bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide sequencing as a first-tier screening test for short tandem repeat expansions
Authors: Rajan-Babu Indhu-Shree , Peng Junran J. , Chiu Readman ,   IMAGINE Study, Birch Patricia , Couse Madeline , Guimond Colleen , Lehman Anna , Mwenifumbo Jill , van Karnebeek Clara , Friedman Jan ,   CAUSES Study, Adam Shelin , Souich Christele Du , Elliott Alison , Lehman Anna , Mwenifumbo Jill , Nelson Tanya , van Karnebeek Clara , Friedman Jan , Li Chenkai , Mohajeri Arezoo , Dolzhenko Egor , Eberle Michael A. , Birol Inanc , Friedman Jan M. 
Published: August 2021

Abstract
Background
Screening for short tandem repeat (STR) expansions in next-generation sequencing data can enable diagnosis, optimal clinical management/treatment, and accurate genetic counseling of patients with repeat expansion disorders. We aimed to develop an efficient computational workflow for reliable detection of STR expansions in next-generation sequencing data and demonstrate its clinical utility.

Methods
We characterized the performance of eight STR analysis methods (lobSTR, HipSTR, RepeatSeq, ExpansionHunter, TREDPARSE, GangSTR, STRetch, and exSTRa) on next-generation sequencing datasets of samples with known disease-causing full-mutation STR expansions and genomes simulated to harbor repeat expansions at selected loci and optimized their sensitivity. We then used a machine learning decision tree classifier to identify an optimal combination of methods for full-mutation detection. In Burrows-Wheeler Aligner (BWA)-aligned genomes, the ensemble approach of using ExpansionHunter, STRetch, and exSTRa performed the best (precision = 82%, recall = 100%, F1-score = 90%). We applied this pipeline to screen 301 families of children with suspected genetic disorders.

Results
We identified 10 individuals with full-mutations in the AR, ATXN1, ATXN8, DMPK, FXN, or HTT disease STR locus in the analyzed families. Additional candidates identified in our analysis include two probands with borderline ATXN2 expansions between the established repeat size range for reduced-penetrance and full-penetrance full-mutation and seven individuals with FMR1 CGG repeats in the intermediate/premutation repeat size range. In 67 probands with a prior negative clinical PCR test for the FMR1, FXN, or DMPK disease STR locus, or the spinocerebellar ataxia disease STR panel, our pipeline did not falsely identify aberrant expansion. We performed clinical PCR tests on seven (out of 10) full-mutation samples identified by our pipeline and confirmed the expansion status in all, showing absolute concordance between our bioinformatics and molecular findings.

Conclusions
We have successfully demonstrated the application of a well-optimized bioinformatics pipeline that promotes the utility of genome-wide sequencing as a first-tier screening test to detect expansions of known disease STRs. Interrogating clinical next-generation sequencing data for pathogenic STR expansions using our ensemble pipeline can improve diagnostic yield and enhance clinical outcomes for patients with repeat expansion disorders.
Whole genome resequencing data for rock pigeon (Columba livia)
Authors: Esmailizadeh Ali , Kharrati-Koopaee Hamed , Nanaei Hojjat Assadoullahpour 
Published: August 2021

AbstractObjectiveNavigation is the most important feature of homing pigeons, however no integrated response to genetic mechanism of navigation has been reported. The generated data herein represent whole-genome resequencing data for homing pigeon and three other breeds of rock pigeons. Selective sweep analysis between homing pigeon and other breeds of rock pigeon can provide new insight about identification of candidate genes and biological pathways for homing pigeon ability.Data descriptionWhole-genomes sequence data related to 95 birds from four breeds of rock pigeons including, 29 feral pigeons, 24 Shiraz tumblers, 24 Persian high flyers and 18 homing pigeons were provided. More than 6.94 billion short reads with coverage (average ≈7.50 x) and 407.1 Gb data were produced. Whole genome sequencing was carried out on the Illumina Hiseq 2000 platform using a 350 bp library size and 150 bp paired-end read lengths. The whole genome sequencing data have been submitted at the NCBI SRA Database (PRJNA532675). The presented data set can provide useful genomic information to explain the genetic mechanism of navigation ability of homing pigeons and also testing other genetic hypothesis by genomic analysis.
Evaluation of global and intragenic hypomethylation in colorectal adenomas improves patient stratification and colorectal cancer risk prediction
Authors: Debernardi Carla , Libera Laura , Berrino Enrico , Sahnane Nora , Chiaravalli Anna Maria , Laudi Cristiana , Berselli Mattia , Sapino Anna , Sessa Fausto , Venesio Tiziana , Furlan Daniela 
Published: August 2021

