Miracle-dz/UniFAR-FTUs huggingface dataset:
The relationship between the expression levels of miR-135a and HOXA10 gene in the eutopic and ectopic endometrium

Background: The study of microRNA expression can be effective in the diagnosing and treating different diseases. miR-135a is one of the most important micro-ribonucleic acids involved in endometriosis. Among the genes that become the target of the miR-135a and are subjected to changes in the endometrium of patients with endometriosis is HOXA10 gene which is expressed in the endometrium in response to steroid hormones. Objective: The aim of this study was to evaluate the expression of miR-135a and its relationship with the level of HOXA10 gene expression in both endometrial ectopic and eutopic tissues in patients with endometriosis compared to the control samples. Materials and Methods: In this prospective case-control study, both case-eutopic and case-ectopic tissue samples were obtained from 17 women with endometriosis and the eutopic endometrial tissue was sampled from 17 women with normal endometrium as the control group. The gene's expression of miR-135a and HOXA10 were investigated using quantitative reverse transcription PCR (q-RT PCR). Results: A significant decrease in the expression of HOXA10 gene was detected in case-eutopic during the luteal phase compared to the control samples (p=0.001), while in the case-ectopic, the expression of this gene was increased (p=0.681) compared to the control samples. In addition, the expression miR-135a in the luteal phase showed a remarkable increase in the case-eutopic endometrial tissue (p=0.026) as well as a significant decrease in the case-ectopic endometrial tissue compared to the control samples (p=0.008). Conclusion: Considering the inverse relations between the over-expression of miR-135a and the reduction of HOXA10, it seems that miR-135a may be applied as an endometrial diagnostic and therapeutic biomarker.
What Explains Socioeconomic Inequality in Health-related Quality of Life in Iran? A Blinder-Oaxaca Decomposition

Objectives This study aimed to explain the health-related quality of life (HRQoL) gap between the poorest and the wealthiest quintiles in the capitals of Kermanshah and Kurdistan Provinces (Kermanshah and Sanandaj), in western Iran. Methods This was a cross-sectional study conducted among 1772 adults. Data on socio-demographic characteristics, socioeconomic status (SES), lifestyle factors, body mass index, and HRQoL of participants were collected using a self-administered questionnaire. The slope and relative indices of inequality (SII and RII, respectively) were employed to examine socioeconomic inequality in poor HRQoL. Blinder-Oaxaca (BO) decomposition was used to quantify the contribution of explanatory variables to the gap in the prevalence of poor HRQoL between the wealthiest and the poorest groups. Results The overall crude and age-adjusted prevalence of poor HRQoL among adults was 32.0 and 41.8%, respectively. The SII and RII indicated that poor HRQoL was mainly concentrated among individuals with lower SES. The absolute difference (%) in the prevalence of poor HRQoL between the highest and lowest SES groups was 28.4. The BO results indicated that 49.9% of the difference was explained by different distributions of age, smoking behavior, physical inactivity, chronic health conditions, and obesity between the highest and lowest SES groups, while the remaining half of the gap was explained by the response effect. Conclusions We observed a pro-rich distribution of poor HRQoL among adults in the capitals of Kermanshah and Kurdistan Provinces. Policies and strategies aimed at preventing and reducing smoking, physical inactivity, chronic health conditions, and obesity among the poor may reduce the gap in poor HRQoL between the highest and lowest SES groups in Iran.
Regulatory NLRs Control the RLR-Mediated Type I Interferon and Inflammatory Responses in Human Dendritic Cells

