bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxic culture of umbilical cord mesenchymal stem cell-derived sEVs prompts peripheral nerve injury repair
Authors: Zhu Ziying , Zhang Yujun , Huang Zhihua , Hao Haojie , Yan Muyang 
Published: March 2023

IntroductionRepair and regeneration of the peripheral nerve are important for the treatment of peripheral nerve injury (PNI) caused by mechanical tears, external compression injuries and traction injuries. Pharmacological treatment can promote the proliferation of fibroblasts and Schwann cells (SCs), which longitudinally fill the endoneurial canal and form Bungner’s band, helping the repair of peripheral nerves. Therefore, the development of new drugs for the treatment of PNI has become a top priority in recent years.MethodsHere, we report that small extracellular vesicles (sEVs) produced from umbilical cord mesenchymal stem cells (MSC-sEVs) cultured under hypoxia promote repair and regeneration of the peripheral nerve in PNI and may be a new therapeutic drug candidate.ResultsThe results showed that the amount of secreted sEVs was significantly increased in UC-MSCs compared with control cells after 48 h of culture at 3% oxygen partial pressure in a serum-free culture system. The identified MSC-sEVs could be taken up by SCs in vitro, promoting the growth and migration of SCs. In a spared nerve injury (SNI) mouse model, MSC-sEVs accelerated the recruitment of SCs at the site of PNI and promoted peripheral nerve repair and regeneration. Notably, repair and regeneration in the SNI mouse model were enhanced by treatment with hypoxic cultured UC-MSC-derived sEVs.DiscussionTherefore, we conclude that hypoxic cultured UC-MSC-derived sEVs may be a promising candidate drug for repair and regeneration in PNI.
Excitatory synchronization of rat hippocampal interneurons during network activation in vitro
Authors: Pendeliuk Viktoria S. , Melnick Igor V. 
Published: March 2023

IntroductionHippocampal interneurons (INs) are known to synchronize their electrical activity via mechanisms, which are poorly defined due to immense complexity of neural tissue but seem to depend on local cell interactions and intensity of network activity.MethodsHere, synchronization of INs was studied using paired patch-clamp recordings in a simplified culture model with intact glutamate transmission. The level of network activity was moderately elevated by field electric stimulation, which is probably an analogue of afferent processing in situ.ResultsEven in baseline conditions, ∼45% of spontaneous inhibitory postsynaptic currents (sIPSCs) resulting from firing of individual presynaptic INs coincided between cells within ±1 ms due to simple divergence of inhibitory axons. Brief network activation induced an appearance of ‘hypersynchronous’ (∼80%) population sIPSCs occurring in response to coherent discharges of several INs with jitter ±4 ms. Notably, population sIPSCs were preceded by transient inward currents (TICs). Those were excitatory events capable to synchronize firing of INs, in this respect being reminiscent of so-called fast prepotentials observed in studies on pyramidal neurons. TICs also had network properties consisting of heterogeneous components: glutamate currents, local axonal and dendritic spikelets, and coupling electrotonic currents likely via gap junctions; putative excitatory action of synaptic gamma-aminobutyric acid (GABA) was not involved. The appearance of population excitatory-inhibitory sequences could be initiated and reproduced by firing of a single excitatory cell reciprocally connected with one IN.DiscussionOur data demonstrate that synchronization of INs is initiated and dominated by glutamatergic mechanisms, which recruit, in a whole-sale manner, into supporting action other excitatory means existing in a given neural system.
The controlling nutritional status score and risk factors associated with malnutrition in patients with acute ischemic stroke
Authors: Chen Yuanyuan , Yang Hongyan , Lan Meijuan , Wei Hui , Chen Yanqin 
Published: March 2023

