bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison between left bundle branch area pacing and right ventricular pacing: ventricular electromechanical synchrony and risk of atrial high-rate episodes
Authors: Yang Wang-Yang , Di Bei-Bing , Peng Hui , Sun Zhi-Jun 
Published: April 2024

BackgroundThe electromechanical dyssynchrony associated with right ventricular pacing (RVP) has been found to have adverse impact on clinical outcomes. Several studies have shown that left bundle branch area pacing (LBBAP) has superior pacing parameters compared with RVP. We aimed to assess the difference in ventricular electromechanical synchrony and investigate the risk of atrial high-rate episodes (AHREs) in patients with LBBAP and RVP.MethodsWe consecutively identified 40 patients with atrioventricular block and no prior atrial fibrillation. They were divided according to the ventricular pacing sites: the LBBAP group and the RVP group (including the right ventricular apical pacing (RVA) group and the right side ventricular septal pacing (RVS) group). Evaluation of ventricular electromechanical synchrony was implemented using electrocardiogram and two-dimensional speckle tracking echocardiography (2D-STE). AHRE was defined as event with an atrial frequency of ≥176 bpm lasting for ≥6 min recorded by pacemakers during follow-up.ResultsThe paced QRS duration of the LBBAP group was significantly shorter than that of the other two groups: LBBAP 113.56 ± 9.66 ms vs. RVA 164.73 ± 14.49 ms, p &lt; 0.001; LBBAP 113.56 ± 9.66 ms vs. RVS 148.23 ± 17.3 ms, p &lt; 0.001. The LBBAP group showed shorter maximum difference (TDmax), and standard deviation (SD) of the time to peak systolic strain among the 18 left ventricular segments, and time of septal-to-posterior wall motion delay (SPWMD) compared with the RVA group (TDmax, 87.56 ± 56.01 ms vs. 189.85 ± 91.88 ms, p = 0.001; SD, 25.40 ± 14.61 ms vs. 67.13 ± 27.40 ms, p &lt; 0.001; SPWMD, 28.75 ± 21.89 ms vs. 99.09 ± 46.56 ms, p &lt; 0.001) and the RVS group (TDmax, 87.56 ± 56.01 ms vs. 156.46 ± 55.54 ms, p = 0.003; SD, 25.40 ± 14.61 ms vs. 49.02 ± 17.85 ms, p = 0.001; SPWMD, 28.75 ± 21.89 ms vs. 91.54 ± 26.67 ms, p &lt; 0.001). The interventricular mechanical delay (IVMD) was shorter in the LBBAP group compared with the RVA group (−5.38 ± 9.31 ms vs. 44.82 ± 16.42 ms, p &lt; 0.001) and the RVS group (−5.38 ± 9.31 ms vs. 25.31 ± 21.36 ms, p &lt; 0.001). Comparing the RVA group and the RVS group, the paced QRS duration and IVMD were significantly shorter in the RVS group (QRS duration, 164.73 ± 14.49 ms vs. 148.23 ± 17.3 ms, p = 0.02; IVMD, 44.82 ± 16.42 ms vs. 25.31 ± 21.36 ms, p = 0.022). During follow-up, 2/16 (12.5%) LBBAP patients, 4/11 (36.4%) RVA patients, and 8/13 (61.5%) RVS patients had recorded novel AHREs. LBBAP was proven to be independently associated with decreased risk of AHREs than RVP (log-rank p = 0.043).ConclusionLBBAP generates narrower paced QRS and better intro-left ventricular and biventricular contraction synchronization compared with traditional RVP. LBBAP was associated with a decreased risk of AHREs compared with RVP.
Identification of microRNA biomarkers simultaneously expressed in circulating extracellular vesicles and atherosclerotic plaques
Authors: Brandes Florian , Meidert Agnes S. , Kirchner Benedikt , Yu Mia , Gebhardt Sonja , Steinlein Ortrud K. , Dolch Michael E. , Rantner Barbara , Tsilimparis Nikolaos , Schelling Gustav , Pfaffl Michael W. , Reithmair Marlene 
Published: April 2024

