bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective study of epigenetic alterations responsible for isolated hemihyperplasia/hemihypoplasia and their association with leg length discrepancy
Authors: Shin Chang Ho , Lim Chaemoon , Kim Hwa Young , Yoo Won Joon , Cho Tae-Joon , Choi In Ho , Ko Jung Min 
Published: October 2021

AbstractBackgroundHemihyperplasia and hemihypoplasia result in leg length discrepancy (LLD) by causing skeletal asymmetry. Beckwith–Wiedemann syndrome (BWS) and Silver–Russell syndrome (SRS) are opposite growth-affecting disorders caused by opposite epigenetic alterations at the same chromosomal locus, 11p15, to induce hemihyperplasia and hemihypoplasia, respectively. Because of their somatic mosaicism, BWS and SRS show a wide spectrum of clinical phenotypes. We evaluated the underlying epigenetic alterations and potential epigenotype-phenotype correlations, focusing on LLD, in a group of individuals with isolated hemihyperplasia/hemihypoplasia.ResultsWe prospectively collected paired blood-tissue samples from 30 patients with isolated hemihyperplasia/hemihypoplasia who underwent surgery for LLD. Methylation-specific multiplex-ligation-dependent probe amplification assay (MS-MLPA) and bisulfite pyrosequencing for differentially methylated regions 1 and 2 (DMR1 and DMR2) on chromosome 11p15 were performed using the patient samples. Samples from patients showing no abnormalities in MS-MLPA or bisulfite pyrosequencing were analyzed by single nucleotide polymorphism (SNP) microarray andCDKN1CSanger sequencing. We introduced a metric named as the methylation difference, defined as the difference in DNA methylation levels between DMR1 and DMR2. The correlation between the methylation difference and the predicted LLD at skeletal maturity, calculated using a multiplier method, was evaluated. Predicted LLD was standardized for stature. Ten patients (33%) showed epigenetic alterations in MS-MLPA and bisulfite pyrosequencing. Of these, six and four patients had epigenetic alterations related to BWS and SRS, respectively. The clinical diagnosis of hemihyperplasia/hemihypoplasia was not compatible with the epigenetic alterations in four of these ten patients. No patients showed abnormalities in SNP array or theirCDKN1Csequences. The standardized predicted LLD was moderately correlated with the methylation difference using fat tissue (r = 0.53;p = 0.002) and skin tissue (r = 0.50;p = 0.005) in all patients.ConclusionsIsolated hemihyperplasia and hemihypoplasia can occur as a spectrum of BWS and SRS. Although the accurate differentiation between isolated hemihyperplasia and isolated hemihypoplasia is important in tumor surveillance planning, it is often difficult to clinically differentiate these two diseases without epigenetic tests. Epigenetic tests may play a role in the prediction of LLD, which would aid in treatment planning.
The diagnostic odyssey of autism: a cross-sectional study of 3 age cohorts of children from the 2016–2018 National Survey of Children’s Health
Authors: Hanley Allison , Nguyen Quynh C. , Badawi Deborah Golant , Chen Jie , Ma Tianzhou , Slopen Natalie 
Published: October 2021

Abstract
Background
Autism prevalence has increased rapidly in recent years, however, nationally representative estimates on the ages of first identification and intervention are out of date. Objectives: (1) To estimate the ages at which children with autism receive their first diagnosis, intervention plan, and developmental services; and (2) To evaluate differences in ages at events by birth cohort and sociodemographic characteristics.

Methods
Using cross-sectional data from the 2016–2018 National Survey of Children’s Health (NSCH), we examined associations via linear regression among a sample of 2303 children aged 2–17 years old, who had ever been diagnosed with autism and either (1) ever had a plan for special education or early intervention, or (2) ever received special services to meet developmental needs. Exposures included age cohort, child, household and healthcare provider characteristics.

Results
Most children in the study sample (n = 2303) were over age 6 years, male, of non-Hispanic white race/ethnicity and had mild/moderate autism. Mean ages (years) at first diagnosis was 4.56 (SE = 0.13); first plan was 4.43 (SE = 0.11); and first services was 4.10 (SE = 0.11). After adjustment for exposures and survey year, the middle childhood cohort was 18 months older at first intervention (β = 1.49, 95% CI, 1.18–1.81), and adolescents were 38 months older at first diagnosis (β = 3.16, 95% CI, 2.72–3.60) compared to those in early childhood. Younger ages at events were observed among: Hispanic/Latinx as compared to white children, those with moderate or severe symptoms as compared to mild symptoms, and children who received their diagnosis from a specialist as compared to psychologists or psychiatrists.

