bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early initiation of hydroxyurea (hydroxycarbamide) using individualised, pharmacokinetics‐guided dosing can produce sustained and nearly pancellular expression of fetal haemoglobin in children with sickle cell anaemia
Authors: Quinn Charles T. , Niss Omar , Dong Min , Pfeiffer Amanda , Korpik Jennifer , Reynaud Mary , Bonar Holly , Kalfa Theodosia A. , Smart Luke R. , Malik Punam , Ware Russell E. , Vinks Alexander A. , McGann Patrick T. 
Published: July 2021

SummaryHydroxyurea (hydroxycarbamide) is an effective treatment for sickle cell anaemia (SCA), but clinical responses depend primarily upon the degree of fetal haemoglobin (HbF) induction and the heterogeneity of HbF expression across erythrocytes. The number and characteristics of HbF‐containing cells (F‐cells) are not assessed by traditional HbF measurements. Conventional hydroxyurea dosing (e.g. fixed doses or low starting doses with stepwise escalation) produces a moderate heterocellular HbF induction, but haemolysis and clinical complications continue. Robust, pancellular HbF induction is needed to minimise or fully inhibit polymerisation of sickle haemoglobin. We treated children with hydroxyurea using an individualised, pharmacokinetics‐guided regimen starting at predicted maximum tolerated dose (MTD). We observed sustained HbF induction (mean >30%) for up to 6 years, which was not dependent on genetic determinants of HbF expression. Nearly 70% of patients had ≥80% F‐cells (near‐pancellular), and almost half had ≥90% F‐cells (pancellular). The mean HbF/F‐cell content was ~12 pg. Earlier age of initiation and better medication adherence were associated with high F‐cell responses. In summary, early initiation of hydroxyurea using pharmacokinetics‐guided starting doses at predicted MTD can achieve sustained near‐pancellular or pancellular HbF expression and should be considered an achievable goal for children with SCA treated with hydroxyurea at optimal doses.Clinical trial registration number: NCT02286154 (clinicaltrials.gov).
Long‐term home non‐invasive ventilation in chronic hypercapnic chronic obstructive pulmonary disease patients: Real‐world impact on lung function, acute exacerbations and survival
Authors: Freitas Cláudia , Serino Mariana , Araújo David , Pinto Tiago , Van Zeller Mafalda , Gonçalves Miguel , Drummond Marta 
Published: July 2021

AbstractIntroductionAlthough long‐term home non‐invasive ventilation (H‐NIV) has been used among chronic hypercapnic COPD patients, its clinical benefit is still on debate. We aim to assess the impact of H‐NIV in chronic hypercapnic COPD patients.MethodsCOPD patients who initiated H‐NIV between January 2010 and December 2017 were included. Patients with concomitant respiratory disorders were excluded. Acute exacerbation (AE) before and 2 years after H‐NIV initiation was assessed as main outcome. Secondary outcomes included lung function and gas exchange parameters. Survival since H‐NIV initiation was determined, and factors related with survival were explored.ResultsSeventy‐two patients were enrolled. A decrease in partial pressure of carbon dioxide (PaCO2) in arterial blood (p < 0.001) and an improvement of partial pressure of oxygen (PaO2) (p < 0.001) were achieved using a high‐intensity H‐NIV. Regarding lung function, residual volume (RV) reduced (p = 0.010) and forced‐expiratory volume in 1 s (FEV1) improved (p = 0.043) after H‐NIV initiation. No significant differences in 6‐min walking test (6MWT) were found. Compared with the year before H‐NIV initiation, the number of AE diminished in the first and in the second years of follow‐up (p < 0.001). The median survival was 79.0 months (95% confidence interval [CI], 52.9–105.1), and the covered distance in 6MWT predicted survival (hazard ratio [HR] = 0.026, p = 0.003) in the multivariate analysis.ConclusionsHigh‐intensity H‐NIV significantly improved FEV1 and hyperinflation, decreased frequency of AEs and led to a remarkable median survival, which was independently predicted by the walking distance in 6MWT.
A public and patient consultation process as an aid to design a person‐centred randomized clinical trial
Authors: Rix Jacqueline , Docherty Sharon , Breen Alexander C. , Sewell Philip , Branney Jonathan 
Published: July 2021

