bluuebunny/crossref_metadata_2025_split huggingface dataset:
Twenty-four-hour real-time continuous monitoring of acute focal cerebral ischemia in rabbits based on magnetic inductive phase shift
Authors: Zhao Shuang-Lin , Jin Gui , Bai Ze-Lin , Chen Jing-Bo , Li Meng-Wei , Li Gen , Zhuang Wei , Liu Yue-Ning , Qin Ming-Xin 
Published: November 2020

Abstract

Background
As a serious clinical disease, ischemic stroke is usually detected through magnetic resonance imaging and computed tomography. In this study, a noninvasive, non-contact, real-time continuous monitoring system was constructed on the basis of magnetic induction phase shift (MIPS) technology. The “thrombin induction method”, which conformed to the clinical pathological development process of ischemic stroke, was used to construct an acute focal cerebral ischemia model of rabbits. In the MIPS measurement, a “symmetric cancellation-type” magnetic induction sensor was used to improve the sensitivity and antijamming capability of phase detection.

Methods
A 24-h MIPS monitoring experiment was carried out on 15 rabbits (10 in the experimental group and five in the control group). Brain tissues were taken from seven rabbits for the 2% triphenyl tetrazolium chloride staining and verification of the animal model.

Results
The nonparametric independent-sample Wilcoxon rank sum test showed significant differences (p < 0.05) between the experimental group and the control group in MIPS. Results showed that the rabbit MIPS presented a declining trend at first and then an increasing trend in the experimental group, which may reflect the pathological development process of cerebral ischemic stroke. Moreover, TTC staining results showed that the focal cerebral infarction area increased with the development of time

Conclusions
Our experimental study indicated that the MIPS technology has a potential ability of differentiating the development process of cytotoxic edema from that of vasogenic edema, both of which are caused by cerebral ischemia.
The effect of exercise on anxiety in the elderly worldwide: a systematic review and meta-analysis
Authors: Kazeminia Mohsen , Salari Nader , Vaisi-Raygani Aliakbar , Jalali Rostam , Abdi Alireza , Mohammadi Masoud , Daneshkhah Alireza , Hosseinian-Far Melika , Shohaimi Shamarina 
Published: November 2020

Abstract
Background
Physical activity and exercise are among the most important, simplest, and cheapest approaches to anxiety treatment, especially for the elderly. Their positive effects on improvement of mental disorders in the elderly have attracted a considerable level of attention. Therefore, the present study was conducted to determine the effect of sport on reducing anxiety in the elderly using meta-analysis.

Methods
In this study, national and international databases of SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, ScienceDirect, Scopus, PubMed, and Web of Science were searched to find studies published electronically from 1999 to 2019. Heterogeneity between the collected studies was determined using the Cochran's test (Q) and I2. Due to presence of heterogeneity, the random effects model was used to estimate the standardized mean difference of sport test scores obtained from the measurement of anxiety reduction among the elderly, between the intervention group before and after the test.

Results
In this meta-analysis and systematic review, 19 papers finally met the inclusion criteria. The overall sample size of all collected studies for the meta-analysis was 841 s. Mean anxiety score before and after intervention were 38.7 ± 5.6 33.7 ± 3.4 respectively, denoting a decrease in anxiety score after intervention.

Conclusion
Results of this study indicates that Sport significantly reduces Anxiety in the Elderly. Therefore, a regular exercise program can be considered as a part of the elderly care program.
Conformational changes in myeloperoxidase induced by ubiquitin and NETs containing free ISG15 from systemic lupus erythematosus patients promote a pro-inflammatory cytokine response in CD4+ T cells
Authors: Carrillo-Vázquez Daniel Alberto , Jardón-Valadez Eduardo , Torres-Ruiz Jiram , Juárez-Vega Guillermo , Maravillas-Montero José Luis , Meza-Sánchez David Eduardo , Domínguez-López María Lilia , Varela Jorge Carlos Alcocer , Gómez-Martín Diana 
Published: November 2020

Abstract

Background
Neutrophil extracellular traps (NETs) from patients with systemic lupus erythematosus (SLE) are characterized by lower ubiquitylation and myeloperoxidase (MPO) as a substrate. The structural and functional effect of such modification and if there are additional post-translational modifications (PTMs) are unknown.

