bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of FLOT regimen vs DCF, FOLFOX, and ECF regimens as Perioperative Chemotherapy Treatments for Resectable Gastric Cancer Patients
Authors: Farrokhi Pegah , Sadeghi Alireza , sharifi Mehran , Dadvand Payam , Riechelmann Rachel , Moghaddas Azadeh 
Published: January 2021

AbstractPurposeThis study aimed to compare the efficacy and toxicity of perioperative chemotherapy regimens including ECF, DCF, FOLFOX, and FLOT to identify the most effective chemotherapy regimen with less toxicity.MethodThis retrospective cohort study(2014-2021) was based on 152 eligible resectable gastric cancer patients who had received one of the perioperative chemotherapy regimens including ECF, DCF, FOLFOX, or FLOT, and followed for at least two years. The primary endpoint of this study was Overall Survival (OS), Progression-Free Survival (PFS), Overall Response Rate (ORR), and R0 resection. We also considered toxicity according to CTCAE (v.4.0) criteria as a secondary endpoint.ResultsOf included patients, 32(21%), 51(33.7%), 37(24.3%), and 32(21%) had received ECF, DCF, FOLFOX and FLOT, respectively. After the median 30 months follow-up, overall survival was higher with the FLOT regimen in comparison with other regimens (hazard ratio [HR] = 0. 276). The median OS of the FLOT regimen was 39 months. Besides, the median OS was 28, 25, and 21 months for DCF, FOLOFX, and ECF regimens, respectively. Moreover, a median PFS of 24, 18, 17, and 14 months was observed for FLOT, DCF, FOLFOX, and ECF regimens, respectively (Log-rank <0.001). FLOT regimen showed 84. 4% ORR, was notably higher than other groups (p-value<0. 01).ConclusionsFor resectable gastric cancer patients, the perioperative FLOT regimen led to a significant improvement in patients’ OS and PFS in comparison with ECF, DCF, and FOLFOX regimens. As such, the FLOT regimen could be considered the optimal option for managing resectable gastric cancer patients.
Left ventricular strain does not differentiate amyloidogenic profiles in at-risk individuals withTTRVal142Ile
Authors: Kontorovich Amy R. , Zhao Wenli , Gavalas Michael , Hashemi Helen , Liao Steve L. , Rashed Eman R. , Mitter Sumeet S. , Trivieri Maria Giovanna , Lerakis Stamatios , Kenny Eimear E. , Abul-Husn Noura S. 
Published: January 2021

AbstractObjectivesTo identify echocardiographic signatures featuring left ventricular longitudinal strain (LS) associated with genetic risk for cardiac amyloidosis (CA) due to theTTRVal142Ile (V142I) variant in African American (AA) and Hispanic/Latinx (H/L) individuals.BackgroundHereditary transthyretin amyloidosis (hATTR) can cause CA in ∼60-70% of older V142I carriers, but amyloid deposition progresses over many years. Disease-modifying therapy for CA is now available and early initiation is a priority for improving outcomes. Genomic screening programs and familial cascade genetic testing uncover pre-symptomatic V142I carriers, yet no guidelines exist for early CA detection.MethodsExome sequencing data linked to electronic health records (EHRs) of BioMebiobank participants were queried for AA or H/LTTR- andTTR+ (V142I) subjects without hATTR diagnoses and with prior echocardiograms suitable for retrospective LS analysis. Systemic “red flag” features of ATTR were extracted from EHRs ofTTR+ subjects. Speckle tracking echocardiography was retrospectively applied to determine global (GLS) and segmental LS. Relative apical sparing (RAS) was calculated.Results57TTR+ and 46TTR-age- and ancestry-matched subjects were included. GLS declined with age in females but not males, and was abnormal (<16%) in 18 (31.6%)TTR+ and 7 (15.2%)TTR-subjects (p = 0.066). Apical sparing was observed in 13 (22.8%)TTR+ and 11 (23.9%)TTR-subjects (p = 1.0). After adjusting for relevant demographic and echocardiographic covariates, neither GLS nor RAS was associated withTTR+ V142I status. Red flag features were not associated with GLS or RAS inTTR+ subjects.ConclusionsNeither GLS nor RAS were significantly different betweenTTR+ andTTR-subjects. Since >50% ofTTR+ subjects were ≥ 60 years old, penetrance of CA by echocardiography among unselected V142I carriers may be lower than previously estimated. These findings indicate that surveillance for CA in individuals at increased genetic risk due to V142I should not rely solely on echocardiography, even with LS.
THE AIRBORNE CONTAGIOUSNESS OF RESPIRATORY VIRUSES: A COMPARATIVE ANALYSIS AND IMPLICATIONS FOR MITIGATION
Authors: Mikszewski A. , Stabile L. , Buonanno G. , Morawska L. 
Published: January 2021

