Miracle-dz/UniFAR-FTUs huggingface dataset:
Letrozole,tamoxifen or clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome after pretreatment:a prospective randomized trial

Objective To compare the effects of letrozole,tamoxifen and clomiphene citrate for ovulation induction in women with PCOS.Methods The study comprised a total of 128 infertile women with PCOS.Patients were randomized to treatment with letrozole 5mg/d (44 cycles),tamoxifen 20mg/d (40 cycles) or clomiphene citrate 50mg/d (44 cycles) for 5 days starting on day 5 of menses or withdraw bleeding.The following indexes were compared:number of mature follicles,serum sex hormones,endometrial thickness and pregnancy and miscarriage rates.Results The basal conditions were similar among three groups.Endometrial thickness on day 10 of the cycle was statistically significantly greater in the tamoxifen group (6.4±1.2 mm vs.5.4±1.7 mm and 5.4±1.3 mm,P=0.01). Levels of estradiol were statistically significantly lower in the letrozole group (838.6±678.2 pmol/L vs.2629.2±1931.5 pmol/L and 1971.2±1222.8 pmol/L,P0.001). There were no significant differences in number of mature follicles,endometrial thickness and serum LH and P on HCG day,pregnancy and miscarriage rate per cycle among three groups.Conclusion The results of this study did not show any advantage to the use of letrozole or tamoxifen over clomiphene citrate as a first-line treatment for ovulation induction in women with PCOS after adequate pretreatment.The pre-treatment of metabolism disorder and hyperandrogenism of PCOS may improve the effects of clomiphene citrate in ovulation induction and endometrial growth as well.
Green and Efficient Ultrasonic-Assisted Extraction of Bioactive Components from Salvia miltiorrhiza by Natural Deep Eutectic Solvents

Natural deep eutectic solvents (NaDESs) are recently developed green solvent alternatives to conventional fossil solvents. The present work systematically screened 22 different NaDESs for the ultrasonic-assisted extraction of bioactive components from Salvia miltiorrhiza (SM), a widely used traditional Chinese medical plant. The suitable solvent and extraction condition were optimized in a two-round screening. In comparison with fossil solvents, NaDESs, especially L-proline-lactic acid (L-Pro-Lac) showed significant advantages in the extraction of salvianolic acid B (SAB), tanshinone IIA (TIIA) and cryptotanshinone (CYT). The optimized yields of the three targeting compounds were 42.05, 1.485 and 0.839 mg/g, respectively. The present method was also applied to the pretreatment of SM samples from different geographic origins. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities of NaDES extracts were determined in the study to prove the feasibility of NaDES in bioactive component extraction. The application of NaDESs in the extraction of both hydrophilic and hydrophobic small molecules from SM is proved to be a green and efficient method for pretreatment of herbal materials.
Effects of the dopamine transporter gene on striatal functional connectivity in youths with attention-deficit/hyperactivity disorder

Abstract Background The dopamine transporter gene (DAT1), striatal network dysfunction, and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine the effects of the DAT1 rs27048 (C)/rs429699 (T) haplotype on striatal functional connectivity and visual memory performance in youths with ADHD. Method After excluding those who had excessive head motion, a total of 96 drug-naïve youths with ADHD and 114 typically developing (TD) youths were assessed with the resting-state functional magnetic resonance imaging and the delayed matching to sample (DMS) task for visual memory. We examined the effects of ADHD, DAT1 CT haplotype, and the ADHD × CT haplotype interaction on the functional connectivity of five striatal seeds. We also correlated visual memory performance with the functional connectivity of striatal subregions, which showed significant diagnosis × genotype interactions. Results Compared with TD youths, ADHD youths showed significant hypoconnectivity of the left dorsal caudate (DC) with bilateral sensorimotor clusters. Significant diagnosis × genotype interactions were found in the connectivity between the left DC and the right sensorimotor cluster, and between the right DC and the left dorsolateral prefrontal/bilateral anterior cingulate clusters. Furthermore, the connectivity of the left DC showing significant diagnosis × genotype interactions was associated with DMS performance in youths with ADHD who carried the DAT1 CT haplotype. Conclusions A novel gene-brain-behavior association between the left DC functional connectivity and visual memory performance in ADHD youths with the DAT1 rs27048 (C)/rs429699 (T) haplotype suggests a differential effect of DAT1 genotype altering specific brain function causing neuropsychological dysfunction in ADHD.
Deep and Densely Connected Networks for Classification of Diabetic Retinopathy

