bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heart failure with preserved ejection fraction based on aging and comorbidities
Authors: Lin Ying , Fu Shihui , Yao Yao , Li Yulong , Zhao Yali , Luo Leiming 
Published: July 2021

AbstractHeart failure (HF) with preserved ejection fraction (HFpEF) is a leading cause of hospitalizations and mortality when diagnosed at the age of ≥ 65 years. HFpEF represents multifactorial and multisystemic syndrome and has different pathophysiology and phenotypes. Its diagnosis is difficult to be established based on left ventricular ejection fraction and may benefit from individually tailored approaches, underlying age-related changes and frequent comorbidities. Compared with the rapid development in the treatment of heart failure with reduced ejection fraction, HFpEF presents a great challenge and needs to be addressed considering the failure of HF drugs to improve its outcomes. Further extensive studies on the relationships between HFpEF, aging, and comorbidities in carefully phenotyped HFpEF subgroups may help understand the biology, diagnosis, and treatment of HFpEF. The current review summarized the diagnostic and therapeutic development of HFpEF based on the complex relationships between aging, comorbidities, and HFpEF.
Establishment, validation and evaluation of predictive model for early relapse after R0 resection in hepatocellular carcinoma patients with microvascular invasion
Authors: Zhang Kai , Tao Changcheng , Siqin Tana , Wu Jianxiong , Rong Weiqi 
Published: July 2021

AbstractBackgroundsThis is the first study to build and evaluate a predictive model for early relapse after R0 resection in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI).MethodsThe consecutive HCC patients with MVI who underwent hepatectomy in Cancer Hospital of Chinese Academy of Medical Science from Jan 2014 to June 2019 were retrospectively enrolled and randomly allocated into a derivation (N = 286) and validation cohort (N = 120) in a ratio of 7:3. Cox regression and Logistic regression analyses were performed and a predictive model for postoperative early-relapse were developed.ResultsA total of 406 HCC patients with MVI were included in our work. Preoperative blood alpha-fetoprotein (AFP) level, hepatitis B e antigen (HBeAg) status, MVI classification, largest tumor diameter, the status of serosal invasion, number of tumors, and the status of satellite nodules were incorporated to construct a model. The concordance index (C-index) was 0.737 and 0.736 in the derivation and validation cohort, respectively. The calibration curves showed a good agreement between actual observation and nomogram prediction. The C-index of the nomogram was obviously higher than those of the two traditional HCC staging systems.ConclusionWe have developed and validated a prediction model for postoperative early-relapse in HCC patient with MVI after R0 resection.
Group 2 innate lymphoid cells are numerically and functionally deficient in the triple transgenic mouse model of Alzheimer’s disease
Authors: Fung Ivan Ting Hin , Zhang Yuanyue , Shin Damian S. , Sankar Poornima , Sun Xiangwan , D’Souza Shanti S. , Song Renjie , Kuentzel Marcy L. , Chittur Sridar V. , Zuloaga Kristen L. , Yang Qi 
Published: July 2021

AbstractBackgroundThe immune pathways in Alzheimer’s disease (AD) remain incompletely understood. Our recent study indicates that tissue-resident group 2 innate lymphoid cells (ILC2) accumulate in the brain barriers of aged mice and that their activation alleviates aging-associated cognitive decline. The regulation and function of ILC2 in AD, however, remain unknown.MethodsIn this study, we examined the numbers and functional capability of ILC2 from the triple transgenic AD mice (3xTg-AD) and control wild-type mice. We investigated the effects of treatment with IL-5, a cytokine produced by ILC2, on the cognitive function of 3xTg-AD mice.ResultsWe demonstrate that brain-associated ILC2 are numerically and functionally defective in the triple transgenic AD mouse model (3xTg-AD). The numbers of brain-associated ILC2 were greatly reduced in 7-month-old 3xTg-AD mice of both sexes, compared to those in age- and sex-matched control wild-type mice. The remaining ILC2 in 3xTg-AD mice failed to efficiently produce the type 2 cytokine IL-5 but gained the capability to express a number of proinflammatory genes. Administration of IL-5, a cytokine produced by ILC2, transiently improved spatial recognition and learning in 3xTg-AD mice.ConclusionOur results collectively indicate that numerical and functional deficiency of ILC2 might contribute to the cognitive impairment of 3xTg-AD mice.
Advances in HBV infection and replication systems in vitro
Authors: Xu Ruirui , Hu Pingping , Li Yuwen , Tian Anran , Li Jun , Zhu Chuanlong 
Published: July 2021

Abstract
Background
Hepatitis B virus (HBV) is a DNA virus belonging to the Hepadnaviridae family that has limited tissue and species specificity. Due to the persistence of HBV covalently closed circular DNA (cccDNA) in host cells after HBV infection, current antiviral drugs cannot eradicate HBV. Therefore, the development of an active cell culture system supporting HBV infection has become the key to studying HBV and developing effective therapeutic drugs.

