bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvements in clinical signs of Parkinson’s disease using photobiomodulation: A prospective proof-of-concept study
Authors: Liebert Ann , Bicknell Brian , Laakso E-Liisa , Heller Gillian , Jalilitabaei Parastoo , Tilley Sharon , Mitrofanis John , Kiat Hosen 
Published: May 2021

AbstractBACKGROUNDParkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons.OBJECTIVETo assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT).METHODSTwelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12 weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14 weeks before commencing treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4 weeks of treatment, after 12 weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%.RESULTSMeasures of mobility, cognition, dynamic balance and fine motor skill were significantly improved (p<0.05) with PBM treatment for 12 weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed.CONCLUSIONSPBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted.TRIAL REGISTRATIONAustralian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p, registered on 12/01/2018
Psychometric properties of the Sleep Hygiene Index in a large Italian community sample
Authors: Zagaria Andrea , Ballesio Andrea , Musetti Alessandro , Lenzo Vittorio , Quattropani Maria C. , Borghi Lidia , Margherita Giorgia , Saita Emanuela , Castelnuovo Gianluca , Filosa Maria , Palagini Laura , Plazzi Giuseppe , Lombardo Caterina , Franceschini Christian 
Published: May 2021

AbstractObjective/BackgroundPoor sleep hygiene is considered an exacerbating and perpetuating factor of sleep disturbances and is also associated with poor mental health. The Sleep Hygiene Index (SHI) is a self-report measure assessing adherence to sleep hygiene practices. The aim of this study was to estimate the psychometric properties of the SHI in an Italian representative sample of the general population, following a formative measurement approach.Patients/MethodsParticipants (n=6276; M=33.62, SD=13.45) completed the SHI alongside measures of sleep disturbance, depression, anxiety, and stress. To consider the item formative nature, sets of item-composites weighted by means of canonical correlation analysis was created and a confirmatory factor analysis (CFA) was implemented. Factorial invariance tests were computed considering both presence of sleep problems and presence of emotional distress symptoms as grouping variables.Results and ConclusionsCFA confirmed the unidimensional structure of SHI. Internal consistency was acceptable (ω=0.752). Test-retest reliability at 8-10 months presented an ICC of 0.666. SHI significantly correlated with sleep, depression, anxiety and stress symptoms (r range from 0.358 to 0.500). Configural and metric invariance were reached for both grouping variables. Partial scalar invariance was obtained only across emotional distress groups. People with emotional symptoms reported higher latent means on the sleep hygiene dimension. Findings support the validity and reliability of the Italian version of the SHI. Importantly, the SHI showed robust psychometric properties both in healthy individuals and in individual reporting mental health symptoms. Thus, it is advisable to use this version of the SHI in both research and clinical practice.
A Study On Clinical Profile And Semiology In Complex Partial Seizures And Its Radiological Correlation
Authors: Nandini Priyanka B. , Elongovan S. , Thangaraj M. 
Published: May 2021

AbstractBackgroundEpilepsy is the second most common and frequently encountered neurological disorder which poses huge threat to known healthcare systems worldwide also causing financial, socio economic burden to the community. Complex Partial Seizures are a form of focal epileptic seizures that may impair consciousness.Aim and objectivesOur motivation for the study was to understand the extent of patients with complex partial seizures associated with medial temporal lobe sclerosis.Materials and methodsWe performed a cross sectional study about patients with complex partial seizures in Thanjavur medical college and hospital about their clinical profile and neuro-radiological correlation.Statistical analysis and resultsThrough our multimodal study with EEG, MRI on N=118 (female / male, age range, Most common age group-10-20 years, mean age of 23 years, SD-14 years, 66% males), we observed that atypical febrile seizures and fever provoked seizures has more association (18%) to complex partial seizures and to medial temporal lobe sclerosis in comparison to 12% in an earlier study.ConclusionWe believe this study summarizes the complex partial seizure features, origin, and their link to Medial Temporal lobe Sclerosis in our subject pool from Thajavur, India.LimitationThere are some limitations to our study, especially with no video EEG monitoring and no invasive EEG recording. We aim to improve them in our future studies.
Spatially refined time-varying reproduction numbers of SARS-CoV-2 in Arkansas and Kentucky and their relationship to population size and public health policy, March – November, 2020
Authors: Politis Maria D. , Hua Xinyi , Ogwara Chigozie A. , Davies Margaret R. , Adebile Temitayo M. , Sherman Maya P. , Zhou Xiaolu , Chowell Gerardo , Spaulding Anne C. , Fung Isaac Chun-Hai 
Published: May 2021

