Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigation of the optimal culture time for warmed bovine ovarian tissues before transplantation

Abstract Ovarian tissue cryopreservation by vitrification is an effective technique, but there are still many unresolved issues related to the procedure. The aim of this study was to investigate the optimal culture time of postwarmed ovarian tissues and their viability before ovarian tissue transplantation. The bovine ovarian tissues were used to evaluate the effect of postwarming culture periods (0, 0.25, 0.5, 1, 2, 5, and 24 h) in the levels of residual cryoprotectant, LDH release, ROS generation, gene and protein abundance, and follicle viability and its mitochondrial membrane potential. Residual cryoprotectant concentration decreased significantly after 1 h of culture. The warmed ovarian tissues that underwent between 0 and 2 h of culture time showed similar LDH and ROS levels compared with fresh nonfrozen tissues. The anti-Mullerian hormone transcript abundance did not differ in any of the groups. No increase in the relative transcript abundance and protein level of Caspase 3 and Cleaved-Caspase 3, respectively, in the first 2 h of culture after warming. On the other hand, an increased protein level of double stranded DNA breaks (gamma-H2AX) was observed in postwarmed tissues disregarding the length of culture time, and a temporary reduction in pan-AKT was detected in postwarming tissues between 0 and 0.25 h of culture time. Prolonged culture time lowered the percentage of viable follicles in warmed tissues, but it did not seem to affect the follicular mitochondrial membrane potential. In conclusion, 1–2 h of culture time would be optimal for vitrified-warmed tissues before transplantation. Summary Sentence For ovarian tissue cryopreservation by vitrification, the recommended culture time following warming is between 1 and 2 h before ovarian tissue transplantation. Graphical Abstract
Characterization of a novel HIV-1 circulating recombinant form, CRF91_cpx, comprising CRF02_AG, G, J, and U, mostly among men who have sex with men

ABSTRACT Prospective molecular studies of HIV-1 pol region (2253–5250 in HXB2 genome) sequences from sequenced samples of 269 HIV-1-infected patients in Cyprus (2017–2021) revealed a transmission cluster of 14 unknown HIV-1 recombinants that were not classified as previously established CRFs. The earliest recombinant was collected in September 2017, and the transmission cluster continued to grow until November 2020. Near full-length HIV-1 genome sequences of the 11 of the 14 recombinants were successfully obtained (790–8795 in HXB2 genome) and aligned against a reference dataset of HIV-1 subtypes and CRFs. We employed MEGAX for maximum-likelihood tree construction (GTR model, 1000 bootstrap replicates), Cluster-Picker for phylogenetic clustering analysis (genetic distance ≤0.045, bootstrap support value ≥70%), and REGA-3.0 for subtype determination. Bootscan and similarity plot analyses (sliding window of 400 nucleotides overlapped by 40 nucleotides) were conducted using SimPlot-v3.5. 1, and subregion confirmatory neighbour-joining tree analyses were conducted using MEGAX (Kimura two-parameter model, 1000 bootstrap replicates, ≥70% bootstrap-support value). Exclusive clustering of the HIV-1 recombinants revealed their uniqueness. The recombination analyses illustrated the same unique mosaic pattern with six putative intersubtype recombination breakpoints, seven fragments of subtypes CRF02_AG, G, J and an unclassified fragment. We conclusively characterized the mosaic structure of the novel HIV-1 CRF, named CRF91_cpx, by the Los Alamos HIV Sequence Database. Additionally, we identified a URF of CRF91_cpx with two additional recombination sites, generated by a recombination event between subtype B and CRF91_cpx. Since the identification of CRF91_cpx, two additional patient samples have been entered into the CRF91_cpx transmission cluster, demonstrating active growth.
Efficacy of lasmiditan for the acute treatment of perimenstrual migraine

