bluuebunny/crossref_metadata_2025_split huggingface dataset:
The MC1R r allele does not increase melanoma risk in MITF E318K carriers
Authors: Wallingford Courtney K , Demeshko Anastassia , Krishnakripa Asha Krishnankutty , Smit Darren J , Duffy David L , Betz-Stablein Brigid , Pflugfelder Annette , Jagirdar Kasturee , Holland Elizabeth , Mann Graham J , Primiero Clare A , Yanes Tatiane  , Malvehy Josep , Badenas Cèlia , Carrera Cristina , Aguilera Paula , Olsen Catherine M   , Ward Sarah V , Haass Nikolas K , Sturm Richard A , Puig Susana  , Whiteman David C   , Law Matthew H , Cust Anne E , Potrony Miriam , Soyer H  Peter  , McInerney-Leo Aideen M 
Published: March 2023

Abstract

Background
Population-wide screening for melanoma is not cost-effective, but genetic characterization could facilitate risk stratification and targeted screening. Common Melanocortin-1 receptor (MC1R) red hair colour (RHC) variants and Microphthalmia-associated transcription factor (MITF) E318K separately confer moderate melanoma susceptibility, but their interactive effects are relatively unexplored.

Objectives
To evaluate whether MC1R genotypes differentially affect melanoma risk in MITF E318K+ vs. E318K– individuals.

Materials and methods
Melanoma status (affected or unaffected) and genotype data (MC1R and MITF E318K) were collated from research cohorts (five Australian and two European). In addition, RHC genotypes from E318K+ individuals with and without melanoma were extracted from databases (The Cancer Genome Atlas and Medical Genome Research Bank, respectively). χ2 and logistic regression were used to evaluate RHC allele and genotype frequencies within E318K+/– cohorts depending on melanoma status. Replication analysis was conducted on 200 000 general-population exomes (UK Biobank).

Results
The cohort comprised 1165 MITF E318K– and 322 E318K+ individuals. In E318K– cases MC1R R and r alleles increased melanoma risk relative to wild type (wt), P &lt; 0.001 for both. Similarly, each MC1R RHC genotype (R/R, R/r, R/wt, r/r and r/wt) increased melanoma risk relative to wt/wt (P &lt; 0.001 for all). In E318K+ cases, R alleles increased melanoma risk relative to the wt allele [odds ratio (OR) 2.04 (95% confidence interval 1.67–2.49); P = 0.01], while the r allele risk was comparable with the wt allele [OR 0.78 (0.54–1.14) vs. 1.00, respectively]. E318K+ cases with the r/r genotype had a lower but not significant melanoma risk relative to wt/wt [OR 0.52 (0.20–1.38)]. Within the E318K+ cohort, R genotypes (R/R, R/r and R/wt) conferred a significantly higher risk compared with non-R genotypes (r/r, r/wt and wt/wt) (P &lt; 0.001). UK Biobank data supported our findings that r did not increase melanoma risk in E318K+ individuals.

Conclusions
RHC alleles/genotypes modify melanoma risk differently in MITF E318K– and E318K+ individuals. Specifically, although all RHC alleles increase risk relative to wt in E318K– individuals, only MC1R R increases melanoma risk in E318K+ individuals. Importantly, in the E318K+ cohort the MC1R r allele risk is comparable with wt. These findings could inform counselling and management for MITF E318K+ individuals.
Enhancer RNA IRS2e is essential for IRS2 expression and the oncogenic properties in oral squamous cell carcinoma
Authors: Yan Lingyan , Wang Jiayun , Guo Jihua , Jia Rong 
Published: March 2023