Methods
To assess the expression and functional role of PTMs in NETs of patients with SLE; reactivation, proliferation and cytokine production was evaluated by flow cytometry using co-cultures with dendritic cells (DC) and CD4+ from SLE patients and healthy controls. The impact of ubiquitylation on MPO was assessed by molecular dynamics. The expression of ISG15 in NETs was evaluated by immunofluorescence and Western Blot.

Results
Fifteen patients with SLE and ten healthy controls were included. In the co-cultures of CD4+ lymphocytes with DC stimulated with ubiquitylated MPO or recombinant MPO, a higher expression of IFNγ and IL-17A was found in CD4+ from SLE patients (p < 0.05). Furthermore, with DC stimulated with ubiquitylated MPO a trend towards increased expression of CD25 and Ki67 was found in lupus CD4+ lymphocytes, while the opposite was documented in controls (p < 0.05). Through molecular dynamics we found the K129-K488-K505 residues of MPO as susceptible to ubiquitylation. Ubiquitylation affects the hydration status of the HEME group depending on the residue to which it is conjugated. R239 was found near by the HEME group when the ubiquitin was in K488-K505. In addition, we found greater expression of ISG15 in the SLE NETs vs controls (p < 0.05), colocalization with H2B (r = 0.81) only in SLE samples and increased production of IFNγ in PBMCs stimulated with lupus NETs compared to healthy controls NETs.

Conclusion
The ubiquitylated MPO has a differential effect on the induction of reactivation of CD4+ lymphocytes in patients with SLE, which may be related to structural changes by ubiquitylation at the catalytic site of MPO. Besides a lower ubiquitylation pattern, NETs of patients with SLE are characterized by the expression of ISG15, and the induction of IFNγ by Th1 cells.
Complement peptide C3a receptor 1 promotes optic nerve degeneration in DBA/2J mice
Authors: Harder Jeffrey M. , Williams Pete A. , Braine Catherine E. , Yang Hongtian S. , Thomas Jocelyn M. , Foxworth Nicole E. , John Simon W. M. , Howell Gareth R. 
Published: November 2020

Abstract

Background
The risk of glaucoma increases significantly with age and exposure to elevated intraocular pressure, two factors linked with neuroinflammation. The complement cascade is a complex immune process with many bioactive end-products, including mediators of inflammation. Complement cascade activation has been shown in glaucoma patients and models of glaucoma. However, the function of complement-mediated inflammation in glaucoma is largely untested. Here, the complement peptide C3a receptor 1 was genetically disrupted in DBA/2J mice, an ocular hypertensive model of glaucoma, to test its contribution to neurodegeneration.

Methods
A null allele of C3ar1 was backcrossed into DBA/2J mice. Development of iris disease, ocular hypertension, optic nerve degeneration, retinal ganglion cell activity, loss of RGCs, and myeloid cell infiltration in C3ar1-deficient and sufficient DBA/2J mice were compared across multiple ages. RNA sequencing was performed on microglia from primary culture to determine global effects of C3ar1 on microglia gene expression.

Results
Deficiency in C3ar1 lowered the risk of degeneration in ocular hypertensive mice without affecting intraocular pressure elevation at 10.5 months of age. Differences were found in the percentage of mice affected, but not in individual characteristics of disease progression. The protective effect of C3ar1 deficiency was then overcome by additional aging and ocular hypertensive injury. Microglia and other myeloid-derived cells were the primary cells identified that express C3ar1. In the absence of C3ar1, microglial expression of genes associated with neuroinflammation and other immune functions were differentially expressed compared to WT. A network analysis of these data suggested that the IL10 signaling pathway is a major interaction partner of C3AR1 signaling in microglia.

