Miracle-dz/UniFAR-FTUs huggingface dataset:
Association Between Type of Infertility and Live Birth in Couples With a Single Intrauterine Insemination Resulting in Pregnancy: A Propensity Score Matching Cohort Study

Background Few studies have described the relationship between the type of infertility and live birth in patients treated with intrauterine insemination (IUI). We focused on this issue and attempted to explore it. Methods This retrospective study enrolled 2,256 infertile patients who underwent their first IUI cycle and were subsequently diagnosed with a clinical pregnancy at Ji’an Women and Child Health Care Hospital between 2007 and 2018. Inductees were divided into primary infertility (1,680 patients) and secondary infertility groups (876 patients). Following 1:1 propensity score matching to obtain balanced data, the COX proportional hazards model, landmark analysis, and subgroup analysis were used to assess the association between infertility types and live birth rates. Subsequently, a sensitivity analysis was employed to evaluate the potential effect of unmeasured confounding on outcomes. Results Of the 1,486 patients who were identified as a matched cohort, 743 were in the primary infertility group and the remaining patients were in another group. A total of 1,143 patients had live births during 431,009 person-days of follow-up (average 290.0 days). Throughout the follow-up period, patients with secondary infertility demonstrated more live births than patients with primary infertility (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.04 to 1.30; P = .007). More details were observed in the landmark analysis. Live birth rates were similar in both groups within 316 days of follow-up (HR, 0.84; 95% CI, 0.62 to 1.14; P = .269), whereas the opposite was found between 316 days of follow-up and delivery day (HR, 1.19; 95% CI, 1.06 to 1.34; P = .004). This was also obtained in a subgroup analysis of patients younger than 35 years old and patients treated with natural cycles (NCs) and IUIs. Conclusion Among the infertile patients who underwent a single natural or stimulated cycle followed by IUI and had later pregnancies, full-term young secondary infertility mothers (<35 years of age) had a greater chance of having viable babies than the primary infertility ones. The latter may get more benefits when undergoing ovarian stimulation and IUI rather than NC-IUI.
Dynamic Changes in the Human Milk Metabolome Over 25 Weeks of Lactation

Human milk (HM) provides essential nutrition for ensuring optimal infant growth and development postpartum. Metabolomics offers insight into the dynamic composition of HM. Studies have reported the impact of lactation stage, maternal genotype, and gestational age on HM metabolome. However, the majority of the studies have considered changes within the first month of lactation or sampled with large intervals. This leaves a gap in the knowledge of progressing variation in HM composition beyond the first month of lactation. The objective of this study was to investigate whether the HM metabolome from mothers with term deliveries varies beyond 1 month of lactation, during the period in which HM is considered fully mature. Human milk samples (n = 101) from 59 mothers were collected at weeks 1–2, 3–5, 7–9, and 20–25 postpartum and analyzed using 1H nuclear magnetic resonance spectroscopy. Several metabolites varied over lactation and exhibited dynamic changes between multiple time points. Higher levels of HM oligosaccharides, cis-aconitate, O-phosphocholine, O-acetylcarnitine, gluconate, and citric acid were observed in early lactation, whereas later in lactation, levels of lactose, 3-fucosyllactose, glutamine, glutamate, and short- and medium-chain fatty acids were increased. Notably, we demonstrate that the HM metabolome is dynamic during the period of maturity.
ICAM-1 on Breast Cancer Cells Suppresses Lung Metastasis but Is Dispensable for Tumor Growth and Killing by Cytotoxic T Cells

