bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and MMP10, MMP23 in inflammatory bowel disease: Cross‐sectional study
Authors: Fonseca‐Camarillo Gabriela , Furuzawa‐Carballeda Janette , Martínez‐Benitez Braulio , Barreto‐Zuñiga Rafael , Yamamoto‐Furusho Jesús K. 
Published: August 2020

AbstractIt has been reported that EMMPRIN is involved in the regulation of immune response and the induction of MMPs production by fibroblasts. The aim of this study was to describe the intestinal gene expression and protein production of EMMPRIN, MMP23 and MMP10 in patients with ulcerative colitis (UC) and Crohn’s disease (CD) and compared them with a control group. Gene expression of EMMPRIN, MMP10 and MMP23B was measured by RT‐PCR. In order to determine EMMPRIN and MMP protein expression, colonic tissues were immunostained. The results of the study showed EMMPRIN gene expression was upregulated in rectal mucosa from active (a)UC versus aCD patients (P = .045), remission (r)CD group (P = .0009) and controls (P < .0001). We detected differences between rUC and aCD (P = .004), rCD (P < .0001) or control group (P < .0001). EMMPRIN showed a higher expression in mucosa (intraepithelial lymphocytes), submucosa and adventitia (endothelial cells) from aCD patients. MMP23 levels were increased in aUC and aCD compared to rUC and rCD and the control group (P = .0001). EMMPRIN+/MMP23+─expressing cells were localized mainly in mucosa, muscular and adventitia from active UC patients. MMP10 gene expression was increased in aUC versus CD patients and the control group (P = .0001). MMP10 gene expression is associated with inflammation in UC patients (P = .0001, r2 = .585). EMMPRIN+/MMP10+─producing cells were found mainly in all intestinal layers and perivascular inflammatory infiltrates from aUC patients. In conclusion, EMMPRIN, MMP23 and MMP10 were upregulated in patients with active UC versus remission UC , CD and control groups suggesting that, they are involved in the inflammatory process.
Integrating high‐intensity interval training into the workplace: The Work‐HIIT pilot RCT
Authors: Eather Narelle , Babic Mark , Riley Nicholas , Harris Nigel , Jung Mary , Jeffs Mikeelie , Barclay Briana , Lubans David R. 
Published: August 2020

The purpose of this study was to assess the feasibility and preliminary efficacy of a high‐intensity interval training (HIIT) intervention integrated into the workplace on physical and mental health outcomes in a sample of adults. The Work‐HIIT intervention was evaluated at the University of Newcastle (March‐July 2019). University employees (18+ years) who self‐identified as predominantly sedentary at work (n = 47, 43.0 ± 10.7 years; 41 female) were recruited, screened, and randomized after baseline assessments into Work‐HIIT (n = 24) or wait‐list control (n = 23) conditions. Participants were asked to attend 2‐3 researcher‐facilitated HIIT sessions/week (weeks 1‐8). Sessions included a 2‐minute gross‐motor warm‐up, followed by various combinations of aerobic and muscular fitness exercises lasting 8 minutes (using 30:30 second work: rest intervals). Program feasibility was assessed using measures of satisfaction, compliance, adherence, fidelity, and retention. Physiological and psychological outcomes were measured at baseline and 9 weeks. Feasibility data were investigated using descriptive statistics and efficacy outcomes determined using linear mixed models and Cohen's d effect sizes. Participant ratings showed high levels of satisfaction (4.6/5); 71% of participants attended ≥2 sessions/wk and averaged 85.9% HRmax across all sessions (including rest and work intervals). Small‐to‐medium positive effects resulted for cardiorespiratory fitness [+2.9 laps, 95% CI (−4.19‐10.14); d = 0.34] and work productivity [+0.26, d = 0.47]. Large positive effects resulted for muscular fitness [push‐ups +3.5, d = 0.95; standing jump +10.1 cm, d = 1.12]; HIIT self‐efficacy [+16.53, d = 1.57]; sleep [weekday +0.76 hours, d = 1.05]; and autonomous motivation [+0.23, d = 0.76]. This study supports the feasibility and preliminary efficacy of facilitator‐led Work‐HIIT as a time‐efficient, enjoyable, and convenient workplace exercise option for adults.
Teaching students to estimate complex probabilities of board game events through simulation
Authors: Lyford Alex , Czekanski Michael 
Published: August 2020

