Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined therapy with L-Thyroxine and L-Triiodothyronine compared to L-Thyroxine alone in the treatment of primary hypothyroidism

OBJECTIVE: The objective of this study was to compare various parameters in patients with hypothyroidism receiving either monotherapy with L-Thyroxine (L-T4) or combination therapy with L-T4 and L-Triiodothyronine (L-T3). DESIGN: We conducted a randomized, controlled trial in 36 premenopausal women with hypothyroidism. The patients were divided into two groups: Group A (n=20) received only L-T4, while Group B received the combination L-T4 and L-T3. The treatment period lasted for 6 months. RESULTS: At baseline, the various parameters examined did not differ in the two groups. No significant difference between monotherapy and combined therapy was demonstrated on TSH level, ECG monitoring, densitometry, or thyroid symptoms score. The lipid profile was better during combined treatment compared to L-T4 alone; in Group A during treatment with L-T4 the levels of cholesterol and Low Density Lipoprotein (LDL) Cholesterol were unchanged, while in group B total cholesterol and LDL decreased (p<0.05). The changes in osteocalcin levels did not differ in the two groups, whereas the levels of urine deoxypyridinoline at the end of therapy were higher in the group with combination therapy, compared to monotherapy. CONCLUSION: Compared with L-T4 alone, replacement therapy with the combination of L-T4+L-T3 shows favourable changes in serum lipid profile, but higher activation of bone resorption.
Ethylene Signaling Modulates Cortical Microtubule Reassembly in Response to Salt Stress1[OPEN]

The plant hormone ethylene and its associated signaling pathway are involved in cortical microtubule reassembly, a process that is critical for the salt stress response in Arabidopsis. Regulation of cortical microtubule reorganization is essential for plant cell survival under high salinity conditions. In response to salt stress, microtubules undergo rapid depolymerization followed by reassembly to form a new microtubule network that promotes cell survival; however, the upstream regulatory mechanisms for this recovery response are largely unknown. In this study, we demonstrate that ethylene signaling facilitates salt stress-induced reassembly of cortical microtubules in Arabidopsis (Arabidopsis thaliana). Microtubule depolymerization was not affected under salt stress following the suppression of ethylene signaling with Ag+ or in ethylene-insensitive mutants, whereas microtubule reassembly was significantly inhibited. ETHYLENE-INSENSITIVE3, a key transcription factor in the ethylene signaling pathway, was shown to play a central role in microtubule reassembly under salt stress. In addition, we performed functional characterization of the microtubule-stabilizing protein WAVE-DAMPENED2-LIKE5 (WDL5), which was found to promote ethylene-associated microtubule reassembly and plant salt stress tolerance. These findings indicate that ethylene signaling regulates microtubule reassembly by up-regulating WDL5 expression in response to salt stress, thereby implicating ethylene signaling in salt-stress tolerance in plants.
The Risks of Opioid Treatment: Perspectives of Primary Care Practitioners and Patients from Safety-Net Clinics

Background: Patients with a history of substance use are more likely than those without substance use to experience chronic noncancer pain (CNCP), to be prescribed opioids, and to experience opioid misuse or overdose. Primary care practitioners (PCPs) in safety-net settings care for low-income patients with CNCP and substance use, usually without specialist consultation. To inform communication related to opioid risk, we explored PCPs’ and patients’ perceptions of the risks of chronic opioid therapy. Methods: We conducted semistructured interviews with 23 PCPs and 46 of their patients, who had a history of CNCP and substance use. We recruited from 6 safety-net health care settings in the San Francisco Bay Area. We transcribed interviews verbatim and analyzed transcripts using grounded theory methodology. Results: (1) PCPs feared harming patients and the community by opioid prescribing. PCPs emphasized fear of opioid overdose. (2) Patients did not highlight concerns about the adverse health consequences of opioids, except for addiction. (3) Both patients and PCPs were concerned about PCPs’ medicolegal risks related to opioid prescribing. (4) Patients reported feeling stigmatized by policies aimed at reducing opioid misuse. Conclusion: We identified differences in how clinicians and patients perceive opioid risk. To improve the informed consent process for opioid therapy, patients and PCPs need to have a shared understanding of the risks of opioids and engage in discussions that promote patient autonomy and safety. As clinics implement opioid prescribing policies, clinicians must develop effective communication strategies in order to educate patients about opioid risks and decrease patients’ experiences of stigma and discrimination.
Ephrin-B2/Fc promotes proliferation and migration, and suppresses apoptosis in human umbilical vein endothelial cells

