bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between different GLP-1 receptor agonists and gastrointestinal adverse reactions: A real-world disproportionality study based on FDA adverse event reporting system database
Authors: Liu Lulu , Chen Jia , Wang Lei , Chen Chen , Chen Li 
Published: December 2022

ObjectiveGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) have significantly improved clinical effects on glycemic control. However, real-world data concerning the difference in gastrointestinal adverse events (AEs) among different GLP-1 RAs are still lacking. Our study aimed to characterize and compare gastrointestinal AEs among different marketed GLP-1 RAs (exenatide, liraglutide, dulaglutide, lixisenatide, and semaglutide) based on real-world data.MethodsDisproportionality analysis was used to evaluate the association between GLP-1 RAs and gastrointestinal adverse events. Data were extracted from the US FDA Adverse Event Reporting System (FAERS) database between January 2018 and September 2022. Clinical characteristics, the time-to-onset, and the severe proportion of GLP-1 RAs-associated gastrointestinal AEs were further analyzed.ResultsA total of 21,281 reports of gastrointestinal toxicity were analyzed out of 81,752 adverse event reports, and the median age of the included patients was 62 (interquartile range [IQR] 54–70) years old. Overall GLP-1 RAs were associated with increased risk of gastrointestinal system disorders (ROR, 1.46; 95% CI, 1.44–1.49), which were further attributed to liraglutide (ROR, 2.39; 95% CI, 2.28–2.51), dulaglutide (ROR, 1.39; 95% CI, 1.36-1.42), and semaglutide (ROR, 3.00; 95% CI, 2.89–3.11). Adverse events uncovered in the labels included gastroesophageal reflux disease, gastritis, bezoar, breath odor, intra-abdominal hematoma, etc. Furthermore, it was observed that semaglutide had the greatest risk of nausea (ROR, 7.41; 95% CI, 7.10–7.74), diarrhea (ROR, 3.55; 95% CI, 3.35–3.77), vomiting (ROR, 6.67; 95% CI, 6.32–7.05), and constipation (ROR, 6.17; 95% CI, 5.72–6.66); liraglutide had the greatest risk of abdominal pain upper (ROR, 4.63; 95% CI, 4.12–5.21) and pancreatitis (ROR, 32.67; 95% CI, 29.44–36.25). Most gastrointestinal AEs tended to occur within one month. Liraglutide had the highest severe rate of gastrointestinal AEs (23.31%), while dulaglutide had the lowest, with a severe rate of 12.29%.ConclusionGLP-1 RA were significantly associated with gastrointestinal AEs, and the association was further attributed to liraglutide, dulaglutide, and semaglutide. In addition, semaglutide had the greatest risk of nausea, diarrhea, vomiting, constipation, and pancreatitis, while liraglutide had the greatest risk of upper abdominal pain. Our study provided valuable evidence for selecting appropriate GLP-1 RAs to avoid the occurrence of GLP-1 RA-induced gastrointestinal AEs.
Top 100 #PCOS influencers: Understanding who, why and how online content for PCOS is influenced
Authors: Elhariry Maiar , Malhotra Kashish , Solomon Michelle , Goyal Kashish , Kempegowda Punith 
Published: December 2022

