bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sjögren’s syndrome: novel insights from proteomics and miRNA expression analysis
Authors: Kamounah Sarah , Sembler-Møller Maria Lynn , Nielsen Claus Henrik , Pedersen Anne Marie Lynge 
Published: May 2023

IntroductionSjögren’s syndrome (SS) is a systemic autoimmune disease, which affects the exocrine glands leading to glandular dysfunction and, particularly, symptoms of oral and ocular dryness. The aetiology of SS remains unclear, and the disease lacks distinctive clinical features. The current diagnostic work-up is complex, invasive and often time-consuming. Thus, there is an emerging need for identifying disease-specific and, ideally, non-invasive immunological and molecular biomarkers that can simplify the diagnostic process, allow stratification of patients, and assist in monitoring the disease course and outcome of therapeutic intervention in SS.MethodsThis systematic review addresses the use of proteomics and miRNA-expression profile analyses in this regard.Results and discussionOut of 272 papers that were identified and 108 reviewed, a total of 42 papers on proteomics and 23 papers on miRNA analyses in saliva, blood and salivary gland tissue were included in this review. Overall, the proteomic and miRNA studies revealed considerable variations with regard to candidate biomarker proteins and miRNAs, most likely due to variation in sample size, processing and analytical methods, but also reflecting the complexity of SS and patient heterogeneity. However, interesting novel knowledge has emerged and further validation is needed to confirm their potential role as biomarkers in SS.
How to communicate with patients in written asynchronous online conversations: an intervention study with undergraduate medical students in a cross-over design
Authors: Festl-Wietek Teresa , Erschens Rebecca , Griewatz Jan , Zipfel Stephan , Herrmann-Werner Anne 
Published: May 2023

IntroductionThe patient-physician encounter is the core element in the treatment of patients and the diagnosis of disease. In these times of digitalization, patient-physician communication is increasingly taking place online: patients embrace new possibilities offered digitally, and physicians are encouraged to adapt accordingly. Since a huge part of online communication is written, this study aims to investigate how medical students communicate with patients online by focusing on their written competencies and whether an intervention might improve their competencies.MethodsThis study was performed in an explanatory cross-sectional manner with a cross-over design. Second-year medical students participated. An intervention was developed on how to formulate an appropriate written response to a patient’s request and integrated a longitudinal communication class. The intervention consists of education on general set-up (e.g., greetings), syntax, spelling, content and kind of communication (e.g., appreciative attitude). After meeting a patient in a simulated role play medical students received the patient’s request via a digital platform. The control group had the same simulated role play and the same task but they received the intervention on communication afterwards. Intervention and control group were statistically compared based on a checklist.ResultsTwenty-nine medical students took part in the study. The results showed that the medical students had basic competencies in dealing with written communication independent if they received the intervention (CG: M = 3.86 ± 1.23 vs. IG: M = 4.07 ± 1.03; p = 0.625). Similar results were also for the emotional competency ratings (MCG = 3.36 ± 1.08; MIG = 3.67 ± 0.98; p = 0.425).The intervention was able to lead to a more appreciative response toward patient.DiscussionIntervention on basic competencies such as simple language and clear presentation might not be needed as an integral part in medical education. However, medical students should learn how to present empathic and authentic behavior in written online communication.
Causal relationship in gut microbiota and upper urinary urolithiasis using Mendelian randomization
Authors: Zhang Ruiqiao , Zhao Weijie , Zhao Ruijie , Zhao Yunhai , Zhang Yanlong , Liang Xuezhi 
Published: May 2023

