bluuebunny/crossref_metadata_2025_split huggingface dataset:
GLP-1RAs caused gastrointestinal adverse reactions of drug withdrawal: a system review and network meta-analysis
Authors: Zhang Ziqi , Zhang Qiling , Tan Ying , Chen Yu , Zhou Xiqiao , Liu Su , Yu Jiangyi 
Published: July 2023

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly reduce postprandial blood glucose, inhibit appetite, and delay gastrointestinal emptying. However, it is controversial that some patients are intolerant to GLP-1RAs.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials (RCTs) using GLP-1RAs with documented withdrawal due to gastrointestinal adverse reactions (GI AEs) from their inception to September 28, 2022. After extracting the information incorporated into the studies, a random-effects network meta-analysis was performed within a frequentist framework.Results64 RCTs were finally enrolled, which included six major categories of the GLP-1RA. The sample size of the GLP-1RAs treatment group was 16,783 cases. The risk of intolerable gastrointestinal adverse reactions of Liraglutide and Semaglutide was higher than that of Dulaglutide. Meanwhile, the higher the dose of the same GLP-1RA preparation, the more likely to cause these adverse reactions. These intolerable GI AEs were not significantly related to drug homology or formulations and may be related to the degree of suppression of the appetite center.ConclusionDulaglutide caused the lowest intolerable GI AEs, while Liraglutide and Semaglutide were the highest. For Semaglutide, the higher the dose, the more likely it is to drive GI AEs. Meanwhile, the risk of these GI AEs is independent of the different formulations of the drug. All these findings can effectively guide individualized treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359346, identifier CRD42022359346.
Predicted lean body mass in relation to cognitive function in the older adults
Authors: Gong Hong-Jian , Tang Xingyao , Chai Yin-He , Qiao Yu-Shun , Xu Hui , Patel Ikramulhaq , Zhang Jin-Yan , Zhou Jian-Bo 
Published: July 2023

BackgroundPrevious findings about lean body mass (LBM) and cognitive function remain unclear. We aimed to examine this association by using data from the National Health and Nutrition Examination Survey (NHANES).MethodsUsing data from the NHANES 2011-2014, we conducted logistic regression models to investigate the relation between the predicted LBM and domain-specific cognitive function assessed by Digit Symbol Substitution Test (DSST), Consortium to Establish a Registry for Alzheimer’s Disease Word Learning test (CERAD-WL) and Delayed Recall test (CERAD-DR), and Animal Fluency (AF) for information processing speed, memory, and executive function, respectively. Cognitive impairment was defined as the lowest quartile of each cognitive test in the total population. Sex-stratified analysis was further made.ResultsA total of 2955 participants aged 60 and above (mean [SD] age, 69.17[0.20] years; 1511 female [51.13%]) were included in the study. After being adjusted for social economic factors, anthropometric parameters, and diseases, we found a positive association between predicted LBM and information processing speed (Odds ratio of DSST impairment= 0.95, 95%CI= 0.91 to 0.99) regardless of body mass index and sex. Compared with patients in the first quartile of predicted LBM, those in the fourth quartile had an odds ratio of 0.355 (95% confidence interval 0.153-0.822) for DSST impairment. No significant relation in other cognitive tests and predicted LBM was found whether stratified by sex or not.ConclusionOur findings point to the association between predicted lean body mass and cognitive dysfunction in information processing speed, which could be used for early detection and prevention of deterioration of cognitive function among older adults.
A novel scatterplot-based method to detect copy number variation (CNV)
Authors: Qiao Jia-Lu , Levinson Rebecca T. , Chen Bowang , Engelter Stefan T. , Erhart Philipp , Gaynor Brady J. , McArdle Patrick F. , Schlicht Kristina , Krawczak Michael , Stenman Martin , Lindgren Arne G. , Cole John W. , Grond-Ginsbach Caspar 
Published: July 2023

