bluuebunny/crossref_metadata_2025_split huggingface dataset:
Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice
Authors: López-Cauce Beatriz , Puerto Marta , García Juan José , Ponce-Alonso Manuel , Becerra-Aparicio Federico , del Campo Rosa , Peligros Isabel , Fernández-Aceñero María J. , Gómez-Navarro Yésica , Lara José M. , Miranda-Bautista José , Marín-Jiménez Ignacio , Bañares Rafael , Menchén Luis 
Published: January 2023

BackgroundDysbiosis and mucin depletion are related with intestinal barrier dysfunction and seems to be an early pathophysiological event in inflammatory bowel disease (IBD). The objective of this work is to study these parameters in the natural history of colitis in IL-10 deficient mice (IL-10−/−).MethodsWild type (WT) and IL-10−/−. mice were followed until sacrifice at 3, 5, 10, 20, 57, and 70 weeks. Body weight, colonic weight/length ratio and in vivo intestinal permeability were registered. Expression of inflammatory and adhesion molecules in the colon was explored by qPCR as Mucin-2 (MUC-2) and molecules involved in goblet cell maturation Interleukin-18 (IL-18) and WAP Four-Disulfide Core Domain 2 (WFDC2), the endoplasmic reticulum stress markers X-box-binding protein (Xbp-1) and Reticulon-4B (RTN-4B). Bacterial composition in feces and colonic mucosa was determined by massive sequencing of the V3–V4 regions of 16S rDNA gene.ResultsIL-10-/- mice showed histological inflammation at weeks 20 and 57, but most notably the intestinal permeability was significantly higher from week 10. Concordantly, the number of goblet cells and expression of MUC-2, IL-18, WFDC2 and Xbp-1 were significantly lower in KO from week 10. Nevertheless, no significant differences were found in the mRNA expression of MUC-2 or Xbp-1 between both groups—derived colon organoids. Significant bacterial differences began at week 5, being the Akkermansia deficiency in KO the most relevant result.ConclusionGut microbiota alterations and mucin depletion are associated with early intestinal barrier dysfunction and precede overt gut inflammation in this animal model of IBD.
Effect of static magnetic field on marine mollusc Elysia leucolegnote
Authors: Fei Fan , Zhang Peng , Li Xinyu , Wang Shun , Feng Erhui , Wan Yinglang , Xie Can 
Published: January 2023

Artificial magnetic fields are unavoidable environment for offshore marine organisms. With the substantially increasing submarine cables, the impact of magnetic field generated by cables on marine organisms has gradually attracted people’s attention. However, there are few studies on the effect of magnetic field on molluscs. To explore whether magnetic fields could interfere with the physiological functions of offshore molluscs, here we systematically analyzed the change of metabolism and transcriptome of Elysia leucolegnote exposed to either geomagnetic field or 1.1 T static magnetic field. The blood glucose and lipid levels, as well as the activities of antioxidant enzymes in E. leucolegnote were significantly increased upon the exposure to high static magnetic field for 10 days. Meanwhile, the activities of enzymes related to digestive performance and liver functions were decreased. Possible mechanisms were further revealed through comparative transcriptome analysis. A total of 836 differentially expressed genes were identified, 352 of which were up-regulated and 484 of which were down-regulated after exposure to the high static magnetic field. The up-regulated differential genes were mainly concentrated in lysosomal and apoptotic pathways, and down-regulated differential genes were mainly involved in digestive and immune systems including phagocytosis. This pattern was further confirmed by RT-qPCR analysis. In conclusion, prolonged exposure to a 1.1 T static magnetic field increased oxidative stress and blood glucose and lipid levels, and decreased immunity and physiological conditions in E. leucolegnote. The data we presented here provides a comprehensive view of metabolism change and gene expression pattern of E. leucolegnote exposed to static magnetic field. It may expand our knowledge on the magnetic field effects on offshore mollusc at molecular level, and contribute to clarification of the interaction between marine animals and artificial magnetic fields, which is certainly ecologically important.
Effectiveness of vortioxetine in patients with major depressive disorder and comorbid Alzheimer’s disease in routine clinical practice: An analysis of a post-marketing surveillance study in South Korea
Authors: Cumbo Eduardo , Adair Michael , Åstrom Daniel Oudin , Christensen Michael Cronquist 
Published: January 2023

