bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and External Validation of a Model to Predict Overall Survival in Patients With Resected Gallbladder Cancer
Authors: de Savornin Lohman Elise A.J. , de Bitter T.J.J. , Hannink G. , Wietsma M.F.T. , Vink-Borger E. , Nagtegaal I.D. , Hugh T.J. , Gill A.J. , Bhimani N. , Ahadi M. Seyed , van der Post R.S. , de Reuver Philip R. 
Published: August 2021

Objective:
The aim of this study was to develop and validate a clinical prediction model to predict overall survival in patients with nonmetastatic, resected gallbladder cancer (GBC).

Background:
Although several tools are available, no optimal method has been identified to assess survival in patients with resected GBC.

Methods:
Data from a Dutch, nation-wide cohort of patients with resected GBC was used to develop a prediction model for overall survival. The model was internally validated and a cohort of Australian GBC patients who underwent resection was used for external validation. The performance of the American Joint Committee on Cancer (AJCC) staging system and the present model were compared.

Results:
In total, 446 patients were included; 380 patients in the development cohort and 66 patients in the validation cohort. In the development cohort median survival was 22 months (median follow-up 75 months). Age, T/N classification, resection margin, differentiation grade, and vascular invasion were independent predictors of survival. The externally validated C-index was 0.75 (95%CI: 0.69–0.80), implying good discriminatory capacity. The discriminative ability of the present model after internal validation was superior to the ability of the AJCC staging system (Harrell C-index 0.71, [95%CI: 0.69–0.72) vs. 0.59 (95% CI: 0.57–0.60)].

Conclusion:
The proposed model for the prediction of overall survival in patients with resected GBC demonstrates good discriminatory capacity, reasonable calibration and outperforms the authoritative AJCC staging system. This model can be a useful tool for physicians and patients to obtain information about survival after resection and is available from https:// gallbladderresearch.shinyapps.io/Predict_GBC_survival/.
Effects of Subnormothermic Regulated Hepatic Reperfusion on Mitochondrial and Transcriptomic Profiles in a Porcine Model
Authors: Kim Joohyun , Zimmerman Michael A. , Shin Woo Young , Boettcher Brent T. , Lee Ju-Seog , Park Jong-In , Ali Muhammed , Yang Meiying , Mishra Jyotsna , Hagen Catherine E. , McGraw Joseph E. , Mathison Angela , Woehlck Harvey J. , Lomberk Gwen , Camara Amadou K. S. , Urrutia Raul A. , Stowe David F. , Hong Johnny C. 
Published: August 2021

Objective:We sought to investigate the biological effects of pre-reperfusion treatments of the liver after warm and cold ischemic injuries in a porcine donation after circulatory death model.Summary of Background Data:Donation after circulatory death represents a severe form of liver ischemia and reperfusion injury that has a profound impact on graft function after liver transplantation.Methods:Twenty donor pig livers underwent 60 minutes of in situ warm ischemia after circulatory arrest and 120 minutes of cold static preservation prior to simulated transplantation using an ex vivo perfusion machine. Four reperfusion treatments were compared: Control-Normothermic (N), Control- Subnormothermic (S), regulated hepatic reperfusion (RHR)-N, and RHR-S (n = 5 each). The biochemical, metabolic, and transcriptomic profiles, as well as mitochondrial function were analyzed.Results:Compared to the other groups, RHR-S treated group showed significantly lower post-reperfusion aspartate aminotransferase levels in the reperfusion effluent and histologic findings of hepatocyte viability and lesser degree of congestion and necrosis. RHR-S resulted in a significantly higher mitochondrial respiratory control index and calcium retention capacity. Transcriptomic profile analysis showed that treatment with RHR-S activated cell survival and viability, cellular homeostasis as well as other biological functions involved in tissue repair such as cytoskeleton or cytoplasm organization, cell migration, transcription, and microtubule dynamics. Furthermore, RHR-S inhibited organismal death, morbidity and mortality, necrosis, and apoptosis.Conclusion:Subnormothermic RHR mitigates IRI and preserves hepatic mitochondrial function after warm and cold hepatic ischemia. This organ resuscitative therapy may also trigger the activation of protective genes against IRI. Sub- normothermic RHR has potential applicability to clinical liver transplantation.
Modulation of Xenogeneic T-cell Proliferation by B7 and mTOR Blockade of T Cells and Porcine Endothelial Cells
Authors: Li Shu , Xu He , Kirk Allan D. 
Published: August 2021

