bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of exercise and GLP-1 receptor agonist treatment reduces severity of metabolic syndrome, abdominal obesity, and inflammation: a randomized controlled trial
Authors: Sandsdal Rasmus M. , Juhl Christian R. , Jensen Simon B. K. , Lundgren Julie R. , Janus Charlotte , Blond Martin B. , Rosenkilde Mads , Bogh Adrian F. , Gliemann Lasse , Jensen Jens-Erik B. , Antoniades Charalambos , Stallknecht Bente M. , Holst Jens J. , Madsbad Sten , Torekov Signe S. 
Published: February 2023

Abstract
Background
Identifying and reducing cardiometabolic risks driven by obesity remains a healthcare challenge. The metabolic syndrome is associated with abdominal obesity and inflammation and is predictive of long-term risk of developing type 2 diabetes and cardiovascular disease in otherwise healthy individuals living with obesity. Therefore, we investigated the effects of adherent exercise, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), or the combination on severity of metabolic syndrome, abdominal obesity, and inflammation following weight loss.

Methods
This was a randomized, double-blinded, placebo-controlled trial. During an 8-week low-calorie diet (800 kcal/day), 195 adults with obesity and without diabetes lost 12% in body weight. Participants were then evenly randomized to four arms of one-year treatment with: placebo, moderate-to-vigorous exercise (minimum of 150 min/week of moderate-intensity or 75 min/week of vigorous-intensity aerobic physical activity or an equivalent combination of both), the GLP-1 RA liraglutide 3.0 mg/day, or a combination (exercise + liraglutide). A total of 166 participants completed the trial. We assessed the prespecified secondary outcome metabolic syndrome severity z-score (MetS-Z), abdominal obesity (estimated as android fat via dual-energy X-ray absorptiometry), and inflammation marker high-sensitivity C-reactive protein (hsCRP). Statistical analysis was performed on 130 participants adherent to the study interventions (per-protocol population) using a mixed linear model.

Results
The diet-induced weight loss decreased the severity of MetS-Z from 0.57 to 0.06, which was maintained in the placebo and exercise groups after one year. MetS-Z was further decreased by liraglutide (− 0.37, 95% CI − 0.58 to − 0.16, P < 0.001) and the combination treatment (− 0.48, 95% CI − 0.70 to − 0.25, P < 0.001) compared to placebo. Abdominal fat percentage decreased by 2.6, 2.8, and 6.1 percentage points in the exercise, liraglutide, and combination groups compared to placebo, respectively, and hsCRP decreased only in the combination group compared with placebo (by 43%, P = 0.03).

Conclusion
The combination of adherent exercise and liraglutide treatment reduced metabolic syndrome severity, abdominal obesity, and inflammation and may therefore reduce cardiometabolic risk more than the individual treatments.
Trial registration EudraCT number: 2015-005585-32, ClinicalTrials.gov: NCT04122716
Chimeric Hepatitis B core virus-like particles harboring SARS-CoV2 epitope elicit a humoral immune response in mice
Authors: Sazegari Sima , Akbarzadeh Niaki Malihe , Afsharifar Alireza , Niazi Ali , Derakhshandeh Abdollah , Moradi Vahdat Maryam , Hemmati Farshad , Eskandari Mohammad Hadi 
Published: February 2023

Abstract
Background
Virus-like particles are an interesting vector platform for vaccine development. Particularly, Hepatitis B virus core antigen has been used as a promising VLP platform. It is highly expressed in different recombinant expression systems, such as E. coli, and self-assembled in vitro. It effectively improves the immunogenicity of foreign antigenic epitopes on its surface. Various foreign antigens from bacteria, viruses, and protozoa can be genetically inserted into such nanoparticles. The effective immunogenicity due to VLP vaccines has been reported. However, no research has been performed on the SARS-CoV2 vaccine within this unique platform through genetic engineering. Considering the high yield of target proteins, low cost of production, and feasibility of scaling up, E. coli is an outstanding expression platform to develop such vaccines. Therefore, in this investigation, we planned to study and develop a unique HBc VLP-based vaccine against SARS-Cov2 utilizing the E. coli expression system due to its importance.

