bluuebunny/crossref_metadata_2025_split huggingface dataset:
On Quantitative Assessment of Effective Cement Bonding to Guarantee Wellbore Integrity
Authors: Santos Livio , Dahi Taleghani Arash 
Published: April 2021

Abstract
Methane leakage due to compromised wellbore cement integrity may result in operational complications and environmental contaminations in oil and gas wells. In this work, the problem of fluid-driven fracture propagation at the cement interfaces is revisited by a thorough and comprehensive consideration of the non-uniform cement bonding to the formation along the wellbore. While previous works were mainly focused on discharge without attention to mechanical failure or mechanical failure without ties to seepage rate; here, we couple these two analyses to provide a practical aspect of this approach. As revealed by cement evaluation logs, the quality of the cement behind the casing varies and may include flaws in the form of channels or pockets of mud residuals. A novel methodology, initiated with laboratory-scale cement bonding properties using the push-out test, is introduced to estimate the cohesive properties of the cement interface, considering mud removal and mud residuals in the rock. Then, the measured cohesive properties are applied to a field-scale numerical model with an embedded cohesive layer between cement and formation to evaluate the susceptibility of the wellbore to develop cement debonding. The excessive fluid pressure at the casing shoe is assumed to be the source for the fracture initiation. The proposed numerical model has been tested against actual sustained casing pressure (SCP) field tests for validation purposes. This model may estimate the geometry of leakage pathways and predict leakage flowrate within acceptable ranges. The effect of several key factors in the development of SCP due to the cement debonding is investigated. The results show that the early stage of SCP buildup is controlled by the cohesive properties of the cement interfaces (i.e., cement properties), but the cohesive properties have minor effects on the stabilized pressure. The method proposed herein presents a method to evaluate the cement bond quantitatively to be further integrated into cement design.
Peak Blood Lactate Concentration and Its Arrival Time Following Different Track Running Events in Under-20 Male Track Athletes
Authors: Gupta Subir , Stanula Arkadiusz , Goswami Asis 
Published: April 2021

Purpose: To determine (1) the time of arrival of peak blood lactate concentration ([BLa]peak) followed by various track events and (2) significant correlation, if any, between average velocity and [BLa]peak in these events. Methods: In 58 under-20 male track athletes, heart rate was recorded continuously and blood lactate concentration was determined at various intervals following 100-m (n = 9), 200-m (n = 8), 400-m (flat) (n = 9), 400-m hurdles (n = 8), 800-m (n = 9), 1500-m (n = 8), 3000-m steeplechase (n = 7), and 5000-m (n = 10) runs. Results: The [BLa]peak, in mmol/L, was recorded highest following the 400-m run (18.27 [3.65]) followed by 400-m hurdles (16.25 [3.14]), 800-m (15.53 [3.25]), 1500-m (14.71 [3.00]), 200-m (14.42 [3.40]), 3000-m steeplechase (11.87 [1.48]), 100-m (11.05 [2.36]), and 5000-m runs (8.65 [1.60]). The average velocity of only the 400-m run was found to be significantly correlated (r = .877, p < 0.05) with [BLa]peak. The arrival time of [BLa]peak following 100-m, 200-m, 400-m, 400-m hurdles, 800-m, 1500-m, 3000-m steeplechase, and 5000-m runs was 4.44 (0.83), 4.13 (0.93), 4.22 (0.63), 3.75 (0.83), 3.34 (1.20), 2.06 (1.21), 1.71 (1.44), and 1.06 (1.04) minutes, respectively, of the recovery period. Conclusion: In under-20 runners, (1) [BLa]peak is highest after the 400-m run, (2) the time of appearance of [BLa]peak varies from one event to another but arrives later after sprint events than longer distances, and (3) the 400-m (flat) run is the only event wherein the performance is significantly correlated with the [BLa]peak.
Aerobic and Anaerobic Power Distribution During Cross-Country Mountain Bike Racing
Authors: Prinz Bernhard , Simon Dieter , Tschan Harald , Nimmerichter Alfred 
Published: April 2021

