bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coconuts and curtain cakes: The production of wh-questions in ASD
Authors: Sukenik Nufar , Morin Eléonore , Friedmann Naama , Prevost Philippe , Tuller Laurice 
Published: February 2021

Background and aims Children with autism spectrum disorders (ASD) have been found to exhibit difficulties in wh-question production. It is unclear whether these difficulties are pragmatic or syntactic in nature. The current study used a question elicitation task to assess the production of subject and object wh-questions of children with ASD in two different languages (Hebrew and French) wherein the syntactic structure of wh-questions is different, a fact that may contribute to better understanding of the underlying deficits affecting wh-question production. Crucially, beyond the general correct/error rate we also performed an in-depth analysis of error types, comparing syntactic to pragmatic errors and comparing the distribution of errors in the ASD group to that of children with typical development (TD) and children with Developmental Language Disorder (DLD). Results Correct production rates were found to be similar for the ASD and DLD groups, but error analysis revealed important differences between the ASD groups in the two languages and the DLD group. The Hebrew- and French ASD groups were found to produce pragmatic errors, which were not found in children with DLD. The pragmatic errors were similar in the two ASD groups. Syntactic errors were affected by the structure of each language. Conclusions Our results have shown that although the two ASD groups come from different countries and speak different languages, the correct production rates and more importantly, the error types were very similar in the two ASD groups, and very different compared to TD children and children with DLD. Implications: Our results highlight the importance of creating research tasks that test different linguistic functions independently and strengthen the need for conducting fine-grained error analysis to differentiate between groups and gain insights into the deficits underlying each of them.
JMJD6 promotes self-renewal and regenerative capacity of hematopoietic stem cells
Authors: Lawson Hannah , Sepulveda Catarina , van de Lagemaat Louie N. , Durko Jozef , Barile Melania , Tavosanis Andrea , Georges Elise , Shmakova Alena , Timms Penny , Carter Roderick N. , Allen Lewis , Campos Joana , Vukovic Milica , Guitart Amelie V. , Giles Peter , O’Shea Marie , Vernimmen Douglas , Morton Nicholas M. , Rodrigues Neil P. , Göttgens Berthold , Schofield Christopher J. , Lengeling Andreas , O’Carroll Dónal , Kranc Kamil R. 
Published: February 2021

Abstract
Lifelong multilineage hematopoiesis critically depends on rare hematopoietic stem cells (HSCs) that reside in the hypoxic bone marrow microenvironment. Although the role of the canonical oxygen sensor hypoxia-inducible factor prolyl hydroxylase has been investigated extensively in hematopoiesis, the functional significance of other members of the 2-oxoglutarate (2-OG)-dependent protein hydroxylase family of enzymes remains poorly defined in HSC biology and multilineage hematopoiesis. Here, by using hematopoietic-specific conditional gene deletion, we reveal that the 2-OG–dependent protein hydroxylase JMJD6 is essential for short- and long-term maintenance of the HSC pool and multilineage hematopoiesis. Additionally, upon hematopoietic injury, Jmjd6-deficient HSCs display a striking failure to expand and regenerate the hematopoietic system. Moreover, HSCs lacking Jmjd6 lose multilineage reconstitution potential and self-renewal capacity upon serial transplantation. At the molecular level, we found that JMJD6 functions to repress multiple processes whose downregulation is essential for HSC integrity, including mitochondrial oxidative phosphorylation (OXPHOS), protein synthesis, p53 stabilization, cell cycle checkpoint progression, and mTORC1 signaling. Indeed, Jmjd6-deficient primitive hematopoietic cells display elevated basal and maximal mitochondrial respiration rates and increased reactive oxygen species (ROS), prerequisites for HSC failure. Notably, an antioxidant, N-acetyl-l-cysteine, rescued HSC and lymphoid progenitor cell depletion, indicating a causal impact of OXPHOS-mediated ROS generation upon Jmjd6 deletion. Thus, JMJD6 promotes HSC maintenance and multilineage differentiation potential by suppressing fundamental pathways whose activation is detrimental for HSC function.
Zinc limitation in Klebsiella pneumoniae profiled by quantitative proteomics influences transcriptional regulation and cation transporter-associated capsule production
Authors: Sukumaran A. , Pladwig S. , Geddes-McAlister J. 
Published: February 2021

Abstract
Background
Microbial organisms encounter a variety of environmental conditions, including changes to metal ion availability. Metal ions play an important role in many biological processes for growth and survival. As such, microbes alter their cellular protein levels and secretion patterns in adaptation to a changing environment. This study focuses on Klebsiella pneumoniae, an opportunistic bacterium responsible for nosocomial infections. By using K. pneumoniae, we aim to determine how a nutrient-limited environment (e.g., zinc depletion) modulates the cellular proteome and secretome of the bacterium. By testing virulence in vitro, we provide novel insight into bacterial responses to limited environments in the presence of the host.

