bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological intervention to restore connectivity deficits of neuronal networks derived from ASD patient iPSC with a TSC2 mutation
Authors: Alsaqati Mouhamed , Heine Vivi M , Harwood Adrian J. 
Published: June 2020

Abstract
BackgroundTuberous sclerosis complex (TSC) is a rare genetic multisystemic disorder resulting from autosomal dominant mutations in the TSC1 or TSC2 genes. It is characterised by hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway and has severe neurodevelopmental and neurological components including autism, intellectual disability and epilepsy. In human and rodent models, loss of the TSC proteins causes neuronal hyperexcitability and synaptic dysfunction, although the consequences of these changes for the developing central nervous system is currently unclear.MethodsHere we apply Multi-electrode array (MEA)-based assays to study the effects of TSC2 loss on neuronal network activity using Autism Spectrum Disorder (ASD) patient-derived iPSCs. We examine both temporal synchronisation of neuronal bursting, and spatial connectivity between electrodes across the network.ResultsWe find that TSC2 patient-derived neurons with a functional loss of TSC2, in addition to possessing neuronal hyperactivity, develop a dysfunctional neuronal network with reduced synchronisation of neuronal bursting and lower spatial connectivity. These deficits of network function are associated with elevated expression of genes for inhibitory GABA signalling and decreased expression of those for glutamate signalling, indicating an imbalance of synaptic inhibitory-excitatory signalling. mTORC1 activity functions within a homeostatic triad of protein kinases, AMP-dependent protein Kinase 1 (AMPK), mTORC1 and Unc-51 like Autophagy Activating Kinase 1 (ULK1) that orchestrate the interplay of anabolic cell growth and catabolic autophagy while balancing energy and nutrient homeostasis. The mTORC1 inhibitor rapamycin suppresses neuronal hyperactivity, but does not increase network activity, whereas activation of AMPK restores network activity without affecting the network burst length or regularity. In contrast, the ULK1 activator, LYN-1604 increases the network behaviour, shortens the network burst lengths, and reduces the number of uncorrelated spikes.LimitationsAlthough a robust and consistent phenotype is observed across multiple independent iPSC clones, the results are based on iPSC from one patient. There may be more subtle differences between patients with different TSC2 mutations or differences of polygenic background within their genomes. This may affect the severity of the network deficit or the pharmacological response between TSC2 patients.ConclusionsOur observations suggest that there is a reduction in the network connectivity of the in vitro neuronal network associated with ASD patients with TSC2 mutation, which may arise via an excitatory/inhibitory imbalance due to increased GABA signalling at inhibitory synapses. This deficit can be effectively suppressed via activation of ULK1.
Treating COVID-19 Positive Cancer Patients with Radiation Therapy: Case Report From Epicenter of The Pandemic.
Authors: Parashar Bhupesh , Ames John W , Lee Lucille , Madu Chika , Narayana Ashwatha , Potters Louis 
Published: June 2020

Abstract
Coronavirus -19 (Sars-cov-2 or Covid-19) pandemic has resulted in unprecedented clinical challenges across the globe. Outcomes of patients with this infection are likely dependent on underlying comorbidities that predicts worse outcome in older patients. However, it is unknown whether Covid-19 infected cancer patients receiving radiation therapy (RT) have any different outcome than non-infected patients. We present the first series of Covid-19 infected patients that received RT for malignancy, their outcome, and toxicities.
Characterization of the leaf microbiome from whole-genome sequencing data of the 3000 rice genomes project
Authors: Roman-Reyna Veronica , Pinili Dale , Borja Frances Nikki , Quibod Ian Lorenzo , Groen Simon C. , Alexandrov Nikolai , Mauleon Ramil , Oliva Ricardo 
Published: June 2020