Main body
This review summarizes the significant research achievements in HBV cell culture systems in vitro, including embryonic hepatocytes and primary hepatocytes, which support the virus infection process most similar to that in the body and various liver tumor cells. The discovery of the bile-acid pump sodium-taurocholate co-transporting polypeptide (NTCP) as the receptor of HBV has advanced our understanding of HBV biology. Subsequently, various liver cancer cells overexpressing NTCP that support HBV infection have been established, opening a new door for studying HBV infection. The fact that induced pluripotent stem cells that differentiate into hepatocyte-like cells support HBV infection provides a novel idea for the establishment of an HBV cell culture system.

Conclusion
Because of the host and tissue specificity of HBV, a suitable in vitro HBV infection system is critical for the study of HBV pathogenesis. Nevertheless, recent advances regarding HBV infection in vitro offer hope for better studying the biological characteristics of HBV, the pathogenesis of hepatitis B, the screening of anti-HBV drugs and the mechanism of carcinogenesis.
Association between frequency of spicy food consumption and hypertension: a cross-sectional study in Zhejiang Province, China
Authors: Wang Hao , Chen Lingli , Shen Dun , Cao Yuan , Zhang Xiaoyi , Xie Kaixu , Wang Chunmei , Zhu Shuiqing , Pei Pei , Guo Yu , Bragg Fiona , Yu Min , Chen Zhengming , Li Liming 
Published: July 2021

Abstract
Background
Hypertension is a known risk factor for multiple chronic diseases. Existing literature on the association between frequency of spicy food consumption and hypertension shows mixed findings.

Methods
The analyses are based on the Tongxiang baseline dataset of the China Kadoorie Biobank prospective study, including data from electronic questionnaires, physical measurements and blood sample collection. A total of 53,916 participants aged 30–79 years were included in the final analysis. Multivariable logistic regression was used to estimate the association of spicy food consumption with hypertension, and multiple linear regression was performed to explore the association of spicy food consumption with systolic and diastolic blood pressure.

Results
Of the 53,916 participants, 23,921 had prevalent hypertension. 12.3% of participants reported consuming spicy food weekly. Among female participants, after adjusting for socio-demographic status, lifestyle factors, BMI, waist circumference, sleep duration and snoring, when compared with females who never consumed spicy food, the odds ratios (95% CI) for hypertension were 1.02 (0.96–1.08), 0.90 (0.79–1.01), and 0.88 (0.78–0.99), respectively, for females who consumed spicy food less than once weekly, 1–2 times weekly, and ≥ 3 times weekly (Ptrend = 0.04). The corresponding odds ratios for males were 1.02 (0.95–1.09), 1.07 (0.95–1.20), and 0.91 (0.81–1.01), respectively (Ptrend = 0.39). Among current alcohol drinkers, compared to participants who never consumed spicy food, the odds ratio (95% CI) for hypertension among participants consuming spicy food daily was 0.98 (0.80–1.20). The corresponding figure for non-current drinkers was 0.72 (0.62–0.84). The association was stronger among non-current alcohol drinkers than among current drinkers (Pheterogeneity = 0.02).

Conclusions
Frequency of spicy food consumption is inversely associated with hypertension in females, but not in males.
Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease
Authors: Chu Xiaojing , Jaeger Martin , Beumer Joep , Bakker Olivier B. , Aguirre-Gamboa Raul , Oosting Marije , Smeekens Sanne P. , Moorlag Simone , Mourits Vera P. , Koeken Valerie A. C. M. , de Bree Charlotte , Jansen Trees , Mathews Ian T. , Dao Khoi , Najhawan Mahan , Watrous Jeramie D. , Joosten Irma , Sharma Sonia , Koenen Hans J. P. M. , Withoff Sebo , Jonkers Iris H. , Netea-Maier Romana T. , Xavier Ramnik J. , Franke Lude , Xu Cheng-Jian , Joosten Leo A. B. , Sanna Serena , Jain Mohit , Kumar Vinod , Clevers Hans , Wijmenga Cisca , Netea Mihai G. , Li Yang 
Published: July 2021

Abstract
Background
Recent studies highlight the role of metabolites in immune diseases, but it remains unknown how much of this effect is driven by genetic and non-genetic host factors.