Objective: Most methods to detect copy number variation (CNV) have high false positive rates, especially for small CNVs and in real-life samples from clinical studies. In this study, we explored a novel scatterplot-based method to detect CNVs in microarray samples.Methods: Illumina SNP microarray data from 13,254 individuals were analyzed with scatterplots and by PennCNV. The data were analyzed without the prior exclusion of low-quality samples. For CNV scatterplot visualization, the median signal intensity of all SNPs located within a CNV region was plotted against the median signal intensity of the flanking genomic region. Since CNV causes loss or gain of signal intensities, carriers of different CNV alleles pop up in clusters. Moreover, SNPs within a deletion are not heterozygous, whereas heterozygous SNPs within a duplication show typical 1:2 signal distribution between the alleles. Scatterplot-based CNV calls were compared with standard results of PennCNV analysis. All discordant calls as well as a random selection of 100 concordant calls were individually analyzed by visual inspection after noise-reduction.Results: An algorithm for the automated scatterplot visualization of CNVs was developed and used to analyze six known CNV regions. Use of scatterplots and PennCNV yielded 1019 concordant and 108 discordant CNV calls. All concordant calls were evaluated as true CNV-findings. Among the 108 discordant calls, 7 were false positive findings by the scatterplot method, 80 were PennCNV false positives, and 21 were true CNVs detected by the scatterplot method, but missed by PennCNV (i.e., false negative findings).Conclusion: CNV visualization by scatterplots allows for a reliable and rapid detection of CNVs in large studies. This novel method may thus be used both to confirm the results of genome-wide CNV detection software and to identify known CNVs in hitherto untyped samples.
Identification of runs of homozygosity associated with male fertility in Italian Brown Swiss cattle
Authors: Pacheco Hendyel A. , Rossoni Attilio , Cecchinato Alessio , Peñagaricano Francisco 
Published: July 2023

Intensive selection for improved productivity has been accompanied by an increase in inbreeding rates and a reduction in genetic diversity. The increase in inbreeding tends to impact performance, especially fitness-related traits such as male fertility. Inbreeding can be monitored using runs of homozygosity (ROH), defined as contiguous lengths of homozygous genotypes observed in an individual’s chromosome. The goal of this study was to evaluate the presence of ROH in Italian Brown Swiss cattle and assess its association with bull fertility. First, we evaluated the association between ROH and male fertility using 1,102 Italian Brown Swiss bulls with sire conception rate records and 572 K SNPs spanning the entire genome. Second, we split the entire population into 100 high-fertility and 100 low-fertility bulls to investigate the potential enrichment of ROH segments in the low-fertility group. Finally, we mapped the significant ROH regions to the bovine genome to identify candidate genes associated with sperm biology and male fertility. Notably, there was a negative association between bull fertility and the amount of homozygosity. Four different ROH regions located in chromosomes 6, 10, 11, and 24 were significantly overrepresented in low-fertility bulls (Fisher’s exact test, p-value &lt;0.01). Remarkably, these four genomic regions harbor many genes such as WDR19, RPL9, LIAS, UBE2K, DPF3, 5S-rRNA, 7SK, U6, and WDR7 that are related to sperm biology and male fertility. Overall, our findings suggest that inbreeding and increased homozygosity have a negative impact on male fertility in Italian Brown Swiss cattle. The quantification of ROH can contribute to minimizing the inbreeding rate and avoid its negative effect on fitness-related traits, such as male fertility.
TLR7/TLR8 activation and susceptibility genes synergize to breach gut barrier in a mouse model of lupus
Authors: Ma Longhuan , Terrell Morgan , Brown Josephine , Castellanos Garcia Abigail , Elshikha Ahmed , Morel Laurence 
Published: July 2023