Diabetes has recently emerged as a worldwide problem, and diabetic retinopathy is an abnormal state associated with the human retina. Due to the increase in daily screen-related activities of modern human beings, diabetic retinopathy is more prevalent among adults, leading to minor and major blindness. Doctors and clinicians are unable to perform early diagnoses due to the large number of patients. To solve this problem, this study introduces a classification model for retinal images that distinguishes between the various stages of diabetic retinopathy. This work involves deploying deep and densely connected networks for retinal image analysis with training from scratch. Dense connections between the convolutional layers of the network are an essential factor to enhance accuracy owing to the deeper supervision between layers. Another factor is the growth rate that further assists our model in learning more sophisticated feature maps regarding retinal images from every stage of the network. We compute the area under the curve, sensitivity, and specificity, particularly for messidor-2 and EyePACS. Compared to existing approaches, our method achieved better results, with an approximate rise rate of 0.01, 0.03, and 0.01, respectively. Therefore, computer-aided programs can help in diagnostic centers as automated detection systems.
Acceptability, Feasibility, and Efficacy Potential of a Multimodal Acceptance and Commitment Therapy Intervention to Address Psychosocial and Advance Care Planning Needs among Anxious and Depressed Adults with Metastatic Cancer.

Background: Adults with metastatic cancer frequently report anxiety and depression symptoms, which may impact health behaviors such as advance care planning (ACP). Objective: The study leveraged acceptance and commitment therapy (ACT), an evidence-based approach for reducing distress and improving health behaviors, and adapted it into a multimodal intervention (M-ACT) designed to address the psychosocial and ACP needs of anxious and depressed adults with metastatic cancer. The study evaluated M-ACT's acceptability, feasibility, and efficacy potential. Design: The study was designed as a single-arm intervention development and pilot trial. Setting/Subjects: The trial enrolled 35 anxious or depressed adults with stage IV cancer in community oncology clinics, with a referred-to-enrolled rate of 69% and eligible-to-enrolled rate of 95%. Measurements: M-ACT alternated four in-person group sessions with three self-paced online sessions. Acceptability and feasibility were assessed through enrollment, attendance, and satisfaction ratings. Outcomes and theorized intervention mechanisms were evaluated at baseline, midintervention, postintervention, and two-month follow-up. Results: Participant feedback was used to refine the intervention. Of participants starting the intervention, 92% completed, reporting high satisfaction. One-quarter did not begin M-ACT due to health declines, moving, or death. Completers showed significant reductions in anxiety, depression, and fear of dying and increases in ACP and sense of life meaning. In this pilot, M-ACT showed no significant impact on pain interference. Increases in two of three mechanism measures predicted improvement on 80% of significant outcomes. Conclusions: The M-ACT intervention is feasible, acceptable, and shows potential for efficacy in community oncology settings; a randomized trial is warranted.
The Relationship Between Nurses' Work-Related Variables, Colleague Solidarity, And Job Motivation.

AIMS The study was conducted to evaluate the effects of nurses' work-related variables and colleague solidarity on their job motivation. BACKGROUND The motivation of nurses is an important measure in effective and efficient provision of healthcare services. METHODS The sample of this descriptive study included 172 nurses working at a private hospital in Turkey. The Colleague Solidarity Scale for Nurses, Nurses' Job Motivation Scale, and Demographic and Work-Related Variables Questionnaire were used for data collection. Data were analyzed using descriptive statistics, Pearson's correlation, and backward multiple regression analysis. RESULTS There was a positive correlation between the scores on the Colleague Solidarity Scale for Nurses and the Nurses' Job Motivation Scale (r: 0.56, p < 0.001). Of the nine independent variables evaluated in the multiple regression analysis, five had a significant effect on the job motivation of nurses (R2 : 0.39, p < 0.001, Durbin-Watson: 2.12). CONCLUSION The results of the study show that the three sub-dimensions of the Colleague Solidarity Scale for Nurses, salary and career opportunities were important factors affecting job motivation. IMPLICATIONS FOR NURSING MANAGEMENT In order to increase nurses' job motivation, nurse managers should work to improve collegial solidarity, create career opportunities, and develop salary policies.
Risk Factors for Recurrent Arterial Ischemic Stroke in Children and Young Adults

