bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide whole-blood transcriptome profiling across inherited bone marrow failure subtypes
Authors: Walne Amanda J. , Vulliamy Tom , Bewicke-Copley Findlay , Wang Jun , Alnajar Jenna , Bridger Maria G. , Ma Bernard , Tummala Hemanth , Dokal Inderjeet 
Published: October 2021

Abstract
Gene expression profiling has long been used in understanding the contribution of genes and related pathways in disease pathogenesis and susceptibility. We have performed whole-blood transcriptomic profiling in a subset of patients with inherited bone marrow failure (IBMF) whose diseases are clinically and genetically characterized as Fanconi anemia (FA), Shwachman-Diamond syndrome (SDS), and dyskeratosis congenita (DC). We hypothesized that annotating whole-blood transcripts genome wide will aid in understanding the complexity of gene regulation across these IBMF subtypes. Initial analysis of these blood-derived transcriptomes revealed significant skewing toward upregulated genes in patients with FA when compared with controls. Patients with SDS or DC also showed similar skewing profiles in their transcriptional status revealing a common pattern across these different IBMF subtypes. Gene set enrichment analysis revealed shared pathways involved in protein translation and elongation (ribosome constituents), RNA metabolism (nonsense-mediated decay), and mitochondrial function (electron transport chain). We further identified a discovery set of 26 upregulated genes at stringent cutoff (false discovery rate &lt; 0.05) that appeared as a unified signature across the IBMF subtypes. Subsequent transcriptomic analysis on genetically uncharacterized patients with BMF revealed a striking overlap of genes, including 22 from the discovery set, which indicates a unified transcriptional drive across the classic (FA, SDS, and DC) and uncharacterized BMF subtypes. This study has relevance in disease pathogenesis, for example, in explaining the features (including the BMF) common to all patients with IBMF and suggests harnessing this transcriptional signature for patient benefit.
Asparaginase enzyme activity levels and toxicity in childhood acute lymphoblastic leukemia: a NOPHO ALL2008 study
Authors: Lynggaard Line Stensig , Rank Cecilie Utke , Hansen Stefan Nygaard , Gottschalk Højfeldt Sofie , Henriksen Louise Tram , Jarvis Kirsten Brunsvig , Ranta Susanna , Niinimäki Riitta , Harila-Saari Arja , Wolthers Benjamin O , Frandsen Thomas L. , Heyman Mats , Schmiegelow Kjeld , Albertsen Birgitte Klug 
Published: October 2021

Abstract
Asparaginase treatment is a mainstay in contemporary treatment of acute lymphoblastic leukemia (ALL), but substantial asparaginase-related toxicity may lead to jeopardized protocol compliance and compromises survival. We investigated the association between risk of asparaginase-associated toxicities (AspTox) and asparaginase enzyme activity (AEA) levels in 1155 children aged 1.0 to 17.9 years, diagnosed with ALL between July 2008 and March 2016, and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. Patients with ≥2 blood samples for AEA measurement drawn 14 ± 2 days after asparaginase administration were included (6944 trough values). AEA was measurable (or &gt;0 IU/L) in 955 patients, whereas 200 patients (17.3%) had asparaginase inactivation and few AspTox recorded. A time-dependent multiple Cox model of time to any first asparaginase-associated toxicity adjusted for sex and age was used. For patients with measurable AEA, we found a hazard ratio (HR) of 1.17 per 100 IU/L increase in median AEA (95% confidence interval [CI], 0.98-1.41; P = .09). For pancreatitis, thromboembolism, and osteonecrosis, the HRs were 1.40 (95% CI, 1.12-1.75; P = .002), 0.99 (95% CI, 0.70-1.40; P = .96), and 1.36 (95% CI, 1.04-1.77; P = .02) per 100 IU/L increase in median AEA, respectively. No significant decrease in the risk of leukemic relapse was found: HR 0.88 per 100 IU/L increase in AEA (95% CI, 0.66-1.16; P = .35). In conclusion, these results emphasize that overall AspTox and relapse are not associated with AEA levels, yet the risk of pancreatitis and osteonecrosis increases with increasing AEA levels.
Inactivated Pseudomonas PE(ΔIII) exotoxin fused to neutralizing epitopes of PEDV S proteins produces a specific immune response in mice
Authors: Sun Leqiang , Tang Yajie , Yan Keji , Chen Huanchun , Zhang Huawei 
Published: October 2021