Background.
Activation of porcine endothelial cells (PECs) is the mechanistic centerpiece of xenograft rejection. This study sought to characterize the immuno-phenotype of human T cells in response to PECs and to explore the immuno-modulation of B7 and mammalian target of rapamycin blockade of T cells and/or PECs during xeno-responses.

Methods.
Rapid memory T-cell (TM) responses to PECs were assessed by an intracellular cytokine staining. T-cell proliferation to PEC with or without belatacept or rapamycin was evaluated by a mixed lymphocyte-endothelial cell reaction (MLER). Additionally, rapamycin-pretreated PECs were used in MLER. Cell phenotypes were analyzed by flow cytometry.

Results.
Tumor necrosis factor-α/interferon-γ producers were detected in CD8+ cells stimulated by human endothelium but not PECs. MLER showed proliferation of CD4+ and CD8+ cells with predominantly memory subsets. Purified memory and naive cells proliferated following PEC stimulation with an increased frequency of TM in PEC-stimulated naive cells. Proliferating cells upregulated programmed cell death-1 (PD-1) and CD2 expression. Belatacept partially inhibited T-cell proliferation with reduced CD2 expression and frequency of the CD8+CD2highCD28− subset. Rapamycin dramatically inhibited PEC-induced T-cell proliferation, and rapamycin-preconditioned PECs failed to induce T-cell proliferation. PD-1 blockade did not restore T-cell proliferation to rapamycin-preconditioned PECs.

Conclusions.
Humans lack rapid TM-mediated responses to PECs but induce T-cell proliferative responses characterized largely as TM with increasing CD2 and PD-1 expression. B7-CD28 and mammalian target of rapamycin blockade of T cells exhibit dramatic inhibitory effects in altering xeno-proliferating cells. Rapamycin alters PEC xeno-immunogenicity leading to inhibition of xeno-specific T-cell proliferation independent of PD-1–PD ligand interaction.
EEG Biomarkers of Repository Corticotropin Injection Treatment
Authors: Tanritanir Ahmet , Vieluf Solveig , Jafarpour Saba , Wang Xiaofan , Loddenkemper Tobias 
Published: August 2021

Purpose:
Hypsarrhythmia is one of the major diagnostic and treatment response criteria in infantile spasms (IS). The clinical and electrophysiological effect of repository corticotropin injection treatment on IS was evaluated using electrophysiological biomarkers.

Methods:
Consecutive infants (<24 months) treated with repository corticotropin injection for IS were included in this retrospective descriptive study. Inclusion criteria were (1) clinical IS diagnosis, (2) repository corticotropin injection treatment, and (3) consecutive EEG recordings before and after repository corticotropin injection treatment. Patients with tuberous sclerosis complex were excluded. Response to treatment was defined as freedom from IS for at least 7 consecutive days during the treatment and resolution of hypsarrhythmia. The authors defined “relapse” as the recurrence of seizures after an initial response. Electrophysiological biomarker assessment included evaluation of semiautomatic spike counting algorithm, delta power, and delta coherence calculation during non-REM sleep EEG.

Results:
One hundred fifty patients (83 males; 55%; median age of IS onset: 5.9 months) with complete data were included, including 101 responders (67%, 71 with sustained response, and 30 relapses). Fifty patients (33%) with complete EEG data also underwent advanced EEG analysis. Baseline delta coherence was higher in sustained responders than in nonresponders or patients who relapsed. Greater decreases in semiautomatic spike counting algorithm, delta power, and delta coherence were found in sustained responders compared with nonresponders or patients who relapsed.

