bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depression and type 2 diabetes risk: a Mendelian randomization study
Authors: Liu Kaiyuan , Zhou Diyi , Chen Lijun , Hao Sida 
Published: August 2024

BackgroundExtensive observational evidence has suggested an association between depression and type 2 diabetes (T2D). However, the causal relationships between these two diseases require further investigation. This study aimed to evaluate the bidirectional causal effect between two types of depression and T2D using two-sample Mendelian randomization (MR).MethodsWe applied two-step MR techniques, using single-nucleotide polymorphisms (SNPs) as the genetic instruments for analysis. We utilized summary data from genome-wide association studies (GWASs) for major depression (MD), depressive status (frequency of depressed mood in the last two weeks), T2D, and other known T2D risk factors such as obesity, sedentary behavior (time spent watching television), and blood pressure. The analysis utilized inverse variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, MR pleiotropy residual sum, and outlier methods to determine potential causal relationships.ResultsThe study found that MD was positively associated with T2D, with an odds ratio (OR) of 1.26 (95% CI: 1.10-1.43, p = 5.6×10-4) using the IVW method and an OR of 1.21 (95% CI: 1.04-1.41, p = 0.01) using the weighted median method. Depressive status was also positively associated with T2D, with an OR of 2.26 (95% CI: 1.03-4.94, p = 0.04) and an OR of 3.62 (95% CI: 1.33-9.90, p = 0.01) using the IVW and weighted median methods, respectively. No causal effects of MD and depressive status on T2D risk factors were observed, and T2D did not influence these factors.ConclusionOur study demonstrates a causal relationship between depression and an increased risk of developing T2D, with both major depression and depressive status being positively associated with T2D.
Prenatal diagnosis of the recurrent 1q21.1 microdeletions in fetuses with ultrasound anomalies and review of the literature
Authors: Liu Lei , Lei Tingying , Guo Fei , Ma Chunling , Zhen Li , Zhang Lina , Li Dongzhi 
Published: August 2024

ObjectiveThe recurrent 1q21.1 microdeletion syndrome is an autosomal dominant disorder and is characterized by dysmorphic facial features, microcephaly, developmental delay, and congenital defects. However, most studies on the distal deletions in the 1q21.1 region were diagnosed postnatally. This study aimed to provide a better understanding of the ultrasound and molecular findings of fetuses with recurrent 1q21.1 microdeletions in prenatal diagnosis.MethodsIn this retrospective study, we reported 21 cases with the recurrent 1q21.1 microdeletion syndrome diagnosed at our prenatal diagnostic center from January 2016 to January 2023. The clinical data were reviewed for these cases, including the maternal demographics, indications for invasive testing, ultrasound findings, CMA results, and pregnancy outcomes.ResultsIn the study, a total of 21 cases with recurrent 1q21.1 microdeletions were diagnosed prenatally by CMA. Fifteen cases were described with ultrasound indications, and the most common findings are as follows: increased nuchal translucency (NT) (26.7%), intrauterine growth retardation (IUGR) (26.7%), congenital heart defects (CHD) (20%), and congenital anomalies of the kidney and urinary tract (CAKUT) (13.3%). All the cases with the distal 1q21.1 deletions contain the common minimal region (located between BP3 and BP4) and eight OMIM genes. Parental studies to determine the inheritance of the deletion were performed for eight cases, and half of the cases were inherited from one of the parents. Pregnancy outcomes were available for nine cases; eight (88.9%) pregnancies were determined to be terminated and one (11.1%) was full-term delivery.ConclusionTo our knowledge, this is the largest study to find that fetuses with recurrent 1q21.1 microdeletions were closely associated with increased NT, CHD, IUGR, and CAKUT. In addition, ours is the first study to report that cerebral ventriculomegaly might be associated with recurrent 1q21.1 microdeletions. More comprehensive studies are needed for a better understanding of the prenatal phenotype–genotype relationship of the recurrent 1q21.1 microdeletion syndrome in future.
Pre-vaccination Schistosoma mansoni and hookworm infections are associated with altered vaccine immune responses: a longitudinal analysis among adolescents living in helminth-endemic islands of Lake Victoria, Uganda
Authors: Natukunda Agnes , Zirimenya Ludoviko , Nkurunungi Gyaviira , Nassuuna Jacent , Nkangi Ronald , Mutebe Alex , Corstjens Paul L. A. M. , van Dam Govert J. , Elliott Alison M. , Webb Emily L. 
Published: August 2024