Conclusions
C3AR1 was identified as a damaging neuroinflammatory factor. These data help suggest complement activation causes glaucomatous neurodegeneration through multiple mechanisms, including inflammation. Microglia and infiltrating myeloid cells expressed high levels of C3ar1 and are the primary candidates to mediate its effects. C3AR1 appeared to be a major regulator of microglia reactivity and neuroinflammatory function due to its interaction with IL10 signaling and other immune related pathways. Targeting myeloid-derived cells and C3AR1 signaling with therapies is expected to add to or improve neuroprotective therapeutic strategies.
Cryopreserved, Thin, Laser-Etched Osteochondral Allograft maintains the functional components of articular cartilage after 2 years of storage
Authors: Rorick Carolyn B. , Mitchell Jordyn A. , Bledsoe Ruth H. , Floren Michael L. , Wilkins Ross M. 
Published: November 2020

Abstract

Background
Despite improvements in treatment options and techniques, articular cartilage repair continues to be a challenge for orthopedic surgeons. This study provides data to support that the 2-year Cryopreserved, Thin, Laser-Etched Osteochondral Allograft (T-LE Allograft) embodies the necessary viable cells, protein signaling, and extracellular matrix (ECM) scaffold found in fresh cartilage in order to facilitate a positive clinical outcome for cartilage defect replacement and repair.

Methods
Viability testing was performed by digestion of the graft, and cells were counted using a trypan blue assay. Growth factor and ECM protein content was quantified using biochemical assays. A fixation model was introduced to assess tissue outgrowth capability and cellular metabolic activity in vitro. Histological and immunofluorescence staining were employed to confirm tissue architecture, cellular outgrowth, and presence of ECM. The effects of the T-LE Allograft to signal bone marrow-derived mesenchymal stem cell (BM-MSC) migration and chondrogenic differentiation were evaluated using in vitro co-culture assays. Immunogenicity testing was completed using flow cytometry analysis of cells obtained from digested T-LE Allografts and fresh articular cartilage.

Results
Average viability of the T-LE Allograft post-thaw was found to be 94.97 ± 3.38%, compared to 98.83 ± 0.43% for fresh articular cartilage. Explant studies from the in vitro fixation model confirmed the long-term viability and proliferative capacity of these chondrocytes. Growth factor and ECM proteins were quantified for the T-LE Allograft revealing similar profiles to fresh articular cartilage. Cellular signaling of the T-LE Allograft and fresh articular cartilage both exhibited similar outcomes in co-culture for migration and differentiation of BM-MSCs. Flow cytometry testing confirmed the T-LE Allograft is immune-privileged as it is negative for immunogenic markers and positive for chondrogenic markers.

Conclusions
Using our novel, proprietary cryopreservation method, the T-LE Allograft, retains excellent cellular viability, with native-like growth factor and ECM composition of healthy cartilage after 2 years of storage at − 80 °C. The successful cryopreservation of the T-LE Allograft alleviates the limited availably of conventionally used fresh osteochondral allograft (OCA), by providing a readily available and simple to use allograft solution. The results presented in this paper supports clinical data that the T-LE Allograft can be a successful option for repairing chondral defects.
Highly variable effect of sonication to dislodge biofilm-embedded Staphylococcus epidermidis directly quantified by epifluorescence microscopy: an in vitro model study
Authors: Sandbakken Erik T. , Witsø Eivind , Sporsheim Bjørnar , Egeberg Kjartan W. , Foss Olav A. , Hoang Linh , Bjerkan Geir , Løseth Kirsti , Bergh Kåre 
Published: November 2020

Abstract

Background
In cases of prosthetic joint infections, culture of sonication fluid can supplement culture of harvested tissue samples for correct microbial diagnosis. However, discrepant results regarding the increased sensitivity of sonication have been reported in several studies. To what degree bacteria embedded in biofilm are dislodged during the sonication process has to our knowledge not been fully elucidated. In the present in vitro study, we have evaluated the effect of sonication as a method to dislodge biofilm by quantitative microscopy.

Methods
We used a standard biofilm method to cover small steel plates with biofilm forming Staphylococcus epidermidis ATCC 35984 and carried out the sonication procedure according to clinical practice. By comparing area covered with biofilm before and after sonication with epifluorescence microscopy, the effect of sonication on biofilm removal was quantified. Two series of experiments were made, one with 24-h biofilm formation and another with 72-h biofilm formation.
Confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) were used to confirm whether bacteria were present after sonication. In addition, quantitative bacteriology of sonication fluid was performed.