ABSTRACTPurposeTo examine the time-varying reproduction number, Rt, for COVID-19 in Arkansas and Kentucky and investigate the impact of policies and preventative measures on the variability in Rt.MethodsArkansas and Kentucky county-level COVID-19 cumulative case count data (March 6-November 7, 2020) were obtained. Rt was estimated using the R package ‘EpiEstim’, by county, region (Delta, non-Delta, Appalachian, non-Appalachian), and policy measures.ResultsThe Rt was initially high, falling below 1 in May or June depending on the region, before stabilizing around 1 in the later months. The median Rt for Arkansas and Kentucky at the end of the study were 1.15 (95% credible interval [CrI], 1.13, 1.18) and 1.10 (95% CrI, 1.08, 1.12), respectively, and remained above 1 for the non-Appalachian region. Rt decreased when facial coverings were mandated, changing by -10.64% (95% CrI, -10.60%, -10.70%) in Arkansas and -5.93% (95% CrI, -4.31%, -7.65%) in Kentucky. The trends in Rt estimates were mostly associated with the implementation and relaxation of social distancing measures.ConclusionsArkansas and Kentucky maintained a median Rt above 1 during the entire study period. Changes in Rt estimates allows quantitative estimates of potential impact of policies such as facemask mandate.
A genome-first approach to rare variants in hypertrophic cardiomyopathy genes MYBPC3 and MYH7 in a medical biobank
Authors: Park Joseph , Packard Elizabeth A , Levin Michael G , Judy Renae L ,   Regeneron Genetics Center, Damrauer Scott M , Day Sharlene M , Ritchie Marylyn D , Rader Daniel J 
Published: May 2021

Abstract‘Genome-first’ approaches to analyzing rare variants can reveal new insights into human biology and disease. Because pathogenic variants are often rare, new discovery requires aggregating rare coding variants into ‘gene burdens’ for sufficient power. However, a major challenge is deciding which variants to include in gene burden tests. Pathogenic variants in MYBPC3 and MYH7 are well-known causes of hypertrophic cardiomyopathy (HCM), and focusing on these ‘positive control’ genes in a genome-first approach could help inform variant selection methods and gene burdening strategies for other genes and diseases. Integrating exome sequences with electronic health records among 41,759 participants in the Penn Medicine BioBank, we evaluated the performance of aggregating predicted loss-of-function (pLOF) and/or predicted deleterious missense (pDM) variants in MYBPC3 and MYH7 for gene burden phenome-wide association studies (PheWAS). The approach to grouping rare variants for these two genes produced very different results: pLOFs but not pDM variants in MYBPC3 were strongly associated with HCM, whereas the opposite was true for MYH7. Detailed review of clinical charts revealed that only 38.5% of patients with HCM diagnoses carrying an HCM-associated variant in MYBPC3 or MYH7 had a clinical genetic test result. Additionally, 26.7% of MYBPC3 pLOF carriers without HCM diagnoses had clear evidence of left atrial enlargement and/or septal/LV hypertrophy on echocardiography. Our study shows the importance of evaluating both pLOF and pDM variants for gene burden testing in future studies to uncover novel gene-disease relationships and identify new pathogenic loss-of-function variants across the human genome through genome-first analyses of healthcare-based populations.
Impact of Sepsis Identification and Treatment Time on In-Hospital Mortality, Length of Stay, and Hours in the Intensive Care Unit
Authors: Sudat Sylvia EK 
Published: May 2021