BackgroundVariations in vaccine responses have been observed between populations. A role for helminth infections has been proposed due to their immunomodulatory properties. In a secondary analysis of data from a randomised trial assessing effects of anthelminthic treatment on vaccine responses, we examined associations between helminth infections at baseline prior to vaccine administration, and vaccine responses among adolescents (9-17 years) in Koome Islands, Lake Victoria, Uganda.MethodsParticipants received BCG [week 0], yellow fever (YF-17D), oral typhoid (Ty21a), HPV-prime [week 4], and HPV-boost, tetanus/diphtheria [week 28]. Outcomes were BCG-specific interferon-γ ELISpot responses and antibody responses to yellow-fever-, typhoid-, HPV-, tetanus- and diphtheria-specific antigens measured at two time points post vaccination. S. mansoni infection was determined as positive if either the plasma Circulating Anodic Antigen (CAA) assay or stool PCR were positive. Hookworm and Strongyloides were determined by stool PCR. Linear mixed effects regression was used to assess associations.ResultsAmong 478 adolescents, 70% were Schistosoma mansoni (Sm) infected and 23% hookworm infected at baseline. Sm was associated with lower Salmonella Typhi O:LPS-specific IgG responses (adjusted geometric mean ratio (aGMR) 0.69 (0.57-0.83)), and hookworm with higher diphtheria-specific IgG (aGMR 1.16 (1.02, 1.31)) and lower HPV-16-specific IgG (aGMR 0.70 (0.55, 0.90)) post-vaccination. High Sm intensity was associated with lower BCG-specific interferon-γ and S. Typhi O:LPS-specific IgG.ConclusionsWe found inverse associations between Sm and responses to two live vaccines, whereas hookworm was positively associated with diphtheria-specific IgG. These findings support the hypothesis that helminth infections can modulate vaccine responses, while also highlighting potential heterogeneity in the direction of these effects.
Safety analysis of quinolones use in minors—based on the FAERS database
Authors: Li Yanwei , Wang Jing , Wang ChengLiang , Chen Li 
Published: August 2024

ObjectiveThis study utilizes the FDA Adverse Event Reporting System (FAERS) to investigate adverse drug event (ADE) signals linked to quinolones use (ciprofloxacin, moxifloxacin, levofloxacin, ofloxacin) in minors, offering insights for clinical use.MethodsMinors were categorized into four age groups. ADE reports for these quinolones from the first quarter of 2015 to the third quarter of 2023 were extracted from the FAERS database. Data analysis used reporting odds ratio (ROR) and the MHRA method.ResultsMost ADE cases in minors involved ciprofloxacin (575)and levofloxacin (477). In the infant group, various injury, poisoning, and procedural complication events were more frequently associated with ciprofloxacin, levofloxacin, and moxifloxacin (19.83%, 31.25%, and 100.00%, respectively). In the preschool children group, psychiatric disorders were more frequently reported with levofloxacin and ofloxacin use (59.00% and 47.62%, respectively). Ocular disorders were notably associated with moxifloxacin in the children group (62.50%), In the adolescent group, more gastrointestinal diseases occurred with ciprofloxacin (12.96%).ConclusionADE occurrence with quinolones in minors varies by age. Strict adherence to indications, rational use, avoiding prolonged use, and monitoring for short-term reactions are essential. Enhanced monitoring of interactions and drug education are crucial to reducing ADE.
Exploring barriers to the effective use of computer-based simulation in pharmacy education: a mixed-methods case study
Authors: Gharib Ahmed M. , Peterson Gregory M. , Bindoff Ivan K. , Salahudeen Mohammed S. 
Published: August 2024

