bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-Invasive Brain Stimulation Modulates GABAergic Activity In Neurofibromatosis 1
Authors: Garg Shruti , Williams Steve , Jung JeYoung , Pobric Gorana , Nandi Tulika , Lim Ben , Vassallo Grace , Green Jonathan , Evans D. Gareth , Stagg Charlotte J , Parkes Laura , Stivaros Stavros 
Published: September 2021

Abstract
BackgroundNeurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive phenotypes common to neurodevelopmental conditions such as Autism Spectrum Disorder (ASD) & Attention Deficit Hyperactivity Disorder (ADHD). GABAergic dysregulation underlies working memory impairments seen in NF1. This mechanistic experimental study investigates how inter-individual differences in GABA relate to working memory and whether application of anodal transcranial direct current stimulation (atDCS) can modulate of GABA and working memory.Methods31 adolescents with NF1 were recruited to a single-blind, sham-controlled cross-over trial. Baseline assessments included detailed working memory tests and parent reported measures. Each participant had two study visits, one with atDCS and another with sham intervention applied to the left Dorsolateral Prefrontal Cortex (DLPFC) inside the scanner. Magnetic Resonance Spectroscopy was collected before and after aTDCS/sham intervention in the left DLPFC and occipital cortex.ResultsHigher baseline GABA was associated with faster response times (RT) on verbal and visuospatial working memory measures. No correlation was observed between baseline GABA and working memory accuracy. AtDCS was associated with significantly greater reduction in GABA, as compared to sham in the left DLPFC. There was no effect of atDCS on Glx in left DLPFC and no significant effect of atDCS on GABA or Glx in the occipital cortex. There was no effect of atDCS on behavioural measures of working memory.LimitationsLimitations of this study include use of brief behavioural outcome measures post tDCS chosen to reduce participant burden and the lack of a healthy control group. The GABA levels measured in this study will contain contributions from co-edited macromolecule signal (so-called GABA+), but the relative contribution of these macromolecular signals are thought to be constant unlikely to account for within participant/session GABA changes. ConclusionsThis first such study in adolescents with NF1, showed that atDCS modulates inhibitory activity in the DLPFC. This focussed mechanism trial presents a highly promising approach to understanding complex neural pathology in neurodevelopmental disorders. Given the strong evidence linking GABA abnormalities to cognitive deficits across neurodevelopmental conditions such as ASD, modulation of GABA using atDCS offers a promising novel therapeutic approach. ClinicalTrials.gov Identifier: NCT0499142. Registered 5th August 2021; retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04991428
Does Spiritual Health Contribute To The Oral Health Behaviors in Adolescents?
Authors: Ghasemi Hadi , Namdari Mahshid , Khorankeh Reza , Bakhshandeh Soheila 
Published: September 2021

Abstract
In a search for any correlation between spiritual health and oral health among adolescents, a cross-sectional study was performed. Junior high school students from three cities in Iran, were selected by multi-stage random sampling. They answered a questionnaire including questions on oral health-related behaviors and spiritual health. Majority of the students reported close ties with God. From 20–120, the mean score of spiritual health in these students was 94.29 (± 15.38). Students with higher spiritual health scores more frequently reported acceptable level of brushing, dental visit, and no smoking (p < 0.01). This indicates the significance of spiritual health in achieving healthy behaviors.
Compound Heterozygous Splicing Variants In KIAA0586 Cause Fetal Short-Rib Thoracic Dysplasia And Cerebellar Malformation: The Use of Whole Exome Sequencing In Prenatal Diagnosis
Authors: Zhao Qianying , Xu Bocheng , Xiang Qinqin , Tan Yu , Xie Hanbin , Gao Qianqian , Wen Lingyi , Wang He , Yang Mei , Liu Shanling 
Published: September 2021

