bluuebunny/crossref_metadata_2025_split huggingface dataset:
TAK1 inhibition improves myoblast differentiation and alleviates fibrosis in a mouse model of Duchenne muscular dystrophy
Authors: Xu Dengqiu , Li Sijia , Wang Lu , Jiang Jingwei , Zhao Lei , Huang Xiaofei , Sun Zeren , Li Chunjie , Sun Lixin , Li Xihua , Jiang Zhenzhou , Zhang Luyong 
Published: November 2020

AbstractBackgroundTransforming growth factor‐β‐activated kinase 1 (TAK1) plays a key role in regulating fibroblast and myoblast proliferation and differentiation. However, the TAK1 changes associated with Duchenne muscular dystrophy (DMD) are poorly understood, and it remains unclear how TAK1 regulation could be exploited to aid the treatment of this disease.MethodsMuscle biopsies were obtained from control donors or DMD patients for diagnosis (n = 6 per group, male, 2–3 years, respectively). Protein expression of phosphorylated TAK1 was measured by western blot and immunofluorescence analysis. In vivo overexpression of TAK1 was performed in skeletal muscle to assess whether TAK1 is sufficient to induce or aggravate atrophy and fibrosis. To explore whether TAK1 inhibition protects against muscle damage, mdx (loss of dystrophin) mice were treated with adeno‐associated virus (AAV)‐short hairpin TAK1 (shTAK1) or NG25 (a TAK1 inhibitor). Serum analysis, skeletal muscle performance and histology, muscle contractile function, and gene and protein expression were performed.ResultsWe found that TAK1 was activated in the dystrophic muscles of DMD patients (n = 6, +72.2%, P < 0.001), resulting in fibrosis ( +65.9% for fibronectin expression, P < 0.001) and loss of muscle fibres (−32.5%, P < 0.01). Moreover, TAK1 was activated by interleukin‐1β, tumour necrosis factor‐α, and transforming growth factor‐β1 (P < 0.01). Overexpression of TAK1 by AAV vectors further aggravated fibrosis (n = 8, +39.6% for hydroxyproline content, P < 0.01) and exacerbated muscle wasting (−31.6%, P < 0.01) in mdx mice; however, these effects were reversed in mdx mice by treatment with AAV‐short hairpin TAK1 (shTAK1) or NG25 (a TAK1 inhibitor). The molecular mechanism underlying these effects may be related to the prevention of TAK1‐mediated transdifferentiation of myoblasts into fibroblasts, thereby reducing fibrosis and increasing myoblast differentiation.ConclusionsOur findings show that TAK1 activation exacerbated fibrosis and muscle degeneration and that TAK1 inhibition can improve whole‐body muscle quality and the function of dystrophic skeletal muscle. Thus, TAK1 inhibition may constitute a novel therapy for DMD.
Rapid acute care genomics: Challenges and opportunities for genetic counselors
Authors: Lynch Fiona , Nisselle Amy , Gaff Clara L. , McClaren Belinda 
Published: November 2020

AbstractGenomic medicine in pediatric acute care is showing great promise, with rapid results from exome and genome sequencing returned within days providing critically important information for treatment and management of seriously ill children. Many have suggested that rapid acute care genomics presents novel genetic counseling issues. This is due to the need for rapid response to referrals, the immense emotional distress that parents are likely to experience when their child is in acute care, and the unfamiliar environment of the acute care setting. To explore the practice of genetic counselors in this setting, we conducted qualitative interviews with 16 genetic counselors (GCs), representing a large proportion of GCs at the frontline of providing genetic counseling in acute care settings in Australia. Interviews revealed themes describing genetic counseling in acute care, including practical challenges of counseling within a rapid turnaround time, similarities with other contexts such as prenatal counseling, and the need for education of other health professionals. Interestingly, GCs did not raise concerns in the interviews for parents’ ability to provide informed consent for rapid genomic sequencing. GCs also encountered practical and organizational challenges with counseling in this setting where 24‐hr care is provided, at odds with traditional ‘9 to 5’ Genetics service delivery. Working closely in a multidisciplinary team was common and participants believed that GCs are well positioned to take a leading role in the education of other health professionals as rapid acute care genomics becomes routine clinical practice. Despite views that genetic counseling practice in rapid acute care genomics is unique, these exploratory data suggest that GCs are flexible, adaptable, and sufficiently skilled to deliver patient‐centered counseling in this setting. Our work indicates GCs are ready and willing to contribute at an early stage of adoption of genomic investigations in acute care.
Seroprevalence of Helicobacter pylori and its association with metabolic syndrome in a rural community of Bangladesh
Authors: Rahman M. Masudur , Kibria Md. Golam , Sultana Nigar , Akhter Mahfuza , Begum Hasina , Haque Md. Ahshanul , Haque Rashidul , Sarker Shafiqul Alam , Ahmed Faruque , Hasan Mahmud 
Published: November 2020

