bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrinsic dialogues between the two hemispheres in middle-aged male alcoholics: a resting-state functional MRI study
Authors: Dai Xiyong , Zhang Jianlong , Gao Lei , Yu Jinming , Li Yuanchun , Du Baoguo , Huang Xiangyi , Zhang Haibo 
Published: January 2021

Background
The purpose of this study was to investigate the interhemispheric intrinsic connectivity measured by resting-state functional MRI (R-fMRI) in middle-aged male alcoholics.

Methods
Thirty male alcoholics (47.33 ± 8.30 years) and 30 healthy males (47.20 ± 6.17 years) were recruited and obtained R-fMRI data. Inter- and intrahemispheric coordination was performed by using voxel-mirrored homotopic connectivity (VMHC) and seed-based functional connectivity analysis.

Results
We found significantly decreased VMHC in a set of regions in male alcoholics patients, including lateral temporal, inferior frontal gyrus, insular/insulae operculum, precuneus/posterior cingulate gyrus, and pars triangularis (P < 0.05, corrected). Subsequent seed-based functional connectivity analysis demonstrated disrupted functional connectivity between the regions of local homotopic connectivity deficits and other areas of the brain, particularly the areas subserving the default, salience, primary somatomotor, and language systems.

Conclusions
Middle-aged male alcoholic subjects demonstrated prominent reductions in inter- and intrahemispheric functional coherence. These abnormal changes may reflect degeneration of system/network integration, particularly the domains subserving default, linguistic processing, and salience integration.
Salivary markers and coronavirus disease 2019: insights from cross-talk between the oral microbiome and pulmonary and systemic low-grade inflammation and implications for vascular complications
Authors: AbdelMassih Antoine , Hassan Alaa A. , Abou-Zeid Aya S. , Hassan Aya , Hussein Engy , Gadalla Mahenar , Hussein Mahinour , Eid Maryam A. , Elahmady Maryam , El Nahhas Nadine , Emad Nadine , Zahra Nihal , Aboushadi Nour , Ibrahim Nourhan , Mokhtar Sherouk , Ismail Habiba-Allah , El-Husseiny Nadine , Moharam Reham Khaled , Menshawey Esraa , Menshawey Rahma 
Published: January 2021

To date, coronavirus disease 2019 (COVID-19) has affected over 6.2 million individuals worldwide, including 1.46 million deaths. COVID-19 complications are mainly induced by low-grade inflammation-causing vascular degeneration. There is an increasing body of evidence that suggests that oral dysbiotic taxa are associated with worse prognosis in COVID-19 patients, especially the Prevotella genus, which was retrieved from nasopharyngeal and bronchoalveolar lavage samples in affected patients. Oral dysbiosis may act by increasing the likelihood of vascular complications through low-grade inflammation, as well as impairing respiratory mucosal barrier mechanisms against SARS-CoV-2. Salivary markers can be used to reflect this oral dysbiosis and its subsequent damaging effects on and the lungs and vasculature. Salivary sampling can be self-collected, and is less costly and less invasive, and thus may be a superior option to serum markers in risk stratification of COVID-19 patients. Prospective studies are needed to confirm such hypothesis.
Video Abstract: http://links.lww.com/CAEN/A28
Prognostic significance of BMI after PCI treatment in ST-elevation myocardial infarction A cohort study from the Swedish Coronary Angiography and Angioplasty Registry
Authors: Jamaly Shabbar , Redfors Björn , Omerovic Elmir , Carlsson Lena , Karason Kristjan 
Published: January 2021