Conclusions:
Repository corticotropin injection treatment was associated with a 67% response rate in patients with IS. Computational biomarkers beyond hypsarrhythmia may provide additional information during IS treatment, such as early determination of treatment response and outcome assessment.
Estimating the effects of accelerated partner therapy (APT) on reinfection of index cases with chlamydia: a mathematical modelling study
Authors: Althaus Christian L. , Estcourt Claudia S. , Low Nicola 
Published: August 2021

ABSTRACTObjectivesThe expected effects of accelerated partner therapy (APT) on the reinfection of treated index cases by untreated partners withChlamydia trachomatis(chlamydia) remain unclear. We analyzed data from the LUSTRUM cluster cross-over randomised controlled trial (RCT) using a mathematical model and quantified the effects of offering APT on the probability of successful partner treatment.MethodsWe extended a previously developed mathematical model to compute the probability of chlamydia reinfection of index cases by their untreated partners with chlamydia. We fitted the model to data from the RCT and estimated the probability of successful treatment of the partner of index cases using a Bayesian framework.ResultsWe estimated the median probability of reinfection with chlamydia at 16.3% (50% credible interval, CrI: 12.7-20.0%) without partner treatment and 2.3% (50% CrI: 1.7-3.6%) when partner treatment is 100% successful. The observed rates of reinfection in the RCT were 6.7% (95% confidence interval, CI: 5.6-8.0%) during the control period (standard partner notification (PN)) and 4.8% (95% CI: 3.7-5.9%) during the intervention period where APT was offered in addition to standard PN. These rates correspond to a median probability of successful partner treatment of 63% (50% CrI: 47-76%) during the control period and 78% (50% CrI: 65-87%) during the intervention period.ConclusionsOur study suggests that the observed reduction in reinfection with chlamydia when offering APT is consistent with a higher probability of successful partner treatment.
COVID-19 in Connecticut institutions of higher education during the 2020-2021 academic year
Authors: Schultes Olivia , Clarke Victoria , Paltiel A. David , Cartter Matthew , Sosa Lynn , Crawford Forrest W. 
Published: August 2021

AbstractBackgroundDuring the 2020-2021 academic year, many institutions of higher education reopened to residential students while pursuing strategies to mitigate the risk of SARS-CoV-2 transmission on campus. Reopening guidance emphasized PCR or antigen testing for residential students and social distancing measures to reduce the frequency of close interpersonal contact. Connecticut colleges and universities employed a variety of approaches to reopening campuses to residential students.MethodsWe used data on testing, cases, and social contact in 18 residential college and university campuses in Connecticut to characterize institutional reopening strategies and COVID-19 outcomes. We compared institutions’ fall 2020 COVID-19 plans, submitted to the Connecticut Department of Public Health, and analyzed contact rates and COVID-19 outcomes throughout the academic year.ResultsIn census block groups containing residence halls, fall student move-in resulted in a 475% (95% CI 373%-606%) increase in average contact, and spring move-in resulted in a 561% (441%-713%) increase in average contact. The relationship between test frequency and case rate per residential student was complex: institutions that tested students infrequently detected few cases but failed to blunt transmission, while institutions that tested students more frequently detected more cases and prevented further spread. In fall 2020, each additional test per student per week was associated with a reduction of 0.0014 cases per student per week (95% CI: -0.0028, -0.000012). Residential student case rates were associated with higher case rates in the town where the school was located, but it is not possible to determine whether on-campus infections were transmitted to the broader community or vice versa.ConclusionsCampus outbreaks among residential students might be avoided or mitigated by frequent testing, social distancing, and mandatory vaccination. Vaccination rates among residential students and surrounding communities may determine the necessary scale of residential testing programs and social distancing measures during the 2021-2022 academic year.
Development and use analysis of ‘gestioemocional.cat’, a web app for promoting emotional self-care and access to professional mental health resources during the covid-19 pandemic
Authors: Fidel-Kinori SG , Carot-Sans G , Cuartero-Barbanoj A , Valero-Bover D , Piera-Jimenez J , Romà-Monfà R , Garcia-Ribatallada E , Perez-Sust P , Blanch-Andreu J , Ramos-Quiroga JA 
Published: August 2021

