bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pooled analysis of all-cause and cause-specific mortality among Nordic military veterans following international deployment
Authors: Pethrus Carl-Martin , Vedtofte Mia Sadowa , Neovius Kristian , Borud Einar K , Neovius Martin 
Published: April 2022

ObjectivesTo investigate all-cause and cause-specific mortality risks, including deaths from external, cardiovascular and cancer causes, among deployed Nordic military veterans in comparison to the general population in each country.DesignPooled analysis.SettingDenmark, Norway, Finland and Sweden.ParticipantsMilitary veterans deployed between 1990 and 2010 were followed via nationwide registers and compared with age-sex-calendar-year-specific rates in the general population using pooled standardised mortality ratios (SMRs).Main outcomesAll-cause and cause-specific mortality retrieved from each country’s Causes of Death Register, including deaths from external, cardiovascular and cancer causes.ResultsAmong 83 584 veterans 1152 deaths occurred of which 343 were from external causes (including 203 suicides and 129 traffic/transport accidents), 134 from cardiovascular causes and 297 from neoplasms. Veterans had a lower risk of death from any cause (pooled SMR 0.58, 95% CI 0.52 to 0.64), external causes (0.71, 95% CI 0.64 to 0.79), suicide (0.77, 95% CI 0.67 to 0.89), cardiovascular causes (0.54, 95% CI 0.46 to 0.64) and neoplasms (0.78, 95% CI 0.70 to 0.88). There was no difference regarding traffic/transport accidents for the whole period (1.10, 95% CI 0.92 to 1.31) but the pooled point estimate was elevated, though not statistically significant, during the first 5 years (1.17, 95% CI 0.89 to 1.53) but not thereafter (1.01, 95% CI 0.77 to 1.34). For all other causes of death, except suicide, statistically significantly lower risk among veterans was observed both during the first 5 years and thereafter. For suicide, no difference was observed beyond 5 years. Judged from the country-specific SMR estimates, there was a high degree of consistency although statistically significant heterogeneity was found for all-cause mortality.ConclusionsNordic military veterans had lower overall and cause-specific mortality than the general population for most outcomes, as expected given the predeployment selection process. Though uncommon, fatal traffic/transport accidents were an exception with no difference between deployed military veterans and the general population.
Aneurysmal subarachnoid haemorrhage—cerebral vasospasm and prophylactic ibuprofen: a randomised controlled pilot trial protocol
Authors: Dayyani Mojtaba , Mousavi Mohammadi Ermia , Ashoorion Vahid , Sadeghirad Behnam , Javedani Yekta Mohammadreza , Grotta James C , Gonzalez Nestor R , Zabihyan Samira 
Published: April 2022

IntroductionCerebral vasospasm (CVS) is the leading cause of mortality and morbidity following aneurysmal subarachnoid haemorrhage (aSAH). One of the recently implicated underlying mechanisms of CVS is inflammatory cascades. Specific feasibility objectives include determining the ability to recruit 30 participants over 24 months while at least 75% of them comply with at least 75% of the study protocol and being able to follow 85% of them for 3 months after discharge.Methods and analysisThis is a feasibility study for a randomised controlled trial. Eligible participants are adult patients who are 18 years of age and older with an aSAH confirmed by a brain CT scan, and CT angiography, or magnetic resonance angiography, or digital subtraction angiography who admitted to the emergency department within 12 hours of the ictus. Eligible subjects will be randomised 1:1 for the administration of either ibuprofen or a placebo, while both groups will concomitantly be treated by the standard of care for 2 weeks. Care givers, patients, outcome assessors and data analysts will be blinded. This will be the first study to investigate the preventive effects of a short-acting non-steroidal anti-inflammatory drug on CVS and the key expected outcome of this pilot study is the feasibility and safety assessment of the administration of ibuprofen in patients with aSAH. The objectives of the definitive trial would be to assess the effect of ibuprofen relative to placebo on mortality, CVS, delayed cerebral ischaemia, and level of disability at 3-month follow-up.Ethics and disseminationThis study is approved by Mashhad University of Medical Sciences ethical committee (IR.MUMS.MEDICAL.REC.1398.225). Results from the study will be submitted for publication regardless of whether or not there are significant findings.Trial registration numberISRCTN14611625.
MYCNamplification and International Neuroblastoma Risk Group stratification on fine-needle aspiration biopsy and their correlation to survival in neuroblastoma
Authors: Bhardwaj Neha , Rohilla Manish , Trehan Amita , Bansal Deepak , Kakkar Nandita , Srinivasan Radhika 
Published: April 2022