Abstract
Background
Aberrant DNA hypomethylation of the long interspersed nuclear elements (LINE-1 or L1) has been recognized as an early event of colorectal transformation. Simultaneous genetic and epigenetic analysis of colorectal adenomas may be an effective and rapid strategy to identify key biological features leading to accelerated colorectal tumorigenesis. In particular, global and/or intragenic LINE-1 hypomethylation of adenomas may represent a helpful tool for improving colorectal cancer (CRC) risk stratification of patients after surgical removal of polyps. To verify this hypothesis, we analyzed a cohort of 102 adenomas derived from 40 high-risk patients (who developed CRC in a post-polypectomy of at least one year) and 43 low-risk patients (who did not develop CRC in a post-polypectomy of at least 5 years) for their main pathological features, the presence of hotspot variants in driver oncogenes (KRAS, NRAS, BRAF and PIK3CA), global (LINE-1) and intragenic (L1-MET) methylation status.

Results
In addition to a significantly higher adenoma size and an older patients’ age, adenomas from high-risk patients were more hypomethylated than those from low-risk patients for both global and intragenic LINE-1 assays. DNA hypomethylation, measured by pyrosequencing, was independent from other parameters, including the presence of oncogenic hotspot variants detected by mass spectrometry. Combining LINE-1 and L1-MET analyses and profiling the samples according to the presence of at least one hypomethylated assay improved the discrimination between high and low risk lesions (p = 0.005). Remarkably, adenomas with at least one hypomethylated assay identified the patients with a significantly (p < 0.001) higher risk of developing CRC. Multivariable analysis and logistic regression evaluated by the ROC curves proved that methylation status was an independent variable improving cancer risk prediction (p = 0.02).

Conclusions
LINE-1 and L1-MET hypomethylation in colorectal adenomas are associated with a higher risk of developing CRC. DNA global and intragenic hypomethylation are independent markers that could be used in combination to successfully improve the stratification of patients who enter a colonoscopy surveillance program.

Graphic abstract
Childhood growth and development and DNA methylation age in mid-life
Authors: Maddock Jane , Castillo-Fernandez Juan , Wong Andrew , Ploubidis George B. , Kuh Diana , Bell Jordana T. , Hardy Rebecca 
Published: August 2021

Abstract
Background
In the first study of its kind, we examine the association between growth and development in early life and DNAm age biomarkers in mid-life.

Methods
Participants were from the Medical Research Council National Survey of Health and Development (n = 1376). Four DNAm age acceleration (AgeAccel) biomarkers were measured when participants were aged 53 years: AgeAccelHannum; AgeAccelHorvath; AgeAccelLevine; and AgeAccelGrim. Exposure variables included: relative weight gain (standardised residuals from models of current weight z-score on current height, and previous weight and height z-scores); and linear growth (standardised residuals from models of current height z-score on previous height and weight z-scores) during infancy (0–2 years, weight gain only), early childhood (2–4 years), middle childhood (4–7 years) and late childhood to adolescence (7–15 years); age at menarche; and pubertal stage for men at 14–15 years. The relationship between relative weight gain and linear growth and AgeAccel was investigated using conditional growth models. We replicated analyses from the late childhood to adolescence period and pubertal timing among 240 participants from The National Child and Development Study (NCDS).

Results
A 1SD increase in relative weight gain in late childhood to adolescence was associated with 0.50 years (95% CI 0.20, 0.79) higher AgeAccelGrim. Although the CI includes the null, the estimate was similar in NCDS [0.57 years (95% CI − 0.01, 1.16)] There was no strong evidence that relative weight gain and linear growth in childhood was associated with any other AgeAccel biomarker. There was no relationship between pubertal timing in men and AgeAccel biomarkers. Women who reached menarche ≥ 12 years had 1.20 years (95% CI 0.15, 2.24) higher AgeAccelGrim on average than women who reached menarche < 12 years; however, this was not replicated in NCDS and was not statistically significant after Bonferroni correction.

