bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy-mediated occludin degradation contributes to blood–brain barrier disruption during ischemia in bEnd.3 brain endothelial cells and rat ischemic stroke models
Authors: Kim Kyeong-A , Kim Donghyun , Kim Jeong-Hyeon , Shin Young-Jun , Kim Eun-Sun , Akram Muhammad , Kim Eun-Hye , Majid Arshad , Baek Seung-Hoon , Bae Ok-Nam 
Published: March 2020

AbstractBackgroundThe blood–brain barrier (BBB) maintains homeostasis of the brain environment by tightly regulating the entry of substances from systemic circulation. A breach in the BBB results in increased permeability to potentially toxic substances and is an important contributor to amplification of ischemic brain damage. The precise molecular pathways that result in impairment of BBB integrity remain to be elucidated. Autophagy is a degradation pathway that clears damaged or unnecessary proteins from cells. However, excessive autophagy can lead to cellular dysfunction and death under pathological conditions.MethodsIn this study, we investigated whether autophagy is involved in BBB disruption in ischemia, using in vitro cells and in vivo rat models. We used brain endothelial bEnd.3 cells and oxygen glucose deprivation (OGD) to simulate ischemia in culture, along with a rat ischemic stroke model to evaluate the role of autophagy in BBB disruption during cerebral ischemia.ResultsOGD 18 h induced cellular dysfunction, and increased permeability with degradation of occludin and activation of autophagy pathways in brain endothelial cells. Immunostaining revealed that occludin degradation is co-localized with ischemic autophagosomes. OGD-induced occludin degradation and permeability changes were significantly decreased by inhibition of autophagy using 3-methyladenine (3-MA). Enhanced autophagic activity and loss of occludin were also observed in brain capillaries isolated from rats with middle cerebral artery occlusion (MCAO). Intravenous administration of 3-MA inhibited these molecular changes in brain capillaries, and recovered the increased permeability as determined using Evans blue.ConclusionsOur findings provide evidence that autophagy plays an important role in ischemia-induced occludin degradation and loss of BBB integrity.
The elevated admission white blood cell count relates to adverse surgical outcome of acute Stanford type a aortic dissection
Authors: Ma Mingjia , Shi Juan , Feng Xin , Wang Jing , Liu Ligang , Wei Xiang 
Published: March 2020

Abstract
Background
The purpose of the study was to examine the association between white blood cell count (WBCc) on admission and early outcome in patients with the acute Stanford type A aortic dissection (TAAD).

Methods
From January 2012 to December 2018, we retrospectively evaluated a series of 331 consecutive patients underwent surgery for TAAD in Tongji Hospital. The patients were divided into 2 groups based on the WBCc, i.e. the normal WBCc group (WBCc≤11 × 109/L) and leukocytosis group (WBCc> 11 × 109/L). The perioperative data were compared between the 2 groups. The in-hospital mortality and the compositive adverse event including multi-organ dysfunction syndrome, postoperative stroke, tracheotomy, and re-exploration for stopping bleeding were set as end points. Cox regression were used to assess the potential risk factors.

Results
The in-hospital mortality was nearly 3 time higher in the leukocytosis group than in the normal WBCc group (20.9% vs.8.1%, P = 0.001), and 15.1% overall. For the circulatory arrest, there was significant higher mortality in patients with leukocytosis than normal WBCc group (26.1%vs.8.9%, P = 0.001). After adjustment for confounding factors, the leukocytosis was found to be a strong independent predictor of in-hospital mortality (odds ratio = 3.10; 95% confidence interval 1.38 to 6.97, P = 0.006). The leukocytosis was also a risk factor of adverse events (odds ratio = 1.80; 95% confidence interval 1.07 to 3.04, P = 0.027).

