bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Controlled Trial of the Effect of Repetitive Transcranial Magnetic Stimulation of the Motor Cortex on Lower Extremity Spasticity in Hereditary Spastic Paraplegia
Authors: Bastani Pouya B. , Kordjazi Mohsen , Oveisgharan Shahram , Abdi Siamak 
Published: November 2021

Introduction:Hereditary spastic paraplegia refers to a group of conditions characterized by a slow progression of spasticity in lower limbs resulting in gait abnormalities. Current treatment options have proven to be insufficient in terms of symptom alleviation. In this study, we tested the effectiveness of repetitive transcranial magnetic stimulation (rTMS) on lower limb spasticity in patients with hereditary spastic paraplegia.Methods:Eight patients were randomly assigned to receive either five sessions of active 5 Hz-rTMS (n= 4) or sham rTMS (n= 4). The primary outcome was a change in spasticity assessed by the modified Ashworth scale. Secondary outcomes were change in 10 m walking test, Fugl-Meyer assessment of lower extremity motor function, and quality-of-life short-form survey scores. Assessment of the outcomes was done before, upon completion, and 1 month after the intervention. We analyzed the data using repeated-measure analysis of variance.Results:Mean age of the participants was 38.5 (SD = 5.4) years, and 50% were women. Compared with sham rTMS, real rTMS was effective in decreasing modified Ashworth scale (rTMS × time: F [df = 2] = 7.44;P= 0.008). Real rTMS group had lower modified Ashworth scale scores at the end of rTMS sessions (estimate = −0.938; SE = 0.295;P= 0.019) and at the end of follow-up (estimate = −0.688; SE = 0.277;P= 0.048) compared with the sham rTMS group. Real and sham rTMS groups were not different in the secondary outcomes.Conclusions:Repetitive transcranial magnetic stimulation is an effective method in reducing lower limb spasticity of patients with hereditary spastic paraplegia.
Spike-Associated Networks Predict Postsurgical Outcomes in Children With Refractory Epilepsy
Authors: Bear Joshua J. , Sargent Jenifer L. , O'Neill Brent R. , Chapman Kevin E. , Ghosh Debashis , Kirsch Heidi E. , Tregellas Jason R. 
Published: November 2021

Purpose:
Up to half of the children undergoing epilepsy surgery will continue to have seizures (szs) despite a cortical resection or ablation. Functional connectivity has shown promise in better identifying the epileptogenic zone. We hypothesized that cortical areas showing high information outflow during interictal epileptiform discharges are part of the epileptogenic zone.

Methods:
We identified 22 children with focal epilepsy who had undergone stereo electroencephalography, surgical resection or ablation, and had ≥1 year of postsurgical follow-up. The mean phase slope index, a directed measure of functional connectivity, was calculated for each electrode contact during interictal epileptiform discharges. The positive predictive value and negative predictive value for a sz-free outcome were calculated based on whether high information outflow brain regions were resected.

Results:
Resection of high outflow (z-score ≥ 1) and very high outflow (z-score ≥ 2) electrode contacts was associated with higher sz freedom (high outflow: χ2 statistic = 59.1; P < 0.001; very high outflow: χ2 statistic = 31.3; P < 0.001). The positive predictive value and negative predictive value for sz freedom based on resection at the electrode level increased at higher z-score thresholds with a peak positive predictive value of 0.86 and a peak negative predictive value of 0.9.

Conclusions:
Better identification of the epileptogenic zone has the potential to improve epilepsy surgery outcomes. If the surgical plan can be modified to include these very high outflow areas, more children might achieve sz freedom. Conversely, if deficits from resecting these areas are unacceptable, ineffective surgeries could be avoided and alternative therapies offered.
Beamforming seizures from the temporal lobe
Authors: Dominguez Luis Garcia , Tarazi Apameh , Valiante Taufik , Wennberg Richard 
Published: November 2021