Abstract
The crucial roles of enhancer RNAs (eRNAs) in the regulation of gene expression in human diseases have drawn wider and wider attention in recent years. However, the specific expression profile and function of eRNAs are still rarely discussed in oral squamous cell carcinoma (OSCC), the most common subtype of head and neck squamous cell carcinoma (HNSC). In this study, we aimed to investigate the expression and function of an uncharacterized eRNA, insulin receptor substrate 2 enhancer RNA (IRS2e), in OSCC. We found that IRS2e was overexpressed in HNSC and its overexpression was positively correlated with a poor prognosis. The downregulation of IRS2e by short hairpin RNA significantly inhibited cell growth and induced cellular apoptosis and cell-cycle arrest in OSCC cells. Furthermore, the ablation of IRS2e inhibited tumor growth in vivo. Mechanically, IRS2e is essential for the expression of insulin receptor substrate 2 (IRS2), an oncogene nearby IRS2e in chromosome 13. Altogether, our study demonstrated that IRS2e is a novel oncogenic eRNA required for oncogene IRS2 expression in OSCC.
Functional gradients in prefrontal regions and somatomotor networks reflect the effect of music training experience on cognitive aging
Authors: Guo Sijia , Feng Liangfeng , Ding Rui , Long Siyu , Yang Hua , Gong Xun , Lu Jing , Yao Dezhong 
Published: March 2023

AbstractStudies showed that the top-down control of the prefrontal cortex (PFC) on sensory/motor cortices changes during cognitive aging. Although music training has demonstrated efficacy on cognitive aging, its brain mechanism is still far from clear. Current music intervention studies have paid insufficient attention to the relationship between PFC and sensory regions. Functional gradient provides a new perspective that allows researchers to understand network spatial relationships, which helps study the mechanism of music training that affects cognitive aging. In this work, we estimated the functional gradients in four groups, young musicians, young control, older musicians, and older control. We found that cognitive aging leads to gradient compression. Compared with young subjects, older subjects presented lower and higher principal gradient scores in the right dorsal and medial prefrontal and the bilateral somatomotor regions, respectively. Meanwhile, by comparing older control and musicians, we found a mitigating effect of music training on gradient compression. Furthermore, we revealed that the connectivity transitions between prefrontal and somatomotor regions at short functional distances are a potential mechanism for music to intervene in cognitive aging. This work contributes to understanding the neuroplasticity of music training on cognitive aging.
Screening Antibacterial Constituents of Scutellaria Radix Based on Spectrum–Effect Relationships Between HPLC Fingerprints and the Inhibition of Oral Bacteria
Authors: Huang Zhen , Yu Yi , Yang Hai-Li , Wang Yu-Fei , Huang Jin-Lian , Xiao Lei , Liang Ming , Qi Jin 
Published: March 2023

Abstract
Scutellaria Radix (SR) is a widely used traditional Chinese medicine in clinics for the therapy of upper respiratory tract infectious diseases. Modern pharmacological investigations indicate that SR exerts a significant bacteriostatic effect on different oral bacteria, but few studies have systematically investigated the main active constituents of SR causing this activity. Spectrum–effect correlation analysis was applied to screening anti-oral-microbial constituents from SR. The aqueous extract of SR was divided into fractions of different polarity and the active fraction was screened using the agar diffusion method. Eighteen batches of SR were further prepared and the chromatography fingerprint was established using high-performance liquid chromatography. The antibacterial activities of these constituents were examined against different oral bacteria. Finally, the spectrum–effect relationship between the fingerprint and those antibacterial effects was analyzed by gray correlation analysis and partial least squares regression. Five active constituents were screened out and their antibacterial activity was systematically confirmed by a knockout/in strategy combined with a biofilm extraction method, which indicated that these five compounds were responsible for the antibacterial activity of SR. These results form the basis for further development and improved quality control of SR in the treatment of oral diseases.
Cardiomyocyte-specific PCSK9 deficiency compromises mitochondrial bioenergetics and heart function
Authors: Laudette Marion , Lindbom Malin , Arif Muhammad , Cinato Mathieu , Ruiz Mario , Doran Stephen , Miljanovic Azra , Rutberg Mikael , Andersson Linda , Klevstig Martina , Henricsson Marcus , Bergh Per-Olof , Bollano Entela , Aung Nay , Gustav Smith J , Pilon Marc , Hyötyläinen Tuulia , Orešič Matej , Perkins Rosie , Mardinoglu Adil , Levin Malin C , Borén Jan 
Published: March 2023