AbstractBackground and AimAs the interrelationship between Helicobacter pylori, metabolic syndrome (MetS), and non‐alcoholic fatty liver disease (NAFLD) is controversial, we undertook a community‐based study with the aim to find the seroprevalence of H. pylori and its relationship with MetS and NAFLD.MethodsThis door‐to‐door survey was conducted among the adult subjects (≥18 years) of two villages (Charcharia of Dhaka district and Kharrah of Munshiganj district) of Bangladesh. Interviews using a structured questionnaire, clinical examination, anthropometric measurements, ultrasonogram of the liver, and biochemical tests were performed.ResultsOf 1021 subjects, 781 responded (76.49%), and 767 were included in the final analysis (mean age 40.35 ± 15.56 years; female 63.5%). Anti‐H. pylori antibodies were found in 418 of 767 (54.5%). There were no H. pylori serostatus association with MetS and diabetes mellitus (DM) in univariate or multivariate analysis (all P > 0.05). However, H. pylori seropositive subjects had lower systolic blood pressure (odds ratio [OR] = −2.95 [−5.58, −0.32]) and low density lipoprotein ‐cholesterol (OR −7.79 [−15, −0.57]) compared to seronegative subjects in the linear regression model. Seronegativity of H. pylori was associated with NALFD in univariate (P = 0.007) but not multivariate analysis (P = 0.086). There were no differences in the frequency of H. pylori seropositivity among the participants with nonobese compared to obese NAFLD (19/42 [45%] vs 43/99 [43.4%], P = 0.844).ConclusionIn a rural community of Bangladesh, about 55% of the population were H. pylori seropositive, which was more common among the underweight than normal or obese subjects. However, there was no relationship observed between H. pylori seroprevalence and MetS, DM, or NAFLD.
Assessment of ADCY9 polymorphisms and colorectal cancer risk in the Chinese Han population
Authors: Li Haiyue , Liu Yuanwei , Liu Jianfeng , Sun Yao , Wu Jiamin , Xiong Zichao , Zhang Yi , Li Bin , Jin Tianbo 
Published: November 2020

AbstractBackgroundRecently, ADCY9 has been found to be highly expressed in colon cancer, and high ADCY9 expressionis a poor prognostic factor of colon cancer. However, no study has reported on the relationship between single nucleotide polymorphisms (SNPs) of ADCY9 and colorectal cancer risk in the Chinese Han population.MethodsTo evaluate the association between four ADCY9 SNPs and colorectal cancer risk, we performed a case–control study including 511 colorectal cancer patients and 511 healthy controls. SNPs were genotyped using the Agena MassARRAY platform (Agena Bioscience, San Diego, CA, USA). The distributions of alleles and genotypes frequencies between the case and control groups were compared using chi‐squared. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression adjusted for age and gender to assess the association between SNPs and colorectal cancer risk.ResultsThe overall analysis found that rs2230742 was associated with an increased risk of colorectal cancer (AA versus GG: OR = 3.54, 95% CI = 1.16–10.86, p = 0.027; recessive model: OR = 3.55, 95% CI = 1.16–10.85, p = 0.027). Stratification analysis showed that rs2230742 was associated with an increased rectal cancer risk; rs11076810 was associated with a reduced colorectal cancer risk for age > 59 years. No association was observed between other two SNPs and colorectal cancer risk.ConclusionsOur findings suggest that ADCY9 polymorphisms (rs2230742 and rs11076810) have an effect on colorectal cancer risk in the Chinese Han population. Future association and functional studies are required to confirm our findings and explore the mechanism of ADCY2 in colorectal cancer.
Convenient method for the synthesis of some novel chiral methyl 2‐(2‐oxo‐2H‐benzo[e][1,3]oxazin‐3(4H)‐yl)propanoate derivatives and biological evaluation of their antioxidant, cytotoxic, and molecular docking properties
Authors: Matam Sivakumar , Kaliyan Prabakaran , Selvaraj Loganathan , Muthu Seenivasa Perumal , Lohanathan Bharathi Priya , Viswanadhan Vijaya Padma , Makala Himesh , Venkatasubramanian Ulaganathan 
Published: November 2020