AbstractBackgroundObesity along with clustering of cardiovascular risk factors is a promoter for coronary artery disease. On the other hand, a high BMI appears to exert a protective effect with respect to outcomes after a coronary artery event, termed the obesity paradox.MethodsThe Swedish Coronary and Angiography and Angioplasty registry (SCAAR) collects information on all patients who undergo percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in Sweden along with demographic- and procedure-related data. We studied the predictability of four categories of BMI for 1-year all-cause mortality in people with STEMI undergoing PCI.ResultsAmong 25,384 patients, mean (SD) age 67.7 (12.1) years and 71.1% male, who underwent PCI for STEMI a total of 5,529 (21.8%) died within one year. Using normal-weight (BMI 18.5-24.9 kg/m2) as a reference, subjects with obesity (BMI ≥30 kg/m2) had a low 1-year all-cause mortality risk in unadjusted analysis, HR 0.59 (95% CI 0.53– 0.67). However, after adjustment for age, sex and other covariates the difference became non-significant, HR 0.88 (95% CI: 0.75-1.02). Patients with overweight (BMI 25.0-29.9 kg/m2) had the lowest 1-year mortality risk in analysis adjusted for age, sex and other covariates, HR 0.87 (95% CI 0.79-0.95), whereas those with underweight (BMI <18.5 kg/m2) had the highest mortality in both unadjusted HR 2.22 (95% CI 1.69–2.92) and adjusted analysis, HR 1.72 (95% CI: 1.31-2.26).ConclusionThe protective effect of obesity with respect to 1-year mortality after coronary intervention became non-significant after adjusting for age, sex and relevant co-variates. Instead, overweight people displayed the lowest risk and underweight individuals the highest risk for adjusted all-cause mortality
Hidden Parameters Impacting Resurgence of SARS-CoV-2 Pandemic*
Authors: Zhang Yi , Kapoor Sanjiv 
Published: January 2021

The spread of the COVID-19 virus has had an enormous impact on the world’s health and socioeconomic system. While lockdowns, which severely limit the movement of the population, have been implemented in March 2020 and again recently, the psychological and economic cost are severe. Removal of these restrictions occurred with varying degrees of success.To study the resurgence of the virus in some communities we consider an epidemiological model, SIR-SD-L, that incorporates introduction of new population due to the removal of lockdown and identify parameters that impact the spread of the virus. This compartmental model of the epidemic incorporates a social distance metric based on progression of the infections; it models the dynamic propensity of infection spread based on the current infections relative to the susceptible population. The model is validated using data on growth of infections, hospitalizations and death, considering 24 counties in multiple US states and a categorization of the lockdown removal policies after the first lockdown. Model parameters, which include a compartment for the isolated population, are used to determine the rate at which the susceptible population increases to fit the rate of infections. Along with social distancing mandates, we identify active infections and the susceptible population as important factors in the resurgence of infections. We measure the efficacy of the lockdown removal policy via a ratio, PIR, which evaluates to less than 1 for counties where social distancing measures were mandated and which delayed complete re-opening of closed spaces like bars and restaurants. For other counties this ratio is greater than 1.We also studied infection growth in the 24 US counties with respect to a release policy derived from CDC guidelines and compared against strategies that delay the removal of lockdown.Our results illustrate that guidelines for deciding when lockdown rules are to be relaxed should consider the current state of the infectious population and the remaining susceptible population, hidden parameters that are deducible from models such as SIR-SD-L, and not limit policy considerations to the rate of new infections alone. This is especially true for counties where the growth rate of the virus is initially slow and misleading. Emphasis on social distancing is critical.
Factors associated with deaths due to COVID-19 versus other causes: population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform
Authors: Bhaskaran K , Bacon SCJ , Evans SJW , Bates CJ , Rentsch CT , MacKenna B , Tomlinson L , Walker AJ , Schultze A , Morton CE , Grint D , Mehrkar A , Eggo RM , Inglesby P , Douglas IJ , McDonald HI , Cockburn J , Williamson EJ , Evans D , Curtis HJ , Hulme WJ , Parry J , Hester F , Harper S , Spiegelhalter D , Smeeth L , Goldacre B 
Published: January 2021