Breast tumors and their derived circulating cancer cells express the leukocyte β2 integrin ligand Intercellular adhesion molecule 1 (ICAM-1). We found that elevated ICAM-1 expression in breast cancer cells results in a favorable outcome and prolonged survival of breast cancer patients. We therefore assessed the direct in vivo contribution of ICAM-1 expressed by breast cancer cells to breast tumorigenesis and lung metastasis in syngeneic immunocompetent mice hosts using spontaneous and experimental models of the lung metastasis of the C57BL/6-derived E0771 cell line, a luminal B breast cancer subtype. Notably, the presence of ICAM-1 on E0771 did not alter tumor growth or the leukocyte composition in the tumor microenvironment. Interestingly, the elimination of Tregs led to the rapid killing of primary tumor cells independently of tumor ICAM-1 expression. The in vivo elimination of a primary E0771 tumor expressing the ovalbumin (OVA) model neoantigen by the OVA-specific OVA-tcr-I mice (OT-I) transgenic cytotoxic T lymphocytes (CTLs) also took place normally in the absence of ICAM-1 expression by E0771 breast cancer target cells. The whole lung imaging of these cells by light sheet microscopy (LSM) revealed that both Wild type (WT)- and ICAM-1-deficient E0771 cells were equally disseminated from resected tumors and accumulated inside the lung vasculature at similar magnitudes. ICAM-1-deficient breast cancer cells developed, however, much larger metastatic lesions than their control counterparts. Strikingly, the vast majority of these cells gave rise to intravascular tumor colonies both in spontaneous and experimental metastasis models. In the latter model, ICAM-1 expressing E0771- but not their ICAM-1-deficient counterparts were highly susceptible to elimination by neutrophils adoptively transferred from E0771 tumor-bearing donor mice. Ex vivo, neutrophils derived from tumor-bearing mice also killed cultured E0771 cells via ICAM-1-dependent interactions. Collectively, our results are a first indication that ICAM-1 expressed by metastatic breast cancer cells that expand inside the lung vasculature is involved in innate rather than in adaptive cancer cell killing. This is also a first indication that the breast tumor expression of ICAM-1 is not required for CTL-mediated killing but can function as a suppressor of intravascular breast cancer metastasis to lungs.
An Outdoor Access Period Improves Chicken Cecal Microbiota and Potentially Increases Micronutrient Biosynthesis

Characterizing the gut microbiota of free-range and alternative poultry production systems provides information, which can be used to improve poultry welfare, performance, and environmental sustainability. Gut microbiota influence not only the health and metabolism of the host but also the presence of zoonotic agents contaminating food of animal origin. In this study, the composition and diversity of the cecal microbiota community of free-range grown chickens were characterized by 16S rDNA high-throughput Illumina sequencing. Significant differences were observed in the composition of chicken cecal microbiota at the time points of 28 days of age (Indoor group) and 56 days of age (Outdoor group), i.e., before and after the outdoor access period of chicken groups. The Outdoor group showed a richer and more complex microbial community, characterized by the onset of new phyla such as Deferribacterota and Synergistota, while the Indoor group showed an increase in Campylobacterota. At the species level, it is noteworthy that the occurrence of Mucispirillum schaedleri in Outdoor group is known to potentially stimulate mucus layer formation in the distal intestinal tract, thus being associated with a healthy gut. We also report a significant decrease in the Outdoor group of Helicobacter pullorum, highlighting that the lower abundance at the age of slaughter reduced the possibility to contaminate chickens' carcasses and, consequently, its zoonotic potential. As revealed by a mutual exclusion study in network analysis, H. pullorum was present only if Bacteroides barnesiae, an uncultured organism of the genus Synergistes, and Bacteroides gallinaceum were absent. Finally, microbiome predictive analysis revealed an increase of vitamins and micronutrient biosyntheses such as queuosine (Q) and its precursor pre Q0, in the Outdoor group, suggesting that the outdoor evolved microbiota of chickens do contribute to the vitamin pool of the gut and the biosynthesis of micronutrients involved in vital cell processes.
Mitochondrial DNA variation in Parkinson’s disease: Analysis of “out-of-place” population variants as a risk factor