Abstract
Background: Short-rib thoracic dysplasia (SRTD) and Joubert syndrome (JS) are rare genetic ciliopathies, both patients can manifest cerebellar malformation and variable developmental delays. However, neither could be easily diagnosed during pregnancy due to limited fetal phenotype. Here, we investigated a fetus with short limbs, polydactyly initially and uncovered a compound heterozygous pathogenesis through whole exome sequencing (WES).Results: Merely short limbs and polydactyly of the fetus were detected during second trimester of gestation. Two variants (c.3940+1G>A and c.3303G>A), affecting splicing of KIAA0586 gene, were identified from amniocytes through WES. The presence and effect of these mutations were further validated on DNA and RNA level through Sanger sequencing. More intensive fetal monitoring was applied; deformed cerebellar malformation and restricted thoracic cage of the fetus were additionally uncovered. Conclusion: Herein, we discovered a genetic pathogenesis of KIAA0586 gene associated with SRTD and/or JS in a fetus with mild ultrasound anomalies initially. With the information of prenatal WES and distinct phenotypes of the fetus uncovered by imaging examination, we could reach more accurate clinical diagnosis and provide valuable prognosis information for parents.
Platelet Derived Extracellular Vesicles Promote in Vitro Gingival Wound Healing.
Authors: Antich-Rosselló Miquel , Munar-Bestard Marta , Forteza-Genestra Maria Antònia , Calvo Javier , Gayà Antoni , Monjo Marta , Ramis Joana Maria 
Published: September 2021

Abstract
Purpose: Gingival regeneration aims at restoring the architecture and functionality of oral damaged tissue. Different biomaterials or biological materials have been tested for tissue repair, such as platelet concentrates like platelet lysate (PL). In this article, the use of extracellular vesicles (EVs) derived from PL and their combination with hyaluronic acid biomaterials (HA) in wound healing was investigated.Methods: EVs were isolated by size exclusion chromatography from PL. In addition, HA gels were formulated with PL or EVs. EVs or HA combined with EVs (HA-EVs) were tested in vitro for biocompatibility (LDH activity and metabolic activity) and by a wound healing assay and gene expression analysis.Results: EVs and EVs-HA treatments were biocompatible and showed an increase in wound healing compared to control. Moreover, changes in gene expression related to extracellular matrix remodeling were observed in gingival keratinocytes and gingival fibroblasts after the treatment with EVs.Conclusion: EVs can be combined with HA biomaterials, showing good biocompatibility and preserving their activity and functionality. Therefore, platelet derived EVs emerge as promising candidates for oral regeneration with the possibility to combine them with biomaterials in order to enhance their application in clinical use.
Host Tau Genotype Specifically Regulates and Designs Tau Seeding and Spreading Following Intracerebral Injection of Identical Tau ADInoculum
Authors: Andrés-Benito Pol , Carmona Margarita , Jordán Mónica , Rio José Antonio del , Ferrer Isidro 
Published: September 2021

Abstract
BackgroundSeveral studies have demonstrated the capacity for seeding and spreading of tau-enriched fractions of brain homogenates from AD and other human and mouse tauopathies following intracerebral inoculation into transgenic mice bearing human tau or mutant human tau and into WT mice. However, little attention has been paid about the importance of host tau in tau seeding. MethodsThe brains of four adult murine genotypes expressing different forms of tau—WT (murine 4Rtau), P301S (human 4Rtau expressing the P301S mutation), hTau (homozygous transgenic mice knock-out for murine tau protein and heterozygous expressing human forms of 3Rtau and 4Rtau proteins), and mtWt (homozygous transgenic mice knock-out for murine tau protein)—were analyzed following unilateral hippocampal inoculation of sarkosyl-insoluble tau fractions from the same AD case. ResultsNo tau deposits were identified in inoculated mtWT mice. Involvement of CA1 neurons was higher and that of oligodendrocytes lower in inoculated hTau when compared with inoculated WT and P301S mice. tau-P Ser422, PHF1, and MAP2-P immunoreactivity was moderate or weak in WT and P301S, but strong i in inoculated hTau mice. p38-P and SAPK/JNK-P were observed in recruited phospho-tau deposits in inoculated WT, P301S, and hTau mice. However, CK1-δ, GSK-3β-P Ser9, AKT-P Ser473, PKAα/β-P Tyr197, and CLK1 were identified in neurons with tau deposits only in inoculated hTau. Finally, 3Rtau deposits predominated in inoculated WT and P301S, and 4Rtau deposits in hTau transgenic mice. ConclusionsOur results reveal that a) host tau is mandatory for tau seeding and spreading following tau inoculation; b) tau seeding and spreading is characterized by major genotype-dependent biochemical changes linked to post-translational tau modifications including tau phosphorylation and tau nitration at different sites, c) it is accompanied by genotype-dependent activation of various kinases thus pointing to a complex molecular response in the receptive host cells; d) tau seeding and spreading is accompanied by modifications in tau splicing with variable expression of new 3Rtau and 4Rtau isoforms; e) selective regional and cellular vulnerabilities, and different molecular compositions of the deposits are dependent on the host tau genotypes injected with identical AD tau inoculum.
A Novel Machine Learning-Based Radiomic Model for Diagnosing High Bleeding Risk Esophageal Varices in Cirrhotic Patients
Authors: Yan Yijie , Li Yue , Fan Chunlei , Zhang Yuening , Zhang Shibin , Wang Zhi , Huang Tehui , Ding Zhenjia , Hu Keqin , Li Lei , Ding Huiguo 
Published: September 2021