ABSTRACTBackgroundMortality from COVID-19 shows a strong relationship with age and pre-existing medical conditions, as does mortality from other causes. However it is unclear how specific factors are differentially associated with COVID-19 mortality as compared to mortality from other causes.MethodsWorking on behalf of NHS England, we carried out a cohort study within the OpenSAFELY platform. Primary care data from England were linked to national death registrations. We included all adults (aged ≥18 years) in the database on 1st February 2020 and with >1 year of continuous prior registration, the cut-off date for deaths was 9th November 2020. Associations between individual-level characteristics and COVID-19 and non-COVID deaths were estimated by fitting age- and sex-adjusted logistic models for these two outcomes.Results17,456,515 individuals were included. 17,063 died from COVID-19 and 134,316 from other causes. Most factors associated with COVID-19 death were similarly associated with non-COVID death, but the magnitudes of association differed. Older age was more strongly associated with COVID-19 death than non-COVID death (e.g. ORs 40.7 [95% CI 37.7-43.8] and 29.6 [28.9-30.3] respectively for ≥80 vs 50-59 years), as was male sex, deprivation, obesity, and some comorbidities. Smoking, history of cancer and chronic liver disease had stronger associations with non-COVID than COVID-19 death. All non-white ethnic groups had higher odds than white of COVID-19 death (OR for Black: 2.20 [1.96-2.47], South Asian: 2.33 [2.16-2.52]), but lower odds than white of non-COVID death (Black: 0.88 [0.83-0.94], South Asian: 0.78 [0.75-0.81]).InterpretationSimilar associations of most individual-level factors with COVID-19 and non-COVID death suggest that COVID-19 largely multiplies existing risks faced by patients, with some notable exceptions. Identifying the unique factors contributing to the excess COVID-19 mortality risk among non-white groups is a priority to inform efforts to reduce deaths from COVID-19.FundingWellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, Health Data Research UK.
Estimating the effects of non-pharmaceutical interventions on the number of new infections with COVID-19 during the first epidemic wave
Authors: Banholzer Nicolas , van Weenen Eva , Lison Adrian , Cenedese Alberto , Seeliger Arne , Kratzwald Bernhard , Tschernutter Daniel , Salles Joan Puig , Bottrighi Pierluigi , Lehtinen Sonja , Feuerriegel Stefan , Vach Werner 
Published: January 2021

AbstractThe novel coronavirus (SARS-CoV-2) has rapidly developed into a global epidemic. To control its spread, countries have implemented non-pharmaceutical interventions (NPIs), such as school closures, gathering bans, or even stay-at-home orders. Here we study the effectiveness of seven NPIs in reducing the number of new infections, which was inferred from the reported cases of COVID-19 using a semi-mechanistic Bayesian hierarchical model. Based on data from the first epidemic wave ofn= 20 countries (i.e., the United States, Canada, Australia, the EU-15 countries, Norway, and Switzerland), we estimate the relative reduction in the number of new infections attributed to each NPI. Among the NPIs considered, event bans were most effective, followed by venue and school closures, whereas stay-at-home orders and work bans were least effective. With this retrospective cross-country analysis, we provide estimates regarding the effectiveness of different NPIs during the first epidemic wave.
Sensitivity of Estimated Tacrolimus Population Pharmacokinetic Profile to Inaccurate Assumptions about Dose Timing and Absorption: An Investigation in Real-World and Simulated Data
Authors: Williams Michael L. , Weeks Hannah L. , Beck Cole , Choi Leena 
Published: January 2021