BackgroundAt the University of Tasmania (UTAS), pharmacy education traditionally relies on placements to provide students with hands-on experience. However, these placements have become increasingly limited due to logistical challenges and growing student numbers. Computer-based simulation (CBS) has the potential to offer a scalable, effective alternative to enhance learning and critical thinking. However, integrating CBS in pharmacy education faces several barriers that must be addressed for successful implementation.ObjectiveTo gain insight into pharmacy educators’ and students’ views regarding the barriers, and potential solutions, to integrating CBS in pharmacy practice education.MethodsThis mixed-methods case study involved semi-structured interviews with pharmacy educators and quantitative surveys with pharmacy students. The data underwent thematic coding for interview transcripts and statistical analysis for survey responses. The findings were integrated by examining convergence, complementarity, and discrepancy, revealing insights into how pharmacy students and educators perceive implementation barriers and improvement strategies for CBS.ResultsTen interviews were conducted, and 75 survey responses were collected, with a 62.5% response rate. Key barriers to CBS integration included educators’ heavy workload, scepticism about CBS’s educational value, and general integration challenges. Students, however, showed high acceptance of CBS, with 70.7% agreeing that CBS could assess their knowledge, 69.3% emphasising its role in developing problem-solving skills, and 80% viewing CBS as a complement to classroom study. Proposed solutions for enhancing CBS uptake included additional institutional support by appointing dedicated simulation technicians, leveraging champions to advocate for CBS, and aligning CBS with educational objectives.ConclusionA significant gap between students’ readiness and educators’ hesitancy to use CBS in pharmacy education was identified. While students are eager to adopt new technologies, educators expressed reservations, primarily due to workload concerns and uncertainties about the efficacy of CBS. The feedback from educators suggests that institutions may see improved uptake by employing dedicated support personnel and initiating targeted training programs. Future research should focus on exploring barriers and facilitators, using larger and more diverse samples, and gaining deeper insights into decision-makers’ perspectives to enhance the integration and efficacy of CBS in pharmacy education.
Conjugal plasmid transfer in the plant rhizosphere in the One Health context
Authors: Riva Francesco , Dechesne Arnaud , Eckert Ester M. , Riva Valentina , Borin Sara , Mapelli Francesca , Smets Barth F. , Crotti Elena 
Published: August 2024

IntroductionHorizontal gene transfer (HGT) of antibiotic resistance genes (ARGs) is one of the primary routes of antimicrobial resistance (AMR) dissemination. In the One Health context, tracking the spread of mobile genetic elements (MGEs) carrying ARGs in agri-food ecosystems is pivotal in understanding AMR diffusion and estimating potential risks for human health. So far, little attention has been devoted to plant niches; hence, this study aimed to evaluate the conjugal transfer of ARGs to the bacterial community associated with the plant rhizosphere, a hotspot for microbial abundance and activity in the soil. We simulated a source of AMR determinants that could enter the food chain via plants through irrigation.MethodsAmong the bacterial strains isolated from treated wastewater, the strain Klebsiella variicola EEF15 was selected as an ARG donor because of the relevance of Enterobacteriaceae in the AMR context and the One Health framework. The strain ability to recolonize lettuce, chosen as a model for vegetables that were consumed raw, was assessed by a rifampicin resistant mutant. K. variicola EEF15 was genetically manipulated to track the conjugal transfer of the broad host range plasmid pKJK5 containing a fluorescent marker gene to the natural rhizosphere microbiome obtained from lettuce plants. Transconjugants were sorted by fluorescent protein expression and identified through 16S rRNA gene amplicon sequencing.Results and discussionK. variicola EEF15 was able to colonize the lettuce rhizosphere and inhabit its leaf endosphere 7 days past bacterial administration. Fluorescence stereomicroscopy revealed plasmid transfer at a frequency of 10−3; cell sorting allowed the selection of the transconjugants. The conjugation rates and the strain’s ability to colonize the plant rhizosphere and leaf endosphere make strain EEF15::lacIq-pLpp-mCherry-gmR with pKJK5::Plac::gfp an interesting candidate to study ARG spread in the agri-food ecosystem. Future studies taking advantage of additional environmental donor strains could provide a comprehensive snapshot of AMR spread in the One Health context.
Comparison of spontaneous brain activity in distinguishing parkinsonian variant of multiple system atrophy from Parkinson’s disease at an early stage
Authors: Wang Shichan , Xiao Yi , Hou Yanbing , Li Chunyu , Zhang Lingyu , Ou Ruwei , Wei Qianqian , Lin Junyu , Yang Tianmi , Che Ningning , Jiang Qirui , Zheng Xiaoting , Liu Jiyong , Shang Huifang 
Published: August 2024