Results
Insertion of the selected epitope was done into the major immunodominant region (MIR) of truncated (149 residues) hepatitis B core capsid protein. The chimeric protein was constructed in PET28a+ and expressed through the bacterial E. coli BL21 expression system. However, the protein was expressed in inclusion body forms and extracted following urea denaturation from the insoluble phase. Following the extraction, the vaccine protein was purified using Ni2 + iminodiacetic acid (IDA) affinity chromatography. SDS-PAGE and western blotting were used to confirm the protein expression. Regarding the denaturation step, the unavoidable refolding process was carried out, so that the chimeric VLP reassembled in native conformation. Based on the transmission electron microscopy (TEM) analysis, the HBC VLP was successfully assembled. Confirming the assembled chimeric VLP, we explored the immunogenic effectivity of the vaccine through mice immunization with two-dose vaccination with and without adjuvant. The utilization of adjuvant was suggested to assess the effect of adjuvant on improving the immune elicitation of chimeric VLP-based vaccine. Immunization analysis based on anti-spike specific IgG antibody showed a significant increase in antibody production in harvested serum from immunized mice with HBc-VLP harboring antigenic epitope compared to HBc-VLP- and PBS-injected mice.

Conclusions
The results approved the successful production and the effectiveness of the vaccine in terms of humoral IgG antibody production. Therefore, this platform can be considered a promising strategy for developing safe and reasonable vaccines; however, more complementary immunological evaluations are needed.
A novel circRNA, hsa_circ_0069382, regulates gastric cancer progression
Authors: Wang Haoying , Yuan Hao , Guo Qinghong , Zeng Xi , Liu Mengxiao , Ji Rui , Chen Zhaofeng , Guan Quanlin , Zheng Ya , Wang Yuping , Zhou Yongning 
Published: February 2023

AbstractAberrant expression of circRNAs is closely associated with the progression of gastric cancer; however, the specific mechanisms involved remain unclear. Our aim was to identify new gastric cancer biomarkers and explore the molecular mechanisms of gastric cancer progression. Therefore, we analyzed miRNA and circRNA microarrays of paired early-stage gastric cancer samples. Our study identified a new circRNA called hsa_circ_0069382, that had not been reported before and was expressed at low levels in gastric cancer tissues. Our study also included bioinformatics analyses which determined that the high expression of hsa_circ_0069382 regulated the BTG anti-proliferation factor 2 (BTG2)/ focal adhesion kinase (FAK) axis in gastric cancer lines by sponging for miR-15a-5p. Therefore, proliferation, invasion, and migration of gastric cancer is impacted. miR-15a-5p overexpression partially restored the effects of hsa_circ_0069382. This study provides potential new therapeutic options and a future direction to explore for gastric cancer treatment, and biomarkers.Graphical Abstract
A novel Menin-MLL1 inhibitor, DS-1594a, prevents the progression of acute leukemia with rearranged MLL1 or mutated NPM1
Authors: Numata Masashi , Haginoya Noriyasu , Shiroishi Machiko , Hirata Tsuyoshi , Sato-Otsubo Aiko , Yoshikawa Kenji , Takata Yoshimi , Nagase Reina , Kashimoto Yoshinori , Suzuki Makoto , Schulte Nina , Polier Gernot , Kurimoto Akiko , Tomoe Yumiko , Toyota Akiko , Yoneyama Tomoko , Imai Emi , Watanabe Kenji , Hamada Tomoaki , Kanada Ryutaro , Watanabe Jun , Kagoshima Yoshiko , Tokumaru Eri , Murata Kenji , Baba Takayuki , Shinozaki Taeko , Ohtsuka Masami , Goto Koichi , Karibe Tsuyoshi , Deguchi Takao , Gocho Yoshihiro , Yoshida Masanori , Tomizawa Daisuke , Kato Motohiro , Tsutsumi Shinji , Kitagawa Mayumi , Abe Yuki 
Published: February 2023

Abstract
Background
Mixed lineage leukemia 1-rearranged (MLL1-r) acute leukemia patients respond poorly to currently available treatments and there is a need to develop more effective therapies directly disrupting the Menin‒MLL1 complex. Small-molecule–mediated inhibition of the protein‒protein interaction between Menin and MLL1 fusion proteins is a potential therapeutic strategy for patients with MLL1-r or mutated-nucleophosmin 1 (NPM1c) acute leukemia. In this study, we preclinically evaluated the new compound DS-1594a and its salts.

Methods
We evaluated the preclinical efficacy of DS-1594a as well as DS-1594a·HCl (the HCl salt of DS-1594a) and DS-1594a·succinate (the succinic acid salt of DS-1594a, DS-1594b) in vitro and in vivo using acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) models.