Conclusions
Children with autism receive their first diagnosis, intervention plans and developmental services at younger ages than they had in the past. Future research is needed to identify the mechanisms for these improvements in early identification and intervention to accelerate additional progress.
Targeting MUS81 promotes the anticancer effect of WEE1 inhibitor and immune checkpoint blocking combination therapy via activating cGAS/STING signaling in gastric cancer cells
Authors: Li Chengguo , Shen Qian , Zhang Peng , Wang Tao , Liu Weizhen , Li Ruidong , Ma Xianxiong , Zeng Xiangyu , Yin Yuping , Tao Kaixiong 
Published: October 2021

Abstract
Background
Identification of genomic biomarkers to predict the anticancer effects of indicated drugs is considered a promising strategy for the development of precision medicine. DNA endonuclease MUS81 plays a pivotal role in various biological processes during malignant diseases, mainly in DNA damage repair and replication fork stability. Our previous study reported that MUS81 was highly expressed and linked to tumor metastasis in gastric cancer; however, its therapeutic value has not been fully elucidated.

Methods
Bioinformatics analysis was used to define MUS81-related differential genes, which were further validated in clinical tissue samples. Gain or loss of function MUS81 cell models were constructed to elucidate the effect and mechanism of MUS81 on WEE1 expression. Moreover, the antitumor effect of targeting MUS81 combined with WEE1 inhibitors was verified using in vivo and in vitro assays. Thereafter, the cGAS/STING pathway was evaluated, and the therapeutic value of MUS81 for immunotherapy of gastric cancer was determined.

Results
In this study, MUS81 negatively correlated with the expression of cell cycle checkpoint kinase WEE1. Furthermore, we identified that MUS81 regulated the ubiquitination of WEE1 via E-3 ligase β-TRCP in an enzymatic manner. In addition, MUS81 inhibition could sensitize the anticancer effect of the WEE1 inhibitor MK1775 in gastric cancer in vitro and in vivo. Interestingly, when MUS81 was targeted, it increased the accumulation of cytosolic DNA induced by MK1775 treatment and activated the DNA sensor STING-mediated innate immunity in the gastric cancer cells. Thus, the WEE1 inhibitor MK1775 specifically enhanced the anticancer effect of immune checkpoint blockade therapy in MUS81 deficient gastric cancer cells.

Conclusions
Our data provide rational evidence that targeting MUS81 could elevate the expression of WEE1 by regulating its ubiquitination and could activate the innate immune response, thereby enhancing the anticancer efficacy of WEE1 inhibitor and immune checkpoint blockade combination therapy in gastric cancer cells.
Association of exposure to hydrocarbon air pollution with the incidence of atopic dermatitis in children
Authors: Wang Chieh , Wei Chang-Ching , Wan Lei , Lin Cheng-Li , Tsai Jeng-Dau 
Published: October 2021

Abstract
Background
There is growing evidence suggesting that air pollution may act as an important environmental risk factor in the development and aggravation of childhood atopic dermatitis (AD).

Methods
We collected data from the Taiwan National Health Insurance (NHI) research database and linked the data to the Taiwan Air Quality-Monitoring Database. From January 1, 2000 to December 31, 2012; children aged below 18 years were selected from the database and followed longitudinally until the diagnosis of AD, withdrawal from the NHI, or December 31, 2012. Children with missing data or those diagnosed with AD before enrolment in this study were excluded. We measured the incidence rate and hazard ratios (HRs) for AD and stratified them by quartiles (Q1–Q4) of air pollutant concentration. Multivariable Cox proportional hazards models were also applied by adjusting for age, sex, monthly income, and level of urbanization.

Results
When compared with the concentrations of pollutants in the Q1 quartile, the adjusted HR for AD increased with an increase in the exposure concentrations of total hydrocarbons (THCs), non-methane hydrocarbons (NMHCs), and methane (CH4) from 1.65 (95% confidence interval [CI]: 1.47–1.84) to 10.6 (95% CI: 5.85–7.07), from 1.14 (95% CI: 1.06–1.24) to 2.47 (95% CI: 2.29–2.66), and from 1.70 (95% CI: 1.52–1.89) to 11.9 (95% CI: 10.8–13.1), respectively. Patients exposed to higher levels of THCs, NMHCs, and CH4 exhibited greater incidence rates of childhood AD.