AimsRisk stratification as per the International Neuroblastoma Risk Group (INRG) stratification is important for management of neuroblastoma. INRG incorporates various parameters including histological category as per the International Neuroblastoma Pathology Classification (INPC) andMYCNamplification, which were evaluated in fine needle aspiration biopsy (FNAB) samples of neuroblastoma patients to ascertain their impact in our population.MethodsThis was a retrospective study including 60 neuroblastoma cases diagnosed on FNAB, staged and stratified by INRG. Mitosis Karyorrhexis Index (MKI), INPC morphological category andMYCNstatus by fluorescence in situ hybridisation (n=46) were evaluated and correlated to outcome.ResultsThe mean age was 29 months (21 days to 9 years) with 27 and 33 children </≥18 months; male: female ratio of 1.6: 1; INRG stage-30(M), 20(L2), 2(L1) and 2(MS); INRG-36 high-risk, 13 intermediate-risk and 11 low-risk categories, respectively. MKI was high, intermediate and low in 39, 4 and 7 cases, respectively. INPC morphological type included 2 ganglioneuroblastomas and 58 neuroblastomas, graded further as 25 undifferentiated and 33 poorly differentiated tumours.MYCNwas amplified in 48% (22/46) cases and correlated with undifferentiated morphology (p=0.01). At a mean follow-up of 469 (7-835) days, 22/50 were disease free and 28/50 had relapsed/died. The overall survival correlated with age (p=0.03), stage (p=0.01), INRG group (p=0.0001) and tumour grade (p=0.036).MYCNstatus independently did not correlate with age (p=0.5), INRG stage (p=0.2) and overall survival (p=0.4).ConclusionFNAB is a complete modality for diagnosing neuroblastoma and providing all information required for risk stratification as per INRG including MKI,MYCNamplification, INPC category. Our cohort with predominant high-risk neuroblastoma cases highlights regional variation.
Flow control in the middle cerebral artery during thrombectomy: the effect of anatomy, catheter size and tip location
Authors: Neidlin Michael , Yousefian Ehsan , Luisi Claudio , Sichtermann Thorsten , Minkenberg Jan , Hasan Dimah , Ridwan Hani , Steinseifer Ulrich , Wiesmann Martin , Nikoubashman Omid 
Published: April 2022

BackgroundCatheter size, location and circle of Willis anatomy impact the flow conditions during interventional stroke therapy. The aim of the study was to systematically investigate the influence of these factors on flow control in the middle cerebral artery by means of a computational model based on 100 patients with stroke who received endovascular treatment.MethodsThe dimensions of the cervical and intracranial cerebral arteries of 100 patients who received endovascular mechanical thrombectomy for acute ischemic stroke were measured and a three-dimensional model of the circle of Willis was created based on these data. Flow control in the middle cerebral artery with variations in catheter size, catheter location and configurations of collateral vessels was determined using a computational model. A total of 48 scenarios were analyzed.ResultsFlow reversal with a distal aspiration catheter alone was not possible in the internal carotid artery and only sometimes possible in the middle cerebral artery (14 of 48 cases). The Catalyst 7 catheter was more often successful in achieving flow reversal than Catalyst 5 or 6 catheters (p<0.001). In a full circle of Willis anatomy, flow reversal was almost never possible. The absence of one or more communicating arteries significantly influenced flow direction compared with the full anatomy with all communicating arteries present (p=0.028).ConclusionChoosing the biggest possible aspiration catheter and locating it in the middle cerebral artery significantly increases the chances of successful flow control. Flow through the collaterals may impair the flow, and circle of Willis anatomy should be considered during aspiration thrombectomy.
An Estimation Approach to Optimize Energy Consumption in Wireless Sensor Network: A Health-Care Application
Authors: Hachicha Marwa , Halima Riadh Ben , Jemal Ahmed 
Published: April 2022