BackgroundThe overlapping clinical manifestations in parkinsonian variant of multiple system atrophy (MSA-P) and Parkinson’s Disease (PD) can complicate clinical diagnostic accuracy, particularly in the early stage. The study aims to uncover the patterns of brain function in the initial phase of the two conditions.MethodsWe recruited 24 MSA-P patients, 34 PD patients and 27 healthy controls (HC). Voxel-wise fractional amplitude of low-frequency fluctuation (fALFF) was compared to characterize regional brain function, followed by seed-based functional connectivity (FC) analysis. Receiver operating characteristic (ROC) analyses were used to examine the diagnostic accuracy of fALFF.ResultsCompared to HC, decreased fALFF was observed in the bilateral basal ganglia (BG) of MSA-P patients, while decreased fALFF was identified in the left BG of PD patients. Additionally, elevated fALFF was found in the superior cerebellum for MSA-P patients and the temporo-occipital cortex for PD patients. Furthermore, PD patients exhibited increased FC in the cortico-striatal loop compared to MSA-P patients. The fALFF of the left caudate distinguished MSA-P from HC with an area under the curve (AUC) of 0.838 (p &lt; 0.001) and from PD with an AUC of 0.772 (p &lt; 0.001). The fALFF of the left putamen distinguished PD from HC with an AUC of 0.736 (p = 0.002).ConclusionOur findings indicated common and distinct abnormalities in spontaneous brain activity within BG, cerebellum, and cortices in early-stage MSA-P and PD patients. PD patients employed more compensatory mechanisms than MSA-P patients. Furthermore, fALFF may aid in early differentiation between MSA-P and PD.
Magnitude and predictors of elasticity of demand for morphine are similar in male and female rats
Authors: Harris Andrew C. , Muelken Peter , Liu Shirelle X. , Smethells John R. , LeSage Mark G. , Gewirtz Jonathan C. 
Published: August 2024

IntroductionSex differences in vulnerability to opioid use disorder (OUD) have been reported in some clinical and preclinical studies, but findings are mixed and further research is needed in this area. The goal of this study was to compare elasticity of demand (reinforcement efficacy) in an i.v. morphine self-administration (SA) model in male and female rats using a translationally relevant behavioral economics approach. Rate of acquisition and predictors of individual differences in demand (e.g., cumulative morphine infusions during acquisition) were also evaluated in both sexes.Materials, methods, and resultsAcquisition of morphine SA (0.4 mg/kg/infusion) under a fixed ratio (FR) 1 schedule of reinforcement was slower and infusions earned were lower in females than in males (n = 30–31/sex), but infusions earned did not differ between sexes during the FR 2 and FR 3 phases of acquisition. Increases in the FR response requirement across sessions during demand testing (FR 1–FR 96) resulted in a progressive reduction in morphine infusions in both sexes. Morphine consumption was well-described by an exponential demand function in both sexes and was associated with considerable individual vulnerability. There were no sex differences in elasticity of demand (rate of decline in morphine consumption with increasing price) or intensity of demand (consumption at zero price). A higher number of infusions earned during the FR 2 and FR 3 phases of acquisition and greater maximum response rates during demand testing were associated with lower demand elasticity (i.e., greater reinforcing efficacy) in both males and females, whereas other relationships were sex-specific (e.g., higher intensity of demand was associated with lower elasticity of demand in males but not in females).ConclusionOur findings indicate similar elasticity of demand and predictors of individual differences in demand for morphine in male and female rats, although sex differences were observed in initial rate of acquisition and in some correlations between morphine SA measures. These data are consistent with findings of similar OUD vulnerability in males and females in some human and animal studies.
Novel insights into mechanisms of inhibition of colonic motility by loperamide
Authors: Parkar Nabil , Spencer Nick J. , Wiklendt Luke , Olson Trent , Young Wayne , Janssen Patrick , McNabb Warren C. , Dalziel Julie E. 
Published: August 2024

