Miracle-dz/UniFAR-FTUs huggingface dataset:
Bisphenol S Alters the Steroidome in the Preovulatory Follicle, Oviduct Fluid and Plasma in Ewes With Contrasted Metabolic Status

Bisphenol A (BPA), a plasticizer and endocrine disruptor, has been substituted by bisphenol S (BPS), a structural analogue that had already shown adverse effects on granulosa cell steroidogenesis. The objective of this study was to assess the effect of chronic exposure to BPS, a possible endocrine disruptor, on steroid hormones in the ovary, oviduct and plasma using the ewe as a model. Given the interaction between steroidogenesis and the metabolic status, the BPS effect was tested according to two diet groups. Eighty adult ewes were allotted to restricted (R) and well-fed (WF) groups, that were further subdivided into two subgroups. Ewes were exposed to 50 µg BPS/kg/day in their diet (R50 and WF50 groups) or were unexposed controls (R0 and WF0 groups). After at least 3 months of BPS exposure, preovulatory follicular fluid, oviduct fluid and plasma were collected and steroid hormones were analyzed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). A deleterious effect of restricted diet on the volume of oviduct fluid and numbers of pre-ovulatory follicles was observed. Exposure to BPS impaired estradiol concentrations in both follicular and oviduct fluids of well-fed ewes and progesterone, estradiol and estrone concentrations in plasma of restricted ewes. In addition, a significant interaction between metabolic status and BPS exposure was observed for seven steroids, including estradiol. In conclusion, BPS acts in ewes as an endocrine disruptor with differential actions according to metabolic status.
The Long-Term and Short-Term Efficacy of Immunotherapy in Non-Small Cell Lung Cancer Patients With Brain Metastases: A Systematic Review and Meta-Analysis

Background Although immunotherapy has been widely used, there is currently no research comparing immunotherapy for non-small cell lung cancer (NSCLC) patients with brain metastases (BMs). This meta-analysis addresses a gap in the comparison of immunotherapy efficacy, including immune checkpoint inhibitors (ICIs), chemotherapy (CT), radiotherapy (RT), and ICI combined CT or RT. Methods A search of Pubmed, Cochrane, EMBASE, and ClinicalTrial.gov was conducted to identify studies which enrolled NSCLC patients with BM treated with ICIs. The outcomes consisted of intracerebral overall response rate (iORR), intracerebral disease control rate (iDCR), extracranial overall response rate (EORR), distant brain failure (DBF), local control (LC), progression-free survival (PFS), and overall survival (OS). Results A total of 3160 participants from 46 trials were included in the final analysis. Patients treated with immunotherapy were associated with a longer PFS (0.48, 95%CI: 0.41-0.56), and a longer OS (0.64, 95%CI: 0.60-0.69) compared with immunotherapy-naive patients. In prospective studies, dual ICI combined CT and ICI combined CT achieved a better OS. The hazard ratio (HR) of dual ICI combined CT versus dual ICI was 0.61, and the HR of ICI combined CT versus ICI monotherapy was 0.58. Moreover, no statistical difference in PFS, OS, EORR, iORR, iDCR, and EDCR was found between patients with ICI monotherapy and ICI combined cranial radiotherapy. Concurrent ICI combined RT was shown to decrease the rate of DBF (OR = 0.15, 95% CI: 0.03-0.73) compared with RT after ICI. Patients treated with WBRT might have an inferior efficacy than those with SRS because the iORR of SRS was 0.75 (0.70, 0.80) and WBRT was 0. Furthermore, no obvious difference in PFS and OS was observed among the three different types of ICI, which targets PD-1, PD-L1, and CTLA-4, respectively. Conclusions Patients treated with ICI got superior efficacy to those without ICI. Furthermore, dual ICI combined CT and ICI combined CT seemed to be optimal for NSCLC patients with BM. In terms of response and survival, concurrent administration of SRS and ICI led to better outcomes for patients with BMs than non-concurrent or non-SRS. Importance of the Study In the new era of immunotherapy, our meta-analysis validated the importance of immunotherapy for non-small cell lung cancer (NSCLC) patients with brain metastases (BMs). By comparing the long-term and short-term impacts of various regimens, all immunotherapy treatments had superior efficacy to immunotherapy-naive. At the same time, through pairwise comparison in immunotherapy, our findings can help clinicians to make treatment decisions for NSCLC patients with BMs. Systematic Review Registration https://www.crd. york.ac. uk/PROSPERO/display_record. php? RecordID=269621, identifier CRD42021269621.
The Common Haplotype GATGACA in Surfactant-Protein B Gene Is Protective for Respiratory Distress Syndrome in Preterm Neonates

