bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Essential Tremor Alter the Axonal Excitability Properties of Lower Motor Neurons?
Authors: Kim Yerim , Kim Young Eun , Lee Joo Young , Ma Hyeo-Il , Shim Soon Kyung , Yoon Sun min , Bae Jong Seok 
Published: December 2020

Purpose:
Automated nerve excitability testing has identified that the altered excitability of lower motor neuron (LMN) axons in central diseases is because of trans-synaptic plasticity. Essential tremor (ET) is considered a central disorder caused by an altered cerebellar circuit. This study aimed to identify alterations in the excitability of distal motor axons in subjects with ET, with the intention of clarifying whether a trans-synaptic mechanism or LMN adaptation for tremor affects the LMNs of subjects with ET.

Methods:
Twenty-one consecutive patients diagnosed with ET underwent a clinical and electrophysiological evaluation. For the enrolled cases and 45 age- and gender-matched healthy controls, automated nerve excitability testing with threshold tracking techniques (QTRACS software with TRONDF multiple-excitability protocol) was used to evaluate multiple nerve excitability indices in distal median nerve motor axons.

Results:
The automated protocol calculated the strength–duration time constant, parameters of threshold electrotonus and current–threshold relationship, and the recovery cycle of excitability. Comparisons of the automated nerve excitability testing parameters revealed no significant differences between the ET and control groups in any of strength–duration time constant, threshold electrotonus, current–threshold relationship, and recovery cycle, whereas the rheobase was higher in the ET group (3.4 ± 1.1 vs. 2.3 ± 1.1, mean ± standard error mean; P < 0.01).

Conclusions:
With the exception of an increased rheobase in ET subjects, no significant differences were observed in LMN excitability between the ET subjects and their controls. The extent of plasticity or adaptation in LMNs may be limited to a major change in central processes that exert marked effects on the pool of LMNs.
Impact of small sample sizes on the internal quality control: statistical uncertainties in the determination of root mean square deviations with respect to the sample mean (RMSD) or to a target value (RMSTD)
Authors: Beier Christian 
Published: December 2020

AbstractInsufficient statistics due to small considered sample sizes can cause distinct problems in internal quality control (IQC) approaches. This issue concerns most of the currently applied IQC concepts either directly (if a root-mean-square-deviation metric is evaluated) or indirectly (if the IQC concept facilitates a standard deviation that was self-evaluated based on a very limited number (n≤30) of control measures). In clinical chemistry a famous example for the latter case is the common implementation of the Westgard Sigma Rules approach.This study quantifies the statistical uncertainties in the determination of root mean square (total) deviations related to the sample mean (RMSD) or to a target value (RMSTD). It is clearly shown that RMS(T)D values based on small data sets with n<50 samples are accompanied by a significant statistical uncertainty that needs to be considered in adequate IQC limit definitions. Two mathematical models are derived to reliably estimate an optimal adaptation function to adjust IQC limits to short charts of control measures.This article provides the theoretical background for the novel IQC method “Statistical Monitoring by Adaptive RMSTD Tests” (SMART) intended to monitor limited available numbers of recent control measures (usually n<20). The study also addresses a general problem in specificity of an IQC resulting from too small sample sizes during the evaluation period of the applied in-control standard deviation.
A demonstration of cone function plasticity after gene therapy in achromatopsia
Authors: Farahbakhsh Mahtab , Anderson Elaine J. , Rider Andy , Greenwood John A. , Hirji Nashila , Zaman Serena , Jones Pete R. , Schwarzkopf D. Samuel , Rees Geraint , Michaelides Michel , Dekker Tessa M. 
Published: December 2020