Purpose: To determine aerobic and anaerobic demands of mountain bike cross-country racing. Methods: Twelve elite cyclists (7 males;  = 73.8 [2.6] mL·min-1·kg−1, maximal aerobic power [MAP] = 370 [26] W, 5.7 [0.4] W·kg−1, and 5 females;  = 67.3 [2.9] mL·min−1·kg−1, MAP = 261 [17] W, 5.0 [0.1] W·kg−1) participated over 4 seasons at several (119) international and national races and performed laboratory tests regularly to assess their aerobic and anaerobic performance. Power output, heart rate, and cadence were recorded throughout the races. Results: The mean race time was 79 (12) minutes performed at a mean power output of 3.8 (0.4) W·kg−1; 70% (7%) MAP (3.9 [0.4] W·kg−1 and 3.6 [0.4] W·kg−1 for males and females, respectively) with a cadence of 64 (5) rev·min−1 (including nonpedaling periods). Time spent in intensity zones 1 to 4 (below MAP) were 28% (4%), 18% (8%), 12% (2%), and 13% (3%), respectively; 30% (9%) was spent in zone 5 (above MAP). The number of efforts above MAP was 334 (84), which had a mean duration of 4.3 (1.1) seconds, separated by 10.9 (3) seconds with a mean power output of 7.3 (0.6) W·kg−1 (135% [9%] MAP). Conclusions: These findings highlight the importance of the anaerobic energy system and the interaction between anaerobic and aerobic energy systems. Therefore, the ability to perform numerous efforts above MAP and a high aerobic capacity are essential to be competitive in mountain bike cross-country.
Investigating the Lowest Threshold of Vascular Benefits from LDL Cholesterol Lowering with a PCSK9 mAb Inhibitor (Alirocumab) in Patients with Stable Cardiovascular Disease (INTENSITY-HIGH): protocol and study rationale for a randomised, open label, parallel group, mechanistic study
Authors: Cacciottolo Paul J , Kostapanos Michalis S , Hernan Sancho Elena , Pavey Holly , Kaloyirou Fotini , Vamvaka Evangelia , Helmy Joanna , Hubsch Annette , McEniery Carmel M , Wilkinson Ian B , Cheriyan Joseph 
Published: April 2021

IntroductionElevated low-density lipoprotein cholesterol (LDL-C) is a strong independent risk predictor of cardiovascular (CV) events, while interventions to reduce it remain the only evidence-based approach to reduce CV morbidity and mortality. Secondary prevention statin trials in combination with ezetimibe and/or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors showed that there is no ‘J shaped curve’ in LDL-C levels with regard to CV outcomes. The lowest threshold beyond which reduction of LDL-C confers no further CV benefits has not been identified.The INTENSITY-HIGH study seeks to explore physiological mechanisms mediating CV benefits of LDL-C lowering by PCSK9 inhibition in patients with established cardiovascular disease (CVD). The study examines the changes in measures of endothelial function and vascular inflammation imaging following intervention with PCSK9 and against standard of care.Methods and analysisThis is a single-centre, randomised, open label, parallel group, mechanistic physiological study. It will include approximately 60 subjects with established CVD, with LDL-C of <4.1 mmol/L on high-intensity statins. All eligible participants will undergo 18-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) scanning of the aorta and carotid arteries, as well as baseline endothelial function assessment. Subsequently, they will be randomised on a 1:1 basis to either alirocumab 150 mg or ezetimibe 10 mg/day. Repeat FDG-PET/CT scan and vascular assessments will be undertaken after 8 weeks of treatment. Any changes in these parameters will be correlated with changes in lipid levels and systemic inflammation biomarkers.Ethics and disseminationThe study received a favourable opinion from the Wales Research Ethics Committee 4, was registered on clinicaltrials.gov and conformed to International Conference for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice. The results of this study will be reported through peer-reviewed journals and conference presentations.Trial registration numberNCT03355027.
Qualitative analysis of stakeholder interviews to identify the barriers and facilitators to the adoption of point-of-care diagnostic tests in the UK
Authors: Huddy Jeremy R , Ni Melody Zhifang , Barlow James , Hanna George B 
Published: April 2021

ObjectivesThis study investigated the barriers and facilitators to the adoption of point-of-care tests (POCTs).DesignQualitative study incorporating a constant comparative analysis of stakeholder responses to a series of interviews undertaken to design the Point-of-Care Key Evidence Tool.SettingThe study was conducted in relation to POCTs used in all aspects of healthcare.ParticipantsForty-three stakeholders were interviewed including clinicians (incorporating laboratory staff and members of trust POCT committees), commissioners, industry, regulators and patients.ResultsThematic analysis highlighted 32 barriers in six themes and 28 facilitators in eight themes to the adoption of POCTs. Six themes were common to both barriers and facilitators (clinical, cultural, evidence, design and quality assurance, financial and organisational) and two themes contained facilitators alone (patient factors and other (non-financial) resource use).ConclusionsFindings from this study demonstrate the complex motivations of stakeholders in the adoption of POCT. Most themes were common to both barriers and facilitators suggesting that good device design, stakeholder engagement and appropriate evidence provision can increase the likelihood of a POCT device adoption. However, it is important to realise that while the majority of identified barriers may be perceived or mitigated some may be absolute and if identified early in device development further investment should be carefully considered.
Prevalence and factors associated with depression, anxiety and stress among healthcare workers of Trinidad and Tobago during COVID-19 pandemic: a cross-sectional study
Authors: Nayak B Shivananda , Sahu Pradeep Kumar , Ramsaroop Koomatie , Maharaj Shivanand , Mootoo William , Khan Sharaz , Extavour Rian Marie 
Published: April 2021