BackgroundSeveral reports in recent years have found an association between gut microbiota and upper urinary urolithiasis. However, the causal relationship between them remains to be clarified.MethodsGenetic variation is used as a tool in Mendelian randomization for inference of whether exposure factors have a causal effect on disease outcomes. We selected summary statistics from a large genome-wide association study of the gut microbiome published by the MiBioGen consortium with a sample size of 18,340 as an exposure factor and upper urinary urolithiasis data from FinnGen GWAS with 4,969 calculi cases and 213,445 controls as a disease outcome. Then, a two-sample Mendelian randomization analysis was performed by applying inverse variance-weighted, MR-Egger, maximum likelihood, and weighted median. In addition, heterogeneity and horizontal pleiotropy were excluded by sensitivity analysis.ResultsIVW results confirmed that class Deltaproteobacteria (OR = 0.814, 95% CI: 0.666–0.995, P = 0.045), order NB1n (OR = 0.833, 95% CI: 0.737–0.940, P = 3.15 × 10−3), family Clostridiaceae1 (OR = 0.729, 95% CI: 0.581–0.916, P = 6.61 × 10−3), genus Barnesiella (OR = 0.695, 95% CI: 0.551–0.877, P = 2.20 × 10−3), genus Clostridium sensu_stricto_1 (OR = 0.777, 95% CI: 0.612–0.986, P = 0.0380), genus Flavonifractor (OR = 0.711, 95% CI: 0.536–0.944, P = 0.0181), genus Hungatella (OR = 0.829, 95% CI: 0.690–0.995, P = 0.0444), and genus Oscillospira (OR = 0.758, 95% CI: 0.577–0.996, P = 0.0464) had a protective effect on upper urinary urolithiasis, while Eubacterium xylanophilum (OR =1.26, 95% CI: 1.010–1.566, P = 0.0423) had the opposite effect. Sensitivity analysis did not find outlier SNPs.ConclusionIn summary, a causal relationship was found between several genera and upper urinary urolithiasis. However, we still need further randomized controlled trials to validate.
Landscapes of gut microbiome and bile acid signatures and their interaction in HBV-associated acute-on-chronic liver failure
Authors: Bao Zhiwei , Wei Runan , Zheng Xiaoping , Zhang Ting , Bi Yunjiao , Shen Sijia , Zou Pengfei , Zhang Junjie , Yan Huadong , Li Ming D. , Yang Zhongli , Gao Hainv 
Published: May 2023

IntroductionSubmassive hepatic necrosis (SMHN, defined as necrosis of 15–90% of the entire liver on explant) is a likely characteristic pathological feature of ACLF in patients with hepatitis B cirrhosis. We aimed to comprehensively explore microbiome and bile acids patterns across enterhepatic circulation and build well-performing machine learning models to predict SMHN status.MethodsBased on the presence or absence of SMHN, 17 patients with HBV-related end-stage liver disease who received liver transplantation were eligible for inclusion. Serum, portal venous blood, and stool samples were collected for comparing differences of BA spectra and gut microbiome and their interactions. We adopted the random forest algorithm with recursive feature elimination (RF-RFE) to predict SMHN status.ResultsBy comparing total BA spectrum between SMHN (−) and SMHN (+) patients, significant changes were detected only in fecal (P = 0.015). Compared with the SMHN (+) group, the SMHN (−) group showed that UDCA, 7-KLCA, 3-DHCA, 7-KDCA, ISOLCA and α-MCA in feces, r-MCA, 7-KLCA and 7-KDCA in serum, γ-MCA and 7-KLCA in portal vein were enriched, and TUDCA in feces was depleted. PCoA analysis showed significantly distinct overall microbial composition in two groups (P = 0.026). Co-abundance analysis showed that bacterial species formed strong and broad relationships with BAs. Among them, Parabacteroides distasonis had the highest node degree. We further identified a combinatorial marker panel with a high AUC of 0.92.DiscussionOur study demonstrated the changes and interactions of intestinal microbiome and BAs during enterohepatic circulation in ACLF patients with SMHN. In addition, we identified a combinatorial marker panel as non-invasive biomarkers to distinguish the SMHN status with high AUC.
The association between cognitive impairment, gait speed, and Walk ratio
Authors: Knapstad Mari Kalland , Naterstad Ingvill , Bogen Bård 
Published: May 2023