AbstractPorcine epidemic diarrhea (PED) caused by the porcine epidemic diarrhea virus (PEDV), is a severe infectious and devastating swine disease that leads to serious economic losses in the swine industry worldwide. An increased number of PED cases caused by variant PEDV have been reported in many countries since 2010. S protein is the main immunogenic protein containing some B-cell epitopes that can induce neutralizing antibodies of PEDV. In this study, the construction, expression and purification of Pseudomonas aeruginosa exotoxin A (PE) without domain III (PEΔIII) as a vector was performed for the delivery of PEDV S-A or S-B. PE(ΔIII) PEDV S-A and PE(ΔIII) PEDV S-B recombinant proteins were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis. The immunogenicity of PEDV S-A and PEDV S-B subunit vaccines were evaluated in mice. The results showed that PEDV-S-B vaccine could not only induce specific humoral and Th1 type-dominant cellular immune responses, but also stimulate PEDV-specific mucosal immune responses in mice. PEDV-S-B subunit vaccine is a novel candidate mucosal vaccine against PEDV infection.
Passive case detection for canine visceral leishmaniasis control in urban Brazil: Determinants of population uptake
Authors: Luz João Gabriel G. , Carvalho Amanda G. de , Dias João Victor L. , Marciano Luis Claudio L. , Vlas Sake J. de , Fontes Cor Jesus F. , Coffeng Luc E. 
Published: October 2021

Background
In Brazil, the transmission of Leishmania infantum in urban settings is closely related to infection among dogs, with occasional transmission to humans. Serological screening of dogs for Leishmania spp. infection on requests of their owners (passive case detection) represents a frequent, but little studied, practice within the scope of Brazilian public health. This study identified factors associated with canine visceral leishmaniasis (CVL) diagnosis-seeking behavior of dog owners in Rondonópolis (236,000 inhabitants), a municipality in Central-Western Brazil where VL is endemic. Also, we evaluated the profile of dog owners and their animals screened on free demand.

Methodology/Principal findings
Using mixed effects negative binomial regression, we modelled the number of dogs screened for Leishmania infection on free demand per neighborhood from 2011 to 2016 as a function of time-dependent predictors (current or recent canine seropositivity and human VL incidence), distance to the screening site, and demographic variables. We assessed potential delays in the effect of time-dependent predictors on the outcome. Among 12,536 dogs screened for Leishmania infection, 64.2% were tested during serosurveys and 35.8% were tested on free demand. Of these, 63.9% were positive. Uptake of screening under free demand was strongly associated with higher levels of canine seropositivity in the neighborhood (current or recent) and decreasing distance to the screening site. A subsample of dog owners (n = 93) who sought CVL screening between 2016 and 2017 were interviewed in more detail. Owners with better socioeconomic status and dogs with apparent CVL clinical manifestations prevailed among them.

Conclusions/Significance
To support timely CVL management, passive case detection along with awareness activities aimed at dog owners should be encouraged in endemic areas. Screening sites should be prioritized in accessible zones, as well as in socio-economically disadvantage areas. In parallel, CVL active case detection should be continued as a surveillance tool to guide control actions.
Health effects of immediate telework introduction during the COVID-19 era in Japan: A cross-sectional study
Authors: Niu Qian , Nagata Tomohisa , Fukutani Naoto , Tezuka Masato , Shimoura Kanako , Nagai-Tanima Momoko , Aoyama Tomoki 
Published: October 2021

Background
Telework has been widely discussed in several fields; however, there is a lack of research on the health aspects of teleworking. The current study was conducted to determine the health effects of teleworking during an emergency statement as evidence for future policy development.

Method
This was a cross-sectional study in which we administered an online questionnaire to 5,214 general workers (response rate = 36.4%) from June 2020 to August 2020. Based on working methods during the pandemic, workers were categorized into the office group (n = 86) and telework group (n = 1597), and we characterized their demographics, changes in lifestyle, telework status, physical symptoms, and mental health.