Background Perimenstrual migraine attacks in women with menstrual migraine is difficult to treat. This post-hoc analysis evaluated the efficacy of lasmiditan, a high affinity and selective 5-HT1F receptor agonist, for perimenstrual attacks. Methods Patients from two randomized, double-blind, placebo-controlled clinical trials (MONONOFU and CENTURION) were instructed to treat an attack with a single dose of study medication within four hours of pain onset. After dosing, the proportion of patients who achieved freedom from migraine-related head pain, most bothersome symptom, and disability was reported at baseline up to 48 hours after dose and pooled data were evaluated. Results A total of 303 patients (MONONOFU N = 78; CENTURION N = 225) treated perimenstrual migraine attacks with lasmiditan 50 mg (N = 24), 100 mg (N = 90), 200 mg (N = 110), and placebo (N = 79). More patients achieved migraine-related head pain freedom with lasmiditan 200 mg versus placebo at all time points assessed. At 2 hours, 33.6% of patients in the 200-mg group (p < 0.001), and 16.7% of patients in the 100-mg (p = 0.11) and 50-mg (p = 0.19) groups were pain free, compared with 7.6% in the placebo group. Conclusions Lasmiditan treatment of perimenstrual migraine attacks was associated with freedom from migraine-related head pain at two hours, early onset of efficacy, and sustained efficacy. Clinical Trial registration: NCT03962738 and NCT03670810
Stratifying the autistic phenotype using electrophysiological indices of social perception

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social communication, but also great heterogeneity. To offer individualized medicine approaches, we need to better target interventions by stratifying autistic people into subgroups with different biological profiles and/or prognoses. We sought to validate neural responses to faces as a potential stratification factor in ASD by measuring neural (electroencephalography) responses to faces (critical in social interaction) in N = 436 children and adults with and without ASD. The speed of early-stage face processing (N170 latency) was on average slower in ASD than in age-matched controls. In addition, N170 latency was associated with responses to faces in the fusiform gyrus, measured with functional magnetic resonance imaging, and polygenic scores for ASD. Within the ASD group, N170 latency predicted change in adaptive socialization skills over an 18-month follow-up period; data-driven clustering identified a subgroup with slower brain responses and poor social prognosis. Use of a distributional data-driven cutoff was associated with predicted improvements of power in simulated clinical trials targeting social functioning. Together, the data provide converging evidence for the utility of the N170 as a stratification factor to identify biologically and prognostically defined subgroups in ASD. Description N170 latency to faces relates to fusiform activity and ASD genetics, predicts social prognosis, and could improve power in clinical trials. Exploiting face processing in patients with ASD The heterogeneity observed in patients with autism spectrum disorder (ASD) highlights the need for better patient stratification methods. Here, Mason et al. evaluated the use of the speed of early-stage face processing (N170 latency) for patient stratification and prognosis in subjects with ASD and age-matched healthy individuals. N170 latency was slower in individuals with ASD and correlated with response to faces measured with fMRI and with polygenic risk score. Among subjects with ASD, the N170 values stratified patients according to socialization prognosis and improved power in a simulated clinical trial. The results suggest that including N170 evaluation in patient stratification might help the design and development of patient-specific therapies for ASD.
Outcome of Nasal Layer Reinforcement With Autologous Dermis in Cleft Palate Repair on Postoperative Fistula Formation

Objective Palatal fistulae are challenging complications following cleft palate repair. The addition of acellular dermal matrix (ADM) to cleft palate repair has been shown to reduce fistula formation in previous studies. The use of autologous dermal graft has all the structural advantages of ADM, has less rejection and immunogenic potential, and is cost effective. Design A prospective study. Participants Patients with Group II and III cleft palate (Nagpur Classification) without prior intervention for palatal repair in the Department of Plastic Surgery at PGIMER from January 2020 till June 2021. Intervention The addition of autologous dermal graft for palatoplasty. Main outcome Outcome of the study was fistula development or exposure of dermal graft. Results Autologous dermal graft was harvested of average dimension of 8.73 cm2 (range 5.25-18 cm2) from groin region. Sixteen patients were included in the study. Among them, 2 patients (12.5%) developed postoperative fistula (Type III &V Pittsburgh Classification). Conclusion Our study showed that the rates of postoperative fistula formation are comparable with prior literature using artificial dermal matrices.
Medication regimen complexity and its association with adherence and blood pressure control among hypertensive patients at selected hospitals of South Gondar Zone: A hospital based cross sectional study