Unique members of the nucleotide-binding domain leucine-rich repeat (NLR) family have been found to regulate intracellular signaling pathways initiated by other families of pattern recognition receptors (PRR) such as Toll-like receptors (TLRs) and retinoic-acid inducible gene I (RIG-I)-like receptors (RLRs). Plasmacytoid dendritic cells (pDCs), the most powerful type I interferon (IFN) producing cells, preferentially employ endosomal TLRs to elicit antiviral IFN responses. By contrast, conventional DCs (cDCs) predominantly use cytosolic RLRs, which are constitutively expressed in them, to sense foreign nucleic acids. Previously we have reported that, though RIG-I is absent from resting pDCs, it is inducible upon TLR stimulation. In the recent study we investigated the regulatory ability of NLRs, namely NLRC5 and NLRX1 directly associated with the RLR-mediated signaling pathway in DC subtypes showing different RLR expression, particularly in pDCs, and monocyte-derived DCs (moDCs). Here we demonstrate that similarly to RLRs, NLRC5 is also inducible upon TLR9 stimulation, whereas NLRX1 is constitutively expressed in pDCs. Inhibition of NLRC5 and NLRX1 expression in pDCs augmented the RLR-stimulated expression of type I IFNs but did not affect the production of the pro-inflammatory cytokines TNF, IL-6, and the chemokine IL-8. Further we show that immature moDCs constantly express RLRs, NLRX1 and NLRC5 that are gradually upregulated during their differentiation. Similarly to pDCs, NLRX1 suppression increased the RLR-induced production of type I IFNs in moDCs. Interestingly, RLR stimulation of NLRX1-silenced moDCs leads to a significant increase in pro-inflammatory cytokine production and IκBα degradation, suggesting increased NF-κB activity. On the contrary, NLRC5 does not seem to have any effect on the RLR-mediated cytokine responses in moDCs. In summary, our results indicate that NLRX1 negatively regulates the RLR-mediated type I IFN production both in pDCs and moDCs. Further we show that NLRX1 inhibits pro-inflammatory cytokine secretion in moDCs but not in pDCs following RLR stimulation. Interestingly, NLRC5 suppresses the RLR-induced type I IFN secretion in pDCs but does not appear to have any regulatory function on the RLR pathway in moDCs. Collectively, our work demonstrates that RLR-mediated innate immune responses are primarily regulated by NLRX1 and partly controlled by NLRC5 in human DCs.
Recommendations for hormone therapy in hysterectomized women: importance of new data in clinical management

Women with a prior hysterectomy with and without oophorectomy represent special cohorts among those who require menopausal hormone therapy (HT), as a progestogen is not required for endometrial protection. This is relevant in light of recent research demonstrating superiority of estrogen therapy alone compared with estrogen plus a progestogen with respect to breast cancer risk and perhaps even cardiovascular protection. No longer is it appropriate to lump all HT regimens together when advising patients. Unfortunately, there is a general reluctance in the healthcare community to prescribe HT even a decade after publication of the results of the Women’s Health Initiative trial. However, with subsequent research showing a favorable benefit/risk balance of short-term estrogen therapy in symptomatic, recently menopausal women, especially those who have undergone hysterectomy with oophorectomy, the need for educating patients and providers on the matter cannot be overemphasized.
Pathogen enrichment sequencing (PenSeq) enables population genomic studies in oomycetes

Summary The oomycete pathogens Phytophthora infestans and P. capsici cause significant crop losses world‐wide, threatening food security. In each case, pathogenicity factors, called RXLR effectors, contribute to virulence. Some RXLRs are perceived by resistance proteins to trigger host immunity, but our understanding of the demographic processes and adaptive evolution of pathogen virulence remains poor. Here, we describe PenSeq, a highly efficient enrichment sequencing approach for genes encoding pathogenicity determinants which, as shown for the infamous potato blight pathogen Phytophthora infestans, make up < 1% of the entire genome. PenSeq facilitates the characterization of allelic diversity in pathogen effectors, enabling evolutionary and population genomic analyses of Phytophthora species. Furthermore, PenSeq enables the massively parallel identification of presence/absence variations and sequence polymorphisms in key pathogen genes, which is a prerequisite for the efficient deployment of host resistance genes. PenSeq represents a cost‐effective alternative to whole‐genome sequencing and addresses crucial limitations of current plant pathogen population studies, which are often based on selectively neutral markers and consequently have limited utility in the analysis of adaptive evolution. The approach can be adapted to diverse microbes and pathogens.
Patients’ satisfaction and subjective happiness after refractive surgery for myopia