AbstractBackgroundSurgical treatment of drug-resistant temporal lobe epilepsy (TLE) depends on proper identification of the seizure onset zone (SOZ), and differentiation of mesial, temporolimbic seizure onsets from temporal neocortical seizure onsets. Non-invasive source imaging using electroencephalography (EEG) and magnetoencephalography (MEG) can provide accurate information on interictal spike localization; however, EEG and MEG have low sensitivity for epileptiform activity restricted to deep temporolimbic structures. Moreover, in mesial temporal lobe epilepsy (MTLE), interictal spikes frequently arise in neocortical foci distant from the SOZ, rendering interictal spike localization potentially misleading for presurgical planning.MethodsIn this study, we used two different beamformer techniques applied to the MEG signal of ictal events acquired during EEG-MEG recordings in six patients with TLE (three neocortical, three MTLE). The ictal source localization results were compared to the patients’ ground truth SOZ localizations determined from intracranial EEG and/or clinical, neuroimaging and postsurgical outcome evidence.ResultsBeamformer analysis proved to be highly accurate in all cases and able to reliably identify focal seizure onsets localized to mesial, temporolimbic structures. In three patients, interictal spikes were either absent, too complex for inverse dipole modeling, or localized to anterolateral temporal neocortex distant to a mesial temporal SOZ.ConclusionsThis report demonstrates the suitability of MEG beamformer analysis of ictal events in TLE, which can supersede or complement the traditional analysis of interictal spikes. The method outlined is applicable to any type of epileptiform event, greatly expanding the information value of MEG and broadening its utility for presurgical recording in epilepsy.
Surveillance of NK cell subsets and cytokine profile in patients with Rocky Mountain Spotted Fever
Authors: Maynez-Prieto Carolina , Adame-Gallegos Jaime R. , Ramírez-López Moisés , Quintana-Mendías Estefanía , Estrada-Aguirre Blanca E. , Baquera-Arteaga Maribel , Manzanera-Ornelas Diana , Guevara-Macías Enrique , Espino-Solís Gerardo P. 
Published: November 2021

AbstractIntroductionThe intracellular pathogen Rickettsia rickettsii causes tick-borne spotted fever (also called Rocky Mountain spotted fever (RMSF) and is increasingly recognized as an emerging cause of febrile illness in Mexico. However, little is known about the early immune responses to infection.MethodologyFour RMSF pediatric patients on acute phase and eight healthy controls from Chihuahua, Mexico were recruited. The natural killer cell (NK) immunophenotype and the cytokine profile in peripheral blood were characterized by flow cytometry.ResultsThere was a decrease in total NK (CD3-CD56+) and activation receptor (CD56+NKG2D+) in NK population in patients at day 3 after hospitalization, when compared to healthy controls. Regarding to the NK cytotoxic population (CD16brightCD56dim) there was an observed decrease in patients only, between day 3 and on hospital admission. Interleukin and chemokine levels measured were significantly increased in patients upon admission compared to controls (IL-6, IL-8, IL-10, IP-10, MCP-1 and MIG).ConclusionsThis study shows that circulating NK cells are numerically decreased, while cytokines induce a pro-inflammatory process in patients.
Sustained negative mental health outcomes among healthcare workers over the first year of the COVID-19 pandemic: a prospective cohort study
Authors: Mediavilla Roberto , Fernández-Jiménez Eduardo , Martinez-Morata Irene , Jaramillo Fabiola , Andreo-Jover Jorge , Morán-Sánchez Inés , Mascayano Franco , Moreno-Küstner Berta , Minué Sergio , Ayuso-Mateos José Luis , Bryant Richard A. , Bravo-Ortiz María-Fe , Martínez-Alés Gonzalo ,   the COVID-19 HEalth caRe wOrkErS – Spain (HEROES-SPA) Group
Published: November 2021