AbstractRecent advances in regenerative therapy have placed the treatment of many previously incurable eye diseases within arms-reach (Ciulla et al., 2020). Achromatopsia (ACHM) is a severe monogenic heritable retinal disease that disrupts cone function from gestation, leaving patients with complete colour blindness, low acuity, photosensitivity, and nystagmus (Hirji, Aboshiha, et al., 2018). In non-primate animal models of ACHM, retinal gene-replacement therapy has successfully induced cone function in the young (Alexander et al., 2007; Carvalho et al., 2011), but it was yet to be determined if and when these therapies could effectively impact cone-mediated pathways in the human brain. Here we demonstrate in children with ACHM that gene therapy can yield substantial improvement in cone-mediated vision, via cascading effects on signal transmission from retina to cortex. To measure the effects of treatment in children with ACHM (CNGA3- and CNGB3-associated, all aged 10+ years), we developed novel visual stimuli, calibrated to selectively activate cone photoreceptors. We used these in behavioural psychophysics and functional MRI with population receptive field mapping, pre- and post-treatment. The results of treatment, contextualized against data from 12 untreated ACHM patients and 25 normal-sighted, revealed that six months post-therapy, two patients displayed novel responses to our cone-selective stimuli in the visual cortex, with a retinotopic organisation characteristic of normal-sighted individuals, not present in untreated ACHM. This was paired with significant improvement in cone-mediated perception specific to the treated eye, and self-reports of improved vision. Two other patients did not show a post-treatment effect, potentially reflecting individual differences in therapeutic outcome. Together, these data show that gene replacement therapy in humans with ACHM can activate dormant cone pathways despite long-term deprivation. This offers great promise for regenerative therapies, and their ability to trigger the neural plasticity needed to cure congenital vision loss in human patients.
Functional connectivity of dorsolateral prefrontal cortex predicts cocaine relapse
Authors: Zhai Tianye , Salmeron Betty Jo , Gu Hong , Adinoff Bryon , Stein Elliot A. , Yang Yihong 
Published: December 2020

AbstractBackgroundRelapse is one of the most perplexing problems of addiction. The dorsolateral prefrontal cortex (DLPFC) is crucially involved in numerous cognitive and affective processes that are implicated in phenotypes of addiction, and is one of the most frequently reported brain regions with aberrant functionality in substance use disorders. However, the DLPFC is an anatomically large and functionally heterogeneous region, and the specific DLPFC-based circuits that contribute to drug relapse remain unknown.MethodsWe systematically investigated the relationship of cocaine relapse with 98 DLPFC functional circuits defined by evenly sampling the entire bilateral DLPFC in a cohort of cocaine dependent patients (n=43, 5F) following a psychosocial treatment intervention. A Cox regression model was utilized to predict relapse likelihood based on DLPFC functional connectivity strength.ResultsFunctional connectivity from 3 of the 98 DLPFC loci, one on the left and two on the right hemisphere, significantly predicted cocaine relapse with an accuracy of 83.9%, 84.7% and 85.4%, respectively. Combining all three significantly improved prediction validity to 87.5%. Protective and risk circuits related to these DLPFC loci were identified that are known to support “bottom up” drive to use drug and “top down” control over behavior together with social emotional, learning and memory processing.ConclusionThree DLPFC-centric circuits were identified that predict relapse to cocaine use with high accuracy. These functionally distinct DLPFC-based circuits provide insights into the multiple roles played by the DLPFC in cognitive and affective functioning that affects treatment outcome. The identified DLPFC loci may serve as potential neuromodulation targets for addiction treatment and as clinically relevant biomarkers of its efficacy.
Identifying communities at risk for COVID-19-related burden across 500 U.S. Cities and within New York City
Authors: Patel Chirag J , Deonarine Andrew , Lyons Genevieve , Lakhani Chirag M , Manrai Arjun K 
Published: December 2020