Results
Our results showed that MLL1-r or NPM1c human leukemic cell lines were selectively and highly sensitive to DS-1594a·HCl, with 50% growth inhibition values < 30 nM. Compared with cytrabine, the standard chemotherapy drug as AML therapy, both DS-1594a·HCl and DS-1594a·succinate mediated the eradication of potential leukemia-initiating cells by enhancing differentiation and reducing serial colony-forming potential in MLL1-r AML cells in vitro. The results were confirmed by flow cytometry, RNA sequencing, RT‒qPCR and chromatin immunoprecipitation sequencing analyses. DS-1594a·HCl and DS-1594a·succinate exhibited significant antitumor efficacy and survival benefit in MOLM-13 cell and patient-derived xenograft models of MLL1-r or NPM1c acute leukemia in vivo.

Conclusion
We have generated a novel, potent, orally available small-molecule inhibitor of the Menin-MLL1 interaction, DS-1594a. Our results suggest that DS-1594a has medicinal properties distinct from those of cytarabine and that DS-1594a has the potential to be a new anticancer therapy and support oral dosing regimen for clinical studies (NCT04752163).
Prognosis-related molecular subtyping in head and neck squamous cell carcinoma patients based on glycolytic/cholesterogenic gene data
Authors: Zhou Zekun , Tang Jianfei , Lu Yixuan , Jia Jia , Luo Tiao , Su Kaixin , Dai Xiaohan , Zhang Haixia , Liu Ousheng 
Published: February 2023

Abstract
Background
Head and neck squamous cell carcinoma (HNSCC) remains an unmet medical challenge. Metabolic reprogramming is a hallmark of diverse cancers, including HNSCC.

Methods
We investigated the metabolic profile in HNSCC by using The Cancer Genome Atlas (TCGA) (n = 481) and Gene Expression Omnibus (GEO) (n = 97) databases. The metabolic stratification of HNSCC samples was identified by using unsupervised k-means clustering. We analyzed the correlations of the metabolic subtypes in HNSCC with featured genomic alterations and known HNSCC subtypes. We further validated the metabolism-related subtypes based on features of ENO1, PFKFB3, NSDHL and SQLE expression in HNSCC by Immunohistochemistry. In addition, genomic characteristics of tumor metabolism that varied among different cancer types were confirmed.

Results
Based on the median expression of coexpressed cholesterogenic and glycolytic genes, HNSCC subtypes were identified, including glycolytic, cholesterogenic, quiescent and mixed subtypes. The quiescent subtype was associated with the longest survival and was distributed in stage I and G1 HNSCC. Mutation analysis of HNSCC genes indicated that TP53 has the highest mutation frequency. The CDKN2A mutation frequency has the most significant differences amongst these four subtypes. There is good overlap between our metabolic subtypes and the HNSCC subtype.

Conclusion
The four metabolic subtypes were successfully determined in HNSCC. Compared to the quiescent subtype, glycolytic, cholesterogenic and mixed subtypes had significantly worse outcome, which might offer guidelines for developing a novel treatment strategy for HNSCC.
Puff, Puff, Don’t Pass: harm reduction for cannabis use during a viral respiratory pandemic
Authors: Assaf Ryan D. , Javanbakht Marjan , Gorbach Pamina M. , Arah Onyebuchi A. , Shoptaw Steven J. , Cooper Ziva D. 
Published: February 2023

Abstract
Background
Prior to the COVID-19 pandemic, cannabis use social practices often involved sharing prepared cannabis (joints/blunts/cigarettes) and cannabis-related paraphernalia. Previous studies have demonstrated that sharing paraphernalia for cannabis, tobacco, and crack cocaine is a risk factor for respiratory viral and bacterial infections. Although COVID-19 is a respiratory viral infection that spreads through droplets and airborne transmission, it is unclear if many individuals adopted harm reduction practices around sharing cannabis. This study: quantifies the prevalence of sharing prepared non-medical cannabis and cannabis-related paraphernalia reported before and during the pandemic; assesses changes in sharing of non-medical cannabis from before to during the pandemic; assess the association between frequency of non-medical cannabis use and sharing of cannabis during the pandemic; and describes how respondents obtained their cannabis and the reasons for changing their cannabis use during the pandemic to explain differences in sharing patterns.