ObjectivesTo determine the prevalence and factors associated with depression, anxiety and stress among healthcare workers (HCWs) during COVID-19 pandemic.DesignCross-sectional online survey.SettingHCWs from four major hospitals within the Regional Health Authorities of Trinidad and Tobago.Participants395 HCWs aged ≥18 years.Main outcome measuresDepression, anxiety and stress scores.ResultsAmong the 395 HCWs, 42.28%, 56.2% and 17.97% were found to have depression, anxiety and stress, respectively. In the final stepwise regression model, contact with patients with confirmed COVID-19, p<0.001 (95% CI 3.072 to 6.781) was reported as significant predictors of depression. Further, gender, p<0.001 (95% CI 2.152 to 5.427) and marital status, p<0.001 (95% CI 1.322 to 4.270) of the HCWs were considered to be correlated with anxiety. HCWs who had contact with patients with suspected COVID-19 had lower depression, p<0.001 (95% CI −5.233 to −1.692) and stress, p<0.001 (95% CI −5.364 to −1.591).ConclusionsThis study has depicted the prevalence and evidence of depression, anxiety and stress among HCWs during the COVID-19 pandemic. The findings of the study will serve as supportive evidence for the timely implementation of further planning of preventative mental health services by the Ministry of Health, for frontline workers within the public and private health sectors.
Hemogram as Marker of In-Hospital Mortality in Covid-19
Authors: López-Escobar Alejandro , Madurga Rodrigo , Castellano José María , Ruiz de Aguiar Santiago , Velázquez Sara , Bucar Marina , Jimeno Sara , Ventura Paula Sol 
Published: April 2021

The clinical impact of COVID-19 disease calls for the identification of routine variables to identify patients at increased risk of death. Current understanding of moderate-to-severe COVID-19 pathophysiology points toward an underlying cytokine release driving a hyperinflammatory and procoagulant state. In this scenario, white blood cells and platelets play a direct role as effectors of such inflammation and thrombotic response. We investigate whether hemogram-derived ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and the systemic immune-inflammation index may help to identify patients at risk of fatal outcomes. Activated platelets and neutrophils may be playing a decisive role during the thromboinflammatory phase of COVID-19 so, in addition, we introduce and validate a novel marker, the neutrophil-to-platelet ratio (NPR). Two thousand and eighty-eight hospitalized patients with COVID-19 admitted at any of the hospitals of HM Hospitales group in Spain, from March 1 to June 10, 2020, were categorized according to the primary outcome of in-hospital death. Baseline values, as well as the rate of increase of the four ratios analyzed were significantly higher at hospital admission in patients who died than in those who were discharged (p<0.0001). In multivariable logistic regression models, NLR (OR 1.05; 95% CI 1.02 to 1.08, p=0.00035) and NPR (OR 1.23; 95% CI 1.12 to 1.36, p<0.0001) were significantly and independently associated with in-hospital mortality. According to our results, hemogram-derived ratios obtained at hospital admission, as well as the rate of change during hospitalization, may easily detect, primarily using NLR and the novel NPR, patients with COVID-19 at high risk of in-hospital mortality.
CD122-directed interleukin-2 treatment mechanisms in bladder cancer differ from αPD-L1 and include tissue-selective γδ T cell activation
Authors: Reyes Ryan Michael , Deng Yilun , Zhang Deyi , Ji Niannian , Mukherjee Neelam , Wheeler Karen , Gupta Harshita B , Padron Alvaro S , Kancharla Aravind , Zhang Chenghao , Garcia Myrna , Kornepati Anand V R , Boyman Onur , Conejo-Garcia Jose R , Svatek Robert S , Curiel Tyler J 
Published: April 2021