BackgroundWith the exponential increase in digital space of social media platforms, a new group called social media influencers are driving online content of polycystic ovary syndrome (PCOS) which eventually influences behaviour and decision-making process. The objective of this study was to identify the top 100 social media (Twitter) influencers and organizations from across the globe who are advocating for PCOS. We further explored the origin and journey of these social media influencers.MethodsWe identified the top 100 PCOS influencers and organizations between July and August 2022 using three social network analysis tools- Cronycle, Symplur and SocioViz. These influencers were invited to a semi-structured interview to explore why they chose to become an influencer and the support they have to deliver their online content. Two independent authors coded the anonymised transcripts from these interviews and broad themes were identified by thematic inductive analysis.Results95.0% of individual influencers and 80% of organisations are from high-income countries. Most influencers in our study agree that social media is an essential tool in the present day to raise awareness of PCOS. However, they reiterated social media also has significant disadvantages that require consideration and caution. Most influencers were driven by poor personal experience and worked voluntarily to reduce misinformation and improve the experiences of women diagnosed with PCOS in the future. Although there is an interest in working together, there is currently minimal collaborative work between influencers.ConclusionThere is a global inequity of #PCOS influencers online. Establishing standards and support based on evidence may help develop more influencers, especially in low- and middle-income countries, so we can counter misinformation and provide locally acceptable guidance.
Extrinsic and intrinsic factors drive the timing of gestation and reproductive success of Scandinavian brown bears
Authors: Lemière Lucie , Thiel Alexandra , Fuchs Boris , Gilot-Fromont Emmanuelle , Hertel Anne G. , Friebe Andrea , Kindberg Jonas , Støen Ole-Gunnar , Arnemo Jon M. , Evans Alina L. 
Published: December 2022

IntroductionClimate change is altering the reproductive phenology of many organisms, but the factors that influence the timing of gestation in ursids are still poorly understood. Higher temperatures in spring are already causing an earlier den exit in some brown bear populations, and a temporal mismatch between hibernation and reproduction could have dramatic consequences for reproductive success. Therefore, understanding the factors that control the timing of these events is important to forecast the consequences of climate change on population growth rates.MethodsIn this study, we used abdominal temperature loggers and GPS collars with acceleration sensors on 23 free-ranging pregnant female brown bears living in two areas in Sweden (61°N and 67°N latitude) to pinpoint hibernation and reproductive events. We investigated how intrinsic and extrinsic factors influence the termination of embryonic diapause and parturition, as well as their impact on reproductive success.ResultsThe termination of embryonic diapause was later in the northern area compared to the southern area and occurred earlier when ambient temperature at den entry was higher in both areas. In the southern area, young adults (i.e., females = 7 years old) had a delayed parturition when bilberry abundance was low the year of mating. Additionally, young adults had a lower reproductive success than adults and their probability to reproduce successfully was dependent on bilberry abundance, whereas adult females were not affected by this parameter.DiscussionAs den exit occurs later in the northern study area, we suggest that a later parturition might ensure that females lactate their cubs in the den for a reasonable amount of time while fasting. Similarly, a later parturition combined with an earlier emergence could allow young adults to spend less time in the den lactating if they could not reach an optimal body condition prior to hibernation. But as a result, their cubs are younger and more vulnerable when they leave the den leading to lower survival rates. Our results suggest that a decreased berry abundance in the fall could impact the reproductive and hibernation phenology of Scandinavian brown bear females and lead to a lower cub survival with potential consequences on the population dynamics.
Analysis of miRNA rare variants in amyotrophic lateral sclerosis and in silico prediction of their biological effects
Authors: Brusati Alberto , Ratti Antonia , Pensato Viviana , Peverelli Silvia , Gentilini Davide , Dalla Bella Eleonora , Sorce Marta Nice , Meneri Megi , Gagliardi Delia , Corti Stefania , Gellera Cinzia , Lauria Pinter Giuseppe , Ticozzi Nicola , Silani Vincenzo 
Published: December 2022