Background Respiratory distress syndrome (RDS), a disorder of primary surfactant deficiency resulting in pulmonary insufficiency, remains a significant problem for preterm neonates. Associations between genetic variants of surfactant proteins and RDS have been reported, but haplotypes of the surfactant protein B gene (SFTPB) have not been studied. The aim of the study was to prove the hypothesis that certain haplotypes of SFTPB may be protective or risk factors for RDS. Methods The study was performed with 149 preterm infants, born <34 weeks of gestation, with 86 infants with mild RDS or without RDS (control group) and 63 infants with severe RDS (patient group). RDS was considered severe if multiple doses of exogenous surfactant and/or mechanical ventilation within the first 72 h of life were needed. The venous blood sample was used for the analysis of gene polymorphisms associated with RDS, genotyping, and haplotype estimation. Multivariate logistic regression analysis and the odds ratio were calculated to detect the contribution of the studied variables to the development of RDS. Results A new association of the common single nucleotide polymorphism (SNP) rs2304566 with RDS in premature infants was detected. Analysis of rs2304566 polymorphisms using a logistic regression model showed that there are two significant predictors inversely related to the occurrence of RDS (Apgar score of 5 min, CT and TT genotype in rs2304566 polymorphism). Gestational age, birth weight, and sex have border significance. Moreover, in the patient group, the frequency of the GATGACA haplotype in the SFTPB gene was lower (p = 0.037), and the GATGGCA haplotype was higher (p = 0.059) in comparison with the control group. Conclusion The common haplotype GATGACA of the SFTPB gene can be protective against RDS in preterm infants. The trend of a higher frequency of GATGGCA in the SFTPB gene in infants with severe RDS suggests that this haplotype may be a risk factor for RDS susceptibility.
Application of CRISPR/Cas Genomic Editing Tools for HIV Therapy: Toward Precise Modifications and Multilevel Protection

Although highly active antiretroviral therapy (HAART) can robustly control human immunodeficiency virus (HIV) infection, the existence of latent HIV in a form of proviral DNA integrated into the host genome makes the virus insensitive to HAART. This requires patients to adhere to HAART for a lifetime, often leading to drug toxicity or viral resistance to therapy. Current genome-editing technologies offer different strategies to reduce the latent HIV reservoir in the body. In this review, we systematize the research on CRISPR/Cas-based anti-HIV therapeutic methods, discuss problems related to viral escape and gene editing, and try to focus on the technologies that effectively and precisely introduce genetic modifications and confer strong resistance to HIV infection. Particularly, knock-in (KI) approaches, such as mature B cells engineered to produce broadly neutralizing antibodies, T cells expressing fusion inhibitory peptides in the context of inactivated viral coreceptors, or provirus excision using base editors, look very promising. Current and future advancements in the precision of CRISPR/Cas editing and its delivery will help extend its applicability to clinical HIV therapy.
Non-Alcoholic Fatty Liver Disease (NAFLD) Is an Independent Risk Factor for Developing New-Onset Diabetes After Acute Pancreatitis: A Multicenter Retrospective Cohort Study in Chinese Population