Conclusions
The WBCc within 24 h of admission for TAAD is a strong and independent predictor of in-hospital mortality as well as short-term clinical events. The results of this study have important clinical implications for risk-stratifying patients with TAAD.
Framework and approach for measuring performance and progress of mental health systems and services in India: National Mental Health Survey 2015–2016
Authors:   the NMHS collaborators group, Arvind Banavaram Anniappan , Gururaj Gopalkrishna , Rao Girish N. , Pradeep Banandur S. , Mathew Varghese , Benegal Vivek , Gautham Melur Sukumar , Senthil Amudhan , Kokane Arun , Chavan Bir Singh , Dalal P. K. , Ram Daya , Pathak Kangkan , Lenin Singh R. K. , Singh Lokesh Kumar , Sharma Pradeep , Saha Pradeep Kumar , Ramasubramaniam C. , Mehta Ritambhara Y. , Shibukumar T. M. 
Published: March 2020

Abstract
Background
Previous attempts of Mental Health Systems Assessment in India were restricted in scope and scale. Information on all aspects of mental health systems (leadership/governance, legislation, financing, service delivery, workforce, access to essential medicines, information systems, intersectoral activities, and monitoring and evaluation) was scarcely available. The National Mental Health Survey-Mental Health Systems Assessment (NMHS-MHSA), a unique endeavor, assessed the performance of mental health systems and services through health systems assessment framework. The present paper discusses the design and methodology adopted under NMHS-MHSA along with emphasizing its implication for India and other LMICs.

Methods
NMHS-MHSA was undertaken in 12 Indian states by contextually adapting WHO-AIMS instrument. Data was collated from several secondary sources including interviews of key stakeholders. Utilizing the data a set of 15-quantitative, 5-morbidity and 10-qualitative indicators were developed to summarize the functional status of mental health systems in the surveyed states. This information was authenticated through state level stakeholder’s consultation and consensus building workshops following which a state mental health systems report card with indicators was developed.

Conclusion
The process and robust method of data compilation enabled NMHS-MHSA to be a reliable and comprehensive method for assessing mental health systems at the state level. It’s envisaged that the assessment provides requisite impetus for strengthening mental health program and mental health systems in India. Being less resource intensive, low -and middle- income countries can adopt NMHS-MHSA tool and methodology to assess their mental health systems with contextual modifications.
Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memory
Authors: Kong Qingnuan , Yu Ming , Zhang Meng , Wei Chuang , Gu Huating , Yu Shaoyang , Sun Wei , Li Nan , Zhou Yu 
Published: March 2020

Abstract
Aim
Active changes in neuronal DNA methylation and demethylation appear to act as controllers of synaptic scaling and glutamate receptor trafficking in learning and memory formation. DNA methyltransferases (DNMTs), including proteins encoded by Dnmt1, Dnmt3a and Dnmt3b, are dominant enzymes carrying out DNA methylation. Our previous study demonstrated the important roles that DNMT1 and DNMT3a play in synaptic function and memory. In this study, we aim to explore the role of DNMT3b and its-mediated DNA methylation in memory processes.

Methods
Dnmt3b was knocked down specifically in dorsal CA1 neurons of adult mice hippocampus by AAV-syn-Cre-GFP virus injection. Behavioral tests were used to evaluate memory performance. Gene expression microarray analysis followed by quantitative RT-PCR were performed to find differential expression genes.

Results
Dnmt3bflox/flox mice receiving Cre-virus infection showed impaired novel object-place recognition (NPR) and normal novel object recognition (NOR), in comparison to mice receiving control GFP-virus infection. Microarray analysis revealed differential expression of K+ channel subunits in the hippocampus of Dnmt3bflox/flox mice receiving Cre-virus injection. Increased Kcne2 expression was confirmed by following qRT-PCR analysis. We also found that NPR training and testing induced up-regulation of hippocampal Dnmt1 and Dnmt3a mRNA expression in control mice, but not in Cre-virus injected mice. Our findings thus demonstrate that conditional Dnmt3b deletion in a sub-region of the hippocampus impairs a specific form of recognition memory that is hippocampus-dependent.
Treating non-responders: pitfalls and implications for cancer immunotherapy trial design
Authors: Xu Zhenzhen , Park Yongsoek , Liu Ke , Zhu Bin 
Published: March 2020