AbstractStudents are typically introduced to probability through calculating simple events like flipping a coin. While these calculations can be done by hand, more complex probabilistic events, both in class and in the real world, require the use of computers. In this paper, we introduce a new tool—an R shiny web app and associated CRAN package based on the board game “CamelUp”—to help students explore these probability calculations through simulation in a fun context. Through this app and in conjunction with the board game Camel Up, we present some sample activities for helping students better understand and make in‐game probabilistic decisions.
Donor‐dependent aging of young and old red blood cell subpopulations: Metabolic and functional heterogeneity
Authors: Mykhailova Olga , Olafson Carly , Turner Tracey R. , DʼAlessandro Angelo , Acker Jason P. 
Published: August 2020

AbstractBackgroundCharacteristics of red blood cells (RBCs) are influenced by donor variability. This study assessed quality and metabolomic variables of RBC subpopulations of varied biologic age in red blood cell concentrates (RCCs) from male and female donors to evaluate their contribution to the storage lesion.Study Design and MethodsRed blood cell concentrates from healthy male (n = 6) and female (n = 4) donors were Percoll separated into less dense (“young”, Y‐RCCs) and dense (“old”, O‐RCCs) subpopulations, which were assessed weekly for 28 days for changes in hemolysis, mean cell volume (MCV), hemoglobin concentration (MCHC), hemoglobin autofluorescence (HGB), morphology index (MI), oxygen affinity (p50), rigidity, intracellular reactive oxygen species (ROS), calcium ([Ca2+]), and mass spectrometry–based metabolomics.ResultsYoung RCCs having disc‐to‐discoid morphology showed higher MCV and MI, but lower MCHC, HGB, and rigidity than O‐RCCs, having discoid‐to‐spheroid shape. By Day 14, Y‐RCCs retained lower hemolysis and rigidity and higher p50 compared to O‐RCCs. Donor sex analyses indicated that females had higher MCV, HGB, ROS, and [Ca2+] and lower hemolysis than male RBCs, in addition to having a decreased rate of change in hemolysis by Day 28. Metabolic profiling indicated a significant sex‐related signature across all groups with increased markers of high membrane lipid remodeling and antioxidant capacity in Y‐RCCs, whereas O‐RCCs had increased markers of oxidative stress and decreased coping capability.ConclusionThe structural, functional, and metabolic dissimilarities of Y‐RCCs and O‐RCCs from female and male donors demonstrate RCC heterogeneity, where RBCs from females contribute less to the storage lesion and age slower than males.
Annexin A1‐derived peptide Ac2‐26 facilitates wound healing in diabetic mice
Authors: Huang Jun‐Jie , Xia Chong‐Jian , Wei Ying , Yao Yi , Dong Miao‐Wu , Lin Ke‐Zhi , Yu Lin‐Sheng , Gao Yuan , Fan Yan‐Yan 
Published: August 2020

AbstractImpaired wound healing is a common complication of diabetes. In diabetic wounds, macrophages present dysfunctional efferocytosis and abnormal phenotypes, which could result in excessive neutrophil accumulation and prolonged inflammation, thereby eventually hindering wound repair. ANXA1 N‐terminal peptide Ac2‐26 exhibits a high potential in mitigating inflammation and improving repair; however, its efficacy in diabetic wound repair remains unclear. In this study, a cutaneous excisional wound model was built in genetically diabetic mice. Ac2‐26 or a vehicle solution was employed locally in wound sites. Subsequently, wound zones were measured and sampled at different time intervals post‐wounding. Using hematoxylin‐eosin and Masson's trichrome staining, we observed the histopathological variations and collagen deposition in wound samples. Based on immunohistochemistry and immunofluorescence, the numbers of neutrophils, macrophages, and CD206‐positive macrophages in the wound samples were determined. Cytokine expression in wound samples was studied by immunoblot assay. Results showed that Ac2‐26 treatment could facilitate diabetic wound closure, down‐regulate the number of neutrophils, and improve angiogenesis and collagen deposition. In addition, Ac2‐26 application expedited macrophage recruitment and up‐regulated the percentage of macrophages expressing CD206, which is a marker for M2 macrophages. Moreover, Ac2‐26 inhibited the expressions of TNF‐α and IL‐6 and up‐regulated the expressions of IL‐10, TGF‐β, and VEGFA during diabetic wound healing. Hence, based on the aforementioned findings, Ac2‐26 application in diabetic wounds could exert anti‐inflammatory and pro‐repair effects by reducing neutrophil accumulation and facilitating M2 macrophage development.
MAKING SPACE FOR THE METHODOLOGICAL MOSAIC: THE FUTURE OF THE FIELD OF SCIENCE‐AND‐RELIGION
Authors: Wright Jaime 
Published: August 2020