Abstract
Background: The crop microbial communities are shaped by interactions between the host, microbes and the environment, however, their relative contribution is beginning to be understood. Here, we explore these interactions in the leaf bacterial community across 3,024 rice accessions.Findings: By using unmapped DNA sequencing reads as microbial reads, we characterized the structure of the rice bacterial microbiome. We identified central bacteria taxa that emerge as microbial “hubs” and may have an influence on the network of host-microbe interactions. We found regions in the rice genome that might control the assembly of these microbial hubs. To our knowledge this is one of the first studies that uses raw data from plant genome sequencing projects to characterize the leaf bacterial communities. Conclusion: We showed, that the structure of the rice leaf microbiome is modulated by multiple interactions among host, microbes, and environment. Our data provide insight into the factors influencing microbial assemblage in the rice leaf and also opens the door for future initiatives to modulate rice consortia for crop improvement efforts.
Clinical and pathological findings of SARS-CoV-2 infection and concurrent IgA nephropathy: A case report
Authors: Liu Liu 
Published: June 2020

Abstract
Background: Since the Coronavirus Disease 2019 (COVID-19) outbreak, there is limited data on the clinical characteristics, treatment strategies and prognosis of COVID-19 in patients with concurrent renal disease. The kidney is believed to have a predisposition for COVID-19 due to its abundant angiotensin-converting enzyme 2 (ACE2) expression, which acts as a cell entry receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent postmortem investigations reveal renal involvement in COVID-19, and case reports describe collapsing glomerulopathy in African American patients with COVID-19. However, there is limited data regarding IgA nephropathy in the setting of COVID-19.Case presentation: In the present case, we report a 65-year old Chinese woman who presented with macroscopic hematuria, worsening proteinuria and decreased renal function after COVID-19 infection. She received a renal biopsy during COVID-19 infection. The renal biopsy revealed IgA nephropathy without any evidence for SARS-Cov-2. The findings suggest that the renal abnormalities were a consequence of exacerbation of this patient’s underlying glomerular disease after COVID-19 infection. After a regimen of 3-day course of glucocorticoid and angiotensin II receptor blocker therapy, the patient recovered and remained stable upon follow-up. Conclusions: It is important to consider the underlying glomerular disease exacerbation rather than virus induced injury when dealing with renal abnormalities in patients with COVID-19.
Health and Support Service Needs of Individuals With Disability From Culturally and Linguistically Diverse Backgrounds: A Scoping Review Protocol
Authors: Pho Jacqueline Nhu Quynh , Tan Aidan Christopher , Chaudhary Katrina , Hines Sonia , Ellison Caroline , Isaac Vivian , Lim David 
Published: June 2020

Abstract
Background: All individuals should have the right to engage meaningfully in occupations that meet their aspirations and life goals as well as promote their health and wellbeing. For individuals with disability, meaningful engagement in occupations is supported by timely, effective and adaptive health and support services. However, research has revealed multiple barriers preventing utilisation of these services by individuals with disability from culturally and linguistically diverse (CALD) backgrounds. This review aims to identify gaps and solutions in health and support services of individuals with disability from CALD backgrounds to meaningfully engage in occupations.Methods: A scoping review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews and follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review guidelines. A detailed search strategy will be used to search CINAHL, PubMed, Embase, Scopus, PsychInfo, JBI and Cochrane Library, as well as grey literature in Trove, Mednar and OpenGrey. Studies will be screened for eligibility against specific inclusion and exclusion criteria for relevant studies. Data will be extracted using the JBI data extraction instrument and presented in a diagrammatic or tabular form accompanied with a narrative summary.Discussion: The scoping review will present the health and support service needs of individuals with disability from CALD backgrounds and will extend the current reviews as it focuses the engagement in meaningful occupation. Findings from this review have the potential to inform local policy discussions and practice-based disability care.
Examining aptitude and barriers to Evidence Based Medicine among trainees at an ACGME-I accredited program
Authors: Mahmoud Mai , Laws Saad , Kamal Antoun , Mohanadi Dabia Al , Mohammed Ahmed Al , Mahfoud Ziyad 
Published: June 2020