Abstract
Background & aims: To develop and validate a novel machine learning-based radiomic model (RM) for diagnosing high bleeding risk esophageal varices (HREV) in cirrhosis. Methods: In training cohort, total 218 cirrhotic patients for mild esophageal varices (EV) and 240 for HREV RM were enrolled for training and internal validation. In external validation cohort, 159 and 340 cirrhotic patients were respectively used for mild EV and HREV RM validation. Interesting regions of liver, spleen, and esophagus were labeled on the portal venous-phase enhanced CT images. RM was assessed by area under the receiver operating characteristic curves (AUROC), sensitivity, specificity, calibration and decision curve analysis (DCA). Results: The AUROC of mild EV RM in training and internal validation was 0.943 and 0.732, sensitivity and specificity was 0.863, 0.773 and 0.763, 0.763. The AUROC, sensitivity and specificity was 0.654, 0.773 and 0.632 in external validation. Interestingly, the AUROC of HREV RM in training and internal validation was 0.983 and 0.834, sensitivity and specificity was 0.948, 0.916 and 0.977, 0.969. The AUROC, sensitivity and specificity was 0.736, 0.690 and 0.762 in external validation. Calibration and DCA indicated RM had good performance in clinical practice. Compared with Baveno VI and its expanded criteria, HREV RM had a higher accuracy and net reclassification improvement reached 49.0% and 32.8%. Conclusion: A novel non-invasive RM for diagnosing HREV in cirrhotic patients with highly accuracy was developed. However, this RM still needs to be validated by a multi-center large cohort.
Unintended Socio-Economic and Health Consequences of COVID-19 among Slum Dwellers in Kampala, Uganda
Authors: Nuwematsiko Rebecca , Nabiryo Maxencia , Bomboka John Bosco , Nalinya Sarah , Musoke David , Okello Daniel , Wanyenze Rhoda K. 
Published: September 2021

Abstract
BackgroundTo reduce the spread of COVID-19, several countries in Africa instituted countrywide lockdowns and other public health measures. Whereas lockdowns contributed to the control of the pandemic, there were concerns about the unintended consequences of these measures especially in the most vulnerable populations. We assessed unintended socio-economic and health consequences due to the COVID-19 pandemic and the mitigation measures in slums in Kampala to inform the on-going and future pandemic response strategies.MethodsThis was a mixed methods cross-sectional study conducted in Bwaise I and Bwaise III slums of Kawempe division, Kampala Uganda from October to December 2020. We used systematic sampling to randomly select 425 household heads for the face-to-face quantitative interviews. We also conducted six focus group discussions (FGDs) with slum dwellers and used photovoice among eight Community Health Workers (CHWs) to document unintended socio-economic and health consequences. Quantitative data were imported into STATA version 14.0 for analysis, while qualitative data were analysed thematically using NVivo version 12. Modified Poisson regression analysis was conducted to establish factors associated with impact on access to food.ResultsMost respondents reported limited access to food (71.1%; 302/425); disruption in education (77.1%; 270/350); drop in daily income and wages (86.1%; 329/382) and loss of employment (63.1; 125/198). Twenty five percent of the respondents (25.4%; 86/338) reported domestic violence as one of the challenges. Seven themes emerged from the qualitative findings on the impact of COVID-19 including: limited access to food; negative impact on children’s rights (child labour and early pregnancies) and education; poor housing and lack of accommodation; negative social behaviours; negative impact on family and child care; reduced income and employment; and negative impact on health and access to health care services. Conclusion The slum dwellers of Bwaise I and Bwaise III experienced several negative socio-economic consequences of COVID-19 and its prevention measures that severely affected their wellbeing. Children experienced severe consequences such as child labour and early pregnancies among the girls. Response activities should be contextualised to different settings and protocols to protect the vulnerable groups in the community such as children and women should be developed and mainstreamed in response activities.
Rosaniline Hydrochloride Encapsulated MCM-48: Fluorescent and Electrochemical Sensor for Dopamine
Authors: Kalita Sarojmoni , Das Diganta Kumar 
Published: September 2021

