bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significance of fatty liver index to detect prevalent ischemic heart disease: evidence from national health and nutrition examination survey 1999–2016
Authors: Niu Yuyu , Wang Guifang , Feng Xianjun , Niu Hongyi , Shi Wenrui 
Published: October 2023

BackgroundNon-alcoholic fatty liver disease (NAFLD) contributes to the development of ischemic heart disease via multiple mechanisms. Fatty liver index (FLI) has been proposed as an accurate, convenient, and economic surrogate of the severity of NAFLD. Our present study aims to assess the association between FLI and the prevalent IHD and to evaluate the potential value of FLI to refine the detection of prevalent IHD in the general population.MethodsOur work recruited 32,938 subjects from the National Health and Nutrition Examination Survey 1999–2016. IHD was diagnosed according to the subjects’ self-report. FLI was determined based on triglycerides, BMI, γ-glutamyltransferase, and waist circumference.Results2,370 (7.20%) subjects were diagnosed with IHD. After adjustment of age, sex, race, current smoking, current drinking, PIR, BMI, WC, TC, TG, GGT, Scr, FPG, SBP, anti-hypertensive therapy, anti-diabetic therapy, and lipid-lowering therapy, one standard deviation increase of FLI resulted in a 27.0% increment of the risk of prevalent IHD. In the quartile analysis, we observed a 1.684 times risk of prevalent IHD when comparing the fourth quartile with the first quartile, and there was a trend towards higher risk across the quartiles. The smooth curve fitting displayed a linear relationship between FLI and the presence of IHD without any threshold or saturation effect. Subgroup analysis revealed a robust association in conventional cardiovascular subpopulations, and the association could be more prominent in female subjects and diabetes patients. ROC analysis demonstrated an incremental value of FLI for detecting prevalent IHD after introducing it to conventional cardiovascular risk factors (AUC: 0.823 vs. 0.859, P for comparison &lt;0.001). Also, results from reclassification analysis implicated that more IHD patients could be correctly identified by introducing FLI into conventional cardiovascular risk factors (continuous net reclassification index: 0.633, P &lt; 0.001; integrated discrimination index: 0.034, P &lt; 0.001).ConclusionThe current analysis revealed a positive and linear relationship between FLI and the prevalent IHD. Furthermore, our findings suggest the incremental value of FLI to refine the detection of prevalent IHD in the general population.
No evidence of a causal relationship between ankylosing spondylitis and cardiovascular disease: a two-sample Mendelian randomization study
Authors: Zhong Yan , Chen YingWen , Zhang XinYue , Cai WenJun , Zhao ChangWei , Zhao WenHai 
Published: October 2023

ObjectiveObservational studies have suggested an increased risk of cardiovascular disease in individuals with ankylosing spondylitis. However, these studies are prone to confounding factors and reverse causality. To address these limitations, we conducted a Mendelian randomization study to assess the causal relationship between AS and CVD.MethodsThe study population comprises 9,069 individuals with ankylosing spondylitis and 509,093 individuals with either of six common cardiovascular diseases and a related indicator. Causal analysis using summary effect estimates and inverse variance weighting were employed as the main methods.ResultsThe CAUSE analysis showed no evidence of a causal relationship between AS and CVD. The odds ratios for total CVD, heart failure, myocardial infarction, valvular heart disease, ischemic heart disease, and venous thromboembolism, Arterial stiffness index, were as follows: OR, 1.01; 95% confidence interval, 0.96–1.05; P = 0.91; OR, 1.03; 95% CI, 0.99–1.08; P = 0.50; OR, 0.94; 95% CI, 0.86–1.03; P = 0.53; OR, 0.99; 95% CI, 0.94–1.04; P = 0.99; OR, 0.98; 95% CI, 0.91–1.04; P = 0.94; OR, 0.98; 95% CI, 0.91–1.04; P = 0.99; β, −0.0019; 95% CI, 0.97–1.01; P = 0.99. The IVW and weighted median methods also yielded consistent results, and no heterogeneity or pleiotropy was found. Likewise, a reverse Mendelian randomization analysis did not uncover a heritable causal relationship between AS and CVD.ConclusionThis Mendelian randomization study does not support a causal relationship between AS and CVD. Further research is needed to confirm this association.
Efficacy and safety of sodium-glucose cotransporter-2 inhibitors for heart failure with mildly reduced or preserved ejection fraction: a systematic review and meta-analysis of randomized controlled trials
Authors: Cheema Huzaifa Ahmad , Shafiee Arman , Athar Mohammad Mobin Teymouri , Rafiei Mohammad Ali , Mehmannavaz Atefe , Jafarabady Kyana , Shahid Abia , Ahmad Adeel , Ijaz Sardar Hassan , Dani Sourbha S. , Minhas Abdul Mannan Khan , Nashwan Abdulqadir J. , Fudim Marat , Fonarow Gregg C. 
Published: October 2023