AbstractBackgroundThe infectious emission rate is a critical input parameter for airborne contagion models, but data are limited due to reliance on estimates from chance superspreading events. A predictive estimation approach for the quanta emission rate (ERq) was recently proposed for SARS-CoV-2 using the droplet volume concentration of various expiratory activities. This study assesses the strength of the approach and uses novel predictive estimates of ERq to compare the contagiousness of respiratory pathogens.MethodsWe applied the predictive approach to SARS-CoV-1, SARS-CoV-2, MERS, measles virus, adenovirus, rhinovirus, coxsackievirus, seasonal influenza virus and Mycobacterium tuberculosis (TB) and compared ERq estimates to values reported in literature. We calculated infection risk in a prototypical classroom and barracks to assess the relative ability of ventilation to mitigate airborne transmission.ResultsOur median standing and speaking ERq estimate for SARS-CoV-2 (2.6 quanta hour (h)-1) is similar to active, untreated TB (3.1 h-1), higher than seasonal influenza (0.17 quanta h-1), and lower than measles virus (15 quanta h-1). We calculated event reproduction numbers above 1 for SARS-CoV-2, measles virus, and untreated TB in both the classroom and barracks for an activity level of standing and speaking at low, medium and high ventilation rates of 2.3, 6.6 and 14 liters per second per person, respectively.ConclusionsOur predictive ERq estimates are consistent with the range of values reported over decades of research. In congregate settings, current ventilation standards are unlikely to control the spread of viruses with upper quartile ERq values above 10 quanta h-1, such as SARS-CoV-2, indicating the need for additional control measures.
In-silicoStructural and Molecular Docking-Based Drug Discovery Against Viral Protein (VP40) of Marburg Virus: A Causative Agent of MAVD
Authors: Quazi Sameer , Golani Tanya , Akhta Nashat , Thomas Christina Elsa , Haider Zeshan 
Published: January 2021

AbstractThe Marburg virus (MARV) is reported to induce extreme hemorrhagic fever (MHF) with a high degree of infectivity and lethality in both human and non-human primates. An appropriate vaccination for this virus’s treatment is not yet usable, and thus needs intensive attempts on multiple scales. In this study, we employed the Computer-Aided Drug Design (CADD) based approach to identify the drug-like compounds inhibiting the replication of the Viral protein (VP40) of MARV. Our database search using an online database “PubChem” retrieved ∼3000 compounds structure-based similarity. Lipinski’s rule was applied to evaluate further the drug-like compounds, followed by molecular docking-based screening, and the selection of screening ligand complex with VP40 based on S-score (lower than reference Favipiravir inhibitor) and root-mean-square-deviation (RMSD) value (probably less than 2) using AutoDock 4.2. Resultantly, ∼100 compounds were identified having strong interaction with VP40 of MARV. After evaluating their binding energy using the AutoDock 4.2 software, four compounds (CID-67534452, CID-72201087, CID-123273976, CID-153708661) were identified that showed strongest binding energy with VP40 of MARV and strong inhibition effect than the Favipiravir. Robust binding energy, useful ADMET parameters and drug-likeness suggest that these candidates “CID-67534452, CID-72201087, CID-123273976, CID-153708661” have tremendous potential to stop the replication of MARV, hence might lead to the cure of MAVD.
Population Pharmacokinetics of Oxcarbazepine: A Systematic Review
Authors: Chen Yue-ting , Wang Chen-yu , Yin Yi-wei , Li Zi-ran , Lin Wei-wei , Zhu Min , Jiao Zheng 
Published: January 2021

