bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variants in CDH23 Cause Broad Spectrum of Hearing Loss: From Non-Syndromic to Syndromic Hearing Loss as Well as From Congenital to Age-Related Hearing Loss
Authors: Usami Shin-ichi , Isaka Yuichi , Miyagawa Maiko , Nishio Shin-ya 
Published: June 2021

Abstract
Variants in the CDH23 gene are known to be responsible for both syndromic hearing loss (Usher syndrome type ID: USH1D) and non-syndromic hearing loss (DFNB12). Our series of studies demonstrated that CDH23 variants cause broad phenotypes of non-syndromic hearing loss (DFNB12); from congenital profound hearing loss to late-onset high frequency-involved progressive hearing loss. In this study, using genetic and clinical data from more than 10,000 patients, the mutational spectrum, clinical characteristics and genotype/phenotype correlations were evaluated. The present results reconfirmed that the variants in CDH23 are an important cause of non-syndromic sensorineural hearing loss. In addition, we showed that the mutational spectrum in the Japanese population, which is probably representative of the east Asian population in general, and the frequent CDH23 variants that might be due to some founder effects. The present study demonstrated CDH23 variants cause a broad range of phenotypes, from non-syndromic to syndromic hearing loss as well as from congenital to age-related hearing loss. Genotype (variant combination) and phenotype (association of retinal pigmentosa, onset age) are shown to be well correlated, and are thought to be related to the residual function defined by the CDH23 variants.
Highly selective behaviour of gastric adenoma after administration of EMR composition and its HCT116-based model
Authors: Jakabčin Patrik , Kello Martin , Záň Jozef , Kolář Josef , Ulicny Jozef 
Published: June 2021

Abstract
When applying improved composition of solution used during endoscopic mucosal resection (EMR), we have observed unexpectedly large and quantitatively significant difference in response of adenoma vs. healthy tissue of surrounding GIT tract, namely the selective reaction enhancing the volume and differentiated colour. The in vitro experiments on model neoplasia cell line HCT116 suggest, that the robust differences in response of starving cells can be traced down principally to the tetrastarch digestion of neoplastic tissue and enhanced metabolic rate of neoplastic cells. The neoplastic tissue grows into several intestine layers so that submucosal injection of iso-oncotic tetrastarch compound leads to degradation of starch and production of oncotic molecules in submucosa transported by facilitated transport into neoplastic tissue. The colour distinction of the reporting dye is due to concentration differences of three separated compartments, further enhancing the utility of the contrasting mixture. The diffusion dynamics shall be tuneable by optimizing starch composition improving desirable pharmacokinetics.
Identification and Validation of a Hypoxia-related lncRNA Signature for Prognostic Prediction in Endometrial Cancer
Authors: Liu Hongyang , Wan Junhu , Feng Quanling , Li Jingyu , Liu Jun , Cui Shihong 
Published: June 2021

Abstract
Background: Endometrial cancer (EC) is one of the most common types of gynecological cancer. Hypoxia is an important clinical feature and regulates various tumor processes. However, the prognostic value of hypoxia-related lncRNA in EC remains to be further elucidated. Here, we aimed to characterize the molecular features of EC by the development of a classification system based on the expression profile of hypoxia-related lncRNA.Methods: Univariate Cox regression analysis was used to identify hypoxia-related lncRNAs associated with overall survival. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct gene signature. Multivariate Cox regression analysis and receiver operating characteristic (ROC) curve analysis were also performed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEEG) pathway, and Gene Set Enrichment Analysis (GESA) were used to identify hypoxia-related lncRNA pathway. Western blot and real-time PCR were used to detect target gene expression. The cell proliferation was determined by using WST-1 assay.Results: Based on univariate Cox regression analysis, we identified 17 hypoxia-related lncRNAs significantly associated with overall survival. Next, the least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct a multigene signature in the TCGA EC cohort. The risk score was confirmed as an independent predictor for overall survival in multivariate Cox regression analysis and receiver operating characteristic (ROC) curve analysis. Besides, the survival time of EC patients in different risk group was significantly correlated to clinicopathologic factors, such as age, stage and grade. Furthermore, hypoxia-related lncRNA associated with the high-risk group were involved in various aspects of the malignant progression of EC via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEEG) pathway, and Gene Set Enrichment Analysis (GESA). Besides, using CIBERSORT analysis, we found a different immune cell environment characterization of EC between different cluster and risk group. Moreover, the risk score was closely correlated to immunotherapy response, microsatellite instability and tumor mutation burden (TMB). Finally, we select one hypoxia-related lncRNA SOS1-IT1 to validate its role in hypoxia and EC progression. Interestingly, we found SOS1-IT1 was overexpressed in tumor tissues, and closely correlated with clinicopathological parameters of EC. The expression level of SOS1-IT1 was significantly increased under hypoxia condition. Additionally, the important hypoxia regulatory factor HIF-1α can directly bind SOS1-IT1 promoter region, and affect its expression level. Conclusions: In summary, this study established a new EC classification based on the hypoxia-related lncRNA signature, thereby provide a novel sight to understand the potential mechanism of human EC development.
Accelerated Diastolic Dysfunction in Premenopausal Women with Rheumatoid Arthritis
Authors: Kim GeeHee , Park Yune-Jung 
Published: June 2021