AbstractBackgroundInvolving patients and members of the public, together with researchers, in decisions about how studies are designed and conducted can create a study that is more person‐centred. The aim of this consultation process was to explore ways of designing a study which takes the person into consideration for the randomized clinical study entitled ‘Biomechanical Effects of Manual Therapy—A Feasibility Study’ using the novel approach of usability testing.DesignPatient and public volunteers were sought with experience of low back pain. Volunteers were invited to participate in usability testing (a physical walkthrough) of the proposed study method. This was followed by a discussion of areas where usability testing could not be used, such as recruitment strategies, continuity of participant care and dissemination of results. Resulting feedback was considered by the research team and alterations to the original study method were incorporated, provided the research questions could be answered and were practical within the resources available.ResultsAdditional recruitment strategies were proposed. Alterations to the study included reduction in study time burden; completion of study paperwork in a quieter location; continuity of participant care after the study; and methods of dissemination of overall study results to participants.ConclusionThe consultation process used the unique method of usability testing, together with a post‐usability discussion, and resulted in alterations to the future study which may facilitate making it more person‐centred.Patient and Public ContributionPatients and public developed the future study design but did not participate in manuscript preparation.
Understanding consumer’ switching intention toward traceable agricultural products: Push‐pull‐mooring perspective
Authors: Nguyen Thi Hong Nhung , Yeh Quey‐Jen , Huang Ching‐Ying 
Published: July 2021

AbstractFood traceability systems (FTSs) have been increasingly implemented in the food supply chain as a feasible solution to categorize the safety and quality of food. Governments across the world are striving to build public trust and to shift demand to traceable agricultural products (TAPs). This article stresses an important subject by focusing on consumer’ switching intention toward TAPs as product switching has a great impact on food producers and sellers. A total of 478 valid samples were collected from Taiwanese consumers via an online survey. By applying the Push‐Pull‐Mooring (PPM) model, the empirical results of PLS‐SEM analyses identified critical factors and their impacts on consumer switching intention: perceived risk uncertainty associated with non‐traceable food; perceived quality of TAP‐labeled food, willingness to pay a premium price, and health consciousness. Theoretically, this study sheds new light on the literature of migration studies, by examining consumer behavior toward FTSs, it is posited that the PPM theoretical model can predict switching decisions in the food sector. Practically, the findings suggested that FTS is a viable risk‐relieving strategy that should be utilized more heavily to boost consumer retention related to credible food options.
An Efficient Test for Homogeneity of Mean Directions on the Hyper‐sphere
Authors: Kulkarni Hemangi V. , SenGupta Ashis 
Published: July 2021

SummaryThe paper aims to develop a universally implementable efficient test for testing homogeneity of mean directions of several independent hyper‐spherical populations. Conventional tests are valid only under highly concentrated and/or large‐size groups. Focusing on the popular Langevin distribution on ad‐hyper‐sphere, the present work extends the very recent results for the circular case. The hurdle of the nuisance non‐location‐scale concentration parameterκis overcome through a variant of the integrated likelihood ratio test (ILRT), yielding a simple and elegant test statistic. Analytically, second‐order accurate asymptotic chi‐squared distribution of ILRT is established. Extensive simulation study demonstrates that ILRT uniformly outperforms its peers, notably under highly dispersed groups, which is precisely the target parametric region, and is robust under a large class of alternate distributions. Five real‐life data analyses from diverse disciplines, including the emerging field of vectorcardiography and a novel application to compositional data analysis in the context of drug development, illustrate applications of the findings.
Overreaction‐based momentum in the real estate investment trust market
Authors: Chen Tsung‐Yu , Huang Guan‐Ying , Wu Zhen‐Xing 
Published: July 2021

AbstractThis paper examines cross‐sectional return predictability in a real estate investment trust (REIT) market by using a continuing overreaction measure constructed based on the weighted average of signed volumes. We show that (a) trading strategies that involve buying REITs with an upward continuing overreaction and selling REITs with a downward continuing overreaction generate intermediate‐term momentum and long‐term return reversals; (b) the continuing overreaction measure provides superior predictive power in future REIT returns compared with the traditional predictor measured by past returns; and (c) overreaction‐based momentum is more pronounced when the market state continues in the same direction. Evidence from the REIT market provides direct support for the return prediction of the model based on investor overconfidence and biased self‐attribution rather than the model based on dividend growth theory.
Poverty on the rise: The impact of the COVID‐19 lockdown on the informal sector of Gweru, Zimbabwe
Authors: Dzawanda Beauty , Matsa Mark , Nicolau Melanie 
Published: July 2021