AbstractA population pharmacokinetic (PK) study with 363 subjects was performed using real-world data extracted from electronic heath records (EHRs) to estimate the tacrolimus population PK profile. As population PK studies for oral medications performed using EHR data often assume a regular dosing schedule as prescribed without incorporating exact dosing time, we assessed the sensitivity of the PK parameter estimates to assumptions about dose timing using last-dose times extracted by our own natural language processing system, medExtractR. We also investigated the sensitivity of estimations to absorption rate constants that are often fixed at a published value in tacrolimus population PK analysis. There was no appreciable difference in parameters estimates with vs. without last-dose time incorporated in the data and our sensitivity analysis revealed little difference between parameters estimated assuming a range of absorption rate constants. We also conducted simulation studies to investigate how drug PK profiles and experimental designs such as concentration measurements affects sensitivity to incorrect assumptions about dose timing and absorption rates. Our findings suggest that drugs with a slower elimination rate (or a longer half-life) are less sensitive to dose timing errors and that experimental designs which only allow for trough blood concentrations are usually insensitive to deviation in absorption rate.
The impact of Spike mutations on SARS-CoV-2 neutralization
Authors: Rees-Spear C , Muir L , Griffith SA , Heaney J , Aldon Y , Snitselaar JL , Thomas P , Graham C , Seow J , Lee N , Rosa A , Roustan C , Houlihan CF , Sanders RW , Gupta R , Cherepanov P , Stauss H , Nastouli E , Doores KJ , van Gils MJ , McCoy LE 
Published: January 2021

AbstractMultiple SARS-CoV-2 vaccines have shown protective efficacy, which is most likely mediated by neutralizing antibodies recognizing the viral entry protein, Spike. Antibodies from SARS-CoV-2 infection neutralize the virus by focused targeting of Spike and there is limited serum cross-neutralization of the closely-related SARS-CoV. As new SARS-CoV-2 variants are rapidly emerging, exemplified by the B.1.1.7, 501Y.V2 and P.1 lineages, it is critical to understand if antibody responses induced by infection with the original SARS-CoV-2 virus or the current vaccines will remain effective against virus variants. In this study we evaluate neutralization of a series of mutated Spike pseudotypes including a B.1.1.7 Spike pseudotype. The analyses of a panel of Spike-specific monoclonal antibodies revealed that the neutralizing activity of some antibodies was dramatically reduced by Spike mutations. In contrast, polyclonal antibodies in the serum of patients infected in early 2020 remained active against most mutated Spike pseudotypes. The majority of serum samples were equally able to neutralize the B.1.1.7 Spike pseudotype, however potency was reduced in a small number of samples (3 of 36) by 5–10-fold. This work highlights that changes in the SARS-CoV-2 Spike can alter neutralization sensitivity and underlines the need for effective real-time monitoring of emerging mutations and their impact on vaccine efficacy.
Saccades along spatial neural circuit discontinuities
Authors: Malevich Tatiana , Hafed Ziad M. 
Published: January 2021

AbstractSaccades are realized by six extraocular muscles that define the final reference frame for eyeball rotations. However, upstream of the nuclei innervating the eye muscles, eye movement commands are represented in two-dimensional retinocentric coordinates, as is the case in the superior colliculus (SC). In such spatial coordinates, the horizontal and vertical visual field meridians, relative to the line of sight, are associated with neural tissue discontinuities due to routing of binocular retinal outputs when forming retinotopic sensory-motor maps. At the level of the SC, a functional discontinuity along the horizontal meridian was additionally discovered, beyond the structural vertical discontinuity associated with hemifield lateralization. How do such neural circuit discontinuities influence purely cardinal saccades? Using thousands of saccades from 3 rhesus macaque monkeys and 14 human subjects, we show how the likelihood of purely horizontal or vertical saccades is infinitesimally small, nulling a discontinuity problem. This does not mean that saccades are sloppy. On the contrary, saccades exhibit remarkable direction and amplitude corrections to account for small initial eye position deviations due to fixational variability: “purely” cardinal saccades can deviate, with an orthogonal component of as little as 0.03 deg, to correct for tiny target position deviations from initial eye position. In humans, probing perceptual target localization additionally revealed that saccades show different biases from perception when targets deviate slightly from purely cardinal directions. These results demonstrate a new functional role for fixational eye movements in visually-guided behavior, and they motivate further neurophysiological investigations of saccade trajectory control in the brainstem.New and NoteworthyPurely cardinal saccades are often characterized as being straight. We show how a small amount of curvature is inevitable, alleviating an implementational problem of dealing with neural circuit discontinuities in the representations of the visual meridians. The small curvature functionally corrects for minute variability in initial eye position due to fixational eye movements. Saccades are far from sloppy; they deviate by as little as <1% of the total vector size to adjust their landing position.
Off-label use in Palliative Care – more common than expected. A retrospective chart review
Authors: Hagemann Vera , Bausewein Claudia , Rémi Constanze 
Published: January 2021