AbstractBackgroundWhile it is well-known that older individuals with certain comorbidities are at highest risk for complications related to COVID-19 including hospitalization and death, we lack tools to identify communities at highest risk with fine-grained spatial and temporal resolution. Information collected at a county level obscures local risk and complex interactions between clinical comorbidities, the built environment, population factors, and other social determinants of health.MethodsWe develop a robust COVID-19 Community Risk Score (C-19 Risk Score) that summarizes the complex disease co-occurrences for individual census tracts with unsupervised learning, selected on their basis for association with risk for COVID complications, such as death. We mapped the C-19 Risk Score onto neighborhoods in New York City and associated the score with C-19 related death. We further predict the C-19 Risk Score using satellite imagery data to map the built environment in C-19 Risk.ResultsThe C-19 Risk Score describes 85% of variation in co-occurrence of 15 diseases that are risk factors for COVID complications among 26K census tract neighborhoods (median population size of tracts: 4,091). The C-19 Risk Score is associated with a 40% greater risk for COVID-19 related death across NYC (April and September 2020) for a 1SD change in the score (Risk Ratio for 1SD change in C19 Risk Score: 1.4, p < .001). Satellite imagery coupled with social determinants of health explain nearly 90% of the variance in the C-19 Risk Score in the United States in held-out census tracts (R2 of 0.87).ConclusionsThe C-19 Risk Score localizes COVID-19 risk at the census tract level and predicts COVID-19 related morbidity and mortality.
Evaluation of the Effect of Zinc, Quercetin, Bromelain and Vitamin C on COVID-19 Patients
Authors: Kamel Amr , Abdelseed Heba , Albalawi Yousef , Aslsalameen Eman , Almutairi Yousef , Alkattan Abdullah 
Published: December 2020

AbstractCoronavirus disease 2019 (COVID-19) is an infectious disease caused by a new strain of coronavirus. There are three phases of COVID-19: early infection stage, pulmonary stage and hyper-inflammation stage respectively. It is important to prevent lung or other organs injuries by preventing phase-II and phase-III via pharmacological or non-pharmacological treatments. This was a case series study done on twenty-two patients confirmed to be infected with SARS-CoV-2 and diagnosed with COVID-19. Patients in this study have been used quercetin 800 mg, bromelain 165 mg, zinc acetate 50 mg and ascorbic acid 1 g once daily as supplements for 3 to 5 days during SARS-CoV-2 infection. The aim of this study is to evaluate the safety and efficacy of quercetin, bromelain, zinc and ascorbic acid combination supplements on patients with COVID-19. The mean levels of WBC, ANC, ALC, AMC and AST were normal among all included patients before and after taking quercetin, bromelain, zinc and ascorbic acid supplements (P-value > 0.05). Quercetin 800 mg, bromelain 165 mg, zinc acetate 50 mg and ascorbic acid 1 g once daily supplements were safe for patients infected with SARS-CoV-2 and may prevent poor prognosis. Randomized clinical trials needed in the future to ensure the efficacy of quercetin, bromelain, zinc and vitamin c combination.
Effectiveness of prolotherapy vs local anesthetic infiltration guided by ultrasound in the treatment of shoulder pain syndrome
Authors: Lira-Lucio Juan A. , Ochoa-Gaítan Guillermo , Hernández-Escobar Lizeth , Padilla-Rivera Christian I. , Hernández Porras Berenice C. , Juarez-Lemus Ángel M. , Ochoa-Millan Jose Guillermo , Jimenez-Contreras Roberto J. , Roldán-Rodríguez Enrique 
Published: December 2020

BACKGROUNDChronic Shoulder Pain (CSP) is a health problem that affects almost 67% of the general population. Almost a third of patients with acute shoulder pain syndrome don’t respond to initial therapy with analgesics and need interventional therapy. Corticosteroid injection is the standard therapy. Prolotherapy has been demonstrated to be effective in other chronic pain syndromes, but not in CSP. The aim of this study was to determine the effectiveness of prolotherapy compared to local anesthetic injection in the treatment of chronic shoulder painMETHODSRetrospective and comparative study of 77 patients from the National Institute of Oncology in Mexico City who received treatment for Chronic Shoulder Pain guided by ultrasound between 2017-2019. 57 patients were kept in the study for further analysis. 39 received infiltration with corticosteroids and 17 prolotherapy. Effectiveness of therapies was determined based on the decrease in VAS score in next follow-up session. Statistical analysis were performed with SPSS and RStudio Software.RESULTS51% of patients with Chronic Shoulder Pain were unemployed. 84% of the patients needed 3 different types of analgesics before they received ultrasound guided local treatment. Prolotherapy was as efficient as local anesthetic injection, no matter basal pain severity or underlying shoulder diagnosis, despite prolotherapy being more used as treatment for Rotator Cuff Tendinopathy.CONCLUSIONSProlotherapy and corticosteroid injection guided by ultrasound have the same efficacy in pain relief for chronic shoulder pain in oncologic patients.
Building a Best-in-Class Automated De-identification Tool for Electronic Health Records Through Ensemble Learning
Authors: Murugadoss Karthik , Rajasekharan Ajit , Malin Bradley , Agarwal Vineet , Bade Sairam , Anderson Jeff R. , Ross Jason L. , Faubion William A. , Halamka John D. , Soundararajan Venky , Ardhanari Sankar 
Published: December 2020