BackgroundGait speed has been found to be associated with cognitive function. However, gait speed is an unspecific measure that may not be informative about gait patterns. The Walk ratio (step length divided by step frequency) can be measured without specialized equipment, and has been suggested as an indicator of central gait control. However, the association with cognitive function is unknown.Research questionIs there a relationship between Walk ratio and cognitive function, and gait speed and cognitive function?MethodsThis was a systematic literature review of studies where spatiotemporal gait parameters was reported in populations with cognitive impairment. The search was performed through PubMed, PEDro, AMED, Cochrane, Embase, MEDLINE, and PsycINFO. The studies had to contain either the Walk ratio, or report average step length and average step frequency. In the latter case, the average step length was divided by the average step frequency. The studies also had to report gait speed and the minimal mental state examination (MMSE). Studies testing patients on treadmills or that did not state the exclusion of patients with neurologic or orthopedic diseases, possible affecting gait ability, were excluded.ResultsA total of 24 studies were included, consisting of 909 patients with cognitive impairment and 4,108 healthy controls. The patient group had a lower Walk ratio (mean difference 0.07, p ≤ 0.001) and gait speed (mean difference 0.26, p ≤ 0.001) than the healthy controls. Using linear regression models, we found an association between the MMSE and the Walk ratio (R2 = 0.29, p &lt; 0.001) and gait speed (R2 = 0.41, p &lt; 0.001) in separate, unadjusted models. In a final model with Walk ratio, gait speed and age, Walk ratio was not significantly associated with MMSE, while gait speed was.SignificanceOur results suggest that preferred gait speed may be preferable to the Walk ratio when assessing older adults with cognitive impairment.
Intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin-induced model of Alzheimer’s disease-like pathology
Authors: Stanojevic Jelena B. , Zeljkovic Milica , Dragic Milorad , Stojanovic Ivana R. , Ilic Tihomir V. , Stevanovic Ivana D. , Ninkovic Milica B. 
Published: May 2023

IntroductionIntracerebroventricularly (icv) injected streptozotocin (STZ) is a widely used model for sporadic Alzheimer’s disease (sAD)-like pathology, marked by oxidative stress-mediated pathological progression. Intermittent theta burst stimulation (iTBS) is a noninvasive technique for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for several neurological diseases, including AD. The present study aims to investigate the effect of the iTBS protocol on the animal model of STZ-induced sAD-like pathology in the context of antioxidant, anti-inflammatory, and anti-amyloidogenic effects in the cortex, striatum, hippocampus, and cerebellum.MethodsMale Wistar rats were divided into four experimental groups: control (icv normal saline solution), STZ (icv STZ—3 mg/kg), STZ + iTBS (STZ rats subjected to iTBS protocol), and STZ + Placebo (STZ animals subjected to placebo iTBS noise artifact). Biochemical assays and immunofluorescence microscopy were used to evaluate functional and structural changes.ResultsThe icv STZ administration induces oxidative stress and attenuates antioxidative capacity in all examined brain regions. iTBS treatment significantly reduced oxidative and nitrosative stress parameters. Also, iTBS decreased Aβ-1-42and APP levels. The iTBS enhances antioxidative capacity reported as elevated activity of its enzymatic and non-enzymatic components. In addition, iTBS elevated BDNF expression and attenuated STZ-induced astrogliosis confirmed by decreased GFAP+/VIM+/C3+cell reactivity in the hippocampus.DiscussionOur results provide experimental evidence for the beneficial effects of the applied iTBS protocol in attenuating oxidative stress, increasing antioxidant capacity and decreasing reactive astrogliosis in STZ-administrated rats.
Behavioral domains in compulsive rats: implications for understanding compulsive spectrum disorders
Authors: Martín-González Elena , Olmedo-Córdoba Manuela , Prados-Pardo Ángeles , Cruz-Garzón Daniel J. , Flores Pilar , Mora Santiago , Moreno-Montoya Margarita 
Published: May 2023

IntroductionCompulsive behavior has been proposed as a transdiagnostic trait observed in different neuropsychiatric disorders, such as obsessive-compulsive disorder, autism, and schizophrenia. Research Domain Criteria (RDoC) strategy could help to disentangle the neuropsychological basis of compulsivity for developing new therapeutic and preventive approaches. In preclinical research, the selection of high-drinker (HD) vs. low-drinker (LD) animals by schedule-induced polydipsia (SIP) is considered a putative model of compulsivity, which includes a well-differentiated behavioral pattern.MethodsThe purpose of this research was to assess the cognitive control and the negative valence system domains in a phenotype of compulsive HD rats. After the selection of animals as HD or LD, we assessed behavioral inflexibility by probabilistic spatial reversal learning (PSRL), motor and cognitive impulsivity by variable delay-to-signal (VDS), and risky decision-making by rodent gambling task (rGT).ResultsHD rats performed fewer reversals and showed less probability of pressing the same lever that was previously reinforced on PSRL, more premature responses after the exposure to longer delays on VDS, and more disadvantageous risky choices on rGT. Moreover, HD animals performed more perseverative responses under the punishment period on rGT.DiscussionThese results highlight that HD compulsive phenotype exhibits behavioral inflexibility, insensitivity to positive feedback, waiting impulsivity, risky decision-making, and frustrative non-reward responsiveness. Moreover, these findings demonstrate the importance of mapping different behavioral domains to prevent, treat, and diagnose compulsive spectrum disorders correctly.
Development and characterization of novel jGCaMP8f calcium sensor variants with improved kinetics and fluorescence response range
Authors: Tran Oanh , Hughes Holly J. , Carter Tom , Török Katalin 
Published: May 2023