AimsWe sought to conduct a meta-analysis to evaluate the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF).MethodsWe searched the Cochrane Library, MEDLINE (via PubMed), Embase, and ClinicalTrials.gov till March 2023 to retrieve all randomized controlled trials of SGLT2i in patients with HFpEF or HFmrEF. Risk ratios (RRs) and standardized mean differences (SMDs) with their 95% conﬁdence intervals (95% CIs) were pooled using a random-effects model.ResultsWe included data from 14 RCTs. SGLT2i reduced the risk of the primary composite endpoint of first HF hospitalization or cardiovascular death (RR 0.81, 95% CI: 0.76, 0.87; I2 = 0%); these results were consistent across the cohorts of HFmrEF and HFpEF patients. There was no significant decrease in the risk of cardiovascular death (RR 0.96, 95% CI: 0.82, 1.13; I2 = 36%) and all-cause mortality (RR 0.97, 95% CI: 0.89, 1.05; I2 = 0%). There was a significant improvement in the quality of life in the SGLT2i group (SMD 0.13, 95% CI: 0.06, 0.20; I2 = 51%).ConclusionThe use of SGLT2i is associated with a lower risk of the primary composite outcome and a higher quality of life among HFpEF/HFmrEF patients. However, further research involving more extended follow-up periods is required to draw a comprehensive conclusion.Systematic Review RegistrationPROSPERO (CRD42022364223).
Effects of family and neighborhood vulnerability on dual language learner and monolingual children’s preschool outcomes
Authors: Frechette Liz , Castle Sherri , Jeon Shinyoung , Horm Diane , Martinez Irving , Vega Ruvalcaba Denise , Schaefer Shawn 
Published: October 2023

IntroductionResearch has documented that home and neighborhood contexts of children from low-income families are associated with lower cognitive and social–emotional skills than their higher-income peers. Even though over a third of young children growing up in poverty are dual language learners (DLLs), little research has examined how contextual effects differ between DLL and monolingual children. The current study examines how these two contexts, neighborhood vulnerability and family socioeconomic risk, impact executive function (EF) and social–emotional skills in DLL and monolingual preschoolers.MethodsA secondary analysis was completed on data from two Head Start programs. A series of cross-classified models with interactions were conducted to examine the moderating role of DLL status on associations between neighborhood vulnerability and family risk and preschoolers’ EF and social-emotional skills.ResultsProficient bilingual children’s EF skills were not impacted by neighborhood risks, suggesting that proficient bilingual children may have more opportunities to grow their EF skills when switching between English and Spanish regardless of neighborhood context. An unexpected result occurred for emergent bilingual children who were reported to demonstrate fewer behavior problems regardless of family risk, highlighting the importance of ensuring all DLL families have access to resources to promote their children’s social–emotional skills; and teachers have the proper training to support the behaviors of children in their classroom with varying levels of English proficiency.DiscussionAlthough speaking two languages may be a protective factor for young DLLs growing up in poverty, little research has examined how contextual effects differ between DLL and monolingual children. The current study contributes by examining how DLL status, especially two different DLL statuses (i.e., Proficient Bilinguals and Emergent Bilinguals), may vary as a buffer in moderating the negative associations between collective neighborhood vulnerability, individual family risk, and children’s EF and social–emotional skills.
Targeting myeloid-derived suppressor cells with gemcitabine to enhance efficacy of adoptive cell therapy in bladder cancer
Authors: Bazargan Sarah , Bunch Brittany , Ojwang‘ Awino Maureiq E. , Blauvelt Jamie , Landin Annick , Ali Johannes , Abrahams Dominique , Cox Cheryl , Hall Amy M. , Beatty Matthew S. , Poch Michael , Rejniak Katarzyna A. , Pilon-Thomas Shari 
Published: October 2023