Conclusions
The present study demonstrated that exposure to higher concentrations of THCs, NMHCs, and CH4 were associated with an increased risk of childhood AD.
Is there an optimal place to hold the endotracheal tube during direct laryngoscopy for patients undergoing surgery under general anesthesia? Protocol for a randomized controlled trial
Authors: Sahoo Manisha , Tripathy Swagata , Mishra Nitasha 
Published: October 2021

Abstract
Background
Endotracheal intubation by direct laryngoscopy is a widely performed lifesaving technique. Although there are guidelines for optimal size and depth of insertion of an endotracheal tube (ETT) for successful intubation, there is no consensus on the point at which it should be held along its length. This will arguably affect the time, ease, and success of the technique due to a difference in visualization and torque applied to the ETT after glottic visualization. We aim to compare the effect of 2 different sites of holding the ETT on time to intubation (TTI), intubation difficulty scale (IDS), and complications.

Methods
ASA 1–2 patients (>18 years) posted for surgery under general anesthesia, undergoing supervised intubation by anesthesia trainees (experience < 18 months), will be included. Patients with an anticipated difficult airway or unanticipated difficulty—CL grade 3 or 4 requiring the use of airway adjuncts—will be excluded. Patients will be randomized by a computer-generated number list, and allocation concealed with opaque sealed envelopes. The two sites for holding the ETT will be group 1 at 19 cm and group 2 at 24 cm. ETT marked at the selected site will be handed by the technician once the optimum position of the table, patient, and laryngoscopic view is confirmed by the intubator. The entire procedure will be video recorded. Two blinded assessors will independently review the videos to document the time to intubation and intubation difficulty score. A postoperative sore throat will be recorded.

Sample size
To detect a 20% difference in time to intubation between groups with a significance level of 5% and power of 85%, we will need a total of 298 patients. Accounting for data loss, we plan to recruit 180 patients in each group.

Discussion
This will be the first study to assess whether the site of holding the tube has any impact on the ease and time taken for intubation. The findings of this study will provide scientific evidence for suggesting an appropriate place for holding the ETT during direct laryngoscopy procedures.

Trial registration
Clinical Trials Registry India CTRI/2019/09/021201
Photodynamic therapy for synovial hyperplasia in patients with refractory rheumatoid arthritis: a study protocol for a randomized, double-blind, blank-controlled prospective trial
Authors: Zhao Xiaofeng , Zuo Fangfang , Chen Ensheng , Bi Yanan , Cao Yanyan , Yuan Yi , Li Kaiqin , Xuan Yanan , Li Libo , Wan Lijuan , Zhang Xiangqun , Yan Feifei , Zhou Jiyuan , Yin Kun , Xiao Changhong 
Published: October 2021

Abstract
Background
Persistent synovial hyperplasia with inflammation in rheumatoid arthritis is one of the main pathogeneses of refractory rheumatoid arthritis (RRA). Photodynamic therapy (PDT) causes less trauma than steroid injections or arthroscopic synovectomy while providing stronger targeting and more durable curative effects. The aim of this trial was to evaluate the short-, medium-, and long-term clinical efficacy of PDT when applied as a treatment for RRA synovial hyperplasia and synovitis.

Methods and analysis
This protocol is for a single-center, randomized, double-blind, blank-controlled prospective trial. A sample of 126 RRA patients will be randomly divided into 3 groups: the control group, the “PDT once” group, and the “PDT twice” group, with 42 participants per group. The trial will be conducted by the Rheumatology and Immunology Department of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University. The Ultrasound Compound Score of Synovitis (UCSS) has been selected as the primary outcome measure. The secondary outcome measures include knee joint clinical assessments, ratio of relapse, duration of remission, Disease Activity Score in 28 joints (DAS28), inflammation indexes, serum concentrations of specific antibodies, and changes in articular structures as detected by X-ray scans in the 48th week. The improvement ratios of the UCSS at the 8th, 24th, and 48th weeks (compared with baseline) reflect short-, medium-, and long-term time frames, respectively.