Conclusions
Our findings generally do not support an association between growth and AgeAccel biomarkers in mid-life. However, we found rapid weight gain during pubertal development, previously related to higher cardiovascular disease risk, to be associated with older AgeAccelGrim. Given this is an exploratory study, this finding requires replication.
Adipose-derived stem cells alleviate radiation-induced dermatitis by suppressing apoptosis and downregulating cathepsin F expression
Authors: Yao Chaoling , Zhou Yue , Wang Hui , Deng Feiyan , Chen Yongyi , Zhu Xiaomei , Kong Yu , Pan Lijun , Xue Lei , Zhou Xiao , Shi Chunmeng , Sheng Xiaowu 
Published: August 2021

Abstract
Background
Radiation-induced dermatitis is a serious side effect of radiotherapy, and very few effective treatments are currently available for this condition. We previously demonstrated that apoptosis is an important feature of radiation-induced dermatitis and adipose-derived stem cells (ADSCs) are one of the most promising types of stem cells that have a protective effect on acute radiation-induced dermatitis. Cathepsin F (CTSF) is a recently discovered protein that plays an important role in apoptosis. In this study, we investigated whether ADSCs affect chronic radiation-induced dermatitis, and the underlying mechanisms involved.

Methods
ADSCs were isolated from male Sprague-Dawley (SD) rats and characterized. For in vivo studies, rats were randomly divided into control and ADSC-treated groups, and cultured ADSCs were transplanted into radiation-induced dermatitis model rats. The effects of ADSC transplantation were determined by skin damage scoring, histopathological analysis, electron microscopy, immunohistochemical staining, and western blotting analysis of apoptosis-related proteins. To evaluate the effects of ADSCs in vitro, radiation-induced apoptotic cells were treated with ADSC culture supernatant, and apoptosis-related protein expression was investigated by TUNEL staining, flow cytometry, and western blotting.

Results
In the in vivo studies, skin damage, inflammation, fibrosis, and apoptosis were reduced and hair follicle and sebaceous gland regeneration were enhanced in the ADSC group compared with the control group. Further, CTSF and downstream pro-apoptotic proteins (Bid, BAX, and caspase 9) were downregulated, while anti-apoptotic proteins (Bcl-2 and Bcl-XL) were upregulated. In vitro, ADSCs markedly attenuated radiation-induced apoptosis, downregulated CTSF and downstream pro-apoptotic proteins, and upregulated anti-apoptotic proteins.

Conclusion
ADSCs protect against radiation-induced dermatitis by exerting an anti-apoptotic effect through inhibition of CTSF expression. ADSCs may be a good therapeutic candidate to prevent the development of radiation-induced dermatitis.
QPHAR: quantitative pharmacophore activity relationship: method and validation
Authors: Kohlbacher Stefan M. , Langer Thierry , Seidel Thomas 
Published: August 2021

AbstractQSAR methods are widely applied in the drug discovery process, both in the hit‐to‐lead and lead optimization phase, as well as in the drug-approval process. Most QSAR algorithms are limited to using molecules as input and disregard pharmacophores or pharmacophoric features entirely. However, due to the high level of abstraction, pharmacophore representations provide some advantageous properties for building quantitative SAR models. The abstract depiction of molecular interactions avoids a bias towards overrepresented functional groups in small datasets. Furthermore, a well‐crafted quantitative pharmacophore model can generalise to underrepresented or even missing molecular features in the training set by using pharmacophoric interaction patterns only. This paper presents a novel method to construct quantitative pharmacophore models and demonstrates its applicability and robustness on more than 250 diverse datasets. fivefold cross-validation on these datasets with default settings yielded an average RMSE of 0.62, with an average standard deviation of 0.18. Additional cross-validation studies on datasets with 15–20 training samples showed that robust quantitative pharmacophore models could be obtained. These low requirements for dataset sizes render quantitative pharmacophores a viable go-tomethod for medicinal chemists, especially in the lead-optimisation stage of drug discovery projects.
Hermite–Hadamard-type inequalities for geometrically r-convex functions in terms of Stolarsky’s mean with applications to means
Authors: Latif Muhammad Amer 
Published: August 2021

AbstractIn this paper, we obtain new Hermite–Hadamard-type inequalities for r-convex and geometrically convex functions and, additionally, some new Hermite–Hadamard-type inequalities by using the Hölder–İşcan integral inequality and an improved power-mean inequality.
Impact of vaccine supplies and delays on optimal control of the COVID-19 pandemic: mapping interventions for the Philippines
Authors: Estadilla Carlo Delfin S. , Uyheng Joshua , de Lara-Tuprio Elvira P. , Teng Timothy Robin , Macalalag Jay Michael R. , Estuar Maria Regina Justina E. 
Published: August 2021

Abstract
Background
Around the world, controlling the COVID-19 pandemic requires national coordination of multiple intervention strategies. As vaccinations are globally introduced into the repertoire of available interventions, it is important to consider how changes in the local supply of vaccines, including delays in administration, may be addressed through existing policy levers. This study aims to identify the optimal level of interventions for COVID-19 from 2021 to 2022 in the Philippines, which as a developing country is particularly vulnerable to shifting assumptions around vaccine availability. Furthermore, we explore optimal strategies in scenarios featuring delays in vaccine administration, expansions of vaccine supply, and limited combinations of interventions.