AbstractAimsPro-protein convertase subtilisin-kexin type 9 (PCSK9), which is expressed mainly in the liver and at low levels in the heart, regulates cholesterol levels by directing low-density lipoprotein receptors to degradation. Studies to determine the role of PCSK9 in the heart are complicated by the close link between cardiac function and systemic lipid metabolism. Here, we sought to elucidate the function of PCSK9 specifically in the heart by generating and analysing mice with cardiomyocyte-specific Pcsk9 deficiency (CM-Pcsk9−/− mice) and by silencing Pcsk9 acutely in a cell culture model of adult cardiomyocyte-like cells.Methods and resultsMice with cardiomyocyte-specific deletion of Pcsk9 had reduced contractile capacity, impaired cardiac function, and left ventricular dilatation at 28 weeks of age and died prematurely. Transcriptomic analyses revealed alterations of signalling pathways linked to cardiomyopathy and energy metabolism in hearts from CM-Pcsk9−/− mice vs. wild-type littermates. In agreement, levels of genes and proteins involved in mitochondrial metabolism were reduced in CM-Pcsk9−/− hearts. By using a Seahorse flux analyser, we showed that mitochondrial but not glycolytic function was impaired in cardiomyocytes from CM-Pcsk9−/− mice. We further showed that assembly and activity of electron transport chain (ETC) complexes were altered in isolated mitochondria from CM-Pcsk9−/− mice. Circulating lipid levels were unchanged in CM-Pcsk9−/− mice, but the lipid composition of mitochondrial membranes was altered. In addition, cardiomyocytes from CM-Pcsk9−/− mice had an increased number of mitochondria–endoplasmic reticulum contacts and alterations in the morphology of cristae, the physical location of the ETC complexes. We also showed that acute Pcsk9 silencing in adult cardiomyocyte-like cells reduced the activity of ETC complexes and impaired mitochondrial metabolism.ConclusionPCSK9, despite its low expression in cardiomyocytes, contributes to cardiac metabolic function, and PCSK9 deficiency in cardiomyocytes is linked to cardiomyopathy, impaired heart function, and compromised energy production.
Intestinal Epithelial Cell-specific Deletion of Cytokine-inducible SH2-containing Protein Alleviates Experimental Colitis in Ageing Mice
Authors: Hu Xiaoming , Jiao Fuxin , Deng Jiali , Zhou Ziheng , Chen Shanghai , Liu Changqin , Liu Zhanju , Guo Feifan 
Published: March 2023

Abstract

Background and Aims
The incidence of inflammatory bowel disease [IBD] in the elderly has increased in recent years. However, the mechanisms underlying the ageing-related IBD susceptibility remain elusive. Cytokine-inducible SH2-containing protein [CISH] is involved in regulating metabolism, the expansion of intestinal tuft cells and type-2 innate lymphoid cells, and ageing-related airway inflammation. Here, we investigated the role of CISH in ageing-related colitis susceptibility.

Methods
CISH and phosphorylated signal transducer and activator of transcription-3 [p-STAT3] levels were evaluated in the colons of ageing mice and older ulcerative colitis [UC] patients. Mice with intestinal epithelial cell-specific knockout of Cish [CishΔIEC] and Cish-floxed mice were administered dextran sodium sulphate [DSS] or trinitrobenzene sulphonic acid [TNBS] to induce colitis. Colonic tissues were analysed in quantitative real-time polymerase chain reaction, immunoblotting, immunohistochemical, and histological staining experiments. Differentially expressed genes from colonic epithelia were analysed by RNA sequencing.

Results
Ageing increased the severity of DSS-induced colitis and the expression of colonic epithelial CISH in mice. CishΔIEC prevented DSS- or TNBS-induced colitis in middle-aged mice but not in young mice. RNA-sequencing analysis revealed that CishΔIEC significantly suppressed DSS-induced oxidative stress and proinflammatory responses. During ageing in the CCD841 cell model, knockdown of CISH decreased ageing-induced oxidative stress and proinflammatory responses, whereas these effects were compromised by knocking down or inhibiting STAT3. The increase in CISH expression was higher in the colonic mucosa of older patients with UC than in that of healthy controls.