BackgroundVortioxetine has demonstrated procognitive effects in patients with major depressive disorder (MDD). We assessed the effectiveness and safety of vortioxetine in a cohort of patients with MDD and comorbid Alzheimer’s disease participating in a large post-marketing surveillance study in South Korea.MethodsSubgroup analysis of a 6-month, prospective, multicenter, non-interventional cohort study in outpatients with MDD with a pre-baseline diagnosis of Alzheimer’s disease receiving vortioxetine in routine care settings (n = 207). Patients were assessed at baseline and after 8 weeks; a subset of patients was also assessed after 24 weeks. Depression severity was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) scale, cognitive symptoms using the Perceived Deficits Questionnaire–Depression, Korean version (PDQ-K), and cognitive performance using the Digit Symbol Substitution Test (DSST).ResultsMost patients were receiving a mean daily vortioxetine dose of 5 mg/day (174/190 patients; 91.6%). After 24 weeks of vortioxetine treatment, 71.4% of patients (40/56) had experienced overall clinical improvement (i.e., CGI–Improvement score ≤3) and 51.9% (28/54) had achieved remission from depressive symptoms (i.e., MADRS total score ≤10 points). Respective mean changes in MADRS, PDQ-K, and DSST total scores from baseline to week 24 were −11.5 (p &lt; 0.0001), −5.1 (p = 0.03), and +3.8 points (p = 0.0524). Adverse events were reported by 27 patients (13.0%) and were mostly mild (89.2%).ConclusionPatients with MDD and comorbid Alzheimer’s disease receiving vortioxetine in routine care settings in South Korea demonstrated clinically meaningful improvements in depressive symptoms, cognitive symptoms, and objective cognitive performance over the 6-month treatment period. Treatment with vortioxetine was well tolerated in this patient cohort, with reported adverse events consistent with the established tolerability profile of vortioxetine.
The expression pattern of GDF15 in human brain changes during aging and in Alzheimer’s disease
Authors: Chiariello Antonio , Valente Sabrina , Pasquinelli Gianandrea , Baracca Alessandra , Sgarbi Gianluca , Solaini Giancarlo , Medici Valentina , Fantini Valentina , Poloni Tino Emanuele , Tognocchi Monica , Arcaro Marina , Galimberti Daniela , Franceschi Claudio , Capri Miriam , Salvioli Stefano , Conte Maria 
Published: January 2023

IntroductionGrowth Differentiation Factor 15 (GDF15) is a mitochondrial-stress-responsive molecule whose expression strongly increases with aging and age-related diseases. However, its role in neurodegenerative diseases, including Alzheimer’s disease (AD), is still debated.MethodsWe have characterized the expression of GDF15 in brain samples from AD patients and non-demented subjects (controls) of different ages.ResultsAlthough no difference in CSF levels of GDF15 was found between AD patients and controls, GDF15 was expressed in different brain areas and seems to be predominantly localized in neurons. The ratio between its mature and precursor form was higher in the frontal cortex of AD patients compared to age-matched controls (p &lt; 0.05). Moreover, this ratio was even higher for centenarians (p &lt; 0.01), indicating that aging also affects GDF15 expression and maturation. A lower expression of OXPHOS complexes I, III, and V in AD patients compared to controls was also noticed, and a positive correlation between GDF15 and IL-6 mRNA levels was observed. Finally, when GDF15 was silenced in vitro in dermal fibroblasts, a decrease in OXPHOS complexes transcript levels and an increase in IL-6 levels were observed.DiscussionAlthough GDF15 seems not to be a reliable CSF marker for AD, it is highly expressed in aging and AD brains, likely as a part of stress response aimed at counteracting mitochondrial dysfunction and neuroinflammation.
Transcranial alternating current stimulation combined with sound stimulation improves cognitive function in patients with Alzheimer’s disease: Study protocol for a randomized controlled trial
Authors: Liu Yang , Liu Shuzhen , Tang Can , Tang Keke , Liu Di , Chen Meilian , Mao Zhiqi , Xia Xuewei 
Published: January 2023