IntroductionGenetically encoded biosensors for monitoring intracellular calcium changes have advanced our understanding of cell signaling and neuronal activity patterns in health and disease. Successful application of GCaMP biosensors to a wide range of biological questions requires that sensor properties such as brightness and dynamic range, ligand affinity and response kinetics be tuned to the specific conditions or phenomena to be investigated. Random as well as rational targeted mutations of such sensor molecules have led to a number of important breakthroughs in this field, including the calcium sensors GCaMP6f and GCaMP6fu. jGCaMP8f of the most recently developed generation is promising a step-change in in vivo imaging with further increased fluorescence dynamic range. Here, we critically examine the biophysical properties of jGCaMP8f and report development by rational design of two novel variants of jGCaMP8f.MethodsWe determined the in vitro biophysical properties of jGCaMP8f and selected variants by fluorescence spectroscopies and compared their performance monitoring intracellular Ca2+ transients with previously developed fast and bright GCaMP sensors by live cell imaging.ResultsWe demonstrate that the physiologically highly relevant Mg2+ not only majorly affects the kinetic responses of GCaMPs but also their brightness and fluorescence dynamic range. We developed novel variants jGCaMP8f L27A which has threefold faster off-kinetics and jGCaMP8f F366H which shows a ∼3-fold greater dynamic range than jGCaMP8f, in vitro as well as in HEK293T cells and endothelial cell line HUVEC in response to ATP stimulation.DiscussionWe discuss the importance of optimization of biosensors for studying neurobiology in the context of the novel variants of jGCaMP8f. The jGCaMP8f F366H variant with a large dynamic range has the potential to improve in vivo imaging outcomes with increased signal-to-noise ratio. The L27A variant with faster kinetics than jGCaMP8f has larger cellular responses than previous fast GCaMP variants. The jGCaMP8f generation and novel improved variants presented here will further increase the application potential of GECIs in health and disease.
Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis
Authors: Lv Xiaofeng , Hu Zeng , Liang Fangqi , Liu Shanshan , Gong Haiping , Du Jihang , Deng Xinmin , Qian Jun-Hui , Nie Qian , Luo Jian 
Published: May 2023

BackgroundPrevious epidemiological and other studies have shown an association between ischemic stroke (IS) and frozen shoulder (FS). However, the causal relationship between them remains unclear. Therefore, the present study aimed to investigate the causal relationship between IS and FS using a two-sample Mendelian randomization method.MethodsOur research was divided into two stages: discovery and replication. The data were extracted from publicly available genome-wide association studies (GWAS). We selected a large sample of IS (n = 440, 328) and its subtypes (large-artery atherosclerotic stroke (LAS), cardioembolic stroke (CES), and stroke caused by small-vessel disease (SVS) and lacunar stroke (n = 254, 959) as exposure data. Additionally, we selected a large sample of FS as outcome data (n = 451, 099). Inverse variance weighting (IVW) was applied as the primary analysis method. The weighted median, MR-Egger, simple model, and weighted model were used as complementary analysis methods to assess causal effects. Moreover, heterogeneity was analyzed using Cochran's Q-test with IVW and MR-Egger. The MR-Egger intercept and MR-PRESSO analysis methods were used for pleiotropy testing. The stability of the results was also assessed using a leave-one-out analysis.ResultsIn the discovery stage, the IVW approach revealed an odds ratio (OR) of 1.207 with a 95% confidence interval (CI) of 1.027–1.417 and a P-value of 0.022. This suggests a causal association between IS levels and an increased risk of FS. In the subtype studies of IS, the findings were negative. However, during the replication stage, a significant causal link was found between selected lacunar strokes and FS with an OR of 1.252, a 95% CI of 1.105–1.419, and a P-value of 0.0004. All studies had no pleiotropy or heterogeneity, and the findings were robust.ConclusionsOur study confirmed the causal relationship between any IS level and increased risk of FS. Furthermore, the same results were obtained in the replication stage with lacunar stroke as an exposure factor. However, there was no direct causal relationship between the subtypes of IS and FS. Our study provides theoretical support for shoulder care for patients with IS.
Auditory P300 in individuals with high schizotypy: associations of schizotypal traits with amplitude and latency under different oddball conditions
Authors: Deng Jue , Chen Siwei , Ou Yuanhua , Zhang Yuanjun , Lin Ziyue , Shen Yane , Ye Yiduo 
Published: May 2023

