bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the ability of multiple reanalysis datasets to simulate snow depth variability over mainland China from 1981 to 2018
Authors: Zhang Hongbo , Zhang Fan , Che Tao , Yan Wei , Ye Ming 
Published: October 2021

AbstractThough the use of reanalysis datasets to analyze snow changes is increasingly popular, the snow depth variability in China simulated by multiple reanalysis datasets has not been well evaluated. Also, the extent of regional snow depth variability and its driving mechanisms are still unknown. In this study, monthly snow depth observations from 325 stations during the period of 1981–2018 were taken to evaluate the ability of five reanalysis datasets (JRA55, MERRA2, GLDAS2, ERA5, and ERA5L) to simulate the spatial and temporal variability of snow depth in China. The evaluation results indicate that MERRA2 has the lowest root-mean-square deviation of snow depth and a high spatial correlation coefficient with observations. This may be partly related to the high accuracy of precipitation and temperature in MERRA2. Also, the 31 combinations of the five reanalysis datasets do not yield better accuracy in snow depth than MERRA2 alone. This is because the other four datasets have larger uncertainty. Based on MERRA2, four hotspot regions with significant snow depth changes from 1981–2018 were identified, including the central Xinjiang (XJ-C), the southern part of the Northeastern Plain and Mountain (NPM-S), and the southwestern (TP-SW) and southeastern (TP-SE) of the Tibetan Plateau. Snow depth changes mostly occurred in spring in TP-SW and winter in XJ-C, NPM-S, and TP-SE. The snow depth increase in XJ-C, NPM-S, and TP-SW is mainly caused by increased seasonal precipitation, while the snow depth decrease in TP-SE is attributed to the combined effects of decreased precipitation and warming temperature in winter.
Clinical significance of serum S100A10 in lung cancer
Authors: Hou Yu-Lei , Zhang Jian-Hong , Guo Jin-Bao , Chen Hui 
Published: October 2021

Objective To investigate the clinical significance of serum S100 calcium-binding protein A10 (S100A10) levels in lung cancer. Methods This prospective study enrolled patients with lung cancer, patients with benign lung nodules and healthy control subjects. Serum S100A10 levels and three biomarkers were measured and compared between the groups. Associations between serum S100A10 and clinical characteristics in patients with lung cancer were investigated. The diagnostic efficacy of serum S100A10 and carcinoembryonic antigen for lung cancer was calculated. Results The study enrolled 82 patients with lung cancer, 21 with benign lung nodules and 50 healthy controls. Serum S100A10 levels were significantly higher in patients with lung cancer compared with patients with benign lung nodules and healthy control subjects. Serum S100A10 levels of patients with advanced lung cancer were significantly higher than those with early stage disease. Patients with lymph node metastases had significantly higher serum S100A10 levels than patients without lymph node metastases. The cut-off serum S100A10 value for lung cancer detection was 1.34 ng/ml, which had a sensitivity of 48.2%, a specificity of 76.2% and an area under the curve of 0.63. Conclusion Serum S100A10 was significantly correlated with disease stage and lymph node metastasis. It has the potential to be a tumour biomarker for lung cancer.
Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study
Authors: Bar-Or Amit , Wiendl Heinz , Montalban Xavier , Alvarez Enrique , Davydovskaya Maria , Delgado Silvia R , Evdoshenko Evgeniy P , Giedraitiene Natasa , Gross-Paju Katrin , Haldre Sulev , Herrman Craig E , Izquierdo Guillermo , Karelis Guntis , Leutmezer Fritz , Mares Miroslav , Meca-Lallana Jose E , Mickeviciene Dalia , Nicholas Jacqueline , Robertson Derrick S , Sazonov Denis V , Sharlin Kenneth , Sundaram Bharathy , Totolyan Natalia , Vachova Marta , Valis Martin , Bagger Morten , Häring Dieter A , Ludwig Inga , Willi Roman , Zalesak Martin , Su Wendy , Merschhemke Martin , Fox Edward J 
Published: October 2021

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUC τ) and maximum plasma concentration ( Cmax) for Weeks 8–12. B-cell depletion and safety/tolerability were assessed. Results: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUC τ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. Conclusion: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.
Instrumental-variable estimation of large-T panel-data models with common factors
Authors: Kripfganz Sebastian , Sarafidis Vasilis 
Published: October 2021

