bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Methods for Gut Microbiota Modification in Lipopolysaccharide-Associated Encephalopathy
Authors: Li Suyan , Guo Hui , Xu Xin , Hua Ranliang , Zhao Qian , Li Jian , Lv Jian , Li Jianguo 
Published: February 2021

ABSTRACT

Objective:
To compare the efficacy of four therapeutic methods to modify gut microbiota dysbiosis and brain dysfunction in septic rats.

Methods:
Rats were treated with fecal microbiota transplantation, prebiotics, probiotics, and synbiotics after exposure to lipopolysaccharide. The diversity and composition of gut microbiota, electroencephalogram values, and the concentrations of TNF-α, IL-1β, and IL-6 in the cortex were analyzed.

Results:
Fecal microbiota transplantation was the most efficacious method to restore intestinal microbial diversity and exert the best corrective effects in modulating microbial composition in septic rats. More interestingly, fecal microbiota transplantation exerted the best protective effects in brain dysfunction in septic rats.

Conclusion:
Among the four methods, fecal microbiota transplantation was the most useful method to modify the dysbiosis of intestinal microbiota and improve brain function in septic rats. These findings reveal the protective consequence of microbiota modification, and the findings suggest opportunities to improve brain function in sepsis.
Estimating the Impact of Extended Delay to Surgery for Stage I Non-small-cell Lung Cancer on Survival
Authors: Mayne Nicholas R. , Elser Holly C. , Darling Alice J. , Raman Vignesh , Liou Douglas Z. , Colson Yolonda L. , D’Amico Thomas A. , Yang Chi-Fu Jeffrey 
Published: February 2021

Objective:
The purpose of this study is to evaluate the impact of extended delay to surgery for stage I NSCLC.

Summary of Background Data:
During the COVID-19 pandemic, patients with NSCLC may experience delays in care, and some national guidelines recommend delays in surgery by >3 months for early NSCLC.

Methods:
Using data from the National Lung Screening Trial, a multi-center randomized trial, and the National Cancer Data Base, a multi-institutional oncology registry, the impact of “early” versus “delayed” surgery (surgery received 0–30 vs 90–120 days after diagnosis) for stage I lung adenocarcinoma and squamous cell carcinoma (SCC) was assessed using multivariable Cox regression analysis with penalized smoothing spline functions and propensity score-matched analyses.

Results:
In Cox regression analysis of the National Lung Screening Trial (n = 452) and National Cancer Data Base (n = 80,086) cohorts, an increase in the hazard ratio was seen the longer surgery was delayed. In propensity score-matched analysis, no significant differences in survival were found between early and delayed surgery for stage IA1 adenocarcinoma and IA1-IA3 SCC (all P > 0.13). For stage IA2-IB adenocarcinoma and IB SCC, delayed surgery was associated with worse survival (all P < 0.004).

Conclusions:
The mortality risk associated with an extended delay to surgery differs across patient subgroups, and difficult decisions to delay care during the COVID-19 pandemic should take substage and histologic subtype into consideration.
Postacute Care Utilization and Episode of Care Payments Following Common Elective Operations
Authors: Ehlers Anne P. , Howard Ryan , Lai Yen-Ling , Waljee Jennifer F. , Delaney Lia D. , Nathan Hari , Dimick Justin B. , Telem Dana A. 
Published: February 2021

Objective:
To describe PAC utilization and associated payments for patients undergoing common elective procedures.

Summary of Background Data:
Utilization and costs of PAC are well described for benchmarked conditions and operations but remain understudied for common elective procedures.

Methods:
Cross-sectional study of adult patients in a statewide administrative claims database undergoing elective cholecystectomy, ventral or incisional hernia repair (VIHR), and groin hernia repair from 2012 to 2019. We used multivariable logistic regression to estimate the odds of PAC utilization, and multivariable linear regression to determine the association of 90-day episode of care payments and PAC utilization.