AbstractIntroductionOxcarbazepine is commonly used as a first-line drug in the treatment of partial seizures. Due to the high pharmacokinetic variability of oxcarbazepine, many population pharmacokinetic models have been developed to optimise the dosing regimen of oxcarbazepine.Areas coveredThis review summarize the published population pharmacokinetic studies of oxcarbazepine in children and adults. The quality of the identified reports from the PubMed and Embase databases was also evaluated. We also explored the significant covariates that may have an impact on the dosage regimen and clinical use of oxcarbazepine.Expert OpinionThe oxcarbazepine dose regimen was dependent on weight and co-administration with enzyme-inducing medications. In order to achieve more accurate treatment, we should establish PK / PD model of OXC to evaluate the effectiveness of dose adjustment from pharmacodynamic indicators. Furthermore, exploring the pharmacokinetic in specifical patients, such as infants is essential to improve its safety.Article highlightsIn this review, we identified weight, renal function, and co-administered medications as covariates that most likely to influence oxcarbazepine pharmacokinetics.Comparing to adult patients, paediatric patients show a higher clearance per kilogramme weigh which lead to higher doses per kilogramme; they may also require therapeutic drug monitoring owing to a larger variation in clearance.Further studies are essential to evaluate oxcarbazepine pharmacokinetics in special populations such as infants.
Passing the Test: A Model-based analysis of safe school-reopening strategies
Authors: Bilinski Alyssa , Salomon Joshua A. , Giardina John , Ciaranello Andrea , Fitzpatrick Meagan C. 
Published: January 2021

AbstractBackgroundThe COVID-19 pandemic has induced historic educational disruptions. In December 2020, at least two-thirds of US public school students were not attending full-time in-person education. The Biden Administration has expressed that reopening schools is a priority.ObjectiveTo compare risks of SARS-COV-2 transmission in schools across different school-based prevention strategies and levels of community transmission.DesignWe developed an agent-based network model to simulate transmission in elementary and high school communities, including home, school, and inter-household interactions.SettingWe parameterized school structure based on average US classrooms, with elementary schools of 638 students and high schools of 1,451 students. We varied daily community incidence from 1 to 100 cases per 100,000 population.Patients (or Participants)We simulated students, faculty/staff, and adult household members.InterventionsWe evaluated isolation of symptomatic individuals, quarantine of an infected individual’s contacts, reduced class sizes, alternative schedules, staff vaccination, and weekly asymptomatic screening.MeasurementsWe projected transmission among students, staff and families during one month following introduction of a single infection into a school. We also calculated the number of infections expected for a typical 8-week quarter, contingent on community incidence rate.ResultsSchool transmission risk varies according to student age and community incidence and is substantially reduced with effective, consistent mitigation measures. Nevertheless, when transmission occurs, it may be difficult to detect without regular, frequent testing due to the subclinical nature of most infections in children. Teacher vaccination can reduce transmission to staff, while asymptomatic screening both improves understanding of local circumstances and reduces transmission, facilitating five-day schedules at full classroom capacity.LimitationsThere is uncertainty about susceptibility and infectiousness of children and low precision regarding the effectiveness of specific prevention measures, particularly with emergence of new variants.ConclusionWith controlled community transmission and moderate school-based prevention measures, elementary schools can open with few in-school transmissions, while high schools require more intensive mitigation. Asymptomatic screening should be a key component of school reopenings, allowing reopening at higher community incidence while still minimizing transmission risk.
Emulator-based Bayesian optimization for efficient multi-objective calibration of an individual-based model of malaria
Authors: Reiker Theresa , Golumbeanu Monica , Shattock Andrew , Burgert Lydia , Smith Thomas A. , Filippi Sarah , Cameron Ewan , Penny Melissa A. 
Published: January 2021

ABSTRACTIndividual-based models have become important tools in the global battle against infectious diseases, yet model complexity can make calibration to biological and epidemiological data challenging. We propose a using a Bayesian optimization framework employing Gaussian process or machine learning emulator functions to calibrate a complex malaria transmission simulator. We demonstrate our approach by optimizing over a high-dimensional parameter space with respect to a portfolio of multiple fitting objectives built from datasets capturing the natural history of malaria transmission and disease progression. Our approach quickly outperforms previous calibrations, yielding an improved final goodness of fit. Per-objective parameter importance and sensitivity diagnostics provided by our approach offer epidemiological insights and enhance trust in predictions through greater interpretability.
The World Mortality Dataset: Tracking excess mortality across countries during the COVID-19 pandemic
Authors: Karlinsky Ariel , Kobak Dmitry 
Published: January 2021