In this article, we introduce the xtivdfreg command, which implements a general instrumental-variables (IV) approach for fitting panel-data models with many time-series observations, T, and unobserved common factors or interactive effects, as developed by Norkute et al. (2021, Journal of Econometrics 220: 416–446) and Cui et al. (2020a , ISER Discussion Paper 1101). The underlying idea of this approach is to project out the common factors from exogenous covariates using principal-components analysis and to run IV regression in both of two stages, using defactored covariates as instruments. The resulting two-stage IV estimator is valid for models with homogeneous or heterogeneous slope coefficients and has several advantages relative to existing popular approaches. In addition, the xtivdfreg command extends the two-stage IV approach in two major ways. First, the algorithm accommodates estimation of unbalanced panels. Second, the algorithm permits a flexible specification of instruments. We show that when one imposes zero factors, the xtivdfreg command can replicate the results of the popular Stata ivregress command. Notably, unlike ivregress, xtivdfreg permits estimation of the two-way error-components paneldata model with heterogeneous slope coefficients.
Cost-effectiveness of diagnostic strategies for venous thromboembolism: a systematic review
Authors: Zhang Yuan , Begum Housne A. , Grewal Himmat , Etxeandia-Ikobaltzeta Itziar , Morgano Gian Paolo , Khatib Rasha , Nieuwlaat Robby , Ding Chengyi , Wiercioch Wojtek , Mustafa Reem A. , Lim Wendy , Schünemann Holger J. 
Published: October 2021

Abstract
Guideline developers consider cost-effectiveness evidence in decision making to determine value for money. This consideration in the guideline development process can be informed either by formal and dedicated economic evaluations or by systematic reviews of existing studies. To inform the American Society of Hematology guideline on the diagnosis of venous thromboembolism (VTE), we conducted a systematic review focused on the cost-effectiveness of diagnostic strategies for VTE within the guideline scope. We systematically searched Medline (Ovid), Embase (Ovid), National Health Service Economic Evaluation Database, and the Cost-effectiveness Analysis Registry; summarized; and critically appraised the economic evidence on diagnostic strategies for VTE. We identified 49 studies that met our inclusion criteria, with 26 on pulmonary embolism (PE) and 24 on deep vein thrombosis (DVT). For the diagnosis of PE, strategies including d-dimer to exclude PE were cost-effective compared with strategies without d-dimer testing. The cost-effectiveness of computed tomography pulmonary angiogram (CTPA) in relation to ventilation-perfusion (V/Q) scan was inconclusive. CTPA or V/Q scan following ultrasound or d-dimer results could be cost-effective or even cost saving. For DVT, studies supporting strategies with d-dimer and/or ultrasound were cost-effective, supporting the recommendation that for patients at low (unlikely) VTE risk, using d-dimer as the initial test reduces the need for diagnostic imaging. Our systematic review informed the American Society of Hematology guideline recommendations about d-dimer, V/Q scan and CTPA for PE diagnosis, and d-dimer and ultrasound for DVT diagnosis.
Spotlight on eltrombopag in pediatric ITP in China: a long-term observational study in real-world practice
Authors: Cheng Xiaoling , Fu LingLing , Ma Jingyao , Gu Hao , Chen Zhenping , Zhao Libo , Wang Xiaoling , Wu Runhui 
Published: October 2021