Conclusions
CISH might be a proinflammatory regulator in ageing; therefore, targeted therapy against CISH may provide a novel strategy for treating ageing-related IBD.
Alerting trends in epidemiology for calcific aortic valve disease, 1990–2019: An age–period–cohort analysis for the Global Burden of Disease Study 2019
Authors: Shu Songren , Yang Yicheng , Sun Bo , Su Zhanhao , Fu Mengxia , Xiong Changming , Zhang Xueyi , Hu Shengshou , Song Jiangping 
Published: March 2023

Abstract

Aims
To assess the trends in calcific aortic valve disease (CAVD) epidemiology, with an emphasis on CAVD mortality, leading risk factors, and their associations with age, period, and birth cohort.

Methods and results
Prevalence, disability-adjusted life years, and mortality were derived from the Global Burden of Disease Study 2019. The age–period–cohort model was employed to study the detailed trends of CAVD mortality and its leading risk factors. Globally, CAVD showed unsatisfactory results from 1990 to 2019, with the CAVD deaths of 127 000 in 2019. CAVD mortality was substantially reduced in high socio-demographic index (SDI) countries [−1.45%, 95% confidence interval (CI) (−1.61 to −1.30)], mildly increased in high-middle SDI countries [0.22%, 95% CI (0.06–0.37)], and unchanged in other SDI quintiles. There was a noticeable transition in CAVD deaths from younger to older populations globally. The CAVD mortality increased exponentially with age, and the male had higher mortality than the female before 80 years old. Favourable period [0.69, 95% CI (0.66–0.72)] and birth effects [0.30, 95% CI (0.22–0.43)] were mainly observed in high SDI countries, while unfavourable effects were mostly noticed in high-middle SDI countries. High systolic blood pressure was the leading risk factor of CAVD deaths globally, and it showed favourable trends in high SDI regions.

Conclusion
Although CAVD mortality reduction was observed globally, unfavourable period, and cohort effects were found in many countries. Increase of mortality rate among the population ≥85 years was the common challenge across all SDI quintiles, stressing the necessity to further improve health care for CAVD patients worldwide.
STereotactic Arrhythmia Radioablation (STAR): the Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe
Authors: Grehn Melanie , Mandija Stefano , Miszczyk Marcin , Krug David , Tomasik Bartłomiej , Stickney Kristine E , Alcantara Pino , Alongi Filippo , Anselmino Matteo , Aranda Ricardo Salgado , Balgobind Brian V , Boda-Heggemann Judit , Boldt Leif-Hendrik , Bottoni Nicola , Cvek Jakub , Elicin Olgun , De Ferrari Gaetano Maria , Hassink Rutger J , Hazelaar Colien , Hindricks Gerhard , Hurkmans Coen , Iotti Cinzia , Jadczyk Tomasz , Jiravsky Otakar , Jumeau Raphaël , Kristiansen Steen Buus , Levis Mario , López Manuel Algara , Martí-Almor Julio , Mehrhof Felix , Møller Ditte Sloth , Molon Giulio , Ouss Alexandre , Peichl Petr , Plasek Jiri , Postema Pieter G , Quesada Aurelio , Reichlin Tobias , Rordorf Roberto , Rudic Boris , Saguner Ardan M , ter Bekke Rachel M A , Torrecilla José López , Troost Esther G C , Vitolo Viviana , Andratschke Nicolaus , Zeppenfeld Katja , Blamek Slawomir , Fast Martin , de Panfilis Ludovica , Blanck Oliver , Pruvot Etienne , Verhoeff Joost J C 
Published: March 2023

AbstractThe EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions’ experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% &gt; 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.
Evaluating metabolic and genomic data for predicting grain traits under high night temperature stress in rice
Authors: Bi Ye , Yassue Rafael Massahiro , Paul Puneet , Dhatt Balpreet Kaur , Sandhu Jaspreet , Do Phuc Thi , Walia Harkamal , Obata Toshihiro , Morota Gota 
Published: March 2023