Tumor growth and metastasis are angiogenesis dependent. Angiogenic growth involves endothelial cell proliferation, migration, and invasion. Ephrin-B2 is a ligand for Eph receptor tyrosine kinases and is an important mediator in vascular endothelial growth factor-mediated angiogenesis. However, research offer controversial information regarding effects of ephrin-B2 on vascular endothelial cells. In this paper, proteome analyses showed that ephrin-B2/Fc significantly activates multiple signaling pathways related to cell proliferation, survival, and migration and suppresses apoptosis and cell death. Cytological experiments further confirm that ephrin-B2/Fc stimulates endothelial cell proliferation, triggers dose-dependent migration, and suppresses cell apoptosis. Results demonstrate that soluble dose-dependent ephrinB2 can promote proliferation and migration and inhibit apoptosis of human umbilical vein endothelial cells. These results also suggest that ephrinB2 prevents ischemic disease and can potentially be a new therapeutic target for treating angiogenesis-related diseases and tumors.
Prevalence and Factors Associated with Female Sexual Dysfunction in Beijing, China

Background: Female sexual dysfunction (FSD) is a highly prevalent and often underestimated problem. However, large-scale, population-based epidemiological surveys of FSD are scarce in China. The present study was conducted to evaluate the prevalence and the potential risk factors of FSD across a selection of social groups in Beijing, China, based on the Female Sexual Function Index (FSFI). Methods: A cross-sectional study based on the multiple-stage cluster sampling was performed with adult women throughout the Dongcheng and Shunyi districts of Beijing. The Chinese version of FSFI was used, as well as questions on demographic characteristics, the disease-related context, and social relationships. Results: A total of 6000 consecutive women entered this study, with an actual response from 5024 women, corresponding to a response rate of 83.7%. A total of 4697 (78.3%) questionnaires were effective. The prevalence of adult FSD in Beijing was 2973 (63.3%) using a score of 26.55 as the boundary value, whereas the total mean FSFI score was 23.92 ± 6.37. However, 1423 (30.3%) women did not seek help. By multivariate logistic regression analysis, the possible potential risk factors included age (odds ratio [OR] = 1.051), dissatisfaction with the spouse's sexual ability (OR = 3.520), poor marital affection (OR = 2.087), spouse sexual difficulties (OR = 1.720), dissatisfaction with married life (OR = 1.476), living in a rural area (OR = 1.292), chronic pelvic pain (OR = 1.261), chronic disease (OR = 1.534), previous pelvic surgery (OR = 1.605), vaginal delivery (OR = 2.285), lower education (OR = 3.449) and postmenopausal (OR = 3.183). Conclusions: As suggested by the FSFI scores, female sexual problems are highly prevalent in Beijing. Dissatisfaction with the spouse's sexual ability, poor marital affection, sexual difficulties of the spouse, dissatisfaction with the marriage, rural life, CPP, and postmenopausal were conceivable risk factors for FSD in Beijing women.
K313, a novel benzoxazole derivative, exhibits anti‐inflammatory properties via inhibiting GSK3β activity in LPS‐induced RAW264.7 macrophages

Benzoxazole and its derivatives have been widely studied in recent years due to their various biological properties. A previous study has demonstrated that K313 (1H‐indole‐2,3‐dione 3‐(1,3‐benzoxazol‐2‐ylhydrazone)), a novel benzoxazole derivative, inhibits T cell proliferation to yield immunosuppressive effects. However, there are no related reports about its anti‐inflammatory effects. In the present study, we investigated the anti‐inflammatory properties and the underlying molecular mechanism of K313 in lipopolysaccharide (LPS)‐induced RAW264.7 macrophages. K313 dose‐dependently (5, 10, and 20 μM) inhibited LPS‐stimulated nitric oxide (NO), interleukin (IL)‐6, tumor necrosis factor (TNF)‐α, and 3‐nitrotyrosine (3‐NT) production and significantly decreased the gene transcription levels of inducible nitric oxide (iNOS), IL‐6, and TNF‐α. In addition, the results showed that the inflammatory cytokines suppressed by K313 were not regulated by p65 NF‐κB, ERK1/2, AKT, or p38 MAPK. Instead, K313 increased phosphorylation of glycogen synthase kinase‐3 beta (GSK‐3β) (Ser9) resulting in GSK‐3β deactivation. Moreover, in LPS‐stimulated RAW264.7 macrophages, K313 and lithium chloride (LiCl) had a synergistic effect on the anti‐inflammatory response. These results indicated that K313 exhibited anti‐inflammatory properties and revealed the potential mechanism. K313 can increase GSK‐3β (Ser9) phosphorylation to decrease GSK‐3β activation in LPS‐induced RAW264.7 macrophages.
Antigen-Induced but Not Innate Memory CD8 T Cells Express NKG2D and Are Recruited to the Lung Parenchyma upon Viral Infection