Mitochondrial DNA (mtDNA), a potential source of mitochondrial dysfunction, has been implicated in Parkinson’s disease (PD). However, many previous studies investigating associations between mtDNA population variation and PD reported inconsistent or contradictory findings. Here, we investigated an alternative hypothesis to determine whether mtDNA variation could play a significant role in PD risk. Emerging evidence suggests that haplogroup-defining mtDNA variants may have pathogenic potential if they occur “out-of-place” on a different maternal lineage. We hypothesized that the mtDNA of PD cases would be enriched for out-of-place variation in genes encoding components of the oxidative phosphorylation complexes. We tested this hypothesis with a unique dataset comprising whole mitochondrial genomes of 70 African ancestry PD cases, two African ancestry control groups (n = 78 and n = 53) and a replication group of 281 European ancestry PD cases and 140 controls from the Parkinson’s Progression Markers Initiative cohort. Significantly more African ancestry PD cases had out-of-place variants than controls from the second control group (P < 0.0125), although this association was not observed in the first control group nor the replication group. As the first mtDNA study to include African ancestry PD cases and to explore out-of-place variation in a PD context, we found evidence that such variation might be significant in this context, thereby warranting further replication in larger cohorts.
Adaptation and Validation of a Test for the Evaluation of Tactical Knowledge in Soccer: Test de Conocimiento Táctico Ofensivo en Fútbol for the Brazilian Context (TCTOF-BRA)

Background Studies and tests to assess the tactical domain of young soccer players are recent, and few instruments meet the majority of quality criteria. Objective To adapt and validate the Test de Conocimiento Táctico Ofensivo en Fútbol (TCTOF) for the Brazilian context (TCTOF-BRA). Methods The article consists of two studies. Study 1 (n = 111) included the translation, theoretical/semantic analysis, back translation, cross-cultural equivalence, and content and face validity (pre-test). In study 2 (n = 768), a theoretical and empirical item analysis was carried out, followed by construct validity [exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and the known-groups method] and reliability (internal consistency and repeatability). Results In the cross-cultural evaluation, the Coefficient of content validity total (CCVt) of the instrument was 0.96 and in the content validity, the CCVt of the instrument was 0.87. The face validity was confirmed (>95%). After theoretical and empirical analysis, 15 questions were included in the Teste de Conhecimento Tático Ofensivo no Futebol (TCTOF-BRA). The EFA showed a model with adequate fit (KMO = 0.69; Bartlett p < 0.001), with a factor structure considered very good, composed of four factors (decision making, operational tactical principles, collective tactical-technical elements, and rules). The CFA by the Asymptotically Distribution-Free estimation method demonstrated good and very good goodness of fit indices (X2/df = 1.54, GFI = 0.99, CFI = 0.94, TLI = 0.92, PGFI = 0.71, PCFI = 0.76, RMSEA = 0.03, and ECVI = 0.26). The known-groups method showed significant differences (p < 0.01) and effect sizes varying from small-to-medium to large. With respect to reliability, coefficients of 0.89 (CR) and 0.74 (KR20) for internal consistency and 0.85 for repeatability were found. Conclusion The TCTOF-BRA presented satisfactory evidence, demonstrating it to be an instrument with valid and reliable measures for the evaluation of tactical knowledge (declarative and theoretical procedural), based on specific knowledge and decision making (cognitive domain), of Brazilian young soccer players from 12 to 17.9 years old.
Adipokines, Hepatokines and Myokines: Focus on Their Role and Molecular Mechanisms in Adipose Tissue Inflammation

Chronic low-grade inflammation in adipose tissue (AT) is a hallmark of obesity and contributes to various metabolic disorders, such as type 2 diabetes and cardiovascular diseases. Inflammation in ATs is characterized by macrophage infiltration and the activation of inflammatory pathways mediated by NF-κB, JNK, and NLRP3 inflammasomes. Adipokines, hepatokines and myokines — proteins secreted from AT, the liver and skeletal muscle play regulatory roles in AT inflammation via endocrine, paracrine, and autocrine pathways. For example, obesity is associated with elevated levels of pro-inflammatory adipokines (e.g., leptin, resistin, chemerin, progranulin, RBP4, WISP1, FABP4, PAI-1, Follistatin-like1, MCP-1, SPARC, SPARCL1, and SAA) and reduced levels of anti-inflammatory adipokines such as adiponectin, omentin, ZAG, SFRP5, CTRP3, vaspin, and IL-10. Moreover, some hepatokines (Fetuin A, DPP4, FGF21, GDF15, and MANF) and myokines (irisin, IL-6, and DEL-1) also play pro- or anti-inflammatory roles in AT inflammation. This review aims to provide an updated understanding of these organokines and their role in AT inflammation and related metabolic abnormalities. It serves to highlight the molecular mechanisms underlying the effects of these organokines and their clinical significance. Insights into the roles and mechanisms of these organokines could provide novel and potential therapeutic targets for obesity-induced inflammation.
Gene-Regulatory Potential of 25-Hydroxyvitamin D3 and D2

