Miracle-dz/UniFAR-FTUs huggingface dataset:
Revealing the impact of lifestyle stressors on the risk of adverse pregnancy outcomes with multitask machine learning

Psychosocial and stress-related factors (PSFs), defined as internal or external stimuli that induce biological changes, are potentially modifiable factors and accessible targets for interventions that are associated with adverse pregnancy outcomes (APOs). Although individual APOs have been shown to be connected to PSFs, they are biologically interconnected, relatively infrequent, and therefore challenging to model. In this context, multi-task machine learning (MML) is an ideal tool for exploring the interconnectedness of APOs on the one hand and building on joint combinatorial outcomes to increase predictive power on the other hand. Additionally, by integrating single cell immunological profiling of underlying biological processes, the effects of stress-based therapeutics may be measurable, facilitating the development of precision medicine approaches. Objectives The primary objectives were to jointly model multiple APOs and their connection to stress early in pregnancy, and to explore the underlying biology to guide development of accessible and measurable interventions. Materials and Methods In a prospective cohort study, PSFs were assessed during the first trimester with an extensive self-filled questionnaire for 200 women. We used MML to simultaneously model, and predict APOs (severe preeclampsia, superimposed preeclampsia, gestational diabetes and early gestational age) as well as several risk factors (BMI, diabetes, hypertension) for these patients based on PSFs. Strongly interrelated stressors were categorized to identify potential therapeutic targets. Furthermore, for a subset of 14 women, we modeled the connection of PSFs to the maternal immune system to APOs by building corresponding ML models based on an extensive single cell immune dataset generated by mass cytometry time of flight (CyTOF). Results Jointly modeling APOs in a MML setting significantly increased modeling capabilities and yielded a highly predictive integrated model of APOs underscoring their interconnectedness. Most APOs were associated with mental health, life stress, and perceived health risks. Biologically, stressors were associated with specific immune characteristics revolving around CD4/CD8 T cells. Immune characteristics predicted based on stress were in turn found to be associated with APOs. Conclusions Elucidating connections among stress, multiple APOs simultaneously, and immune characteristics has the potential to facilitate the implementation of ML-based, individualized, integrative models of pregnancy in clinical decision making. The modifiable nature of stressors may enable the development of accessible interventions, with success tracked through immune characteristics.
Phenotype and genotype analyses of Chinese patients with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations

Background: Autosomal dominant mental retardation type 5 (MRD5), a rare neurodevelopmental disorder (NDD) characterized by intellectual disability (ID), developmental delay (DD), and epilepsy predominantly, is caused by a heterozygous mutation in the SYNGAP1 gene. SYNGAP1 mutations have been rarely reported in the Chinese population. Here, we present an investigation of SYNGAP1 mutations in a clinical cohort with ID and DD in Shandong, a northern province in China, to further explore the genotype and phenotype correlations. Methods: A retrospective study was conducted on 10 children with SYNGAP1 mutations presenting ID, DD, and epilepsy who were diagnosed between January 2014 and May 2022. Clinical data and genetic tests were collected. Treatment and regular follow-ups were carried out to pay close attention to the prognosis of the patients. Results: We described 10 unrelated affected individuals with SYNGAP1 mutations, displaying ID, DD, epilepsy, or seizures. All mutations of SYNGAP1 in the 10 patients were de novo, except patient 3 whose father was unavailable, including five nonsense mutations, two frameshift mutations, two splicing mutations, and one codon deletion. Among these mutations, five were novel and the other five were previously reported. Significantly, all patients with epilepsy were sensitive to anti-seizure drugs, especially sodium valproate. Furthermore, rehabilitation training seemed to exert a more improved effect on motor development than language development for the patients. Conclusion The 10 patients carrying SYNGAP1 mutations were diagnosed as MRD5. Five novel genetic mutations were found, which expanded the mutational spectrum of the SYNGAP1 gene. The identification of these mutations in this study helps explore the relationship between genotypes and phenotypes and contributes to genetic counseling and therapeutic intervention for patients with MRD5.
Intermediate role of gut microbiota in vitamin B nutrition and its influences on human health

Vitamin B consists of a group of water-soluble micronutrients that are mainly derived from the daily diet. They serve as cofactors, mediating multiple metabolic pathways in humans. As an integrated part of human health, gut microbiota could produce, consume, and even compete for vitamin B with the host. The interplay between gut microbiota and the host might be a crucial factor affecting the absorbing processes of vitamin B. On the other hand, vitamin B supplementation or deficiency might impact the growth of specific bacteria, resulting in changes in the composition and function of gut microbiota. Together, the interplay between vitamin B and gut microbiota might systemically contribute to human health. In this review, we summarized the interactions between vitamin B and gut microbiota and tried to reveal the underlying mechanism so that we can have a better understanding of its role in human health.
Adapting to the projected epidemics of Fusarium head blight of wheat in Korea under climate change scenarios