AbstractBackgroundConventional trial design and analysis strategies fail to address the typical challenge of immune-oncology (IO) studies: only a limited percentage of treated patients respond to the experimental treatment. Treating non-responders, we hypothesize, would in part drive non-proportional hazards (NPH) patterns in Kaplan-Meier curves that violates the proportional hazards (PH) assumption required by conventional strategies. Ignoring such violation incurred from treating non-responders in the design and analysis strategy may result in underpowered or even falsely negative studies. Hence, designing innovative IO trials to address such pitfall becomes essential.MethodsWe empirically tested the hypothesis that treating non-responders in studies of inadequate size is sufficient to cause NPH patterns and thereby proposed a novel strategy,p-embedded, to incorporate the dichotomized response incurred from treating non-responders, as measured by the baseline proportion of responders among treated patientsp%, into the design and analysis procedures, aiming to ensure an adequate study power when the PH assumption is violated.ResultsEmpirical studies confirmed the hypothetical cause contributes to the manifestation of NPH patterns. Further evaluations revealed a significant quantitative impact ofp% on study efficiency. The p-embedded strategy incorporating the properly pre-specifiedp% ensures an adequate study power whereas the conventional design ignoring it leads to a severe power loss.ConclusionThe p-embedded strategy allows us to quantify the impact of treating non-responders on study efficiency. Implicit in such strategy is the solution to mitigate the occurrence of NPH patterns and enhance the study efficiency for IO trials via enrolling more prospective responders.
The Prospective Lynch Syndrome Database reports enable evidence-based personal precision health care
Authors: Møller Pål 
Published: March 2020

AbstractThe aims of the Prospective Lynch Syndrome Database (PLSD) are to provide empirical prospectively observed data on the incidences of cancer in different organs, survival following cancer and the effects of interventions in carriers of pathogenic variants of the mismatch repair genes (path_MMR) categorized by age, gene and gender. Although PLSD is assumption-free, as with any study the ascertainment procedures used to identify the study cohort will introduce selection biases which have to be declared and considered in detail in order to provide robust and valid results. This paper provides a commentary on the methods used and considers how results from the PLSD reports should be interpreted. A number of the results from PLSD were novel and some in conflict with previous assumptions. Notably, colonoscopic surveillance did not prevent colo-rectal cancer, survival after colo-rectal, endometrial and ovarian cancer was good, no survival gain was observed with more frequent colonoscopy, new causes of cancer-related death were observed in survivors of first cancers due to later cancers in other organs, variants in the different MMR genes caused distinct multi-cancer syndromes characterized by different penetrance and phenotypes. The www.PLSD.eu website together with the InSiGHT database website (https://www.insight-group.org/variants/databases/) now facilitate evidence-based personalized precision health care for individual carriers at increased risk of cancer. The arguments are summarized in a final discussion on how to conceptualize current knowledge for the different practical purposes of treating cancers, genetic counselling and prevention, and for understanding /research on carcinogenetic mechanisms.
Ultraplexing: increasing the efficiency of long-read sequencing for hybrid assembly with k-mer-based multiplexing
Authors: Dilthey Alexander T. , Meyer Sebastian A. , Kaasch Achim J. 
Published: March 2020

AbstractHybrid genome assembly has emerged as an important technique in bacterial genomics, but cost and labor requirements limit large-scale application. We present Ultraplexing, a method to improve per-sample sequencing cost and hands-on time of Nanopore sequencing for hybrid assembly by at least 50% compared to molecular barcoding while maintaining high assembly quality. Ultraplexing requires the availability of Illumina data and uses inter-sample genetic variability to assign reads to isolates, which obviates the need for molecular barcoding. Thus, Ultraplexing can enable significant sequencing and labor cost reductions in large-scale bacterial genome projects.
Resistance against macrocyclic lactones in Psoroptes ovis in cattle
Authors: van Mol Wouter , De Wilde Nathalie , Casaert Stijn , Chen Zhenzhen , Vanhecke Marieke , Duchateau Luc , Claerebout Edwin 
Published: March 2020

Abstract
Background
Psoroptic mange is an important disease in Belgian Blue cattle. Treatment failure of macrocyclic lactones against Psoroptes ovis has been reported, but clear evidence of in vivo resistance is lacking. This study assessed the efficacy of macrocyclic lactone products on 16 beef farms in Belgium and the Netherlands in vivo and in vitro.

Methods
On each farm a group of animals (n = 7–14) with psoroptic mange was treated with two subcutaneous injections of a macrocyclic lactone product with 7–10 days interval (15 farms) or a single injection with a long-acting macrocyclic lactone (1 farm). In vivo efficacy was assessed by the reduction in mite counts, clinical index (proportion of the body surface affected by lesions), the proportion of the animals with negative mite counts after the first treatment round and the number of treatment rounds needed to obtain zero mites counts in all animals. A mite population was categorized as sensitive when the mite count reduction after the first treatment round > 95% and the lower limit of the uncertainty interval > 90%. Resistance was detected when both parameters were below their threshold and suspected when one parameter was too low. In vitro knockdown and mortality were evaluated in a contact test.