Abstract
Background Evidence-based medicine (EBM) promotes critical thinking and produces better patients’ outcome. Accreditation Council for Graduate Medical Education (ACGME) competencies require trainees to locate, appraise and apply clinical evidence to patients care. Despite the emphasis that ACGME place on EBM, few organizations provide adequate training in EBM. This is even more critical in regions where medical trainees matriculate from diverse backgrounds of undergraduate medical education, where EBM may not be emphasized nor taught at all. EBM practice has a history of research in the West, however, EBM has not been widely studied in the Middle East. Methods Clinicians and trainees at Hamad Medical Corporation (HMC) matriculate from many countries in the Middle East and North Africa (MENA) and Asia. Trainees’ various backgrounds in medical education hypothesize different levels and experiences of EBM. To assess trainees EBM attitudes and knowledge in the internal medicine department at HMC in Doha, Qatar, we surveyed residents and fellows using a two-part survey. The first part was adapted from the evidence-based practice inventory by Kaper to assess trainees’ attitudes and perceptions of EBM. Trainees were also asked to complete the ACE tool to assess their knowledge proficiency regarding different elements of EBM. The results from the two were analyzed. Results The average score on the ACE tool among the participants was around 9 out of 15. Most participants rated themselves as beginners or intermediate in their EBM capabilities. Higher ACE scores were observed from participants with educational background from South Asia, and among those with more favorable attitudes towards EBM. Participants also reported reasonable capabilities of doing EBM and favorable atmosphere at work for EBM implementation. Lack of knowledge, resources and time were the most reported barriers for doing EBM. Conclusions Earlier adoption of EBM education and practices leads to increased competence and it should be taught and evaluated in the undergraduate and GME programs. This's especially true since it's known that EBM practices lead to better patient outcomes. In a setting where matriculating clinicians arrive from heterogeneous educational backgrounds and EBM experiences, it is important to assess and continuously implement EBM training.
Education of Pharmacists in Ghana: Evolving Curriculum, Context and Practice in the Journey from Dispensing Certificate to Doctor of Pharmacy Certificate.
Authors: Koduah Augustina , Kretchy Irene , Sekyi-Brown Reginald , Asiedu-Danso Michelle , Ohene-Agyei Thelma , Duwiejua Mahama 
Published: June 2020

Abstract
Background: Understanding the origin and evolution of education of pharmacists is important for practice and health system reforms. In Ghana, education of pharmacists started in the 1880s with the training of dispensers in a government hospital. Over the years, the curriculum and institutional arrangements changed and currently pharmacists are trained in universities. In this study we explored how and why education of pharmacists evolved in Ghana. Methods: We used a case study design to systematically describe education of pharmacists reforms. Data was collected from October 2018 and December 2019 through document review and in-depth interviews. The data was analysed based on institutional arrangements and contextual factors influencing reforms from the 1880s through 2012, when the Doctor of pharmacy programme was initiated in Ghana. Results: Reforms occurred around four main periods when institutional arrangements including the certificate awarded and expected roles were modified by educators and government. These are: (1) the Certificate of dispensing with dispenser-in-training and nurse-dispenser schemes (1880s to 1942), when dispensers were trained to assist doctors in dispensing or directly diagnosing and treating specific disease conditions. (2) the Diploma and Certificate of competency with the dispenser-in-training and pupil pharmacist schemes (1943 to 1960), where in addition to existing roles, pharmacists operated village dispensers. (3) the Bachelor of pharmacy degree (1961 to 2017), when pharmacists were trained mainly as medicines experts with a strong science base on all aspects of medicines from production, distribution and use; and over time with a gradual move to patient-oriented practice. (4) the Doctor of pharmacy degree (2012 to date), where in addition to existing roles, trainees are exposed to advance professional practice experiences. Important factors influencing the reforms included, health systems demands for village dispensaries and clinically oriented pharmacists, and harmonization with regional and international training and practice. Conclusion: Reasons influencing education of pharmacists reforms are context specific and are driven by historical experiences, national and international expectations as well as educators and regulators abilities to influence change. These reforms call for direct corresponding change in professional practice laws and regulation to enable pharmacists contribute fully to health care delivery in Ghana.
Derivation of "specific population who could benefit from Rosuvastatin": A secondary analysis on randomised controlled trial to uncover novel value of Rosuvastatin for precise treatment of ARDS
Authors: Zhang Shi , Lu Zhonghua , Wu Zongsheng , Xie Jianfeng , Yang Yi , Qiu Haibo 
Published: June 2020

Abstract
Background

The high heterogeneity of ARDS contributes to paradoxical conclusions from previous investigations of rosuvastatin for ARDS. Identification of the population (phenotype) who could benefit from rosuvastatin is a novel exploration for precise treatment of ARDS.