BackgroundNew therapeutics in development for bladder cancer need to address the recalcitrant nature of the disease. Intravesical adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) can potentially induce durable responses in bladder cancer while maximizing T cells at the tumor site. T cells infused into the bladder directly encounter immunosuppressive populations, such as myeloid derived suppressor cells (MDSCs), that can attenuate T cell responses. Intravesical instillation of gemcitabine can be used as a lymphodepleting agent to precondition the bladder microenvironment for infused T cell products.MethodsUrine samples from bladder cancer patients and healthy donors were analyzed by flow cytometry and cytometric bead array for immune profiling and cytokine quantification. MDSCs were isolated from the urine and cocultured with stimulated T cells to assess effects on proliferation. An orthotopic murine model of bladder cancer was established using the MB49-OVA cell line and immune profiling was performed. MDSCs from tumor-bearing mice were cocultured with OT-I splenocytes to assess T cell proliferation. Mice received intravesical instillation of gemcitabine and depletion of immune cells was measured via flow cytometry. Bladder tumor growth of mice treated with intravesical gemcitabine, OT-I transgenic T cells, or combination was monitored via ultrasound measurement.ResultsIn comparison to healthy donors, urine specimen from bladder cancer patients show high levels of MDSCs and cytokines associated with myeloid chemotaxis, T cell chemotaxis, and inflammation. T cells isolated from healthy donors were less proliferative when cocultured with MDSCs from the urine. Orthotopic murine bladder tumors also presented with high levels of MDSCs along with enrichment of cytokines found in the patient urine samples. MDSCs isolated from spleens of tumor-bearing mice exerted suppressive effects on the proliferation of OT-I T cells. Intravesical instillation of gemcitabine reduced overall immune cells, MDSCs, and T cells in orthotopic bladder tumors. Combination treatment with gemcitabine and OT-I T cells resulted in sustained anti-tumor responses in comparison to monotherapy treatments.ConclusionMDSCs are enriched within the microenvironment of bladder tumors and are suppressive to T cells. Gemcitabine can be used to lymphodeplete bladder tumors and precondition the microenvironment for intravesical ACT.
DNA metabarcoding reveals evidence of inter- and intra-guild predation by Scylla paramamosain in a marine ecosystem
Authors: Saqib Hafiz Sohaib Ahmed , Yuan Ye , Kazmi Syed Shabi Ul Hassan , Tayyab Muhammad , Xiang Zifei , Ikhwanuddin Mhd , Ma Hongyu 
Published: October 2023

IntroductionCrustacean predators exhibit diverse trophic interactions across various habitats in aquatic ecosystems. To assess their ecological roles, it is essential to understand their complete dietary spectrum. Recently, DNA-based techniques such as DNA metabarcoding and high-throughput sequencing have provided insights into trophic networks and their response to environmental drivers.MethodsIn this study, we used these methods to investigate the impact of salinity gradients on the trophic networks of mud crabs (Scylla paramamosain) in marine ecosystems.ResultsOur results revealed that mud crabs prey on a wide range of taxa, including crabs (other than the host species), fish, shrimps, and other prey factions. Salinity gradients had a significant influence on the specific prey items, such as high predation on Metapenaeus, and Trigonopterus species in high salinity sites. Notably, crabs exhibited a greater infestation of Portunion parasites in environments with high salinity levels, in contrast to environments with lower salinity levels. Ordination analysis showed that mud crabs adapt their diet according to environmental constraints.DiscussionFurthermore, the results indicate that mud crabs showed opportunistic predation behavior as they were observed preying on other Portunidae species sharing the same trophic guild. Overall, these findings demonstrate the dietary plasticity and associated parasite infestation of an important crustacean predator, and provide evidence that environmental changes may affect incidences of the associated parasites as well as the specific predator-prey interactions indirectly through fluctuations in marine ecosystems.
Assessing larval fish diversity and conservation needs in the Luzon strait using DNA barcoding
Authors: Li Haitao , Chen Yiyong , Li Xi , Zhou Peng , Xiong Xiaofei 
Published: October 2023