AbstractComparing the impact of the COVID-19 pandemic between countries or across time is difficult because the reported numbers of cases and deaths can be strongly affected by testing capacity and reporting policy. Excess mortality, defined as the increase in all-cause mortality relative to the expected mortality, is widely considered as a more objective indicator of the COVID-19 death toll. However, there has been no global, frequently-updated repository of the all-cause mortality data across countries. To fill this gap, we have collected weekly, monthly, or quarterly all-cause mortality data from 94 countries and territories, openly available as the regularly-updated World Mortality Dataset. We used this dataset to compute the excess mortality in each country during the COVID-19 pandemic. We found that in several worst-affected countries (Peru, Ecuador, Bolivia, Mexico) the excess mortality was above 50% of the expected annual mortality. At the same time, in several other countries (Australia, New Zealand) mortality during the pandemic was below the usual level, presumably due to social distancing measures decreasing the non-COVID infectious mortality. Furthermore, we found that while many countries have been reporting the COVID-19 deaths very accurately, some countries have been substantially underreporting their COVID-19 deaths (e.g. Nicaragua, Russia, Uzbekistan), sometimes by two orders of magnitude (Tajikistan). Our results highlight the importance of open and rapid all-cause mortality reporting for pandemic monitoring.
Specific pattern of melanin-concentrating hormone (MCH) neuron degeneration in Alzheimer’s disease and possible clinical implications
Authors: Mladinov Mihovil , Oh Jun Yeop , Petersen Cathrine , Eser Rana , Li Song Hua , Theofilas Panos , Spina Salvatore , Seeley William W. , Bittencourt Jackson C. , Neylan Thomas C. , Grinberg Lea T. 
Published: January 2021

ABSTRACTStudy ObjectivesThe lateral hypothalamic area (LHA) is one of the key regions orchestrating sleep and wake control. It is the site of wake-promoting orexinergic and sleep-promoting melanin-concentrating hormone (MCH) neurons, which share a close anatomical and functional relation. The aim of the study was to investigate the degeneration of MCH neurons in Alzheimer’s disease (AD) and progressive supranuclear palsy (PSP), and relate the new findings to our previously reported pattern of degeneration of wake-promoting orexinergic neuronsMethodsPost-mortem human brain tissue of subjects with AD, PSP and controls was examined using unbiased stereology. Double immunohistochemistry with MCH- and tau-antibodies on formalin-fixed, celloidin embedded tissue was performed.ResultsThere was no difference in the total number of MCH neurons between AD, PSP and controls, but a significant loss of non-MCH neurons in AD patients (p=0.019). The proportion of MCH neurons was significantlyhigherin AD (p=0.0047). No such a difference was found in PSP. In PSP, but not AD, the proportion of tau+ MCH neurons waslowerthan the proportion of tau+ non-MCH neurons (p=0.002). When comparing AD to PSP, the proportion of tau+MCH neurons was higher in AD (p<0.001).ConclusionsMCH neurons are more vulnerable to AD than PSP pathology. High burden of tau-inclusions, but comparably milder loss of MCH neurons in AD, together with previously reported orexinergic neuronal loss may lead to a hyperexcitability of the MCH system in AD, contributing to wake-sleep disorders in AD. Further experimental research is needed to understand why MCH neurons are more resistant to tau-toxicity compared to orexinergic neurons.STATEMENT OF SIGNIFICANCEThis is the first study to investigate the involvement of melanin-concentrating hormone (MCH) neurons in patients with Alzheimer’s disease and progressive supranuclear palsy. MCH neurons are key regulators of sleep and metabolic functions, and one of the major neuronal populations of the lateral hypothalamic area (LHA), but still underexplored in humans. Uncovering the pathology of this neuronal population in neurodegenerative disorders will improve our understanding of the complex neurobiology of the LHA and the interaction between MCH and orexinergic neurons. This new knowledge may open new strategies for treatment interventions. Further, this study represents a fundament for future research on MCH neurons and the LHA in tauopathies.
Safety and efficacy of long-acting insulins (degludec and glargine) among type 2 diabetic Asian Population: A Systematic Review and Meta-Analysis
Authors: Kant R , Yadav P , Garg M , Bahurupi Y , Kumar B 
Published: January 2021