AbstractThe informal sector in Zimbabwe employs more than 80 per cent of the population, whose livelihood strategies are under severe threat because of the COVID‐19 lockdown. This paper examines the effects of the lockdown on the informal sector in Gweru. Anchored within the legalist theory of informality, the paper analyses the response of government to the plight of the informal sector in Zimbabwe. A qualitative research design was applied and convenience sampling implemented to select 30 individuals whose livelihood depended on informal cross‐border trade, informal transport, forex trading, hairdressing, and street vending. Results reveal that despite many involved in the informal sector having lost their means of survival during the COVID‐19 lockdown, the government introduced additional restrictions on this sector, thus almost destroying it. In the absence of government assistance, many have adapted their operations, albeit through illegal activities. The study offers recommendations that may ensure the survival of the informal sector beyond the COVID‐19 pandemic. This is important, given that the informal sector is the largest contributor to household income and food security in Zimbabwe.
Diabetic foot ulcer, the effect of resource‐poor environments on healing time and direct cost: A cohort study during Syrian crisis
Authors: Alsabek Mhd Belal , Abdul Aziz Abdul Razzak 
Published: July 2021

AbstractDiabetic foot ulcer (DFU) is one of the slowest healing wounds that hurt the human body. Many studies from developed countries are concerned about materials, procedures, and equipment that accelerate the healing time. In Sweden, the diabetic foot management costs around 24965$/patient. In this review, we would evaluate the healing time of DFUs during what is considered one of the worst humanitarian crisis of the 21st century. 1747 DFUs were studied from the main diabetic foot clinic in Damascus (2014‐2019). We predicted many variables that could prolong the healing time. The cost according to these variables was also reported. The SINBAD Classification was performed to grade the severity of ulcers. We noticed that the median healing time for DFUs was 8 weeks. Almost half of these ulcers healed between 3 and 12 weeks. The time of healing for men was significantly longer than that for women. While the presence of infection doubled the median time of healing, the presence of peripheral artery disease doubled the mean of the direct health care cost. The location of the ulcer acted as another independent risk factor. In conclusion, DFUs face many barriers to heal during a crisis.The environment with resource‐poor settings should be added to the traditional risk factors that delay the healing of DFUs for months or even years. More studies from disaster are as are needed to evaluate low‐cost materials that could be cost effective in applying standard care of the diabetic foot.
Effect of ultrasound intensity on the functional characteristics of rennet‐coagulated skim milk
Authors: Hammam Ahmed R. A. , Martinez‐Monteagudo Sergio I. , Metzger Lloyd E. , Alsaleem Khalid A. 
Published: July 2021

AbstractThe objective of this study was to examine the impact of ultrasound energy density (USED) on the functional properties of rennet‐coagulated skim milk. Skim pasteurized milk was ultrasonicated at 106 W and 375 W at two different times (3 and 9 min) to produce different USED levels (190.4, 570.7, 674.3, and 2016.9 J g−1). The rheological and textural properties of ultrasonicated milk samples were determined during the rennet coagulation as compared to nonsonicated skim milk. The rennet coagulation time was doubled when 674.3 J g−1 was applied to skim milk; however, applying 2016.9 J g−1 did not lead to milk coagulation. Additionally, gel firmness of rennet‐coagulated milk increased significantly from 80 g to 130 g when USED boosted from 190.4 to 674.3 J g−1. The coagulum strength and curd‐firming rate decreased significantly when USED elevated to 2016.9 J g−1. The outcome provides that using suitable USED could be utilized efficiently in the cheese industry to prolong the renneting time of milk.Practical ApplicationsThe ultrasound process can be applied to milk before making different dairy products, such as cheese or other dairy products that need rennet for coagulation to improve the characteristics of those products. Also, ultrasound can be utilized to fractionate dairy components to improve the functionality or yield of products.
CDE4 encodes a pentatricopeptide repeat protein involved in chloroplast RNA splicing and affects chloroplast development under low‐temperature conditions in rice
Authors: Liu Xinyong , Zhang Xichun , Cao Ruijie , Jiao Guiai , Hu Shikai , Shao Gaoneng , Sheng Zhonghua , Xie Lihong , Tang Shaoqing , Wei Xiangjin , Hu Peisong 
Published: July 2021

