bluuebunny/crossref_metadata_2025_split huggingface dataset:
Executive functioning and neurodevelopmental disorders in early childhood: a prospective population-based study
Authors: Otterman D. Louise , Koopman-Verhoeff M. Elisabeth , White Tonya J. , Tiemeier Henning , Bolhuis Koen , Jansen Pauline W. 
Published: October 2019

Abstract

Background
Executive functioning deficits are common in children with neurodevelopmental disorders. However, prior research mainly focused on clinical populations employing cross-sectional designs, impeding conclusions on temporal neurodevelopmental pathways. Here, we examined the prospective association of executive functioning with subsequent autism spectrum disorder (ASD) traits and attention-deficit/hyperactivity disorder (ADHD) traits.

Methods
This study included young children from the Generation R Study, a general population birth cohort. The Brief Rating Inventory of Executive Function-Preschool Version was used to assess parent-reported behavioral executive functioning when the children were 4 years old. ASD traits were assessed at age 6 (n = 3938) using the parent-reported Social Responsiveness Scale. The Teacher Report Form was used to assess ADHD traits at age 7 (n = 2749). Children with high scores were screened to determine possible clinical ASD or ADHD diagnoses. We were able to confirm an ASD diagnosis for n = 56 children by retrieving their medical records and established an ADHD diagnosis for n = 194 children using the Diagnostic Interview Schedule for Children-Young Child version (DISC-YC). Data were analyzed using hierarchical linear and logistic regressions.

Results
Impaired executive functioning was associated with more ASD and ADHD traits across informants (for ASD traits and diagnoses: β = 0.33, 95% CI [0.30–0.37]; OR = 2.69, 95% CI [1.92–3.77], respectively; for ADHD traits and diagnoses: β = 0.12, 95% CI [0.07–0.16]; OR = 2.32, 95% CI [1.89–2.85], respectively). Deficits in all subdomains were associated with higher levels of ASD traits, whereas only impaired inhibition, working memory, and planning/organization were associated with more ADHD traits.

Conclusions
The findings of the current study suggest a graded association of executive functioning difficulties along the continuum of ASD and ADHD and that problems in executive functioning may be a precursor of ASD and ADHD traits from an early age onwards.
Process development for pandemic influenza VLP vaccine production using a baculovirus expression system
Authors: Lai Chia-Chun , Cheng Yu-Chieh , Chen Pin-Wen , Lin Ting-Hui , Tzeng Tsai-Teng , Lu Chia-Chun , Lee Min-Shi , Hu Alan Yung-Chih 
Published: October 2019

Abstract

Background
Influenza viruses cause hundreds of thousands of respiratory diseases worldwide each year, and vaccination is considered the most effective approach for preventing influenza annual epidemics or pandemics. Since 1950, chicken embryonated eggs have been used as the main method for producing seasonal influenza vaccines. However, this platform has the main drawback of a lack of scale-up flexibility, and thus, egg-based vaccine manufacturers cannot supply sufficient doses within a short period for use for pandemic prevention. As a result, strategies for reducing the manufacturing time and increasing production capacity are urgently needed. Non-virion vaccine methods have been considered an alternative strategy against an influenza pandemic, and the purpose of maintaining an immunogenic capsule structure with infectious properties appears to be met by the virus-like particle (VLP) platform.

Results
An influenza H7N9-TW VLP production platform using insect cells, which included the expression of hemagglutinin (HA), NA, and M1 proteins, was established. To scale up H7N9-TW VLP production, several culture conditions were optimized to obtain a higher production yield. A high level of dissolved oxygen (DO) could be critical to H7N9-TW VLP production. If the DO was maintained at a high level, the HA titer obtained in the spinner flask system with ventilation was similar to that obtained in a shake flask. In this study, the HA titer in a 5-L bioreactor with a well-controlled DO level was substantially improved by 128-fold (from 4 HA units (HAU)/50 μL to 512 HAU/50 μL).

