bluuebunny/crossref_metadata_2025_split huggingface dataset:
MSTN-edited born calves obtained by precision breeding, using CRISPR/Cas9 and SCNT
Authors: Suvá Mariana , Baston Juan Ignacio , Wiedenmann Elisabet , Arnold Victoria , de Rozas Belen Pose Ortiz , Jordan Roberto , Ghetti Alberto , Moro Lucia Natalia , Vichera Gabriel 
Published: November 2023

Abstract
Gene editing in cattle offers great potential in the livestock industry. To enhance beef productivity, the aim of this study was to obtain MSTN-edited calves by combining CRISPR/Cas9 edition in cell culture with somatic cell nuclear transfer (SCNT) technology. In the first experiment (E1), gene editing efficiency was evaluated using plasmid-based CRISPR/Cas9 edition in fetal fibroblasts (BFF-E1 cells). The bioinformatic predicted edition rate (BPE) in BFF-E1 was 96%, and all cloned blastocysts generated using these cells as nuclear donors presented bi-allelic edition. In a second experiment (E2), Cas9 protein and trac:crRNA oligoribonucleotide (RNP) were used for MSTN gene editing of one fetal fibroblast (BFF-E2-male) and two mesenchymal stem cell lines (MSC-E2-male and MSC-E2-fem) from price-winning animals. The BPEs were 58.8%, 31% and 59% in cells, and 64%, 73.3% and 66.6% in SCNT embryos, respectively. Heterozygous and wild-type embryos were obtained in all E2 groups. One MSTN-edited calf was born from MSC-E2-femed group. Sequencing analysis revealed heterozygous biallelic edition in exon 2, consisting of an insertion of a thymine (T) base, and a deletion of 18 nucleotides (MSTNKO/-6). A second generation MSTNKO/-6 cloned calf was obtained. In conclusion, high rates of edited blastocysts with valuable genetic background and the birth of two edited calves for the MSTN gene were achieved through RNP-based editing. The protocol described in this work establishes the basis to induce gene editions with productive or biomedical relevance.
Quantifying Travel Time, Mapping and Validating Health Facility Catchment Areas in Blantyre, Malawi
Authors: Kalonde Patrick , Tsoka Owen , Chiepa Blessings , Baluwa Chifuniro , Nkolokosa Clinton , Mategula Donnie , Muthukrishnan Suresh , Feasey Nicholas , Henrion Marc , Stanton Michelle , Ray Nicolas , Terlouw Dianne , Longbottom Joshua , Chirombo James 
Published: November 2023

Abstract
Mapping health facility catchment areas is important for estimating the population that uses the health facility, as a denominator for capturing spatial patterns of disease burden across space. Mapping activities to generate catchment areas are expensive exercises and are often not repeated on a regular basis. In this work, we demonstrated the generation of facility catchment areas in Blantyre, Malawi using crowdsourced road data and open-source mapping tools. We also observed travel speeds associated with different means of transportation were made in five randomly selected residential communities within Blantyre city. AccessMod version 5.8 was used to process the generated data to quantify travel time and catchment areas of health facilities in Blantyre city. When these catchments were compared with georeferenced patients originating, an average of 94.2 percent of the patients came from communities within the generated catchments. The study suggests that crowdsourced data resources can be used for the delineation of catchment areas and this information can confidently be used in efforts to stratify the burden of diseases such as malaria.
Comprehensive study on influence of maturity duration and position of boll formation on seed quality in Asiatic Cotton (Gossypium arboreum)
Authors: Paul Debashis , Santhy V. , Chandra Subhash , Singh Amarpreet , Kumar Rishi 
Published: November 2023