BackgroundIt is well known that opiates slow gastrointestinal (GI) transit, via suppression of enteric cholinergic neurotransmission throughout the GI tract, particularly the large intestine where constipation is commonly induced. It is not clear whether there is uniform suppression of enteric neurotransmission and colonic motility across the full length of the colon. Here, we investigated whether regional changes in colonic motility occur using the peripherally-restricted mu opioid agonist, loperamide to inhibit colonic motor complexes (CMCs) in isolated mouse colon.MethodsHigh-resolution video imaging was performed to monitor colonic wall diameter on isolated whole mouse colon. Regional changes in the effects of loperamide on the pattern generator underlying cyclical CMCs and their propagation across the full length of large intestine were determined.ResultsThe sensitivity of CMCs to loperamide across the length of colon varied significantly. Although there was a dose-dependent inhibition of CMCs with increasing concentrations of loperamide (10 nM - 1 μM), a major observation was that in the mid and distal colon, CMCs were abolished at low doses of loperamide (100 nM), while in the proximal colon, CMCs persisted at the same low concentration, albeit at a significantly slower frequency. Propagation velocity of CMCs was significantly reduced by 46%. The inhibitory effects of loperamide on CMCs were reversed by naloxone (1 μM). Naloxone alone did not change ongoing CMC characteristics.DiscussionThe results show pronounced differences in the inhibitory action of loperamide across the length of large intestine. The most potent effect of loperamide to retard colonic transit occurred between the proximal colon and mid/distal regions of colon. One of the possibilities as to why this occurs is because the greatest density of mu opioid receptors are located on interneurons responsible for neuro-neuronal transmission underlying CMCs propagation between the proximal and mid/distal colon. The absence of effect of naloxone alone on CMC characteristics suggest that the mu opioid receptor has little ongoing constitutive activity under our recording conditions.
Does tinnitus amplify the effects of healthy eating patterns and physical activity on the sleep disturbance or sleep insufficiency, based on the case study of NHANES survey in the United States
Authors: Chen Jia , Zou Wujun , Li Hao , Luo Yu , Lu Kaifu , Yi Xuelian , Li Hong , Shi Zhu , Meng Juan 
Published: August 2024

ObjectiveExploring whether the presence of tinnitus amplifies the effects of an individual’s dietary patterns and physical activity on sleep disturbance or sleep insufficiency.Study designThis study extracted data from the five National Health and Nutrition Examination Surveys (NHANES) between 2009 and 2018, including individuals who had undergone complete questionnaires on tinnitus, dietary habits, physical activity, and sleep. Multivariate logistic regression, restricted cubic spline (RCS) and subgroup analyses were conducted to explore the associations of dietary habits, physical activity, and tinnitus with sleep disturbance and sleep insufficiency.ResultsA total of 7,440 participants were enrolled in this study, of whom 1,795 participants were evaluated as sleep disturbance (24.13%), and 2,281 were sleep insufficiency (30.66%). With adjusting confounding factors of demographic and socioeconomic variables, among overall population, participants with tinnitus showed a significantly increased risk of sleep disturbance [adjusted odds ratio (aOR) = 2.08, 95% confidence interval (CI): 1.83–2.36), and sleep insufficiency (aOR = 1.31, 95% CI: 1.15–1.49). Poor dietary habits also increased the risk of sleep disturbance (aOR = 1.08, 95% CI: 1.04–1.12), as does lack of physical activity (aOR = 1.14, 95% CI: 1.03–1.27); but neither exposure factors significantly increased the risk of sleep insufficiency. The non-linear trend analyses of RCS found that the influence of exposure factors on sleep disturbance experiencing a steady or small decline trend after rising. In addition, the results of the subgroup analysis showed that in tinnitus patients, poor dietary habits and lack of physical activity both significantly increased the risk of sleep disturbance, and poor dietary habits also increased the risk of sleep insufficiency remarkable, but lack of physical activity did not. In healthy participants, poor dietary habits were only significantly associated the sleep disturbance, while lack of physical inactivity even had a protective effect against sleep insufficiency.ConclusionCompared to the general population, tinnitus significantly amplified the effects of poor dietary patterns and physical inactivity on sleep disturbance and sleep insufficiency. For tinnitus patients, adjusting a healthy diet and increasing exercise could more effectively promote their sleep health.