BackgroundAtherosclerosis is a widespread disorder of the cardiovascular system. The early detection of plaques by circulating biomarkers is highly clinically relevant to prevent the occurrence of major complications such as stroke or heart attacks. It is known that extracellular vesicles (EVs) are important in intercellular communication in atherosclerotic disorders and carry many components of their cells of origin, including microRNAs (miRNAs). In this study, we test the assumption that miRNAs present in material acquired from plaques in patients undergoing surgery for atherosclerotic carotid artery stenosis are also expressed in circulating EVs obtained from the identical patients. This would allow the adoption of a liquid biopsy approach for the detection of plaques.MethodsWe studied 22 surgical patients with atherosclerotic carotid arterial stenosis and 28 healthy controls. EVs were isolated from serum by precipitation. miRNA expression profiles of serum-derived EVs were obtained by small RNA sequencing and in plaque material simultaneously acquired from patients. A comparative analysis was performed to identify circulating atherosclerosis-associated miRNAs that are also detectable in plaques.ResultsSeven miRNAs were found to be differentially regulated in patient serum compared with the serum of healthy controls. Of these, miR-193b-5p, miR-193a-5p, and miR-125a-3p were significantly upregulated in patients compared with that in healthy controls and present in both, circulating EVs and plaque material. An overrepresentation analysis of experimentally validated mRNA targets revealed an increased regulation of inflammation and vascular growth factors, key players in atherosclerosis and plaque formation.ConclusionOur findings suggest that circulating EVs reflect plaque development in patients with symptomatic carotid artery stenosis, which can serve as biomarker candidates for detecting the presence of atherosclerotic plaques.
Causal relationship between basal metabolic rate and kidney function: a bidirectional two-sample mendelian randomization study
Authors: Zhou Chaomin , Peng Yanzhe , Zhan Lin , Zha Yan 
Published: April 2024

BackgroundThe relationship between basal metabolic rate (BMR) and Chronic kidney disease (CKD) remains unclear and controversial. In this study, we investigated the causal role of BMR in renal injury, and inversely, whether altered renal function causes changes in BMR.MethodsIn this two-sample mendelian randomization (MR) study, Genetic data were accessed from published genome-wide association studies (GWAS) for BMR ((n = 454,874) and indices of renal function, i.e. estimated glomerular filtration rate (eGFR) based on creatinine (n =1, 004, 040), CKD (n=480, 698), and blood urea nitrogen (BUN) (n =852, 678) in European. The inverse variance weighted (IVW) random-effects MR method serves as the main analysis, accompanied by several sensitivity MR analyses. We also performed a reverse MR to explore the causal effects of the above indices of renal function on the BMR.ResultsWe found that genetically predicted BMR was negatively related to eGFR, (β= −0.032, P = 4.95*10-12). Similar results were obtained using the MR-Egger (β= −0.040, P = 0.002), weighted median (β= −0.04, P= 5.35×10-11) and weighted mode method (β= −0.05, P=9.92×10-7). Higher BMR had a causal effect on an increased risk of CKD (OR =1.36, 95% CI = 1.11-1.66, P =0.003). In reverse MR, lower eGFR was related to higher BMR (β= −0.64, P = 2.32×10-6, IVW analysis). Bidirectional MR supports no causal association was observed between BMR and BUN. Sensitivity analyses confirmed these findings, indicating the robustness of the results.ConclusionGenetically predicted high BMR is associated with impaired kidney function. Conversely, genetically predicted decreased eGFR is associated with higher BMR.
Old-growth forests in the Dinaric Alps of Bosnia-Herzegovina and Montenegro: a continental hot-spot for research and biodiversity
Authors: Motta Renzo , Alberti Giorgio , Ascoli Davide , Berretti Roberta , Bilic Srdjan , Bono Alessia , Milic Curovic , Vojislav Dukić , Finsinger Walter , Garbarino Matteo , Govedar Zoran , Keren Srdjan , Meloni Fabio , Ruffinatto Flavio , Nola Paola 
Published: April 2024