Results:
Among 34,717 patients undergoing elective cholecystectomy, 0.7% utilized PAC resulting in significantly higher payments ($19,047 vs $7830, P < 0.001). Among 29,826 patients undergoing VIHR, 1.7% utilized PAC resulting in significantly higher payments ($19,766 vs $9439, P < 0.001). Among 37,006 patients undergoing groin hernia repair, 0.3% utilized PAC services resulting in significantly higher payments ($14,886 vs $8062, P < 0.001). We found both modifiable and non-modifiable risk factors associated with PAC utilization. Morbid obesity was associated with PAC utilization following VIHR [odds ratio (OR) 1.61, 95% confidence interval (CI) 1.29–2.02, P < 0.001]. Male sex was associated with lower odds of PAC utilization for VIHR (OR 0.43, 95% CI 0.35–0.51, P < 0.001) and groin hernia repair (OR 0.62, 95% CI 0.39–0.98, P = 0.039).

Conclusions:
We found both modifiable (eg, obesity) and nonmodifiable (eg, female sex) patient factors that were associated with PAC. Optimizing patients to reduce PAC utilization requires an understanding of patient risk factors and systems and processes to address these factors.
Epidemiological and Genomic analysis of a Sydney Hospital COVID-19 Outbreak
Authors: Tennant Elaine , Figtree Melanie , Tallon Jo , Bull Rowena A , Yeang Malinna , Deveson Ira W , Ferguson James M , Adikari Thiruni , Holmes Edward C , Hal Sebastiaan Van , Hammond Jillian M , Stevanovski Igor , Mitsakos Katerina , Hilditch-Roberts Drew , Rawlinson William , Hudson Bernard 
Published: February 2021

AbstractAustralia’s early COVID-19 experience involved clusters in northern Sydney, including hospital and aged-care facility (ACF) outbreaks. We explore transmission dynamics, drivers and outcomes of a metropolitan hospital COVID-19 outbreak that occurred in the context of established local community transmission. A retrospective cohort analysis is presented, with integration of viral genome sequencing, clinical and epidemiological data. We demonstrate using genomic epidemiology that the hospital outbreak (n=23) was linked to a concurrent outbreak at a local aged care facility, but was phylogenetically distinct from other community clusters. Thirty day survival was 50% for hospitalised patients (an elderly cohort with significant comorbidities) and 100% for staff. Staff who acquired infection were unable to attend work for a median of 26.5 days (range 14-191); an additional 140 staff were furloughed for quarantine. Transmission from index cases showed a wide dispersion (mean 3.5 persons infected for every patient case and 0.6 persons infected for every staff case). One patient, who received regular nebulised medication prior to their diagnosis being known, acted as an apparent superspreader. No secondary transmissions occurred from isolated cases or contacts who were quarantined prior to becoming infectious. This analysis elaborates the wide-ranging impacts on patients and staff of nosocomial COVID-19 transmission and highlights the utility of genomic analysis as an adjunct to traditional epidemiological investigations. Delayed case recognition resulted in nosocomial transmission but once recognised, prompt action by the outbreak management team and isolation with contact and droplet (without airborne) precautions were sufficient to prevent transmission within this cohort. Our findings support current PPE recommendations in Australia but demonstrate the risk of administering nebulised medications when COVID-19 is circulating locally.
Association between Functional Inhibitors of Acid Sphingomyelinase and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID-19: results from an observational multicenter study
Authors: Hoertel Nicolas , Sánchez-Rico Marina , Gulbins Erich , Kornhuber Johannes , Carpinteiro Alexander , Lenze Eric J. , Reiersen Angela M. , Abellán Miriam , de la Muela Pedro , Vernet Raphaël , Blanco Carlos , Beeker Nathanaël , Neuraz Antoine , Gorwood Philip , Alvarado Jesús M. , Meneton Pierre , Limosin Frédéric 
Published: February 2021