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and/or lower motor neurons and characterized by complex etiology. Familial cases show high genetic heterogeneity and sporadic cases (90%) are associated with several genetic and environmental risk factors. Among the genetic risk factors, the contribution of non-coding elements, such as microRNAs (miRNAs), to ALS disease susceptibility remains largely unexplored.Aim: This work aims to identify rare variants in miRNA genes in sporadic ALS (sALS) patients which may cause a defective miRNA maturation or altered target gene recognition by changing miRNA secondary structure or seed sequence, respectively.Methods: Rare variants located in miRNA loci with a minor allele frequency (MAF) &lt; 0.01 were extracted from whole genome sequencing (WGS) data of 100 sALS patients. The secondary pre-miRNA structures were predicted using MiRVas to evaluate the impact of the variants on RNA folding process. Human TargetScan was used to retrieve all the potential target genes of miRNAs with variants in the seed region. Over Representation Analysis (ORA) was conducted to compare the lists of target genes for the reference and mutated miRNAs in the seed sequence.Results: Our analysis identified 86 rare variants in 77 distinct miRNAs and distributed in different parts of the miRNA precursors. The presence of these variants changed miRNA secondary structures in ∼70% of MiRVas predictions. By focusing on the 6 rare variants mapping within the seed sequence, the predicted target genes increased in number compared to the reference miRNA and included novel targets in a proportion ranging from 30 to 82%. Interestingly, ORA revealed significant changes in gene set enrichment only for mutated miR-509-1 and miR-941-3 for which the Gene Ontology term related to “nervous system development” was absent and present, respectively, compared to target lists of the reference miRNA.Conclusion: We here developed a workflow to study miRNA rare variants from WGS data and to predict their biological effects on miRNA folding, maturation and target gene recognition. Although this in silico approach certainly needs functional validation in vitro and in vivo, it may help define the role of miRNA variability in ALS and complex diseases.
HIF-1α/BNIP3L induced cognitive deficits in a mouse model of sepsis-associated encephalopathy
Authors: Zhao Lina , Song Yu , Zhang Ying , Liu Haiying , Shen Yuehao , Fan Yan , Li Yun , Xie Keliang 
Published: December 2022

ObjectiveSepsis Associated Encephalopathy (SAE) is a common complication in critically ill patients and perioperative period, but its pathogenesis is still unclear. This study aimed to explore the effect of the HIF-1α (hypoxia-inducible factor-1α)/BNIP3L (Bcl-2/adenovirus E1B 19-kDa interaction protein) signaling pathway on SAE.MethodsC57BL/6J male mice were divided into four groups, using a random number table method: control group, sham group, sepsis group, sepsis+HIF-1α activity inhibitor (echinomycin) group. Sepsis was induced by cecal ligation and puncture (CLP). At 24 h after surgery, brain tissue was sampled. HE was staining to observe changes in the hippocampus structure. Fluoroscopy observes changes in mitochondrial structure. Western blot, QT-PCR, and immunofluorescence were used to assess the amount of expression of HIF-1α and BNIP3L in the hippocampus and mitochondrion of hippocampus neurons. Observation of neuronal apoptosis by TUNEL staining. Seven days after surgery, mice were tested in a Morris water maze test to assess cognitive function after CLP.ResultsOur results show that CLP-induced hippocampus-dependent cognitive deficits were accompanied with increased HIF 1a and decreased BNIP3L, increased protein levels of TNF-α, IL-6, and IL-β, and damage to mitochondrial structures and neuronal apoptosis in the hippocampus. In addition, administration of echinomycin rescues cognitive deficits, ameliorates HIF-1α and BNIP3L-mediated neuronal pyroptosis and damaged mitochondrial structures, and decreases the expression of TNF-α and IL-6 in the hippocampus.ConclusionsHIF-1α and the BNIP3L promote mitochondrial damage, and neuronal apoptosis and the expression of inflammatory factors may be the mechanism of SAE in critically ill patients and perioperative period
Roles of the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis
Authors: Zhang Tian-Ping , Li Rui , Wang Li-Jun , Huang Qian , Li Hong-Miao 
Published: December 2022