Conclusions
In this study, a multigene expression platform and an effective upstream process were developed. Notably, a high H7N9-TW VLP yield was achieved using a two-step production strategy while a high DO level was maintained. The upstream process, which resulted in high VLP titers, could be further used for large-scale influenza VLP vaccine production.
The high-affinity IgG receptor FcγRI modulates peripheral nerve injury-induced neuropathic pain in rats
Authors: Liang Yingxia , Zhang Zhiyu , Juan Zhaodong , Zhang Rui , Zhang Can 
Published: October 2019

Abstract
The Fc gamma receptor I (FcγRI; CD64) is the high-affinity receptor of the immunoglobulin G protein (IgG). It is usually expressed in immune cells and has recently been identified to distribute in the nervous system and play critical roles in various neurological disorders. Presently, the impacts of FcγRI in neuropathic pain was largely unknown. Here, we aimed to investigate the impacts of FcγRI in neuropathic pain through pain-related neurobehavioral studies and underlying mechanisms by biochemical methods in animal and cell models. Specifically, we first utilized the chronic constriction injury (CCI) rat model that displayed neuropathic pain related symptoms and signs, including thermal hyperalgesia and mechanical allodynia. These neurobehavioral defects were significantly attenuated by the anti-FcγRI antibody, which was associated with reduced levels of neuropeptide substance P, C3, and TNF-α. Furthermore, we validated our animal findings using the embryonically neural crest-originated PC12 cell model. We found that stimulation of the IgG immune complex led to increased levels of FcγRI and inflammatory mediators, which were attenuated by the anti-FcγRI antibody in these cells. Collectively, our results from animal and cell-based studies suggest that FcγRI is a critical player for peripheral nerve injury-induced neuropathic pain by mediating pain-related immunological events, which therefore may provide a new therapeutic target for protection against chronic pain.
A pilot study of alternative TrkAIII splicing in Merkel cell carcinoma: a potential oncogenic mechanism and novel therapeutic target
Authors: Cappabianca Lucia , Guadagni Stefano , Maccarone Rita , Sebastiano Michela , Chiominto Alessandro , Farina Antonietta Rosella , Mackay Andrew Reay 
Published: October 2019

AbstractBackgroundMerkel cell carcinomas (MCCs) are rare, aggressive, therapeutically-challenging skin tumours that are increasing in incidence and have poor survival rates. The majority are caused by genomic Merkel cell polyomavirus (MCPyV) integration and MCPyV T-antigen expression. Recently, a potential oncogenic role for the tropomyosin-related tyrosine kinase A receptor (TrkA) has been proposed in MCC. Alternative TrkAIII splicing is a TrkA oncogenic activation mechanism that can be promoted by SV40 large T-antigen, an analogue of MCPyV large T-antigen. In this pilot study, therefore, we have evaluated TrkAIII splicing as a novel potential oncogenic mechanism and therapeutic target in MCPyV positive MCC.MethodsFormalin-fixed paraffin-embedded MCC tissues, consisting of 10 stage IV, 1 stage IIIB, 1 stage IIB, 4 stage IIA and 2 stage I tumours, from patients diagnosed and treated from September 2006 to March, 2019, at the University of L’Aquila, L’Aquila, Italy, were compared to 3 primary basal cell carcinomas (BCCs), 3 primary squamous cell carcinomas (SCCs) and 2 normal skin samples by RT-PCR for MCPyV large T-antigen, small T-antigen, VP-1 expression and alternative TrkAIII splicing and by indirect IF for evidence of intracellular TrkA isoform expression and activation.Results9 of 10 Recurrent stage IV MCCs were from patients (P.1–3) treated with surgery plus loco-regional Melphalan chemotherapy and remaining MMCs, including 1 stage IV tumour, were from patients treated with surgery alone (P. 4–11). All MCPyV positive MCCs exhibiting MCPyV large T-antigen expression (17 of 18MCCs, 90%) exhibited alternative TrkAIII mRNA splicing (100%), which was exclusive in a significant number and predominant (> 50%) in all stage IV MCCs and the majority of stage 1-III MCCs. MCCs with higher TrkAIII to 18S rRNA expression ratios also exhibited strong or intermediate immunoreactivity to anti-TrkA antibodies, consistent with cytoplasmic TrkAIII expression and activation. In contrast, the MCPyV negative MCC, BCCs, SCCs and normal skin tissues all exhibited exclusive fully-spliced TrkA mRNA expression, associated with variable immunoreactivity for non-phosphorylated but not phosphorylated TrkA.ConclusionsMCPyV positive MCCs but not MCPyV negative MCC, BCCs and SCCs exhibit predominant alternative TrkAIII splicing, with evidence of intracellular TrkAIII activation. This establishes a new potential MCC subset, unveils a novel potential MCPyV oncogenic mechanism and identifies TrkAIII as a novel potential therapeutic target in MCPyV positive MCC.
Prevalence and spectrum of MLH1, MSH2, and MSH6 pathogenic germline variants in Pakistani colorectal cancer patients
Authors: Rashid Muhammad Usman , Naeemi Humaira , Muhammad Noor , Loya Asif , Lubiński Jan , Jakubowska Anna , Yusuf Muhammed Aasim 
Published: October 2019

Abstract

Background
Pathogenic germline variants in MLH1, MSH2 and MSH6 genes account for the majority of Lynch syndrome (LS). In this first report from Pakistan, we investigated the prevalence of pathogenic MLH1/MSH2/MSH6 variants in colorectal cancer (CRC) patients.