Fusarium head blight (FHB) of wheat, mainly caused by Fusarium graminearum Schwabe, is an emerging threat to wheat production in Korea under a changing climate. The disease occurrence and accumulation of associated trichothecene mycotoxins in wheat kernels strongly coincide with warm and wet environments during flowering. Recently, the International Panel for Climate Change released the 6th Coupled Model Intercomparison Project (CMIP6) climate change scenarios with shared socioeconomic pathways (SSPs). In this study, we adopted GIBSIM, an existing mechanistic model developed in Brazil to estimate the risk infection index of wheat FHB, to simulate the potential FHB epidemics in Korea using the SSP245 and SSP585 scenarios of CMIP6. The GIBSIM model simulates FHB infection risk from airborne inoculum density and infection frequency using temperature, precipitation, and relative humidity during the flowering period. First, wheat heading dates, during which GIBSIM runs, were predicted over suitable areas of winter wheat cultivation using a crop development rate model for wheat phenology and downscaled SSP scenarios. Second, an integrated model combining all results of wheat suitability, heading dates, and FHB infection risks from the SSP scenarios showed a gradual increase in FHB epidemics towards 2100, with different temporal and spatial patterns of varying magnitudes depending on the scenarios. These results indicate that proactive management strategies need to be seriously considered in the near future to minimize the potential impacts of the FHB epidemic under climate change in Korea. Therefore, available wheat cultivars with early or late heading dates were used in the model simulations as a realistic adaptation measure. As a result, wheat cultivars with early heading dates showed significant decreases in FHB epidemics in future periods, emphasizing the importance of effective adaptation measures against the projected increase in FHB epidemics in Korea under climate change.
The potential diagnostic accuracy of urine formaldehyde levels in Alzheimer’s disease: A systematic review and meta-analysis

Background Formaldehyde (FA), a toxic aldehyde, has been shown to be associated with a variety of cognitive disorders, including Alzheimer’s disease (AD). There is increasing evidence that FA levels are significantly increased in AD patients and may be involved in the pathological process of AD. The aim of this study was to assess the potential diagnostic value of urine FA levels in AD using meta-analysis techniques. Methods Original reports of morning urine FA levels in AD patients and healthy controls (HCs) were included in the meta-analysis. Standardized mean differences (SMD) were calculated using a random-effects model, heterogeneity was explored using methodological, age, sex difference and sensitivity analyses, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic value of urine FA levels in AD. Results A total of 12 studies were included, and the urine FA levels of 874 AD patients and 577 HCs were reviewed. Compared with those in HCs, the FA levels were significantly increased in AD patients. The heterogeneity of the results did not affect their robustness, and results of the area under the curve (AUC) suggested that urine FA levels had good potential diagnostic value. Conclusion Urine FA levels are involved in AD disease progression and are likely to be useful as a potential biomarker for clinical auxiliary diagnosis. However, further studies are needed to validate the results of this study.
Does China’s poverty alleviation policy improve the quality of the ecological environment in poverty-stricken areas?

Poverty eradication and environmental protection as the two global goals of sustainable development. China’s poverty alleviation policy attempts to achieve green development in poverty-stricken areas by eliminating poverty while also promoting environmental protection. Since the Poverty-stricken counties on the Qinghai-Tibet Plateau also have the dual attributes of ecological degradation and ecological fragility, it is of great significance to study the impact of poverty alleviation policy on their environment. In this research, taking poverty alleviation policy as the entry point, based on panel data and Remote Sensing Ecological Index for poverty-stricken counties on the Qinghai-Tibet Plateau from 2011 to 2019, and using the difference-in-differences (DID) method to verify the impact of policy on environmental quality. The main findings of the study were: 1) The poverty alleviation policy has a significant improvement effect on the ecological environment quality of counties in the Qinghai-Tibet Plateau region, and this conclusion still holds in a series of robustness tests using methods including the changing sample size method and the variable replacement method. Moreover, the policy effect has a certain time lag and its effect persists in the long term; 2) It is mainly due to the increased level of government public expenditure and the easing of government financial pressure that has contributed to the improvement of environmental quality in poverty-stricken areas; 3) Policy heterogeneity suggests that industrial poverty eradication policies are more conducive to promoting synergistic economic and environmental development in poverty-stricken areas.
Effects of metabolic cancer therapy on tumor microenvironment