BackgroundMounting evidence suggests that increased gut permeability, or leaky gut, and the resulting translocation of pathobionts or their metabolites contributes to the pathogenesis of Systemic Lupus Erythematosus. However, the mechanisms underlying the induction of gut leakage remain unclear. In this study, we examined the effect of a treatment with a TLR7/8 agonist in the B6.Sle1.Sle2.Sle3 triple congenic (TC) mouse, a spontaneous mouse model of lupus without gut leakage.Materials and methodsLupus-prone mice (TC), TC.Rag1-/- mice that lack B and T cells, and congenic B6 healthy controls were treated with R848. Gut barrier integrity was assessed by measuring FITC-dextran in the serum following oral gavage. Claudin-1 and PECAM1 expression as well as the extent of CD45+ immune cells, B220+ B cells, CD3+ T cells and CD11b+ myeloid cells were measured in the ileum by immunofluorescence. NKp46+ cells were measured in the ileum and colon by immunofluorescence. Immune cells in the ileum were also analyzed by flow cytometry.ResultsR848 decreased gut barrier integrity in TC but not in congenic control B6 mice. Immunofluorescence staining of the ileum showed a reduced expression of the tight junction protein Claudin-1, endothelial cell tight junction PECAM1, as well as an increased infiltration of immune cells, including B cells and CD11b+ cells, in R848-treated TC as compared to untreated control mice. However, NKp46+ cells which play critical role in maintaining gut barrier integrity, had a lower frequency in treated TC mice. Flow cytometry showed an increased frequency of plasma cells, dendritic cells and macrophages along with a decreased frequency of NK cells in R848 treated TC mice lamina propria. In addition, we showed that the R848 treatment did not induce gut leakage in TC.Rag1-/- mice that lack mature T and B cells.ConclusionsThese results demonstrate that TLR7/8 activation induces a leaky gut in lupus-prone mice, which is mediated by adaptive immune responses. TLR7/8 activation is however not sufficient to breach gut barrier integrity in non-autoimmune mice.
Network proteomic analysis identifies inter-alpha-trypsin inhibitor heavy chain 4 during early human Achilles tendon healing as a prognostic biomarker of good long-term outcomes
Authors: Wu Xinjie , Chen Junyu , Sun Wei , Hart David A. , Ackermann Paul W. , Ahmed Aisha S. 
Published: July 2023

The suboptimal or protracted regeneration of injured connective tissues often results in significant dysfunction, pain, and functional disability. Despite the prevalence of the condition, few studies have been conducted which focused on biomarkers or key molecules involved in processes governing healing outcomes. To gain insight into injured connective tissue repair, and using the Achilles tendon as a model system, we utilized quantitative proteomic and weighted co-expression network analysis of tissues acquired from Achilles tendon rupture (ATR) patients with different outcomes at 1-year postoperatively. Two modules were detected to be associated with prognosis. The initial analysis identified inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) as a biomarker or hub protein positively associated with better healing outcomes. Additional analysis identified the beneficial role of ITIH4 in inflammation, cell viability, apoptosis, proliferation, wound healing, and for the synthesis of type I collagen in cultured fibroblasts. Functionally, the effects of ITIH4 were found to be mediated by peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathways. Taken together, these findings suggest that ITIH4 plays an important role in processes of connective tissue repair and advocate for the potential of ITIH4 as a therapeutic target for injured connective tissue repair.Trial registrationhttp://clinicaltrials.gov, identifiers NCT02318472, NCT01317160.
Productive arts engagement at the Tokyo Fuji Art Museum and its health effects on the older Japanese population: results of a randomized controlled trial
Authors: Hayashi Yoko , Matskiv Jacqueline , Galery Kevin , Beauchet Olivier 
Published: July 2023

BackgroundThis randomized controlled trial aims to compare changes in mental and physical health in older Japanese community-dwellers who participated in a productive art-based activity at the Tokyo Fuji Art Museum (intervention group) and in their counterparts, who did not participate in the intervention (control group).MethodsA total of 73 older community-dwellers living in Tokyo participated in a single-blind RCT in two parallel groups (intervention group versus control group). The intervention was 2 h of productive art-based activities per week. The weekly sessions were carried out at the Tokyo Fuji Art Museum over a 12-week period. The control group did not participate in any productive art-based activity over the study period. Well-being, quality of life and frailty were assessed before the first, and after the last, art-based activity. These outcomes were assessed with the same schedule in both groups.ResultsThe intervention group saw a significant improvement in their quality of life (p &lt; 0.044) and mixed results on their physical health (i.e., decreased frailty status) when compared to the control group. The comparison of changes in frailty scores between M0 and M3 showed improvement in the intervention group (p = 0.014), but when adjusted for baseline characteristics by linear regressions, revealed only a trend (p = 0.070). No conclusive effect was shown with well-being.InterpretationThis RCT showed mixed health effects of productive art engagement in older Japanese community-dwellers in Tokyo. Benefits were reported for quality of life and mixed effects were observed for frailty, while no significant effect was found for well-being.Clinical Trial Registration: Ethic committee of Shobi University, Tokyo (Japan), ref. A-2021-1; Clinical Trial Number NCT03679715.
Hepatocyte growth factor combined with adenosine deaminase as biomarker for diagnosis of tuberculous pleural effusion
Authors: Zheng Sheng-Cai , Huang Zhong-Yin , Zhai Kan , Shi Huan-Zhong , Shao Ming-Ming 
Published: July 2023

