bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steatohepatitic hepatocellular carcinoma: morphological diagnostic criteria and clinicopathological characteristics
Authors: Trapani Loïc , Beaufrère Aurélie , Hobeika Christian , Codjia Tatiana , Albuquerque Miguel , Bouattour Mohammed , Lesurtel Mickael , Cauchy François , Paradis Valerie 
Published: June 2022

Abstract
According to the WHO, steatohepatitic hepatocellular carcinoma (SH-HCC) is a distinct HCC subtype. Its prevalence and prognosis vary depending on the study, probably because of lack of a consensus pathological definition. The objectives of the study were to carefully describe the morphological features of SH-HCC to propose a relevant pathological definition and evaluate its impact on prognosis. We conducted a single-centre retrospective study including 297 surgically resected HCC. Pathological features of the tumor including SH criteria (steatosis, ballooning, Mallory-Denk bodies, fibrosis, and inflammation) were assessed. The diagnosis of SH-HCC was initially based upon the presence of at least 4 of the 5 SH criteria and the SH component represented > 50% of the tumor area. According to this definition, a total of 39 (13%) HCC cases corresponded to SH-HCC and 30 cases (10%) corresponded to HCC with SH component (< 50%). SH criteria were distributed as follows: ballooning :100% in SH-HCC vs 11% in non–SH-HCC, fibrosis:100% vs 81%, inflammation:100% vs 67%, steatosis :92% vs 8%, and Mallory-Denk bodies :74% vs 3%. Five-year recurrence-free survival (RFS) and 5-year overall survival (OS) were similar for SH-HCC and non–SH-HCC cases (p = 0.413; and p = 0.866, respectively). The percentage of SH component does not impact OS and DFS (p = 0.589; and p = 0.443). Based on these results, we propose a simplified definition of SH-HCC based on ballooning as a major criterion with at least 2 other SH criteria regardless the extent of SH component. Eighty-three HCC (28%) corresponded to SH-HCC according to this definition, including all HCC classified initially as SH-HCC and HCC NOS with SH contingent. Finally, we confirm in a large cohort the high prevalence of SH-HCC and propose a simplified SH-HCC definition that could be easily applied in routine practice.
Relationship between clozapine exposure and the onset of appendicitis in schizophrenia patients: a retrospective cohort study
Authors: Kawakita Yuta , Takeshima Masahiro , Komatsu Kazunari , Imanishi Aya , Fujiwara Dai , Itoh Yu , Mishima Kazuo 
Published: June 2022

Abstract
Objective:Clozapine may cause serious side effects despite benefits in patients with schizophrenia. Thus, an accurate understanding of the side-effect profile of clozapine is extremely important in the management of its administration to patients with schizophrenia. Our aim was to validate the relationship between clozapine exposure and appendicitis onset in patients with schizophrenia.Methods:In this study, we retrospectively compared the incidence and cumulative incidence of appendicitis in patients with schizophrenia with and without a history of clozapine exposure. Among the patients with schizophrenia who visited our hospital between June 2009 and August 2021, we extracted those with a history of clozapine treatment. Patients with a history of taking clozapine were defined as the clozapine exposure group, while the others were defined as the clozapine non-exposure group. Patients with a history of appendectomy or clozapine use at other hospitals were excluded. Results:There were 65 patients in the clozapine exposure group and 400 patients in the clozapine non-exposure group who met the inclusion criteria. The exposure group exhibited a remarkably higher incidence of appendicitis during the observation period than the non-exposure group (863 cases vs. 124 cases per 100,000 person-years). In particular, if limited to the period of clozapine exposure, the incidence of appendicitis is extremely high, at 2,086 cases per 100,000 person-years. Moreover, the multivariable analysis showed that clozapine exposure during adolescence is a risk factor for appendicitis onset.Conclusions:Clozapine exposure is associated with appendicitis onset in patients with schizophrenia.
Modifiable lifestyle factors have a larger contribution to colorectal neoplasms than family history
Authors: Wang Shuyuan , Yuan Zhen , Wang Yuqi , Zhao Xuanzhu , Gao Weifeng , Li Hongzhou , Zhao Yuanshun , Zhang Zili , Liang Shuiqing , Liu Zhaoce , Zhang Qinghuai , Ma Hong , Zhang Xipeng , Cui Wei , Zhang Chunze 
Published: June 2022