Results
Epifluorescence microscopy enabled visualization of biofilm before and after sonication. CLSM and SEM confirmed coccoid cells on the surface after sonication. Biofilm was dislodged in a highly variable manner.

Conclusion
There is an unexpected high variation seen in the ability of sonication to dislodge biofilm-embedded S. epidermidis in this in vitro model.
Emergent surgical removal of a migrated atrial septal defect occluder: case report
Authors: Wen Bi , He Juan 
Published: November 2020

Abstract

Background
Atrial septal defect (ASD) closure has been widely accepted and is now routinely performed using a percutaneous approach under especially echocardiographic guidance Transesophageal echocardiography (TEE). One major complication is dislocation of occluder device during or after the device implantation. Surgical removal may be required, especially when the device stuck in the left ventricular outflow tract (LVOT).

Case introduction
A 21-year-old female was admitted to our department for percutaneous closure of secundum ASD. Percutaneous closure under the guidance of TEE was recommended for the patients. During device implantation, the TEE showed dislocation of the 22 mm ASD occluder device, stucked into the LVOT and behind the anterior mitral leaflet, producing severe LVOT obstruction Fig. 1). We herein present a safe and quick technique for surgical removal of an ASD occlude device located in the LVOT.

Conclusion
This technique provides a safe method for surgical removal of malposition and migration ASD occluder device.
The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects
Authors: Kim Yoo-Mi , Choi Jin-Ho , Kim Gu-Hwan , Sohn Young Bae , Ko Jung Min , Lee Beom Hee , Cheon Chong Kun , Lim Han Hyuk , Heo Sun-Hee , Yoo Han-Wook 
Published: November 2020

Abstract

Background
Gaucher disease (GD) is caused by a deficiency of β-glucocerebrosidase, encoded by GBA. Haplotype analyses previously demonstrated founder effects for particular GBA mutations in Ashkenazi Jewish and French-Canadian populations. This study aimed to investigate the clinical characteristics and mutation spectrum of GBA in Korean GD patients and to identify founder effect of GBA p.G85E in non-neuronopathic GD patients.

Results
The study cohort included 62 GD patients from 58 unrelated families. Among them, 18 patients from 17 families harbored the p.G85E mutation. Haplotype analysis was performed for 9 probands and their parents for whom DNA samples were available. In 58 unrelated probands, the GBA mutation p.L483P was the most common (30/116 alleles, 26%), followed by p.G85E (16%), p.F252I (13%), and p.R296Q (9%). The median age at diagnosis of the 18 patients harboring the p.G85E mutation was 3.8 (range 1.2–57) years. No patients developed neurological symptoms during follow-up periods of 2.2–20.3 (median 13.9) years. The size of the shared haplotype containing GBA p.G85E was 732 kbp, leading to an estimated age of 3075 years.

Conclusion
The GBA p.G85E mutation, which appears to be neuroprotective despite producing distinctive visceromegaly and skeletal symptoms, exhibited a potential founder effect in Korean GD patients.
Clinical and genetic characteristics and prenatal diagnosis of patients presented GDD/ID with rare monogenic causes
Authors: Lin Liling , Zhang Ying , Pan Hong , Wang Jingmin , Qi Yu , Ma Yinan 
Published: November 2020

Abstract

Background
Global developmental delay/intellectual disability (GDD/ID), used to be named as mental retardation (MR), is one of the most common phenotypes in neurogenetic diseases. In this study, we described the diagnostic courses, clinical and genetic characteristics and prenatal diagnosis of a cohort with patients presented GDD/ID with monogenic causes, from the perspective of a tertiary genetic counseling and prenatal diagnostic center.

Method
We retrospectively analyzed the diagnostic courses, clinical characteristics, and genetic spectrum of patients presented GDD/ID with rare monogenic causes. We also conducted a follow-up study on prenatal diagnosis in these families. Pathogenicity of variants was interpreted by molecular geneticists and clinicians according to the guidelines of the American College of Medical Genetics and Genomics (ACMG).