AbstractImmune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and risk of hemorrhage. Treatment with eltrombopag increases and maintains hemostatic platelet counts; however, to date, long-term data are lacking on the outcome of children with ITP who are treated with eltrombopag. This prospective, observational, longitudinal cohort study evaluated the efficacy and safety of eltrombopag in pediatric patients with persistent or chronic ITP. For the 116 pediatric patients enrolled, duration of eltrombopag treatment was at least 3 months. Median effective dose was 25 mg/day, 50 mg/day, and 50 mg/day, respectively, for children age 5 years or younger, 6 to 11 years, or 12 years or older. In all, 89 patients (76.7%) achieved overall response, 53 (45.7%) achieved complete response, and 36 (31.0%) achieved response. Median platelet counts increased by week 1 and were sustained throughout the treatment period. During treatment with eltrombopag, the proportion of patients with grade 1 to 4 bleeding symptoms decreased from 83.61% at baseline to 9.88% at 6 months when only grade 1 was reported. Forty-three patients (37.1%) reported using concomitant medications at study entry, which was reduced to 1 patient (2.5%) who needed concomitant medications at 12 months. All adverse events were grade 1 or 2 according to Common Terminology Criteria for Adverse Events. No serious adverse events, cataracts, malignancies, or thromboses were reported during the study. Long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts and reducing bleeding in most pediatric patients with persistent or chronic ITP. Combined with future studies, these findings will help establish how eltrombopag should best be used in the management of pediatric patients with East Asian ancestry.
Economic evaluation of regular transfusions for cerebral infarct recurrence in the Silent Cerebral Infarct Transfusion Trial
Authors: Hsu Peter , Gay James C. , Lin Chyongchiou J. , Rodeghier Mark , DeBaun Michael R. , Cronin Robert M. 
Published: October 2021

AbstractIn 2020, the American Society of Hematology published evidence-based guidelines for cerebrovascular disease in individuals with sickle cell anemia (SCA). Although the guidelines were based on National Institutes of Health–sponsored randomized controlled trials, no cost-effectiveness analysis was completed for children with SCA and silent cerebral infarcts. We conducted a cost-effectiveness analysis comparing regular blood transfusion vs standard care using SIT (Silent Cerebral Infarct Transfusion) Trial participants. This analysis included a modified societal perspective with direct costs (hospitalization, emergency department visit, transfusion, outpatient care, and iron chelation) and indirect costs (special education). Direct medical costs were estimated from hospitalizations from SIT hospitals and unlinked aggregated hospital and outpatient costs from SIT sites by using the Pediatric Health Information System. Indirect costs were estimated from published literature. Effectiveness was prevention of infarct recurrence. An incremental cost-effectiveness ratio using a 3-year time horizon (mean SIT Trial participant follow-up) compared transfusion vs standard care. A total of 196 participants received transfusions (n = 90) or standard care (n = 106), with a mean age of 10.0 years. Annual hospitalization costs were reduced by 54% for transfusions vs standard care ($4929 vs $10 802), but transfusion group outpatient costs added $22 454 to $137 022 per year. Special education cost savings were $2634 over 3 years for every infarct prevented. Transfusion therapy had an incremental cost-effectiveness ratio of $22 025 per infarct prevented. Children with preexisting silent cerebral infarcts receiving blood transfusions had lower hospitalization costs but higher outpatient costs, primarily associated with the oral iron chelator deferasirox. Regular blood transfusion therapy is cost-effective for infarct recurrence in children with SCA. This trial is registered at www.clinicaltrials.gov as #NCT00072761.
Bistable auto-aggregation phenotype in Lactiplantibacillus plantarum emerges after cultivation in in vitro colonic microbiota
Authors: Isenring Julia , Geirnaert Annelies , Lacroix Christophe , Stevens Marc J. A. 
Published: October 2021

Abstract
Background
Auto-aggregation is a desired property for probiotic strains because it is suggested to promote colonization of the human intestine, to prevent pathogen infections and to modulate the colonic mucosa. We recently reported the generation of adapted mutants of Lactiplantibacillus plantarum NZ3400, a derivative of the model strain WCFS1, for colonization under adult colonic conditions of PolyFermS continuous intestinal fermentation models. Here we describe and characterize the emerge of an auto-aggregating phenotype in L. plantarum NZ3400 derivatives recovered from the modelled gut microbiota.