ObjectivesMalnutrition is an independent risk factor for poor outcomes in patients who suffered an acute ischemic stroke (AIS). The controlling nutritional status (CONUT) score can provide information for nutritional management in AIS patients. However, the risk factors associated with the CONUT score have not been established to date. Therefore, in this study, we aimed to investigate the CONUT score of patients with AIS and explore the potential risk factors associated with it.MethodsWe conducted a retrospective review of the data from consecutive AIS patients who were recruited in the CIRCLE study. Within 2 days of admission, we gathered the CONUT score, the Nutritional Risk Screening 2002, the Modified Rankin Scale, the National Institutes of Health Neurological Deficit Score (NIHSS), and demographic data from medical records. We used chi-squared tests to examine admission, and a logistic regression analysis was performed to explore the risk factors associated with CONUT in patients with AIS.ResultsA total of 231 patients with AIS participated in the study, with a mean age of 62.32 ± 13.0 years and a mean NIHSS of 6.77 ± 3.8. Of these patients, 41(17.7%) had hyperlipidemia. In terms of nutritional assessment, 137(59.3%) patients with AIS had high CONUT scores, 86(37.2%) patients with AIS had low or high BMI, and 117(50.6%) patients with AIS had NRS-2002 scores below 3. The chi-squared tests showed that age, NIHSS, body mass index (BMI), and hyperlipidemia were associated with the CONUT score (P &lt; 0.05). The logistic regression analysis showed that low NIHSS scores (OR = 0.055 95% CI: 0.003–0.893), younger age (OR = 0.159 95% CI: 0.054–0.469), and hyperlipidemia (OR = 0.303 95% CI: 0.141–0.648) were independently associated with lower CONUT scores (P &lt; 0.05), whereas BMI was not found to be independently associated with the CONUT.ConclusionsMore than half of the patients with AIS were at risk of malnutrition, with age and neurological deficits being identified as risk factors for nutritional control. Hyperlipidemia was found to be a protective factor of the CONUT, while NRS-2002 and BMI did not affect the nutritional control in patients with AIS.
Cocktail-party listening and cognitive abilities show strong pleiotropy
Authors: Mathias Samuel R. , Knowles Emma E. M. , Mollon Josephine , Rodrigue Amanda L. , Woolsey Mary K. , Hernandez Alyssa M. , Garret Amy S. , Fox Peter T. , Olvera Rene L. , Peralta Juan M. , Kumar Satish , Göring Harald H. H. , Duggirala Ravi , Curran Joanne E. , Blangero John , Glahn David C. 
Published: March 2023

IntroductionThe cocktail-party problem refers to the difficulty listeners face when trying to attend to relevant sounds that are mixed with irrelevant ones. Previous studies have shown that solving these problems relies on perceptual as well as cognitive processes. Previously, we showed that speech-reception thresholds (SRTs) on a cocktail-party listening task were influenced by genetic factors. Here, we estimated the degree to which these genetic factors overlapped with those influencing cognitive abilities.MethodsWe measured SRTs and hearing thresholds (HTs) in 493 listeners, who ranged in age from 18 to 91 years old. The same individuals completed a cognitive test battery comprising 18 measures of various cognitive domains. Individuals belonged to large extended pedigrees, which allowed us to use variance component models to estimate the narrow-sense heritability of each trait, followed by phenotypic and genetic correlations between pairs of traits.ResultsAll traits were heritable. The phenotypic and genetic correlations between SRTs and HTs were modest, and only the phenotypic correlation was significant. By contrast, all genetic SRT–cognition correlations were strong and significantly different from 0. For some of these genetic correlations, the hypothesis of complete pleiotropy could not be rejected.DiscussionOverall, the results suggest that there was substantial genetic overlap between SRTs and a wide range of cognitive abilities, including abilities without a major auditory or verbal component. The findings highlight the important, yet sometimes overlooked, contribution of higher-order processes to solving the cocktail-party problem, raising an important caveat for future studies aiming to identify specific genetic factors that influence cocktail-party listening.
Habituation deficit of visual evoked potentials in migraine patients with hypermobile Ehlers-Danlos syndrome
Authors: Maestrini Ilaria , Rocchi Lorenzo , Puledda Francesca , Viganò Alessandro , Giuliani Giada , Jannini Tommaso Benedetto , Celletti Claudia , Altieri Marta , Camerota Filippo , Toscano Massimiliano , Di Piero Vittorio 
Published: March 2023