Abstract
Asiatic/Desi cotton (G. arboreum) is in demand in the North zone due to its higher price, tolerance to major sucking insects and better suitability under Cotton-Mustard Cropping system. The production of vigorous seeds in desi cotton is still a major challenge and, the present study was formulated to address this issue. An experiment with nine varieties in RBD was conducted for two years (2020-21 and 2021-22) to ascertain the influence of maturity duration and boll position on seed quality parameters in cotton. The tagged bolls for each genotype were harvested seperately from bottom (up-to 40 cm), middle (41–80 cm) and top position (more than 80 cm of plant height) at 140 days after sowing (DAS), 150 DAS, 160 DAS and 170 DAS respectively, and the seeds obtained after ginning were used for conducting experiments. Genotype, picking time, plant stratum and their interaction influenced the seed physiological parameters significantly. The highest mean germination (%) was observed in the seeds picked at 140 DAS (83.72%) followed by 150 DAS (83.14%) after which a significant decline in germination (%) was noticed. Significantly (P < 0.05) higher Seed vigour index-I (SV-I) & SV-II was noted in the seeds harvested during 140 DAS (2027.77 & 1435.44) to 150 DAS (2158.11 & 1254.21). A gradual decrease in terms of seed vigour parameters after 150 DAS suggested picking of matured bolls during 140 to 150 (DAS) for obtaining seeds with better quality in desi cotton.
CS-6-Induced p62 Accumulation Exacerbates DNA Damage: A Mechanistic Insight into Colorectal Cancer Suppression
Authors: Gong Yitong , Cui Xuehui , Dong Menghan , Wang Liushuyue , Li Defang , Shi Zhen , Bi Sixue 
Published: November 2023

Abstract
Gamabufotalin (CS-6), a bufadienolide derived from Chansu, its role in colorectal cancer (CRC) remains unexplored. CS-6 treatment significantly inhibited CRC SW620 and DLD1 cell viability and colony formation in vitro. Furthermore, CS-6 treatment-induced DNA damage and cell cycle arrest in SW620 and DLD1 cells. Proteomics analysis and the western blot assay revealed that CS-6 treatment upregulated p62 expression, an autophagic substrate involved in the regulation of DNA double-strand damage repair. Knockdown of p62 in this study significantly alleviated CS-6-induced DNA damage and the downregulation of cyclin expression in SW620 and DLD1 cells. Additionally, the results indicated increased expression of microtubule-associated protein 1A/1B light chain 3B (LC3B) and reduced binding between B-cell lymphoma-2 (Bcl2) and beclin-1, suggesting that CS-6 treatment activated early-stage autophagy in CRC cells. However, inhibition of late-stage autophagy and autophagy-related protein 5 (ATG5) with chloroquine and si-ATG5, respectively, further indicated that CS-6-induced autophagy defects led to p62 accumulation, exacerbated cell proliferation inhibition, and aggravated DNA damage. In conclusion, this study suggests that CS-6 may exert its anti-tumor effects in CRC by inducing autophagy defects, resulting in p62 accumulation and DNA damage.
Rapid improvement in pulmonary hypertension related with hereditary hemorrhagic telangiectasia by iloprost inhalation in a postpartum patient, a case report
Authors: Hao Shengyu , Muhetaer Yaxiaerjiang , Zheng Xin , Long Yuliang , Song Jieqiong , Zhong Ming 
Published: November 2023

Abstract
Background
Postpartum pulmonary arterial hypertension (PAH) complicated with hereditary hemorrhagic telangiectasia (HHT) is a rare condition. Diagnosing and treating PAH in patients with HHT can be challenging. To the best of our knowledge, no previous reports have investigated the efficacy of pulmonary vasodilators in improving hemodynamics in postpartum patients with this disease.
Case presentation
In this paper, we report a postpartum case of HHT combined with PAH, which presented with aggravation of dyspnea. Genetic testing revealed that the patient carried a heterozygous variant of activin receptor-like kinase 1 (ACVRL1).
Conclusions
The patient received virous treatments, including diuretics, anticoagulants, disidenafil, macitentan, inhalation of nitric oxide (iNO), and iloprost. Changes in PaO2/FiO2, pulmonary artery systolic pressure (PASP), and NT-proBNP suggested that, with the exception of iloprost inhalation, the other treatments appeared to have limited efficacy.
IRGM/Irgm1 Increases Autophagy to Inhibit Activation of NLRP3 Inflammasome in Inflammatory Injury Induced Acute Liver Failure
Authors: Wang Yadong , Zhang Xing , Hu Yangyang , Wang Wei , Ji Ru , Li Ziyue , Yu Weiyan , Wu Zhinian , Xiao Ying , Guo Tingyu , Qi Zeqiang , Zhao Caiyan 
Published: November 2023