AbstractObjectiveTo characterize the evolution of healthcare workers’ mental health status over the 1-year period following the initial COVID-19 pandemic outbreak and to examine baseline characteristics associated with resolution or persistence of mental health problems over time.MethodsWe conducted an 8-month follow-up cohort study. Eligible participants were healthcare workers working in Spain. Baseline data were collected during the initial pandemic outbreak. Survey-based self-reported measures included COVID-19-related exposures, sociodemographic characteristics, and three mental health outcomes (psychological distress, depression symptoms, and posttraumatic stress disorder symptoms). We examined three longitudinal trajectories in mental health outcomes between baseline and follow-up assessments (namelyasymptomatic/stable, recovering, andpersistently symptomatic/worsening).ResultsWe recruited 1,807 participants. Between baseline and follow-up assessments, the proportion of respondents screening positive for psychological distress and probable depression decreased, respectively, from 74% to 56% and from 28% to 21%. Two-thirds remained asymptomatic/stable in terms of depression symptoms and 56% remained symptomatic or worsened over time in terms of psychological distress.ConclusionsPoor mental health outcomes among healthcare workers persisted over time. Occupational programs and mental health strategies should be put in place.
Behaviour, booster vaccines and waning immunity: modelling the medium-term dynamics of SARS-CoV-2 transmission in England in the Omicron era
Authors: Barnard Rosanna C. , Davies Nicholas G. ,   Centre for Mathematical Modelling of Infectious Diseases COVID-19 working group, Jit Mark , Edmunds W. John 
Published: November 2021

AbstractEngland has experienced a heavy burden of COVID-19, with multiple waves of SARS-CoV-2 transmission since early 2020 and high infection levels following the emergence and spread of Omicron variants since late 2021. In response to rising Omicron cases, booster vaccinations were accelerated and offered to all adults in England. Using a model fitted to more than 2 years of epidemiological data, we project potential dynamics of SARS-CoV-2 infections, hospital admissions and deaths in England to December 2022. We consider key uncertainties including future behavioural change and waning immunity, and assess the effectiveness of booster vaccinations in mitigating SARS-CoV-2 disease burden between October 2021 and December 2022. If no new variants emerge, SARS-CoV-2 transmission is expected to decline, with low levels remaining in the coming months. The extent to which projected SARS-CoV-2 transmission resurges later in 2022 depends largely on assumptions around waning immunity and to some extent, behaviour and seasonality.
Favipiravir for treatment of outpatients with asymptomatic or uncomplicated COVID-19: a double-blind randomized, placebo-controlled, phase 2 trial
Authors: Holubar Marisa , Subramanian Aruna , Purington Natasha , Hedlin Haley , Bunning Bryan , Walter Katharine S. , Bonilla Hector , Boumis Athanasia , Chen Michael , Clinton Kimberly , Dewhurst Liisa , Epstein Carol , Jagannathan Prasanna , Kaszynski Richard H. , Panu Lori , Parsonnet Julie , Ponder Elizabeth L. , Quintero Orlando , Sefton Elizabeth , Singh Upinder , Soberanis Luke , Truong Henry , Andrews Jason R. , Desai Manisha , Khosla Chaitan , Maldonado Yvonne 
Published: November 2021

AbstractBackgroundFavipiravir is an oral, RNA-dependent RNA polymerase inhibitor with in vitro activity against SARS-CoV2. Despite limited data, favipiravir is administered to patients with COVID-19 in several countries.MethodsWe conducted a phase 2 double-blind randomized controlled outpatient trial of favipiravir in asymptomatic or mildly symptomatic adults with a positive SARS-CoV2 RT-PCR within 72 hours of enrollment. Participants were randomized 1:1 to receive placebo or favipiravir (1800 mg BID Day 1, 800mg BID Days 2-10). The primary outcome was SARS-CoV-2 shedding cessation in a modified intention-to-treat (mITT) cohort of participants with positive enrollment RT-PCRs. Using SARS-CoV-2 deep sequencing, we assessed favipiravir’s impact on mutagenesis.ResultsFrom July 8, 2020 - March 23, 2021, we randomized 149 participants with 116 included in the mITT cohort. The participants’ mean age was 43 years (SD 12.5) and 57 (49%) were women. We found no difference in time to shedding cessation by treatment arm overall (HR 0.76 favoring placebo, 95% confidence interval [CI] 0.48 – 1.20) or in sub-group analyses (age, sex, high-risk comorbidities, seropositivity or symptom duration at enrollment). We observed no difference in time to symptom resolution (initial: HR 0.84, 95% CI 0.54 – 1.29; sustained: HR 0.87, 95% CI 0.52 – 1.45). We detected no difference in accumulation of transition mutations in the viral genome during treatment.ConclusionsOur data do not support favipiravir use at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher doses of favipiravir are effective and safe for patients with COVID-19.Trial registration numberNCT04346628SummaryIn this phase 2 double-blind randomized controlled outpatient trial of favipiravir in asymptomatic or uncomplicated patients with COVID-19, we found no difference in time to shedding cessation or time to symptom resolution by treatment arm.
Whole Genome Sequencing Illuminates the Developmental Signatures of Human Language Ability
Authors: Koomar Tanner , Casten Lucas G , Thomas Taylor R , Koh Jin-Young , Hofamman Dabney , Thenuwara Savantha , Momany Allison , O’Brien Marlea , Murray Jeffrey , Tomblin J Bruce , Michaelson Jacob J 
Published: November 2021