Results
L. plantarum isolates were recovered from reactor effluent of four different adult microbiota and from spontaneously formed reactor biofilms. Auto-aggregation was observed in L. plantarum recovered from all microbiota and at higher percentage when recovered from biofilm than from effluent. Further, auto-aggregation percentage increased over time of cultivation in the microbiota. Starvation of the gut microbiota by interrupting the inflow of nutritive medium enhanced auto-aggregation, suggesting a link to nutrient availability. Auto-aggregation was lost under standard cultivation conditions for lactobacilli in MRS medium. However, it was reestablished during growth on sucrose and maltose and in a medium that simulates the abiotic gut environment. Remarkably, none of these conditions resulted in an auto-aggregation phenotype in the wild type strain NZ3400 nor other non-aggregating L. plantarum, indicating that auto-aggregation depends on the strain history. Whole genome sequencing analysis did not reveal any mutation responsible for the auto-aggregation phenotype. Transcriptome analysis showed highly significant upregulation of LP_RS05225 (msa) at 4.1–4.4 log2-fold-change and LP_RS05230 (marR) at 4.5–5.4 log2-fold-change in all auto-aggregating strains compared to non-aggregating. These co-expressed genes encode a mannose-specific adhesin protein and transcriptional regulator, respectively. Mapping of the RNA-sequence reads to the promoter region of the msa-marR operon reveled a DNA inversion in this region that is predominant in auto-aggregating but not in non-aggregating strains. This strongly suggests a role of this inversion in the auto-aggregation phenotype.

Conclusions
L. plantarum NZ3400 adapts to the in vitro colonic environment by developing an auto-aggregation phenotype. Similar aggregation phenotypes may promote gut colonization and efficacy of other probiotics and should be further investigated by using validated continuous models of gut fermentation such as PolyFermS.
A novel 4.25 kb heterozygous deletion in PAX6 in a Chinese Han family with congenital aniridia combined with cataract and nystagmus
Authors: Qian Tianwei , Chen Chong , Li Caihua , Gong Qiaoyun , Liu Kun , Wang Gao , Schrauwen Isabelle , Xu Xun 
Published: October 2021

Abstract
Background
The aim of this study is to identify the genetic defect in a Chinese family with congenital aniridia combined with cataract and nystagmus.

Methods
Complete ophthalmic examinations, including slit-lamp biomicroscopy, dilated indirect ophthalmoscopy, anterior segment photography, and anterior segment optical coherence tomography (OCT) were performed. Blood samples were collected from all family members and genomic DNA was extracted. Genome sequencing was performed in all family members and Sanger sequencing was used to verify variant breakpoints.

Results
All the thirteen members in this Chinese family, including seven patients and six normal people, were recruited in this study. The ophthalmic examination of affected patients in this family was consistent with congenital aniridia combined with cataract and nystagmus. A novel heterozygous deletion (NC_000011.10:g.31802307_31806556del) containing the 5′ region of PAX6 gene was detected that segregated with the disease.

Conclusion
We detected a novel deletion in PAX6 responsible for congenital aniridia in the affected individuals of this Chinese family. The novel 4.25 kb deletion in PAX6 gene of our study would further broaden the genetic defects of PAX6 associated with congenital aniridia.
Validation of screening tools for common mental health disorders in the methadone maintenance population in Hanoi, Vietnam
Authors: Mughal Anisa Y. , Stockton Melissa A. , Bui Quynh , Go Vivian , Ha Tran Viet , Pence Brian W. , Gaynes Bradley N. 
Published: October 2021

Abstract
Background
Common mental health disorders (CMDs), including depression, anxiety and post-traumatic stress disorder (PTSD) may worsen both HIV and drug use outcomes, yet feasible tools to accurately identify CMDs have received limited study in this population. We aimed to validate the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder screen (GAD-7) and Primary Care PTSD screen for DSM-5 (PC-PTSD-5) in a methadone maintenance therapy (MMT) patient population in Hanoi, Vietnam.

Methods
We conducted a cross-sectional survey. The PHQ-9, GAD-7, and PC-PTSD-5 were administered to MMT patients. A blinded interviewer administered the Mini-International Neuropsychiatric Interview (MINI) as the reference gold standard. Total scores of each tool were compared with the MINI diagnoses using a receiver operating characteristic curves, and we identified the optimal respective cut-off scores using the Youden’s Index.

Results
We enrolled 400 MMT patients. Approximately 99.3% were male (n = 397) and 21.8% (n = 87) were HIV positive. The prevalence of major depressive disorder, generalized anxiety disorder and PTSD, respectively, was 10.5, 4 and 2%. Optimal cut-off scores for the PHQ-9, GAD-7 and PC-PTSD were ≥ 5, ≥3, and ≥ 4 with a sensitivity/specificity of 95.2%/91.9, 93.8%/87.5, and 62.5%/95.2%.