Results
Analysis of intra- and extracellular changes identified 2380 proteins from the total cellular proteome (cell pellet) and 246 secreted proteins (supernatant). Specifically, HutC, a repressor of the histidine utilization operon, showed significantly increased abundance under zinc-replete conditions, which coincided with an expected reduction in expression of genes within the hut operon from our validating qRT-PCR analysis. Additionally, we characterized a putative cation transport regulator, ChaB that showed significantly higher abundance under zinc-replete vs. -limited conditions, suggesting a role in metal ion homeostasis. Phenotypic analysis of a chaB deletion strain demonstrated a reduction in capsule production, zinc-dependent growth and ion utilization, and reduced virulence when compared to the wild-type strain.

Conclusions
This is first study to comprehensively profile the impact of zinc availability on the proteome and secretome of K. pneumoniae and uncover a novel connection between zinc transport and capsule production in the bacterial system.
Genome-wide identification of chitinase genes in Thalassiosira pseudonana and analysis of their expression under abiotic stresses
Authors: Cheng Haomiao , Shao Zhanru , Lu Chang , Duan Delin 
Published: February 2021

Abstract
Background
The nitrogen-containing polysaccharide chitin is the second most abundant biopolymer on earth and is found in the cell walls of diatoms, where it serves as a scaffold for biosilica deposition. Diatom chitin is an important source of carbon and nitrogen in the marine environment, but surprisingly little is known about basic chitinase metabolism in diatoms.

Results
Here, we identify and fully characterize 24 chitinase genes from the model centric diatom Thalassiosira pseudonana. We demonstrate that their expression is broadly upregulated under abiotic stresses, despite the fact that chitinase activity itself remains unchanged, and we discuss several explanations for this result. We also examine the potential transcriptional complexity of the intron-rich T. pseudonana chitinase genes and provide evidence for two separate tandem duplication events during their evolution.

Conclusions
Given the many applications of chitin and chitin derivatives in suture production, wound healing, drug delivery, and other processes, new insight into diatom chitin metabolism has both theoretical and practical value.
Molecular characterization of the viral structural protein genes in the first outbreak of dengue virus type 2 in Hunan Province, inland China in 2018
Authors: Guan Jiaoqiong , He Zhanlong , Qin Meng , Deng Xialin , Chen Jun , Duan Suqin , Gao Xiaojun , Pan Yue , Chen Junying , Yang Yaping , Feng Shijun , Sun Qiangming 
Published: February 2021

Abstract
Background
An unexpected dengue outbreak occurred in Hunan Province in 2018. This was the first dengue outbreak in this area of inland China, and 172 cases were reported.

Methods
To verify the causative agent of this outbreak and characterise the viral genes, the genes encoding the structural proteins C/prM/E of viruses isolated from local residents were sequenced followed by mutation and phylogenetic analysis. Recombination, selection pressure, potential secondary structure and three-dimensional structure analyses were also performed.

Results
Phylogenetic analysis revealed that all epidemic strains were of the cosmopolitan DENV-2 genotype and were most closely related to the Zhejiang strain (MH010629, 2017) and then the Malaysia strain (KJ806803, 2013). Compared with the sequence of DENV-2SS, 151 base substitutions were found in the sequences of 89 isolates; these substitutions resulted in 20 non-synonymous mutations, of which 17 mutations existed in all samples (two in the capsid protein, six in the prM/M proteins, and nine in the envelope proteins). Moreover, amino acid substitutions at the 602nd (E322:Q → H) and 670th (E390: N → S) amino acids may have enhanced the virulence of the epidemic strains. One new DNA binding site and five new protein binding sites were observed. Two polynucleotide binding sites and seven protein binding sites were lost in the epidemic strains compared with DENV-2SS. Meanwhile, five changes were found in helical regions. Minor changes were observed in helical transmembrane and disordered regions. The 429th amino acid of the E protein switched from a histamine (positively charged) to an asparagine (neutral) in all 89 isolated strains. No recombination events or positive selection pressure sites were observed. To our knowledge, this study is the first to analyse the genetic characteristics of epidemic strains in the first dengue outbreak in Hunan Province in inland China.