Introduction Despite the availability of effective antihypertensive medications, blood pressure (BP) control is suboptimal. High medication regimen complexity index (MRCI) is known to reduce adherence and may be the reason for poor BP control. However, there is no data in the present study areas. Hence, the aim of this study was to assess MRCI and its association with adherence and BP control among hypertensive patients at selected hospitals of South Gondar Zone. Methods A hospital based cross sectional study was conducted from December 1, 2020 to February 30, 2021 at selected hospitals of South Gondar Zone. Medication regimen complexity and adherence was evaluated using 65-item validated tool called MRCI (Text removed at time of retraction. See retraction notice for more information.). Multivariable logistic regression analysis was done to determine the association between predictive and outcome variables. Results About 3.3% of participants were classified as having high HTN specific MRCI whereas 34.75% of participants were classified as having high patient level MRCI. (Text removed at time of retraction. See retraction notice for more information.) Being illiterate, and having low HTN MRCI were more likely to have controlled BP in adjusted analyses. On the contrary, (Text removed at time of retraction. See retraction notice for more information.) not having health insurance, and having lower monthly income were less likely to have controlled BP. Conclusion A considerable proportion of patients had high MRCI. Having low HTN MRCI was more likely to have controlled BP. Simplification of a complex medication regimen for patients with HTN should be sought by physicians and pharmacists to improve BP control.
CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice

Abstract Spermatogenesis is sustained by homeostatic balance between the self-renewal and differentiation of spermatogonial stem cells, which is dependent on the strict regulation of transcription factor and chromatin modulator gene expression. Chromodomain helicase DNA-binding protein 4 is highly expressed in spermatogonial stem cells but roles in mouse spermatogenesis are not fully understood. Here, we report that the germ-cell-specific deletion of chromodomain helicase DNA-binding protein 4 resulted in complete infertility in male mice, with rapid loss of spermatogonial stem cells and excessive germ cell apoptosis. Chromodomain helicase DNA-binding protein 4-knockdown in cultured spermatogonial stem cells also promoted the expression of apoptosis-related genes and thereby activated the tumor necrosis factor signaling pathway. Mechanistically, chromodomain helicase DNA-binding protein 4 occupies the genomic regulatory region of key apoptosis-related genes, including Jun and Nfkb1. Together, our findings reveal the determinant role of chromodomain helicase DNA-binding protein 4 in spermatogonial stem cells survival in vivo, which will offer insight into the pathogenesis of male sterility and potential novel therapeutic targets. Summary Sentence After chromodomain helicase DNA-binding protein 4 knockout, excessive apoptosis of germ cells and male infertility were caused by upregulated expression of apoptosis genes which were accompanied by abnormal activation of TNF signaling pathway. Graphical Abstract
Electrodynamical control of the ambient ionization near the equatorial anomaly crest in the Indian zone during counter electrojet days

The variability of ambient ionization near the crest of the equatorial anomaly on the days of counter electrojet (CEJ) is studied using a long‐term (1980–1990) database of total electron content (TEC) obtained from Calcutta (geographic: longitude, 88.38°E; latitude, 22.58°N; dip: 32°N), situated virtually below the northern crest of the equatorial anomaly, in conjunction with the equatorial electrojet (EEJ) data of the Indian subcontinent and foF2 data from the equatorial stations. On the days of CEJ events the diurnal variations of TEC exhibit deviations (decreases) from monthly mean values, but the feature is not regular throughout the observing period. A larger percentage of CEJ days show decreases in the descending phase (1980–1985) of solar cycle compared to the ascending one (1986–1990). During low to moderate solar activity years the ionosphere near the anomaly crest is found to be more susceptible to CEJ related equatorial electrodynamics than in the high solar activity periods. On the seasonal basis, though the solstitial months of ascending phase exhibit higher percentage occurrence of decreases, the feature is not so prominent in the descending epoch. An attempt is made to relate the decreases in TEC with the prevailing electrodynamics at the magnetic equator for which EEJ, under quiet geomagnetic conditions, may be treated as a proxy index. A statistical analysis reveals positive correlations of TEC decreases with strength and duration of CEJ but anticorrelations with rising slope, strength, and time‐integrated value of EEJ as well as initiation time of CEJ. To represent better correspondence of the TEC variability with the equatorial electrodynamics a function combining various EEJ parameters has been generated, which seems to exhibit significant association with TEC decreases on the days of CEJ events.
Vanillic acid and vitamin C attenuated di-2-ethylhexyl phthalate-induced testicular toxicity in adult male rats