Methods
Consecutive cases (n = 212) were recruited at the Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC), between November 2007 to March 2011. Patients with a family history of > 3 or 2 HNPCC-associated cancers were classified as HNPCC (n = 9) or suspected-HNPCC (n = 20), respectively (group 1; n = 29). Cases with no family history were designated as non-HNPCC (group 2; n = 183). MLH1/MSH2/MSH6 genes were comprehensively screened in group 1. Pathogenic/likely pathogenic variants identified in group 1 were subsequently evaluated in group 2.

Results
Eight distinct pathogenic/likely pathogenic MLH1/MSH2 variants were found in group 1 (10/29; 34.5%), belonging to HNPCC (5/9; 55.6%) and suspected-HNPCC (5/20; 25%) families and in group 2 (2/183; 1.1%) belonging to non-HNPCC. Overall, three recurrent variants (MSH2 c.943-1G > C, MLH1 c.1358dup and c.2041G > A) accounted for 58.3% (7/12) of all families harboring pathogenic/likely pathogenic MLH1/MSH2 variants. Pathogenic MSH6 variants were not detected.

Conclusion
Pathogenic/likely pathogenic MLH1/MSH2 variants account for a substantial proportion of CRC patients with HNPCC/suspected-HNPCC in Pakistan. Our findings suggest that HNPCC/suspected-HNPCC families should be tested for these recurrent variants prior to comprehensive gene screening in this population.
Enhanced recovery after surgery (ERAS) pathway for primary hip and knee arthroplasty: study protocol for a randomized controlled trial
Authors: Li Jingyi , Zhu Haibei , Liao Ren 
Published: October 2019

Abstract

Background
With the substantially growing trend of the aging populations in China and the rest of the world, the number of total hip and total knee arthroplasty (THA and TKA) cases are increasing dramatically. It is important to develop practical strategies to improve the quality of healthcare and better outcome for patients undergoing THA and TKA. Enhanced recovery after surgery (ERAS) pathways have been reported to promote earlier recovery and be beneficial for patients. We propose the hypothesis that the ERAS pathway could reduce the length of stay (LOS) in hospital for patients undergoing primary THA or TKA.

Methods/Design
This trial is a prospective, open-labelled, multi-centered, randomized controlled trial that will test the superiority of the ERAS pathway in term of LOS in hospital for the patients undergoing primary THA or TKA compared to current non-ERAS clinical practice. A total of 640 patients undergoing primary THA or TKA will be randomly allocated to either ERAS pathway (ERAS group) or conventional care according to individual participating center (non-ERAS group). The primary outcome is the total LOS in hospital; the secondary outcomes include postoperative LOS, all-cause mortality by 30 days after operation, in-hospital complications, early mobilization, postoperative pain control, total in-hospital cost, and readmission rate by 30 days after discharge from the hospital.

Discussion
This trial is designed to evaluate the superiority of the ERAS pathway to conventional non-ERAS clinical practice in reducing the LOS. The results may provide new insight into the clinical applications of the ERAS pathway for THA and TKA.

Trial registration
National Institutes of Health Clinical Trials Registry, NCT03517098. Registered on 4 May 2018.
Molecular investigation and phylogeny of species of the Anaplasmataceae infecting animals and ticks in Senegal
Authors: Dahmani Mustapha , Davoust Bernard , Sambou Masse , Bassene Hubert , Scandola Pierre , Ameur Tinhinene , Raoult Didier , Fenollar Florence , Mediannikov Oleg 
Published: October 2019

Abstract

Background
Our study aimed to assess the diversity of the species of Anaplasmataceae in Senegal that infect animals and ticks in three areas: near Keur Momar Sarr (northern region), Dielmo and Diop (Sine Saloum, central region of Senegal), and in Casamance (southern region of Senegal).