Targeting tumor metabolism for cancer therapy is an old strategy. In fact, historically the first effective cancer therapeutics were directed at nucleotide metabolism. The spectrum of metabolic drugs considered in cancer increases rapidly – clinical trials are in progress for agents directed at glycolysis, oxidative phosphorylation, glutaminolysis and several others. These pathways are essential for cancer cell proliferation and redox homeostasis, but are also required, to various degrees, in other cell types present in the tumor microenvironment, including immune cells, endothelial cells and fibroblasts. How metabolism-targeted treatments impact these tumor-associated cell types is not fully understood, even though their response may co-determine the overall effectivity of therapy. Indeed, the metabolic dependencies of stromal cells have been overlooked for a long time. Therefore, it is important that metabolic therapy is considered in the context of tumor microenvironment, as understanding the metabolic vulnerabilities of both cancer and stromal cells can guide new treatment concepts and help better understand treatment resistance. In this review we discuss recent findings covering the impact of metabolic interventions on cellular components of the tumor microenvironment and their implications for metabolic cancer therapy.
Definition of trAnscatheter heart Valve orIeNtation in biCuspId aortic valve: The DA VINCI pilot study

Objectives To assess the impact of conventional transcatheter heart valve (THV) commissural alignment techniques on THV/coronary overlap and coronary access (CA) after transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BAV). Background Specific Evolut Pro/Pro + and Acurate Neo2 THV orientations are associated with reduced neo-commissural overlap with coronary ostia in tricuspid aortic anatomy. Whether standard orientation techniques are effective also in the setting of BAV anatomy has not been studied. Methods The DA VINCI (Definition of trAnscatheter aortic Valve orIeNtation in biCuspId aortic valve) pilot study is a prospective registry enrolling consecutive patients with severe BAV stenosis undergoing TAVR with last generation supra-annular tall-frame THVs implanted with a cusp overlap view-based commissural alignment. Patients underwent pre- and post-TAVR computed tomography (CT) and coronary angiography. The study endpoint was the rate of favorable THV/coronary overlap, defined as an angle > 40° between the THV commissural post and coronary ostia. Other endpoints were the rates of successful THV alignment with respect to the raphe and of selective CA after TAVR. Moreover, different virtual THV alignment models were tested to identify which one would produce the lower degree of THV/coronary overlap. Results Thirty-four patients with type 1 BAV with right-left raphe undergoing TAVR (23 with Evolut Pro/Pro + and 11 with Acurate Neo2) were included. At pre-TAVR CT, moderate/severe cusp asymmetry was found in 50% of patients, severe coronary ostia eccentricity was observed in 47.1% for the RCA vs. 8.8% for the LCA (P < 0.007). Correct TVH orientation was achieved in 29 cases. At post-TAVR CT, optimal THV alignment/mild misalignment to the raphe was observed in 86.2%, but a moderate/severe overlap with the coronaries was seen in 13.7% for the RCA and 44.8% for the LCA (P = 0.019). After TAVR, selective RCA cannulation was possible in 82.8% vs. 75.9% for the LCA (P = 0.74), while combined selective CA of both coronaries was possible in less than two-thirds of the patients. Virtual THV alignment in the coronary ostia overlap view assuming a hypothetical circular THV expansion would produce an optimal THV/coronary overlap in almost 90% of cases. Conclusion Given cusp asymmetry and coronary ostia eccentricity of BAV combined with potential THV asymmetrical expansion, conventional commissural alignment techniques are associated with higher rates of THV misalignment and of moderate/severe neo-commissure overlap with the coronary ostia as compared to tricuspid aortic stenosis, resulting in lower rates of selective CA after TAVR. A modified THV orientation technique based on the coronary ostia overlap view might be preferable in BAV patients.
Potential roles of the gut microbiota in the manifestations of drug use disorders

Drug use disorders (DUDs) not only cause serious harm to users but also cause huge economic, security, and public health burdens to families and society. Recently, several studies have shown that gut microbiota (GM) can affect the central nervous system and brain functions. In this review, we focus on the potential role of the GM in the different stages of DUDs. First, the GM may induce individuals to seek novel substances. Second, the gut microbiota is involved in the decomposition and absorption of drugs. Symptoms of individuals who suffer from DUDs are also related to intestinal microorganisms. Third, the effects of the GM and its metabolites on drug relapse are mainly reflected in the reward effect and drug memory. In conclusion, recent studies have preliminarily explored the relationship between GM and DUDs. This review deepens our understanding of the mechanisms of DUDs and provides important information for the future development of clinical treatment for DUDs.
Effects of leadership style on coach-athlete relationship, athletes’ motivations, and athlete satisfaction