The pool of memory-phenotype CD8 T cells is composed of Ag-induced (AI) and cytokine-induced innate (IN) cells. IN cells have been described as having properties similar to those of AI memory cells. However, we found that pathogen-induced AI memory cells can be distinguished in mice from naturally generated IN memory cells by surface expression of NKG2D. Using this marker, we described the increased functionalities of AI and IN memory CD8 T cells compared with naive cells, as shown by comprehensive analysis of cytokine secretion and gene expression. However, AI differed from IN memory CD8 T cells by their capacity to migrate to the lung parenchyma upon inflammation or infection, a process dependent on their expression of ITGA1/CD49a and ITGA4/CD49d integrins.
Protocol for a randomised controlled trial of the effect of dapagliflozin, metformin and exercise on glycaemic variability, body composition and cardiovascular risk in prediabetes (the PRE-D Trial)

Introduction The primary aim of this study is to compare the efficacy of three short-term glucose-lowering interventions (exercise, metformin and dapagliflozin) on glycaemic variability in overweight or obese men and women with elevated diabetes risk (ie, prediabetes, defined as haemoglobin A1c (HbA1c)39–47 mmol/mol / 5.7%–6.4%). The secondary aims are to investigate the effects of the interventions on body composition and cardiometabolic risk factors. Methods and analysis The Pre-D Trial is an investigator-initiated, randomised, controlled, parallel, open-label, superiority trial. The study aims to assign 120 participants in a 1:1:1:1 ratio to receive one of four interventions for 13 weeks: (1) dapagliflozin (10 mg once daily); (2) metformin (850 mg twice daily); (3) exercise (interval training, 5 days a week, 30 min per session); or (4) control (lifestyle advice). After the 13 weeks of intervention, a follow-up period of 13 weeks will follow to study the long-term effects of the interventions. The primary endpoint is reduction from baseline to end-of treatment (13 weeks) in mean amplitude of glycaemic excursions measured by continuous glucose monitoring. The secondary endpoints include concomitant changes in various measures of glucose metabolism, body weight, cardiorespiratory fitness, blood pressure, plasma lipids, objectively measured physical activity and dietary intake. Ethics and dissemination The study protocol has been approved by the Ethics Committee of the Capital Region and the Danish Medicines Agency. Approval of data and biobank storage has been obtained from the Danish Data Protection Board. The study will be carried out according to the Declaration of Helsinki and to the regulations for good clinical practice. The results from this trial will allow a number of research questions concerning the effect of exercise versus dapagliflozin or metformin in HbA1c-defined prediabetes to be addressed. Trial registration NCT02695810
MicroRNAs and Autophagy: Fine Players in the Control of Chondrocyte Homeostatic Activities in Osteoarthritis

Osteoarthritis (OA) is a debilitating degenerative disease of the articular cartilage with a multifactorial etiology. Aging, the main risk factor for OA development, is associated with a systemic oxidative and inflammatory phenotype. Autophagy is a central housekeeping system that plays an antiaging role by supporting the clearance of senescence-associated alterations of macromolecules and organelles. Autophagy deficiency has been related to OA pathogenesis because of the accumulation of cellular defects in chondrocytes. Microribonucleic acids (microRNAs or miRs) are a well-established class of posttranscriptional modulators belonging to the family of noncoding RNAs that have been identified as key players in the regulation of cellular processes, such as autophagy, by targeting their own cognate mRNAs. Here, we present a state-of-the-art literature review on the role of miRs and autophagy in the scenario of OA pathogenesis. In addition, a comprehensive survey has been performed on the functional connections of the miR network and the autophagy pathway in OA by using “microRNA,” “autophagy,” and “osteoarthritis” as key words. Discussion of available evidence sheds light on some aspects that need further investigation in order to reach a more comprehensive view of the potential of this topic in OA.
Regeneration of Cartilage Surfaces

Injuries to hyaline articular cartilage elicit considerable musculoskeletal morbidity; on arthroscopic examination, these injuries are typically present in nearly 60% of knee joints. 1 The lack of neural innervation and the avascular morphology in hyaline articular cartilage compromises its ability for self-repair. Current treatments of focal defects include microfracture (chondroplasty), 2 autologous chondrocyte implantation, 3 osteochondral autograft transfer system, and mosaicplasty. Microfracture, the current standard treatment, involves penetration of subchondral bone to induce bleeding from the marrow stroma; however, this repair yields fibrocartilage, which is mechanically and biochemically inferior to native hyaline cartilage. Overall, these treatments were developed to relieve pain, restore function, and delay the progressive deterioration of cartilaginous lesions. Significant degeneration of the
Brute-Force Search Strategies for Single-Trace and Few - Traces Template Attacks on the DES Round Keys of a Recent Smart Card