Abstract
Background: Screening recommendations for colorectal cancer (CRC) are mainly based on family history rather than lifestyle risk factors. We aimed to assess and compare risk factors for colorectal neoplasm (CRN) and evaluate trends in the detection rates of CRNs during the first 10 years of a screening program.Methods: This large cross-sectional study included 89,535 individuals who underwent colonoscopies within the CRC screening program in Tianjin, China, from 2012-2020. Of these, 41,221 average-risk individuals with completed and high-quality questionnaires were included for analysis.Results: Among 41,221 individuals, 17,823 (39.3%) individuals had nonadvanced CRN, 2,688 (6.0%) had advanced adenomas, and 693 (1.5%) had CRC. The population attributable fractions (PAFs) of current smoking, alcohol consumption, physical activity, BMI and family history of CRC, respectively, were 8.9%, 2.6%, 1.9%, 5.8%, and 1.1% for males with nonadvanced CRN; 12.3%, 7.3%, 4.9%, 7.2%, and 0.8% for males with advanced CRN; 3.4%, 0.4%, 2.1%, 7.8%, and 0.7% for females with nonadvanced CRN; and 4.3%, 0.2%, 8.2%, 8.5%, and -0.6% for females with advanced CRN. The PAFs of selected lifestyle factors were 19.9% for males with nonadvanced CRN, 29.0% for males with advanced CRN, 9.7% for females with nonadvanced CRN and 13.8% for females with advanced CRN.Conclusions: Modifiable lifestyle factors, including smoking, alcohol consumption, physical activity and BMI, have a larger contribution to CRN than family history of CRC. These findings may be helpful for optimizing risk stratification in population-based screening and cancer control strategies in China.
Multi-tissue architecture of the adaptive immune receptor repertoire in the cynomolgus macaque
Authors: Zhu Yan , Tang Haipei , Guan Junjie , Xie Wenxi , Chen Sen , Lan Chunhong , Ma Cuiyu , Zeng Huikun , Yang Xiujia , Wang Qi-Long , Wei Lai , Zhang Zhenhai , Yu Xueqing 
Published: June 2022

Abstract
The adaptive immune receptor repertoire (AIRR), consisting of B and T cell receptors (BCRs and TCRs), is critical for human health, and the constitution of the AIRR is tissue-specific. However, the similarity of AIRRs in different tissues, especially with respect to BCR isotypes, remains unclear. Because it is extremely hard to acquire multi-organ tissues from human donors, we investigated the AIRR architecture of the cynomolgus macaque (CM) – the predominant non-human primate model in biomedical research. Using ultra-deep TCR and isotype-specific BCR repertoire sequencing from 22 and 25 tissues, respectively, in three CMs, we revealed 85 novel IGHV allele candidates, 57 of which were verifiable using Sanger sequencing, and 117 TRBV allele candidates. These novel IGHV and TRBV alleles are specific to individual CMs, which suggests high genetic heterogeneity. We also found heterogeneous patterns of V gene usage that varied by individual, isotype (for BCRs only), tissue group, and tissue. The large and small intestines of the CMs contained a high number of intra-group shared clones, but fewer shared clones were identified in other tissues, suggesting a heterogeneous distribution of TCR and BCR repertoires. Importantly, most of the public clones are shared between tissues and have considerable similarity to those of humans. We also observed significantly higher mutation burdens in the public clones and the inter-tissue shared IgM and IgD clones, which suggests that these clones are targeting common antigens. This study reveals the extensive heterogeneity of the AIRRs at the individual, tissue group, and tissue levels and has broad fundamental and clinical implications. The data generated here will serve as an invaluable resource for future studies on adaptive immunity in health and diseases.
The improvement effect of working through the Silver Human Resources Center on pre-frailty among older people: A two-year follow-up study
Authors: Morishita-Suzuki Kumi , Nakamura-Uehara Momomi , Ishibashi Tomoaki 
Published: June 2022