ObjectivesMigraine is one of the most frequent clinical manifestations of hypermobile Ehlers-Danlos syndrome (hEDS). The comorbidity between these two diseases has been only partially investigated. We aimed to observe whether neurophysiological alterations described in migraineurs in visual evoked potentials (VEPs) were present in hEDS patients with migraine.MethodsWe enrolled 22 hEDS patients with migraine (hEDS) and 22 non-hEDS patients with migraine (MIG), with and without aura (according to ICHD-3), as well as 22 healthy controls (HC). Repetitive pattern reversal (PR)-VEPs were recorded in basal conditions in all participants. During uninterrupted stimulation, 250 cortical responses were recorded (4,000 Hz sample rate) and divided into epochs of 300 ms after the stimulus. Cerebral responses were divided into five blocks. The habituation was calculated as the slope interpolating the amplitudes in each block, for both the N75-P100 and P100-N145 components of PR-VEP.ResultsWe observed a significant habituation deficit of the P100-N145 component of PR-VEP in hEDS compared to HC (p = 0.002), unexpectedly more pronounced than in MIG. We observed only a slight habituation deficit of N75-P100 in hEDS, with a slope degree that was intermediate between MIG and HC.DiscussionhEDS patients with migraine presented an interictal habituation deficit of both VEPs components like MIG. Pathophysiological aspects underlying the pathology could account for the peculiar pattern of habituation in hEDS patients with migraine characterized by a pronounced habituation deficit in the P100-N145 component and a less clear-cut habituation deficit in the N75-P100 component with respect to MIG.
Gene network reveals LASP1, TUBA1C, and S100A6 are likely playing regulatory roles in multiple sclerosis
Authors: Karimi Nafiseh , Motovali-Bashi Majid , Ghaderi-Zefrehei Mostafa 
Published: March 2023

IntroductionMultiple sclerosis (MS), a non-contagious and chronic disease of the central nervous system, is an unpredictable and indirectly inherited disease affecting different people in different ways. Using Omics platforms genomics, transcriptomics, proteomics, epigenomics, interactomics, and metabolomics database, it is now possible to construct sound systems biology models to extract full knowledge of the MS and recognize the pathway to uncover the personalized therapeutic tools.MethodsIn this study, we used several Bayesian Networks in order to find the transcriptional gene regulation networks that drive MS disease. We used a set of BN algorithms using the R add-on package bnlearn. The BN results underwent further downstream analysis and were validated using a wide range of Cytoscape algorithms, web based computational tools and qPCR amplification of blood samples from 56 MS patients and 44 healthy controls. The results were semantically integrated to improve understanding of the complex molecular architecture underlying MS, distinguishing distinct metabolic pathways and providing a valuable foundation for the discovery of involved genes and possibly new treatments.ResultsResults show that the LASP1, TUBA1C, and S100A6 genes were most likely playing a biological role in MS development. Results from qPCR showed a significant increase (P &lt; 0.05) in LASP1 and S100A6 gene expression levels in MS patients compared to that in controls. However, a significant down regulation of TUBA1C gene was observed in the same comparison.ConclusionThis study provides potential diagnostic and therapeutic biomarkers for enhanced understanding of gene regulation underlying MS.
Serum neurofilament light chain levels are associated with early neurological deterioration in minor ischemic stroke
Authors: Li Jie , Zhang Ping , Zhu Yalan , Duan Yong , Liu Shan , Fan Jie , Chen Hong , Wang Chun , Yi Xingyang 
Published: March 2023

ObjectivesPatients with minor ischemic stroke (MIS) frequently suffer from early neurological deterioration (END) and become disabled. Our study aimed to explore the association between serum neurofilament light chain (sNfL) levels and END in patients with MIS.MethodsWe conducted a prospective observational study in patients with MIS [defined as a National Institutes of Health Stroke Scale (NIHSS) score 0–3] admitted within 24 h from the onset of symptoms. sNfL levels were measured at admission. The primary outcome was END, defined as an increase in the NIHSS score by ≥2 points within 5 days after admission. Univariate and multivariate analyses were performed to explore the risk factors associated with END. Stratified analyses and interaction tests were conducted to identify variables that might modify the association between sNfL levels and END.ResultsA total of 152 patients with MIS were enrolled, of which 24 (15.8%) developed END. The median sNfL level was 63.1 [interquartile range (IQR), 51.2–83.4] pg/ml on admission, which was significantly higher than that of 40 age- and sex-matched healthy controls (median 47.6, IQR 40.8–56.1 pg/ml; p &lt; 0.001). Patients with MIS with END had a higher level of sNfL (with ND: median 74.1, IQR 59.5–89.8 pg/ml; without END: median 61.2, IQR 50.5–82.2 pg/ml; p = 0.026). After adjusting for age, baseline NIHSS score, and potential confounding factors in multivariate analyses, an elevated sNfL level (per 10 pg/mL) was associated with an increased risk of END [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.04–1.77; p = 0.027). Stratified analyses and interaction tests demonstrated that the association between sNfL and END did not change by age group, sex, baseline NIHSS score, Fazekas' rating scale, hypertension, diabetes mellitus, intravenous thrombolysis, and dual antiplatelet therapy in patients with MIS (all p for interaction &gt; 0.05). END was associated with an increased risk of unfavorable outcomes (modified Rankin scale score ranging from 3 to 6) at 3 months.ConclusionEarly neurological deterioration is common in minor ischemic stroke and is associated with poor prognosis. The elevated sNfL level was associated with an increased risk of early neurological deterioration in patients with minor ischemic stroke. sNfL might be a promising biomarker candidate that can help to identify patients with minor ischemic stroke at high risk of neurological deterioration, for reaching individual therapeutic decisions in clinical practice.
Individual response to transcranial direct current stimulation as a function of working memory capacity and electrode montage
Authors: Menze Inga , Mueller Notger G. , Zaehle Tino , Schmicker Marlen 
Published: March 2023