IntroductionAccurate species identification and biodiversity assessment of larval fish are essential for effective management and conservation of fisheries resources, as it allows for the estimation of parent stocks, assessment of future recruitment, and prediction of spawning and nursing grounds. However, traditional morphology-based identification methods have inherent limitations, highlighting the need for accurate and efficient techniques to address these challenges effectively. The Luzon Strait, a crucial channel connecting the South China Sea to Western Pacific Ocean, is renowned for its fish biodiversity. However, our knowledge of the biodiversity status of larval fish species in this region remains insufficient.MethodsHere we employed DNA barcoding to assess larval fish species diversity in the Luzon Strait and adjacent waters. We investigated the species composition, diversity, and geographical distribution of larval fish communities in the region. Moreover, we assessed habitat types, human uses, and IUCN conservation status of each larval fish species.ResultsA total of 385 larval fish individuals were collected from 15 stations, and 354 individuals were successfully barcoded and identified, representing 147 species from 93 genera, 44 families, and 22 orders. The interspecific Kimura 2-parameter (K2P) divergence exhibited a significant increase of approximately 55-fold higher than intraspecific divergence. The phylogenetic neighbor-joining tree confirmed the distinct lineages for each taxonomic level, demonstrating the feasibility of DNA barcoding. We observed notable variations in fish species diversity and community composition among sampling stations. Non-metric multidimensional scaling analysis revealed greater diversity and dissimilarity of larval fish community compositions in the western regions compared to the eastern regions. This pattern corresponded to the grouping based on the path of the Kuroshio current, suggesting its influence on the fish community structure. Additionally, economically valuable species were identified at these stations, highlighting their ecological significance as potential spawning or nursery grounds for larval fish. We also examined the habitat type, human use, and conservation status of each larval fish species, providing comprehensive insights into their ecological significance and conservation needs.DiscussionThe establishment of a local DNA sequences database through DNA barcoding will greatly enhance the accuracy of species identification in environmental DNA (eDNA) metabarcoding applications. Altogether, this study offers valuable information for identifying important spawning and nursing grounds of fish populations, thereby supporting sustainable management and conservation of fisheries resources in this region.
Chinese Clinical Trial Registry 13-year data collection and analysis: geographic distribution, financial support, research phase, duration, and disease categories
Authors: Fan Ruitai , Zheng Yufei , Zhou Runze , Beeraka Narasimha M. , Sukocheva Olga A. , Zhao Ruiwen , Li Shijie , Zhao Xiang , Liu Chunying , He Song , Mahesh P. A. , Gurupadayya B. M. , Nikolenko Vladimir N. , Zhao Di , Liu Junqi 
Published: October 2023

ObjectiveTo evaluate the current status of trial registration on the Chinese Clinical Trial Registry (ChiCTR).DesignIn this descriptive study, a multi-dimensional grouping analysis was conducted to estimate trends in the annual trial registration, geographical distribution, sources of funding, targeted diseases, and trial subtypes.SettingWe have analyzed all clinical trial records (over 30,000) registered on the Chinese Clinical Trial Registry (ChiCTR) from 2007 to 2020 executed in China.Main outcome(s) and measure(s)The main outcome was the baseline characteristics of registered trials. These trials were categorized and analyzed based on geographical distribution, year of implementation, disease type, resource and funding type, trial duration, trial phase, and the type of experimental approach.ResultsFrom 2008 to 2017, a consistent upward trend in clinical trial registrations was observed, showing an average annual growth rate of 29.2%. The most significant year-on-year (yoy%) growth in registrations occurred in 2014 (62%) and 2018 (68.5%). Public funding represented the predominant source of funding in the Chinese healthcare system. The top five ChiCTR registration sites for all disease types were highly populated urban regions of China, including Shanghai (5,658 trials, 18%), Beijing (5,127 trials, 16%), Guangdong (3,612 trials, 11%), Sichuan (2,448 trials, 8%), and Jiangsu (2,196 trials, 7%). Trials targeting neoplastic diseases accounted for the largest portion of registrations, followed by cardio/cerebrovascular disease (CCVD) and orthopedic diseases-related trials. The largest proportions of registration trial duration were 1–2 years, less than 1 year, and 2–3 years (at 27.36, 26.71, and 22.46%). In the case of the research phase, the top three types of all the registered trials are exploratory research, post-marketing drugs, and clinical trials of new therapeutic technology.Conclusion and relevanceOncological and cardiovascular diseases receive the highest share of national public funding for medical clinical trial-based research in China. Publicly funded trials represent a major segment of the ChiCTR registry, indicating the dominating role of public governance in this health research sector. Furthermore, the growing number of analyzed records reflect the escalation of clinical research activities in China. The tendency to distribute funding resources toward exceedingly populated areas with the highest incidence of oncological and cardiovascular diseases reveals an aim to reduce the dominating disease burden in the urban conglomerates in China.
Pathogenicity and functional analysis of CFAP410 mutations causing cone-rod dystrophy with macular staphyloma
Authors: Yang Shaoqing , Li Ya , Yang Lin , Guo Qingge , You Ya , Lei Bo 
Published: October 2023