BackgroundThe number of patients with Alzheimer’s disease (AD) worldwide is increasing yearly, but the existing treatment methods have poor efficacy. Transcranial alternating current stimulation (tACS) is a new treatment for AD, but the offline effect of tACS is insufficient. To prolong the offline effect, we designed to combine tACS with sound stimulation to maintain the long-term post-effect.Materials and methodsTo explore the safety and effectiveness of tACS combined with sound stimulation and its impact on the cognition of AD patients. This trial will recruit 87 patients with mild to moderate AD. All patients were randomly divided into three groups. The change in Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) scores from the day before treatment to the end of treatment and 3 months after treatment was used as the main evaluation index. We will also explore the changes in the brain structural network, functional network, and metabolic network of AD patients in each group after treatment.DiscussionWe hope to conclude that tACS combined with sound stimulation is safe and tolerable in 87 patients with mild to moderate AD under three standardized treatment regimens. Compared with tACS alone or sound alone, the combination group had a significant long-term effect on cognitive improvement. To screen out a better treatment plan for AD patients. tACS combined with sound stimulation is a previously unexplored, non-invasive joint intervention to improve patients’ cognitive status. This study may also identify the potential mechanism of tACS combined with sound stimulation in treating mild to moderate AD patients.Clinical Trial RegistrationClinicaltrials.gov, NCT05251649. Registered on February 22, 2022.
Early detection and monitoring of hearing loss in vestibular migraine: Extended high-frequency hearing
Authors: Guo Zhaoqi , Wang Jun , Liu Dan , Tian E. , Chen Jingyu , Kong Weijia , Zhang Sulin 
Published: January 2023

BackgroundVestibular migraine (VM) presents mainly with recurrent vestibular symptoms and migraine. A great number of patients with VM have cochlea symptoms such as tinnitus, hearing loss.MethodsA cross-sectional study was conducted on patients with definite VM (dVM) and probable VM (pVM) who met the diagnostic criteria. Auditory-vestibular tests and psychological assessments were performed. Logistic regression was used to evaluate the predictive effect of EHF pure tone audiometry (PTA) for standard frequency (SF) hearing loss.ResultsFifteen patients with pVM and 22 patients with dVM were recruited. Overall, the two most vertigo types were vestibulo-visual symptoms (83.78%) and internal vertigo (54.05%). A vertigo attack persisted for &lt;5 min in approximately 57% of patients, compared with 5 min to 72 h in 43%, and lasted longer than 72 h in 8%. Approximately 87% of patients had psychological disorders. Most patients with VM (92%) suffered from some degree of EHF hearing impairment, and 68% had SF hearing loss, which is substantially higher than their complaints (43%). Moreover, the mean EHF hearing threshold cutoff value (57 dB HL) worked well in predicting SF hearing loss (area under curve, AUC, 0.827), outperforming distortion product optoacoustic emission (AUC, 0.748).ConclusionVM has a wide range of clinical manifestations. Hearing loss had a considerably higher rate compared to actual complaints. Moreover, patients with VM tended to have bilateral EHF and high-frequency hearing loss. The effectiveness of the mean EHF hearing threshold cutoff value in predicting hearing loss supported its use in the early detection of hearing loss and monitoring disease progression.
Electroacupuncture attenuates LPS-induced depression-like behavior through kynurenine pathway
Authors: Wu Xingying , Hu Rong , Jiang Shuo , Di Zhong , Chen Yi , Shi Mengting , Chen Bowen , He Kelin , Qian Kecheng , Guo Qin , Ma Ruijie 
Published: January 2023