IntroductionAccording to various censuses, Europe has less than 1.5 million ha of old-growth forests (OGF). Most of them are in the boreal zone, while their presence in the temperate zone is residual and fragmented.In the framework of the EU biodiversity strategy, it has been adopted a broad definition of OGF which includes late-seral forests and forests with some management legacies. However, research purposes need to identify strictly defined OGFs characterized by structure, disturbance history, and processes typical and exclusive of the last stage of the forest dynamic.MethodsThe present paper wants to contribute to this debate by presenting a research network of four mixed (Fagus-Abies-Picea) montane OGFs in the Dinaric Alps (Lom, BiH; Janj, BiH; Perućica, BiH; Biogradska Gora, MNE), summarizing 20 years of multidisciplinary research by focusing on the structural characteristics and the disturbance history of the whole network and their coherency with strict OGF indicators. These sites were selected in relatively structurally uniform study areas, where 142 permanent plots have been established since 2002.Results and discussionThe study sites have a high living (747–1,201 m3 ha−1) and coarse woody debris (CWD) biomass (304–410 m3 ha−1), resulting in the highest forest carbon sink at the continental level (398–484  Mg C ha−1). The presence of large and old trees is one of the critical characteristics of the old-growth stage: in Lom and Perućica, there are 19 trees and 14  ha−1 larger than 1 m at breast height, respectively, and 14 trees and 15 trees ha−1 older than 400  years. In the last three centuries, continuous small-scale disturbances have driven forest dynamics, developing stands characterized by gap-phase dynamics and quasi-equilibrium structure. The Dinaric OGF network presents robust indicators of old-growthness, similar structural characteristics, and dynamic processes across all four sites. Identifying this sub-set of OGF using strict criteria is critical for recognizing conservation priorities and for quantifying, along an old-growthness chronosequence, the current structural differences of managed or recently abandoned forests. Besides, only OGF selected with rigorous criteria can act as a reliable reference for ecological restoration and sustainable forest management as a benchmark for carbon sink and for quantifying the impact of climate change on forests.
Identification of molecular subtypes based on chromatin regulator-related genes and experimental verification of the role of ASCL1 in conferring chemotherapy resistance to breast cancer
Authors: Li Yilun , Yang Xiaolu , Geng Cuizhi , Liu Yunjiang , Tang Tiantian , Zhang Lina , Liu Fei , Zhang Meng , Hao Jun , Ma Li 
Published: April 2024

ObjectiveThe aim of this study was to identify the molecular subtypes of breast cancer based on chromatin regulator-related genes.MethodsThe RNA sequencing data of The Cancer Genome Atlas–Breast Cancer cohort were obtained from the official website, while the single-cell data were downloaded from the Gene Expression Omnibus database (GSE176078). Validation was performed using the Molecular Taxonomy of Breast Cancer International Consortium dataset. Furthermore, the immune characteristics, tumor stemness, heterogeneity, and clinical characteristics of these molecular subtypes were analyzed. The correlation between chromatin regulators and chemotherapy resistance was examined in vitro using the quantitative real-time polymerase chain reaction (qRT-PCR) and Cell Counting Kit-8 (CCK8) assays.ResultsThis study identified three stable molecular subtypes with different prognostic and pathological features. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein–protein interaction analyses revealed that the differentially expressed genes were associated with disease processes, such as mitotic nuclear division, chromosome segregation, condensed chromosome, and specific chromosome region. The T stage and subtypes were correlated with the clinical features. Tumor heterogeneity (mutant-allele tumor heterogeneity, tumor mutational burden, purity, and homologous recombination deficiency) and tumor stemness (RNA expression-based stemness score, epigenetically regulated RNA expression-based stemness score, DNA methylation-based stemness score, and epigenetically regulated DNA methylation-based stemness score) significantly varied between the three subtypes. Furthermore, Western blotting, qRT-PCR, and CCK8 assays demonstrated that the expression of ASCL1 was positively correlated with chemotherapy resistance in breast cancer.ConclusionThis study identified the subtypes of breast cancer based on chromatin regulators and analyzed their clinical features, gene mutation status, immunophenotype, and drug sensitivity. The results of this study provide effective strategies for assessing clinical prognosis and developing personalized treatment strategies.
The clinical and pathological features of Kimura disease in pediatric patients
Authors: Liu Lili , Zhang Wen , Huang Minjie , Li Kaiji , Zhu Li’ou , Ke Liqin , Huang Juan , Wu Ying 
Published: April 2024