Conclusions
The causative agent is likely to come from Zhejiang Province, a neighbouring province where dengue fever broke out in 2017. This study may help clarify the intrinsic geographical relatedness of DENV-2 and contribute to further research on pathogenicity and vaccine development.
Stakeholder consensus for decision making in eye-gaze control technology for children, adolescents and adults with cerebral palsy service provision: findings from a Delphi study
Authors: Karlsson Petra , Griffiths Tom , Clarke Michael T. , Monbaliu Elegast , Himmelmann Kate , Bekteshi Saranda , Allsop Abigail , Pereksles René , Galea Claire , Wallen Margaret 
Published: February 2021

AbstractBackgroundLimited research exists to guide clinical decisions about trialling, selecting, implementing and evaluating eye-gaze control technology. This paper reports on the outcomes of a Delphi study that was conducted to build international stakeholder consensus to inform decision making about trialling and implementing eye-gaze control technology with people with cerebral palsy.MethodsA three-round online Delphi survey was conducted. In Round 1, 126 stakeholders responded to questions identified through an international stakeholder Advisory Panel and systematic reviews. In Round 2, 63 respondents rated the importance of 200 statements generated by in Round 1. In Round 3, 41 respondents rated the importance of the 105 highest ranked statements retained from Round 2.ResultsStakeholders achieved consensus on 94 of the original 200 statements. These statements related to person factors, support networks, the environment, and technical aspects to consider during assessment, trial, implementation and follow-up. Findings reinforced the importance of an individualised approach and that information gathered from the user, their support network and professionals are central when measuring outcomes. Information required to support an application for funding was obtained.ConclusionThis Delphi study has identified issues which are unique to eye-gaze control technology and will enhance its implementation with people with cerebral palsy.
Successful recovery following musculoskeletal trauma: protocol for a qualitative study of patients’ and physiotherapists’ perceptions
Authors: Middlebrook N. , Heneghan N. R. , Falla D. , Silvester L. , Rushton A. B. , Soundy A. A. 
Published: February 2021

AbstractBackgroundAnnually in the UK, 40,000–90,000 people are involved in a traumatic incident. Severity of injury and how well people recover from their injuries varies, with physiotherapy playing a key role in the rehabilitation process. Recovery is evaluated using multiple outcome measures for perceived levels of pain severity and quality of life. It is unclear however, what constitutes a successful recovery from injury throughout the course of recovery from the patient perspective, and whether this aligns with physiotherapists’ perspectives.MethodsA qualitative study using two approaches: Interpretive Phenomenological Analysis (IPA) using semi-structured interviews and thematic analysis following the Kreuger framework for focus groups. A purposive sample of 20 patients who have experienced musculoskeletal trauma within the past 4 weeks and 12 physiotherapists who manage this patient population will be recruited from a single trauma centre in the UK. Semi-structured interviews with patients at 4 weeks, 6 and 12 months following injury, and 2 focus groups with physiotherapists will be undertaken at one time point. Views and perceptions on the definition of recovery and what constitutes a successful recovery will be explored using both methods, with a focus on the lived experience and patient journey following musculoskeletal trauma, and how this changes through the process of recovery. Data from both the semi-structured interviews and focus groups will be analysed separately and then integrated and synthesised into key themes ensuring similarities and differences are identified. Strategies to ensure trustworthiness e.g., reflexivity will be employed.DiscussionRecovery following musculoskeletal trauma is complex and understanding of the concept of successful recovery and how this changes over time following an injury is largely unknown. It is imperative to understand the patient perspective and whether these perceptions align with current views of physiotherapists. A greater understanding of recovery following musculoskeletal trauma has potential to change clinical care, optimise patient centred care and improve efficiency and clinical decision making during rehabilitation. This in turn can contribute to improved clinical effectiveness, patient outcome and patient satisfaction with potential service and economic cost savings. This study has ethical approval (IRAS 287781/REC 20/PR/0712).
A short-term approach for promoting oral health of internally displaced children with PTSD: the key is improving mental health—results from a quasi-randomized trial
Authors: Hamid Sulaf , Dashash Mayssoon , Latifeh Youssef 
Published: February 2021