Results
The results showed that the workers’ residence, marital status, management positions, and employee status affected the choice of the work method. During the emergency, teleworkers experienced more changes in their habits than office workers. In terms of exercise habits, 67.0% of the individuals belonging to the office-telework (OT) group exercised less. Approximately half of the teleworkers were satisfied with their telework, and those in the OT group were less satisfied with their telework than those in the telework-telework (TT) group, and they reported an increase in both working hours and meeting hours. Work-family conflict was more pronounced in the TT group than in the two other groups. Only 13.2% of individuals did not experience any stress in the past 30 days, and all three groups showed varying degrees of anxiety and depressive tendencies. In addition, all teleworkers experienced adverse physical symptoms before and after the emergency.

Conclusion
Health issues associated with teleworking should be given adequate attention.
Binocular treatment for amblyopia: A meta-analysis of randomized clinical trials
Authors: Roda Matilde , Pellegrini Marco , Di Geronimo Natalie , Vagge Aldo , Fresina Michela , Schiavi Costantino 
Published: October 2021

Background
To date, there is still no consensus regarding the effect of binocular treatment for amblyopia. The purpose of this systematic review and meta-analysis was to summarize the available evidence to determine whether binocular treatment is more effective than patching in children with amblyopia.

Methods
Four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials) were searched for studies that compared binocular treatment and patching in children with amblyopia. The outcome measures were visual acuity and stereopsis. Pooled effects sizes were calculated with a random-effect model. The standardized difference in means (SDM) with 95% confidence intervals (CI) was calculated. Sensitivity analysis and assessment of publication bias were performed.

Results
Five randomized clinical trials were included. No significant difference in visual acuity between patients treated with binocular treatment and patching was observed (SDM = -0.12; 95% CI: -0.45–0.20; P = 0.464). No significant difference in stereopsis between patients treated with binocular treatment and patching was observed (SDM = -0.07; 95% CI: -0.61–0.48; P = 0.809). For both variables, the between-study heterogeneity was high (respectively, I2 = 61% and I2 = 57%).

Conclusions
This meta-analysis found no convincing evidence supporting the efficacy of binocular treatment as an alternative to conventional patching. Therefore, the binocular treatment cannot fully replace traditional treatment but, to date, it can be considered a valid complementary therapy in peculiar cases. Further studies are required to determine whether more engaging therapies and new treatment protocols are more effective.
Prevalence and predictors of depression, anxiety, and stress among adults in Ghana: A community-based cross-sectional study
Authors: Amu Hubert , Osei Eric , Kofie Philip , Owusu Richard , Bosoka Samuel Adolf , Konlan Kennedy Diema , Kim Eunji , Orish Verner Ndudiri , Maalman Raymond Saa-Eru , Manu Emmanuel , Parbey Phyllis Atta , Saah Farrukh Ishaque , Mumuni Hadiru , Appiah Prince Kubi , Komesuor Joyce , Ayanore Martin Amogre , Amenuvegbe Gregory Kofi , Kim Siwoo , Jung Hajun , Adjuik Martin , Tarkang Elvis Enowbeyang , Alhassan Robert Kaba , Donkor Ernestina Safoa , Zottor Francis Bruno , Kweku Margaret , Amuna Paul , Kim So Yoo , Gyapong John Owusu 
Published: October 2021

Introduction
Over the past two decades, there have been several global interventions including the Sustainable Development Goals (SDGs), aimed at improving health outcomes. Despite efforts by countries to achieve the SDG targets, mental health challenges remain major public health concerns globally. We examined the prevalence and predictors of depression, anxiety, and stress as well as the comorbidities of these mental health issues among adults.

Materials and methods
This was a community-based cross-sectional study conducted among 2456 adults in four districts of the Volta Region of Ghana using data from the UHAS-Yonsei University Partnership Project. We analysed the data using frequency, percentage, mean, standard deviation, correlation, and binary logistic regression.

Results
Overall, 51.8% of the participants had at least one of the mental health issues examined. The prevalence of a mental health issue was 25.2%, 53.3%, and 9.7% for depression, anxiety, and stress respectively. Participants constituting 8.3% experienced all three mental health issues as comorbidities. Participants’ level of formal education and income significantly predicted depression, anxiety, and stress respectively at the multivariable level. Adults with a tertiary level of education were, for instance, 68% (AOR = 0.32, 95%CI = 0.15–0.66), 65% (AOR = 0.35, 95%CI = 0.17–0.73), and 50% (AOR = 0.50, 95%CI = 0.33–0.76) less likely to experience depression, anxiety, and stress, respectively compared with those who had no formal education.