Methods
Embedding our work within the local policy landscape, we apply optimal control theory to the compartmental model of COVID-19 used by the Philippine government’s pandemic surveillance platform and introduce four controls: (a) precautionary measures like community quarantines, (b) detection of asymptomatic cases, (c) detection of symptomatic cases, and (d) vaccinations. The model is fitted to local data using an L-BFGS minimization procedure. Optimality conditions are identified using Pontryagin’s minimum principle and numerically solved using the forward–backward sweep method.

Results
Simulation results indicate that early and effective implementation of both precautionary measures and symptomatic case detection is vital for averting the most infections at an efficient cost, resulting in $$>99\%$$

>
99
%

reduction of infections compared to the no-control scenario. Expanding vaccine administration capacity to 440,000 full immunizations daily will reduce the overall cost of optimal strategy by $$25\%$$

25
%

, while allowing for a faster relaxation of more resource-intensive interventions. Furthermore, delays in vaccine administration require compensatory increases in the remaining policy levers to maintain a minimal number of infections. For example, delaying the vaccines by 180 days (6 months) will result in an $$18\%$$

18
%

increase in the cost of the optimal strategy.

Conclusion
We conclude with practical insights regarding policy priorities particularly attuned to the Philippine context, but also applicable more broadly in similar resource-constrained settings. We emphasize three key takeaways of (a) sustaining efficient case detection, isolation, and treatment strategies; (b) expanding not only vaccine supply but also the capacity to administer them, and; (c) timeliness and consistency in adopting policy measures.

Graphic Abstract
Preliminary Evidence for the Clinical Utility of Tactile Somatosensory Assessments of Sport-Related mTBI
Authors: McGeown Joshua P. , Hume Patria A. , Kara Stephen , King Doug , Theadom Alice 
Published: August 2021

Abstract
Objectives
To evaluate the clinical utility of tactile somatosensory assessments to assist clinicians in diagnosing sport-related mild traumatic brain injury (SR-mTBI), classifying recovery trajectory based on performance at initial clinical assessment, and determining if neurophysiological recovery coincided with clinical recovery.

Research Design
Prospective cohort study with normative controls.

Methods
At admission (n = 79) and discharge (n = 45/79), SR-mTBI patients completed the SCAT-5 symptom scale, along with the following three components from the Cortical Metrics Brain Gauge somatosensory assessment (BG-SA): temporal order judgement (TOJ), TOJ with confounding condition (TOJc), and duration discrimination (DUR). To assist SR-mTBI diagnosis on admission, BG-SA performance was used in logistic regression to discriminate cases belonging to the SR-mTBI sample or a healthy reference sample (pooled BG-SA data for healthy participants in previous studies). Decision trees evaluated how accurately BG-SA performance classified SR-mTBI recovery trajectories.

Results
BG-SA TOJ, TOJc, and DUR poorly discriminated between cases belonging to the SR-mTBI sample or a healthy reference sample (0.54–0.70 AUC, 47.46–64.71 PPV, 48.48–61.11 NPV). The BG-SA evaluated did not accurately classify SR-mTBI recovery trajectories (> 14-day resolution 48%, ≤14–day resolution 54%, lost to referral/follow-up 45%). Mann-Whitney U tests revealed differences in BG-SA TOJc performance between SR-mTBI participants and the healthy reference sample at initial clinical assessment and at clinical recovery (p < 0.05).