AbstractPentatricopeptide repeat (PPR) proteins play important roles in the post‐transcriptional modification of organellar RNAs in plants. However, the function of most PPR proteins remains unknown. Here, we characterized the rice (Oryza sativa L.) chlorophyll deficient 4 (cde4) mutant which exhibits an albino phenotype during early leaf development, with decreased chlorophyll contents and abnormal chloroplasts at low‐temperature (20°C). Positional cloning revealed that CDE4 encodes a P‐type PPR protein localized in chloroplasts. In the cde4 mutant, plastid‐encoded polymerase (PEP)‐dependent transcript levels were significantly reduced, but transcript levels of nuclear‐encoded genes were increased compared to wild‐type plants at 20°C. CDE4 directly binds to the transcripts of the chloroplast genes rpl2, ndhA, and ndhB. Intron splicing of these transcripts was defective in the cde4 mutant at 20°C, but was normal at 32°C. Moreover, CDE4 interacts with the guanylate kinase VIRESCENT 2 (V2); overexpression of V2 enhanced CDE4 protein stability, thereby rescuing the cde4 phenotype at 20°C. Our results suggest that CDE4 participates in plastid RNA splicing and plays an important role in rice chloroplast development under low‐temperature conditions.
Validation of a flash glucose monitoring system in outpatient diabetic cats
Authors: Shea Emily K. , Hess Rebecka S. 
Published: July 2021

AbstractBackgroundInterstitial glucose (IG) concentration measurement using a flash glucose monitoring system (FGMS) is a noninvasive, affordable, and informative method to regulate patients with diabetes mellitus (DM) but has not been fully validated in outpatient cats with DM.ObjectivesTo further validate the FreeStyle Libre FGMS in outpatient diabetic cats.AnimalsEight client‐owned cats with DM.MethodsProspective observational validation study. Tissue glue was used to attach the sensor to the cat. Lin's concordance correlation coefficient (ρc) was used to compare IG concentrations measured by the FGMS to blood glucose concentrations measured using an automated biochemistry analyzer (ABA) and point‐of‐care glucometer (POCG).ResultsData from 15 sensor placements in 8 cats were analyzed. Paired IG and ABA glucose concentrations (139 samples) had excellent correlation (ρc = 0.96) as did IG and POCG glucose concentrations (142 samples,ρc = 0.92). Sensor failure or displacement were recorded for 12/15 (80%) sensor placements. Median time of sensor activity was 7 days (range, 2‐13 days).Conclusions and Clinical ImportanceIn outpatient cats with DM, the FGMS‐measured IG concentration correlated well with ABA‐measured blood glucose concentration, but a high rate of sensor failures was observed.
High prevalence of celiac disease in autoimmune hepatitis: Systematic review and meta‐analysis
Authors: Haggård Linnea , Glimberg Ida , Lebwohl Benjamin , Sharma Rajani , Verna Elizabeth C. , Green Peter H. R. , Ludvigsson Jonas F. 
Published: July 2021