Conclusions
The prevalence of CMDs in the MMT population was lower than expected. A lower cut-off score may be considered when screening for CMDs in this population. Further research should investigate the validity of somatic symptom-based screening tools among other drug-using or MMT populations.
Variants of the cry 1 gene may influence the effect of fat intake on resting metabolic rate in women with overweight of obesity: a cross-sectional study
Authors: Mirzababaei Atieh , Daneshzad Elnaz , Shiraseb Farideh , Pourreza Sanaz , Setayesh Leila , Clark Cain C. T. , Tangestani Hadith , Abaj Faezeh , Yarizadeh Habib , Mirzaei Khadijeh 
Published: October 2021

AbstractBackgroundPrevious studies have shown that the minor allele (C allele) for Cry 1 rs2287161, may be associated with increased risk of cardiovascular diseases (CVDs). Low resting metabolic rate (RMR) caused by the diet has been shown to have, potentially, unfavorable effects on obesity. This study sought to investigate the interactions between the Cry 1 Gene and fat intake on RMR in women with overweight of obesity.MethodsThis comparative cross-sectional study was conducted on 377 Iranian women with overweight of obesity. A food frequency questionnaire (FFQ), with 147 items, was used to assess dietary intake. Individuals were categorized into two groups based on the rs2287161 genotype. Body composition, dietary intake, and RMR were assessed for all participants.ResultsThere was a significant difference between genotypes for fasting blood sugar (FBS) (P = 0.04), fat free mass (FFM) (P = 0.0009), RMR per FFM (P = 0.05), RMR per body mass index (BMI) (P = 0.02), and RMR deviation (P = 0.01). Our findings also showed significant interactions between total fat and C allele carrier group on RMR per kg body weight, RMR per body surface area (BSA), RMR per FFM, and RMR deviation (P for interaction < 0.1), in addition to a significant interaction between CC + CG group genotype and polyunsaturated fatty acids (PUFA) intake on RMR per BMI (P for interaction =0.00) and RMR per kg (P for interaction = 0.02) and RMR per BSA (P = 0.07), compared to the GG group, after control for confounder factors.ConclusionThese results highlight that dietary compositions, gene variants, and their interaction, should be acutely considered in lower RMR.
Patient-public engagement strategies for health system improvement in sub-Saharan Africa: a systematic scoping review
Authors: Ankomah Samuel Egyakwa , Fusheini Adam , Ballard Christy , Kumah Emmanuel , Gurung Gagan , Derrett Sarah 
Published: October 2021

Abstract
Background
Actively involving patients and communities in health decisions can improve both peoples’ health and the health system. One key strategy is Patient-Public Engagement (PPE). This scoping review aims to identify and describe PPE research in Sub-Saharan Africa; systematically map research to theories of PPE; and identify knowledge gaps to inform future research and PPE development.

Methods
The review followed guidelines for conducting and reporting scoping reviews. A systematic search of peer-reviewed English language literature published between January 1999 and December 2019 was conducted on Scopus, Medline (Ovid), CINAHL and Embase databases. Independent full text screening by three reviewers followed title and abstract screening. Using a thematic framework synthesis, eligible studies were mapped onto an engagement continuum and health system level matrix to assess the current focus of PPE in Sub-Saharan Africa.

Results
Initially 1948 articles were identified, but 18 from 10 Sub-Saharan African countries were eligible for the final synthesis. Five PPE strategies implemented were: 1) traditional leadership support, 2) community advisory boards, 3) community education and sensitisation, 4) community health volunteers/workers, and 5) embedding PPE within existing community structures. PPE initiatives were located at either the ‘involvement’ or ‘consultation’ stages of the engagement continuum, rather than higher-level engagement. Most PPE studies were at the ‘service design’ level of the health system or were focused on engagement in health research. No identified studies reported investigating PPE at the ‘individual treatment’ or ‘macro policy/strategic’ level.

Conclusion
This review has successfully identified and evaluated key PPE strategies and their focus on improving health systems in Sub-Saharan Africa. PPE in Sub-Saharan Africa was characterised by tokenism rather than participation. PPE implementation activities are currently concentrated at the ‘service design’ or health research levels. Investigation of PPE at all the health system levels is required, including prioritising patient/community preferences for health system improvement.