ABSTRACTObjectiveThe objective of this study was to examine the impact of timely treatment and identification of sepsis on patient outcomes at Sutter Health, a mixed-payer healthcare system in northern California, US.MethodsThis observational, retrospective analysis considered electronic health record (EHR) data for individuals who presented with sepsis during 2016-17 at any of Sutter Health’s 22 emergency departments (ED). Impacts were assessed for the timing of broad-spectrum antibiotic and intravenous (IV) fluid initiation, first vital signs, sepsis screening, and lactate results. Outcomes were in-hospital mortality, hospital length of stay (LOS) and intensive care unit (ICU) hours for patients discharged alive.ResultsThe final sample size was 35,847 (N=9,638 severe sepsis, N=5,309 septic shock). Early fluid initiation had the largest estimated impacts: a mortality reduction of 2.85%[2.03%,3.68%] overall and 2.94%[1.44%,4.48%] for severe sepsis (within 1 hour of sepsis presentation), and 14.66%[9.23%,20.07%] for septic shock (within 3 hours); reduced LOS (days) 1.39[1.08,1.71] overall, 2.30[1.31,3.21] severe sepsis, 3.07[1.21,4.94] septic shock; and fewer ICU hours 25.93[16.95,34.66] overall, 35.06[14.7,56.99] severe sepsis, 41.99[15.70,70.68] septic shock (within 3 hours). Sepsis screening within 30 minutes was also associated with mortality reductions (3.88%[2.96%,4.90%] overall, 1.74%[0.08%,3.50%] severe sepsis, 6.78%[3.12%,10.33%] septic shock). The greatest improvement opportunity was estimated for joint initiation of antibiotics and IV fluids, with a modest additional mortality reduction of 0.80%[0.47%,1.17%] overall, 0.77%[0.34%,1.19%] severe sepsis, 2.94%[1.83%,3.97%] septic shock; LOS reduction of 0.37[0.28,0.46] overall, 0.29[0.17,0.43] severe sepsis, 0.25[0.01,0.51] septic shock (within 1 hour); ICU hours reduction of 4.85[3.26,6.57] overall, 5.07[2.55,7.67] severe sepsis, 3.85[1.69,6.24] septic shock (within 3 hours).
Ileal derived organoids from Crohn’s disease patients show unique transcriptomic and secretomic signatures
Authors: Niklinska-Schirtz Barbara Joanna , Venkateswaran Suresh , Anbazhagan Murugadas , Kolachala Vasantha L , Prince Jarod , Dodd Anne , Chinnadurai Raghavan , Gibson Gregory , Denson Lee A. , Cutler David J. , Jegga Anil G. , Matthews Jason D. , Kugathasan Subra 
Published: May 2021

AbstractBackgroundWe used patient derived organoids (PDOs) to study the epithelial-specific transcriptional and secretome signatures of the ileum during CD with varying phenotypes to screen for disease profiles and potential druggable targets.MethodsRNA sequencing was performed on isolated intestinal crypts and 3-week-old PDOs derived from ileal biopsies of CD patients (n= 8 B1, inflammatory; n= 8 B2, stricturing disease) and non-IBD controls (n= 13). Differentially expressed (DE) genes were identified by comparing CD vs control, B1 vs B2, and inflamed vs non-inflamed. DE genes were used for computational screening to find candidate small molecules that could potentially reverse B1and B2 gene signatures. The secretome of a second cohort (n= 6 non-IBD controls, n=7 CD; 5 non-inflamed, 2 inflamed) was tested by Luminex using cultured organoid conditioned media.ResultsWe found a 90% similarity in both the identity and abundance of protein coding genes between PDOs and intestinal crypts (15,554 transcripts of 19,900 genes). DE analysis identified 814 genes among disease group (CD vs non-IBD control), 470 genes different between the CD phenotypes, and 5 FDR significant genes between inflamed and non-inflamed CD. The PDOs showed both similarity and diversity in the levels and types of soluble cytokines and growth factors they released. Perturbagen analysis revealed potential candidate compounds to reverse B2 disease phenotype to B1 in PDOs.ConclusionPDOs are similar at the transcriptome level with the in vivo epithelium and retain disease-specific gene expression for which we have identified secretome products, druggable targets and corresponding pharmacological agents. Targeting the epithelium could reverse a stricturing phenotype and improve outcomes.
PONT: A Protocol for Online Neuropsychological Testing
Authors: Saban William , Ivry Richard B. 
Published: May 2021