IntroductionAttempts to improve cognitive abilities via transcranial direct current stimulation (tDCS) have led to ambiguous results, likely due to the method’s susceptibility to methodological and inter-individual factors. Conventional tDCS, i.e., using an active electrode over brain areas associated with the targeted cognitive function and a supposedly passive reference, neglects stimulation effects on entire neural networks.MethodsWe investigated the advantage of frontoparietal network stimulation (right prefrontal anode, left posterior parietal cathode) against conventional and sham tDCS in modulating working memory (WM) capacity dependent transfer effects of a single-session distractor inhibition (DIIN) training. Since previous results did not clarify whether electrode montage drives this individual transfer, we here compared conventional to frontoparietal and sham tDCS and reanalyzed data of 124 young, healthy participants in a more robust way using linear mixed effect modeling.ResultsThe interaction of electrode montage and WM capacity resulted in systematic differences in transfer effects. While higher performance gains were observed with increasing WM capacity in the frontoparietal stimulation group, low WM capacity individuals benefited more in the sham condition. The conventional stimulation group showed subtle performance gains independent of WM capacity.DiscussionOur results confirm our previous findings of WM capacity dependent transfer effects on WM by a single-session DIIN training combined with tDCS and additionally highlight the pivotal role of the specific electrode montage. WM capacity dependent differences in frontoparietal network recruitment, especially regarding the parietal involvement, are assumed to underlie this observation.
Extramural vascular invasion nomogram before radical resection of rectal cancer based on magnetic resonance imaging
Authors: Tian Lianfen , Li Ningqin , Xie Dong , Li Qiang , Zhou Chuanji , Zhang Shilai , Liu Lijuan , Huang Caiyun , Liu Lu , Lai Shaolu , Wang Zheng 
Published: March 2023

PurposeThis study verified the value of magnetic resonance imaging (MRI) to construct a nomogram to preoperatively predict extramural vascular invasion (EMVI) in rectal cancer using MRI characteristics.Materials and methodsThere were 55 rectal cancer patients with EMVI and 49 without EMVI in the internal training group. The external validation group consisted of 54 rectal cancer patients with EMVI and 55 without EMVI. High-resolution rectal T2WI, pelvic diffusion-weighted imaging (DWI) sequences, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were used. We collected the following data: distance between the lower tumor margin and the anal margin, distance between the lower tumor margin and the anorectal ring, tumor proportion of intestinal wall, mrT stage, maximum tumor diameter, circumferential resection margin, superior rectal vein width, apparent diffusion coefficient (ADC), T2WI EMVI score, DWI and DCE-MRI EMVI scores, demographic information, and preoperative serum tumor marker data. Logistic regression analyses were used to identify independent risk factors of EMVI. A nomogram prediction model was constructed. Receiver operating characteristic curve analysis verified the predictive ability of the nomogram. P &lt; 0.05 was considered significant.ResultTumor proportion of intestinal wall, superior rectal vein width, T2WI EMVI score, and carbohydrate antigen 19-9 were significant independent predictors of EMVI in rectal cancer and were used to create the model. The areas under the receiver operating characteristic curve, sensitivities, and specificities of the nomogram were 0.746, 65.45%, and 83.67% for the internal training group, respectively, and 0.780, 77.1%, and 71.3% for the external validation group, respectively.Data conclusionA nomogram including MRI characteristics can predict EMVI in rectal cancer preoperatively and provides a valuable reference to formulate individualized treatment plans and predict prognosis.
Detection of missed deaths in cancer registry data to reduce bias in long-term survival estimation
Authors: Dahm Stefan , Barnes Benjamin , Kraywinkel Klaus 
Published: March 2023