AbstractTen chiral methyl 2‐(2‐oxo‐2H‐benzo[e][1,3]oxazin‐3(4H)‐yl)propanoate derivatives 6a‐6j have been synthesized from optically pure amino methyl phenol 5 and 4‐nitrophenyl chloroformate. These derivatives 6a‐6j are characterized by 1H NMR, 13C NMR, FT‐IR, and HRMS spectral techniques. Optical purity of these derivatives was confirmed by chiral HPLC method. Ten synthesized ester derivatives 6a‐6j were screened for their in vitro antioxidant activity. Among the compounds 6b‐d and 6h‐j have exhibited comparable antioxidant activity with ascorbic acid as a standard. Compounds 6a and 6e‐g have shown moderate antioxidant activity. Further, the in vitro cytotoxicity of these compounds were studied through MTT cell proliferation assay in addition the effect on LDH leakage and NO release. Among the derivatives, 6j showed extremely best activity and the IC50 value (12.54 ± 0.71 μM) is very close to doxorubicin (7.2 ± 0.58 μM) as a standard. Compounds 6b, 6h, and 6i showed better inhibition next to compound 6j on the viability of HepG2 cells with an IC50 value (μM) of 56.02 ± 1.4, 41.76 ± 0.58, and 38.17 ± 0.34, respectively. Also, molecular docking studies have been carried out with STAT‐3 (PDB ID: 1BG1) and BCL‐2 (PDB ID: 4AQ3) proteins against the four active compounds 6b, 6h, 6i, and 6j. The binding energies of the tested compounds were in the range of −7.76 to −8.41 kcal/mol, which is very close to doxorubicin (−8.53 kcal/mol) as a standard. These molecular docking results are in good agreement with the in vitro studies.
Impact of Obesity and Visceral Fat on Mortality in Hematopoietic Stem Cell Transplantation
Authors: Pereira Andrea Z , de Almeida‐Pitito Bianca , Eugenio Gisele Cristine , Ruscitto do Prado Rogério , Silva Cinthya Correa , Hamerschlak Nelson 
Published: November 2020

AbstractRationale: Many studies have shown the importance of body composition parameters, muscle, and fat mass, evaluated by several methods in hematopoietic stem cell transplantation (HSCT) outcomes. Ultrasound (US) is an efficient and low‐cost method to evaluate body composition, even though there have not been many studies in HSCT. Objectives: Our goal was to investigate the muscle, visceral fat (VF), and echogenicity before HSCT and after engraftment, evaluated by US and its association with outcomes. Methods: All adult patients with hematological malignances admitted for HSCT autologous and allogeneic were eligible to enter this prospective study. Their thigh muscle thickness, VF, and echogenicity were evaluated by US on the first day of hospitalization (baseline) and after engraftment (15–25 days post‐HSCT). Results: We evaluated 50 patients; 42% were male and 58% had undergone allogeneic HSCT. Most patients were <55 years old (68%) and had normal body mass index (50%). We found a significant reduction of right and left muscle thickness (P < .001) and echogenicity (P = .002) after engraftment compared with baseline. Our elderly patients had significantly bigger right‐thigh muscle thickness (P = .02) and more VF (P = .009). The following data were higher in obese patients: right and left muscle thickness (P < .001), VF (P = .003), and echogenicity (P = .04). Death in the first 100 days had a positive association with obesity (P = 0.001) and VF (P = .002). VF was the only variable independent of HSCT type and age in mortality risk. Conclusion: Obesity and VF had an important impact in mortality. US could be a useful tool and strategy for evaluating body composition in HSCT patients.
A comparison of oncological outcomes after abdominoperineal excision before and after the implementation of a selective perineal flap closure program
Authors: Murphy Claudine , Stephens Ian , OꞌFlanagan Grace , OꞌByrne Lisa , Reynolds Ian S. , Ajmal Nadeem , O'Sullivan John Barry , OꞌNeill Brian , Deasy Joseph , Burke John P. , McNamara Deborah A. 
Published: November 2020