AbstractA major challenge for neuropsychological research arises from the fact that we are dealing with a limited resource: The patients. Not only is it difficult to identify and recruit these individuals, but their ability to participate in research projects can be limited by their medical condition. As such, sample sizes are small and considerable time (e.g., 2 yrs) is required to complete a study. To address limitations inherent to lab-based neuropsychological research, we developed a protocol for online neuropsychological testing (PONT). We describe the implementation of PONT and provide the required information and materials for recruiting participants, conducting remote neurological evaluations, and testing patients in an automated, self-administered manner. The protocol can be easily tailored to target a broad range of patient groups, especially those that can be contacted via support groups or multi-site collaborations. To highlight the operation of PONT and describe some of the unique challenges that arise in on-line neuropsychological research, we summarize our experience using PONT in a research program involving individuals with Parkinson’s disease and spinocerebellar ataxia. In a 10-month period, by contacting 646 support group coordinators, we were able to assemble a participant pool with over 100 patients in each group from across the United States. Moreover, we completed six experiments (n>300) exploring their performance on a range of tasks examining motor and cognitive abilities. The efficiency of PONT in terms of data collection, combined with the convenience it offers the participants, promises a new approach that can increase the impact of neuropsychological research.
In-field genetic stock identification of overwintering coho salmon in the Gulf of Alaska: Evaluation of Nanopore sequencing for remote real-time deployment
Authors: Deeg Christoph M. , Sutherland Ben J. G. , Ming Tobi J. , Wallace Colin , Jonsen Kim , Flynn Kelsey L. , Rondeau Eric B. , Beacham Terry D. , Miller Kristina M. 
Published: May 2021

AbstractGenetic stock identification (GSI) by single nucleotide polymorphism (SNP) sequencing has become the gold standard for stock identification in Pacific salmon, which are found in mixed-stocks during the oceanic phase of their lifecycle. Sequencing platforms currently applied require large batch sizes and multi-day processing in specialized facilities to perform genotyping by the thousands. However, recent advances in third-generation single-molecule sequencing platforms, like the Oxford Nanopore minION, provide base calling on portable, pocket-sized sequencers and hold promise for the application of real-time, in-field stock identification on variable batch sizes. Here we report and evaluate utility and comparability of at-sea stock identification of coho salmon Oncorhynchus kisutch based on targeted SNP amplicon sequencing on the minION platform during the International Year of the Salmon Signature Expedition to the Gulf of Alaska in the winter of 2019. Long read sequencers are not optimized for short amplicons, therefore we concatenate amplicons to increase coverage and throughput. Nanopore sequencing at-sea yielded stock assignment for 50 of the 80 assessed individuals. Nanopore-based SNP calls agreed with Ion Torrent based genotypes in 83.25%, but assignment of individuals to stock of origin only agreed in 61.5% of individuals highlighting inherent challenges of Nanopore sequencing, such as resolution of homopolymer tracts and indels. However, poor representation of assayed coho salmon in the queried baseline dataset contributed to poor assignment confidence on both platforms. Future improvements will focus on lowering turnaround time, accuracy, throughput, and cost, as well as augmentation of the existing baselines, specifically in stocks from coastal northern BC and Alaska. If successfully implemented, Nanopore sequencing will provide an alternative method to the large-scale laboratory approach. Genotyping by amplicon sequencing in the hands of diverse stakeholders could inform management decisions over a broad expanse of the coast by allowing the analysis of small batches in remote areas in near real-time.
Metformin Suppresses Monocyte Immunometabolic Activation by SARS-CoV-2 and Spike Protein Subunit 1
Authors: Cory Theodore J. , Emmons Russell S. , Yarbro Johnathan R. , Davis Kierstin L. , Pence Brandt D. 
Published: May 2021