Abstract
Background:Although the health benefits of working in old age are well known, no research has examined them among older people with pre-frailty. We examined the improvement effect of working through the Silver Human Resources Center (SHRC) on pre-frailty among older people in Japan. Methods:We carried out a two-year longitudinal survey from 2017 to 2019. Among 5,199 older people, the analysis included 531 participants who were judged to be of pre-frailty status at baseline and who completed both surveys. We utilized the records of participants’ work through the SHRC from 2017 to 2019. The evaluation of the frequency of working through the SHRC was categorized as “less-working” (i.e., less than a few times a month), “moderate-working” (i.e., one to two times a week), and “frequent-working” (i.e., more than three times a week). The transition of frailty status was classified as “improved” (from pre-frailty to robust) and “non-improved” (from pre-frailty to pre-frailty or frailty). Logistic regression was used to assess the influence of the frequency of working through the SHRC on the improvement of pre-frailty. The analysis model was adjusted for age, sex, working for financial reward, years of membership, community activities, and health status at baseline. Inverse-probability weighting was used to correct for survival bias in the follow-up period.Results: The improvement rate of pre-frailty during follow-up was 28.9% among the less-working, 40.2% in the moderate-working, and 36.9% in the frequent-working groups. The improvement rate in the less-working group was significantly lower than that in the other two groups (φ = -2.4). Multivariable logistic regression analysis showed that individuals in the moderate-working group had significantly higher odds of pre-frailty improvement than those in the less-working group (OR: 1.47, 95% CI: 1.14 - 1.90), and no significant differences were found between the frequent-working and less-working groupsConclusions:We found that the participants engaged in moderate working through the SHRC significantly increased their rate of pre-frailty improvement, while frequent working showed no significant association. Therefore, in the future it is important to provide moderate work to older people with pre-frailty according to their health status.
Alginate Co-probiotics Bioencapsulation Facilitates Artemia to Improve Immune Parameters, Gene Expression, Feed Digestibility and Resistance Against Vibrio spp
Authors: Yudiati Ervia , Yulianto Bambang , Sunaryo Sunaryo , Santoso Adi , Suryono Chrisna Adi , Azhar Nuril 
Published: June 2022

Abstract
Alginate is known as an immunostimulant; however, the comprehensive and simultaneous study on its co-activity with Lactobacillus bulgaricus resolves the relationship of feed digestibility, hematological parameters, and upregulation of the regulation of feed digestibility immune-related gene expression, and disease-resistant in Artemia has not been covered. This study aimed to determine the effect of alginate with Lactobacillus bulgaricus bio encapsulated Artemia in Vibrio vulnificus, V. parahaemolyticus, and V. harveyi challenged. Compared to the non-probiotic alginate, co-probiotic L. bulgaricus activated and improved the mortality rate of 400 ppm alginate from 100% to 30–70% at 36 hours with CMI of 276–702 ± 0.00-101.82 and a mortality reduction of 41.21–74.59 ± 0.05–15.90%. The co-activity of 400 ppm alginate and L. bulgaricus resulted in the higher Phenol Oxidase and Superoxide Dismutase Activity. Beta-glucan and proPO gene expression was also upregulated 233.44% and 185.17%, respectively. The gut evacuation time and fullness have also resulted in better performance than 800 ppm alginate without probiotics. Alginate and L. bulgaricus probiotics have cooperated synergically through pre and probiotic mechanisms. This Artemia bio model defines that this combination will reduce alginate as an immunostimulant and cut off the large-scale utilization in ponds.
Exploration of metabolites from gut microbiota against nonalcoholic fatty liver disease: A network pharmacology-based study
Authors: Oh Ki-Kwang , Gupta Haripriya , Min Byeong Hyun , Ganesan Raja , Sharma Satya Priya , Won Sung Min , Jeong Jin Ju , Lee Su Been , Cha Min Gi , Kwon Goo Hyun , Jeong Min Kyo , Hyun Ji Ye , Eom Jung A , Park Hee Jin , Yoon Sang Jun , Choi Mi Ran , Kim Dong Joon , Suk Ki Tae 
Published: June 2022