Results
The proportion of the animals with negative mite counts after the first treatment round varied from 0 to 80%. All farms needed two or more treatments rounds to obtain zero mite counts on all animals. Clinical index only started to reduce after the second treatment round. Mite populations from three farms were categorized as sensitive, one as suspected resistant and 12 as resistant. No correlation was found between in vitro lethal dose 50 and knockdown dose 50 values and in vivo efficacy parameters.

Conclusions
Unambiguous treatment failure was detected on 12 out of 16 farms, confirming the presence of macrocyclic lactone resistance on Belgian Blue beef farms. In vitro parameters could not discriminate the farms based on their in vivo sensitivity. The mean reduction in mite counts and the lower limit of the confidence interval are proposed as parameters to identify acaricide resistance.
Multiplex cytokine and antibody profile in cystic echinococcosis patients during a three-year follow-up in reference to the cyst stages
Authors: Li Zhi-Dan , Mo Xiao-Jin , Yan Shuai , Wang Dong , Xu Bin , Guo Jian , Zhang Ting , Hu Wei , Feng Yu , Zhou Xiao-Nong , Feng Zheng 
Published: March 2020

Abstract
Background
Cystic echinococcosis (CE) is a worldwide parasitic zoonosis caused by infection of the larval stage of tapeworm Echinococcus granulosus. In human CE, the parasites develop and form cysts in internal organs. The differentiated cysts can be classified into five types based on WHO-IWGE standard CE1-5 representing different developmental stages. Infection with E. granulosus triggers hosts’ humoral and cellular response, displaying elevated serum antibodies and Th1 and Th2 cytokines, which are presumed to be in association with the disease outcome. Identification of immunological markers for evaluation of disease progression has been a growing concern. However, the distinctive profile of cytokines and antibodies associated with the cyst progression has not been ascertained.

Methods
To better understand the interaction between host immune response and disease outcome, the present study followed-up four CE patients over three years by yearly measuring serum level of 27 cytokines, total IgG and isotypes, and ultrasound scanning, beginning in year 1 for all patients with CE1 and CE2 cysts before treatment and continued in year 2 with CE4 and in year 3 with CE3-CE5 post-treatment.

Results
Nine cytokines including Th1-type IL-2, Th17-type IL-17A, and inflammatory cytokines IL-1β, IL-1Rα and TNF-α, chemokines IL-8, MIP-1α, MIP-1β, and growth factor G-CSF were significantly elevated in patients with cyst type CE1, compared to the normal controls, and then declined to a normal level at CE4 and CE5. Examining the antibody production, we found that serum specific IgG was significantly increased in patients with active and transitional cysts, specifically the total IgG at CE1/CE3/CE4-CE5, IgG4 at CE1 and IgG1 at CE1/CE3 cyst status, in comparison with the normal controls, but showed no significant changes between the cyst stages.

Conclusions
Our findings provide new information on the profile of multiplex cytokines and serum antibodies associated with cyst stages in cystic echinococcosis patients through a three-year follow-up, implying that further studies using an approach combining cyst-associated immune parameters may aid in identifying immunological markers for differentiation of disease progression.
Genetic variation in Austrostrongylus thylogale Johnston & Mawson, 1940 (Nematoda: Trichostrongylida) from the tammar wallaby, Notamacropus eugenii (Gray), and the quokka, Setonix brachyurus (Quoy & Gaimard) (Marsupialia: Macropodidae) in Australia
Authors: Sukee Tanapan , Huynh Tony , Beveridge Ian , Jabbar Abdul 
Published: March 2020

Abstract
Background
Australian marsupials harbour a diverse array of helminth parasites. Despite current attempts to assess the extent of this diversity in macropodid hosts, it has been suggested that unique parasite fauna of Australian wildlife is difficult to document comprehensively due to the common occurrence of cryptic species. This paper assessed genetic variation within Austrostrongylus thylogale Johnston & Mawson, 1940 from the tammar wallaby, Notamacropus eugenii (Gray), and the quokka, Setonix brachyurus (Quoy & Gaimard), from different localities using the molecular characterisation of the internal transcribed spacers (ITS) within the nuclear ribosomal DNA.