Purpose The purpose of this study was to assess patients’ satisfaction and change in subjective happiness after laser-assisted in situ keratomileusis (LASIK). Patients and methods This was a retrospective cross-sectional study of 307 patients (mean age, 34.3 years; range, 20–63 years) who underwent bilateral LASIK surgery and ocular examinations, including subjective refraction and visual acuity axial length measurements at Minamiaoyama Eye Clinic. Patients also completed questionnaires on their satisfaction with the surgery, and on the subjective happiness scale (SHS) within 1 month before and 1 month after surgery. A multiple regression analysis was performed to determine the independent predictors of the SHS score. Results In total, 91.2% of the patients were satisfied with surgery (very satisfied: n=155; satisfied: n=125). The SHS score increased postoperatively from 5.2±0.9 to 5.3±0.9 (P<0.001). The multiple regression analysis revealed that the preoperative SHS score (β=0.77; P<0.001) and satisfaction with surgery (β=−0.11; P=0.05) were predictors of postoperative SHS score. Conclusion LASIK may contribute to increased patient happiness.
Treatment of Anterior Vaginal Wall Prolapse Using Transvaginal Anterior Mesh With Apical Fixation: A Prospective Multicenter Study With up to 2 Years of Follow-up

Purpose To evaluate the safety and efficacy of a surgical polypropylene mesh for correction of anterior vaginal prolapse, with or without apical defects, by providing simultaneous reinforcement at the anterior and apical aspects of the vagina with a single-incision approach. Methods This was a prospective, multicenter, single-arm study involving women with baseline stage ≥2 anterior and/or apical vaginal wall prolapse according to the Pelvic Organ Prolapse Quantification (POP-Q) system. The primary endpoint was defined as achievement of POP-Q stage ≤1 status. Additionally, patient-reported outcomes were assessed using the International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS). The device under evaluation was Calistar A, which is fixed posteriorly to the sacrospinous ligaments with a novel tissue-anchoring system (TAS) and anteriorly to the obturator internus muscles. Postoperative follow-ups were scheduled at 7 days and at 6, 12, and 24 months. Results Ninety-seven women were treated and assessed for the primary outcome. They were followed for up to 2 years (n=43), with a median of 12 months. Objective cure was achieved in 86 of the 97 patients (88.7%) (P<0.0005). The mean reduction in the ICIQ-VS scores was in the range of 70%–90% for every time point (P<0.05). No bleeding or surgical revision was reported. Mesh exposure occurred in 7 patients (7.2%), urinary retention in 5 (5.2%), de novo dyspareunia in 3 (3.1%), and urinary tract infections in 7 (7.2%). Conclusions This midterm follow-up showed that apical and anterior vaginal reinforcement with a polypropylene implant fixed with a TAS provided good anatomical correction, with no major complications.
The Outcome-Representation Learning Model: A Novel Reinforcement Learning Model of the Iowa Gambling Task

The Iowa Gambling Task (IGT) is widely used to study decision-making within healthy and psychiatric populations. However, the complexity of the IGT makes it difficult to attribute variation in performance to specific cognitive processes. Several cognitive models have been proposed for the IGT in an effort to address this problem, but currently no single model shows optimal performance for both short- and long-term prediction accuracy and parameter recovery. Here, we propose the Outcome-Representation Learning (ORL) model, a novel model that provides the best compromise between competing models. We test the performance of the ORL model on 393 subjects' data collected across multiple research sites, and we show that the ORL reveals distinct patterns of decision-making in substance-using populations. Our work highlights the importance of using multiple model comparison metrics to make valid inference with cognitive models and sheds light on learning mechanisms that play a role in underweighting of rare events.
SOX2, a stemness gene, induces progression of NSCLC A549 cells toward anchorage-independent growth and chemoresistance to vinblastine

Background Non-small cell lung cancer (NSCLC) is difficult to treat successfully. This intractability is mainly due to the cancer progressing through invasion, metastasis, chemotherapeutic resistance and relapse. Stemness has been linked to the various steps of cancer progression in a variety of tumors, yet little is known regarding its role in NSCLC. Purpose In this study, we sought to determine the role of SOX2, a master regulator of pluripotency, in the growth of extracellular matrix (ECM)-detached cells during cancer progression. Methods We established a three-dimensional (3D) Poly-2-hydroxyethyl methacrylate (poly-HEMA) culture of lung adenocarcinoma (LUAD) A549 cells as an ECM-detached cell growth model and examined the role of stemness genes using siRNA and small molecule inhibitor in comparison to standard two dimensional (2D) culture. Results In poly-HEMA culture, A549 cells formed substratum-detached spheroids with characteristics of intermediate epithelial to mesenchymal transition (EMT) and exhibited greater expression of SOX2 than did control 2D cells. Knockdown of SOX2 markedly suppressed the growth of A549 cell aggregates in poly-HEMA culture conditions and furthermore increased their sensitivity to the anticancer drug vinblastine with concomitant downregulation of the activity of the anti-apoptotic AKT kinase. Interestingly, a small molecule, RepSox, which replaces SOX2, stimulated A549 cell growth in poly-HEMA 3D culture condition. Conclusion Our findings strongly indicate that SOX2 contributes to anchorage-independent growth and chemoresistance via its downstream signaling mediator AKT kinase during the disease progression of NSCLC. SOX2 may therefore be an invaluable therapeutic target of NSCLC.
Raw regulates glial population of the eye imaginal disc