Result
We systematically investigate circulating metabolites in a cohort of 500 healthy subjects (500FG) in whom immune function and activity are deeply measured and whose genetics are profiled. Our data reveal that several major metabolic pathways, including the alanine/glutamate pathway and the arachidonic acid pathway, have a strong impact on cytokine production in response to ex vivo stimulation. We also examine the genetic regulation of metabolites associated with immune phenotypes through genome-wide association analysis and identify 29 significant loci, including eight novel independent loci. Of these, one locus (rs174584-FADS2) associated with arachidonic acid metabolism is causally associated with Crohn’s disease, suggesting it is a potential therapeutic target.

Conclusion
This study provides a comprehensive map of the integration between the blood metabolome and immune phenotypes, reveals novel genetic factors that regulate blood metabolite concentrations, and proposes an integrative approach for identifying new disease treatment targets.
Efficacy of i-PRF in regenerative endodontics therapy for mature permanent teeth with pulp necrosis: study protocol for a multicentre randomised controlled trial
Authors: Liang Yuee , Ma Rongyang , Chen Lijuan , Dai Xingzhu , Zuo Shiya , Jiang Weiyi , Hu Naiming , Deng Zilong , Zhao Wanghong 
Published: July 2021

Abstract
Background
Dental pulp necrosis, a common health problem, is traditionally treated with root canal therapy; however, it fails in restoring the vitality of damaged pulp. Most studies regarding regenerative endodontic therapy (RET) are limited to the treatment of immature necrotic teeth. Given that injectable platelet-rich fibrin (i-PRF) has shown great potential in regenerative medicine as a novel platelet concentration, this study is designed to explore whether i-PRF can serve as a biological scaffold, extending the indications for RET and improving the clinical feasibility of RET in mature permanent teeth with pulp necrosis.

Methods
This is a randomised, double-blind, controlled, multicentre clinical trial designed to evaluate the clinical feasibility of RET for mature permanent teeth with pulp necrosis and to compare the efficacy of i-PRF and blood clots as scaffolds in RET. A total of 346 patients will be recruited from three centres and randomised at an allocation ratio of 1:1 to receive RET with either a blood clot or i-PRF. The changes in subjective symptoms, clinical examinations, and imaging examinations will be tracked longitudinally for a period of 24 months. The primary outcome is the success rate of RET after 24 months. The secondary outcome is the change in pulp vitality measured via thermal and electric pulp tests. In addition, the incidence of adverse events such as discolouration, reinfection, and root resorption will be recorded for a safety evaluation.

Discussion
This study will evaluate the clinical feasibility of RET in mature permanent teeth with pulp necrosis, providing information regarding the efficacy, benefits, and safety of RET with i-PRF. These results may contribute to changes in the treatment of pulp necrosis in mature permanent teeth and reveal the potential of i-PRF as a novel biological scaffold for RET.

Trial registration
ClinicalTrials.govNCT04313010. Registered on 19 March 2020
Stress tolerance enhancement via SPT15 base editing in Saccharomyces cerevisiae
Authors: Liu Yanfang , Lin Yuping , Guo Yufeng , Wu Fengli , Zhang Yuanyuan , Qi Xianni , Wang Zhen , Wang Qinhong 
Published: July 2021