Graphical abstract Abstract Di-2-ethylhexyl phthalate (DEHP) is an extensively used plasticizer which has raised some concerns about its safety on human health. This study aimed at evaluating the effects of vanillic acid (VA) and vitamin C (VC) supplementation on DEHP-induced testicular toxicity. Thirty-five adult male Wistar rats were randomly divided into 7 groups (A–G) (n = 5) receiving distilled water; 250 mg/kg bw of DEHP only; 30 mg/kg bw of VA and 250 mg/kg bw of DEHP; 30 mg/kg bw of VC and 250 mg/kg bw of DEHP; 30 mg/kg bw of DEHP plus 30 mg/kg bw of VA and 30 mg/kg bw of VC; 30 mg/kg bw of VA only; and 30 mg/kg bw of VC only, respectively. At the end of the experiment, blood was taken from the heart via cardiac puncture and stored, semen was collected from the caudal epididymis for immediate sperm analysis, while the testes were excised and preserved for histological examination and biochemical analysis. The results showed a significant decrease (P < 0.05) in body weights, sperm motility, sperm volume, sperm viability and count, antioxidant levels, and reproductive hormonal levels, with a significant increase (P < 0.05) in sperm morphological defect and lipid peroxidation level in DEHP-only group compared with the control but was ameliorated after VA and VC administration compared to the DEHP-only treated animals. VA and VC supplementation attenuated the toxic effects of DEHP on the testicular functions, morphology, and semen characterization of the experimental adult male Wistar rats. Lay summary Male infertility is considered when identifiable female causes of infertility are excluded and semen quantity and quality fail to fulfil World Health Organization criteria. From conception through to adulthood, people are exposed to limitless environmental toxicants among which di-2-ethylhexyl phthalate (DEHP) commonly found in personal care products, cosmetics, and medical devices is prevalent. The present study elaborated on the importance of taking antioxidant-rich foods containing vitamin C and vanillic acid, such as those found in various fruits, olives, whole wheat, and cereal grains, in combating infertility caused by environmental toxicants. An experiment was carried out on rats to see the effect of vanillic acid and vitamin C supplementation on preventing DEHP-induced testicular toxicity. The testicles and semen were analyzed from five rats in each treated and control groups. The data led us to conclude that vanillic acid and vitamin C supplementation do have attenuating effects on DEHP-induced testicular toxicity, due to their high antioxidant and anti-inflammatory properties.
Cognitive Task Performance and Subjective Cognitive Symptoms in Individuals With Chronic Fatigue Syndrome or Fibromyalgia: A Cross-Sectional Analysis of the Lifelines Cohort Study

ABSTRACT Objective This study examined cognitive task performance and self-reported cognitive functioning in individuals with chronic fatigue syndrome (CFS) and fibromyalgia (FM) in a population-based sample and investigated the role of mood and anxiety disorders as well as severity of the physical symptoms. Methods This study was performed in 79,966 participants (mean [standard deviation] age = 52.9 [12.6] years, 59.2% women) from the Lifelines general population. Symptoms consistent with the diagnostic criteria for CFS and FM were assessed using questionnaires. Two comparison groups were used: participants with self-reported medical disorders with well-defined pathophysiology (i.e., multiple sclerosis and rheumatic arthritis) and controls without these diseases. Objective task performance was based on the computerized CogState cognitive battery and subjective cognitive symptoms using the concentration subscale of the Checklist Individual Strength. Results Cognitive task performance was poorer in individuals with CFS versus controls without disease and controls with a medical disorder, although the severity of cognitive dysfunction was mild. Participants meeting the criteria for CFS (n = 2461) or FM (n = 4295) reported more subjective cognitive symptoms compared with controls without a medical disorder (d = 1.53, 95% confidence interval [CI] = 1.49–1.57 for CFS; d = 1.25, 95% CI = 1.22–1.29 for FM) and participants with a medical disease (d = 0.62, 95% CI = 0.46–0.79 for CFS; d = 0.75, 95% CI = 0.70–0.80 for FM). These differences remained essentially the same when excluding participants with comorbid mood or anxiety disorders or adjusting for physical symptom severity. Conclusions Subjective cognitive symptoms and, to a lesser extent, suboptimal cognitive task performance are more prevalent in individuals with CFS or FM compared with controls without these conditions.
FGFRL1 and FGF genes are associated with height, hypertension, and osteoporosis