Glia are critical for proper development, support, and function of the nervous system. The Drosophila eye has proven an excellent model for gaining significant insight into the molecular mechanisms regulating glial development and function. Recent studies have demonstrated that Raw is required in glia of the central and peripheral nervous systems; however, the function of Raw in glia of the developing eye has not been explored. These studies demonstrate that raw knockdown results in a reduction in the number of glia in the third instar eye imaginal disc and reduced glial spreading across the field of differentiating photoreceptor neurons. Expression of a raw enhancer trap reveals that raw is expressed in eye disc glia. Exploration of the mechanism by which raw knockdown results in glial reduction reveals that Raw is required for glial proliferation and migration into the eye disc. In addition, Raw negatively regulates Jun N‐terminal kinase (JNK) signaling in glia of the developing eye and increased JNK signaling results in a reduction in the number of glia populating the eye disc, similar to that observed upon raw knockdown. Thus, Raw functions as a critical regulator of glial population of the eye imaginal disc by regulating glial proliferation and migration and inhibiting JNK signaling.
Immunotherapy combined with epidermal growth factor receptor-tyrosine kinase inhibitors in non-small-cell lung cancer treatment

In recent years, targeted therapy and immunotherapy have played important roles in the treatment of patients with non-small-cell lung cancer (NSCLC). Drugs that target epidermal growth factor receptor (EGFR) mutations (eg, gefitinib, erlotinib, icotinib, and osimertinib) are among the most commonly used targeted therapies. Afatinib is an irreversible second-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI), and the LUX-Lung 3 trial demonstrated the superiority of afatinib to cisplatin and pemetrexed in the frontline treatment of treatment-naïve patients with advanced EGFR mutation adenocarcinoma of the lung. Although these drugs show significant therapeutic efficacy, most patients invariably experience disease progression resulting in death. Immunotherapy targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) has now been approved for the first-line treatment of patients with advanced NSCLC. These can produce sustained clinical responses by reversing negative regulators of T-cell function; however, immunotherapy response rates remain low, and only a few patients ultimately benefit from this approach. Here, we discuss the potential of EGFR-TKIs for inducing antitumor immunity and the feasibility of their combination with immunotherapy (including PD-1/PD-L1 inhibitors) in NSCLC patients and the associated challenges for clinical application.
Musculoskeletal pain in adults born preterm: Evidence from two birth cohort studies

Individuals born preterm are at risk of later developmental problems and long‐term morbidities. There is conflicting evidence regarding musculoskeletal pain in young adulthood. We investigated the prevalence of self‐reported musculoskeletal pain in young adults born across the range of preterm birth compared with a term‐born reference group.
T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1