BackgroundAnti-programmed death-ligand 1 (αPD-L1) immunotherapy is approved to treat bladder cancer (BC) but is effective in <30% of patients. Interleukin (IL)-2/αIL-2 complexes (IL-2c) that preferentially target IL-2 receptor β (CD122) augment CD8+antitumor T cells known to improve αPD-L1 efficacy. We hypothesized that the tumor microenvironment, including local immune cells in primary versus metastatic BC, differentially affects immunotherapy responses and that IL-2c effects could differ from, and thus complement αPD-L1.MethodsWe studied mechanisms of IL-2c and αPD-L1 efficacy using PD-L1+mouse BC cell lines MB49 and MBT-2 in orthotopic (bladder) and metastatic (lung) sites.ResultsIL-2c reduced orthotopic tumor burden and extended survival in MB49 and MBT-2 BC models, similar to αPD-L1. Using antibody-mediated cell depletions and genetically T cell-deficient mice, we unexpectedly found that CD8+T cells were not necessary for IL-2c efficacy against tumors in bladder, whereas γδ T cells, not reported to contribute to αPD-L1 efficacy, were indispensable for IL-2c efficacy there. αPD-L1 responsiveness in bladder required conventional T cells as expected, but not γδ T cells, altogether defining distinct mechanisms for IL-2c and αPD-L1 efficacy. γδ T cells did not improve IL-2c treatment of subcutaneously challenged BC or orthotopic (peritoneal) ovarian cancer, consistent with tissue-specific and/or tumor-specific γδ T cell contributions to IL-2c efficacy. IL-2c significantly altered bladder intratumoral γδ T cell content, activation status, and specific γδ T cell subsets with antitumor or protumor effector functions. Neither IL-2c nor αPD-L1 alone treated lung metastatic MB49 or MBT-2 BC, but their combination improved survival in both models. Combination treatment efficacy in lungs required CD8+T cells but not γδ T cells.ConclusionsMechanistic insights into differential IL-2c and αPD-L1 treatment and tissue-dependent effects could help develop rational combination treatment strategies to improve treatment efficacy in distinct cancers. These studies also provide insights into γδ T cell contributions to immunotherapy in bladder and engagement of adaptive immunity by IL-2c plus αPD-L1 to treat refractory lung metastases.
Rapid corticosteroid taper versus standard of care for immune checkpoint inhibitor induced nephritis: a single-center retrospective cohort study
Authors: Lee Meghan D , Seethapathy Harish , Strohbehn Ian A , Zhao Sophia H , Boland Genevieve M , Fadden Riley , Sullivan Ryan , Reynolds Kerry L , Sise Meghan E 
Published: April 2021

BackgroundCurrent guidelines for treatment of immune checkpoint inhibitor (ICI)-induced nephritis are not evidence based and may lead to excess corticosteroid exposure. We aimed to compare a rapid corticosteroid taper to standard of care.MethodsRetrospective cohort study in patients with ICI-induced nephritis comparing a rapid taper beginning with 60 mg/day prednisone and tapered to 10 mg within 3 weeks to a historical control group that began 60 mg/day tapered to 10 mg within 6 weeks (standard of care). Renal recovery was defined as creatinine returning to within 1.5-fold baseline. The log-rank test compared the differences in time to renal recovery between the groups. We report rates of renal recovery at 30, 60 and 90 days, and timing and outcomes of ICI rechallenge.ResultsThirteen patients received rapid corticosteroid taper and 14 patients received standard of care. Baseline characteristics were similar between groups. The median time to ≤10 mg/day prednisone was 20 days (IQR 15–25) in the rapid-taper group compared with 38 days (IQR 30–58) in the standard-of-care group. There was no significant difference in the time to renal recovery between the groups, though numerically higher numbers of patients recovered by 30 days, 11 (85%) in the rapid-taper arm versus 6 (46%) in the standard of care arm. Exposure to other nephritis-causing medications (proton pump inhibitor or trimethoprim-sulfamethoxazole) during the corticosteroid taper was more common in the standard of care group, 9 (64%) versus rapid-taper group, 2 (15%), and was associated with longer time to renal recovery, 20 days (IQR 14–101) versus 13 days (IQR 7–34) in those that discontinued nephritis-causing medications. Fifteen (56%) of patients were rechallenged with ICIs, and only two (13%) developed recurrent nephritis.ConclusionsPatients with ICI-induced nephritis have excellent kidney outcomes when treated with corticosteroids that are tapered over 3 weeks.
Prognostic impact of early tumor shrinkage and depth of response in patients with microsatellite instability-high metastatic colorectal cancer receiving immune checkpoint inhibitors
Authors: Fucà Giovanni , Corti Francesca , Ambrosini Margherita , Intini Rossana , Salati Massimiliano , Fenocchio Elisabetta , Manca Paolo , Manai Chiara , Daniel Francesca , Raimondi Alessandra , Morano Federica , Corallo Salvatore , Prisciandaro Michele , Spallanzani Andrea , Quarà Virginia , Belli Carmen , Vaiani Marta , Curigliano Giuseppe , Cremolini Chiara , De Braud Filippo , Di Bartolomeo Maria , Zagonel Vittorina , Lonardi Sara , Pietrantonio Filippo 
Published: April 2021