Methods
This cross-sectional study used data collected from an anonymous, US-based web survey on cannabis-related behaviors from August to September 2020 (n = 1833). Participants were included if they reported using a mode of inhalation for non-medical cannabis consumption. We calculated proportional changes in sharing cannabis before/during the COVID-19 pandemic. Associations between frequency of cannabis use and cannabis sharing during the COVID-19 pandemic were assessed using logistic regression analysis.

Results
Overall, 1,112 participants reported non-medical cannabis use; 925 (83.2%) reported a mode of cannabis inhalation. More respondents reported no sharing during (24.9%) than before the pandemic (12.4%; p < 0.01); less respondents shared most of the time (19.5% before; 11.2% during; p < 0.01) and always during the pandemic (5.2% before; 3.1% during; p < 0.01). After adjusting for covariates, the odds of any sharing during the pandemic for those who reported ≥ weekly cannabis use was 0.53 (95% CI 0.38, 0.75) compared to those who reported ≤ monthly.

Conclusions
Sharing of prepared cannabis and cannabis-related paraphernalia decreased during the COVID-19 pandemic compared to before the pandemic. This finding suggests potential risk mitigation strategies taken by participants for COVID-19 prevention either directly through behavior change or indirectly through adherence to COVID-19 prevention recommendations. Harm reduction messaging around sharing of cannabis during surges of COVID-19 or other respiratory infections may provide benefit in reducing infection among those who use cannabis, especially as cannabis use in the USA continues to increase.
Modeling the enigma of complex disease etiology
Authors: Schriml Lynn M. , Lichenstein Richard , Bisordi Katharine , Bearer Cynthia , Baron J. Allen , Greene Carol 
Published: February 2023

AbstractBackgroundComplex diseases often present as a diagnosis riddle, further complicated by the combination of multiple phenotypes and diseases as features of other diseases. With the aim of enhancing the determination of key etiological factors, we developed and tested a complex disease model that encompasses diverse factors that in combination result in complex diseases. This model was developed to address the challenges of classifying complex diseases given the evolving nature of understanding of disease and interaction and contributions of genetic, environmental, and social factors.MethodsHere we present a new approach for modeling complex diseases that integrates the multiple contributing genetic, epigenetic, environmental, host and social pathogenic effects causing disease. The model was developed to provide a guide for capturing diverse mechanisms of complex diseases. Assessment of disease drivers for asthma, diabetes and fetal alcohol syndrome tested the model.ResultsWe provide a detailed rationale for a model representing the classification of complex disease using three test conditions of asthma, diabetes and fetal alcohol syndrome. Model assessment resulted in the reassessment of the three complex disease classifications and identified driving factors, thus improving the model. The model is robust and flexible to capture new information as the understanding of complex disease improves.ConclusionsThe Human Disease Ontology’s Complex Disease model offers a mechanism for defining more accurate disease classification as a tool for more precise clinical diagnosis. This broader representation of complex disease, therefore, has implications for clinicians and researchers who are tasked with creating evidence-based and consensus-based recommendations and for public health tracking of complex disease. The new model facilitates the comparison of etiological factors between complex, common and rare diseases and is available at the Human Disease Ontology website.
The role of non-steroidal anti-inflammatory drugs as adjuncts to periodontal treatment and in periodontal regeneration
Authors: Ren Jianhan , Fok Melissa Rachel , Zhang Yunfan , Han Bing , Lin Yifan 
Published: February 2023

AbstractPeriodontitis is the sixth most prevalent chronic disease globally and places significant burdens on societies and economies worldwide. Behavioral modification, risk factor control, coupled with cause-related therapy have been the “gold standard” treatment for managing periodontitis. Given that host inflammatory and immunological responses play critical roles in the pathogenesis of periodontitis and impact treatment responses, several adjunctive strategies aimed at modulating host responses and improving the results of periodontal therapy and maintenance have been proposed. Of the many pharmacological host modulators, we focused on non-steroidal anti-inflammatory drugs (NSAIDs), due to their long history and extensive use in relieving inflammation and pain and reducing platelet aggregation. NSAIDs have been routinely indicated for treating rheumatic fever and osteoarthritis and utilized for the prevention of cardiovascular events. Although several efforts have been made to incorporate NSAIDs into the treatment of periodontitis, their effects on periodontal health remain poorly characterized, and concerns over the risk–benefit ratio were also raised. Moreover, there is emerging evidence highlighting the potential of NSAIDs, especially aspirin, for use in periodontal regeneration. This review summarizes and discusses the use of NSAIDs in various aspects of periodontal therapy and regeneration, demonstrating that the benefits of NSAIDs as adjuncts to conventional periodontal therapy remain controversial. More recent evidence suggests a promising role for NSAIDs in periodontal tissue engineering and regeneration.
Muscle distribution in relation to all-cause and cause-specific mortality in young and middle-aged adults
Authors: Liu Chen-An , Liu Tong , Ge Yi-Zhong , Song Meng-Meng , Ruan Guo-Tian , Lin Shi-Qi , Xie Hai-Lun , Shi Jin-Yu , Zheng Xin , Chen Yue , Shen Liuyi , Deng Li , Shi Han-Ping 
Published: February 2023