Hypertension and osteoporosis are two major disorders, which interact with each other. Specific genetic signals involving the fibroblast growth factor receptor-like 1 (FGFRL1) gene are related to high blood pressure and bone growth in giraffes. FGFRL1 is associated with cardiovascular system and bone formation. We performed an association study to investigate the role of FGFRL1 in hypertension, osteoporosis, and height determination in humans. In addition, we identified three kinds of phenotypes in fibroblast growth factor (FGF) genes and examined their association with the FGFRL1 gene. We identified 42 SNPs in the FGFRL1 gene associated with each trait. We then analyzed the potential functional annotation of each SNP. The FGFRL1 gene was found to be associated with height, hypertension, and osteoporosis, consistent with the results of a previous study. In addition, the FGF2, FGF4, FGF10, FGF18, and FGF22 genes were found to interact with the FGFRL1 gene. Our study suggests that both FGFRL1 and FGFRL1-related genes may determine the height and the prevalence of osteoporosis and hypertension in the Korean population.
Sex Differences in Age-Related Loss of Kidney Function

Significance Statement Although more women than men have CKD, more men develop kidney failure. Sex or gender disparities in health status or access to health care, or sex-specific rates of kidney function decline, may explain sex or gender disparities in CKD epidemiology. In this study of a general northern European population, baseline kidney function (GFR measured by plasma iohexol clearance) was lower in middle-aged women than in men, whereas rate of decline in kidney function during aging was steeper among men. Sex disparities in comorbidity or CKD risk factors did not explain the sex differences in kidney function decline rates. This study suggests that sex differences in kidney function and kidney function decline rates may, in part, explain sex and gender disparities in the epidemiology of CKD. Visual Abstract Background CKD is more prevalent in women, but more men receive kidney replacement therapy for kidney failure. This apparent contradiction is not well understood. Methods We investigated sex differences in the loss of kidney function and whether any sex disparities could be explained by comorbidity or CKD risk factors. In the Renal Iohexol Clearance Survey (RENIS) in northern Europe, we recruited 1837 persons (53% women, aged 50–62 years) representative of the general population and without self-reported diabetes, CKD, or cardiovascular disease. Participants’ GFR was measured by plasma iohexol clearance in 2007–2009 (n=1627), 2013–2015 (n=1324), and 2018–2020 (n=1384). At each study visit, healthy persons were defined as having no major chronic diseases or risk factors for CKD. We used generalized additive mixed models to assess age- and sex-specific GFR decline rates. Results Women had a lower GFR than men at baseline (mean [SD], 90.0 [14.0] versus 98.0 [13.7] ml/min per 1.73 m2; P<0.001). The mean GFR change rate was −0.96 (95% confidence interval [CI], −0.88 to −1.04) ml/min per 1.73 m2 per year in women and −1.20 (95% confidence interval [CI], −1.12 to −1.28) in men. Although the relationship between age and GFR was very close to linear in women, it was curvilinear in men, with steeper GFR slopes at older ages (nonlinear effect; P<0.001). Healthy persons had a slower GFR decline, but health status did not explain the sex difference in the GFR decline. Conclusion Among middle-aged and elderly individuals in the general population, decline in the mean GFR in women was slower than in men, independent of health status.
Analytic Theory of Continued Fractions

Part I: Convergence Theory: The continued fraction as a product of linear fractional transformations Convergence theorems Convergence of continued fractions whose partial denominators are equal to unity Introduction to the theory of positive definite continued fractions Some general convergence theorems Stieltjes type continued fractions Extensions of the parabola theorem The value region problem Part II: Function Theory: J-fraction expansions for rational functions Theory of equations J-fraction expansions for power series Matrix theory of continued fractions Continued fractions and definite integrals The moment problem for a finite interval Bounded analytic functions Hausdorff summability The moment problem for an infinite interval The continued fraction of Gauss Stieltjes summability The Pade table Bibliography Index.