AbstractThis article is a response to Josh Reeves's recent book Against Methodology in Science and Religion: Recent Debates on Rationality and Theology that welcomes Reeves's proposal for an anti‐essentialist future for the field of science‐and‐religion, particularly because it has the potential to move the field beyond current, well‐worn methods: the dominance of Christian theology and doctrine, the importance of credibility strategies, and the dependence upon philosophical discourses. Reeves’ proposal has the potential to open the science‐and‐religion field to other topics, problems, and methods, such as studying lived science‐and‐religion. One way of doing this is to study popular culture and its artifacts such as literature, which portrays a co‐mingling of religion and science at the level of day‐to‐day experiences and practices of characters. For at the level of lived experience, religion and science are not well‐defined disciplines neatly compartmentalized into separate academic departments.
METHODOLOGY IN SCIENCE AND RELIGION: A REPLY TO CRITICS
Authors: Reeves Josh 
Published: August 2020

AbstractDebates about methodology have been central to the emergence of the “field of science of religion.” Two questions that have motivated scholars in that field over the past half century: “is it theoretically justifiable to bring scientific and religious beliefs into dialogue?” and “can theology be rational in the same way as science?” This article responds to commentary on Against Methodology: Recent Debates on Rationality and Theology, a book which critically examines three major methodologists of recent years: Nancey Murphy, Alister McGrath, and J. Wentzel van Huyssteen. Themes raised in the commentary include the status of realism and truth in science, the unity of science, the adequacy of the term “critical realism,” proper ways of seeking legitimacy for an academic discipline, and new directions for the field of science and religion.
Risk of 16 cancers across the full glycemic spectrum: a population-based cohort study using the UK Biobank
Authors: Rentsch Christopher T , Farmer Ruth E , Eastwood Sophie V , Mathur Rohini , Garfield Victoria , Farmaki Aliki-Eleni , Bhaskaran Krishnan , Chaturvedi Nish , Smeeth Liam 
Published: August 2020

IntroductionDiabetes is observed to increase cancer risk, leading to hypothesized direct effects of either hyperglycemia or medication. We investigated associations between glycosylated hemoglobin (HbA1c) across the whole glycemic spectrum and incidence of 16 cancers in a population sample with comprehensive adjustment for risk factors and medication.Research design and methodsLinked data from the UK Biobank and UK cancer registry for all individuals with baseline HbA1c and no history of cancer at enrollment were used. Incident cancer was based on International Classification of Diseases – 10th Edition diagnostic codes. Age-standardized incidence rates were estimated by HbA1c category. Associations between HbA1c, modeled as a restricted cubic spline, and cancer risk were estimated using Cox proportional hazards models.ResultsAmong 378 253 individuals with average follow-up of 7.1 years, 21 172 incident cancers occurred. While incidence for many of the 16 cancers was associated with hyperglycemia in crude analyses, these associations disappeared after multivariable adjustment, except for pancreatic cancer (HR 1.55, 95% CI 1.22 to 1.98 for 55 vs 35 mmol/mol), and a novel finding of an inverse association between HbA1c and premenopausal breast cancer (HR 1.27, 95% CI 1.00 to 1.60 for 25 vs 35 mmol/mol; HR 0.71, 95% CI 0.54 to 0.94 for 45 vs 35 mmol/mol), not observed for postmenopausal breast cancer. Adjustment for diabetes medications had no appreciable impact on HRs for cancer.ConclusionsApart from pancreatic cancer, we did not demonstrate any independent positive association between HbA1c and cancer risk. These findings suggest that the potential for a cancer-inducing, direct effect of hyperglycemia may be misplaced.
Level of confidence in and endorsement of the health system among internet users in 12 low-income and middle-income countries
Authors: Roder-DeWan Sanam , Gage Anna , Hirschhorn Lisa R , Twum-Danso Nana A Y , Liljestrand Jerker , Asante-Shongwe Kwanele , Yahya Talhiya , Kruk Margaret 
Published: August 2020