Conclusions
BG-SA TOJ, TOJc, and DUR appear to have limited clinical utility to assist clinicians with diagnosing SR-mTBI or predicting recovery trajectories under ecologically valid conditions. Neurophysiological abnormalities persisted beyond clinical recovery given abnormal BG-SA TOJc performance observed when SR-mTBI patients achieved clinical recovery.
Lee Silverman Voice Treatment versus standard speech and language therapy versus control in Parkinson’s disease: preliminary cost-consequence analysis of the PD COMM pilot randomised controlled trial
Authors: Scobie Sarah , Jowett Sue , Lambe Tosin , Patel Smitaa , Woolley Rebecca , Ives Natalie , Rick Caroline , Smith Christina , Brady Marion C , Clarke Carl , Sackley Cath 
Published: August 2021

AbstractBackgroundThe PD COMM pilot randomised controlled trial compared Lee Silverman Voice Treatment (LSVT® LOUD) with standard NHS speech and language therapy (SLT) and a control arm in people with Parkinson’s disease (PwPD) with self-reported problems with voice or speech. This analysis compares costs and quality of life outcomes between the trial arms, and considers the validity of the alternative outcome measures for economic evaluations.MethodsA comparison of costs and outcomes was undertaken alongside the PD COMM pilot trial involving three arms: LSVT® LOUD treatment (n = 30); standard NHS SLT (n = 30); and a control arm (n = 29) excluded from receiving therapy for at least 6 months after randomisation unless deemed medically necessary. For all trial arms, resource use and NHS, social care and patient costs and quality of life were collected prospectively at baseline, 3, 6, and 12 months. Total economic costs and outcomes (EQ-5D-3L, ICECAP-O) were considered over the 12-month follow-up period from an NHS payer perspective. Quality of life measures for economic evaluation of SLT for people with Parkinson’s disease were compared.ResultsWhilst there was no difference between arms in voice or quality of life outcomes at 12 months, there were indications of differences at 3 months in favour of SLT, which need to be confirmed in the main trial. The estimated mean cost of NHS care was £3288 per patient per year for the LSVT® LOUD arm, £2033 for NHS SLT, and £1788 for the control arm. EQ-5D-3L was more strongly correlated to voice impairment than ICECAP-O, and was sensitive to differences in voice impairment between arms.ConclusionsThe pilot did not identify an effect of SLT on disease-specific or economic outcomes for PwPD at 12 months; however, there appeared to be improvements at 3 months. In addition to the sample size not powered to detect difference in cost-consequence analysis, many patients in the control arm started SLT during the 12-month period used for economic analysis, in line with the study protocol. The LSVT® LOUD intervention was more intense and therefore more costly. Early indications suggest that the preferred economic outcome measure for the full trial is EQ-5D-3L; however, the ICECAP-O should still be included to capture a broader measure of wellbeing.Trial registrationInternational Standard Randomised Controlled Trial Number Register: ISRCTN75223808. Registered 22 March 2012.
Long noncoding RNA SNHG12 is a potential diagnostic and prognostic biomarker in various tumors
Authors: Wang Xinzhuang , Jiang Qiuyi , Zhang Cheng , Yang Quan , Wang Lixiang , Zhang Jian , Wang Ligang , Chen Xin , Hou Xu , Han Dayong , Wu Jianing , Zhao Shiguang 
Published: August 2021

Abstract
Background
Tumors are the second most common cause of death in humans worldwide, second only to cardiovascular and cerebrovascular diseases. Although methods and techniques for the treatment of tumors continue to improve, the effect is not satisfactory. These may lack effective therapeutic targets. This study aimed to evaluate the value of SNHG12 as a biomarker in the prognosis and clinical characteristics of various cancer patients.

Methods
We analyzed SNHG12 expression and plotted the survival curves of all cancer samples in the TCGA database using the GEPIA tool. Then, we searched for eligible papers up to April 1, 2019, in databases. Next, the data were extracted from studies examining SNHG12 expression, overall survival and clinicopathological features in patients with malignant tumors. We used Review Manager 5.3 and Stata 15 software to analyze the statistical data.

Results
In the TCGA database, abnormally high expression of SNHG12 in tumor samples indicates that the patient has a poor prognosis. Results of meta-analysis is that SNHG12 high expression is related to low overall survival (HR = 2.72, 95% CI = 1.95–3.8, P < 0.00001), high tumor stage (OR = 3.94, 95% CI = 2.80–5.53, P < 0.00001), high grade (OR = 2.04, 95% CI = 1.18–3.51, P = 0.01), distant metastasis (OR = 2.20, 95% CI = 1.40–3.46, P = 0.0006), tumor size (OR = 2.79, 95% CI = 1.89–4.14, P < 0.00001), and lymph node metastasis (OR = 2.66, 95% CI = 1.65–4.29, P < 0.0001).

Conclusions
Our study confirmed that the high expression level of SNHG12 is closely related to the clinicopathological characteristics and prognosis of patients and is a new predictive biomarker for various cancer patients.