Background Numerous studies validated frequent glucose dysfunction in patients with acute pancreatitis (AP). However, the prevalence of new-onset diabetes in individuals after a first episode of AP varies widely among previous studies. This study aims to determine the incidence of post-acute pancreatitis diabetes mellitus (PPDM-A) in Chinese people and further identify potential risk factors that influence diabetes development in patients with AP. Methods This was a multi-center retrospective cohort study including 6009 inpatients with a first attack of AP. A total of 1804 patients with AP without known endocrine pancreatic disorders or other pancreatic exocrine diseases were eligible for analysis. Data was collected from medical records by hospital information system and telephone follow-ups after discharge. The multiple logistic regression analysis was established to evaluate the potential influencing factors of PPDM-A. Results The prevalence of newly diagnosed diabetes after a first episode of AP in China was 6.2%. Data showed that patients who developed PPDM-A were more likely to be younger (X2 = 6.329, P = 0.012), experienced longer hospital stays (X2 = 6.949, P = 0.008) and had a higher frequency of overweight or obesity (X2 = 11.559, P = 0.003) compared to those with normal glycemia. The frequency of stress hyperglycemia on admission (X2 = 53.815, P < 0.001), hyperlipidemia (X2 = 33.594, P < 0.001) and non-alcoholic fatty liver disease (NAFLD) (X2 = 36.335, P < 0.001) were significantly higher among individuals with PPDM-A compared with control group. Also, patients with PPDM-A were more likely to be hyperlipidemic AP (X2 = 16.304, P = 0.001) and show a higher degree of severity (X2 = 7.834, P = 0.020) and recurrence rate (X2 = 26.908, P < 0.001) of AP compared to those without diabetes. In addition, multiple logistic regression analysis indicated that stress hyperglycemia, hyperlipidemia, NAFLD and repeated attacks of AP were the independent influence factors for developing PPDM-A. Conclusion Our study first demonstrated the prevalence of secondary diabetes in Chinese patients after AP. The disorder of glucose metabolism in individuals with AP should be regularly evaluated in clinical practice. Further studies are needed to verify the relationship between liver and pancreas in keeping glucose homeostasis under AP condition.
Advances in the Synthesis and Superconductivity of Lanthanide Polyhydrides Under High Pressure

Room-temperature superconductors have long been the ultimate goal of scientists. Pressure-stabilized hydrides are a new rapidly growing class of high-temperature superconductors and are believed to be a new superconducting system, undoubtedly leading to a surge in the discovery of new hydrogen-rich materials. They are the forefront of physics and material science. Lanthanide polyhydrides formed under pressure are promising conventional superconductors. Especially, both the theoretical and experimental reports on lanthanum superhydrides under pressure, exhibiting superconductivity at temperatures as high as 250 K, have further stimulated an intense search for room-temperature superconductors in hydrides. This review focuses on the recent advances of crystal structures, stabilities, and superconductivity of lanthanide polyhydrides at high pressures, including the experimental results from our group. By using in situ four-probe electrical measurements and the synchrotron X-ray diffraction technique, we have identified several high-temperature superconducting phases: a lanthanum superhydride and two cerium superhydrides. The present work indicates that superconductivity declines along the La–Ce–Pr–Nd series, while magnetism becomes more and more pronounced. These discoveries have enriched the binary system of clathrate superhydrides and provided more hints for studying the role of rare earth metal elements having high-temperature superconductivity.
Case Report: A Novel Non-Canonical Splice Site Variant (c.1638+7T>C) in TRPM6 Cause Primary Homagnesemia With Secondary Hocalcemia

Objective Primary hypomagnesemia with secondary hypocalcemia (HSH) is caused by loss-of-function mutations in the TRPM6 gene encoding the epithelial magnesium channel. It is characterized by hypomagnesemia and secondary hypocalcemia associated with neurological symptoms. Here, we aimed to investigate the genetic defects of the TRPM6 gene found in a girl from China. Methods The genomic DNA of the proband and the parents was extracted for whole-exome sequencing. Sanger sequencing was further performed to validate the candidate variants. Subsequently, the TRPM6 gene deletion was verified by quantitative PCR (qPCR) experiment. The effect of the variant on mRNA splicing was analyzed through a minigene splice assay and reverse transcription PCR (RT-PCR) in vitro. Results The proband presented with the symptoms of generalized seizures, tetany, and muscle spasms, which were refractory to anticonvulsant treatment. Phenotypic data indicated that the patient had hypomagnesemia, poor parathyroid hormone response, and resultant hypocalcemia. The trio whole-exome sequencing identified that the proband carried compound heterozygous variants in the TRPM6 gene, a paternally derived exon 6 deletion, and a maternally derived splicing variant (c.1638+7T>C) in exon 14. The minigene splice assay confirmed that the c.1638+7T>C variant resulted in exon 14 skipping, which caused the alteration of TRPM6 mRNA splicing. Conclusion Our results support that the compound heterozygous variants in TRPM6 are responsible for HSH in this patient. A novel pathogenic splicing variant (c.1638+7T>C) in the intron 14 disturbs the normal TRPM6 mRNA splicing, suggesting that the non-classical splice variant plays a critical role in HSH. This variant is essential for future effective genetic diagnosis.
Identification of a Novel Insertion Site HVT-005/006 for the Generation of Recombinant Turkey Herpesvirus Vector