BackgroundThe simple, rapid, and accurate diagnosis of tuberculous pleural effusion (TPE) remains difficult. This study aimed to determine the accuracy of hepatocyte growth factor (HGF) in the diagnosis of TPE.MethodsWe quantified the expression of HGF, adenosine deaminase (ADA), and interferon gamma (IFN-γ) in pleural effusion (PE) in 97 TPE subjects and 116 non-TPE subjects using an enzyme-linked immunosorbent assay (ELISA) or a fully automatic biochemical analyzer. The diagnostic performance of these three biomarkers was evaluated using a receiver operating characteristic (ROC) curve of subjects by age and gender.ResultsWe discovered that the TPE group had much higher levels of HGF than the non-TPE group, regardless of age or gender, and that there was no statistically significant difference between the two groups’ levels of HGF expression in peripheral plasma. In female TPE patients aged ≤65 years, the AUCs of TPE and non-TPE diagnosed by HGF, ADA or IFN-γ were 0.988, 0.964, and 0.827, respectively. HGF plus ADA had the highest diagnostic efficacy in female TPE patients aged ≤65 years. With HGF plus ADA having a cut-off value of 0.219 for distinguishing TPE from non-TPE, the area under the curve (AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV) were, respectively, 0.998 (95% confidence interval [CI], 0.993–1.000), 100 (95% CI, 89.997–100.000), 96.667 (95% CI, 82.783–99.916), 97.222 (95% CI, 83.594–99.586), and 100.ConclusionThis study confirmed that HGF plus ADA has high diagnostic efficacy in younger female TPE patients and has the potential to be an excellent biomarker.
Locus specific endogenous retroviral expression associated with Alzheimer’s disease
Authors: Dawson Tyson , Rentia Uzma , Sanford Jessie , Cruchaga Carlos , Kauwe John S. K. , Crandall Keith A. 
Published: July 2023

IntroductionHuman endogenous retroviruses (HERVs) are transcriptionally-active remnants of ancient retroviral infections that may play a role in Alzheimer’s disease.MethodsWe combined two, publicly available RNA-Seq datasets with a third, novel dataset for a total cohort of 103 patients with Alzheimer’s disease and 45 healthy controls. We use telescope to perform HERV quantification for these samples and simultaneously perform gene expression analysis.ResultsWe identify differentially expressed genes and differentially expressed HERVs in Alzheimer’s disease patients. Differentially expressed HERVs are scattered throughout the genome; many of them are members of the HERV-K superfamily. A number of HERVs are correlated with the expression of dysregulated genes in Alzheimer’s and are physically proximal to genes which drive disease pathways.DiscussionDysregulated expression of ancient retroviral insertions in the human genome are present in Alzheimer’s disease and show localization patterns that may explain how these elements drive pathogenic gene expression.
Prospective collection of blood plasma samples to identify potential biomarkers for the prehospital stroke diagnosis (ProGrEss-Bio): study protocol for a multicenter prospective observational study
Authors: Geisler Frederik , Haacke Lisa , Lorenz Maren , Schwabauer Eugen , Wendt Matthias , Bernhardt Lydia , Dashti Eman , Freitag Erik , Kunz Alexander , Hofmann-Shen Christina , Zuber Martina , Waldschmidt Carolin , Kandil Farid I. , Kappert Kai , Dang-Heine Chantip , Lorenz-Meyer Irina , Audebert Heinrich J. , Weber Joachim E. 
Published: July 2023

IntroductionIntravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are well-established, evidence-based, time-critical therapies that reduce morbidity and mortality in acute ischemic stroke (AIS) patients. The exclusion of intracerebral hemorrhage (ICH) is mandatory and has been performed by cerebral imaging to date. Mobile stroke units (MSUs) have been shown to improve functional outcomes by bringing cerebral imaging and IVT directly to the patient, but they have limited coverage. Blood biomarkers clearly distinguishing between AIS, ICH, and stroke mimics (SM) could provide an alternative to cerebral imaging if concentration changes are detectable in the hyperacute phase after stroke with high diagnostic accuracy. In this study, we will take blood samples in a prehospital setting to evaluate potential biomarkers. The study was registered in the German Clinical Trials Register (https://drks.de/search/de) with the identifier DRKS00023063.Methods and analysisWe plan a prospective, observational study involving 300 patients with suspected stroke and symptom onset of ≤4.5 h before the collection of biomarkers. Study participants will be recruited from three sites in Berlin, Germany during MSU deployments. The focus of the study is the collection of blood samples from participants at the prehospital scene and from participants with AIS or ICH at a second-time point. All samples will be analyzed using targeted and untargeted analytical approaches. Study-related information about participants, including medical information and discharge diagnoses from the subsequent treating hospital, will be collected and documented in an electronic case report form (eCRF).DiscussionThis study will evaluate whether a single blood biomarker or a combination of biomarkers can distinguish patients with AIS and ICH from patients with stroke and SM in the early phase after symptom onset in the prehospital setting. In addition, the kinetics of blood biomarkers in AIS and ICH patients will be investigated. Our goal is to evaluate new ways to reliably diagnose stroke in the prehospital setting and thus accelerate the application of evidence-based therapies to stroke patients.
Hand-worn devices for assessment and rehabilitation of motor function and their potential use in BCI protocols: a review
Authors: Bates Madison , Sunderam Sridhar 
Published: July 2023

IntroductionVarious neurological conditions can impair hand function. Affected individuals cannot fully participate in activities of daily living due to the lack of fine motor control. Neurorehabilitation emphasizes repetitive movement and subjective clinical assessments that require clinical experience to administer.MethodsHere, we perform a review of literature focused on the use of hand-worn devices for rehabilitation and assessment of hand function. We paid particular attention to protocols that involve brain-computer interfaces (BCIs) since BCIs are gaining ground as a means for detecting volitional signals as the basis for interactive motor training protocols to augment recovery. All devices reviewed either monitor, assist, stimulate, or support hand and finger movement.ResultsA majority of studies reviewed here test or validate devices through clinical trials, especially for stroke. Even though sensor gloves are the most commonly employed type of device in this domain, they have certain limitations. Many such gloves use bend or inertial sensors to monitor the movement of individual digits, but few monitor both movement and applied pressure. The use of such devices in BCI protocols is also uncommon.DiscussionWe conclude that hand-worn devices that monitor both flexion and grip will benefit both clinical diagnostic assessment of function during treatment and closed-loop BCI protocols aimed at rehabilitation.
Investigating the lateralisation of experimentally induced auditory verbal hallucinations
Authors: Mak Olivia , Couth Samuel , Plack Christopher J. , Kotz Sonja A. , Yao Bo 
Published: July 2023

IntroductionAuditory verbal hallucinations (AVHs), or hearing non-existent voices, are a common symptom in psychosis. Recent research suggests that AVHs are also experienced by neurotypical individuals. Individuals with schizophrenia experiencing AVHs and neurotypicals who are highly prone to hallucinate both produce false positive responses in auditory signal detection. These findings suggest that voice-hearing may lie on a continuum with similar mechanisms underlying AVHs in both populations.MethodsThe current study used a monaural auditory stimulus in a signal detection task to test to what extent experimentally induced verbal hallucinations are (1) left-lateralised (i.e., more likely to occur when presented to the right ear compared to the left ear due to the left-hemisphere dominance for language processing), and (2) predicted by self-reported hallucination proneness and auditory imagery tendencies. In a conditioning task, fifty neurotypical participants associated a negative word on-screen with the same word being played via headphones through successive simultaneous audio-visual presentations. A signal detection task followed where participants were presented with a target word on-screen and indicated whether they heard the word being played concurrently amongst white noise.ResultsResults showed that Pavlovian audio-visual conditioning reliably elicited a significant number of false positives (FPs). However, FP rates, perceptual sensitivities, and response biases did not differ between either ear. They were neither predicted by hallucination proneness nor auditory imagery.DiscussionThe results show that experimentally induced FPs in neurotypicals are not left-lateralised, adding further weight to the argument that lateralisation may not be a defining feature of hallucinations in clinical or non-clinical populations. The findings also support the idea that AVHs may be a continuous phenomenon that varies in severity and frequency across the population. Studying induced AVHs in neurotypicals may help identify the underlying cognitive and neural mechanisms contributing to AVHs in individuals with psychotic disorders.