BackgroundPopulation-based cancer survival estimates can provide insight into the real-world impacts of healthcare interventions and preventive services. However, estimation of survival rates obtained from population-based cancer registries can be biased due to missed incidence or incomplete vital status data. Long-term survival estimates in particular are prone to overestimation, since the proportion of deaths that are missed, for example through unregistered emigration, increases with follow-up time. This also applies to registry-based long-term prevalence estimates. The aim of this report is to introduce a method to detect missed deaths within cancer registry data such that long-term survival of cancer patients does not exceed survival in the general population.MethodsWe analyzed data from 15 German epidemiologic cancer registries covering the years 1970-2016 and from Surveillance, Epidemiology, and End Results (SEER)-18 registries covering 1975-2015. The method is based on comparing survival times until exit (death or follow-up end) and ages at exit between deceased patients and surviving patients, stratified by diagnosis group, sex, age group and stage. Deceased patients with both follow-up time and age at exit in the highest percentile were regarded as outliers and used to fit a logistic regression. The regression was then used to classify each surviving patient as a survivor or a missed death. The procedure was repeated for lower percentile thresholds regarding deceased persons until long-term survival rates no longer exceeded the survival rates in the general population.ResultsFor the German cancer registry data, 0.9% of total deaths were classified as having been missed. Excluding these missed deaths reduced 20-year relative survival estimates for all cancers combined from 140% to 51%. For the whites in SEER data, classified missed deaths amounted to 0.02% of total deaths, resulting in 0.4 percent points lower 20-year relative survival rate for all cancers combined.ConclusionThe method described here classified a relatively small proportion of missed deaths yet reduced long-term survival estimates to more plausible levels. The effects of missed deaths should be considered when calculating long-term survival or prevalence estimates.
Survival outcomes and prognostic factors of lung cancer patients with the MET exon 14 skipping mutation: A single-center real-world study
Authors: Gow Chien-Hung , Hsieh Min-Shu , Chen Yi-Lin , Liu Yi-Nan , Wu Shang-Gin , Shih Jin-Yuan 
Published: March 2023

IntroductionThe MET exon 14 skipping (METex14) mutation is an important oncogenic driver in lung cancer. We performed a retrospective analysis of clinical data from lung cancer patients with the METex14 mutation to analyze their survival outcomes and associated prognostic factors.MethodsA one-step reverse transcription-polymerase chain reaction to examine the presence of the METex14 mutation was performed using RNA samples from 1374 lung cancer patients with no detected EGFR and ALK mutations. Pathological features and immunohistochemistry (IHC) results for c-MET were analyzed in patients with METex14-positive tumors.ResultsMETex14 was identified in 69 patients with lung cancer, including 53 adenocarcinoma (ADC) and 16 non-ADC patients. In comparison with patients without the METex14 mutation, lung cancer patients harboring the METex14 mutation were generally elderly individuals, never-smokers, and had poor performance scores. A higher frequency of METex14 mutations was detected in pulmonary sarcomatoid carcinoma (PSC) patients (24.3%, n = 9/37). However, stage IV PSC patients with or without the METex14 mutations showed similarly poor overall survival (OS) (p = 0.429). For all 36 METex14-positive lung ADCs, multivariate analysis showed several poor prognostic factors, including strong c-MET IHC staining (p = 0.006), initial brain metastasis (p = 0.005), and administration of only supportive care (p &lt; 0.001). After excluding seven patients who received only supportive care, we further analyzed 29 stage IV lung ADC patients with METex14 mutations who received anti-cancer treatment. Multivariate analysis showed that pemetrexed treatment (p = 0.003), lung radiotherapy (p = 0.020), initial brain metastasis (p = 0.005), and strong c-MET IHC staining (p = 0.012) were independent prognostic factors for OS in these patients.ConclusionsA higher frequency of METex14 mutations was detected in PSC patients. Stage IV PSC patients with or without the METex14 mutations had similarly poor overall survival. Pemetrexed-based chemotherapy, strong c-MET ICH staining, initial brain metastasis, and lung radiotherapy, may help predict survival outcomes in patients with advanced lung ADCs harboring the METex14 mutation.