Abstract
The dye Rosaniline hydrochloride (RANH) has been successfully incorporated in MCM-48 (designated as RANH@MCM-48) and characterised by various spectroscopic methods including FT-IR, SEM, EDX and N2 adsorption-desorption isotherm. RANH@MCM-48 in aqueous medium acts as fluorescence “on” sensor for neurotransmitter dopamine (DA) in presence of its main biological interfering agents ascorbic acid or vitamin c (AA) along with Glucose, Cholesterol and Uric acid. The limits of detection (LOD) were found to be 65 nM and 51 nM respectively in absence and in presence of AA. The binding of DA to RANH@MCM-48 is found to be reversible with respect to EDTA2-. The fluorescence intensity vs. pH plot shows a narrow fluorescence window of 7.2 to 8.8. RANH@MCM-48 has been successfully applied for DA detection in artificial cerebrospinal fluid (ACF) and bovine serum albumin (BSA) with LOD values 27 nM and 22.5 nM respectively. Platinum disc electrode has been modified with RANH@MCM-48 which showed distinct oxidation peaks with a separation of 0.188 V in cyclic voltammetry (CV). The LOD for DA in presence of AA determined from oxidation current is 77.5 nM. The voltammetric detection of DA is found to be free from common interfering species Na+, K+, Ca2+, Fe2+, Uric acid, Cholesterol and Glucose.
Amenability of Maruca vitrata (Lepidoptera: Crambidae) to gene silencing through exogenous administration and host-delivered dsRNA in pigeonpea (Cajanus cajan L.)
Authors: Chatterjee Madhurima , Yadav Jyoti , Rathinam Maniraj , Karthik Kesiraju , Chowdhary Gopal , Sreevat Rohini , Rao Uma 
Published: September 2021

Abstract
Insect pests are one of the major biotic stresses limiting yield in commercially important food crops. The lepidopteran polyphagous spotted pod borer, Maruca vitrata causes significant economic losses in legumes including pigeonpea. RNAi-based gene silencing has emerged as one of the potential biotechnological tools for crop improvement. We report in this paper, RNAi in M. vitrata through exogenous administration of dsRNA encoding three functionally important genes, Alpha-amylase (α-amylase), Chymotrypsin-like serine protease (CTLP) and Tropomyosin (TPM) into the larval haemolymph and their host-delivered RNAi in pigeonpea. Significant decline in the expression of selected genes supported by over-expression of DICER and generation of siRNA indicated the occurrence of RNAi in the dsRNA-injected larvae. Additionally, the onset of RNAi in the herbivore was demonstrated in pigeonpea, one of the prominent hosts, by host-delivered RNAi. Transgenics in pigeonpea (cv. Pusa992), a highly recalcitrant crop, were developed through a shoot apical meristem-targeted in planta transformation strategy and evaluated. Plant level bioassays in transgenic events characterized and selected at molecular level showed mortality of M. vitrata larvae as well as reduced feeding when compared to wild type. Furthermore, molecular evidences for down regulation of target genes in the insects that fed on transgenics authenticated RNAi. Considering the variability of gene silencing in lepidopteran pests, this study provided corroborative proof for the possibility of gene silencing in M. vitrata through both the strategies.
Cross-cultural Validation of Stool Based Colorectal Cancer Screening Methods in the North West of Iran
Authors: Dolatkhah Roya , Somi Mohammad Hossein , Dastgiri Saeed , Jafarabadi Mohammad Asghari , Abdolahi Hossein Mashhadi , Shanehbandi Daryoush , Asadi Milad , Nezamdoust Marzieh , Dolatkhah Neda , Farassati Faris 
Published: September 2021