Results
Among 81 patients with GDD/ID caused by rare monogenic variants it often took 0.5–4.5 years and 2–8 referrals to obtain genetic diagnoses. Devlopmental delay typically occurred before 3 years of age, and patients usually presented severe to profound GDD/ID. The most common co-existing conditions were epilepsy (58%), microcephaly (21%) and facial anomalies (17%). In total, 111 pathogenic variants were found in 62 different genes among the 81 pedigrees, and 56 variants were novel. The most common inheritance patterns in this outbred Chinese population were autosomal dominant (AD; 47%), following autosomal recessive (AR; 37%), and X-linked (XL; 16%). SCN2A, SHANK3 and STXBP1 were important causal genes. Hot-spot variants were rarely found. By the follow-up, 33 affected families, including 15, 13 and 5 families inherited in AR, AD and XL modes respectively, had undergone prenatal diagnosis. And the recurrence rates are 26.7%, 15.4% and 20% for families inherited in AR, AD, and XL patterns.

Conclusion
Patients presented with GDD/ID caused by rare single gene variants are characterized by early onset, relatively severe symptoms and great clinical variability and genetic heterogeneity. Timely referrals to genetic counseling and prenatal diagnostic laboratories are important for affected families planning to have additional children.
Responding to mental health needs of Syrian refugees in Turkey: mhGAP training impact assessment
Authors: Karaoğlan Kahiloğulları Akfer , Alataş Esra , Ertuğrul Fatmagül , Malaj Altin 
Published: November 2020

Abstract

Background
About 1468 Syrian and Turkish doctors, serving in primary health care, have received the mhGAP training during 2016–2019. As additional training needs were identified, MoH and WHO wanted to understand the usefulness of the training and its impact in responding to the mental health needs of Syrian refugees in Turkey.

Methods
A five component assessment was done in 2019, consisting of feedback of trainees, assessment of increase in knowledge; utilization of service; compliance to treatment guidelines and service user satisfaction. The purpose was to understand the perception of participants on the training; estimate the knowledge gained—attributable to the training; estimate the increase in mental health cases identified and treated; compliance with treatment guidelines; as well as perception of the services received by end-beneficiaries.

Results
Results indicate that most of the respondents were happy with the training, but preferred additional mhGAP training as a refresher course in the future. There was knowledge gained due to the training, 9% for the Syrian and 5% for Turkish doctors. The knowledge gained has helped the practicing doctors to be more attentive and increase the numbers of cases diagnosed after the training for almost all groups of diagnoses. Most doctors, observed during practice, comply with the guidelines shared during the training, but improvement is still needed when it comes to prescription and treatment of certain conditions. The average number of mental health cases identified increased by 38 (%27) cases in the year following the training. We observed over 70% compliance with guidelines for 9 out of 12 criteria in question. The results of the patient exit interviews indicate a high level of satisfaction with the MHPSS services provided. About 95% of beneficiaries were happy with the quality of the service, and 92% having their needs met.

Conclusions
The mhGAP training was found useful. More training should be conducted to fill in the gap in service provision and meet the mental needs of Syrian refugees in Turkey.
Functional identification of potential non-canonical N-glycosylation sites within Cav3.2 T-type calcium channels
Authors: Ficelova Vendula , Souza Ivana A. , Cmarko Leos , Gandini Maria A. , Stringer Robin N. , Zamponi Gerald W. , Weiss Norbert 
Published: November 2020

Abstract
Low-voltage-activated T-type calcium channels are important contributors to nervous system function. Post-translational modification of these channels has emerged as an important mechanism to control channel activity. Previous studies have documented the importance of asparagine (N)-linked glycosylation and identified several asparagine residues within the canonical consensus sequence N-X-S/T that is essential for the expression and function of Cav3.2 channels. Here, we explored the functional role of non-canonical N-glycosylation motifs in the conformation N-X-C based on site directed mutagenesis. Using a combination of electrophysiological recordings and surface biotinylation assays, we show that asparagines N345 and N1780 located in the motifs NVC and NPC, respectively, are essential for the expression of the human Cav3.2 channel in the plasma membrane. Therefore, these newly identified asparagine residues within non-canonical motifs add to those previously reported in canonical sites and suggest that N-glycosylation of Cav3.2 may also occur at non-canonical motifs to control expression of the channel in the plasma membrane. It is also the first study to report the functional importance of non-canonical N-glycosylation motifs in an ion channel.