Arterial ischemic stroke (AIS) experienced at a young age is undoubtedly a serious medical problem. AIS very rarely occurs at a developmental age, whereas in young adults, it occurs with a higher frequency. The etiologic mechanisms of AIS occurring in childhood and adulthood differ. However, for both age populations, neurological consequences of AIS, including post-stroke seizures, motor disability, and recurrence of the disease, are connected to many years of care, rehabilitation, and treatment. Recurrent stroke was observed to increase the risk of patients’ mortality. One of the confirmed risk factors for recurrent stroke in children is the presence of vasculopathies, especially Moyamoya disease and syndrome, and focal cerebral arteriopathy of childhood (FCA). FCA causes a 5-fold increase in the risk of recurrent stroke in comparison with idiopathic AIS. In turn, young adults with recurrent stroke were found to more often suffer from hypertension, diabetes mellitus, or peripheral artery disease than young patients with first-ever stroke. Some reports also indicate relationships between specific genetic polymorphisms and AIS recurrence in both age groups. The aim of the present literature review was to discuss available data regarding the risk factors for recurrent AIS in children and young adults.
Changes in adipose tissue lipolysis gene expression and insulin sensitivity after weight loss

Objective Insulin resistance is a major pathophysiological link between obesity and its metabolic complications. Weight loss (WL) is an effective tool to prevent obesity-related diseases; however, the mechanisms of an improvement in insulin sensitivity (IS) after weight-reducing interventions are not completely understood. The aim of the present study was to analyze the relationships between IS and adipose tissue (AT) expression of the genes involved in the regulation of lipolysis in obese subjects after WL. Methods Fifty-two obese subjects underwent weight-reducing dietary intervention program. The control group comprised 20 normal-weight subjects, examined at baseline only. Hyperinsulinemic-euglycemic clamp and s.c. AT biopsy with subsequent gene expression analysis were performed before and after the program. Results AT expression of genes encoding lipases (PNPLA2, LIPE and MGLL) and lipid-droplet proteins enhancing (ABHD5) and inhibiting lipolysis (PLIN1 and CIDEA) were decreased in obese individuals in comparison with normal-weight individuals. The group of 38 obese participants completed dietary intervention program and clamp studies, which resulted in a significant WL and an improvement in mean IS. However, in nine subjects from this group IS did not improve in response to WL. AT expression of PNPLA2, LIPE and PLIN1 increased only in the group without IS improvement. Conclusions Excessive lipolysis may prevent an improvement in IS during WL. The change in AT PNPLA2 and LIPE expression was a negative predictor of the change in IS after WL.
The genetic polymorphisms of MMP-3 and VDR on susceptibility of lumbar disc degeneration

Purpose To study the impact of genetic polymorphisms of MMP-3(matrix metalloprotein-ase-3) and VDR(vitamin D receptor-Taq) on lumbar intervertebral disc degeneration. Methods A case-control study involving 178 cases diagnosed as lumbar disc degeneration by CT and 284 controls was carried out.Polymerase chain reaction and restriction fragments length polymorphism(PCR-RFLP) were applied to detect the polymorphisms of MMP-3,VDR-Taq and VDR-Apa. Results The frequency of polymorphism genotypes of MMP-3 and VDR-Apa in lumbar disc degeneration cases were significantly higher than that in controls(OR=1.96 and 1.70,respectively),while no difference was found among the distribution of VDR-Taq variant genotypes.Being stratified by gender,lumbar disc degeneration in men was only associated with MMP-3.However,lumbar disc degeneration in women was associated with MMP-3 and VDR-Apa.It was revealed that the polymorphism genotypes of both MMP-3 and VDR-Apa had a synergistic action in risk of lumbar disc degeneration(OR=3.44). Conclusions The polymorphism genotypes of MMP-3 and VDR-Apa are risk genetic factors of lumbar disc degeneration.
Dynamic Transcriptome, Accessible Genome and PGR Cistrome Profiles in the Human Myometrium