Human peripheral blood mononuclear cells (PBMCs) represent a highly responsive primary tissue that is composed of innate and adaptive immune cells. In this study, we compared modulation of the transcriptome of PBMCs by the vitamin D metabolites 25-hydroxyvitamin D3 (25(OH)D3), 25(OH)D2 and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Saturating concentrations of 1,25(OH)2D3, 25(OH)D3 and 25(OH)D2 resulted after 24 h stimulation in a comparable number and identity of target genes, but below 250 nM 25(OH)D3 and 25(OH)D2 were largely insufficient to affect the transcriptome. The average EC50 values of 206 common target genes were 322 nM for 25(OH)D3 and 295 nM for 25(OH)D2 being some 600-fold higher than 0.48 nM for 1,25(OH)2D3. The type of target gene, such as primary/secondary, direct/indirect or up-/down-regulated, had no significant effect on vitamin D metabolite sensitivity, but individual genes could be classified into high, mid and lower responders. Since the 1α-hydroxylase CYP27B1 is very low expressed in PBMCs and early (4 and 8 h) transcriptome responses to 25(OH)D3 and 25(OH)D2 were as prominent as to 1,25(OH)2D3, both vitamin D metabolites may directly control gene expression. In conclusion, at supra-physiological concentrations 25(OH)D3 and 25(OH)D2 are equally potent in modulating the transcriptome of PBMCs possibly by directly activating the vitamin D receptor.
Sex Hormones, Sleep, and Memory: Interrelationships Across the Adult Female Lifespan

As the population of older adults grows, so will the prevalence of aging-related conditions, including memory impairments and sleep disturbances, both of which are more common among women. Compared to older men, older women are up to twice as likely to experience sleep disturbances and are at a higher risk of cognitive decline and Alzheimer’s disease and related dementias (ADRD). These sex differences may be attributed in part to fluctuations in levels of female sex hormones (i.e., estrogen and progesterone) that occur across the adult female lifespan. Though women tend to experience the most significant sleep and memory problems during the peri-menopausal period, changes in memory and sleep have also been observed across the menstrual cycle and during pregnancy. Here, we review current knowledge on the interrelationships among female sex hormones, sleep, and memory across the female lifespan, propose possible mediating and moderating mechanisms linking these variables and describe implications for ADRD risk in later life.
Somatotropic Axis, Pace of Life and Aging

Mice with genetic growth hormone (GH) deficiency or GH resistance live much longer than their normal siblings maintained under identical conditions with unlimited access to food. Extended longevity of these mutants is associated with extension of their healthspan (period of life free of disability and disease) and with delayed and/or slower aging. Importantly, GH and GH-related traits have been linked to the regulation of aging and longevity also in mice that have not been genetically altered and in other mammalian species including humans. Avai+lable evidence indicates that the impact of suppressed GH signaling on aging is mediated by multiple interacting mechanisms and involves trade-offs among growth, reproduction, and longevity. Life history traits of long-lived GH-related mutants include slow postnatal growth, delayed sexual maturation, and reduced fecundity (smaller litter size and increased intervals between the litters). These traits are consistent with a slower pace-of-life, a well-documented characteristic of species of wild animals that are long-lived in their natural environment. Apparently, slower pace-of-life (or at least some of its features) is associated with extended longevity both within and between species. This association is unexpected and may appear counterintuitive, because the relationships between adult body size (a GH-dependent trait) and longevity within and between species are opposite rather than similar. Studies of energy metabolism and nutrient-dependent signaling pathways at different stages of the life course will be needed to elucidate mechanisms of these relationships.
Spectrum of BRAF Aberrations and Its Potential Clinical Implications: Insights From Integrative Pan-Cancer Analysis