AbstractBackgroundQuarantines and nationwide lockdowns dictated for containing the spread of the COVID-19 pandemic may lead to distress and increase the frequency of anxiety and depression symptoms among the general population. During the national lockdown of the first wave of the COVID-19 outbreak in Spain, we developed and launched a Web App (Gestioemocional.cat) to promote emotional self-care in the general population and facilitate contact with healthcare professionals.MethodsGestioemocional.cat targeted all individuals aged 18 years or more and was designed by adapting the contents of a mobile App for adjuvant treatment of post-traumatic stress disorder (i.e., the PTSD Coach App) to the general population and the pandemic/lockdown scenario. We retrospectively assessed the utilization pattern of the Web App using data systematically retrieved from Google Analytics. Data were grouped into three time periods, defined using a join point analysis of COVID-19 incidence in our area: first wave, between-wave period, and second wave.ResultsThe resulting Web App, maintains the navigation structure of the PTSD Coach App, with three main modules: tools for emotional self-care, a self-assessment test, and professional resources for on-demand contact. The self-assessment test combines the Patient Health Questionnaire-2 (PHQ-2) and the 7-item Generalized Anxiety Disorder Scale (GAD-7) and offers professional contact in the advent of a high level of depression and anxiety; contact is prioritized according to a screening questionnaire administered at the time of obtaining individual consent to be contacted. The tools for emotional self-care can be accessed either on-demand or symptom-driven. The utilization analysis showed a high number of weekly accesses during the first wave. In this period, press releases regarding critical events of the pandemic progression and government decisions on containment measures were followed by a utilization peak, irrespective of the sense (i.e., positive or negative) of the information. Positive information pieces (e.g., relaxation of containment measures due to a reduction of COVID-19 cases) resulted in a sharp increase in utilization immediately after information release, followed by a successive decline in utilization. The second wave was characterized by a lower and less responsive utilization of the Web App.ConclusionsmHealth tools may help the general population coping with stressful conditions associated with the pandemic scenario. Future studies shall investigate the effectiveness of these tools among the general population―including individuals without diagnosed mental illnesses―and strategies to reach as many people as possible.
SARS-CoV-2 variants: levels of neutralisation required for protective immunity
Authors: Cromer Deborah , Steain Megan , Reynaldi Arnold , Schlub Timothy E , Wheatley Adam K , Juno Jennifer A , Kent Stephen J , Triccas James A , Khoury David S , Davenport Miles P 
Published: August 2021

AbstractA number of SARS-CoV-2 variants of concern (VOC) have been identified that partially escape serum neutralisation activity elicited by current vaccines. Recent studies have also shown that vaccines demonstrate reduced protection against symptomatic infection with SARS-CoV-2 variants. Here we integrate published data on in vitro neutralisation and clinical protection to understand and predict vaccine efficacy against existing SARS-CoV-2 variants. We find that neutralising activity against the ancestral SARS-CoV-2 is highly predictive of neutralisation of the VOC, with all vaccines showing a similar drop in neutralisation to the variants. Neutralisation levels remain strongly correlated with protection from infection with SARS-CoV-2 VOC (r=0.81, p=0.0005). We apply an existing model relating in vitro neutralisation to protection (parameterised on data from ancestral virus infection) and find this remains predictive of vaccine efficacy against VOC once drops in neutralisation to the VOC are taken into account. Modelling of predicted vaccine efficacy against variants over time suggests that protection against symptomatic infection may drop below 50% within the first year after vaccination for some current vaccines. Boosting of previously infected individuals with existing vaccines (which target ancestral virus) has been shown to significantly increase neutralising antibodies. Our modelling suggests that booster vaccination should enable high levels of immunity that prevent severe infection outcomes with the current SARS-CoV-2 VOC, at least in the medium term.
Serological detection of SARS-CoV-2 IgG using commercially available immunoassays on dried blood spots collected from patients
Authors: Walker Gregory J , Davis Rebecca , Naing Zin , McEntee Brad , Lu Yonghui , Denadija Tatijana , Rawlinson William D 
Published: August 2021