AbstractBackgroundSaccharomyces cerevisiaeis widely used in traditional brewing and modern fermentation industries to produce biofuels, chemicals and other bioproducts, but challenged by various harsh industrial conditions, such as hyperosmotic, thermal and ethanol stresses. Thus, its stress tolerance enhancement has been attracting broad interests. Recently, CRISPR/Cas-based genome editing technology offers unprecedented tools to explore genetic modifications and performance improvement ofS. cerevisiae.ResultsHere, we presented that the Target-AID (activation-induced cytidine deaminase) base editor of enabling C-to-T substitutions could be harnessed to generate in situ nucleotide changes on theS. cerevisiaegenome, thereby introducing protein point mutations in cells. The general transcription factor geneSPT15was targeted, and total 36 mutants with diversified stress tolerances were obtained. Among them, the 18 tolerant mutants against hyperosmotic, thermal and ethanol stresses showed more than 1.5-fold increases of fermentation capacities. These mutations were mainly enriched at the N-terminal region and the convex surface of the saddle-shaped structure of Spt15. Comparative transcriptome analysis of three most stress-tolerant (A140G, P169A and R238K) and two most stress-sensitive (S118L and L214V) mutants revealed common and distinctive impacted global transcription reprogramming and transcriptional regulatory hubs in response to stresses, and these five amino acid changes had different effects on the interactions of Spt15 with DNA and other proteins in the RNA Polymerase II transcription machinery according to protein structure alignment analysis.ConclusionsTaken together, our results demonstrated that the Target-AID base editor provided a powerful tool for targeted in situ mutagenesis inS. cerevisiaeand more potential targets of Spt15 residues for enhancing yeast stress tolerance.
Phenotypic plasticity, canalisation and developmental stability of Triatoma infestans wings: effects of a sublethal application of a pyrethroid insecticide
Authors: Nattero Julieta , Mougabure-Cueto Gastón , Debat Vincent , Gürtler Ricardo E. 
Published: July 2021

Abstract
Background
Triatomine control campaigns have traditionally consisted of spraying the inside of houses with pyrethroid insecticides. However, exposure to sublethal insecticide doses after the initial application is a common occurrence and may have phenotypic consequences for survivors. Here, using Triatoma infestans (the main vector of Chagas disease in the Southern Cone of South America) as a model species, we quantified the effects of exposure to a sublethal dose of pyrethroid insecticide on wing morphology. We tested if the treatment (i) induced a plastic effect (change in the character mean); (ii) altered environmental canalisation (higher individual variation within genotypes); (iii) altered genetic canalisation (higher variation among genotypes); and (iv) altered developmental stability (higher fluctuating asymmetry [FA]).

Methods
Each of 25 full-sib families known to be susceptible to pyrethroid insecticides were split in two groups: one to be treated with a sublethal dose of deltamethrin (insecticide-treated group) and the other to be treated with pure acetone (control group). Wings of the emerging adults were used in a landmark-based geometric morphometry analysis to extract size and shape measurements. Average differences among treatments were measured. Levels of variation among families, among individuals within families and among sides within individuals were computed and compared among treatments.

Results
Wing size and shape were affected by a sublethal dose of deltamethrin. The treated insects had larger wings and a more variable wing size and shape than control insects. For both wing size and shape, genetic variation was higher in treated individuals. Individual variations and variations in FA were also greater in deltamethrin-treated insects than in control ones for all full-sib families; however, the patterns of shape variation associated with genetic variation, individual variation and FA were different.

Conclusions
Insects exposed to a sublethal dose of deltamethrin presented larger, less symmetrical and less canalised wings. The insecticide treatment jointly impaired developmental stability and genetic and environmental canalisation. The divergent patterns of shape variation suggest that the related developmental buffering processes differed at least partially. The morphological modifications induced by a single sublethal exposure to pyrethroids early in life may impinge on subsequent flight performance and consequently affect the dynamics of house invasion and reinfestation, and the effectiveness of triatomine control operations.

Graphical Abstract
Influence of glucocorticoid treatment on trabecular bone score and bone remodeling regulators in early rheumatoid arthritis
Authors: Corrado Addolorata , Rotondo Cinzia , Mele Angiola , Cici Daniela , Maruotti Nicola , Sanpaolo Eliana , Colia Ripalta , Cantatore Francesco Paolo 
Published: July 2021

Abstract
Background
Glucocorticoids (GC) modulate several regulators involved in the pathogenesis of bone changes in rheumatoid arthritis (RA). Trabecular bone score (TBS) allows the indirect assessment of bone quality. The aim of this study was to investigate the effects of GC on TBS and serum levels of bone turnover regulators in patients with recent-onset RA.

Materials and methods
Forty-seven subjects with recent-onset RA (< 6 months) were classified in two groups, low (lGC) and high (hGC) glucocorticoids, according to glucocorticoid dose regimens. Bone mineral density (BMD), TBS, and circulating Dickkopf-1 (Dkk1), sclerostin, osteoprotegerin (OPG), and RANK-L were evaluated at baseline and 6 and 12 months.