The myometrium undergoes structural and functional remodeling during pregnancy. We hypothesize that myometrial genomic elements alter correspondingly in preparation for parturition. Human myometrial tissues from nonpregnant (NP) and term pregnant (TP) human subjects were examined by RNAseq, ATACseq and PGR ChIPseq assays to profile transcriptome, assessible genome and PGR occupancy. NP and TP specimens exhibit 2890 differentially expressed genes, reflecting an increase of metabolic, inflammatory and PDGF signaling, among others, in adaptation to pregnancy. At the epigenome level, patterns of accessible genome change between NP and TP myometrium, leading to altered enrichment of binding motifs for hormone and muscle regulators such as the progesterone receptor (PGR), Krüppel-like factors and MEF2A transcription factors. PGR genome occupancy exhibits a significant difference between the two stages of the myometrium, concomitant with distinct transcriptomic profiles including genes such as ENO1, LHDA, and PLCL1 in the glycolytic and calcium signaling pathways. Over-representation of SRF, MYOD and STAT binding motifs in PGR occupying sites further suggests interactions between PGR and major muscle regulators for myometrial gene expression. In conclusion, changes in accessible genome and PGR occupancy are part of the myometrial remodeling process and may serve as mechanisms to formulate the state-specific transcriptome profiles.
Extracorporeal photopheresis for graft‐vs‐host disease: A literature review and treatment guidelines proposed by the Nordic ECP Quality Group

Extracorporeal photopheresis (ECP) is one of the most used and established therapies for steroid‐refractory graft‐vs‐host disease (GvHD), with a good effect to side effect profile. In this review, we present a summary of present literature and provide evidence‐based treatment guidelines for ECP in GvHD. The guidelines constitute a consensus statement formed by the Nordic ECP Quality Group representing all ECP centres in the Nordic countries, and aims to facilitate harmonisation and evidence‐based practice. In developing the guidelines, we firstly conducted a thorough literature search of original articles and existing guidelines. In total, we identified 26 studies for ECP use in acute GvHD and 36 in chronic GvHD. The studies were generally small, retrospective and heterogeneous regarding patient characteristics, treatment schedule and outcome assessment. In general, a majority of patients achieved partial response or better, but response rates varied by the organs affected. Head‐to‐head comparisons to other treatment modalities were lacking. Overall, we consider the quality of evidence to be low–moderate (GRADE) and encourage future prospective multi‐armed trials to strengthen the present recommendations. However, despite limitations in evidence strength, standardised treatment schedules and regular follow‐up are imperative to ensure the best possible patient outcome.
Quercetin Exerts Age-Dependent Beneficial Effects on Blood Pressure and Vascular Function, But Is Inefficient in Preventing Myocardial Ischemia-Reperfusion Injury in Zucker Diabetic Fatty Rats