AbstractBackgroundAccording to IDF Diabetes Atlas 2019, globally, 463 million people live with Diabetes mellitus. Out of that, 88 million people are in South East Asia. By 2045, it is expected to increase by 51% globally and 74% in South East Asia. Global variation in susceptibility to diabetes, insulin sensitivity, and regimen intensity due to race and ethnic differences pose a challenge regarding the optimal choice of second-line therapy for clinicians. Asian populations are at higher risk of developing diabetes mellitus than the European population. The current study was carried out to see the relative efficacy of currently available long-acting insulins in reducing blood sugar, HbA1c and the occurrence of hypoglycemia as a complication associated with them.MethodsA systematic literature search was done using various search engines (PubMed, Cochrane, Google Scholar, Scopus, and Embase) and included published RCTs in English before December 2019. Further, a manual search was performed by screening the reference list of the identified articles.ResultsWe included four RCTs with 534 participants (349 in the insulin degludec group and 185 in the insulin glargine group) with T2DM. Results show that both insulin glargine and degludec are equally efficacious in reducing fasting blood glucose and HbA1c. However, insulin glargine was associated with lower risks of hypoglycemia.ConclusionsInsulin glargine and degludec are comparable in achieving glycemic control with fewer hypoglycemic episodes in insulin glargine treated group.
Sequencing Data of North American SARS-CoV-2 Isolates Shows Widespread Complex Variants
Authors: Ford Colby T. , Scott Rachel , Machado Denis Jacob , Janies Daniel 
Published: January 2021

Several new variants of the SARS-CoV-2 have been isolated in the United States, Mexico, and Canada. Many of the variants contain single variants of functional significance (e.g. S: N501Y increases transmissibility). To study the occurrence and co-circulation of these variants, we have developed an easy-to-use dashboard at janieslab.github.io/sars-cov-2.We created a multiple sequence alignment workflow and processing script to generate a variant dataset, which populates this dashboard. We then use the features of the dashboard, such as visualization of the single and complex nucleotide variants geospatially and in a color-coded matrix format. Users also interact with the dashboard to filter the underlying data to regions of interest and or variants of interest. The user can export reports based on the desired filters, which we intend to be used for regionally specific pandemic response. We find in Genbank, an isolate from Massachusetts containing [(S: Q677H), (ORF3a: Q57H), (M: A85S), (N: D377Y)] collected on September 11, 2020.Moreover, we find that many viral isolates bear a marker of increased transmissibility (S: N501Y) in linkage with at least one variant of concern isolated from Ohio also range across the Untied States and stretch from British Columbia, Canada to Mexico. When we analyze co-circulation of more complex variant constellations with (S: N501Y), we note that the Upper Midwest and Northeast United States contain these isolates.In summary, the viral variants that have raised concern in a few US States in recent reports are widespread. Based on the increase in the proportion of variant viruses being sampled and some empirical evidence in the United Kingdom, South Africa, and Ohio, these variants are likely to lead to increased transmission of SARS-CoV-2 across North America in the coming months.
Risk perception of COVID-19 and its socioeconomic correlates in the United States: A social media analysis
Authors: Qiao Shan , Li Zhenlong , Liang Chen , Li Xiaoming , Rudisill Caroline Ann 
Published: January 2021

AbstractSocial media analysis provides a new approach to monitoring and understanding risk perceptions regarding COVID-19 over time. Our current understandings of risk perceptions regarding COVID-19 do not disentangle the three dimensions of risk perceptions (perceived susceptibility, perceived severity, and negative emotion) over a long enough timeframe to cover different pandemic phases. The impact of social determinants of health factors on COVID-19-related risk perceptions over time is also not clear. To address these two knowledge gaps, we extracted tweets regarding COVID-19-related risk perceptions and developed index indicators for three dimensions of risk perceptions based on over 297 million geotagged tweets posted by over 3.5 million Twitter users from January to October 2020 in the United States. We also examined correlations between index indicator scores and county-level social determinants of health factors. The three domains of risk perceptions demonstrate different trajectories. Perceived severity kept climbing throughout the whole study period. Perceived susceptibility and negative emotion declined and remained stable at a lower level after peaking on March 11 (WHO named COVID-19 a global pandemic). Attention on risk perceptions was not exactly in accordance with epidemic trends of COVID-19 (cases, deaths). Users from socioeconomically vulnerable counties showed lower attention on perceived severity and susceptibility of COVID-19 than those from wealthier counties. Examination of trends in tweets regarding the multiple domains of risk perceptions throughout stages of the COVID-19 pandemic can help policy makers frame in-time, tailored, and appropriate responses to prevent viral spread and encourage preventive behavior uptake in United States.