AbstractBackgroundPrevious studies investigating the prevalence of celiac disease (CD) in individuals with autoimmune hepatitis (AIH) have shown highly variable results. We therefore aimed to examine the prevalence of CD in individuals with AIH.MethodsTwo professional librarians searched PubMed, EMBASE, Cochrane and Web of Science Core Collection up until 7 February 2020. The search terms included ‘celiac disease’, ‘celiac’, ‘transglutaminases’, ‘gluten’, ‘gliadin’, ‘EMA’, ‘TTG’ and ‘villous’ combined with ‘autoimmune’, ‘hepatitis’, ‘ANA’, ‘SMA’ and ‘LKM’. This search yielded 2419 unique publications. A systematic review based on the PRISMA guidelines resulted in 31 articles eligible for full text review. Fifteen articles were deemed relevant, with 8 being included in our main analysis. A fixed‐effect inverse variance‐weighted model was used, and heterogeneity was calculated.ResultsOur main analysis included 567 individuals with AIH from eight studies, where biopsy‐verified CD (equivalent to Marsh III) was seen in 23 individuals (4.1%). The pooled prevalence of CD in AIH was 3.5% (95% CI = 1.6%‐5.3%) (heterogeneity: P = .874; I2 = 0.0%), which is clearly higher than the 1% CD seen in most general populations. When also including studies where CD had been diagnosed through positive serology without biopsy (15 studies: n = 1817 individuals with AIH), the pooled prevalence of CD was 2.9% (95% CI = 2.1%‐3.8%) (heterogeneity: P < .001; I2 = 66.8%).ConclusionOur results demonstrate a higher prevalence of CD in individuals with AIH compared to the general population. CD screening may be considered in patients with AIH.
The relationship between frailty and cirrhosis etiology: From the Functional Assessment in Liver Transplantation (FrAILT) Study
Authors: Xu Chelsea Q. , Mohamad Yara , Kappus Matthew R. , Boyarsky Brian , Ganger Daniel R. , Volk Michael L. , Rahimi Robert S. , Duarte‐Rojo Andres , McAdams‐DeMarco Mara , Segev Dorry L. , Ladner Daniela P. , Verna Elizabeth C. , Grab Joshua , Tincopa Monica , Dunn Michael A. , Lai Jennifer C. 
Published: July 2021

AbstractBackground & AimsCirrhosis leads to malnutrition and muscle wasting that manifests as frailty, which may be influenced by cirrhosis aetiology. We aimed to characterize the relationship between frailty and cirrhosis aetiology.MethodsIncluded were adults with cirrhosis listed for liver transplantation (LT) at 10 US centrer who underwent ambulatory testing with the Liver Frailty Index (LFI; ‘frail’ = LFI ≥ 4.4). We used logistic regression to associate aetiologies and frailty, and competing risk regression (LT as the competing risk) to determine associations with waitlist mortality (death/delisting for sickness).ResultsOf 1,623 patients, rates of frailty differed by aetiology: 22% in chronic hepatitis C, 31% in alcohol‐associated liver disease (ALD), 32% in non‐alcoholic fatty liver disease (NAFLD), 21% in autoimmune/cholestatic and 31% in ‘other’ (P < .001). In univariable logistic regression, ALD (OR 1.53, 95% CI 1.12‐2.09), NAFLD (OR 1.64, 95% CI 1.18‐2.29) and ‘other’ (OR 1.58, 95% CI 1.06‐2.36) were associated with frailty. In multivariable logistic regression, only ALD (OR 1.40; 95% 1.01‐1.94) and ‘other’ (OR 1.59; 95% 1.05‐2.40) remained associated with frailty. A total of 281 (17%) patients died/were delisted for sickness. In multivariable competing risk regression, LFI was associated with waitlist mortality (sHR 1.05, 95% CI 1.03‐1.06), but aetiology was not (P > .05 for each). No interaction between frailty and aetiology on the association with waitlist mortality was found (P > .05 for each interaction term).ConclusionsFrailty is more common in patients with ALD, NAFLD and ‘other’ aetiologies. However, frailty was associated with waitlist mortality independent of cirrhosis aetiology, supporting the applicability of frailty across all cirrhosis aetiologies.
Model analyses show how biodiversity conservation could reduce infectious diseases in an ecosystem
Authors: Duffy Kevin J. , Collins Obiora C. 
Published: July 2021

AbstractBiodiversity conservation benefits the sustainability of the environment and also the well‐being of humanity. Here we consider the possible importance of biodiversity of resources in limiting disease. With this aim we formulate a dynamical system model for a terrestrial ecosystem that takes into account, biodiversity of resources together with competition among species. The dynamics of the model are explored using appropriate dynamical system analyses. The effects of the competition terms and carrying capacity on the dynamics of the model are considered in terms of which ranges allow sustainability of the system. Simulations illustrate how biodiversity conservation can of itself lead to reduction in infectious diseases in an ecosystem.

The sustainability of the environment is generally improved by robust biodiversity and important for human welfare.
Diseases and their control are also important in natural and human systems.
Here we use models to establish to what extent natural resource biodiversity can reduce the extent of infected resources.
Our results show that biodiversity conservation is a possible control mechanism for reducing infectious diseases in an ecosystem.
These results can help natural resource manages concentrate time and money on biodiversity conservation over and above the already obvious need for such efforts.