Background: Quercetin (QCT) was shown to exert beneficial cardiovascular effects in young healthy animals. The aim of the present study was to determine cardiovascular benefits of QCT in older, 6-month and 1-year-old Zucker diabetic fatty (ZDF) rats (model of type 2 diabetes). Methods: Lean (fa/+) and obese (fa/fa) ZDF rats of both ages were treated with QCT for 6 weeks (20 mg/kg/day). Isolated hearts were exposed to ischemia-reperfusion (I/R) injury (30 min/2 h). Endothelium-dependent vascular relaxation was measured in isolated aortas. Expression of selected proteins in heart tissue was detected by Western blotting. Results: QCT reduced systolic blood pressure in both lean and obese 6-month-old rats but had no effect in 1-year-old rats. Diabetes worsened vascular relaxation in both ages. QCT improved vascular relaxation in 6-month-old but worsened in 1-year-old obese rats and had no impact in lean controls of both ages. QCT did not exert cardioprotective effects against I/R injury and even worsened post-ischemic recovery in 1-year-old hearts. QCT up-regulated expression of eNOS in younger and PKCε expression in older rats but did not activate whole PI3K/Akt pathway. Conclusions: QCT might be beneficial for vascular function in diabetes type 2; however, increasing age and/or progression of diabetes may confound its vasculoprotective effects. QCT seems to be inefficient in preventing myocardial I/R injury in type 2 diabetes and/or higher age. Impaired activation of PI3K/Akt kinase pathway might be, at least in part, responsible for failing cardioprotection in these subjects.
Early childhood deprivation is associated with alterations in adult brain structure despite subsequent environmental enrichment

Significance Millions of children worldwide live in nonfamilial institutions. We studied impact on adult brain structure of a particularly severe but time-limited form of institutional deprivation in early life experienced by children who were subsequently adopted into nurturing families. Institutional deprivation was associated with lower total brain volume in a dose-dependent way. Regionally specific effects were seen in medial prefrontal, inferior frontal, and inferior temporal areas. Deprivation-related alterations in total brain volume were associated with lower intelligence quotient and more attention deficit/hyperactivity disorder symptoms; alterations in temporal volume seemed compensatory, as they were associated with fewer attention deficit/hyperactivity disorder symptoms. We provide evidence that early childhood deprivation is related to alterations in adult brain structure, despite environmental enrichment in intervening years. Early childhood deprivation is associated with higher rates of neurodevelopmental and mental disorders in adulthood. The impact of childhood deprivation on the adult brain and the extent to which structural changes underpin these effects are currently unknown. To investigate these questions, we utilized MRI data collected from young adults who were exposed to severe deprivation in early childhood in the Romanian orphanages of the Ceaușescu era and then, subsequently adopted by UK families; 67 Romanian adoptees (with between 3 and 41 mo of deprivation) were compared with 21 nondeprived UK adoptees. Romanian adoptees had substantially smaller total brain volumes (TBVs) than nondeprived adoptees (8.6% reduction), and TBV was strongly negatively associated with deprivation duration. This effect persisted after covarying for potential environmental and genetic confounds. In whole-brain analyses, deprived adoptees showed lower right inferior frontal surface area and volume but greater right inferior temporal lobe thickness, surface area, and volume than the nondeprived adoptees. Right medial prefrontal volume and surface area were positively associated with deprivation duration. No deprivation-related effects were observed in limbic regions. Global reductions in TBV statistically mediated the observed relationship between institutionalization and both lower intelligence quotient (IQ) and higher levels of attention deficit/hyperactivity disorder symptoms. The deprivation-related increase in right inferior temporal volume seemed to be compensatory, as it was associated with lower levels of attention deficit/hyperactivity disorder symptoms. We provide compelling evidence that time-limited severe deprivation in the first years of life is related to alterations in adult brain structure, despite extended enrichment in adoptive homes in the intervening years.
Extracellular Vesicles from Mesenchymal Stem Cells as Novel Treatments for Musculoskeletal Diseases

Mesenchymal stem/stromal cells (MSCs) represent a promising therapy for musculoskeletal diseases. There is compelling evidence indicating that MSC effects are mainly mediated by paracrine mechanisms and in particular by the secretion of extracellular vesicles (EVs). Many studies have thus suggested that EVs may be an alternative to cell therapy with MSCs in tissue repair. In this review, we summarize the current understanding of MSC EVs actions in preclinical studies of (1) immune regulation and rheumatoid arthritis, (2) bone repair and bone diseases, (3) cartilage repair and osteoarthritis, (4) intervertebral disk degeneration and (5) skeletal muscle and tendon repair. We also discuss the mechanisms underlying these actions and the perspectives of MSC EVs-based strategies for future treatments of musculoskeletal disorders.