AbstractThe natural language portions of electronic health records (EHRs) communicate critical information about disease and treatment progression. However, the presence of personally identifiable information (PII) in this data constrains its broad reuse. Despite continuous improvements in methods for the automated detection of PII, the presence of residual identifiers in clinical notes requires manual validation and correction. However, manual intervention is not a scalable solution for large EHR datasets. Here, we describe an automated de-identification system that employs an ensemble architecture, incorporating attention-based deep learning models and rule-based methods, supported by heuristics for detecting PII in EHR data. Upon detection of PII, the system transforms these detected identifiers into plausible, though fictional, surrogates to further obfuscate any leaked identifier. We evaluated the system with a publicly available dataset of 515 notes from the I2B2 2014 de-identification challenge and a dataset of 10,000 notes from the Mayo Clinic. In comparison with other existing tools considered best-in-class, our approach outperforms them with a recall of 0.992 and 0.994 and a precision of 0.979 and 0.967 on the I2B2 and the Mayo Clinic data, respectively. The automated de-identification system presented here can enable the generation of de-identified patient data at the scale required for modern machine learning applications to help accelerate medical discoveries.
COVID-19 deaths detected in a systematic post-mortem surveillance study in Africa
Authors: Mwananyanda Lawrence , Gill Christopher J. , MacLeod William , Kwenda Geoffrey , Pieciak Rachel , Mupila Zachariah , Mupeta Francis , Forman Leah , Ziko Luunga , Etter Lauren , Thea Donald 
Published: December 2020

ABSTRACTObjectivesLimited SARS CoV 2 testing in many African countries has constrained availability of data on the impact of COVID-19 (CV19). To address this gap, we conducted a systematic post-mortem surveillance study to directly measure the fatal impact of CV19 in an urban African population.DesignWe enrolled deceased individuals at the University Teaching Hospital (UTH) Morgue in Lusaka, Zambia. We obtained nasopharyngeal swabs for testing via reverse-transcriptase quantitative PCR (RT-qPCR) against the SARS-2 Coronavirus. We stratified deaths by CV19 status, by location, age, sex, and underlying risk factors.SettingUTH is Zambia’s largest tertiary care referral hospital and its morgue registers ∼80% of Lusaka’s deaths.ParticipantsParticipants of all ages were enrolled if within 48 hours of death and if the next of kin or representative provided written informed consent.ResultsWe enrolled 372 participants between June and September 2020, and had PCR results for 364 (99.5%). CV19 was detected in 70/364 (19.2%). The median age for CV19+ deaths was 48 years (IQR 36-72 years) and 70% were male. Most CV19+ deaths (51/70, 72.8%) occurred in the community; none had been tested for CV19 antemortem. Among the 19/70 facility deaths, six were tested antemortem. Among the 52/70 CV19 deaths with symptoms data, 44/52 had typical symptoms of CV19 (cough, fever, shortness of breath), of whom only five were tested antemortem. We identified CV19 among seven children; only one had been tested antemortem. The proportion of CV19+ deaths increased with age, but 75.7% of CV19+ deaths were aged <60 years. The five most common co-morbidities among CV19+ deaths were: tuberculosis (31.4%); hypertension (27.1%); HIV/AIDS (22.9%); alcohol use (17.1%); and diabetes (12.9%).ConclusionsContrary to expectations, CV19+ deaths were common in Lusaka. The majority occurred in the community where testing capacity is lacking. Yet few who died at facilities were tested, despite presenting with typical symptoms of CV19. Therefore, CV19 cases were under reported because testing was rarely done, not because CV19 was rare. If our data are generalizable, the impact of CV19 in Africa has been vastly underestimated.
Prevalence of bacterial pathogens and potential role in COVID-19 severity in patients admitted to intensive care units in Brazil
Authors: de Carvalho Fabíola Marques , Lemos Leandro Nascimento , Ciapina Luciane Prioli , Moreira Rennan Garcias , Gerber Alexandra , Guimarães Ana Paula C , Fereguetti Tatiani , de Andrade Zambelli Virgínia Antunes , Avila Renata , de Almeida Tailah Bernardo , da Silva Lima Jheimson , Coutinho Barroso Shana Priscila , Teixeira Mauro Martins , Souza Renan Pedra , Cardoso Cynthia Chester , Aguiar Renato Santana , de Vasconcelos Ana Tereza Ribeiro 
Published: December 2020