Methods

The patient population for this analysis consisted of unique patients with ARDS enrolled in the SAILS trial (Rosuvastatin vs. Placebo). Phenotypes were derived using consensus k means clustering applied to routinely available clinical variables within 6 hours of hospital presentation before receiving placebo or rosuvastatin. Kaplan–Meier statistic was used to estimate the 90 day cumulative mortality for screening specific population who could benefit from rosuvastatin, with cut-off value as P <0.05.

Results

The derivation cohort included 585 patients with ARDS. Of the 4 derived phenotypes, phenotype 3 was identified as "specific population who could benefit from rosuvastatin" since rosuvastatin resulted in a significant reduction in 90 day cumulative mortality for ARDS (hazard ratio [HR] 0.29 [95% CI 0.09, 0.93]; P=0.027). Meanwhile, there were no significant differences in baseline characteristics between those assigned to rosuvastatin and those assigned to placebo. Additionally, rosuvastatin markedly improved the free of cardiovascular failure (10.08±3.79 in Rosuvastatin group vs 7.31±4.94 in Placebo group, P=0.01) and coagulation abnormality (13.65±1.33 vs 12.15±3.77, P=0.02) to day 14 in phenotype 3. Patients classified as phenotype 3 exhibited but not limited to the relative higher platelet count (390.05±79.43×10^9/L), lower CRP (20.23±11.99μg/L) and Creat (1.42±1.08 mg/dl), compared with patients classified as other phenotypes. Besides that, rosuvastatin seemed to increase 90 day mortality for patients in phenotype 4 (HR 2.76[95% CI 0.09, 9.93], P=0.076), with its adverse effect on the reduction of free of renal failure to day 14(4.70±4.99 vs 10.17±4.69, P=0.01). Patients in phenotype 4 showed a relative severe illness baseline features particularly renal failure.

Conclusions

This secondary analysis of SAILS trial identified the specific population who can benefit from rosuvastatin using machine learning applied to clinical variables at the time of hospital presentation, which uncovered a novel value of rosuvastatin for the treatment of ARDS, with validation clinical trials to be warranted to assess these further.
The "State of Implementation" Progress Report (SIPREP): A Pilot Demonstration of a Navigation System for Implementation
Authors: Miech Edward J , Larkin Angela , Lowery Julie C , Butler Andrew J , Pettey Kristin M , Rattray Nicholas A , Penney Lauren S , Myers Jennifer , Damush Teresa M 
Published: June 2020

Abstract
Background: Implementation of new clinical programs across diverse facilities in national healthcare systems like the Veterans Health Administration (VHA) can be extraordinarily complex. Implementation is a dynamic process, influenced heavily by local organizational context and the individual staff at each medical center. It is not always clear in the midst of implementation what issues are most important to whom or how to address them. In recognition of these challenges, implementation researchers within VHA developed a new systemic approach to map the implementation work required at different stages and provide ongoing, detailed and nuanced feedback about implementation progress.Methods: This observational pilot demonstration project details how a novel approach to monitoring implementation progress was applied across two different national VHA initiatives. Stage-specific grids organized the implementation work into columns, rows and cells, identifying specific implementation activities at the site level to be completed along with who was responsible for completing each implementation activity. As implementation advanced, item-level checkboxes were crossed off and cells changed colors, offering a visual representation of implementation progress within and across sites across the various stages of implementation. Results: Applied across two different national initiatives, the SIPREP provided a novel navigation system to guide and inform ongoing implementation within and across facilities. The SIPREP addressed different needs of different audiences, both described and explained how to implement the program, made ample use of visualizations, and revealed both what was happening and not happening within and across sites. The final SIPREP product spanned distinct stages of implementation. Conclusions: The SIPREP made the work of implementation explicit at the facility level (i.e., who does what, and when) and provided a new common way for all stakeholders to monitor implementation progress and to help keep implementation moving forward. This approach could be adapted to a wide range of settings and interventions, and is planned to be integrated into the national deployment of two additional VHA initiatives within the next 12 months.
Male Gender is A Risk Factor For Sever Form of COVID-19 Illness and Worse Outcome in The Middle East
Authors: Hachim Ibrahim Y , Hachim Mahmood Y , Naeem Kashif Bin , Hannawi Haifa , Salmi Issa Al , Hannawi Suad 
Published: June 2020