ABSTRACTSeveral medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS-CoV-2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID-19 in an observational multicenter retrospective study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) who were taking a FIASMA medication, and 1,060 patients (41.4%) who were not. Taking a FIASMA medication was associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58-0.87; p<0.001) and the primary IPW (HR=0.58; 95%CI=0.46-0.72; p<0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one FIASMA class or medication. These results show the potential importance of the ASM/ceramide system as a treatment target in COVID-19. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.
Risk of death among teachers in England and Wales during the Covid19 pandemic
Authors: Lewis Sarah J , Dack Kyle , Relton Caroline L , Munafò Marcus R , Smith George Davey 
Published: February 2021

AbstractObjectivesTo estimate occupation risk from Covid19 among teachers and others working in schools using publicly available data on mortality in England and Wales.DesignAnalysis of national death registration data from the Office for National Statistics.SettingEngland and Wales, March 20th to 28th December 2020, during the Covid19 pandemic.ParticipantsThe total working age population in England and Wales plus those still working aged over 65.Primary and Secondary outcomesDeath with Covid19 as a primary outcome and death from all causes as a secondary outcome.ResultsAcross occupational groups there was a strong correlation between Covid19 mortality and both non-Covid19 and all-cause mortality. The absolute mortality rates for deaths with Covid19 were low amongst those working in schools (from 10 per 100,000 in female primary school teachers to 39 per 100,000 male secondary school teachers) relative to many other occupations (range: 10 to 143 per 100,000 in men; 9 to 50 per 100,000 in women).There was weak evidence that secondary school teachers had slightly higher risks of dying with Covid19 compared to the average for all working aged people, but stronger evidence of a higher risk compared to the average for all professionals; primary school teachers had a lower risk. All-cause mortality was also higher amongst all teachers compared to all professionals. Teaching and lunchtime assistants were not at higher risk of death from Covid19 compared with all working aged people.ConclusionThere was weak evidence that Covid19 mortality risk for secondary school teachers was above expectation, but in general school staff had Covid19 mortality risks which were proportionate to their non-covid mortality risk.Strengths and limitations of this studyWe used routinely collected data on all deaths in England and Wales;, which are near-complete and not susceptible to serious ascertainment biases.We were able to compare mortality data for teachers and other school workers with all other occupational groups and with the working-age population.The number of deaths due to Covid19 were small and thus differences between the specific occupational groups were imprecisely estimated.We did not have access to individual level mortality data so were not able to account for potential confounders such as comorbidities or household size.For those working in school aged over 65 we had neither mortality rates per 100,000 nor total numbers within the group; we only had number of deaths and a 5-year average and we do not know whether the denominators have changed for this group over the last 5 years.
The Public Health Impact of Delaying a Second Dose of the BNT162b2 or mRNA-1273 COVID-19 Vaccine
Authors: Romero-Brufau Santiago , Chopra Ayush , Ryu Alex J , Gel Esma , Raskar Ramesh , Kremers Walter , Anderson Karen , Subramanian Jayakumar , Krishnamurthy Balaji , Singh Abhishek , Pasupathy Kalyan , Dong Yue , O’Horo John C , Wilson Walter R , Mitchell Oscar , Kingsley Thomas C 
Published: February 2021

AbstractObjectivesTo estimate population health outcomes under delayedsecond dose versus standard schedule SARS-CoV-2 mRNA vaccination.DesignAgent-based modeling on a simulated population of 100,000 based on a real-world US county. The simulation runs were replicated 10 times. To test the robustness of these findings, simulations were performed under different estimates for single-dose efficacy and vaccine administration rates, and under the possibility that a vaccine prevents only symptoms but not asymptomatic spread.Settingpopulation level simulation.Participants100,000 agents are included in the simulation, with a representative distribution of demographics and occupations. Networks of contacts are established to simulate potentially infectious interactions though occupation, household, and random interactionsInterventionswe simulate standard Covid-19 vaccination, versus delayed-second-dose vaccination prioritizing first dose. Sensitivity analyses include first-dose vaccine efficacy of 70%, 80% and 90% after day 12 post-vaccination; vaccination rate of 0.1%, 0.3%, and 1% of population per day; assuming the vaccine prevents only symptoms but not asymptomatic spread; and an alternative vaccination strategy that implements delayed-second-dose only for those under 65 years of age.Main outcome measurescumulative Covid-19 mortality over 180 days, cumulative infections and hospitalizations.ResultsOver all simulation replications, the median cumulative mortality per 100,000 for standard versus delayed second dose was 226 vs 179; 233 vs 207; and 235 vs 236; for 90%, 80% and 70% first-dose efficacy, respectively. The delayed-second-dose strategy was optimal for vaccine efficacies at or above 80%, and vaccination rates at or below 0.3% population per day, both under sterilizing and non-sterilizing vaccine assumptions, resulting in absolute cumulative mortality reductions between 26 and 47 per 100,000. The delayed-second-dose for those under 65 performed consistently well under all vaccination rates tested.ConclusionsA delayed-second-dose vaccination strategy, at least for those under 65, could result in reduced cumulative mortality under certain conditions.
Sex differences in the mortality rate for coronavirus disease 2019 compared to other causes of death
Authors: Geldsetzer P. , Mukama T. , Jawad N. , Riffe T. , Rogers A. , Sudharsanan N. 
Published: February 2021