BackgroundKimura disease is characterized by inflammation, with its underlying causes remaining uncertain. There is a lack of comprehensive and systematic research on the pathology of this condition in pediatric patients. Our objective is to study the clinical and pathological attributes of Kimura disease in pediatric patients and investigate the potential diagnostic significance of immunoglobulin E (IgE) in this context.MethodsClinical and laboratory information, pathological characteristics, and follow-up data were correlated to examine the distinctive features. Immunohistochemistry, acid-fast staining, and molecular assay were used to identify the presence of IgE and pathogens.ResultsWe conducted an analysis of five cases of Kimura disease in pediatric patients at our hospital. The patients’ ages ranged from 5 years and 7 months to 14 years and 2 months, with 4 (80%) being male. The most common site was the head and neck region, particularly the postauricular subcutaneous area. Eosinophilia was observed in four patients (80%), and two patients (40%) had elevated serum immunoglobulin E (IgE) levels. Histopathological changes included eosinophilic infiltrates, follicular hyperplasia, and the proliferation of postcapillary venules. Immunohistochemical results supported the reactive nature of the lymphoid process and IgE deposition in the follicle, while no specific pathogens were discovered by special staining. All patients underwent surgical excision, and none experienced recurrence in their original location.ConclusionChildren with Kimura disease show distinct eosinophilic and IgE alterations in both laboratory findings and pathological features. The application of immunohistochemical staining of IgE could serve as a promising marker for diagnosing Kimura disease.
Characterization, histopathology and immunogenicity of the lumpy skin disease virus isolated during 2019–20 in Bangladesh
Authors: Uddin Mohammad Asir , Hossain Muhammad Tofazzal , Rahman A. K. M. Anisur , Siddique Mahbubul Pratik , Kafi Md. Abdul , Hossain Md. Golbar , Chakraborty Sourav , Rahman Mohummad Muklesur , Khasruzzaman A. K. M. , Ward Michael P. , Islam Md. Alimul 
Published: April 2024

IntroductionLumpy skin disease (LSD) is a highly contagious vector-borne viral disease of cattle. LSD has emerged in Bangladesh in 2019, causing significant economic losses due to its high morbidity and mortality. This research was designed to isolate, identify, and assess the immunogenicity of LSD virus (LSDV) using nodular tissue samples obtained from affected cattle during the 2019–20 outbreak across nine districts of Bangladesh.MethodsTo determine the presence of LSDV in nodular tissues, we initially used iiPCR and PCR, followed by histopathological examination. 151 were positive via iiPCR and PCR among the 180 collected samples. The PCR positive 151 samples were then inoculated into 10-day-old embryonated chicken eggs via the CAM route to isolate LSDV, confirmed through PCR. Subsequently, partial sequencing and phylogenetic analysis of the P32 gene were performed to determine the origin of the circulating LSDV strain. The immunogenicity of selected LSDV strains was assessed through an ELISA test.ResultsThe PCR results revealed a distinct positive band at 192 bp in both the nodular tissue samples and the LSDV isolated from chicken embryo inoculations. Microscopic analysis of the nodular lesions revealed thickening of the epidermis, ballooning degeneration of keratinocytes, and proliferation of follicular epithelia. Additionally, mononuclear infiltration was observed at the demarcation line between infected and healthy tissue, with necrosis of muscular tissues beneath the epidermis. The LSDV isolate from Bangladesh exhibited a close genetic relationship with LSDV strains isolated from neighboring and other regional countries including India, Myanmar, and Mongolia. This observation strongly suggests the possibility of a transboundary spread of the LSD outbreak in Bangladesh during 2019–2020. The results of the immunogenicity test showed that the serum antibody titer remained at a protective level for up to 18 months following secondary immunization with inactivated LSDV antigen. This finding suggests that the inactivated LSDV antigen could be a potential vaccine candidate to protect cattle in Bangladesh against LSDV.ConclusionIn conclusion, our research successfully isolated, identified, and characterized LSDV in cattle nodular tissues from the 2019–20 outbreak in Bangladesh. Furthermore, it provided insights into the probable origin of the circulating strain and investigated a potential vaccine candidate to protect cattle in the region from LSDV.
Association between depression and stroke risk in adults: a systematic review and meta-analysis
Authors: Ashraf Farheen , Mustafa Muhammad Saqlain , Shafique Muhammad Ashir , Haseeb Abdul , Mussarat Abdullah , Noorani Amber , Sohail Rangwala Burhanuddin , Kashif Rasool Fatimah , Siddiq Mohammad Arham , Iqbal Javed 
Published: April 2024