ObjectiveThe aim of the current study was to investigate the contributing role of gene variation and transcription levels among the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis (PTB).MethodsA case-control study including 461 PTB patients and 467 normal controls was designed for genotyping. Three SNPs in METTL3 (rs1061027, rs1139130, rs1061026), three SNPs in METTL14 (rs62328061, rs4834698, rs1064034), and two SNPs in WTAP (rs1853259, rs11752345) were genotyped via the SNPscan™ technique. METTL3, METTL14, and WTAP transcription levels were determined in 78 PTB patients and 86 controls via quantitative real-time reverse-transcription PCR.ResultsFrequencies of the METTL14 rs62328061 GG genotype, WTAP rs11752345 CT genotype, and T allele were significantly increased in PTB patients compared to controls. An increased risk of rs62328061 was detected in a recessive model, and a decreased risk of rs11752345 was detected in a dominant model in the PTB group. METTL3 gene variation was not associated with PTB risk. The METTL3 rs1139130 GG genotype was significantly increased with drug resistance, and the G allele was significantly decreased with drug-induced liver injury in PTB patients. A reduced frequency of the METTL14 rs62328061 G allele was associated with leukopenia, a reduced frequency of the WTAP rs11752345 T allele was associated with sputum smear positivity, and a higher frequency of the METTL14 rs4834698 TC genotype was evident in PTB patients with hypoproteinemia. Compared to controls, METTL3, METTL14, and WTAP transcription levels in PTB patients were significantly decreased, and the level of WTAP was increased in PTB patients with drug resistance. METTL3 level was negatively associated with erythrocyte sedimentation rate and aspartate aminotransferase, and METTL14 level was negatively correlated with alanine aminotransferase and aspartate aminotransferase.ConclusionMETTL14 rs62328061 and WTAP rs11752345 variants were associated with the genetic background of PTB, and METTL3, METTL14, and WTAP levels were abnormally decreased, suggesting that these m6A methyltransferases may play important roles in PTB.
Altered anterior cingulate cortex subregional connectivity associated with cognitions for distinguishing the spectrum of pre-clinical Alzheimer’s disease
Authors: Yuan Qianqian , Liang Xuhong , Xue Chen , Qi Wenzhang , Chen Shanshan , Song Yu , Wu Huimin , Zhang Xulian , Xiao Chaoyong , Chen Jiu 
Published: December 2022

BackgroundSubjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are considered part of the early progression continuum of Alzheimer’s disease (AD). The anterior cingulate cortex (ACC), a hub of information processing and regulation in the brain, plays an essential role in AD pathophysiology. In the present study, we aimed to systematically identify changes in the functional connectivity (FC) of ACC subregions in patients with SCD and aMCI and evaluate the association of these changes with cognition.Materials and methodsFunctional connectivity (FC) analysis of ACC sub-regions was performed among 66 patients with SCD, 71 patients with aMCI, and 78 healthy controls (HCs). Correlation analyses were performed to examine the relationship between FC of altered ACC subnetworks and cognition.ResultsCompared to HCs, SCD patients showed increased FC of the bilateral precuneus (PCUN) and caudal ACC, left superior frontal gyrus (SFG) and subgenual ACC, left inferior parietal lobule (IPL) and dorsal ACC, left middle occipital gyrus (MOG) and dorsal ACC, and left middle temporal gyrus (MTG) and subgenual ACC, while aMCI patients showed increased FC of the left inferior frontal gyrus (IFG) and dorsal ACC and left medial frontal gyrus (MFG) and subgenual ACC. Compared to patients with SCD, patients with aMCI showed increased FC of the right MFG and dorsal ACC and left ACC and subgenual ACC, while the left posterior cingulate cortex (PCC) showed decreased FC with the caudal ACC. Moreover, some FC values among the altered ACC subnetworks were significantly correlated with episodic memory and executive function.ConclusionSCD and aMCI, part of the spectrum of pre-clinical AD, share some convergent and divergent altered intrinsic connectivity of ACC subregions. These results may serve as neuroimaging biomarkers of the preclinical phase of AD and provide new insights into the design of preclinical interventions.
Chronic neuroinflammation impairs waste clearance in the rat brain
Authors: Suresh Swathi , Larson Jacob , Jenrow Kenneth Allen 
Published: December 2022