Results
BMD significantly declined after 12 months with no significant difference between the lGC and hGC group, whereas TBS decreased in the hGC group only. Circulating OPG decreased during the follow-up period, the reduction being significantly greater in hGC group; conversely, sclerostin and RANK-L serum increased, in a significantly greater extent in the hGC group. TBS inversely correlated with sclerostin, RANK-L, and Dkk1 circulating levels whereas directly correlated with OPG circulating levels. GC cumulative dose showed an inverse relationship with BMD in both the hGC and lGC groups; TBS values showed an inverse relationship with GC cumulative dose in the hGC group only. GC cumulative dose was associated to higher sclerostin and lower OPG serum levels. TBS did not correlate with disease activity whereas BMD was inversely related to disease activity.

Conclusions
In early RA, GC exposure contributes to the reduction of BMD and affects bone quality depending on dose regimens. TBS could be a useful tool to evaluate the negative effect of GC on bone microarchitecture.

Trial registration
This study was ancillary to a parallel-group observational prospective study which was approved by the medical local ethics committee (protocol number DDG 334/19-06-2019).
Oxidative phenotype induced by aerobic physical training prevents the obesity-linked insulin resistance without changes in gastrocnemius muscle ACE2-Angiotensin(1-7)-Mas axis
Authors: Vecchiatto Bruno , da Silva Rafael C. , Higa Talita S. , Muller Cynthia R. , Américo Anna Laura V. , Fortunato-Lima Vanessa C. , Ferreira Marília M. , Martucci Luiz Felipe , Fonseca-Alaniz Miriam H. , Evangelista Fabiana S. 
Published: July 2021

AbstractBackgroundWe investigate the effect of aerobic physical training (APT) on muscle morphofunctional markers and Angiotensin Converting Enzyme 2/Angiotensin 1-7/Mas receptor (ACE2/Ang 1-7/Mas) axis in an obesity-linked insulin resistance (IR) animal model induced by cafeteria diet (CAF).MethodsMale C57BL/6J mice were assigned into groups CHOW-SED (chow diet, sedentary; n = 10), CHOW-TR (chow diet, trained; n = 10), CAF-SED (n = 10) and CAF-TR (n = 10). APT consisted in running sessions of 60 min at 60% of maximal speed, 5 days per week for 8 weeks.ResultsTrained groups had lower body weight and adiposity compared with sedentary groups. CAF-TR improved the glucose and insulin tolerance tests compared with CAF-SED group (AUC = 28.896 ± 1589 vs. 35.200 ± 1076 mg dL−1120 min−1; kITT = 4.1 ± 0.27 vs. 2.5 ± 0.28% min−1, respectively). CHOW-TR and CAF-TR groups increased exercise tolerance, running intensity at which VO2max was reached, the expression of p-AMPK, p-ACC and PGC1-α proteins compared with CHOW-SED and CAF-SED. Mithocondrial protein expression of Mfn1, Mfn2 and Drp1 did not change. Lipid deposition reduced in CAF-TR compared with CAF-SED group (3.71 vs. 5.53%/area), but fiber typing, glycogen content, ACE2 activity, Ang 1-7 concentration and Mas receptor expression did not change.ConclusionsThe APT prevents obesity-linked IR by modifying the skeletal muscle phenotype to one more oxidative independent of changes in the muscle ACE2/Ang 1-7/Mas axis.
Applicability of human-specific STR systems, GlobalFiler™ PCR Amplification Kit, Investigator 24plex QS Kit, and PowerPlex® Fusion 6C in chimpanzee (Pan troglodytes)
Authors: Singh Abhishek , Sahajpal Vivek , Thakur Mukesh , Sharma Lalit Kumar , Chandra Kailash , Bhandari Deepika , Sharma Arun 
Published: July 2021

Abstract
Objectives
Human identification systems based on STRs are widely used in human population genetics and forensic analysis. This study aimed to validate the cross-reactivity of three widely known human-specific STR identification systems i.e. GlobalFiler™ PCR Amplification Kit, Investigator 24plex QS Kit, and PowerPlex® Fusion 6C in chimpanzee.

Results
The present study revealed the successful amplification of 18 loci using GlobalFiler™ PCR Amplification Kit, 18 loci using Investigator 24plex QS Kit, and 20 loci using PowerPlex® Fusion 6C system. The marker Amelogenin (AMEL) showed differential allele size between male and female revealing the gender identity of chimpanzees and thus validates their application concerning forensic examination, population estimation, and genetic analysis.