Methods
Thirty-seven specimens of A. thylogale collected from N. eugenii (from Parndana, Kangaroo Island, South Australia, and Perup, Western Australia) and S. brachyurus (from Wellington Dam, Western Australia) were characterised using a molecular-phylogenetic approach utilising the first (ITS1) and second (ITS2) internal transcribed spacers.

Results
Genetic variation was detected in both ITS1 and ITS2 between specimens of A. thylogale from N. eugenii and S. brachyurus; however, no variation was detected between specimens collected from N. eugenii from Parndana, South Australia, and Perup, Western Australia. Furthermore, the phylogenetic analyses of ITS sequences showed two clades of A. thylogale originating from two hosts, N. eugenii and S. brachyurus, suggesting the presence of cryptic species.

Conclusions
This study provides evidence of genetic variation within A. thylogale based on collections from two different host species. Morphological studies are required to fully confirm the presence of a new species or cryptic species. Further molecular studies using a larger number of specimens are warranted to explore the genetic variation between A. thylogale from different geographical localities.
Adapted physical activity and cardiac coherence in hematologic patients (APACCHE): study protocol for a randomized controlled trial
Authors: Fournié Claire , Bouscaren Nicolas , Dalleau Georges , Lenclume Victorine , Mohr Catherine , Zunic Patricia , Cabrera Quentin , Verkindt Chantal 
Published: March 2020

Abstract
Background
Hematologic malignancies and their treatments are recognized for their significant long-term adverse effects on health-related quality of life. As a part of cancer treatment, physical exercise is known to improve physical functioning, but there are still questions regarding its impact on psychological and emotional functioning. Nonetheless, heart rate variability biofeedback (HRVB) is recognized for its positive effects on autonomic nervous system balance and emotional self-regulation. The Adapted Physical Activity and Cardiac Coherence in Hematologic Patients (APACCHE) protocol is a randomized, controlled superiority trial designed to evaluate the effects of HRBV training combined with an adaptive physical activity (APA) program compared to APA alone on the post-treatment quality of life of adult hematologic patients.

Methods
Seventy patients aged 18–70 years, with various forms of hematological malignancies, in post-treatment remission within six months prior to beginning the study and who have been prescribed APA by a hematologist, will be randomly allocated in a 1:1 ratio to two 12-week treatment groups: HRVB + APA versus APA alone. APA sessions will consist of aerobic and resistance training for 1-h twice weekly. The HRVB training will consist of controlled breathing exercises with biofeedback of heart rate variability for 10 sessions and will include a daily home-based practice. The primary outcome will be to evaluate health-related quality of life (QLQ-C30, SF-36). The secondary outcomes will be to evaluate fatigue (MFI-20); anxiety and depression (HADS); clinical status with blood pressure, progression-free survival, overall survival, and body mass index; heart rate variability level and cardiac coherence score. All of these assessments will be evaluated initially (T1), 6 weeks after (T2), at the end of the 12 weeks (T3), and then at a 12-week post-intervention follow-up (T4).

Discussion
To our knowledge, this is the first protocol to investigate the additional value of HRVB on physical exercise. In addition, there has been no study previously published about HRVB in hematologic patients. We hypothesize that overall quality of life and psychological and physical functioning will be improved, potentially offering a better understanding of supportive cancer care in hematology and inferring new perspectives in psychophysiological research in cancer.

Trial registration
Current randomized controlled trial was registered 29 November 2017 on Clinical Trials.gov (NCT number: NCT03356171).
An improved approach for studying oscillation of generalized Emden–Fowler neutral differential equation
Authors: Moaaz Osama , Elabbasy Elmetwally M. , Qaraad Belgees 
Published: March 2020

AbstractThe purpose of this work is to study the oscillation criteria for generalized Emden–Fowler neutral differential equation. We establish new oscillation criteria using both the technique of comparison with first order delay equations and the technique of Riccati transformation. Our new criteria are interesting as they improve, simplify, and complement some results that have been published recently in the literature. Moreover, we present an illustrating example.