AbstractA hallmark of COVID-19 is a hyperinflammatory state that is associated with severity. Various anti-inflammatory therapeutics have shown mixed efficacy in treating COVID-19, and the mechanisms by which hyperinflammation occurs are not well understood. Previous research indicated that monocytes, a key innate immune cell, undergo metabolic reprogramming and produce inflammatory cytokines when stimulated with SARS-CoV-2. We hypothesized that binding by the viral spike protein mediates this effect, and that drugs which regulate immunometabolism could inhibit the inflammatory response in monocytes. Monocytes stimulated with recombinant SARS-CoV-2 spike protein subunit 1 showed a dose-dependent increase in glycolytic metabolism that was associated with production of pro-inflammatory cytokines including interleukin-6 and tumor necrosis factor-α. This response was dependent on hypoxia-inducible factor-1α, as chetomin inhibited glycolysis and cytokine production. Inhibition of glycolytic metabolism by 2-deoxyglucose (2-DG) or glucose deprivation also inhibited the glycolytic response, and 2-DG strongly suppressed cytokine production. Glucose-deprived monocytes rescued cytokine production by upregulating oxidative phosphorylation, an effect which was not present in 2-DG-treated monocytes due to the known effect of 2-DG on suppressing mitochondrial metabolism. Finally, pre-treatment of monocytes with metformin strongly suppressed spike protein-mediated cytokine production in monocytes, and abrogated glycolytic and mitochondrial metabolism. Likewise, metformin pre-treatment blocked cytokine induction by SARS-CoV-2 strain WA1/2020 in direct infection experiments in monocytes. In summary, the SARS-CoV-2 spike protein induces a pro-inflammatory immunometabolic response in monocytes that can be suppressed by metformin, and metformin likewise suppresses inflammatory responses to live SARS-CoV-2. This has potential implications for the treatment of hyperinflammation during COVID-19.
Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes
Authors: Petrigliano Frank A. , Liu Nancy Q. , Lee Siyoung , Tassey Jade , Sarkar Arijita , Lin Yucheng , Li Liangliang , Yu Yifan , Geng Dawei , Zhang Jiankang , Shkhyan Ruzanna , Bogdanov Jacob , Van Handel Ben , Ferguson Gabriel B. , Lee Youngjoo , Hinderer Svenja , Tseng Kuo-Chang , Kavanaugh Aaron , Crump J. Gage , Pyle April D. , Schenke-Layland Katja , Billi Fabrizio , Wang Liming , Lieberman Jay , Hurtig Mark , Evseenko Denis 
Published: May 2021

AbstractOsteoarthritis (OA) impacts hundreds of millions of people worldwide, with those affected incurring significant physical and financial burdens. Injuries such as focal defects to the articular surface are a major contributing risk factor for the development of OA. Current cartilage repair strategies are moderately effective at reducing pain but often replace damaged tissue with biomechanically inferior fibrocartilage. Here we describe the development, transcriptomic ontogenetic characterization and quality assessment at the single cell level, as well as the scaled manufacturing of an allogeneic human pluripotent stem cell-derived articular chondrocyte formulation that exhibits long-term functional repair of porcine articular cartilage. These results define a new potential clinical paradigm for articular cartilage repair and mitigation of the associated risk of OA.