Conclusion
The majority of our study participants either experienced depression, anxiety, or stress. There were quite high comorbidities of the mental health issues among the adult population. To accelerate progress towards the achievement of SDG 3.4 target of promoting mental health and wellbeing for all by the year 2030, there is a need for effective implementation of the country’s 2012 Mental Health Act which makes provisions for the establishment of a Mental Health Fund. This could improve the financial circumstances of indigenes as income has been realised in the present study as an important factor influencing depression, anxiety, and stress among the adult population.
Aggression on the psychiatric ward: Prevalence and risk factors. A systematic review of the literature
Authors: Weltens Irene , Bak Maarten , Verhagen Simone , Vandenberk Emma , Domen Patrick , van Amelsvoort Thérèse , Drukker Marjan 
Published: October 2021

Introduction
On psychiatric wards, aggressive behaviour displayed by patients is common and problematic. Understanding factors associated with the development of aggression offers possibilities for prevention and targeted interventions. This review discusses factors that contribute to the development of aggression on psychiatric wards.

Method
In Pubmed and Embase, a search was performed aimed at: prevalence data, ward characteristics, patient and staff factors that are associated with aggressive behaviour and from this search 146 studies were included.

Results
The prevalence of aggressive behaviour on psychiatric wards varied (8–76%). Explanatory factors of aggressive behaviour were subdivided into patient, staff and ward factors. Patient risk factors were diagnosis of psychotic disorder or bipolar disorder, substance abuse, a history of aggression, younger age. Staff risk factors included male gender, unqualified or temporary staff, job strain, dissatisfaction with the job or management, burn-out and quality of the interaction between patients and staff. Staff protective factors were a good functioning team, good leadership and being involved in treatment decisions. Significant ward risk factors were a higher bed occupancy, busy places on the ward, walking rounds, an unsafe environment, a restrictive environment, lack of structure in the day, smoking and lack of privacy.

Conclusion
Despite a lack of prospective quantitative data, results did show that aggression arises from a combination of patient factors, staff factors and ward factors. Patient factors were studied most often, however, besides treatment, offering the least possibilities in prevention of aggression development. Future studies should focus more on the earlier stages of aggression such as agitation and on factors that are better suited for preventing aggression such as ward and staff factors. Management and clinicians could adapt staffing and ward in line with these results.
Prediction of recurrent stroke among ischemic stroke patients with atrial fibrillation: Development and validation of a risk score model
Authors: Kim Beom Joon , Lee Keon-Joo , Park Eun Lyeong , Tanaka Kanta , Koga Masatoshi , Yoshimura Sohei , Itabashi Ryo , Cha Jae-Kwan , Lee Byung-Chul , Akiyama Hisanao , Nagakane Yoshinari , Lee Juneyoung , Toyoda Kazunori ,   for the SAMURAI Study Investigators, Bae Hee-Joon ,   for the CRCS-K Investigators
Published: October 2021

Background
There is currently no validated risk prediction model for recurrent events among patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). Considering that the application of conventional risk scores has contextual limitations, new strategies are needed to develop such a model. Here, we set out to develop and validate a comprehensive risk prediction model for stroke recurrence in AIS patients with AF.

Methods
AIS patients with AF were collected from multicenter registries in South Korea and Japan. A developmental dataset was constructed with 5648 registered cases from both countries for the period 2011‒2014. An external validation dataset was also created, consisting of Korean AIS subjects with AF registered between 2015 and 2018. Event outcomes were collected during 1 year after the index stroke. A multivariable prediction model was developed using the Fine–Gray subdistribution hazard model with non-stroke mortality as a competing risk. The model incorporated 21 clinical variables and was further validated, calibrated, and revised using the external validation dataset.

Results
The developmental dataset consisted of 4483 Korean and 1165 Japanese patients (mean age, 74.3 ± 10.2 years; male 53%); 338 patients (6%) had recurrent stroke and 903 (16%) died. The clinical profiles of the external validation set (n = 3668) were comparable to those of the developmental dataset. The c-statistics of the final model was 0.68 (95% confidence interval, 0.66 ‒0.71). The developed prediction model did not show better discriminative ability for predicting stroke recurrence than the conventional risk prediction tools (CHADS2, CHA2DS2-VASc, and ATRIA).