Turkey herpesvirus (HVT) has been widely used as a successful live virus vaccine against Marek's disease (MD) in chickens for more than five decades. Increasingly, HVT is also used as a highly effective recombinant vaccine vector against multiple avian pathogens. Conventional recombination, or recombineering, techniques that involve the cloning of viral genomes and, more recently, gene editing methods have been used for the generation of recombinant HVT-based vaccines. In this study, we used NHEJ-dependent CRISPR/Cas9-based approaches to insert the mCherry cassette for the screening of the HVT genome and identifying new potential sites for the insertion of foreign genes. A novel intergenic site HVT-005/006 in the unique long (UL) region of the HVT genome was identified, and mCherry was found to be stably expressed when inserted at this site. To confirm whether this site was suitable for the insertion of other exogenous genes, haemagglutinin (HA) of the H9N2 virus was inserted into this site, and a recombinant HVT-005/006-HA was rescued. The recombinant HVT-HA can grow well and express HA protein stably, which demonstrated that HVT-005/006 is a promising site for the insertion of foreign genes.
How Does Employees’ Narcissism Influence Organizational Commitment? The Role of Perceived Supervisor Support and Abusive Supervision

Narcissism has an important influence on employees’ attitudes and behavior. However, research on the mechanism of this process is still relatively scarce. Based on the conservation of resources (COR) theory, this study constructed a conceptual model of the relationship between narcissism and organizational commitment and explored the role of perceived supervisor support and abusive supervision in this process. Data were collected in three waves from 288 participants through an online data collection platform in China. The results indicated that employee narcissism negatively predicts organizational commitment, and this process is mediated by perceived supervisor support. We also discuss the moderating role of abusive supervisors on perceived supervisor support, confirming that external self-value threat affects perceived support of narcissistic individuals. These results contribute to our understanding of the role of narcissism in organizations.
A RE-AIM Framework Analysis of DNA-Based Population Screening: Using Implementation Science to Translate Research Into Practice in a Healthcare System

Introduction: DNA-based population screening has been proposed as a public health solution to identify individuals at risk for serious health conditions who otherwise may not present for medical care. The clinical utility and public health impact of DNA-based population screening is a subject of active investigation. Geisinger, an integrated healthcare delivery system, was one of the first healthcare systems to implement DNA screening programs (MyCode Community Health Initiative (MyCode) and clinical DNA screening pilot) that leverage exome data to identify individuals at risk for developing conditions with potential clinical actionability. Here, we demonstrate the use of an implementation science framework, RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance), to conduct a post-hoc evaluation and report outcomes from these two programs to inform the potential impact of DNA-based population screening. Methods: Reach and Effectiveness outcomes were determined from the MyCode research program, while Adoption and Implementation outcomes were measured using the clinical DNA screening pilot. Reach was defined as the number of patients who were offered and consented to participate in MyCode. Effectiveness of DNA screening was measured by reviewing MyCode program publications and synthesizing findings from themes. Adoption was measured by the total number of DNA screening tests ordered by clinicians at the clinical pilot sites. Implementation was assessed by interviewing a subset of clinical pilot clinicians about the deployment of and recommended adaptations to the pilot that could inform future program dissemination. Results: Reach: As of August 2020, 68% (215,078/316,612) of individuals approached to participate in the MyCode program consented. Effectiveness: Published evidence reported from MyCode demonstrates that DNA screening identifies at-risk individuals more comprehensively than clinical ascertainment based on phenotypes or personal/family history. Adoption: From July 2018 to June 2021, a total of 1,026 clinical DNA screening tests were ordered by 60 clinicians across the three pilot clinic sites. Implementation: Interviews with 14 clinicians practicing at the pilot clinic sites revealed motivation to provide patients with DNA screening results and yielded future implementation strategies. Conclusion: The RE-AIM framework offers a pragmatic solution to organize, analyze, and report outcomes across differently resourced and designed precision health programs that include genomic sequencing and return of clinically actionable genomic information.
Genetic Evidence Supporting a Causal Role of Snoring in Erectile Dysfunction