Abstract

Immune-related GTPase M (IRGM) induces autophagy and suppresses inflammation, but its putative role and signaling mechanism remain undefined in the pathogenesis of liver failure. This study aimed to address how IRGM attenuates inflammatory injury by regulating autophagy in liver failure. In this study, a total of 10 patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and 10 healthy controls were prospectively enrolled. Intrahepatic expression of IRGM/Irgm1, NLRP3 inflammasome (NLRP3, ASC, and caspase-1), autophagy-related proteins (LC3II, P62), and inflammatory cytokines (IL-1β, TNF-α) were measured. Autophagy was activated by rapamycin (4 mg/kg) in an acute liver failure (ALF) mouse model, which was used to further study the expression of Irgm1, NLRP3 inflammasome, autophagy-related proteins, and inflammatory cytokines using both qRT-PCR and Western blot analyses. Irgm1 expression was knocked down using Irgm1 short hairpin RNA (shRNA) in lipopolysaccharide (LPS)-induced AML12 cells to investigate the effects of Irgm1 deletion on autophagy and inflammation. We found that expression of IRGM and autophagy-related proteins was significantly downregulated while the NLRP3 inflammasome was significantly upregulated in the livers of HBV-ACLF patients and the ALF mouse model (all P<0.05). Rapamycin-induced autophagy ameliorated intrahepatic NLRP3 inflammasome activation and decreased inflammation and necrosis in the ALF mice. Irgm1 knockdown decreased autophagy and significantly upregulated NLRP3 inflammasome activation in AML12 cells (all P<0.05). Rapamycin-induced autophagy also protected against hepatocyte injury following LPS stimulation in vitro by inhibiting NLRP3 inflammasome activation. Thus, IRGM/Irgm1 alleviates inflammation-mediated hepatocyte injury by regulating autophagy. This study provides new insight into potential molecular targets to treat liver failure.
Multiomics and machine learning-based analysis of pseudouridine modifications in pan-cancer
Authors: Zhang Jiheng , Xu Lei , Yan Xiuwei , Hu Jiahe , Gao Xin , Zhao Hongtao , Geng Mo , Wang Nan , Hu Shaoshan 
Published: November 2023

Abstract
Pseudouridine widely affects the stability and function of different types of RNA. However, our knowledge of pseudouridine properties in tumors is incomplete. We systematically analyzed pseudouridine synthases (PUSs) expression, genomic aberrations and prognostic features in 10907 samples from 33 tumors. We found that the pseudouridine-associated pathway showed significant abnormalities in tumors and affected patient prognosis. Dysregulation of the expression pattern of PUSs may arise from CNV mutations and aberrant DNA methylation. Functional enrichment analyses determined that the expression of PUSs was closely associated with the MYC, E2F and MTORC1 signaling pathways. In addition, PUSs are involved in the remodeling of the tumor microenvironment (TME) in solid tumors, such as kidney and lung cancers. Particularly in lung cancer, increased expression of PUSs is accompanied by increased immune checkpoint expression and Treg infiltration. The best signature model based on more than 10 random 112 machine learning combinations has good predictive prognostic ability in ACC, DLBC, GBM, KICH, MESO, THYM, TGCT, and PRAD, and is expected to guide immunotherapy for 19 tumors. In addition, the model was effective in identifying patients with tumors amenable to treatment with etoposide, camptothecin, cisplatin, and bexarotene. In conclusion, our work highlights the dysregulated features of PUSs, and their role in TME and prognosis, providing an initial molecular basis for future exploration of pseudouridine. Studies targeting pseudouridine are expected to develop potential diagnostic strategies, evaluate and improve antitumor therapies.
A highly accurate nanopore-based sequencing workflow for culture and PCR-free microbial metagenomic profiling of biological samples
Authors: Ferneyhough Ben , Roddis Matthew , Millington Sam , Clements Chrysolin , West Sean , Parkinson Nick , Quirk Jess , Schilizzi Rosalind , Fischer Michael 
Published: November 2023