Wireless Sensor Network (WSN) is gaining popularity day by day in a large area of applications. However, the operation of WSN is facing a multitude of challenges, mainly in terms of energy consumption since WSN nodes operate with battery power and changing the batteries is a complicated task, as networks may include hundreds to thousands of nodes. In this context, it is very crucial to know the remaining energy value in the battery of the sensor node to take required actions before losing sensor’s function. Sending these measurements is very expensive in terms of energy and reduces the battery lifetime of the sensor and thus of the entire network. In this paper, we are interested in defining a probabilistic approach which aims to estimate these monitoring energy values and optimize energy consumption in WSN. Our approach is based on hidden Markov chains and includes two phases namely a learning phase and a prediction phase. Our approach is implemented as a web service. We illustrate our approach with a sensor-based health-care monitoring case study for COVID-19 patients. To evaluate our approach, we carry out experimentations based on the AvroraZ a simulator with a test for different types of applications and for different energy models: μAMPS-specific model, Mica2-specific model, and Mica2-specific model with actual measurements. These experimentations demonstrate the accuracy and efficiency of our approach. Our results show that periodic WSN applications i.e. applications which send monitoring data periodically, tested with the μAMPS-specific model perform an accuracy of 98.65%. In addition, our approach can perform a gain up to 75% of the battery charge of the sensor with an estimation of three-quarters of the remaining energy values. a https://www.redcad.org/members/benhalima/azem/ .
Influence of Bicarbonates and Salt on the Physicochemical and Sensory Properties of Meatloaf
Authors: Jaico Tracy , Prabhakar Himanshu , Adhikari Koushik , Singh Rakesh K. , Mohan Anand 
Published: April 2022

The changing consumer attitude toward meat products warrants innovation. Recent years have seen a continuous rise in the consumer demand for ready-to-eat meat products that trigger innovations in the manufacture of restructured meat products. This study was designed to develop meatloaf with the intention of using the downgraded stream of trimmed meat and meat by-products, which are known to contain a higher quantity of connecting tissue that causes tenderness issues, moisture retention, mouthfeel, and perceived food quality. The physicochemical effects of sodium bicarbonate, potassium bicarbonate, and salt alone or in combination on physicochemical and sensory characteristics of cooked ground beef were investigated. The results obtained showed that cooked ground beef without salt had the lowest cooked yield. Instrumental textural and sensory analysis revealed that bicarbonate-treated meatloaf samples exhibited significantly better sensory and textural properties than the control (

p

≤
0.05

). Internal cooked color data revealed that meatloaf treated with sodium bicarbonate and potassium bicarbonate had a pinkish-red appearance with a significantly higher a

∗

value (

p

≤
0.05

). The findings provide evidence that inclusion of bicarbonates had a significant tenderizing and juiciness effects with improved sensory attributes of the meatloaf. The evidence presented clearly shows the potential of bicarbonate and salt will exert synergistic effects and improve eating quality and textural and sensorial attributes of meatloaf and other meat products.
Mitochondrial Calcium Uniporter Drives Metastasis and Confers a Targetable Cystine Dependency in Pancreatic Cancer
Authors: Wang Xiuchao , Li Yunzhan , Li Zekun , Lin Shengchen , Wang Hongwei , Sun Jianwei , Lan Chungen , Wu Liangliang , Sun Dongxiao , Huang Chongbiao , Singh Pankaj K. , Hempel Nadine , Trebak Mohamed , DeNicola Gina M. , Hao Jihui , Yang Shengyu 
Published: April 2022

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease with few effective treatments. Here we show that the mitochondrial calcium uniporter (MCU) promotes PDAC cell migration, invasion, metastasis, and metabolic stress resistance by activating the Keap1-Nrf2 antioxidant program. The cystine transporter SLC7A11 was identified as a druggable target downstream of the MCU-Nrf2 axis. Paradoxically, despite the increased ability to uptake cystine, MCU-overexpressing PDAC demonstrated characteristics typical of cystine-deprived cells and were hypersensitive to cystine deprivation-induced ferroptosis. Pharmacologic inhibitors of SLC7A11 effectively induced tumor regression and abrogated MCU-driven metastasis in PDAC. In patient-derived organoid models in vitro and patient-derived xenograft models in vivo, MCU-high PDAC demonstrated increased sensitivity to SLC7A11 inhibition compared with MCU-low tumors. These data suggest that MCU is able to promote resistance to metabolic stress and to drive PDAC metastasis in a cystine-dependent manner. MCU-mediated cystine addiction could be exploited as a therapeutic vulnerability to inhibit PDAC tumor growth and to prevent metastasis.