BackgroundThe aim of this study was to compare the characteristics of auditory P300 between non-clinical individuals with high and low schizotypal traits, and investigate the relationship between schizotypy and P300 under various oddball conditions.MethodsAn extreme-group design was adopted. After screening 1,519 young adults using the Schizotypal Personality Questionnaire (SPQ), sixty-three participants were chosen and divided into two groups (schizotypy group: 31 participants; control group: 32 participants). Basic demographic information was assessed and matched between groups. Depression and anxiety indexes were evaluated and controlled. The P300 component was evoked by an auditory oddball paradigm with different frequencies and durations.Results(1) The duration P300 amplitude at PZ site was significantly weaker in the schizotypy group than in the control group [F(1,54) = 7.455, p = 0.009, ηp2 = 0.121]. (2) In the schizotypy group, the latency of frequency P300 at PZ site under large-variant oddball condition was significantly correlated with total SPQ scores (rp = 0.451, p = 0.018) and disorganized dimension scores (rp = 0.381, p = 0.050). (3) In the control group, significantly negative correlations was found between the negative dimension score of SPQ and the frequency P300 amplitudes under small variant condition (PZ: rp = −0.393, p = 0.043; CPZ: rp = −0.406, p = 0.035). In addition, a significant negative relationship was found between disorganized dimension scores and the duration P300 latency at CPZ site under large-variant oddball condition (rp = −0.518, p = 0.006). Moreover, a significant negative association was found between the duration P300 amplitude at CPZ site under small-variant oddball condition and negative factor scores (rp = −0.410, p = 0.034).ConclusionIndividuals with high schizotypal traits were likely to have deficient attention and hypoactive working memory for processing auditory information, especially the duration of sounds. P300 effects were correlated with negative and disorganized schizotypy, rather than positive schizotypy. There were diverse patterns of relationship between schizotypal traits and P300 under different oddball conditions, suggesting that characteristics and parameters of target stimuli should be considered cautiously when implementing an auditory oddball paradigm for individuals with schizophrenia spectrum.
Association between DRD2/ANKK1 rs1800497 C > T polymorphism and post-traumatic stress disorder susceptibility: a multivariate meta-analysis
Authors: Niu Yu-Ming , Zhang Jie , Tang Hong , Cao Lu-Hua , Jiang Ting-Yun , Hu Yuan-Yuan 
Published: May 2023

BackgroundPrevious studies have suggested that the DRD2/ANKK1 rs1800497 C &gt; T polymorphism plays a critical role in the risk of post-traumatic stress disorder (PTSD). However, published data are inconsistent or even contradictory. Therefore, we conducted a meta-analysis to explore the underlying correlation between the rs1800497 C &gt; T polymorphism and PTSD risk.Materials and methodsA total of five online databases were searched, and all related studies were reviewed up to 1 October 2022. Critical information was extracted, and quality assessment was conducted for all included studies. Multivariate meta-analyses were performed for the genetic model choice, and the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power of the genetic models. In addition, heterogeneity, sensitivity, cumulative analysis, and publication bias were analyzed to guarantee statistical power.ResultOverall, 12 observational studies involving 5,515 subjects were included and analyzed in this meta-analysis. Multivariate analysis indicated that a co-dominant genetic model was most likely the best choice. Pooled results revealed an elevated PTSD risk in mutated homozygote TT carriers in the general population (TT vs. CC: OR = 1.73, 95% CI = 1.14–2.62, P = 0.01, I2 = 58.9%) and other specific subgroups. Moreover, similar results were observed in other genetic models using univariate analysis.ConclusionCurrent evidence suggests that the DRD2/ANKK1 rs1800497 C &gt; T polymorphism may contribute to PTSD susceptibility.