IntroductionPeople’s confidence in and endorsement of the health system are key measures of system performance, yet are undermeasured in low-income and middle-income countries (LMICs). We explored the prevalence and predictors of these measures in 12 countries.MethodsWe conducted an internet survey in Argentina, China, Ghana, India, Indonesia, Kenya, Lebanon, Mexico, Morocco, Nigeria, Senegal and South Africa collecting demographics, ratings of quality, and confidence in and endorsement of the health system. We used multivariable logistic regression to assess the association between confidence/endorsement and self-reported quality of recent healthcare.ResultsOf 13 489 respondents, 62% reported a health visit in the past year. Applying population weights, 32% of these users were very confident that they could receive effective care if they were to ‘become very sick tomorrow’; 30% endorsed the health system, that is, agreed that it ‘works pretty well and only needs minor changes’. Reporting high quality in the last visit was associated with 4.48 and 2.69 greater odds of confidence (95% CI 3.64 to 5.52) and endorsement (95% CI 2.33 to 3.11). Having health insurance was positively associated with confidence and endorsement (adjusted odds ratio (AOR) 1.68, 95% CI 1.49 to 1.90 and AOR 1.34, 95% CI 1.22 to 1.48), while experiencing discrimination in healthcare was negatively associated (AOR 0.67, 95% CI 0.56 to 0.80 and AOR 0.63, 95% CI 0.53 to 0.76).ConclusionConfidence and endorsement of the health system were low across 12 LMICs. This may hinder efforts to gain support for universal health coverage. Positive patient experience was strongly associated with confidence in and endorsement of the health system.
The impact of a health facility construction campaign on health service utilisation and outcomes: analysis of spatially linked survey and facility location data in Ethiopia
Authors: Croke Kevin , Telaye Mengistu Andualem , O'Connell Stephen D. , Tafere Kibrom 
Published: August 2020

BackgroundAccess to health facilities in many low-income and middle-income countries remains low, with a strong association between individuals’ distance to facilities and health outcomes. Yet plausibly causal estimates of the effects of facility construction programmes are rare. Starting in 2004, more than 2800 government health facilities were built in Ethiopia. This study estimates the impact of this programme on maternal health service utilisation and birth outcomes.MethodsWe analyse the impact of Ethiopia’s health centre construction programme on health service utilisation and outcomes, using a difference-in-difference design. We match facility opening years to child birth years in four rounds of Demographic and Health Surveys (DHS) using georeferenced data. We also use event study models to test for pre-trends in the outcomes of interest.ResultsOpening of new health facilities within 5 km increases facility delivery by 7.2 percentage points (95% CI 5.2 to 9.1) and antenatal care by 0.38 visits (95% CI 0.24 to 0.52). It is not significantly associated with changes in caesarean section births or neonatal mortality. Opening of district hospitals increases facility delivery by 18.2 percentage points (95% CI 12.7 to 23.7), and caesarean section births by 6.8 percentage points (95% CI 2.5 to 11.2), but is not associated with reduction of neonatal mortality.ConclusionsEthiopia’s facility construction program improved access to antenatal and delivery care. However, there was no detectable association between facility construction and neonatal mortality. Increased access to care must be combined with health system quality improvements and broader social development initiatives to sustainably improve health outcomes.
Prioritisation by FIT to mitigate the impact of delays in the 2-week wait colorectal cancer referral pathway during the COVID-19 pandemic: a UK modelling study
Authors: Loveday Chey , Sud Amit , Jones Michael E , Broggio John , Scott Stephen , Gronthound Firza , Torr Beth , Garrett Alice , Nicol David L , Jhanji Shaman , Boyce Stephen A , Williams Matthew , Barry Claire , Riboli Elio , Kipps Emma , McFerran Ethna , Muller David C , Lyratzopoulos Georgios , Lawler Mark , Abulafi Muti , Houlston Richard S , Turnbull Clare 
Published: August 2020

ObjectiveTo evaluate the impact of faecal immunochemical testing (FIT) prioritisation to mitigate the impact of delays in the colorectal cancer (CRC) urgent diagnostic (2-week-wait (2WW)) pathway consequent from the COVID-19 pandemic.DesignWe modelled the reduction in CRC survival and life years lost resultant from per-patient delays of 2–6 months in the 2WW pathway. We stratified by age group, individual-level benefit in CRC survival versus age-specific nosocomial COVID-19–related fatality per referred patient undergoing colonoscopy. We modelled mitigation strategies using thresholds of FIT triage of 2, 10 and 150 µg Hb/g to prioritise 2WW referrals for colonoscopy. To construct the underlying models, we employed 10-year net CRC survival for England 2008–2017, 2WW pathway CRC case and referral volumes and per-day-delay HRs generated from observational studies of diagnosis-to-treatment interval.ResultsDelay of 2/4/6 months across all 11 266 patients with CRC diagnosed per typical year via the 2WW pathway were estimated to result in 653/1419/2250 attributable deaths and loss of 9214/20 315/32 799 life years. Risk–benefit from urgent investigatory referral is particularly sensitive to nosocomial COVID-19 rates for patients aged >60. Prioritisation out of delay for the 18% of symptomatic referrals with FIT >10 µg Hb/g would avoid 89% of these deaths attributable to presentational/diagnostic delay while reducing immediate requirement for colonoscopy by >80%.ConclusionsDelays in the pathway to CRC diagnosis and treatment have potential to cause significant mortality and loss of life years. FIT triage of symptomatic patients in primary care could streamline access to colonoscopy, reduce delays for true-positive CRC cases and reduce nosocomial COVID-19 mortality in older true-negative 2WW referrals. However, this strategy offers benefit only in short-term rationalisation of limited endoscopy services: the appreciable false-negative rate of FIT in symptomatic patients means most colonoscopies will still be required.
Combination therapy with T cell engager and PD-L1 blockade enhances the antitumor potency of T cells as predicted by a QSP model
Authors: Ma Huilin , Wang Hanwen , Sové Richard J , Wang Jun , Giragossian Craig , Popel Aleksander S 
Published: August 2020