Significance:
Elevated mitochondrial calcium uptake in PDAC promotes metastasis but exposes cystine addiction and ferroptosis sensitivity that could be targeted to improve pancreatic cancer treatment.
IFNα Potentiates Anti–PD-1 Efficacy by Remodeling Glucose Metabolism in the Hepatocellular Carcinoma Microenvironment
Authors: Hu Bo , Yu Mincheng , Ma Xiaolu , Sun Jialei , Liu Chenglong , Wang Chunyan , Wu Suiyi , Fu Peiyao , Yang Zhen , He Yungang , Zhu Yuanyuan , Huang Cheng , Yang Xinrong , Shi Yinghong , Qiu Shuangjian , Sun Huichuan , Zhu Andrew X. , Zhou Jian , Xu Yang , Zhu Di , Fan Jia 
Published: April 2022

AbstractThe overall response rate for anti–PD-1 therapy remains modest in hepatocellular carcinoma (HCC). We found that a combination of IFNα and anti–PD-1–based immunotherapy resulted in enhanced antitumor activity in patients with unresectable HCC. In both immunocompetent orthotopic and spontaneous HCC models, IFNα therapy synergized with anti–PD-1 and the combination treatment led to significant enrichment of cytotoxic CD27+CD8+ T cells. Mechanistically, IFNα suppressed HIF1α signaling by inhibiting FosB transcription in HCC cells, resulting in reduced glucose consumption capacity and consequentially establishing a high-glucose microenvironment that fostered transcription of the T-cell costimulatory molecule Cd27 via mTOR–FOXM1 signaling in infiltrating CD8+ T cells. Together, these data reveal that IFNα reprograms glucose metabolism within the HCC tumor microenvironment, thereby liberating T-cell cytotoxic capacities and potentiating the PD-1 blockade–induced immune response. Our findings suggest that IFNα and anti–PD-1 cotreatment is an effective novel combination strategy for patients with HCC.Significance:Our study supports a role of tumor glucose metabolism in IFNα-mediated antitumor immunity in HCC, and tumor-infiltrating CD27+CD8+ T cells may be a promising biomarker for stratifying patients for anti–PD-1 therapy.See related commentary by Kao et al., p. 1615.This article is highlighted in the In This Issue feature, p. 1599
Evaluation of Mangalarga Marchador foal development in the first year of life
Authors: Cunha Ligia Amaral , Sodré Ticiane d’El Rei Passos , Pereira Neto Evandro , Souza Vinicius Ricardo Cuña de , Hunka Monica Miranda , Manso Filho Hélio Cordeiro , Coelho Clarisse Simões 
Published: April 2022

The purpose of this study was to examine the development pattern of Mangalarga-Marchador foals by determination of muscle development and deposition of adipose tissue associated with the evaluation of blood-based biomarkers. Thus, 72 Mangalarga Marchador foals (ages ranged from 1-12 mo) were randomly selected and divided into 12 age groups (n=6 per group), evaluated monthly. The thickness of the Longissimus dorsi (LD) and rump fat (RF) were determined through an ultrasound performed on each foal’s left side. Such parameters were used to calculate the percentage of body fat (BF), fat mass (FM), and fat-free mass (FFM). Morphometric measurements were taken on the foal’s right side using a tape measure and a hypsometer. Blood samples were collected for determinations of total proteins, albumin, triglycerides, cholesterol, urea, creatinine, and glucose. Morphometric measurements, the thickness of the LD and RF, weight, BF, FM, and FFM showed differences between age groups (P<0.001). Muscle development and fat deposition in subcutaneous tissue were greater between six and 12 months and average weight gain and FFM were proportionally greater between one and six months. We concluded that morphometric measurements increase steadily and linearly during the first 12 months of life, indicating that it is feasible to use the linear regression formula. Moreover, significant differences between age and biochemical biomarkers may be attributed to nutritional and digestive physiology adaptations during these periods.
Evaluating the Coronary Artery Disease Consortium Model and the Coronary Artery Calcium Score in Predicting Obstructive Coronary Artery Disease in a Symptomatic Mixed Asian Cohort
Authors: Baskaran Lohendran , Neo Yu Pei , Lee Jing Kai , Yoon Yeonyee Elizabeth , Jiang Yilin , Al’Aref Subhi J. , van Rosendael Alexander R. , Han Donghee , Lin Fay Y. , Nakanishi Rine , Maurovich Horvat Pál , Tan Swee Yaw , Villines Todd C. , Bittencourt Marcio S. , Shaw Leslee J. 
Published: April 2022