BackgroundA growing body of evidence suggests that inflammation and changes in glutamate neurotransmission are two pathophysiological mechanisms underlying depression. Electroacupuncture (EA) is a common therapeutic tool for the treatment of depression. However, the potential antidepressant mechanism of EA remains obscure. The change of the kynurenine pathway (KP) is the research priority of antidepressant mechanisms. This study will investigate the role of EA on lipopolysaccharide (LPS)-induced depression-like behavior and explore its possible mechanism of action.MethodsLipopolysaccharide was used to induce depression-like behavior, and EA was given at Hegu (L14) and Taichong (LR3) acupoints in C57BL/6J mice. Depression-like behaviors were measured by behavioral tests, including tail suspension test (TST), sucrose preference test (SPT), force swim test (FST), and open field test (OFT). The levels of inflammatory cytokines IL-1β, IL-6, and TNF-α, and KP enzyme IDO1 were measured by qPCR and enzyme-linked immunosorbent assay (ELISA), while high-performance liquid chromatography (HPLC) was performed to detect the content of prefrontal cortex and hippocampal as well as serum glutamate, tryptophan (TRP), kynurenic (KYN), and quinolinic acid (QA).ResultsThe results showed that (1) as evidenced by increased spontaneous locomotor activities, decreased immobility duration, and a stronger preference for sucrose in the sucrose preference test, EA reversed LPS-challenged depressive-like behavior. (2) EA at L14 and LR3 decreased the levels of inflammatory cytokines, inhibited IDO1, and regulated KP metabolisms, as well as lowered the concentration of glutamate. (3) EA may exert anti-depression effects by acting on the kynurenine pathway.ConclusionThis study evaluated the effects of EA on depression-like behaviors induced by lipopolysaccharide (LPS) and its regulation of inflammation and the glutamatergic system. Our results suggest that EA can ameliorate depression-like behaviors, lower the level of inflammation, and reduce the release of glutamate, possibly through the regulation of the kynurenine pathway in the brain.
A computational approach based on weighted gene co-expression network analysis for biomarkers analysis of Parkinson’s disease and construction of diagnostic model
Authors: Wu Zhaoping , Hu Zhiping , Gao Yunchun , Xia Yuechong , Zhang Xiaobo , Jiang Zheng 
Published: January 2023

BackgroundParkinson’s disease (PD) is a common age-related chronic neurodegenerative disease. There is currently no affordable, effective, and less invasive test for PD diagnosis. Metabolite profiling in blood and blood-based gene transcripts is thought to be an ideal method for diagnosing PD.AimIn this study, the objective is to identify the potential diagnostic biomarkers of PD by analyzing microarray gene expression data of samples from PD patients.MethodsA computational approach, namely, Weighted Gene Co-expression Network Analysis (WGCNA) was used to construct co-expression gene networks and identify the key modules that were highly correlated with PD from the GSE99039 dataset. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was performed to identify the hub genes in the key modules with strong association with PD. The selected hub genes were then used to construct a diagnostic model based on logistic regression analysis, and the Receiver Operating Characteristic (ROC) curves were used to evaluate the efficacy of the model using the GSE99039 dataset. Finally, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to validate the hub genes.ResultsWGCNA identified two key modules associated with inflammation and immune response. Seven hub genes, LILRB1, LSP1, SIPA1, SLC15A3, MBOAT7, RNF24, and TLE3 were identified from the two modules and used to construct diagnostic models. ROC analysis showed that the diagnostic model had a good diagnostic performance for PD in the training and testing datasets. Results of the RT-PCR experiments showed that there were significant differences in the mRNA expression of LILRB1, LSP1, and MBOAT7 among the seven hub genes.ConclusionThe 7-gene panel (LILRB1, LSP1, SIPA1, SLC15A3, MBOAT7, RNF24, and TLE3) will serve as a potential diagnostic signature for PD.
A bibliometric analysis of telerehabilitation services for patients with stroke
Authors: Wu Dan , Zhang Haojie , Leng Yan , Li Kai , Li Shijue , Lo Wai Leung Ambrose 
Published: January 2023

BackgroundRoutine rehabilitation services were disrupted by the COVID-19 pandemic outbreak. Telehealth was identified as an alternative means to provide access to these services. This bibliometric study aimed to analyze the scientific literature to discover trends and topics in the potential applications of telerehabilitation for patients with stroke.MethodsThe Web of Science electronic database was searched to retrieve relevant publications on telerehabilitation. Bibliometric data, including visual knowledge maps of authors, countries, institutions, and references, were analyzed in CiteSpace. Visualization maps were generated in VOSviewer to illustrate recurrent keywords and countries actively involved in this research area.ResultsThe analysis was performed based on 6,787 publications. The number of publications peaked between 2019 and 2021, coinciding with the years of the COVID-19 outbreak. A total of 113 countries in Europe, North America, Asia, and Oceania had at least one publication in this research field, implying global attention in this research area. Nine of the top 10 most productive countries are developed countries, indicating a potentially higher capability to implement a telerehabilitation program.ConclusionThe potential benefits and diversity of telerehabilitation are already highly visible from clinical studies, and further improvements in these technologies are expected to enhance functionality and accessibility for patients. More relevant research is encouraged to understand the barriers to increased adaptation of telerehabilitation services, which will finally translate into a significant therapeutic or preventive impact.
Systemic inflammation response index as a prognostic predictor in patients with acute ischemic stroke: A propensity score matching analysis
Authors: Dang Hui , Mao Wenjuan , Wang Shanshan , Sha Jing , Lu Mingjia , Cong Li , Meng Xuegang , Li Hongyan 
Published: January 2023