Abstract
Objective: Disturbances of diastolic function precede systolic heart failure and, although clinically silent, represent the earliest sign of cardiac involvement. Diastolic dysfunction (DD) is associated with age, gender (female), and hypertension. However, little is known about the age-specific incidence rates and risk factors for DD in patients with rheumatoid arthritis (RA).Methods: We used standard two-dimensional/Doppler echocardiography to screen for the presence of diastolic dysfunction in 61 patients with RA and 107 healthy subjects. All participants were premenopausal women with no history of hypertension. DD includes an impaired relaxation with or without increased left ventricular (LV) filling pressures, pseudonormal filling and restrictive filling based on parameters measured using echocardiography.Results: The two groups were similar with respect to age (P=0.269). Patients with RA had significantly higher LV mass index, LV filling pressure, and lower E/A velocity than controls. All patients had preserved ejection fraction (EF ≥50%). DD was more common in patients with RA at 47% compared to 26% in the controls (P=0.004). Women with RA in the 30- to 49- year age range were over 3.5 times more likely to have DD than those of similar age in the control group (OR=3.54; 95% CI 1.27 to 9.85). Among patients with RA, high CRP levels were independently associated with DD even after adjustment for cardiovascular risk factors (P=0.009).Conclusions: In premenopausal women with RA, DD is much more common and the age of onset is reduced. Early screening of myocardial function may provide an opportunity for preventing future cardiovascular disease.
Resection and Reconstruction is the Procedure of Choice for Giant Cell Lesions of Small Bones: A Case Report and Literature Review
Authors: Li Jiannan , Zhang Weizhong , Wu Guangzhi , zhang zhan 
Published: June 2021

Abstract
Background: Giant cell lesion of small bones (GCLSB), also known as giant cell reparative granuloma, is a rare tumor-like condition occurring in the small bones of the hands and feet. GCLSB lacks specific clinical, radiological, and histological manifestations. There are no standardized protocols for treatment. Case presentation: Here, we report a 16-year-old male with recurrent GCLSB in the proximal phalanx of the left thumb. The lesion was successfully resected with bone grafting. Conclusions: We summarized the characteristics of 33 reported cases of GCLSB from 1983 to date, including gender, age, lesion sites, recurrence, and treatment. We conclude that resection and reconstruction with curettage is the treatment of choice.
Contrasting climate influences on Nothofagus pumilio establishment along elevational gradients
Authors: Aschero Valeria , S Ana M , Guerrido Claudia M , Villalba Ricardo 
Published: June 2021