Abstract
The asymmetric increase in average nighttime temperatures relative to increase in average daytime temperatures due to climate change is decreasing grain yield and quality in rice. Therefore, a better genome-level understanding of the impact of higher night temperature stress on the weight of individual grains is essential for future development of more resilient rice. We investigated the utility of metabolites obtained from grains to classify high night temperature (HNT) conditions of genotypes, and metabolites and single-nucleotide polymorphisms (SNPs) to predict grain length, width, and perimeter phenotypes using a rice diversity panel. We found that the metabolic profiles of rice genotypes alone could be used to classify control and HNT conditions with high accuracy using random forest or extreme gradient boosting. Best linear unbiased prediction and BayesC showed greater metabolic prediction performance than machine learning models for grain-size phenotypes. Metabolic prediction was most effective for grain width, resulting in the highest prediction performance. Genomic prediction performed better than metabolic prediction. Integrating metabolites and genomics simultaneously in a prediction model slightly improved prediction performance. We did not observe a difference in prediction between the control and HNT conditions. Several metabolites were identified as auxiliary phenotypes that could be used to enhance the multi-trait genomic prediction of grain-size phenotypes. Our results showed that, in addition to SNPs, metabolites collected from grains offer rich information to perform predictive analyses, including classification modeling of HNT responses and regression modeling of grain-size-related phenotypes in rice.
Tapping Culture Collections for Fungal Endophytes: First Genome Assemblies for Three Genera and Five Species in theAscomycota
Authors: Hill Rowena , Levicky Quentin , Pitsillides Frances , Junnonen Amy , Arrigoni Elena , Bonnin J Miguel , Kermode Anthony , Mian Sahr , Leitch Ilia J , Buddie Alan G , Buggs Richard J A , Gaya Ester 
Published: March 2023

AbstractThe Ascomycota form the largest phylum in the fungal kingdom and show a wide diversity of lifestyles, some involving associations with plants. Genomic data are available for many ascomycetes that are pathogenic to plants, but endophytes, which are asymptomatic inhabitants of plants, are relatively understudied. Here, using short- and long-read technologies, we have sequenced and assembled genomes for 15 endophytic ascomycete strains from CABI’s culture collections. We used phylogenetic analysis to refine the classification of taxa, which revealed that 7 of our 15 genome assemblies are the first for the genus and/or species. We also demonstrated that cytometric genome size estimates can act as a valuable metric for assessing assembly “completeness”, which can easily be overestimated when using BUSCOs alone and has broader implications for genome assembly initiatives. In producing these new genome resources, we emphasise the value of mining existing culture collections to produce data that can help to address major research questions relating to plant–fungal interactions.
Significant Acceleration of Regional Brain Aging and Atrophy After Mild Traumatic Brain Injury
Authors: Shida Alexander F , Massett Roy J , Imms Phoebe , Vegesna Ramanand V , Amgalan Anar , Irimia Andrei 
Published: March 2023

AbstractBrain regions’ rates of age-related volumetric change after traumatic brain injury (TBI) are unknown. Here, we quantify these rates cross-sectionally in 113 persons with recent mild TBI (mTBI), whom we compare against 3 418 healthy controls (HCs). Regional gray matter (GM) volumes were extracted from magnetic resonance images. Linear regression yielded regional brain ages and the annualized average rates of regional GM volume loss. These results were compared across groups after accounting for sex and intracranial volume. In HCs, the steepest rates of volume loss were recorded in the nucleus accumbens, amygdala, and lateral orbital sulcus. In mTBI, approximately 80% of GM structures had significantly steeper rates of annual volume loss than in HCs. The largest group differences involved the short gyri of the insula and both the long gyrus and central sulcus of the insula. No significant sex differences were found in the mTBI group, regional brain ages being the oldest in prefrontal and temporal structures. Thus, mTBI involves significantly steeper regional GM loss rates than in HCs, reflecting older-than-expected regional brain ages.