AbstractMen are more likely than women to die due to coronavirus disease 2019 (COVID-19). This paper sets out to examine whether the magnitude of the sex differences in the COVID-19 mortality rate are unusual when compared to other common causes of death. In doing so, we aim to provide evidence as to whether the causal pathways for the sex differences in the mortality rate of COVID-19 likely differ from those for other causes of death. We found that sex differences in the age-standardized COVID-19 mortality rate were substantially larger than for the age-standardized all-cause mortality rate and most other common causes of death. These differences were especially large in the oldest age groups.One Sentence SummaryThe sex difference in the mortality rate of coronavirus disease 2019 is substantially larger than for other common causes of death.
HDAC6 promote HCCLM3 cell migration and invasion by regulating TGF-β1 pathway
Authors: Yu Zeyu , Yang Xiaoxiao , Yin Guowen 
Published: February 2021

AbstractHistone deacetylase 6 (HDAC6) have been demonstrated to play critical roles in the progression of tumor migration and invasion in recent years.However, little research has been done on hepatocellular carcinoma (HCC). This study investigated the role of HDAC6 in the migration and invasion of HCCLM3 cells and its potential mechanism. Western blot and immunohistochemistry were used to detect the expression of HDAC6 in normal hepatic cell line LO2 and HCC cell line HCCLM3. Transforming growth factor 1 (TGF-β1) was proved as a direct target of HDAC6 by Western blot and qRT-PCR.The changes of migration and invasion ability of HCCLM3 cells were confirmed by wound healing and Transwell assays.Morphological changes of HCCLM3 cells were observed by microscope.Our study proved that drownregulated HDAC6 supress HCCLM3 cells metastasis and invasion. Meanwhile, our study verified that HDAC6 regulate EMT by targeting TGF-β1.In conclusion, HDAC6 inhibits the EMT of HCCLM3 cells and further inhibits the migration and invasion of HCCLM3 cells by downregulating the expression of TGF-β1.
Epidemiological Philosophy of Pandemics
Authors: Raham Tareef Fadhil 
Published: February 2021

AbstractObjectivesCurrent estimates of the total number of cases of COVID-19 are largely based on previously-determined case fatality rates (CFRs). In this study, we aim to find an association between the Covid-19 number of cases / million inhabitants (M) and mortality rate (MR), and the association of Covid MR −19 and CFR. The background theory in this study is based on two factors: (1) There is no evidence that the CFR is fixed throughout time or place during an epidemic and (2) there is evidence that an increased viral load (density of infection) leads to more fatalities.Study DesignWe chose 31 countries with testing coverage levels of > 400,0000 tests /M and populations greater than 1 million inhabitants.MethodsWe used ANOVA regression analyses to test the associations.ResultsThere was a very highly significant correlation between MR and the total number of cases/ million population inhabitants(M) (P-value 0.0000).The CRF changed with a change in the MR. A very high positive influence of the COVID-19 MR on the CFR (P-value = 0.0002).ConclusionsIncreased number of cases per million inhabitants is associated with increased MR. Increased MR is associated with increased CFR. This finding might explain variable mortality rates that happened during this pandemic and possibly previous pandemics. This evidence will give us an idea of the behavior of epidemics in general.
Predicting hospitalizations related to ambulatory care sensitive conditions with machine learning for population health planning: derivation and validation cohort study
Authors: Yi Seung Eun , Harish Vinyas , Gutierrez Jahir M. , Ravaut Mathieu , Kornas Kathy , Watson Tristan , Poutanen Tomi , Ghassemi Marzyeh , Volkovs Maksims , Rosella Laura 
Published: February 2021