Conclusions
Neither conventional risk stratification tools nor our newly developed comprehensive prediction model using available clinical factors seemed to be suitable for identifying patients at high risk of recurrent ischemic stroke among AIS patients with AF in this modern direct oral anticoagulant era. Detailed individual information, including imaging, may be warranted to build a more robust and precise risk prediction model for stroke survivors with AF.
Parathyroid hormone in Sri Lankan pregnant women: Vitamin D and other determinants
Authors: Kaneshapillai Anusha , Hettiaratchi Usha , Prathapan Shamini , Liyanage Guwani 
Published: October 2021

Introduction
Determinants of parathyroid hormone level during pregnancy have been less frequently studied. We aimed to describe the serum parathyroid hormone (PTH) and its determinants in Sri Lankan pregnant women in a community setting.

Materials and methods
In this cross-sectional analysis, 390 pregnant mothers in their third trimester were enrolled from primary care centers of 15 health divisions in the Colombo District in Sri Lanka. Venous blood was analyzed for a total 25-hydroxyvitamin-D [25(OH)D], serum parathyroid hormone (PTH), serum calcium, and alkaline phosphatase. The bone quality was assessed in terms of speed of sound (SOS) using the quantitative ultrasound scan (QUS). Univariate and multivariate regression analysis was used to examine the determinants of PTH concentration in blood.

Results
Median serum 25(OH)D was 17.5ng/mL. Most (61.6%) were vitamin D deficient (<20ng/mL). Median PTH was 23.7pg/mL. Only 0.8% had hyperparathyroidism (PTH >65pg/mL). The correlation between 25(OH)D and PTH was weak but significant (r = -0.197; p<0.001). SOS Z-score was below the cut-off (≤−2) in fifty-six women (14.7%), and SOS did not relate significantly to PTH. In regression analysis, serum 25(OH)D, serum calcium, body mass index, educational level, and weeks of pregnancy were significant independent variables when adjusted. The model explained 16% of the variation in the PTH level.

Conclusions
A high prevalence of vitamin D deficiency was observed among Sri Lankan pregnant women in the present study. Serum 25(OH)D, calcium, weeks of pregnancy, and educational level were determinants of serum PTH.
Detailing the epidemiological and clinical characteristics of chronic lymphocytic leukaemia in Portugal—Results from a population-based cancer registry cohort study
Authors: Cardoso Borges Fábio , Ramos Adriana , Lourenço António , Gomes da Silva Maria , Miranda Ana ,   on behalf of the ROR-Sul network
Published: October 2021

Background
Chronic lymphocytic leukaemia (CLL) is the most common leukaemia among adults in western countries. Considering the increasing incidence and prevalence of this condition, it is highly relevant to better characterise these patients in Portugal, where data is still scarce.

Methods
To determine incidence, clinical presentation, survival and second malignancies, a population-based historical cohort study was conducted. Cases of interest were identified through the South Region Cancer Registry database and additional data sources. Patients aged ≥18 years, with a confirmed diagnosis of CLL or small lymphocytic lymphoma between January 1st, 2013 and December 31st, 2014 were included. Patients were followed‐up until death or cut-off date (December 31st, 2019).

Results
A total of 496 patients were included and median follow-up time was 5.46 years. Crude incidence rates were 5.03 and 5.22 per 100,000 inhabitants for 2013 and 2014, respectively, and age-adjusted incidence rates were 3.18:100,000 European population for 2013 and 3.35:100,000 European population for 2014. Median age at diagnosis was 71 years and the male/female ratio was 1.40. The majority of patients had leukemic presentation of the disease (86.09%), was diagnosed in Binet stage A (75.58%) and did not present B symptoms (84.01%), anaemia (haemoglobin ≤10g/dL; 90.63%) nor thrombocytopenia (platelet count ≤100 000/μL; 91.73%). Five-year overall survival (OS) rate was 70.53% (95%CI 66.31–74.34) and age, lactate dehydrogenase, Binet stage and a ≥5 Charlson comorbidity index score were independently associated with OS. Standardised-incidence ratios for any second malignancy and cutaneous squamous cell carcinoma were 1.59 (95%CI 1.19–2.08) and 10.15 (95%CI 6.28–15.51), respectively.

Conclusion
Incidence, clinical presentation and survival of CLL Portuguese patients are similar to those reported for other western countries. The increased risk of second malignancies raises concerns and needs adequate clinical watchfulness.