Abstract
Background
Current clinical methods for microbial detection in urine are largely culture based and, due to bias and limitations of accuracy and sensitivity, hamper efforts to adequately diagnose and treat urogenital infections. This leads to frequent instances of prolonged and recurrent suffering for women. We report a new method that utilises 3rd generation long-read nanopore sequencing to produce fast, accurate and fully quantitated microbiome profiles appropriate for clinical use that can be immediately utilised to aid diagnosis and focus treatments in cases of recurrent or chronic urinary tract infection, rUTI, cUTI and persistent bacterial vaginosis, BV. Here, as proof of principle, we apply this methodology to reassess the healthy urogenital microbiomes of asymptomatic female and male samples.
Results
We show that our method is able to accurately and reproducibly detect the levels of a mixture of ten species comprising known amounts of hard to lyse gram-positive bacteria, gram-negative bacteria and yeast. Furthermore, we show that, in accordance with previous studies, the female asymptomatic urinary microbiome is largely composed of uromes dominated by Gardnerella vaginitis or one of several Lactobacillus species, L. crispatus, L. iners or L. jensenii. We also confirm the tight relationship between vaginal and urinary populations of the same individual at species and strain levels and provide more evidence for the previously observed dynamic nature of these microbiomes over a menstrual cycle.
Conclusions
We set out to develop a cost-effective, rapid, unbiased and fully-quantitative microbiome profiling tool appropriate to inform the clinical diagnosis and treatment of common infections.
We feel the workflow outlined here can be applied directly to help the numerous women debilitated with urogenital infection, especially chronic or recurrent UTIs and persistent BV, that are served poorly by the current diagnostic systems.
Type 2 diabetes, obesity and their relation to the risks of thyroid cancer
Authors: Grimmichova Tereza , Kuklikova Vlasta , Bulanova Barbora , Pacesova Petra , Vaclavikova Eliska , Moravcova Jitka , Novak Zdenek , Mastnikova Karolina , Vankova Marketa 
Published: November 2023

Abstract
Purpose
Patients with type 2 diabetes (T2DM) and obesity are generally known to have increased risk of various types of cancer, though studies addressing associations between T2DM/obesity and thyroid cancer are inconclusive. The aim of our study was to evaluate patients in a euthyroid status with histological results.
Methods
A retrospective study in 184 patients was performed. Three cohorts were established according to tumour histology; malignant (M), benign (B) and low-risk carcinoma (MB). Patient histories were taken, and biochemical testing and fine needle biopsy with molecular testing were performed. Fisher’s exact test and Kruskal-Wallis one-way ANOVA of ranks were used for statistical analysis.
Results
The M (39.1%), B (57.6%) and MB (3.3%) cohorts had comparable age (p = 0.4), BMI (p = 0.452), glycaemia (p = 0.834), Hb1AC (p = 0.157) and HOMA-IR (p = 0.235). T2DM patients had larger thyroid gland volumes (28.8 vs 17.6 mL; p = 0.001) compared to the cohort with normal glucose tolerance. Compared to women, men had more frequently present distal metastases (p = 0.017), minimally invasive disease (p = 0.027), more advanced staging (p = 0.01) and positive pathogenic mutations in the TERT gene (p = 0.009); these results were also significant for the diabetic male cohort (p = 0.026).
Conclusion
Type 2 diabetes and obesity are not risk factors for thyroid cancer, but a subgroup of males seem to have thyroid cancers of poorer prognosis. In general, diabetic patients with insulin resistance and hyperinsulinemia are also prone to have a goitre.
Serendipitous Detection of a Concurrent Asymptomatic Pericardial Cyst during Evaluation of a Hepatic Hydatid Cyst: A Unique Case Report
Authors: AlNajjar Rami Hassoun , Kseibi Hala , Asaad Rama , Mansour Marah , Al-Droubi Tarek 
Published: November 2023

Abstract
Introduction
Hydatid disease, caused by the parasite Echinococcus granulosus, is a prevalent parasitic infection found in various regions worldwide, including the Middle East, southern Europe, and Africa. Although hepatic and pulmonary involvements are well-documented, atypical presentations of the disease remain significant.
Case Presentation
This case report discusses a 32-year-old female patient who sought medical attention due to right hypochondrial pain, and pallor. Initial imaging revealed a hepatic cyst, but an incidental finding of a pericardial cyst further complicated the diagnosis. Subsequent evaluations confirmed the presence of a pericardial hydatid cyst, which is an uncommon manifestation of the disease. The patient presented with a multi-organ infection, which included a cardiac cyst—an unusual occurrence in hydatid disease. Additionally, the pericardial cyst was situated in the pericardium, a rare location, accounting for 2–10% of all cardiac cysts. Importantly, this cyst lacked myocardial involvement, adding to its uniqueness.
Conclusion
This case underscores the importance of considering hydatid disease in patients with non-specific symptoms, particularly in endemic regions, as timely diagnosis is crucial in preventing severe complications.
Mendel randomized analysis of the relationship between pulmonary respiratory function and ovarian cancer
Authors: zhang jiaheng , fu lingmei , Junxia Duan , liu huiping 
Published: November 2023