Methods
A total of 204 ticks and 433 blood samples were collected from ruminants, horses, donkeys and dogs. Ticks were identified morphologically and by molecular characterization targeting the 12S rRNA gene. Molecular characterization of species of Anaplasmataceae infecting Senegalese ticks and animals was conducted using the 23S rRNA, 16S rRNA, rpoB and groEL genes.

Results
Ticks were identified as Rhipicephalus evertsi evertsi (84.3%), Hyalomma rufipes (8.3%), Hyalomma impeltatum (4.9%), R. bursa (1.5%) and R. muhsamae (0.9%). The overall prevalence of Anaplasmataceae infection in ticks was 0.9%, whereas 41.1% of the sampled animals were found infected by one of the species belonging to this family. We identified the pathogen Anaplasma ovis in 55.9% of sheep, A. marginale and A. centrale in 19.4% and 8.1%, respectively, of cattle, as well as a putative new species of Anaplasmataceae. Two Anaplasma species commonly infecting ruminants were identified. Anaplasma cf. platys, closely related to A. platys was identified in 19.8% of sheep, 27.7% of goats and 22.6% of cattle, whereas a putative new species, named here provisionally “Candidatus Anaplasma africae”, was identified in 3.7% of sheep, 10.3% of goats and 8.1% of cattle. Ehrlichia canis and Anaplasma platys were identified only from dogs sampled in the Keur Momar Sarr area. Ehrlichia canis was identified in 18.8% of dogs and two R. e. evertsi ticks removed from the same sheep. Anaplasma platys was identified in 15.6% of dogs. Neither of the dogs sampled from Casamance region nor the horses and donkeys sampled from Keur Momar Sarr area were found infected by an Anaplasmataceae species.

Conclusions
This study presents a summary of Anaplasmataceae species that infect animals and ticks in three areas from the northern, central and southern regions of Senegal. To our knowledge, our findings demonstrate for the first time the presence of multiple Anaplasmataceae species that infect ticks and domestic animals in Senegal. We recorded two potentially new species commonly infecting ruminants named here provisionally as Anaplasma cf. platys and “Candidatus Anaplasma africae”. However, E. canis was the only species identified and amplified from ticks. None of the other Anaplasmataceae species identified in animals were identified in the tick species collected from animals.
Mapping genetic interactions in cancer: a road to rational combination therapies
Authors: Tutuncuoglu Beril , Krogan Nevan J. 
Published: October 2019

Abstract
The discovery of synthetic lethal interactions between poly (ADP-ribose) polymerase (PARP) inhibitors and BRCA genes, which are involved in homologous recombination, led to the approval of PARP inhibition as a monotherapy for patients with BRCA1/2-mutated breast or ovarian cancer. Studies following the initial observation of synthetic lethality demonstrated that the reach of PARP inhibitors is well beyond just BRCA1/2 mutants. Insights into the mechanisms of action of anticancer drugs are fundamental for the development of targeted monotherapies or rational combination treatments that will synergize to promote cancer cell death and overcome mechanisms of resistance. The development of targeted therapeutic agents is premised on mapping the physical and functional dependencies of mutated genes in cancer. An important part of this effort is the systematic screening of genetic interactions in a variety of cancer types. Until recently, genetic-interaction screens have relied either on the pairwise perturbations of two genes or on the perturbation of genes of interest combined with inhibition by commonly used anticancer drugs. Here, we summarize recent advances in mapping genetic interactions using targeted, genome-wide, and high-throughput genetic screens, and we discuss the therapeutic insights obtained through such screens. We further focus on factors that should be considered in order to develop a robust analysis pipeline. Finally, we discuss the integration of functional interaction data with orthogonal methods and suggest that such approaches will increase the reach of genetic-interaction screens for the development of rational combination therapies.
Molecular profiling of rheumatoid arthritis patients reveals an association between innate and adaptive cell populations and response to anti-tumor necrosis factor
Authors: Farutin Victor , Prod’homme Thomas , McConnell Kevin , Washburn Nathaniel , Halvey Patrick , Etzel Carol J. , Guess Jamey , Duffner Jay , Getchell Kristen , Meccariello Robin , Gutierrez Bryan , Honan Christopher , Zhao Ganlin , Cilfone Nicholas A. , Gunay Nur Sibel , Hillson Jan L. , DeLuca David S. , Saunders Katherine C. , Pappas Dimitrios A. , Greenberg Jeffrey D. , Kremer Joel M. , Manning Anthony M. , Ling Leona E. , Capila Ishan 
Published: October 2019

Abstract

Background
The goal of this study is to use comprehensive molecular profiling to characterize clinical response to anti-TNF therapy in a real-world setting and identify reproducible markers differentiating good responders and non-responders in rheumatoid arthritis (RA).