Background
The utility of a given pretest probability score in predicting obstructive coronary artery disease (CAD) is population dependent. Previous studies investigating the additive value of coronary artery calcium (CAC) on pretest probability scores were predominantly limited to Western populations. This retrospective study seeks to evaluate the CAD Consortium (CAD2) model in a mixed Asian cohort within Singapore with stable chest pain and to evaluate the incremental value of CAC in predicting obstructive CAD.

Methods and Results

Patients who underwent cardiac computed tomography and had chest pain were included. The CAD2 clinical model comprised of age, sex, symptom typicality, diabetes, hypertension, hyperlipidemia, and smoking status and was compared with the CAD2 extended model that added CAC to assess the incremental value of CAC scoring, as well as to the corresponding locally calibrated local assessment of the heart models. A total of 522 patients were analyzed (mean age 54±11 years, 43.1% female). The CAD2 clinical model obtained an area under the curve of 0.718 (95% CI, 0.668–0.767). The inclusion of CAC score improved the area under the curve to 0.896 (95% CI, 0.867–0.925) in the CAD2 models and from 0.767 (95% CI, 0.721–0.814) to 0.926 (95% CI, 0.900–0.951) in the local assessment of the heart models. The locally calibrated local assessment of the heart models showed better discriminative performance than the corresponding CAD2 models (
P
<0.05 for all).

Conclusions
The CAD2 model was validated in a symptomatic mixed Asian cohort and local calibration further improved performance. CAC scoring provided significant incremental value in predicting obstructive CAD.
Contextualizing National Policies Regulating Access to Low‐Dose Aspirin in America and Europe Using the Full Report of a Transatlantic Patient Survey of Aspirin in Preventive Cardiology
Authors: Jacobsen Alan P. , Lim Zi Lun , Chang Blair , Lambeth Kaleb D. , Das Thomas M. , Gorry Colin , McCague Michael , Sharif Faisal , Mylotte Darren , Wijns William , Serruys Patrick W. J .C. , Blumenthal Roger S. , Martin Seth S. , McEvoy John W. 
Published: April 2022

Background
Aspirin is widely administered to prevent cardiovascular disease (CVD). However, appropriate use of aspirin depends on patient understanding of its risks, benefits, and indications, especially where aspirin is available over the counter (OTC).

Methods and Results

We did a survey of patient‐reported 10‐year cardiovascular risk; aspirin therapy status; form of aspirin access (OTC versus prescription); and knowledge of the risks, benefits, and role of aspirin in CVD prevention. Consecutive adults aged ≥50 years with ≥1 cardiovascular risk factor attending outpatient clinics in America and Europe were recruited. We also systematically reviewed national policies regulating access to low‐dose aspirin for CVD prevention. At each site, 150 responses were obtained (300 total). Mean±SD age was 65±10 years, 40% were women, and 41% were secondary prevention patients. More than half of the participants at both sites did not know (1) their own level of 10‐year CVD risk, (2) the expected magnitude of reduction in CVD risk with aspirin, or (3) aspirin’s bleeding risks. Only 62% of all participants reported that aspirin was routinely indicated for secondary prevention, whereas 47% believed it was routinely indicated for primary prevention (
P
=0.048). In America, 83.5% participants obtained aspirin OTC compared with 2.5% in Europe (
P
<0.001). Finally, our review of European national policies found only 2 countries where low‐dose aspirin was available OTC.

Conclusions
Many patients have poor insight into their objectively calculated 10‐year cardiovascular risk and do not know the risks, benefits, and role of aspirin in CVD prevention. Aspirin is mainly obtained OTC in America in contrast to Europe, where most countries restrict access to low‐dose aspirin.