Background The association between snoring and erectile dysfunction (ED) is inconsistent in multiple observational studies. To clarify the causal association of snoring on ED, we performed this two-sample Mendelian randomization study. Materials and Methods The single nucleotide polymorphisms (SNPs) associated with snoring were retrieved from the UK biobank cohort with 314,449 participants (117,812 cases and 196,637 controls). The summary statistics of ED were obtained from the European ancestry with 223,805 subjects (6,175 cases and 217,630 controls). Single-variable Mendelian randomization (MR) and multivariable MR were used to assess the causal relationship between snoring and ED. Results Snoring increases the risk of ED (Odds ratio [OR] = 3.45, 95% confidence interval [CI] = 1.68 - 7.09, P < 0.001) in the inverse variance weighting estimator. In sensitivity analyses, the ORs for the weighted median, MR robust adjusted profile score, and MR Pleiotropy Residual Sum and Outlier approach, MR-Egger, and maximum likelihood method are 5.70 (95% CI = 1.19 - 27.21, P < 0.05), 3.14 (95% CI = 1.01 - 9.72, P < 0.05), 3.11 (95% CI = 1.63 - 5.91, P < 0.01), 1.23 (95% CI = 0.01 – 679.73, P > 0.05), and 3.59 (95% CI = 1.07 – 12.00, P < 0.05), respectively. No heterogeneity and pleiotropy are observed (P for MR-Egger intercept = 0.748; P for global test = 0.997; P for Cochran’s Q statistics > 0.05). After adjusting for total cholesterol, triglyceride, low-density lipoprotein, and cigarette consumption, the ORs for ED are 5.75 (95% CI = 1.80 - 18.34, P < 0.01), 4.16 (95% CI = 1.10 - 15.81, P < 0.05), 5.50 (95% CI = 1.62 - 18.69, P < 0.01), and 2.74 (95% CI = 1.06 - 7.10, P < 0.05), respectively. Conclusion This study provides genetic evidence supporting the causal role of snoring in ED.
Potential Prognostic Indicators for Patients With Retinal Vein Occlusion

The second most prevalent cause of retinal vascular disease is retinal vein occlusion (RVO). RVO raises intravascular pressure in the capillary and veins, triggering vessel barrier collapse and subsequent leaking of blood or plasma components into the tissue (edema). Macular edema (ME) is a major complication of RVO that results in significant visual impairment. Laser therapy, intravitreal steroid injections, and vascular endothelial growth factor (VEGF) inhibitors are the major therapeutic techniques. Different therapies reduce ME of RVO and improve visual activity. However, some people have no impact on the resolution of ME, while others have a poor visual prognosis despite full ME cure. There are many investigators who studied the relationship between indicators of various instruments with visual activity. However, a summary of those findings is currently lacking. Therefore, we will focus on the predictive factors of different studies associated with positive visual activity outcomes, which would be very useful and important to help address both treatment expectations and methods for patients with RVO.
Impact of the Madden‐Julian Oscillation on the intraseasonal forecast skill of the North Atlantic Oscillation

Using the output of the intraseasonal hindcast experiment conducted with the GEM global atmospheric model during 24 extended winters, the association between the forecast skill of the NAO and the amplitude and phase of the MJO in the initial condition is investigated. It is found that with a lead time up to about one month the NAO forecast skill is significantly influenced by the existence of the MJO signal in the initial condition. A strong MJO leads to a better NAO forecast skill than a weak MJO. An initial state with an MJO phase corresponding to a dipole tropical convection anomaly in the eastern Indian Ocean and western Pacific favors a more skillful NAO forecast than an MJO phase with a single tropical convection anomaly near 120°E. These results indicate that it is possible to increase the skill of the NAO and the extratropical surface air temperature intraseasonal forecast with an improved tropical initialization, a better prediction of the tropical MJO and a better representation of the tropical‐extratropical interaction in dynamical models.