Methods
Whole-blood mRNA, plasma proteins, and glycopeptides were measured in two cohorts of biologic-naïve RA patients (n = 40 and n = 36) from the Corrona CERTAIN (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory coNditions) registry at baseline and after 3 months of anti-TNF treatment. Response to treatment was categorized by EULAR criteria. A cell type-specific data analysis was conducted to evaluate the involvement of the most common immune cell sub-populations. Findings concordant between the two cohorts were further assessed for reproducibility using selected NCBI-GEO datasets and clinical laboratory measurements available in the CERTAIN database.

Results
A treatment-related signature suggesting a reduction in neutrophils, independent of the status of response, was indicated by a high level of correlation (ρ = 0.62; p < 0.01) between the two cohorts. A baseline, response signature of increased innate cell types in responders compared to increased adaptive cell types in non-responders was identified in both cohorts. This result was further assessed by applying the cell type-specific analysis to five other publicly available RA datasets. Evaluation of the neutrophil-to-lymphocyte ratio at baseline in the remaining patients (n = 1962) from the CERTAIN database confirmed the observation (odds ratio of good/moderate response = 1.20 [95% CI = 1.03–1.41, p = 0.02]).

Conclusion
Differences in innate/adaptive immune cell type composition at baseline may be a major contributor to response to anti-TNF treatment within the first 3 months of therapy.
Prediction of protein architectures involved in the signaling-pathway initiating sporulation in Firmicutes
Authors: Martinez-Amador Paola , Castañeda Nori , Loza Antonio , Soto Lizeth , Merino Enrique , Gutierrez-Rios Rosa Maria 
Published: October 2019

Abstract

Objectives
Like many other proteins, those belonging to the signal transduction cascade initiating sporulation (Spo0 pathway) have conserved protein domains (Capra and Laub in Annu Rev Microbiol 66:325–47, 2012). Improvements in bioinformatics applications to discover proteins involved in the initiation of the sporulating cascade in newly sequenced genomes is an important task that requires rigorous comparative genomic methods and manual curation to identify endospore-forming bacteria. This note aims to present a collection of predicted proteins involved in the Spo0 pathway found in the proteomes of fully sequenced and manually curated endospore-forming Firmicutes species. This collection may serve as a guide to conduct future experiments in endospore formers in genomic and metagenomic projects.

Data description
Similar to the report of Davidson et al. (PLoS Genet 14:1–33, 2018), we used Pfam profiles (El-Gebali et al. in Nucleic Acids Res 47:D427–32, 2019) defining each protein and the genomic context surrounding the query gene to predict probable orthologs of the Spo0 pathway in Firmicutes. We present in this note a collection of 325 Firmicutes species organized by phylogenetic class and classified as spore formers, non-spore formers or unknown spore phenotype based on published literature, for which we predicted probable orthologs defining the signal transduction pathway initiating sporulation.
The relationship between addiction to mobile phone and sense of loneliness among students of medical sciences in Kermanshah, Iran
Authors: Jafari Hale , Aghaei Abas , khatony Alireza 
Published: October 2019

Abstract

Objective
Addiction to mobile phone is one of the negative consequences of excessive use of this device. This disorder may also be related to individuals’ loneliness and may reduce or increase the sense of loneliness. Therefore, the present study aimed to investigate the relationship between addiction to mobile phone and sense of loneliness among medical sciences students.

Results
In this descriptive-analytical study, 439 students entered the study by stratified random sampling. The study tool was the mobile phone addiction and SELSA’s sense of loneliness questionnaires. The average score of mobile phone addiction in boys and girls was 73.77 ± 11.48 and 74.64 ± 12.28 from 100, respectively. There was no significant difference between them. According to the rating of mobile phone addiction, 17.8% of the students were in the range of moderate dependency and 10.9% of them were in the range of extreme dependency. Also, 71.3% of the students were identified as mobile phone addicts. The average score of sense of loneliness in boys and girls was 43.22 ± 5.16 and 42.82 ± 5.30, out of 105, respectively. There was no significant difference between them. There was a significant and negative correlation between the scores of mobile phone addiction and sense of loneliness.