Introduction The current study investigated the impacts of autocratic and democratic leadership styles on the coach-athlete relationship, athletes’ motivations, and athlete satisfaction. Methods Survey data were collected from 298 student-athletes (male = 157; 52.7%, female = 141; 47.3%) from 20 different Chinese collegiate sports. The Structural Equation Model was used to test the hypothesized model. Results The results indicated democratic leadership had a direct positive influence on the coach-athlete relationship, while autocratic leadership had no direct effect. Both leadership styles did not influence autonomous motivation. The coach-athlete relationship, meanwhile, had a full mediation effect between democratic leadership and athletes’ motivation and satisfaction. In addition, autonomous motivation had a partial mediation effect between the coach-athlete relationship and athlete satisfaction. Discussion Ultimately, the findings of the current study underscore the need for coaches and administrators to understand the impact of different leadership styles and highlight the importance of democratic leadership in improving athletes’ psychological outcomes.
Alkaline stress reduces root waving by regulating PIN7 vacuolar transport

Root development and plasticity are assessed via diverse endogenous and environmental cues, including phytohormones, nutrition, and stress. In this study, we observed that roots in model plant Arabidopsis thaliana exhibited waving and oscillating phenotypes under normal conditions but lost this pattern when subjected to alkaline stress. We later showed that alkaline treatment disturbed the auxin gradient in roots and increased auxin signal in columella cells. We further demonstrated that the auxin efflux transporter PIN-FORMED 7 (PIN7) but not PIN3 was translocated to vacuole lumen under alkaline stress. This process is essential for root response to alkaline stress because the pin7 knockout mutants retained the root waving phenotype. Moreover, we provided evidence that the PIN7 vacuolar transport might not depend on the ARF-GEFs but required the proper function of an ESCRT subunit known as FYVE domain protein required for endosomal sorting 1 (FREE1). Induced silencing of FREE1 disrupted the vacuolar transport of PIN7 and reduced sensitivity to alkaline stress, further highlighting the importance of this cellular process. In conclusion, our work reveals a new role of PIN7 in regulating root morphology under alkaline stress.
The deubiquitinase USP8 regulates ovarian cancer cell response to cisplatin by suppressing apoptosis

The identification of therapeutic approaches to improve response to platinum-based therapies is an urgent need for ovarian carcinoma. Deubiquitinases are a large family of ubiquitin proteases implicated in a variety of cellular functions and may contribute to tumor aggressive features through regulation of processes such as proliferation and cell death. Among the subfamily of ubiquitin-specific peptidases, USP8 appears to be involved in modulation of cancer cell survival by still poorly understood mechanisms. Thus, we used ovarian carcinoma cells of different histotypes, including cisplatin-resistant variants with increased survival features to evaluate the efficacy of molecular targeting of USP8 as a strategy to overcome drug resistance/modulate cisplatin response. We performed biochemical analysis of USP8 activity in pairs of cisplatin-sensitive and -resistant cells and found increased USP8 activity in resistant cells. Silencing of USP8 resulted in decreased activation of receptor tyrosine kinases and increased sensitivity to cisplatin in IGROV-1/Pt1 resistant cells as shown by colony forming assay. Increased cisplatin sensitivity was associated with enhanced cisplatin-induced caspase 3/7 activation and apoptosis, a phenotype also observed in cisplatin sensitive cells. Increased apoptosis was linked to FLIPL decrease and cisplatin induction of caspase 3 in IGROV-1/Pt1 cells, cisplatin-induced claspin and survivin down-regulation in IGROV-1 cells, thereby showing a decrease of anti-apoptotic proteins. Immunohistochemical staining on 65 clinical specimens from advanced stage ovarian carcinoma indicated that 40% of tumors were USP8 positive suggesting that USP8 is an independent prognostic factor for adverse outcome when considering progression free survival as a clinical end-point. Taken together, our results support that USP8 may be of diagnostic value and may provide a therapeutic target to improve the efficacy of platinum-based therapy in ovarian carcinoma.
The effect of disinfectants and antiseptics on co- and cross-selection of resistance to antibiotics in aquatic environments and wastewater treatment plants

The outbreak of the SARS-CoV-2 pandemic led to increased use of disinfectants and antiseptics (DAs), resulting in higher concentrations of these compounds in wastewaters, wastewater treatment plant (WWTP) effluents and receiving water bodies. Their constant presence in water bodies may lead to development and acquisition of resistance against the DAs. In addition, they may also promote antibiotic resistance (AR) due to cross- and co-selection of AR among bacteria that are exposed to the DAs, which is a highly important issue with regards to human and environmental health. This review addresses this issue and provides an overview of DAs structure together with their modes of action against microorganisms. Relevant examples of the most effective treatment techniques to increase the DAs removal efficiency from wastewater are discussed. Moreover, insight on the resistance mechanisms to DAs and the mechanism of DAs enhancement of cross- and co-selection of ARs are presented. Furthermore, this review discusses the impact of DAs on resistance against antibiotics, the occurrence of DAs in aquatic systems, and DA removal mechanisms in WWTPs, which in principle serve as the final barrier before releasing these compounds into the receiving environment. By recognition of important research gaps, research needs to determine the impact of the majority of DAs in WWTPs and the consequences of their presence and spread of antibiotic resistance were identified.