Abstract
Background: The metabolites of gut microbiota show favorable therapeutic effects on nonalcoholic fatty liver disease (NAFLD), but the active metabolites and mechanisms against NAFLD have not been documented. The aim of the study was to investigate the active metabolites and mechanisms of gut microbiota against NAFLD by network pharmacology. Results: We obtained a total of 208 metabolites from the gutMgene database and retrieved 1,256 targets from similarity ensemble approach (SEA) and 947 targets from the SwissTargetPrediction (STP) database. In the SEA and STP databases, we identified 668 overlapping targets and obtained 237 targets for NAFLD. Thirty-eight targets were identified out of those 237 and 223 targets retrieved from the gutMgene database, and were considered the final NAFLD targets of metabolites from the microbiome. The results of molecular docking tests suggest that, of the 38 targets, mitogen-activated protein kinase 8-compound K and glycogen synthase kinase-3 beta-myricetin complexes might inhibit the Wnt signaling pathway. The microbiota-signaling pathways-targets-metabolites network analysis reveals that Firmicutes, Fusobacteria, the Toll-like receptor signaling pathway, mitogen-activated protein kinase 1, and phenylacetylglutamine are notable components of NAFLD.Conclusion: The key components and potential mechanisms of metabolites from gut microbiota against NAFLD were explored utilizing network pharmacology analyses. This study provides scientific evidence to support the therapeutic efficacy of metabolites for NAFLD and suggests holistic insights for further research.
The DNA binding landscape of four seed-specific bZIP transcription factors in bread wheat: use of Bind-n-seq in vitro analysis
Authors: Shah Koushik , Kaur Raminder , Sharma Nishtha , Jain Prateek , Singh Dalwinder , Mantri Shrikant , Rishi Vikas 
Published: June 2022

Abstract
Sequence-specific transcription factor (TF)-DNA binding is a vital step in biology since it directly regulates genetic information inside the organism. However, the binding sites for many TFs are unknown in plants and animals.Using high-throughput sequencing technologies,studies have shown that TFs, including basic leucine zipper (bZIP), bind to a myriad of sequences, many of which are biologically relevant. bZIPs are eukaryote-specific dimeric TFs, and in plants, they are reported to bind to 8-12 nts sequences (with ACGT core) in the promoter region of many genes. In sedentary plants, they are the conduit for converting environmental cues into gene activity. A key question is what determines bZIP DNA binding specificity.This study adopts the Bind-n-seq methodology, which uses a 108 nts oligonucleotides library with an 18 nts random sequence that either incorporates ACGT tetranucleotides core or a completely random sequence to generate in vitro DNA-bZIP interaction maps of four seed-specific bread wheat bZIPs. Subsequently, de novo binding motifs representing the complete binding landscape for each bZIP were determined. Binding analysis shows a high degree of overlap for bZIP binding to G-box and C-box but with distinct flanking bases, suggesting a discrete role of flanking regions in ordaining TF-DNA binding specificity. From this study binding motifs obtained for Hy5 and Embp-1 show similarity with previously reported sequences, suggesting the protocol's robustness.
Genomic divergence of hatchery and natural origin Chinook salmon (Oncorhynchus tshawytscha) in two supplemented populations
Authors: Ford Michael J , Berntson Ewann , Moran Paul , McKinney Garrett 
Published: June 2022

Abstract
Captive propagation is widely used for the conservation of imperiled populations. There have been concerns about the genetic effects of such propagation, but few studies have measured this directly at a genomic level. Here, we use moderate-coverage (10X) genome sequences from 80 individuals to evaluate the genomic distribution of variation of several paired groups of Chinook salmon (Oncorhynchus tshawytscha). These include 1) captive and natural-origin fish separated by at least one generation, 2) fish within the same generation having high fitness in captivity compared to those with high fitness in the wild, and 3) fish listed as different Evolutionarily Significant Units (ESUs) under the US Endangered Species Act. The distribution of variation between high fitness captive and high fitness natural fish was nearly identical to that expected from random sampling, indicated that differential selection in the two environments did not create large allele frequency differences within a single generation. In contrast, the samples from distinct ESUs were clearly more divergent than expected by chance, including a peak of divergence near the GREB1L gene on chromosome 28, a gene previously associated with variation in time of return to fresh water. Comparison of hatchery and natural-origin fish within a population fell between these extremes, but the maximum value of FST was similar to the maximum between ESUs, including a peak of divergence on chromosome 8 near the slc7a2 and pdgfrl genes. These results suggest that efforts at limiting genetic divergence between captive and natural fish in these populations have successfully kept the average divergence low across the genome, but at a small portion of their genomes, hatchery and natural salmon were as distinct as individuals from different ESUs.
How does Digital Village Construction Influences Carbon Emission? The Case of China
Authors: Hao Aimin , Hou Yirui , Tan Jiayin 
Published: June 2022