Abstract
Predicted warmer temperatures and more frequent extreme climatic events in the southern Andes will affect the dynamics of the Patagonian forests. These environmental changes may differentially alter the probability of Nothofagus pumilio establishment across its altitudinal range of distribution. We monitored fruit rain, seedling emergence and survival at the lower and upper elevation boundaries of N. pumilio forests in Santa Cruz (49° 22'S − 72º 56' W), Argentina. From 2012 to 2018, recruitment and mortality were evaluated biannually in the field. Seedling establishment was tested in relation to drought, based on the SPEI (Standardized Precipitation Evapotranspiration Index), and changes in elevation. Fruit rain was consistently higher at low elevation and the abundance of fruits was not affected by drought intensity. Seedling emergence was ~ 11 to 19 times larger at the upper forest boundary, in particular during years characterized by warm-dry climatic conditions in spring-early summer. In contrast, seedling abundance was ~ 3 times larger at low elevations during relatively cold-wet growing seasons. Over the period 2012 to 2018, dominated by dry-warm spring and summers, survival probability curves for seedlings and juvenile trees were higher at upper than lower elevations. Our results show contrasting effects of climate on tree establishment at the elevation limits, with positive and negative drought effects at high and low elevations, respectively. Predicted increase of extreme drought events during the XXI century could be detrimental for N. pumilio establishment at dry, low-elevation forests.
Increasing nitrogen supply to phosphorus-deficient Medicago sativa decreases shoot growth and enhances root exudation of tartrate to discharge surplus carbon dependent on nitrogen form
Authors: He Honghua , Zhang Zekun , Peng Qi , Chang Chao , Su Rui , Cheng Xiao , Li Yingxin , Pang Jiayin , Du Sheng , Lambers Hans 
Published: June 2021

Abstract
Aims
Carboxylate release by roots has been considered a strategy for mobilization and acquisition of phosphorus (P). However, recently, it was argued that carboxylate release may be a way to discharge surplus carbon produced under conditions that limit plant growth. Plant P status may not be the main factor driving carboxylate release by roots. Instead, plant nitrogen (N) status and/or N:P ratio of the soil or plant may play a more important role in enhancing carboxylate release.
Methods
A greenhouse pot experiment was performed to grow alfalfa in a P-deficient soil, supplied with two rates of P (0 and 20 mg kg− 1) in combination with four forms of nitrogen (N) at five rates (0, 25, 50, 75, and 100 mg kg− 1), to explore the effects of P rate, N form, N rate, and their interactions on plant growth, P and N status, and carboxylate release, and to determine the factors driving carboxylate release.
Results
Nitrogen addition weakened the positive effect of P addition on plant growth, and increased plant N ([N]) and P concentrations ([P]); P addition increased plant [P], but weakened the effect of N addition on plant [N]. The amount of tartrate increased dramatically with increasing N rate, which decreased shoot growth, depending on N form. At high P supply, tartrate exudation correlated negatively with shoot biomass.
Conclusions
Nitrogen addition to P-deficient alfalfa decreased shoot growth and enhanced the release of tartrate, likely to discharge surplus carbon; and the effects varied with N form.
Effect of Energy Density on the Microstructure and Properties of the CrFeCoNiNb High Entropy Cladded Layer
Authors: Song Pengfang , Jiang Fulin , Wang Yuling , Yang Fazhan , Zhong Zhaolin 
Published: June 2021

Abstract
A synergistic combination of mechanical properties and corrosion resistance property is desired for most ocean engineering structural applications. In this paper, we prepared high entropy alloy (HEA) cladded layer of composition CrFeCoNiNb (atomic%). We aim to attain a balance between the mechanical property and the corrosion resistance property through adjusting the energy density. The prepared CrFeCoNiNb cladded layer with the energy density of 116.7J/mm2 exhibited excellent mechanical properties and high corrosion resistance. The improved mechanical properties are attributed to the fine grain strengthening, solid solution strengthening and dispersion strengthening. Whereas the excellent corrosion resistance is due to the fine grained BCC single phase structure and the compact passivation film. The variation of the mechanical properties and corrosion resistance with different energy densities are attribute to the phase composition. The diffraction peak area of the main phase of BCC decreases first and then increases with the increase of energy density, which is the main reason that the hardness of the cladded layer follows the similar trend. The outcome of our research suggests that the prepared CrFeCoNiNb cladded layer could be explored to realise surface strengthening of load-bearing parts in marine engineering equipment.
Outcome of One-Stage Percutaneous Endoscopic Debridement and Lavage Combined with Percutaneous Pedicle Screw Fixation for Lumbar Pyogenic Spondylodiscitis
Authors: Chen Jianquan , Li Zhenyu , Li Yong , Tang Shangde , Lv Zhouming , Wang Xian , Chen Maoshui 
Published: June 2021