AbstractBackground and ObjectivesAbdominoperineal excision (APE) is the operation chosen when a patient has low rectal cancer unamenable to sphincter preserving surgery. Perineal flap reconstruction is associated with less wound morbidity but little is known about oncological outcomes. The objective was to compare outcomes in patients undergoing APE before and after the introduction of a program that utilized flap reconstruction of the perineum.MethodsA retrospective review of a prospectively maintained database was performed. Patients who underwent APE followed by primary closure or flap reconstruction between 1998 and 2018 were selected. The cohorts were divided according to the implementation of the flap reconstruction program in July 2009. Clinicopathological data, recurrence and survival were compared between the cohorts.ResultsOne hundred and forty nine patients underwent APE for rectal adenocarcinoma between 1998 and 2018. There were 57 patients in the pre‐flap era and 92 in the post‐flap era. Forty‐six patients underwent flap reconstruction in the latter cohort (50%). More patients in the post‐flap era underwent neoadjuvant chemoradiotherapy (85.9% vs. 63.2%; p < .01). Margin positivity rates decreased from 21.1% in the pre‐flap era to 10.9% in the post‐flap era (p = .10) and there was an associated improvement in incidence and time to local recurrence (p = .03).ConclusionThe use of perineal flap reconstruction is associated with a longer median time to local recurrence. Perineal flap reconstruction may contribute to reduced margin positivity.
A rapid and innovative extraction and enrichment method for the metaproteomic characterization of dissolved organic matter in groundwater samples
Authors: Capriotti Anna Laura , Aita Sara Elsa , Cavaliere Chiara , Cerrato Andrea , Montone Carmela Maria , Piovesana Susy , Laganà Aldo 
Published: November 2020

AbstractMetaproteomic analysis of aquifer systems provides valuable information on the microbial populations, their influence on drinking water quality, and the effect on human health. In the present paper, an extraction and enrichment method by C18 extra‐wide pore cartridge was developed, optimized, and applied for the first time to the metaproteomic characterization of dissolved organic matter in groundwater samples. In particular, three elution procedures were tested and compared on water spiked with a yeast protein extract to maximize the recovery of proteins from a complex matrix. The maximum protein recovery was obtained by the use of two sequential elution buffers, one employing a denaturing agent and the other one containing an acidified organic solvent. A comprehensive metaproteomic analysis of the dissolved organic matter of groundwater was then performed by nano‐high performance liquid chromatography coupled to high‐resolution mass spectrometry. A total of 239 proteins was identified; in agreement with the current knowledge on proteins in aquifer systems, most identified sequences derived from bacteria, protobacteria, and ciliates. The paper is the first metaproteomic study applied to groundwater samples with particular emphasis on the need for sample pretreatment to obtain comprehensive information on the proteome in dissolved organic matter.
The role of the diffusion process in bimolecular reactions with neighborhood
Authors: de Souza Filho José Cândido , López‐Castillo Alejandro 
Published: November 2020

AbstractWe performed stochastic and deterministic calculations to study simple bimolecular chemical kinetics with a neighborhood, necessary for solid‐state and viscous medium reactions. Regarding the standard deterministic method using ordinary differential equations (ODEs) to describe a bimolecular reaction with the neighborhood, we established a comparison that indicates, in this method, an implicit diffusion process. For example, the reaction is processed in a homogeneous medium, differently from the stochastic method without diffusion. The two methods coincide at the thermodynamic limit (containing little relative fluctuation) when added with the explicit diffusion process on the stochastic model. The irreversible reaction without diffusion was emulated using the ODEs of a reversible reaction, and the inherent residual concentration of the reactions with low or no diffusion occurring in solids or strong viscous media was obtained from pseudochemical equilibrium.
Matching methods in precision oncology: An introduction and illustrative example
Authors: Weymann Deirdre , Laskin Janessa , Jones Steven J.M. , Lim Howard , Renouf Daniel J. , Roscoe Robyn , Schrader Kasmintan A. , Sun Sophie , Yip Stephen , Marra Marco A. , Regier Dean A. 
Published: November 2020