T Cell Leukemia/Lymphoma 1A is expressed during B-cell differentiation and, when over-expressed, acts as an oncogene in mouse (Tcl1a) and human (TCL1A) B-cell chronic lymphocytic leukemia (B-CLL) and T-cell prolymphocytic leukemia (T-PLL). Furthermore, in the murine system Tcl1a is expressed in the ovary, testis and in pre-implantation embryos, where it plays an important role in blastomere proliferation and in embryonic stem cell (ESC) proliferation and self-renewal. We have also observed that Tcl1-/- adult mice exhibit alopecia and deep ulcerations. This finding has led us to investigate the role of TCL1 in mouse skin and hair follicles. We have found that TCL1 is expressed in the proliferative structure (i.e. the secondary hair germ) and in the stem cell niche (i.e. the bulge) of the hair follicle during regeneration phase and it is constitutively expressed in the basal layer of epidermis where it is required for the correct proliferative–differentiation program of the keratinocytes (KCs). Taking advantage of the murine models we have generated, including the Tcl1-/- and the K14-TCL1 transgenic mouse, we have analysed the function of TCL1 in mouse KCs and the molecular pathways involved. We provide evidence that in the epidermal compartment TCL1 has a role in the regulation of KC proliferation, differentiation, and apoptosis. In particular, the colony-forming efficiency (CFE) and the insulin-like growth factor 1 (IGF1)-induced proliferation are dramatically impaired, while apoptosis is increased, in KCs from Tcl1-/- mice when compared to WT. Moreover, the expression of differentiation markers such as cytokeratin 6 (KRT6), filaggrin (FLG) and involucrin (IVL) are profoundly altered in mutant mice (Tcl1-/-). Importantly, by over-expressing TCL1A in basal KCs of the K14-TCL1 transgenic mouse model, we observed a significant rescue of cell proliferation, differentiation and apoptosis of the mutant phenotype. Finally, we found TCL1 to act, at least in part, via increasing phospho-ERK1/2 and decreasing phospho-P38 MAPK. Hence, our data demonstrate that regulated levels of Tcl1a are necessary for the correct proliferation and differentiation of the interfollicular KCs.
Differentiation of self and trait anxiety: A cross-cultural perspective.

Cultural differences are likely to affect the ability to deal with anxiety. We investigated this issue among four cultural groups-Germans and Italians (Europeans living in South Tyrol, Italy), Jews and Arabs (Israelis)-in terms of their levels of differentiation of self, trait anxiety and somatic symptoms. We also examined the relationship of differentiation of self to trait anxiety and somatic symptoms. The sample consisted of 824 students: 387 Israelis (mean age 23.6) and 437 Europeans (mean age 22.3). Israeli participants reported lower levels of trait anxiety than European students. Jewish students reported lower trait anxiety than Arab students (mean difference = -.14, p < .009), while there was no difference between German and Italian students (mean difference = .03, p > .99). Jews reported a significantly lower level of emotional cutoff than Arabs (mean difference = -.45, p < .001), and Germans reported a significantly lower level of emotional reactivity than Italians (mean difference = .29, p < .001). Emotional reactivity and I-position predicted all participants' trait anxiety. On the whole, results point to the importance of examining differentiation of self when trying to reduce trait anxiety, as well as some important cultural differences.
Cold hypersensitivity after hand injuries. A prospective 7-year follow-up

Abstract We studied changes in cold hypersensitivity from 3 to 7 years following severe hand injuries. Data was collected using postal questionnaires 7 years after injury in 71 patients who had participated in a 3-year follow-up from the time of injury. There was no change in cold sensitivity measured using the McCabe Cold Sensitivity Severity scale (CSS) from 3 to 7 years after injury. However, there was a trend toward decreased severity measured using a five-level scale of self-reported cold hypersensitivity. Compared to the 3-year follow-up, fewer respondents rated their condition as severe and two patients had recovered from their cold hypersensitivity at the 7-year follow-up. Furthermore, 21 (30%) of the respondents stated a decrease in cold hypersensitivity during the last 2 years. Limitations in cold associated activities and the importance of being less limited in leisure activities (NRS 0-10) did not change between the two follow-ups. In conclusion, the CSS-scores did not change from 3 to 7 years after injury. Several patients experienced improvements in cold hypersensitivity, but few recovered completely from the condition.
Contingent Attentional Engagement: Stimulus- and Goal-Driven Capture Have Qualitatively Different Consequences

We examined whether shifting attention to a location necessarily entails extracting the features at that location, a process referred to as attentional engagement. In three spatial-cuing experiments (N = 60), we found that an onset cue captured attention both when it shared the target’s color and when it did not. Yet the effects of the match between the response associated with the cued object’s identity and the response associated with the target (compatibility effects), which are diagnostic of attentional engagement, were observed only with relevant-color onset cues. These findings demonstrate that stimulus- and goal-driven capture have qualitatively different consequences: Before attention is reoriented to the target, it is engaged to the location of the critical distractor following goal-driven capture but not stimulus-driven capture. The reported dissociation between attentional shifts and attentional engagement suggests that attention is best described as a camera: One can align its zoom lens without pressing the shutter button.