Abstract
Background
The relationship between muscle and prognosis, especially that between muscle distribution across different body parts, and the related prognosis is not well established.

Objective
To investigate the relationship between muscle distribution and all-cause and cause-specific mortality and their potential modifiers.

Design
Longitudinal cohort study. C-index, IDI, and NRI were used to determine the best indicator of prognosis. COX regression analysis was performed to explore the relationship between variables and outcomes. Interaction and subgroup analyses were applied to identify the potential modifiers.

Participants
A total of 5052 participants (weighted: 124,841,420) extracted from the NHANES 2003–2006 of median age 45 years and constituting 50.3% men were assessed. For validation, we included 3040 patients from the INSCOC cohort in China.

Main measures
Muscle mass and distribution.

Key Results
COX regression analysis revealed that upper limbs (HR = 0.41, 95% CI 0.33–0.51), lower limbs (HR = 0.54, 95% CI 0.47–0.64), trunk (HR = 0.71, 95% CI, 0.59–0.85), gynoid (HR = 0.47, 95% CI 0.38–0.58), and total lean mass (HR = 0.55, 95% CI 0.45–0.66) were all associated with the better survival of participants (P trend < 0.001). The changes in the lean mass ratio of the upper and lower limbs and the lean mass ratio of the android and gynoid attenuated the protective effect of lean mass. Age and sex acted as potential modifiers, and the relationship between lean mass and the prognosis was more significant in men and middle-aged participants when compared to that in other age groups. Sensitive analyses depicted that despite lean mass having a long-term impact on prognosis (15 years), it has a more substantial effect on near-term survival (5 years).

Conclusion
Muscle mass and its distribution affect the prognosis with a more significant impact on the near-term than that on the long-term prognosis. Age and sex acted as vital modifiers.
LINC00543 promotes colorectal cancer metastasis by driving EMT and inducing the M2 polarization of tumor associated macrophages
Authors: Zheng Jinsen , Dou Rongzhang , Zhang Xinyao , Zhong Bo , Fang Chenggang , Xu Qian , Di Ziyang , Huang Sihao , Lin Zaihuan , Song Jialin , Wang Shuyi , Xiong Bin 
Published: February 2023

Abstract
Background
The interaction between the tumor-microenvironment (TME) and the cancer cells has emerged as a key player in colorectal cancer (CRC) metastasis. A small proportion of CRC cells which undergo epithelial-mesenchymal transition (EMT) facilitate the reshaping of the TME by regulating various cellular ingredients.

Methods
Immunohistochemical analysis, RNA immunoprecipitation (RIP), RNA Antisense Purification (RAP), dual luciferase assays were conducted to investigate the biological function and regulation of LINC00543 in CRC. A series in vitro and in vivo experiments were used to clarify the role of LINC00543 in CRC metastasis.

Results
Here we found that the long non-coding RNA LINC00543, was overexpressed in colorectal cancer tissues, which correlated with advanced TNM stage and poorer prognosis of CRC patients. The overexpression of LINC00543 promoted tumorigenesis and metastasis of CRC cells by enhancing EMT and remodeling the TME. Mechanistically, LINC00543 blocked the transport of pre-miR-506-3p across the nuclear-cytoplasmic transporter XPO5, thereby reducing the production of mature miR-506-3p, resulting in the increase in the expression of FOXQ1 and induction of EMT. In addition, upregulation of FOXQ1 induced the expression of CCL2 that accelerated the recruitment of macrophages and their M2 polarization.

Conclusions
Our study showed that LINC00543 enhanced EMT of CRC cells through the pre-miR-506-3p/FOXQ1 axis. This resulted in the upregulation of CCL2, leading to macrophages recruitment and M2 polarization, and ultimately stimulating the progression of CRC.