Abstract
The identification of risk-factors, predicting the disease severity and outcome in novel coronavirus-disease-19 (COVID-19) patients, is essential to improve responsiveness to this pandemic. The association between gender and wide-range of clinical, pathological, and epidemiological factors was studied in 200-patients recruited during March-April 2020. A higher prevalence of COVID-19 infection in male (72%) compared to females (28%). Age and history of previous comorbidities were nearly comparable between genders (P value 0.75 and 0.97, respectively), male-patients had higher incidence of sever-critical form of the disease (44.67%) compared to only 23.22% in female-patients (P < 0.001). A 26.39% and 1.79% of male and female patients needed Intensive-care-unit (ICU) admission(P < 0.001), respectively. Male-patients developed a significant higher rate of lung injury presented as bilateral airspace consolidation in the plain chest X-ray at admission (38.89%) compared to 23.21% in female patient (P = 0.036%). A significant impairment of the renal-function (P = 0.031) and liver-function tests with higher level of lactate-dehydrogenase (LDH) (P < 0.001), serum bilirubin (P < 0.001), alanine-transferase; ALT (P = 0.036), and aspartate-aminotransferase, AST (P = 0.022) in male patients compared to female patients. In conclusion, this is the first detailed analysis in the middle east that thoroughly investigate the role of gender in determining the clinical course and severity of COVID-19 infection. Males compared to their age matched females, with same prevalence of comorbidities were more vulnerable to the sever COVID-19 illness with higher probability for ICU admission.
Expression and predictive value of leucine rich α-2 glycoprotein in ischemic heart disease
Authors: Gao Wei , Wu Runda , Yin Jiasheng , Ma Yuanji , Guo Junjie , Zhong Xin , Huang Dong , Ge Junbo 
Published: June 2020

Abstract
Background : The expression and predictive value of leucine rich α-2 glycoprotein (LRG) in ischemic heart disease, including coronary artery disease (CAD), myocardial infarction (MI) and chronic total occlusion (CTO), remain unclear.Methods : A total of 231 patients were included and divided into 4 groups: control group (N=39), CAD group (N=73), MI group (N=67) and CTO group (N=52). LRG was determined and compared within groups. MI group was then divided into 2 subgroups according to LRG expression. The association between LRG expression and clinical characteristics, peak Troponin T (TNT), left ventricular ejection fraction (LVEF) and in-hospital stay was investigated.Results : LRG expression in MI group was significantly higher than that in control group (37.9±12.8 vs 25.3±8.9, P<0.001). LRG expression in CAD and CTO group were similar with that in control group (CAD vs Con, 23.1±6.8 vs 25.3±8.9, P=0.233; CTO vs Con, 22.0±7.8 vs 25.3±8.9, P=0.082). In MI group, patients with increased LRG had higher peak TNT (4.80 (2.34-10.0) vs 2.46 (0.89-4.98), P=0.002), lower LVEF (48.7±10.2 vs 54.8±8.4, P=0.009) and longer in-hospital stay (10.4±5.4 vs 8.0±2.9, P=0.027). Linear regression showed that LRG was independently associated with in-hospital stay. ROC curve showed the area of LRG under the curve (AUC) was 0.859.Conclusions : LRG expression was elevated in MI patients compared with controls, angiography confirmed CAD and CTO patients. In the MI subgroup, patients with elevated LRG had higher peak TNT, lower LVEF and longer in-hospital stay. Whether LRG is associated with major adverse cardiovascular events and long term prognosis needs further investigation.