Abstract
Objective: To explore the causal relationship between forced vital capacity, forced expiratory volume in 1-second (FEV1) best measure, expiratory volume in 1-second (FEV1), predicted and ovarian cancer by using Mendel randomization method.
Methods: The genome-wide association data of forced vital capacity, forced expiratory volume in 1-second (FEV1) best measure, expiratory volume in 1-second (FEV1), predicted and ovarian cancer were obtained based on the platform of Mendel randomization (MR). SNPs significantly related to forced vital capacity, forced expiratory volume in 1-second (fev1) best measure, expiratory volume in 1-second (fev1) and predicted were determined as tool variables. The causal relationship between forced vital capacity, forced expiratory volume in 1-second (FEV1) best measure, expiratory volume in 1-second (FEV1), predicted and ovarian cancer was detected by two-sample MR research method. MR-Egger regression weighted median method (WME) and weighted inverse variance method (IVW) were used to analyze the causal relationship between forced vital capacity and ovarian cancer.
Results: The results of the study included 463 items related to forced expiratory volume in 1-second (FEV1) best measure, expiratory volume in 1-second (FEV1), SNPs with significantly correlated predicted amount were used as instrumental variables (with P <5×10-8 as the screening condition, linkage disequilibrium coefficient r2 was 0.001, and linkage disequilibrium region width was 10000kb). When assessed by different methods, it was found that forced vital capacity, MR Egger(OR value: 1.002, 95% CI: 0.9962-1. Weighted median(OR value: 1.003,95% ci: 0.9998-1.007), Inverse variance weighted(OR value: 1.002,95% ci: 1.0002-1.005), Simple mode(OR value: 1.007,95% ci:). MR Egger(OR value: 1.0050, 95% ci: 0.9958-1.0143), Weighted median(OR value: 1.0030, 95% CI: 0.9990-1.0069), Inverse variance weighted(OR value: 1.0026, 95% 95%CI ：0.9999-1.0053), Simple mode(OR value: 1.0034, 95% CI: 0.9925-1.0145). Expiratory volume in 1-second (FEV1), MR Egger(OR: 1.0012, 95% CI: 0.9928-1.0097) between predicted and ovarian cancer, Weighted median(OR: 1.0035, 95% CI: 0.9993-1.0076). Inverse variance weighted(OR value: 1.0038,95% ci: 1.0009-1.0066), Simple mode(OR value: 1.0040,95% ci: 0.9926-1.0156), Weighted mode(OR value: 1.0065,95%) There are no abnormal variables in forced vital capacity, forced expiratory volume in 1-second (fev1) best measure and expiratory volume in 1-second (fev1), and the predicted heterogeneity test, and the sensitivity analysis shows that it is robust. No pleiotropic effects were found (the intercept terms of MR-Egger regression were -0.0000053, -0.0000089 and -0.0000090(P=0.6015, 0.5957 and 0.5348).
Conclusion: MR analysis provides strong evidence that forced vital capacity, forced expiratory volume in 1-second (FEV1) best measure and expiratory volume in 1-second (FEV1) are risk factors for ovarian cancer.
Probiotic properties and antioxidant activities of Lactiplantibacillus plantarum HY7720 and its fermentation characteristics in plant-based materials
Authors: Kim Ju-Yeon , Choi Eun Jung , Jang Woo Young , Kim Soo A , Heo Kyeong Heo , Kang Heerim , Kang Jeanne , Kim Yong-Tae , Shim Jae-Jung , Lee Jung-Lyoul 
Published: November 2023

Abstract
Lactiplantibacillus plantarum HY7720 was screened from 22 strains of lactic acid bacteria (LAB) that were isolated from different plant foods, and its growth ability and extracellular vitamin B12-producing capacity in vitamin B12-deficient medium were investigated. HY7720 was resistant to the conditions of the gastrointestinal tract (GIT) and showed high adhesion property to human intestinal epithelial cells. Moreover, the results showed that HY7720 recovered the gene expression levels of tight junction-associated proteins (TJPs) and inhibited the secretion levels of pro-inflammatory cytokines in tumor necrosis factor (TNF)-α-stimulated Caco-2 cells. Furthermore, the ability of HY7720 to ameliorate H2O2-induced cytotoxicity in Caco-2 cells was inhibited by mitogen-activated protein kinase (MAPK) inhibitors. This study also investigated the nutritional qualities of three plant-based materials (brown rice, white rice, and soy milk) fermented using HY7720. Collectively, HY7720 could be used as a promising probiotic strain for the prevention of nutritional deficiencies among people on vegetarian diets.