BackgroundCone-rod dystrophy (CORD) caused by pathogenic variants in CFAP410 is a very rare disease. The mechanisms by which the variants caused the disease remained largely unknown. CFAP410 pathogenic variants were identified in a cone-rod dystrophy with macular staphyloma patient. We explored the pathogenicity and performed functional analysis of two compound heterozygous mutations.MethodsA 6-year-old boy complained decreased vision for 1 year, underwent ocular examinations together with systemic X-ray check. Blood sample was taken for targeted next generation sequencing (Tg-NGS). Pathogenicity of identified variants was determined by ACMG guideline. Mutated plasmids were constructed and transferred to HEK293T cells. Cell cycle, protein stability, and protein ubiquitination level was measured.ResultsThe best-corrected visual acuity of proband was 0.20 bilaterally. Fundus showed macular staphyloma and uneven granular pigment disorder in the periphery of the retina. SS-OCT showed thinning and atrophy of the outer retina, residual ellipsoid zone (EZ) in the fovea. Scotopic and photopic ERG responses severe reduced. Two heterozygous missense pathogenic variants, c.319 T &gt; C (p.Tyr107His) and c.347 C &gt; T (p.Pro116Leu) in exon 4 of the CFAP410, were found and were pathogenic by the ACMG guideline. In vitro, pathogenic variants affect cell cycle. Immunofluorescence and western blotting showed that the mutant proteins decreased expression levels protein stability. Meanwhile, co-IP data suggested that ubiquitination level was altered in cells transferred with the mutated plasmids.ConclusionCompound heterozygous pathogenic variants c.319 T &gt; C and c.347 C &gt; T in CFAP410 caused CORD with macular staphyloma. The pathogenic mechanisms may be associated with alternations of protein stability and degradation through the ubiquitin-proteasome pathway.
A first draft genome of holm oak (Quercus ilex subsp. ballota), the most representative species of the Mediterranean forest and the Spanish agrosylvopastoral ecosystem “dehesa”
Authors: Rey María-Dolores , Labella-Ortega Mónica , Guerrero-Sánchez Víctor M. , Carleial Rômulo , Castillejo María Ángeles , Ruggieri Valentino , Jorrín-Novo Jesús V. 
Published: October 2023

The holm oak (Quercus ilex subsp. ballota) is the most representative species of the Mediterranean Basin and the agrosylvopastoral Spanish “dehesa” ecosystem. Being part of our life, culture, and subsistence since ancient times, it has significant environmental and economic importance. More recently, there has been a renewed interest in using the Q. ilex acorn as a functional food due to its nutritional and nutraceutical properties. However, the holm oak and its related ecosystems are threatened by different factors, with oak decline syndrome and climate change being the most worrying in the short and medium term. Breeding programs informed by the selection of elite genotypes seem to be the most plausible biotechnological solution to rescue populations under threat. To achieve this and other downstream analyses, we need a high-quality and well-annotated Q. ilex reference genome. Here, we introduce the first draft genome assembly of Q. ilex using long-read sequencing (PacBio). The assembled nuclear haploid genome had 530 contigs totaling 842.2 Mbp (N50 = 3.3 Mbp), of which 448.7 Mb (53%) were repetitive sequences. We annotated 39,443 protein-coding genes of which 94.80% were complete and single-copy genes. Phylogenetic analyses showed no evidence of a recent whole-genome duplication, and high synteny of the 12 chromosomes between Q. ilex and Quercus lobata and between Q. ilex and Quercus robur. The chloroplast genome size was 142.3 Kbp with 149 protein-coding genes successfully annotated. This first draft should allow for the validation of omics data as well as the identification and functional annotation of genes related to phenotypes of interest such as those associated with resilience against oak decline syndrome and climate change and higher acorn productivity and nutraceutical value.