BackgroundT cells have been recognized as core effectors for cancer immunotherapy. How to restore the anti-tumor ability of suppressed T cells or improve the lethality of cytotoxic T cells has become the main focus in immunotherapy. Bispecific antibodies, especially bispecific T cell engagers (TCEs), have shown their unique ability to enhance the patient’s immune response to tumors by stimulating T cell activation and cytokine production in an MHC-independent manner. Antibodies targeting the checkpoint inhibitory molecules such as programmed cell death protein 1 (PD-1), PD-ligand 1 (PD-L1) and cytotoxic lymphocyte activated antigen 4 are able to restore the cytotoxic effect of immune suppressed T cells and have also shown durable responses in patients with malignancies. However, both types have their own limitations in treating certain cancers. Preclinical and clinical results have emphasized the potential of combining these two antibodies to improve tumor response and patients’ survival. However, the selection and evaluation of combination partners clinically is a costly endeavor. In addition, despite advances made in immunotherapy, there are subsets of patients who are non-responders, and reliable biomarkers for different immunotherapies are urgently needed to improve the ability to prospectively predict patients’ response and improve clinical study design. Therefore, mathematical and computational models are essential to optimize patient benefit, and guide combination approaches with lower cost and in a faster manner.MethodIn this study, we continued to extend the quantitative systems pharmacology (QSP) model we developed for a bispecific TCE to explore efficacy of combination therapy with an anti-PD-L1 monoclonal antibody in patients with colorectal cancer.ResultsPatient-specific response to TCE monotherapy, anti-PD-L1 monotherapy and the combination therapy were predicted using this model according to each patient’s individual characteristics.ConclusionsIndividual biomarkers for TCE monotherapy, anti-PD-L1 monotherapy and their combination have been determined based on the QSP model. Best treatment options for specific patients could be suggested based on their own characteristics to improve clinical trial efficiency. The model can be further used to assess plausible combination strategies for different TCEs and immune checkpoint inhibitors in different types of cancer.
Contrast-induced encephalopathy: a complication of coronary angiography
Authors: Fernando Tharanga Geethapriya , Nandasiri Shanika , Mendis Sepalika , Senanayake Sunethra , Gooneratne Inuka Kishara , Navinan Rayno , Kadiragamanathan Ambiga , Wickramasinghe Sumudu , Herath Tharuka , Thambirajah Narmathey , Markus Romesh 
Published: August 2020

Contrast-induced encephalopathy is a rare idiosyncratic reaction to contrast material. A 56-year-old woman with hypertension developed a hemiparesis with confusion and disorientation 3 hours after routine coronary angiography. The procedure had been prolonged, and during it she had received 130 mL of iopromide contrast. A metabolic screen was negative, and cerebral angiography and MR scan of brain were normal. She recovered completely by day 5. Contrast-induced encephalopathy should be considered in patients developing focal neurological deficits following coronary angiography. Patients requiring investigations to exclude acute stroke in this setting should not receive additional intravenous or intra-arterial contrast, although MR with gadolinium appears safe. Better awareness of this complication should avoid potentially harmful interventions such as thrombolysis.
Perturbative string theory from Newtonian limit of string geometry theory
Authors: Sato Matsuo , Sugimoto Yuji 
Published: August 2020

AbstractString geometry theory is one of the candidates of the non-perturbative formulation of string theory. In Sato (Int J Mod Phys A 34(23):1950126, 2019), the perturbative string theory is reproduced from a string geometry model coupled with a u(1) gauge field on string manifolds. In this paper, we generalize this result and we show that the perturbative string theory is reproduced from any string geometry model by taking a Newtonian limit.