Abstract
Taking 30 provinces in China from 2011 to 2020 as a research sample, this paper empirically tests the impact of digital village construction on carbon emissions. This study found that there is an "inverted U" curve relationship between digital rural construction and rural carbon emissions. Agricultural planting structure and agricultural technical efficiency are important ways for digital village construction to produce carbon emission reduction effects. This study also found that the higher the level of economic development, the stronger the carbon emission reduction effect of digital village construction. In addition, there are also significant differences in the carbon emission reduction effect of digital village construction in regions with different environmental regulation intensities. Finally, in terms of the relationship between digital economic activities and carbon emission reduction, the research conclusions of this paper have important implications.
Is COVID-19 infection related to renal infarction: A retrospective analysis of the patients in one center
Authors: Kasap Yusuf , Ceviz Kazım , Polat Muhammed Emin , Şenel Samet , Ölçücüoğlu Esin , Taştemur Sedat , Odabaş Öner 
Published: June 2022

Abstract
Objectives
COVID-19 draws attention with increasing case reports of organ thrombosis due to hypercoagulability. In addition, it is seen as an atypical finding to cause renal infarction. In this study, it was stated that it may be among the risk factors for renal infarction due to hypercoagulation caused by COVID-19 infection.
Methods
57151 patients who were admitted to the hospital with complaints of renal infarction (stomach ache, diarrhea, dyspnea and flank pain) during COVID-19 pandemic between 12.03.2020 and 23.11.2021 were retrospectively analyzed. The COVID-19 PCR test positive 26 patients were included in group 1 and COVID-19 PCR test result negative 60 patients were included in group 2.
Results
The 86 renal infarction cases were diagnosed among all patients. 26 (0.46%) of them were in group 1 and 60 (0.0011%) of them were in group 2. The rate of renal infarction diagnosed patients were significantly higher in group 1 when compared with group 2 (p < 0.05).
Conclusion
COVID-19 may be a risk factor for renal infarction.
Levothyroxine Use and Longitudinal Changes in Thigh Muscles in At-Risk Participants for Knee Osteoarthritis: Preliminary Analysis from Osteoarthritis Initiative Cohort
Authors: Mohajer Bahram , Moradi Kamyar , Guermazi Ali , Mammen Jennifer , Hunter David , Roemer Frank , Demehri Shadpour 
Published: June 2022

Abstract
Background
We examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in at-risk participants for knee osteoarthritis (KOA) and their mediatory role in subsequent KOA incidence.
Methods
Using the Osteoarthritis Initiative (OAI) data, we included the thighs and corresponding knees of participants at risk but without established radiographic KOA (baseline Kellgren-Lawrence grade (KL) < 2). Levothyroxine users were defined as self-reported use at all annual follow-up visits until 4th year and were matched with levothyroxine nonusers for potential confounders (KOA risk factors, comorbidities, and relevant medications covariates) using 1:2/3 propensity-score (PS) matching. Using a previously developed and validated deep learning method for thigh segmentation, we assessed the association between levothyroxine use and 4-year longitudinal changes in muscle mass, including cross-sectional area (CSA) and muscle composition biomarkers including intra-MAT (within-muscle fat), contractile percentage (non-fat muscle CSA/total muscle CSA), and specific force (force per CSA). We further assessed whether levothyroxine use is associated with 8-year risk of standard KOA radiographic (KL ≥ 2) and symptomatic incidence (incidence of radiographic KOA and pain on most of the days in the past 12 months). Finally, using a mediation analysis, we assessed whether the association between levothyroxine use and KOA incidence is mediated via muscle changes.
Results
We included 1,043 matched thighs/knees (266:777 levothyroxine users:non-users; average ± SD age: 61 ± 9 years, female/male:4). Levothyroxine use was associated with decreased quadriceps CSAs (mean difference, 95%CI: -16.06 mm2/year, -26.70 – -5.41) but not thigh muscles’ composition (e.g., intra-MAT). Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR), 95%CI: 1.78, 1.15–2.75 and symptomatic KOA incidence (HR, 95%CI: 1.93, 1.19–3.13). Mediation analysis showed that a decrease in quadriceps mass (i.e., CSA) partially mediated the increased risk of KOA incidence associated with levothyroxine use.
Conclusions
Our exploratory analyses suggest that levothyroxine use is associated with loss of quadriceps muscle mass, which partially mediates increased risk of subsequent KOA incidence. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier; and therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal changes of thigh muscles.