Ethics and dissemination
The protocol was approved by the Medical Ethics Committee of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, China (Approval No. granted by the ethics committee: NFZXYEC-2017-005) and then entered in the Chinese Clinical Trials Registry under registration number ChiCTR1800014918 (approval date: February 21, 2018). All procedures are in accordance with Chinese laws and regulations and with the Declaration of Helsinki by the World Medical Association (WMA). Any modifications of this protocol during execution will need additional approval from the Ethics Committee of our hospital.

Trial registration number
ChiCTR1800014918.
Efficiency of donepezil in elderly patients undergoing orthopaedic surgery due to underlying post-operative cognitive dysfunction: study protocol for a multicentre randomised controlled trial
Authors: Zhu Huichen , Cong Lu , Chen Yi , Chen Shaoyi , Chen Lingke , Huang Zhenling , Zhou Jie , Xiao Jie , Huang Yonglei , Su Diansan 
Published: October 2021

Abstract
Background
Post-operative cognitive dysfunction (POCD) is an overarching term used to describe cognitive impairment identified in the preoperative or post-operative period. After surgical operations, older patients are particularly vulnerable to memory disturbances and other types of cognitive impairment. However, the pathogenesis of POCD remains unclear with no confirmed preventable or treatable strategy available. Our previous study demonstrated that the concentration of choline acetyl transferase in the cerebral spinal fluid was a predictive factor of POCD and that donepezil, which is an acetylcholinesterase inhibitor used in clinical settings for the treatment of Alzheimer’s disease, can prevent learning and memory impairment after anaesthesia/surgery in aged mice. This study aimed to determine the critical role of donepezil in preventing cognitive impairment in elderly patients undergoing orthopaedic surgery.

Methods
A multicentre, double-blind, placebo-controlled, crossover clinical trial will be performed to assess the efficacy of donepezil in elderly patients undergoing orthopaedic surgery. Participants (n = 360) will receive donepezil (5 mg once daily) or placebo from 1 day prior to surgery until 5 days after surgery. Neuropsychological tests will be measured at 1 day before the operation and 1 week, 1 month, 6 months and 1 year after the operation.

Discussion
This research project mainly aimed to study the effects of donepezil in elderly patients undergoing orthopaedic surgery due to underlying POCD and to investigate the underlying physiological and neurobiological mechanisms of these effects. The results may provide important implications for the development of effective interfering strategies, specifically regarding cognitive dysfunction therapy using drugs.

Trial registration
ClinicalTrials.govNCT04423276. Registered on 14 June 2020
The potential risk of enzootic Trypanosoma cruzi transmission inside four training and re-training military battalions (BITER) in Colombia
Authors: Cantillo-Barraza Omar , Torres Jeffer , Hernández Carolina , Romero Yanira , Zuluaga Sara , Correa-Cárdenas Camilo A. , Herrera Giovanny , Rodríguez Omaira , Alvarado María Teresa , Ramírez Juan David , Méndez Claudia 
Published: October 2021

Abstract
Background
Colombia’s National Army is one of the largest military institutions in the country based on the number of serving members and its presence throughout the country. There have been reports of cases of acute or chronic cases of Chagas disease among active military personnel. These may be the result of military-associated activities performed in jungles and other endemic areas or the consequence of exposure to Trypanosoma cruzi inside military establishments/facilities located in endemic areas. The aim of the present study was to describe the circulation of T. cruzi inside facilities housing four training and re-training battalions [Battalions of Instruction, Training en Re-training (BITERs)] located in municipalities with historical reports of triatomine bugs and Chagas disease cases. An entomological and faunal survey of domestic and sylvatic environments was conducted inside each of these military facilities.

Methods
Infection in working and stray dogs present in each BITER location was determined using serological and molecular tools, and T. cruzi in mammal and triatomine bug samples was determined by PCR assay. The PCR products of the vertebrate 12S rRNA gene were also obtained and subjected to Sanger sequencing to identify blood-feeding sources. Finally, we performed a geospatial analysis to evaluate the coexistence of infected triatomines and mammals with the military personal inside of each BITER installation.