BackgroundAcute ischemic stroke (AIS), the most common type of stroke, is a major cause of morbidity and mortality worldwide. A growing number of studies have demonstrated that inflammation is a critical mechanism in AIS. Being an easily available and effective inflammatory marker, the systemic inflammation response index (SIRI) shows a high association with mortality in patients with cancer and intracerebral hemorrhage. In this study, we evaluated the potential prognostic role of SIRI in critically ill patients with AIS.MethodsClinic data were extracted from the Medical Information Mart data for the Intensive Care IV (MIMIC-IV) database. The optimal cutoff value of SIRI was determined by X-tile software. The primary outcome was the 90-day all-cause mortality, and the secondary outcomes were 30-day and 1-year all-cause mortality of patients with AIS. Cox proportional hazards regression analyses were used to assess the association between SIRI levels and all-cause mortality, and survival curves were estimated using the Kaplan–Meier method. Furthermore, a 1:1 propensity score matching (PSM) method was performed to balance the influence of potential confounding factors.ResultsA total of 2,043 patients were included in our study. X-tile software indicated that the optimal cutoff value of the SIRI for 90-day mortality was 4.57. After PSM, 444 pairs of score-matched patients were generated. Cox proportional hazard model showed that after adjusting for possible confounders, high SIRI level (≥4.57) was independently associated with the 90-day all-cause mortality in the cohort before PSM (HR = 1.56, 95% CI: 1.30–1.89, p &lt; 0.001) and the PSM subset (HR = 1.47, 95% CI: 1.16–1.86, p = 0.001). The survival curves showed that patients with SIRI ≥4.57 had a significantly lower 90-day survival rate in the cohort before PSM (56.7 vs. 77.3%, p &lt; 0.001) and the PSM subset (61.0 vs. 71.8%, p = 0.001). Consistently, AIS patients with high SIRI levels (≥4.57) presented a significantly high risk of 30-day and 1-year all-cause mortality before and after PSM.ConclusionA higher SIRI (≥4.57) was associated with a higher risk of 90-day, 30-day, and 1-year mortality and was an independent risk factor of mortality in patients with acute ischemic stroke.
Impact of polycyclic aromatic hydrocarbon exposure on cognitive function and neurodegeneration in humans: A systematic review and meta-analysis
Authors: Humphreys Jessica , Valdés Hernández Maria del C. 
Published: January 2023

IntroductionThis article documents an emerging body of evidence concerning the neurological effect of polycyclic aromatic hydrocarbon (PAH) exposure with regard to cognitive function and increased risk of neurodegeneration.MethodsTwo electronic databases, PubMed and Web of Science, were systematically searched.ResultsThe 37/428 studies selected included outcomes measuring cognitive function, neurobehavioral symptoms of impaired cognition, and pathologies associated with neurodegeneration from pre-natal (21/37 studies), childhood (14/37 studies), and adult (8/37 studies) PAH exposure. Sufficient evidence was found surrounding pre-natal exposure negatively impacting child intelligence, mental development, average overall development, verbal IQ, and memory; externalizing, internalizing, anxious, and depressed behaviors; and behavioral development and child attentiveness. Evidence concerning exposure during childhood and as an adult was scarce and highly heterogeneous; however, the presence of neurodegenerative biomarkers and increased concentrations of cryptic “self” antigens in serum and cerebrospinal fluid samples suggest a higher risk of neurodegenerative disease. Associations with lowered cognitive ability and impaired attentiveness were found in children and memory disturbances, specifically auditory memory, verbal learning, and general memory in adults.DiscussionAlthough evidence is not yet conclusive and further research is needed, the studies included supported the hypothesis that PAH exposure negatively impacts cognitive function and increases the risk of neurodegeneration in humans, and recommends considering the introduction of a variable “rural vs. urban” as covariate for adjusting analyses, where the neurological functions affected (as result of our review) are outcome variables.