Abstract
Background
Several studies have demonstrated that mental (MH) and oral health (OH) of displaced children are negatively affected during the wartime. This may be a result of general self-neglect and psychological suffering. Therefore, previous studies suggested that psychosocial support (PSS) is essential during and after humanitarian crises to prevent immediate and long-term MH and OH problems. This study was undertaken to evaluate the effectiveness of a short-term approach in improving (MH) and (OH) of displaced children suffering from posttraumatic stress disorder (PTSD).

Methods
A quasi-randomized clinical trial study was carried out including (118) displaced children suffering from PTSD. The Child Post-Traumatic Stress Reaction Index (CPTSD-RI) was utilized for the diagnosis of PTSD. Children were assigned into two groups (intervention and control group). Children in the intervention group were enrolled in a 6-week PSS program that contained oral health educational components designed especially for this study. Clinical evaluation included plaque index (PI) and gingival index (GI). Oral health related Quality of life (OHRQoL) was also evaluated using child perception questionnaire (CPQ11-14). Study variables were evaluated at baseline and at the end of the program for both groups. Wilcoxon rank test and t-test for independent samples were used for data analysis.

Results
A total of 118 children, aged between 9 and 14 years, participated in the recent study (mean age 11.0 ± 1.4). All participated children were previously diagnosed with PTSD. At baseline, there were no significant differences in the study variables between groups (P > 0.05). At the end of the program, children in the intervention group had significantly decreased PI, GI, CPQ11-14 and CPTSD-RI compared to their baseline scores (P = 0.000). In contrast, controls showed no differences at the end of the program (P > 0.05). Children in the intervention group had significantly (P = 0.000) lower PI (1.52 ± 0.55) and GI (1.48 ± 0.56) when compared to controls (PI = 1.89 ± 0.39, GI = 2.14 ± 0.32) post program. Moreover, the intervention group showed remarkable decline (P < 0.001) in their CPQ11-14 (47.16 ± 12.24) and CPTSD-RI (34.41 ± 12.23) scores compared to controls (CPQ11-14 = 72.65 ± 14.47, CPTSD-RI = 47.91 ± 14.24) post program.

Conclusions
The designed approach could have positive improvements in PTSD symptoms, (OH) and (OHRQoL) of displaced children. Integration between (MH) and (OH) services should be considered during and after humanitarian crises to prevent immediate and long-term MH and OH problems.
Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12619000285156), Date registered: 25/02/2019, retrospectively registered. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377001&isReview=true.
Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification
Authors:   BIOS Consortium, Zhang Xiaoling , van Rooij Jeroen G. J. , Wakabayashi Yoshiyuki , Hwang Shih-Jen , Yang Yanqin , Ghanbari Mohsen , Bos Daniel , Levy Daniel , Johnson Andrew D. , van Meurs Joyce B. J. , Kavousi Maryam , Zhu Jun , O’Donnell Christopher J. 
Published: February 2021

Abstract
Background
Coronary artery calcification (CAC) is a noninvasive measure of coronary atherosclerosis, the proximal pathophysiology underlying most cases of myocardial infarction (MI). We sought to identify expression signatures of early MI and subclinical atherosclerosis in the Framingham Heart Study (FHS). In this study, we conducted paired-end RNA sequencing on whole blood collected from 198 FHS participants (55 with a history of early MI, 72 with high CAC without prior MI, and 71 controls free of elevated CAC levels or history of MI). We applied DESeq2 to identify coding-genes and long intergenic noncoding RNAs (lincRNAs) differentially expressed in MI and high CAC, respectively, compared with the control.

Results
On average, 150 million paired-end reads were obtained for each sample. At the false discovery rate (FDR) < 0.1, we found 68 coding genes and 2 lincRNAs that were differentially expressed in early MI versus controls. Among them, 60 coding genes were detectable and thus tested in an independent RNA-Seq data of 807 individuals from the Rotterdam Study, and 8 genes were supported by p value and direction of the effect. Immune response, lipid metabolic process, and interferon regulatory factor were enriched in these 68 genes. By contrast, only 3 coding genes and 1 lincRNA were differentially expressed in high CAC versus controls. APOD, encoding a component of high-density lipoprotein, was significantly downregulated in both early MI (FDR = 0.007) and high CAC (FDR = 0.01) compared with controls.