Results
In total, 86 specimens were collected: 82 Rhodnius pallescens, two Rhodnius prolixus, one Triatoma dimidiata and one Triatoma maculata. The overall T. cruzi infection rate for R. pallescens and R. prolixus was 56.1 and 100% respectively, while T. dimidiata and T. maculata were not infected. Eight feeding sources were found for the infected triatomines, with opossum and humans being the most frequent sources of feeding (85.7%). Infection was most common in the common opossum Didelphis marsupialis, with infection levels of 77.7%. Sylvatic TcI was the most frequent genotype, found in 80% of triatomines and 75% of D. marsupialis. Of the samples collected from dogs (n = 52), five (9.6%; 95% confidence interval: 3.20–21.03) were seropositive based on two independent tests. Four of these dogs were creole and one was a working dog. The spatial analysis revealed a sympatry between infected vectors and mammals with the military population.

Conclusions
We have shown a potential risk of spillover of sylvatic T. cruzi transmission to humans by oral and vectorial transmission in two BITER installations in Colombia. The results indicate that installations where 100,000 active military personnel carry out training activities should be prioritized for epidemiological surveillance of Chagas disease.

Graphical abstract
Effect of personal activity intelligence (PAI) monitoring in the maintenance phase of cardiac rehabilitation: a mixed methods evaluation
Authors: Hannan Amanda L. , Hing Wayne , Coombes Jeff S. , Gough Suzanne , Climstein Mike , Adsett Geoff , Jayasinghe Rohan , Furness James 
Published: October 2021

Abstract
Background
Personal activity intelligence (PAI) is a single physical activity metric based upon heart rate responses to physical activity. Maintaining 100 PAI/week is associated with a 25% risk reduction in cardiovascular disease mortality and 50 PAI/week provides 60% of the benefits. The effect of utilising this metric within a cardiac population has not been previously investigated. The aim of this study was to determine the effect of PAI monitoring on the amount and/or intensity of physical activity for people in the maintenance phase of cardiac rehabilitation and to explore participants’ perceptions of this approach.

Methods
A concurrent mixed methods approach was undertaken. Participants in the maintenance phase of cardiac rehabilitation monitored PAI for six weeks via a wearable physical activity monitoring device (WPAM). In the first three weeks participants were blinded to their PAI score. A quality-of-life questionnaire (EQ-5D-5L) was completed, and semi-structured interviews conducted to investigate attitudes to PAI monitoring. Daily PAI data was collected throughout the 6-week period.

Results
Twenty participants completed the trial. PAI earned/day was increased after participants could view their data (mean difference: 2.1 PAI/day (95% CI 0.3, 4.0), p = 0.027). The median change in percentage of days participants achieved a Total PAI score of 25 (p = 0.023) and 50 (p = 0.015) were also increased. The mean change in total scores for the EQ-5D-5L and EQVAS were improved after 6 weeks (0.6 ± 1.05; 95% CI (0.11–1.09); p = 0.019); (5.8/100; 95% CI (2.4–9.2); p = 0.002 respectively). Thematic framework analysis identified three global themes (perceptions on the WPAM, PAI and factors affecting exercise). Most participants stated motivation to exercise increased after they could view their PAI data. Many of the participants believed they would continue to use PAI long-term. Others were undecided; the latter primarily due to technical issues and/or preferring devices with greater functionality and attractiveness. All participants would recommend PAI.

Conclusion
This exploratory study showed monitoring PAI via a WPAM increased the amount and/or intensity of physical activity within the cardiac population. Participants found PAI interesting, beneficial, and motivating. If technical issues, aesthetics, and functionality of the WPAM were improved, participants may continue to use the approach long-term. PAI may be a viable strategy to assist people with cardiac disease maintain physical activity adherence.
De novo assembly and annotation of the mangrove cricket genome
Authors: Satoh Aya , Takasu Miwako , Yano Kentaro , Terai Yohey 
Published: October 2021

Abstract
Objectives
The mangrove cricket, Apteronemobius asahinai, shows endogenous activity rhythms that synchronize with the tidal cycle (i.e., a free-running rhythm with a period of ~ 12.4 h [the circatidal rhythm]). Little is known about the molecular mechanisms underlying the circatidal rhythm. We present the draft genome of the mangrove cricket to facilitate future molecular studies of the molecular mechanisms behind this rhythm.

Data description
The draft genome contains 151,060 scaffolds with a total length of 1.68 Gb (N50: 27 kb) and 92% BUSCO completeness. We obtained 28,831 predicted genes, of which 19,896 (69%) were successfully annotated using at least one of two databases (UniProtKB/SwissProt database and Pfam database).