ABSTRACTSerological testing for SARS-CoV-2 antibodies provides important research and diagnostic information relating to COVID-19 immune response and surveillance. A major challenge when addressing protection post-infection or vaccination is the difficulty of specimen collection from infants and children. Dried blood spots (DBS) collected by finger prick or heel prick are a minimally invasive sample collection alternative previously used to detect antibodies to other viruses. In this study we evaluated DBS for the detection of SARS-CoV-2 antibodies on three commercially available enzyme (EIA) and chemiluminescent (CLIA) immunoassays by analysing paired DBS and serum samples collected from 54 subjects. We demonstrate that testing of DBS samples was highly sensitive and specific, and quantitative results strongly correlated with those of paired serum. These results suggest that DBS derived blood is a viable alternative to plasma or serum for use in EIAs and CLIAs, and has particular utility as a minimally invasive collection tool for COVID-19 serological testing of infants and children.
Molecular and serological investigation of the 2021 COVID-19 case surge in Mongolian vaccinees
Authors: Dashdorj Naranjargal J. , Dashdorj Naranbaatar D. , Mishra Mitali , Danzig Lisa , Briese Thomas , Lipkin W. Ian , Mishra Nischay 
Published: August 2021

AbstractA surge in Covid-19 cases in Mongolia in March 2021 resulted in a government-mandated shutdown. This shutdown was relaxed in May 2021 as case numbers decreased and nationwide vaccination rates using Sinopharm, Covishield/AstraZeneca, Sputnik V, and Pfizer/BioNTech vaccines exceeded 50% of the population. Case rates increased again in early June 2021 in both vaccinated and non-vaccinated individuals. To determine whether the surge was due to the emergence of Delta or another variant, or vaccine failure, a rapid, opportunistic investigation was conducted that comprised virus sequence analysis of nasal swab samples from breakthrough cases and antibody assays of plasma from healthy vaccinees. More than 90% of breakthrough infections during the second case surge were due to the Alpha variant. Spike protein ELISA and SARS-CoV-2 neutralization assays data revealed large differences in plasma titers of antibodies to SARS-CoV-2, with mRNA vaccines eliciting higher titers than adenovirus-vectored or killed virus vaccines.
Assessing the sustainability of an integrated rural sanitation and hygiene approach: A repeated cross-sectional evaluation in 10 countries
Authors: Apanga Paschal A. , Freeman Matthew C. , Sakas Zoe , Garn Joshua V. 
Published: August 2021

AbstractIntroductionWhile many studies have implemented programs to increase sanitation coverage throughout the world, there are limited rigorous studies on the sustainability of these sanitation programs.MethodsBetween 2014 and 2018, the rural Sustainable Sanitation and Hygiene for All (SSH4A) approach was implemented by SNV in Sub-Saharan Africa and Asia. Repeated cross-sectional household surveys were administered annually throughout program implementation, and 1-to-2-years following completion of program activities. We characterize to what extent sanitation coverage was sustained 1-2 years after implementation of this SSH4A intervention.ResultsSurveys were conducted in 12 program areas in 10 countries, with 22,666 households receiving a post-implementation survey. Six of 12 program areas (Bhutan, Ghana, Kenya, both Nepal sites, and Tanzania) had similar coverage levels of basic sanitation 1-to-2-years post-implementation, whereas there were varied levels of slippage in the other program areas (both Ethiopia sites, Indonesia, Mozambique, Uganda, and Zambia), ranging from a drop of 63 percentage points in coverage in Ethiopia to a drop of only 4 percentage points in Indonesia. In countries that experienced losses in the coverage of household sanitation, generally sanitation sharing among neighbors did not increase, whereas open defecation did increase. In each of the areas where slippage occurred, the sanitation coverage levels at the final time point were all still higher than the initial time point before SNV started working in these areas. We found a number of factors to be associated with the sustainability of sanitation coverage, including household socio-economic status, having household members with disabilities, baseline sanitation coverage levels of the program areas, and rate of change of coverage during program activities.ConclusionsData revealed sustained gains in sanitation coverage in some program areas, yet slippage in other areas. This work may serve to benchmark sustainability of sanitation interventions in Sub-Saharan Africa and Asia.