BackgroundPrevious reports have established an association between impaired clearance of macromolecular waste from the brain parenchyma and a variety of brain insults for which chronic neuroinflammation is a common pathological feature. Here we investigate whether chronic neuroinflammation is sufficient to impair macromolecular waste clearance from the rat brain.MethodsUsing a rodent model of chronic neuroinflammation induced by a single high-dose injection of lipopolysaccharide, the clearance kinetics of two fluorophore-conjugated dextran tracers were assayed at 8-weeks post-induction. The expression and distribution of amyloid β and aquaporin-4 proteins within selected brain regions were assayed at 36-weeks post-induction, following open-field, novel object recognition, and contextual fear conditioning assays.ResultsChronic neuroinflammation significantly impaired the clearance kinetics of both dextran tracers and resulted in significantly elevated levels of amyloid β within the hippocampus. Aquaporin-4 density on astrocytic endfeet processes was also reduced within multiple brain regions. These pathologies were associated with significantly enhanced contextual fear memory.ConclusionOur results suggest that chronic neuroinflammation is sufficient to compromise the clearance of macromolecular waste from the brain parenchyma and may be the root cause of impaired waste clearance associated with a variety of brain pathologies.
Test-retest reliability of modular-relevant analysis in brain functional network
Authors: Wen Xuyun , Yang Mengting , Hsu Liming , Zhang Daoqiang 
Published: December 2022

IntroductionThe human brain could be modeled as a complex network via functional magnetic resonance imaging (fMRI), and the architecture of these brain functional networks can be studied from multiple spatial scales with different graph theory tools. Detecting modules is an important mesoscale network measuring approach that has provided crucial insights for uncovering how brain organizes itself among different functional subsystems. Despite its successful application in a wide range of brain network studies, the lack of comprehensive reliability assessment prevents its potential extension to clinical trials.MethodsTo fill this gap, this paper, using resting-state test-retest fMRI data, systematically explored the reliabilities of five popular network metrics derived from modular structure. Considering the repeatability of network partition depends heavily on network size and module detection algorithm, we constructed three types of brain functional networks for each subject by using a set of coarse-to-fine brain atlases and adopted four methods for single-subject module detection and twelve methods for group-level module detection.ResultsThe results reported moderate-to-good reliability in modularity, intra- and inter-modular functional connectivities, within-modular degree and participation coefficient at both individual and group levels, indicating modular-relevant network metrics can provide robust evaluation results. Further analysis identified the significant influence of module detection algorithm and node definition approach on reliabilities of network partitions and its derived network analysis results.DiscussionThis paper provides important guidance for choosing reliable modular-relevant network metrics and analysis strategies in future studies.
Lateralization of cerebral blood flow in the auditory cortex of patients with idiopathic tinnitus and healthy controls: An arterial spin labeling study
Authors: Li Xiaoshuai , Zhao Yansheng , Hui Ying , Wu Yuntao , Chen Qian , Shi Huijing , Lv Han , Li Mengning , Zhao Pengfei , Zhang Wenfei , Zhao Xinyu , Li Jing , Cui Liufu , Wang Zhenchang 
Published: December 2022

ObjectivesTo assess the lateralization of cerebral blood flow (CBF) in the auditory cortex of idiopathic tinnitus patients and healthy controls (HCs) using 3D pseudocontinuous arterial spin labeling (pcASL).MethodsThirty-six patients with idiopathic tinnitus and 43 sex- and age-matched HCs underwent 3D-pcASL scanning using a 3.0 T MRI system. For both groups, region of interest analysis was performed on the primary auditory cortex (PAC), auditory associative cortex (AAC), and secondary auditory cortex (SAC). The clinical data of all subjects were analyzed.ResultsIn both tinnitus patients and HCs, CBF of the left PAC was significantly higher than that of the right (HCs: P = 0.02; patients: P = 0.043), but CBF of the right AAC and SAC was significantly higher than that of the left (AAC: HCs, P &lt; 0.001; patients: P &lt; 0.001. SAC: HCs, P &lt; 0.001; patients: P = 0.001). Compared with HCs, tinnitus patients exhibited significantly higher CBF in the bilateral PAC (right: P = 0.008; left: P = 0.022). CBF in the left PAC was positively correlated with tinnitus severity (r = 0.399, P = 0.016).ConclusionThis study confirms the asymmetry of the auditory cortex and investigates the underlying neuropathology of idiopathic tinnitus in terms of CBF.