B-Raf proto-oncogene serine/threonine-protein kinase (BRAF) is frequently altered in multiple cancer types, and BRAF V600 mutations act as a prime target for precision therapy. Although emerging evidence has investigated the role of BRAF, the comprehensive profiling of BRAF expression, alteration and clinical implications across various cancer types has not been reported. In this study, we used the TCGA dataset, covering 10,967 tumor samples across 32 cancer types, to analyze BRAF abnormal expression, DNA methylation, alterations (mutations and amplification/deletion), and their associations with patient survival. The results showed that BRAF expression, alteration frequency, mutation site distribution, and DNA methylation patterns varied tremendously among different cancer types. The expression of BRAF was found higher in PCPG and CHOL, and lower in TGCT and UCS compared to normal tissues. In terms of pathological stages, BRAF expression was significantly differentially expressed in COAD, KIRC, LUSC, and OV. The methylation levels of BRAF were significantly lower in LUSC, HNSC, and UCEC compared to normal tissue. The expression of BRAF and downstream gene (ETS2) was negatively correlated with methylation levels in various cancers. The overall somatic mutation frequency of BRAF was 7.7% for all cancer samples. Most fusion transcripts were found in THCA and SKCM with distinct fusion patterns. The majority of BRAF mutations were oncogenic and mainly distributed in the Pkinase_Tyr domain of THCA, SKCM, COADREAD, and LUAD. The BRAF mutations were divided into five levels according to the clinical targeted therapy implication. The results showed level 1 was mainly distributed in SKCM, COADREAD, and LUAD, while level 3B in THCA. The overall BRAF CNV frequency was about 42.7%, most of which was gain (75.9%), common in GBM, TGCT, and KIRP. In addition, the forest plot showed that increased BRAF expression was associated with poor patient overall survival in LIHC, OV, and UCEC. Taken together, this study provided a novel insight into the full alteration spectrum of BRAF and its implications for treatment and prognosis.
Assessing Emotions of Teaching Assistants in Inclusive Education

Although there are an increasing number of studies on assessing teacher emotions in mainstream education, there is a lack of appropriate measurement tools to evaluate the emotions of teaching assistants (TAs) who need to take care of students with a range of special educational needs (SEN). This study tested the generalizability of the 24-item teacher emotion inventory (TEI), among 204 TAs from 122 secondary schools with inclusive education in Hong Kong. We conducted both confirmatory factor analysis (CFA) and Rasch analysis to test the within-network validity of the TEI. For the between-network validity, we examined the relationships between TAs’ emotions and their attitude toward inclusive education. The Rasch analysis supported the scale’s dimensionality and item fit statistics. The CFA supported the five-factor solution of the TEI. The results also showed statistically significant correlations between positive emotions (joy and love) and TAs’ attitudes toward inclusive education. TAs’ negative emotions (anxiety, anger, and stress) appeared to be negatively correlated with their attitude toward inclusive education. The results supported that TEI is a useful tool to assess the emotions of TAs that play a pivotal role in assisting both school teachers and SEN students, who are more likely to face increased emotional challenges than those not needing to educate SEN students. Implications of this study to enrich the current scope of research on understanding teacher emotions across educational levels and settings are discussed.
The serotonergic system dysfunction in diabetes mellitus

Most peripheral serotonin (5-HT) is synthesized in enterochromaffin cells, and most circulating 5-HT is stored in platelets. As a monoamine, 5-HT has several functions in various non-neuronal and neuronal systems. In the central nervous system, it functions as a neurotransmitter to modulate feeding behavior and mood. Numerous clinical trials have focused on increasing 5-HT activation in the central nervous system, including those involving anti-obesity drugs currently in the market, although severe side effects on peripheral system can lead to the withdrawal of certain drugs. Recent studies have revealed that both the peripheral and central serotonergic systems play a vital role in diabetes and its complications. This review summarizes the roles of the serotonergic system in blood glucose regulation, diabetic macroangiopathy, diabetic peripheral neuropathy, and diabetic encephalopathy, indicating its potential clinical significance as a therapeutic target for the treatment of diabetes and its complications.