Conclusions
We identified transcriptomic signatures of early MI that include differentially expressed protein-coding genes and lincRNAs, suggesting important roles for protein-coding genes and lincRNAs in the pathogenesis of MI.
Reconstructing the household transmission of influenza in the suburbs of Tokyo based on clinical cases
Authors: Saito Masaya M. , Hirotsu Nobuo , Hamada Hiroka , Takei Mio , Honda Keisuke , Baba Takamichi , Hasegawa Takahiro , Kitanishi Yoshitake 
Published: February 2021

AbstractBackgroundInfluenza is a public health issue that needs to be addressed strategically. The assessment of detailed infectious profiles is an important part of this effort. Household transmission data play a key role in estimating such profiles. We used diagnostic and questionnaire-based data on influenza patients at a Japanese clinic to estimate the detailed infectious period (as well as incubation period, symptomatic and infectious periods, and extended infectious period after recovery) and the secondary attack ratio (SAR) of influenza for households of various sizes based on a modified Cauchemez-type model.ResultsThe data were from enrolled patients with confirmed influenza who were treated at the Hirotsu Clinic (Kawasaki, Japan) with a neuraminidase inhibitor (NAI) during six northern hemisphere influenza seasons between 2010 and 2016. A total of 2342 outpatients, representing 1807 households, were included. For influenza type A, the average incubation period was 1.43 days (95% probability interval, 0.03–5.32 days). The estimated average symptomatic and infective period was 1.76 days (0.33–4.62 days); the extended infective period after recovery was 0.25 days. The estimated SAR rose from 20 to 32% as household size increased from 3 to 5. For influenza type B, the average incubation period, average symptomatic and infective period, and extended infective period were estimated as 1.66 days (0.21–4.61), 2.62 days (0.54–5.75) and 1.00 days, respectively. The SAR increased from 12 to 21% as household size increased from 3 to 5.ConclusionAll estimated periods of influenza type B were longer than the corresponding periods for type A. However, the SAR for type B was less than that for type A. These results may reflect Japanese demographics and treatment policy. Understanding the infectious profiles of influenza is necessary for assessing public health measures.
Effect of femoral posterior condyle offset on knee joint function after total knee replacement: a network meta-analysis and a sequential retrospective cohort study
Authors: Zhang Yimin , Wang Jun , Zhang Miao , Xu Yun 
Published: February 2021

Abstract
Background
This study was conducted with the aim to compare the effect of posterior condyle offset (PCO) changes on knee joint function of patients following total knee replacement (TKR).

Methods
Electronic and manual searches were performed in the PubMed, Embase, and Cochrane Library databases from inception to September 2019. Network meta-analysis combined direct and indirect evidence to assess the weighted mean difference (WMD) and surface under the cumulative ranking curves (SUCRA) of different PCO changes (PCO ≤ − 2 mm, − 2 mm < PCO < 0 mm, 0 mm ≤ PCO < 2 mm and PCO ≥ 2 mm) on knee joint function after TKR. Then 103 OA patients undergoing unilateral TKR were included and the effect of PCO on the postoperative knee function was examined.

Results
Totally, 5 cohort studies meeting the inclusion criteria were enrolled in this analysis. The results of meta-analysis showed that patients with 0 mm ≤ PCO < 2 mm after TKR had a better recovery of joint function (flexion contracture: 28.67%; KS functional score: 78.67%; KS knee score: 75.00%) than the remaining three groups. However, the knee flexion (77.00%) of patients with PCO ≤ − 2 mm after TKR was superior to the other three groups. Retrospective study also revealed a significant correlation between PCO changes and the flexion contracture, further flexion and KS functional score of patients after TKR, in which each functional knee score of patients with 0 mm ≤ PCO < 2 mm was better than the others.

Conclusion
These findings suggest a close correlation between PCO magnitude and knee joint function after TKR and that 0 mm ≤ PCO < 2 mm is superior to other changes for joint function after TKR.