AbstractObjectiveTo predict older adults’ risk of avoidable hospitalization related to ambulatory care sensitive conditions (ACSC) using machine learning applied to administrative health data of Ontario, Canada.Design, Setting, and ParticipantsA retrospective cohort study was conducted on a large cohort of all residents covered under a single-payer system in Ontario, Canada over the period of 10 years, between 2008 and 2017. The study included 1.85 million Ontario residents between 65 and 74 years old at any time throughout the study period.Data sourcesAdministrative health data from Ontario, Canada obtained from the ICES Data Repository.Main outcome measuresRisk of hospitalizations due to ACSCs one year after the observation period.ResultsThe study used a total of 1,854,116 patients, split into train, validation, and test sets. The ACSC incidence rates among the data points were 1.1% for all sets. The final XGBoost model achieved an AUC of 80.5% on the held-out test set, and the predictions were well-calibrated. When ranking the predictions made by the model, those at the top 5% of risk as predicted by the model captured 37.4% of those presented with an ACSC-related hospitalization. A variety of features such as the previous number of ambulatory care visits, presence of ACSC-related hospitalizations during the observation window, age, rural residence, and prescription of certain medications were contributors to the prediction. Our model was also able to capture the geospatial heterogeneity of ACSC risk in the province of Ontario, and especially the elevated risk in rural and marginalized regions.ConclusionsThis study aimed to predict the 1-year risk of hospitalization from a series of ambulatory-care sensitive conditions in seniors aged 65 to 74 years old with a single, large-scale machine learning model. The model shows the potential to inform population health planning and interventions to reduce the burden of ACSC-related hospitalizations.
SARS-CoV-2 Viremia is Associated with Distinct Proteomic Pathways and Predicts COVID-19 Outcomes
Authors: Li Yijia , Schneider Alexis M. , Mehta Arnav , Sade-Feldman Moshe , Kays Kyle R. , Gentili Matteo , Charland Nicole C. , Gonye Anna L.K. , Gushterova Irena , Khanna Hargun K. , LaSalle Thomas J. , Lavin-Parsons Kendall M. , Lilly Brendan M. , Lodenstein Carl L. , Manakongtreecheep Kasidet , Margolin Justin D. , McKaig Brenna N. , Parry Blair A. , Rojas-Lopez Maricarmen , Russo Brian C. , Sharma Nihaarika , Tantivit Jessica , Thomas Molly F. , Regan James , Flynn James P. , Villani Alexandra-Chloé , Hacohen Nir , Goldberg Marcia B. , Filbin Michael R. , Li Jonathan Z. 
Published: February 2021

AbstractBackgroundSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) plasma viremia has been associated with severe disease and death in coronavirus disease 2019 (COVID-19) in small-scale cohort studies. The mechanisms behind this association remain elusive.MethodsWe evaluated the relationship between SARS-CoV-2 viremia, disease outcome, inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using qRT-PCR based platform. Proteomic data were generated with Proximity Extension Assay (PEA) using the Olink platform.ResultsThree hundred participants with nucleic acid test-confirmed COVID-19 were included in this study. Levels of plasma SARS-CoV-2 viremia at the time of presentation predicted adverse disease outcomes, with an adjusted odds ratio (aOR) of 10.6 (95% confidence interval [CI] 4.4, 25.5, P<0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and aOR of 3.9 (95%CI 1.5, 10.1, P=0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, endothelium/vasculature and alterations in coagulation pathways.ConclusionsThese results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.