IntroductionStroke is a significant global health concern, and numerous studies have established a link between depression and an increased risk of stroke. While many investigations explore this link, some overlook its long-term effects. Depression may elevate stroke risk through physiological pathways involving nervous system changes and inflammation. This systematic review and meta-analysis aimed to assess the association between depression and stroke.MethodologyWe conducted a comprehensive search of electronic databases (PubMed, Embase, Scopus, and PsycINFO) from inception to 9 April 2023, following the Preferred Reporting Items for Systemic Review and Meta-analysis (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. We included all articles assessing the association between different stroke types and depression, excluding post-stroke depression. Two investigators independently extracted data and assessed quality using the Newcastle–Ottawa Scale and Cochrane Risk of Bias tool, utilizing a random-effects model for data synthesis. The primary outcome was the association of depression with stroke, with a secondary focus on the association of antidepressants with stroke.ResultsThe initial search yielded 10,091 articles, and 44 studies were included in the meta-analysis. The pooled analysis revealed a significant association between depression and stroke risk, with an overall hazard ratio of 1.41 (95% CI 1.32, 1.50; p &lt; 0.00001), indicating a moderately positive effect size. Subgroup analyses showed consistent associations with ischemic stroke (HR = 1.30, 95% CI 1.13, 1.50; p = 0.007), fatal stroke (HR = 1.39, 95% CI 1.24, 1.55; p &lt; 0.000001), and hemorrhagic stroke (HR = 1.33, 95% CI 1.01, 1.76; p = 0.04). The use of antidepressants was associated with an elevated risk of stroke (HR = 1.28, 95% CI 1.05, 1.55; p = 0.01).Conclusion and relevanceThis meta-analysis indicates that depression moderately raises the risk of stroke. Given the severe consequences of stroke in individuals with depression, early detection and intervention should be prioritized to prevent it.Systematic review registrationProspero (CRD42023472136).
Identification of potential drug targets for insomnia by Mendelian randomization analysis based on plasma proteomics
Authors: Yang Ni , Shi Liangyuan , Xu Pengfei , Ren Fang , Lv Shimeng , Li Chunlin , Qi Xianghua 
Published: April 2024

IntroductionInsomnia, a common clinical disorder, significantly impacts the physical and mental well-being of patients. Currently, available hypnotic medications are unsatisfactory due to adverse reactions and dependency, necessitating the identification of new drug targets for the treatment of insomnia.MethodsIn this study, we utilized 734 plasma proteins as genetic instruments obtained from genome-wide association studies to conduct a Mendelian randomization analysis, with insomnia as the outcome variable, to identify potential drug targets for insomnia. Additionally, we validated our results externally using other datasets. Sensitivity analyses entailed reverse Mendelian randomization analysis, Bayesian co-localization analysis, and phenotype scanning. Furthermore, we constructed a protein-protein interaction network to elucidate potential correlations between the identified proteins and existing targets.ResultsMendelian randomization analysis indicated that elevated levels of TGFBI (OR = 1.01; 95% CI, 1.01–1.02) and PAM ((OR = 1.01; 95% CI, 1.01–1.02) in plasma are associated with an increased risk of insomnia, with external validation supporting these findings. Moreover, there was no evidence of reverse causality for these two proteins. Co-localization analysis confirmed that PAM (coloc.abf-PPH4 = 0.823) shared the same variant with insomnia, further substantiating its potential role as a therapeutic target. There are interactive relationships between the potential proteins and existing targets of insomnia.ConclusionOverall, our findings suggested that elevated plasma levels of TGFBI and PAM are connected with an increased risk of insomnia and might be promising therapeutic targets, particularly PAM. However, further exploration is necessary to fully understand the underlying mechanisms involved.
Case Report: A novel RRM2B variant in a Chinese infant with mitochondrial DNA depletion syndrome and collective analyses of RRM2B variants for disease etiology
Authors: Wang Yanjun , Hang Ling , Shou Weihua , Li Cuifen , Dong Fangling , Feng Xingxing , Jin Ruohong , Li Bin , Xiao Shufang 
Published: April 2024

BackgroundThere are few reports of infantile mitochondrial DNA depletion syndrome (MDDS) caused by variants in RRM2B and the correlation between genotype and phenotype has rarely been analyzed in detail. This study investigated an infantile patient with MDDS, from clinical characteristics to genetic causes.MethodsRoutine physical examinations, laboratory assays, which included gas chromatography–mass spectrometry of blood and urine, and MRI scans were performed to obtain an exact diagnosis. Whole-exome sequencing was used to pinpoint the abnormal gene and bioinformatic analyses were performed on the identified variant.ResultsThe case presented with progressive neurologic deterioration, failure to thrive, respiratory distress and lactic acidosis. Sequencing revealed that the patient had a homozygous novel missense variant, c.155T&gt;C (p.Ile52Thr), in exon 2 of the RRM2B gene. Multiple lines of bioinformatic evidence suggested that this was a likely detrimental variant. In addition, reported RRM2B variants were compiled from the relevant literature to analyze disease etiology. We found a distinctive distribution of genotypes across disease manifestations of different severity. Pathogenic alleles of RRM2B were significantly enriched in MDDS cases.ConclusionThe novel variant is a likely genetic cause of MDDS. It expands our understanding of the pathogenic variant spectrum and the contribution of the RRM2B gene to the disease spectrum of MDDS.