1AbstractLanguage is the foundation of human social interaction, education, commerce, and mental health. The heritability underlying language is well-established, but our understanding of its genetic basis — and how it compares to that of more general cognitive functioning— remains unclear. To illuminate the language-specific contributions of rare and common variation, we performed whole genome sequencing in N=350 individuals who were characterized with seven latent language phenotypes. We conducted region, gene, and gene set-based analyses to identify patterns of genetic burden that disproportionately explained these language factors compared to nonverbal IQ. These analyses identified language-specific associations with NDST4 and GRIN2A, with common variant replication of NDST4 in an independent sample. Rare variant burden analyses revealed three distinct functional profiles of genes that make contributions to language: a prenatally-expressed profile with enrichment for chromatin modifiers and broad neuropsychiatric risk, a postnatal cortex-expressed profile with enrichment for ion channels and cognitive/neuropsychiatric associations, and a postnatal, subcortically-expressed profile with enrichment of cilium-related proteins. Compared to a profile strongly associated with nonverbal IQ, these language-related profiles showed less intolerance to damaging variation, suggesting that the selection patterns acting on language differ from patterns linked to intellectual disability. Furthermore, we found evidence that rare potential reversions to an ancestral state are associated with poorer overall specific language ability. The breadth of these variant, gene, and profile associations suggest that while human-specific selection patterns do contribute to language, these are distributed broadly across numerous key mechanisms and developmental periods, and not in one or a few “language genes”.
Human phospho-signaling networks of SARS-CoV-2 infection are rewired by population genetic variants
Authors: Pellegrina Diogo , Bahcheli Alexander T. , Krassowski Michal , Reimand Jüri 
Published: November 2021

ABSTRACTSARS-CoV-2 infection hijacks signaling pathways and induces protein-protein interactions between human and viral proteins. Human genetic variation may impact SARS-CoV-2 infection and COVID-19 pathology; however, the role of genetic variation in these signaling networks remains uncharacterized. We studied human single nucleotide variants (SNVs) affecting phosphorylation sites modulated by SARS-CoV-2 infection, using machine learning to identify amino acid changes altering kinase-bound sequence motifs. We found 2033 infrequent phosphorylation-associated SNVs (pSNVs) that are enriched in sequence motif alterations, potentially reflecting the evolution of signaling networks regulating host defenses. Proteins with pSNVs are involved in viral life cycle processes and host responses, including regulators of RNA splicing and interferon response, as well as glucose homeostasis pathways with potential associations with COVID-19 co-morbidities. Certain pSNVs disrupt CDK and MAPK substrate motifs and replace these with motifs recognized by Tank Binding Kinase 1 (TBK1) involved in innate immune responses, indicating consistent rewiring of infection signaling networks. Our analysis highlights potential genetic factors contributing to the variation of SARS-CoV-2 infection and COVID-19 and suggests leads for mechanistic and translational studies.
Development and Performance verification of colloidal gold labeled SARS-CoV-2 antigen detection method for routine popular screening of COVID-19 with clinical samples in Poland and China
Authors: Guo Chuanxiang , Yao Li , Chen Fengling , Zhang Chao , Chen Wei 
Published: November 2021