AbstractSecondary bacterial and fungal infections are associated with respiratory viral infections and invasive mechanical ventilation. In Coronavirus disease 2019 (COVID-19), lung injury by SARS-CoV-2 and impaired immune response can provide a favorable environment for microorganism growth and colonization in hospitalized individuals. Recent studies suggest that secondary bacterial pneumonia is a risk factor associated with COVID-19. In Brazil, knowledge about microbiota present in COVID-19 patients is incipient. This work describes the microbiota of 21 COVID-19 patients admitted to intensive care units from two Brazilian centers. We identified respiratory, nosocomial and bacterial pathogens as prevalent microorganisms. Other bacterial opportunistic and commensal species are also represented. Virulence factors of these pathogenic species, metabolic pathways used to evade and modulate immunological processes and the interconnection between bacterial presence and virulence in COVID-19 progression are discussed.Article Summary LineWe identified respiratory, nosocomial and bacterial pathogens as prevalent microorganisms in 21 Brazilian COVID-19 patients admitted to Intensive Care Units. Pathogen virulence factors and immune response evasion metabolic pathways are correlated to COVID-19 severity.
The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants
Authors: Kværner Ane Sørlie , Birkeland Einar , Bucher-Johannessen Cecilie , Vinberg Elina , Nordby Jan Inge , Kangas Harri , Bemanian Vahid , Ellonen Pekka , Botteri Edoardo , Natvig Erik , Rognes Torbjørn , Hovig Eivind , Lyle Robert , Ambur Ole Herman , de Vos Willem M. , Bultman Scott , Hjartåker Anette , Landberg Rikard , Song Mingyang , Ursin Giske , Randel Kristin Ranheim , de Lange Thomas , Hoff Geir , Holme Øyvind , Berstad Paula , Rounge Trine B. 
Published: December 2020

AbstractBackgroundColorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions.MethodsThe CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period.DiscussionThe CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome- based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.Trial RegistrationClinicalTrials.gov Identifier: NCT01538550
THE SEARCH FOR AN ASSOCIATION OF HLA ALLELES AND COVID-19 RELATED MORTALITY IN THE RUSSIAN POPULATION
Authors: Cheranev Valery , Bulusheva Irina , Vechorko Valery , Korostin Dmitriy , Rebrikov Denis 
Published: December 2020

AbstractHLA genes play a pivotal role in an immune response via the presentation of pathogen peptides in a complex on the surface of cells of a host organism. Here, we studied the association of class I and class II genes with the severity of COVID-19 infection and HLA allele variants.We performed high-resolution sequencing of class I and class II HLA genes using the sample population of 147 patients who died of COVID-19 and statistically compared our results with the frequencies of the HLA genotypes in a control population of 270 samples.The obtained data demonstrated that 51:05 and 15:18 alleles from locus B* are statistically significantly associated with COVID-19 severity, while C*14:02 allele correlates with the probability of death from COVID-19 for patients without comorbidities.