AbstractObjectiveOff-label drug use seems to be integral to palliative care pharmacotherapy. Balancing potential risks and benefits in the context of limited therapeutic options is challenging. To provide specific support for clinicians in dealing with off-label use, it is essential to understand off-label use in everyday clinical practice.The aim of this pilot study was to quantify and describe off-label use in a palliative care unit.MethodsRetrospective chart review of all adult patients treated on a palliative care unit in 10/2017. All data on drug use e.g. indication, dose, route of administration were extracted and matched with the prescribing information. Identified off-label use was subsequently compared with recommendations in the relevant literature. The main outcome measure was frequency and type of off-label drug use.Results2,352 drug application days (d) and 93 drugs were identified for 28 patients. Of all drugs, 47 (51%) were used off-label at least once. Most off-label uses concerned indication (57%), followed by mode of administration. In drugs highly relevant to palliative care the rate of off-label use was as high as 67%. The extent to which off-label therapy was supported by literature was very variable and ranged from 0 to 88%.ConclusionsThis single-unit data confirms the high prevalence of off-label use in palliative medicine and demonstrates that off-label use in palliative care is very multifaceted. The data presented allows for a more precise characterization of various aspects of off-label use in order to derive concrete further measures for research and clinical practice.What is already known on this subjectOff-label drug use is likely to be common in palliative care, but detailed data is very limitedOff-label drug use is a potential threat for patient safetyPhysicians state to make therapeutic decisions based on their own experience, due to a lack of available evidence and lack of support in assessmentWhat this study addsoff-label use in palliative care is multifacetedthe mode of administration (e.g. combination with other drugs in a syringe driver) is beside indication a common reasons for off label usethe proportion of off-label use without sound evidence is high.
Antipsychotics effects on network-level reconfiguration of cortical morphometry in first-episode schizophrenia
Authors: Jiang Yuchao , Wang Yingchan , Huang Huan , He Hui , Tang Yingying , Su Wenjun , Xu Lihua , Wei Yanyan , Zhang Tianhong , Hu Hao , Wang Jinhong , Wang Jijun , Luo Cheng , Yao Dezhong 
Published: January 2021

AbstractBackgroundCortical thickness reductions are evident in patients with schizophrenia. Associations between antipsychotic medications (APMs) and cortical morphometry have been explored in schizophrenia patients. This raises the question of whether the reconfiguration of morphological architecture by APM plays potential compensatory roles for abnormalities in the cerebral cortex.MethodsStructural MRI were obtained from 127 medication-naive first-episode schizophrenia (FES) patients and 133 matched healthy controls. Patients received 12 weeks of APM and were categorized as responders (n=75) or nonresponders (n=52) at follow-up. Using surface-based morphometry and structural covariance analysis, this study investigated the short-term effects of antipsychotics on cortical thickness and cortico-cortical connectivity. Global efficiency was computed to characterize network integration of the large-scale structural connectome. The relationship between connectivity and cortical thinning was examined by the structural covariance analysis among top-n regions with thickness reduction.ResultsWidespread cortical thickness reductions were observed in pre-APM patients. Post-APM patients showed more reductions in cortical thickness, even in the frontotemporal regions without baseline reductions. Covariance analysis revealed strong cortico-cortical connectivity and higher network integration in responders than in nonresponders. Notably, the nonresponders lacked key nodes of the prefrontal and temporal regions for the covariance network between top-n regions with cortical thickness reductions.ConclusionsAntipsychotic effects are not restricted to a single brain region but rather exhibit a network-level covariance pattern. Neuroimaging connectomics highlights the positive effects of antipsychotics on the reconfiguration of brain architecture, suggesting that abnormalities in regional morphology may be compensated by increasing interregional covariance when symptoms are controlled by antipsychotics.