BackgroundImmune checkpoint inhibitors (ICIs) are the new standard of care in microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC). Since tumor response dynamic parameters already shown a strong association with survival outcomes in patients with mCRC treated with first-line therapy, we investigated the association of early tumor shrinkage (ETS) and depth of response (DoR) in patients with MSI-H/dMMR mCRC treated with ICIs.MethodsThis is a retrospective, multicenter, cohort study in patients with dMMR and/or MSI-high mCRC treated with ICIs (anti-PD-1/PD-L1 with or without anti-CTLA-4 agents) with measurable disease and at least one post-baseline radiological disease reassessment. The Kaplan-Meier method and Cox proportional-hazards regression models were used for survival analyses. A maximally selected statistics method in a Cox regression model for progression-free survival (PFS) was used to determine the optimal cut-offs for ETS and DoR.ResultsWe included a total of 169 patients: 116 (68.6%) were treated with anti-PD-1 monotherapy, whereas 53 (31.4%) with anti-PD-1 plus anti-CTLA-4 agents. Patients with primary progressive disease (N=37, 21.9%), experienced an extremely poor overall survival (OS) and were evaluated separately. In patients with clinical benefit, we observed a significant association between ETS and DoR with both OS and PFS, and we identified a relative reduction of at least 1% as the optimal cut-off for ETS and a relative reduction of at least 50% as the optimal cut-off for DoR.ConclusionsETS and DoR are important prognostic factors in patients with MSI-high mCRC treated with ICIs that might be useful to design treatment intensification/deintensification strategies. A prospective validation of both is warranted.
Brunnian braids over the 2-sphere and Artin combed form
Authors: Duzhin Fedor , Loh Sher En Jessica 
Published: April 2021

Finding homotopy group of spheres is an old open problem in topology. Berrick et al. derive in [A. J. Berrick, F. Cohen, Y. L. Wong and J. Wu, Configurations, braids, and homotopy groups, J. Amer. Math. Soc. 19 (2006)] an exact sequence that relates Brunnian braids to homotopy groups of spheres. We give an interpretation of this exact sequence based on the combed form for braids over the sphere developed in [R. Gillette and J. V. Buskirk, The word problem and consequences for the braid groups and mapping class groups of the two-sphere, Trans. Amer. Math. Soc. 131 (1968) 277–296] with the aim of helping one to visualize the sequence and to do calculations based on it.
Food Insecurity Is an Independent Risk Factor for Depressive Symptoms in Survivors of Digestive Cancers
Authors: Madigan Katelyn E. , Leiman David A. , Palakshappa Deepak 
Published: April 2021

Abstract

Background:
Colorectal and other digestive cancer survivors are at increased risk of depression, which can negatively affect health outcomes. Food insecurity (FI), the lack of consistent access to enough food, can also contribute to these health complications. The objective of this study was to determine the relationship between FI and depressive symptoms within this population.

Methods:
We conducted a cross-sectional analysis of data from the 2007–2016 National Health and Nutrition Examination Survey. We included all adults (≥20 years) with a self-reported history of a digestive cancer (including colorectal, esophageal, stomach, liver, and pancreas cancer). Our primary exposure was household FI, and our outcome of interest was depressive symptoms, as measured by the validated 9-item Patient Health Questionnaire. We used multivariable ordinal logistic regression to test the association between FI and depressive symptoms, controlling for demographic and clinical covariates.

Results:
We included 229 adult digestive cancer survivors (weighted N = 1,510,579). The majority of the study sample was female and non-Hispanic White with mean of 11.0 years since cancer diagnosis; 14.3% reported FI. In multivariable models controlling for demographic and clinical covariates, we found that food insecure digestive cancer survivors had significantly higher odds of depressive symptoms than food secure digestive cancer survivors (OR: 3.25; 95% confidence interval: 1.24–8.55; P = 0.02).

Conclusions:
Among a nationally representative sample of colorectal cancer and other digestive cancer survivors, FI was associated with increased odds of depressive symptoms.

Impact:
This study adds further evidence to the negative impact FI may have on survivors' physical and mental health.