ABSTRACTBackgroundRandomized controlled trials (RCTs) are uncommon in precision oncology. We provide an introduction and illustrative example of matching methods for evaluating precision oncology in the absence of RCTs. We focus on British Columbia's Personalized OncoGenomics (POG) program, which applies whole‐genome and transcriptome analysis (WGTA) to inform advanced cancer care.MethodsOur cohort comprises 230 POG patients enrolled between 2014 and 2015 and matched POG‐naive controls. We generated our matched cohort using 1:1 propensity score matching (PSM) and genetic matching prior to exploring survival differences.ResultsWe find that genetic matching outperformed PSM when balancing covariates. In all cohorts, overall survival did not significantly differ across POG and POG‐naive patients (p > 0.05). Stratification by WGTA‐informed treatment indicated unmatched survival differences. Patients whose WGTA information led to treatment change were at a reduced hazard of death compared to POG‐naive controls in all cohorts, with estimated hazard ratios ranging from 0.33 (95% CI: 0.13, 0.81) to 0.41 (95% CI: 0.17, 0.98).ConclusionThese results signal that clinical effectiveness of precision oncology approaches will depend on rates of genomics‐informed treatment change. Our study will guide future evaluations of precision oncology and support reliable effect estimation when RCT data are unavailable.
Bit‐error‐rate performance of high‐order APPM and AOPPM for non‐Kolmogorov gamma–gamma channel FSO communications
Authors: Xu Meiyong , Ullah Sibghat , Zhang Sihan , Yuan Deyu , Fu Xiujia , Wang Kaimin , Xin Xiangjun 
Published: November 2020

AbstractHigh‐order pulse modulations in free space optics (FSO) communication are of practical value, and non‐Kolmogorov gamma–gamma (GG) channel model is the most suitable for FSO channel. However, research on a system combined with the above is rarely reported. In our work, we propose high‐order (4*32 and 4*64) amplitude and pulse position modulation (APPM) and overlapping amplitude and pulse position modulation (AOPPM) FSO communication system under a modified non‐Kolmogorov GG turbulent channel model. Simulation results present that AOPPM is obviously better than APPM in bit‐error‐rate (BER) performance, and BER performance grows with the increase of modulation order (number of pulse positions). The proposed schemes may provide a reference for system design and practical application.
Multi‐marker quantitative radiomics for mass characterization in dedicated breast CT imaging
Authors: Caballo Marco , Pangallo Domenico R. , Sanderink Wendelien , Hernandez Andrew M. , Lyu Su Hyun , Molinari Filippo , Boone John M. , Mann Ritse M. , Sechopoulos Ioannis 
Published: November 2020

PurposeTo develop and evaluate the diagnostic performance of an algorithm for multi‐marker radiomic‐based classification of breast masses in dedicated breast computed tomography (bCT) images.MethodsOver 1000 radiomic descriptors aimed at quantifying mass and border heterogeneity, morphology, and margin sharpness were developed and implemented. These included well‐established texture and shape feature descriptors, which were supplemented with additional approaches for contour irregularity quantification, spicule and lobe detection, characterization of degree of infiltration, and differences in peritumoral compartments. All descriptors were extracted from a training set of 202 bCT masses (133 benign and 69 malignant), and their individual diagnostic performance was investigated in terms of area under the receiver operating characteristics (ROC) curve (AUC) of single‐feature‐based linear discriminant analysis (LDA) classifiers. Subsequently, the most relevant descriptors were selected through a multiple‐step feature selection process (including stability analysis, statistical significance, evaluation of feature interaction, and dimensionality reduction), and used to develop a final LDA radiomic model for classification of benign and malignant masses, which was then tested on an independent test set of 82 cases (45 benign and 37 malignant).ResultsThe majority of the individual radiomic descriptors showed, on the training set, an AUC value deriving from a linear decision boundary higher than 0.65, with the lower limit of the associated 95% confidence interval (C.I.) not overlapping with random chance (AUC = 0.5). The final LDA radiomic model resulted in a test set AUC of 0.90 (95% C.I. 0.80–0.96).ConclusionsThe proposed multi‐marker radiomic approach achieved high diagnostic accuracy in bCT mass classification, using a radiomic signature based on different feature types. While future studies with larger datasets are needed to further validate these results, quantitative radiomics applied to bCT shows potential to improve the breast cancer diagnosis pipeline.