and this inflammation is known to cause alternative splicing events.MethodsWe used qPCR of normal-appearing white matter and white matter lesions from postmortem MS tissue, in vitro studies, and immunostaining in MS tissue to investigate the alternative splicing of one gene known to be important during recovery in an animal model of MS, PSMB8.ResultsWe found a novel, intron-retained isoform which has not been annotated, upregulated specifically in MS patient white matter lesions. We found that this novel isoform activates the nonsense-mediated decay pathway in primary human astrocytes, the most populous glial cell in the CNS, and is then degraded. Overexpression of this isoform in astrocytes leads to an increased number of processing bodies in vitro, the primary site of mRNA decay. Finally, we demonstrated that MS white matter lesions have a higher burden of processing bodies compared to normal-appearing white matter, predominantly in GFAP-positive astrocytes.DiscussionThe increase in alternative splicing of the PSMB8 gene, the stress that this alternative splicing causes, and the observation that processing bodies are increased in white matter lesions suggests that the lesion microenvironment may lead to increased alternative splicing of many genes. This alternative splicing may blunt the protective or reparative responses of resident glia in and around white matter lesions in MS patients.
Exploring the causal association between genetically determined circulating metabolome and hemorrhagic stroke
Authors: Wang Yaolou , Shen Yingjie , Li Qi , Xu Hangjia , Gao Aili , Li Kuo , Rong Yiwei , Gao Shang , Liang Hongsheng , Zhang Xiangtong 
Published: May 2024

BackgroundHemorrhagic stroke (HS), a leading cause of death and disability worldwide, has not been clarified in terms of the underlying biomolecular mechanisms of its development. Circulating metabolites have been closely associated with HS in recent years. Therefore, we explored the causal association between circulating metabolomes and HS using Mendelian randomization (MR) analysis and identified the molecular mechanisms of effects.MethodsWe assessed the causal relationship between circulating serum metabolites (CSMs) and HS using a bidirectional two-sample MR method supplemented with five ways: weighted median, MR Egger, simple mode, weighted mode, and MR-PRESSO. The Cochran Q-test, MR-Egger intercept test, and MR-PRESSO served for the sensitivity analyses. The Steiger test and reverse MR were used to estimate reverse causality. Metabolic pathway analyses were performed using MetaboAnalyst 5.0, and genetic effects were assessed by linkage disequilibrium score regression. Significant metabolites were further synthesized using meta-analysis, and we used multivariate MR to correct for common confounders.ResultsWe finally recognized four metabolites, biliverdin (OR 0.62, 95% CI 0.40–0.96, PMVMR = 0.030), linoleate (18. 2n6) (OR 0.20, 95% CI 0.08–0.54, PMVMR = 0.001),1-eicosadienoylglycerophosphocholine* (OR 2.21, 95% CI 1.02–4.76, PMVMR = 0.044),7-alpha-hydroxy-3 -oxo-4-cholestenoate (7-Hoca) (OR 0.27, 95% CI 0.09–0.77, PMVMR = 0.015) with significant causal relation to HS.ConclusionWe demonstrated significant causal associations between circulating serum metabolites and hemorrhagic stroke. Monitoring, diagnosis, and treatment of hemorrhagic stroke by serum metabolites might be a valuable approach.
Desensitizing the autonomic nervous system to mitigate anti-GD2 monoclonal antibody side effects
Authors: Mora Jaume , Climent Alejandra , Roldán Mònica , Flores Marta Cecilia , Varo Amalia , Perez-Jaume Sara , Jou Cristina , Celma Mónica S. , Lazaro Juan José , Cheung Irene , Castañeda Alicia , Gorostegui Maite , Rodriguez Eva , Chamorro Saray , Muñoz Juan Pablo , Cheung Nai-Kong 
Published: May 2024

BackgroundAnti-GD2 monoclonal antibodies (mAbs) have shown to improve the overall survival of patients with high-risk neuroblastoma (HR-NB). Serious adverse events (AEs), including pain, within hours of antibody infusion, have limited the development of these therapies. In this study, we provide evidence of Autonomic Nervous System (ANS) activation as the mechanism to explain the main side effects of anti-GD2 mAbs.MethodsThrough confocal microscopy and computational super-resolution microscopy experiments we explored GD2 expression in postnatal nerves of infants. In patients we assessed the ANS using the Sympathetic Skin Response (SSR) test. To exploit tachyphylaxis, a novel infusion protocol (the Step-Up) was mathematically modelled and tested.ResultsThrough confocal microscopy, GD2 expression is clearly visible in the perineurium surrounding the nuclei of nerve cells. By computational super-resolution microscopy experiments we showed the selective expression of GD2 on the cell membranes of human Schwann cells in peripheral nerves (PNs) significantly lower than on NB. In patients, changes in the SSR were observed 4 minutes into the anti-GD2 mAb naxitamab infusion. SSR latency quickly shortened followed by gradual decrease in the amplitude before disappearance. SSR response did not recover for 24 hours consistent with tachyphylaxis and absence of side effects in the clinic. The Step-Up protocol dissociated on-target off-tumor side effects while maintaining serum drug exposure.ConclusionWe provide first evidence of the ANS as the principal non-tumor target of anti-GD2 mAbs in humans. We describe the development and modeling of the Step-Up protocol exploiting the tachyphylaxis phenomenon we demonstrate in patients using the SSR test.
Knowledge, attitudes, and current practices toward lung cancer palliative care management in China: a national survey
Authors: Chen Mengting , Hui Suocheng , Huang Yalan , Yu Huiqing , Yang Hong , Yang Liejun , Tian Ling , Wang Sixiong 
Published: May 2024

ScopeThe present investigation seeks to illuminate the current state and disparities in the knowledge, attitudes, and practices (KAP) among healthcare professionals regarding the management of lung cancer palliative care (LCPC) in China, while simultaneously assessing the prevalence and context of patient-controlled analgesia (PCA) usage in the management of cancer-related pain.MethodsA total of 2093 healthcare practitioners from 706 hospitals across China completed a structured questionnaire that probed various facets of LCPC management. The questionnaire consisted of seven thematic sections, incorporating chi-square tests and Fisher’s exact probabilities to statistically assess the discrepancies in KAP among healthcare professionals across different hospital grades. Ordered data distributions among hospital grades were compared using non-parametric Kruskal-Wallis H and Mann-Whitney U tests. Multiple-choice items were subjected to multiple-response cross-tabulation analysis, while the Spearman rank-order correlation coefficient was employed to gauge potential associations among variables.ResultsAround 84.2% of the respondents perceived anti-tumor therapy to be of equal importance to palliative care. Statistically significant differences (χ² = 27.402, P = 0.002) in satisfaction levels were observed, with participants from Tertiary hospitals demonstrating higher satisfaction compared to those from Secondary and Primary hospitals. Pain emerged as the most prevalent symptom necessitating LCPC. Major impediments to LCPC adoption included patients’ and families’ concerns about the safety of long-term palliative care-related drug use. 31.1% of the respondents cited the most frequent rationale for PCA use as cases involving patients who required systemic administration of large opioid doses or exhibited intolerable adverse reactions to opioids. The principal deterrents against the use of PCA for cancer pain management were (1): apprehension about adverse drug reactions due to overdose (2), concern about the potential for opioid addiction, and (3) the anticipated increase in patients’ economic burdens. Over the preceding 24-month period, 33.9% of the surveyed healthcare practitioners reported no engagement in either online or offline LCPC-related training initiatives.ConclusionThis study emphasizes the pressing need for comprehensive training in LCPC among Chinese health personnels, particularly focusing on the effective management of cancer pain symptoms.