AbstractIn this research, we have constructed and optimized the colloidal gold labeled lateral flow strip (LFS) for rapid detection of antigen of SARS-CoV-2 and rapid screening of COVID-19. Based on the constructed and optimized colloidal gold lateral flow strip, the parameters of the LFS have been well evaluated with the clinical samples in the professional labs. The screening performance have also been evaluated from the aspects including the CT values, age distribution and onset of symptoms. Finally, based on the detection results of 420 clinical samples, the LFS can achieve the screening of COVID-19 with the positive percentage agreement (PPA, sensitivity), negative percent agreement (NPA, specificity), the positive predictive value (PPV) and the negative predictive value (NPV) of 96.8%, 100%, 100% and 96.6%, respectively, indicating the powerful potential for practical screening applications in pandemic control. Of great significance, this developed SARS-CoV-2 antigen detection method has also been successfully utilized for screening of delta-variant of SARS-CoV-2.
Simulating the impact of vaccination rates on the initial stages of a COVID-19 outbreak in New Zealand (Aotearoa) with a stochastic model
Authors: Watson Leighton M. 
Published: November 2021

AbstractAimThe August 2021 COVID-19 outbreak in Auckland has caused the New Zealand government to transition from an elimination strategy to suppression, which relies heavily on high vaccination rates in the population. As restrictions are eased and as COVID-19 leaks through the Auckland boundary, there is a need to understand how different levels of vaccination will impact the initial stages of COVID-19 outbreaks that are seeded around the country.MethodA stochastic branching process model is used to simulate the initial spread of a COVID-19 outbreak for different vaccination rates.ResultsHigh vaccination rates are effective at minimizing the number of infections and hospitalizations. Increasing vaccination rates from 20% (approximate value at the start of the August 2021 outbreak) to 80% (approximate proposed target) of the total population can reduce the median number of infections that occur within the first four weeks of an outbreak from 1011 to 14 (25thand 75thquantiles of 545-1602 and 2-32 for V=20% and V=80%, respectively). As the vaccination rate increases, the number of breakthrough infections (infections in fully vaccinated individuals) and hospitalizations of vaccinated individuals increases. Unvaccinated individuals, however, are 3.3x more likely to be infected with COVID-19 and 25x more likely to be hospitalized.ConclusionThis work demonstrates the importance of vaccination in protecting individuals from COVID-19, preventing high caseloads, and minimizing the number of hospitalizations and hence limiting the pressure on the healthcare system.
Establishing and characterising large COVID-19 cohorts after mapping the Information System for Research in Primary Care in Catalonia to the OMOP Common Data Model
Authors: Burn Edward , Fernández-Bertolín Sergio , Voss Erica A , Blacketer Clair , Aragón Maria , Recalde Martina , Roel Elena , Pistillo Andrea , Raventós Berta , Reyes Carlen , van Sandijk Sebastiaan , Halvorsen Lars , Rijnbeek Peter R , Duarte-Salles Talita 
Published: November 2021

AbstractBackgroundFew datasets have been established that capture the full breadth of COVID-19 patient interactions with a health system. Our first objective was to create a COVID-19 dataset that linked primary care data to COVID-19 testing, hospitalisation, and mortality data at a patient level. Our second objective was to provide a descriptive analysis of COVID-19 outcomes among the general population and describe the characteristics of the affected individuals.MethodsWe mapped patient-level data from Catalonia, Spain, to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). More than 3,000 data quality checks were performed to assess the readiness of the database for research. Subsequently, to summarise the COVID-19 population captured, we established a general population cohort as of the 1st March 2020 and identified outpatient COVID-19 diagnoses or positive test results for SARS-CoV-2, hospitalisations with COVID-19, and COVID-19 deaths during follow-up, which went up until 30th June 2021.FindingsMapping data to the OMOP CDM was performed and high data quality was observed. The mapped database was used to identify a total of 5,870,274 individuals, who were included in the general population cohort as of 1st March 2020. Over follow up, 604,472 had either an outpatient COVID-19 diagnosis or positive test result, 58,991 had a hospitalisation with COVID-19, 5,642 had an ICU admission with COVID-19, and 11,233 had a COVID-19 death. People who were hospitalised or died were more commonly older, male, and with more comorbidities. Those admitted to ICU with COVID-19 were generally younger and more often male than those hospitalised in general and those who died.InterpretationWe have established a comprehensive dataset that captures COVID-19 diagnoses, test results, hospitalisations, and deaths in Catalonia, Spain. Extensive data checks have shown the data to be fit for use. From this dataset, a general population cohort of 5.9 million individuals was identified and their COVID-19 outcomes over time were described.FundingGeneralitat de Catalunya and European Health Data and Evidence Network (EHDEN).