Abstract
Background
This study assessed the therapeutic effect of one-stage percutaneous endoscopic debridement and lavage (PEDL) combined with percutaneous pedicle screw fixation (PPSF) in the treatment of lumbar pyogenic spondylodiscitis.
Methods
From March 2017 to October 2019, 25 patients diagnosed with pyogenic spondylodiscitis underwent PPSF followed by PEDL in our department. Biopsy specimens were examined for microorganisms and evaluated histopathologically. Clinical outcomes were assessed by physical examination, routine serological testing, visual analogue scale (VAS), Oswestry Disability Index (ODI), and imaging studies.
Results
All operations were successful, with no severe surgical complications in any patient and excellent incision healing. Causative bacteria were identified in most cases; Staphylococcus aureus was the most prevalent. The mean follow-up was 25.0 ± 3.8 (range: 20–32) months. Inflammatory markers showed that infection was controlled. The VAS and ODI improved significantly. At the last follow-up, magnetic resonance imaging showed that the infected lesions had disappeared.
Conclusion
PEDL supplementing PPSF may be useful for patients with single-level lumbar pyogenic spondylodiscitis, as it is minimally invasive, especially for patients who cannot undergo conventional open surgery due to poor health or advanced age.
Mercuric Chloride induced Oxidative Stress, Genotoxicity, Haematological Changes and Histopathological Alterations in Fish Channa Punctatus (Bloch, 1793).
Authors: Trivedi Sunil P. , Singh Shefalee , Trivedi Abha , Kumar Manoj 
Published: June 2021

Abstract
The current study was strived to investigate the adverse effects of Mercuric chloride (HgCl2) overload in the fish Channa punctatus. Two sub-lethal test concentrations of HgCl2 viz., 1/20th and 1/10th of 96 h LC50 i.e., 0.03 mg/L and 0.07 mg/L, respectively, were used for exposure. Blood, liver and kidney tissues of the control and exposed specimens were sampled at intervals of 15, 30 and 45 days to assess alterations in oxidative stress, genotoxicity haematological parameters and histopathology. Significant changes in Hb%, RBC count, WBC count, antioxidant enzyme activity viz., super oxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione reductase (GR) were recorded. Micronuclei (MN) induction, nuclear abnormalities (NA) and histopathological alterations were also observed in the exposed fish. Significant (p < 0.05) increase in activities of SOD, CAT, GSH, GR and after 45 d decrease in the level of GSH and GR suggest an undermined anti-oxidative defence system in the fish exposed to HgCl2. Histological examination of liver and kidney showed serious tissue injury and histological alterations. Significant increase in MN and NA frequencies reveal the DNA damage in erythrocytes of fish and haematological changes show the toxicological potential of HgCl2. The observed genotoxicity, biochemical, haematological and histological changes in the present study provide the most extensive insight of HgCl2 stress in Channa punctatus.
Dynamic APACHE II Score to Predict Outcome Among Intensive Care Unit Patients
Authors: Tian Yao , YAO Yang , Zhou Jing , Diao Xin , Chen Hui , Cai Kaixia , Ma Xuan , Wang Shengyu 
Published: June 2021