Abstract
PurposeGlobally, colorectal cancer (CRC) is the third most common cancer and the second leading cause of death from cancer. Incidence and mortality from CRC both can be reduced and prevented using screening and early detection programs. The current study aimed to assess the feasibility of the colorectal cancer screening program in Northwest of Iran.MethodsThe study designed as a cross-cultural analytic study, to evaluate the diagnostic accuracy of stool-based tests compared with colonoscopy, during 2016-2020. All individuals first were assessed with our CRC risk assessment tool, then eligible volunteers entered the study. Colonoscopy was performed on all participants, also stool- based tests including traditional guaiac, high-sensitivity guaiac-based, fecal immunochemical test (FIT), and multitarget stool DNA (Mt-sDNA) panel tests were performed. ResultsMt-sDNA test panel had a sensitivity of 77.8% (95% CI: 40-97.2) for detecting colorectal cancer with a specificity of 91.2% (95% CI: 85.4-95.2). The FIT test alone had a lower sensitivity (66.7%; 95% CI: 29.9-92.5) and almost the same specificity of 93.9% (95% CI: 88.7-97.2) for cancer detection. Mt-sDNA test had better diagnostic accuracy than the FIT (AUC=0.85 vs 0.80), and is a more useful screening test. Positive and negative predictive values for cancer detection for both Mt-sDNA and FIT tests were almost the same results, however Mt-sDNA test had better NPV results than the FIT test alone.ConclusionOur results showed that both Mt-sDNA panel and the FIT test had acceptable cut-off points for cancer detection, however, Mt-sDNA test had better diagnostic accuracy.
D-serine supplement ameliorates MPP+-induced neurotoxicity via attenuating DAPK1-associated pathway in Parkinson's disease models
Authors: Zhang Wenli , Sun Xueying , Liu Jun , Peng Yuanwen , Qin Yuanhua , Xu Yuefei , Zhang Houli , Ding Wenyong , Li Sheng , Ma Li 
Published: September 2021

Abstract
Background: D-serine is reported to modulate neurotransmission via regulating the activation of N-methyl-D-aspartate receptor 1 (NMDAR1) in a narrow range, and dysfunction or dysregulation of NMDAR1 contributes to the pathophysiology of Parkinson's disease (PD), a chronic and progressive neurodegenerative disorder. This study aims to further elucidate the action mechanism of D-serine/NMDAR1 in PD. Methods and Results: At animal level, we found D-Serine and NMDAR1 were cooperatively distributed in mouse brains. Compared to the control mice, a dramatic increase in D-serine content and NMDAR1 expression was revealed in striatum, whereas a significant reduction was found in cortex, hippocampus, cerebellum and brainstem in PD mice. Thus, the tissue-specific D-serine/NMDAR1 was suspected to be associated with PD. Based on the decreased levels of NMDAR1 and D-serine in the MPP+-treated glioma cells, a D-serine supplement was introduced. We found that D-serine supplement enhanced NMDAR1 expression, and triggered neuronal cells to be rescued supporting by parkinsonian parameters including morphological observation, a decreased ROS level, an increased dopamine content, and a declined acetylcholine level. Additionally, a decreased calcium, reduced DAPK1 expression, and raised Bcl2 level were found in neuronal cells supplied with D-serine. Conclusions: We speculated that D-Serine attenuated neuronal cell death via inhibiting DAPK1-related pathway. Additionally, D-serine was confirmed to display an ability to ameliorate the MPTP injury using the MPTP-administrated mice injected with D-serine. Unlike the previous description, D-serine displays a protective effect on neuronal cells. Overall, our finding highlights D-serine as a strong enhancer for NMDAR1 expression and a candidate for PD therapy. This opens up an innovative perspective for neurobiological therapy using D-serine augmentation.
High prevalence of intrathecal IgA synthesis in multiple sclerosis patients
Authors: Muñoz Ursula , Sebal Cristina , Escudero Esther , Sánchez Maria Isabel García , Urcelay Elena , Jayo Asier , Arroyo Rafael , García-Martínez Maria A , Álvarez-Lafuente Roberto , Sádaba María C 
Published: September 2021

Abstract
Introduction: The detection of intrathecal IgA synthesis (IAS) in multiple sclerosis (MS) is cumbersome, for this reason, we developed a highly sensitive assay to assess it in MS. Methods: 151 MS patients and 22 controls with different neurological diseases were recruited. IgA concentration was analyzed by ELISA. Oligoclonal IgA bands to detect IAS were determined by a new ultrasensitive assay based on isoelectrofocusing (IEF). Results: Most individuals showed an IgA concentration within normal range in serum samples (95.95%) but 38.41% of individuals had a low IgA concentration in the cerebrospinal fluid (CSF), with no significant differences observed between MS and control groups, neither in CSF nor in serum. The new IEF was more sensitive than those previously described (0.01 mg/dl of IgA), and clearly identified patients with and without IAS, that was not related with IgA concentration. MS patients showed higher percentage of IAS (43.00%) than the control group (18.20) (p = 0.035), because the incidence was especially higher in MS patients with clinically isolated syndrome (CIS, 66.00%). Conclusions: Intrathecal IgA synthesis is observed more frequently in MS patients than in other neurological diseases, and with higher incidence than assumed in the past.