Abstract
Purpose: The Acute Physiology and Chronic Health Evaluation II (APACHE II) score is used to determine disease severity and predict outcomes in critically ill patients. However, there is no dynamic APACHE II score for predicting outcomes among ICU patients.The aim of this study is to explore the optimal timing to predict the outcomes of ICU patients by dynamically evaluating APACHE II score.Methods: Study data of demographics and comorbidities from the first 24 h after ICU admission were retrospectively extracted from MIMIC-III, a multiparameter intensive care database. The primary outcome was hospital mortality. 90-day mortality was a secondary outcome. APACHE II scores on days 1, 2, 3, 5, 7, 14 and 28 were compared using area under the receiver operating characteristic (AUROC) analysis. Hospital survival was visualised using Kaplan-Meier Curves.Results:A total of 6374 eligible subjects were extracted from the MIMIC-III. Mean APACHE II score on day 1 were 18.4±6.3, hospital and 90-day mortality was 19.1% and 25.8%, respectively.The optimal timing where predicted hospital mortality was on day 3 with an area under the cure of 0.666 (0.607-0.726)(P＜0.0001). The best tradeoff for preciction was found at 17 score, more than 17 score predicted mortality of non-survivors with a sensitivity of 92.8% and PPV of 23.1%. Hosmer-lemeshow goodness of fit test showed that APACHE II 3 has a good predictive calibration ability (X2 =6.198, P=0.625) and consistency of predicted death and actual death was 79.4%. The calibration of APACHE II 1 was poor (X2=294.898, P<0.001).Conclusions: APACHE II on 3 dayis the optimal prognostic marker and 17 score provided the best dignostic accuracy to predict outcomes for ICU patients. These finding will help medical make clinical judgment.
More Often Than Not, We’re in Sync: Patient and Caregiver Well-being Over Time in Stem Cell Transplantation
Authors: Sannes Timothy S , Ranby Krista W , Yusufov Miryam , Brewer Benjamin W , Jacobs Jamie M , Callan Stephanie , Ulrich Gillian R , Pensak Nicole A , Natvig Crystal L , Laudenslager Mark L 
Published: June 2021

Abstract
Background. Hematopoietic stem cell transplantation (HSCT) is an aggressive medical procedure which significantly impacts the shared emotional well-being of patients and family caregivers (FC). Prior work has highlighted the significant overlap in well-being among patients and FCs; however, how this interdependence may change over the course HSCT has received less attention. Methods. We conducted secondary analyses of a supportive intervention delivered to 154 FCs of HSCT patients and examined relationships at baseline, 6 weeks, 3 and 6 months post-HSCT. Actor Partner Interdependence Modeling examined patient quality of life (QOL) and FC anxiety/depression. Results. The data did not fit a multigroup approach limiting our ability to test intervention effects; however, bivariate analyses indicated FC depression significantly correlated to patient QOL at baseline (r =-.32), 6 weeks (r =-.22) and 6 months post-HSCT (r =-.34; p’s<.05); whereas anxiety was only correlated at the first two timepoints (p’s <.05). There was an unexpected, albeit small, partner effect such that worse patient QOL at 6-weeks significantly related to lower FC depression at 3-months (B =.182; p =.026) and changed direction with patient QOL at 3-months being related to more FC depression at 6-months (B =-.192; p =.001). Conclusions. These findings highlight the significant, yet nuanced, interdependence of patient QOL and FC well-being during HSCT. Specifically, greater interdependence was observed between patient QOL and FC depression compared to FC anxiety, suggesting potential treatment targets for patients and their families. Trial was registered at ClinicalTrials.gov Identifier: NCT02037568; first registered: January 16, 2014; https://clinicaltrials.gov/ct2/show/NCT02037568
The power of pathway-based polygenic risk scores
Authors: Choi Shing Wan , Garcia-Gonzalez Judit , Ruan Yunfeng , Wu Hei Man , Johnson Jessica , Hoggart Clive , O’Reilly Paul 
Published: June 2021

Abstract
Polygenic risk scores (PRSs) have been among the leading advances in biomedicine in recent years. As a proxy of genetic liability, PRSs are utilised across multiple fields and applications. While numerous statistical and machine learning methods have been developed to optimise their predictive accuracy, all of these distil genetic liability to a single number based on aggregation of an individual’s genome-wide alleles. This results in a key loss of information about an individual’s genetic profile, which could be critical given the functional sub-structure of the genome and the heterogeneity of complex disease. Here we evaluate the performance of pathway-based PRSs, in which polygenic scores are calculated across genomic pathways for each individual, and we introduce a software, PRSet, for computing and analysing pathway PRSs. We find that pathway PRSs have similar power for evaluating pathway enrichment of GWAS signal as the leading methods, with the distinct advantage of providing estimates of pathway genetic liability at the individual-level. Exemplifying their utility, we demonstrate that pathway PRSs can stratify diseases into subtypes in the UK Biobank with substantially greater power than genome-wide PRSs. Compared to genome-wide PRSs, we expect pathway-based PRSs to offer greater insights into the heterogeneity of complex disease and treatment response, generate more biologically tractable therapeutic targets, and provide a more powerful path to precision medicine.