Abstract. Recently, a new template attack on the DES key scheduling was demonstrated that allows recovery of a sufficiently large portion of the DES key of a widely deployed certified smart card chip using a single EM (electromagnetic) trace during the Exploitation Phase. Firstly, in this paper we show how the results can be improved upon when combining them with the analysis of another leakage channel, the total Hamming distance. Remaining rest entropies as low as ≈ 13 bits have been found for some single–trace attacks, meaning that effectively 42 bits of a single–key DES were recovered in a single trace. The nature of single–trace attacks has it that conventional software countermeasures are rendered useless by this attack, and thus the only remaining remedy is a hardware redesign. Secondly, various brute–force search strategies are compared with each other and an extensive analysis of the statistics of the rest entropy is presented. The analysis is also extended to two–key TDES. Moreover, the amount of brute–force effort can be drastically reduced when having more than one trace available for the attack. Already as few as N = 8 traces during the Exploitation Phase bring about a reduction of the average brute–force effort of the order of 10 bits for single DES, and 22 bits for two–key TDES. For N ≈ 100 we achieve an average brute–force effort of less than 50 bits for two–key TDES. Further analysis reveals that this attack is not equally strong for all DES keys, but that quite a number of weaker DES keys exist where the attack is much stronger. Naturally, any assessment of the severity of this attack will have to be made based on the weakest keys. [This last part constitutes an update to a previous version of this paper. ]
Graphic Depictions: Portrayals of Mental Illness in Video Games

Although studies have examined portrayals of mental illness in the mass media, little attention has been paid to such portrayals in video games. In this descriptive study, the fifty highest‐selling video games in each year from 2011 to 2013 were surveyed through application of search terms to the Wikia search engine, with subsequent review of relevant footage on YouTube. Depiction categories were then assigned based on the extent of portrayal and qualitative characteristics compared against mental illness stereotypes in cinema. Twenty‐three of the 96 surveyed games depicted at least one character with mental illness. Forty‐two characters were identified as portraying mental illness, with most characters classified under a “homicidal maniac” stereotype, although many characters did not clearly reflect cinema stereotypes and were subcategorized based on the shared traits. Video games contain frequent and varied portrayals of mental illness, with depictions most commonly linking mental illness to dangerous and violent behaviors.
The Roles of Age and Attention in General Emotion Regulation, Reappraisal, and Expressive Suppression

Life span emotional development theories propose age differences in emotion regulation tendencies and abilities. Research on age-related positivity has identified age differences in attention to emotional content, which may support emotion regulation in older age. The current research examines the roles of age and attention under various emotion regulation instructions. We measured younger (N = 92) and older (N = 88) adults’ fixation to negative emotional content and continuously rated affect during normal viewing and instructions to regulate. Those instructed to regulate first did so generally, then using detached or positive reappraisal and expressive suppression. Older adults (OAs) fixated less than younger adults (YAs) in negative areas regardless of instructions, suggesting broad age-related attentional tendencies. In contrast to some previous research, between-subjects analyses showed no age differences in effects of either form of reappraisal or suppression on affect. Within-subject analyses showed specific regulation instructions predicted less negative affect than general instructions for both age groups. Attention was unrelated to affect for both YAs and OAs across instructions. In sum, this research presents pervasive attentional preferences away from negative material in OAs as well as evidence of successful reappraisal and suppression in both age groups. Looking patterns, however, seemed unrelated to emotion regulation instructions’ effects on mood for either age group. Age differences in attentional patterns may therefore not translate into age differences in subsequent emotion regulation success.
Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions

Integrins are the core constituents of cell–matrix adhesion complexes such as focal adhesions (FAs) and play key roles in physiology and disease. Integrins fluctuate between active and inactive conformations, yet whether the activity state influences the spatial organization of integrins within FAs has remained unclear. In this study, we address this question and also ask whether integrin activity may be regulated either independently for each integrin molecule or through locally coordinated mechanisms. We used two distinct superresolution microscopy techniques, stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion microscopy (STED), to visualize active versus inactive &bgr;1 integrins. We first reveal a spatial hierarchy of integrin organization with integrin molecules arranged in nanoclusters, which align to form linear substructures that in turn build FAs. Remarkably, within FAs, active and inactive &bgr;1 integrins segregate into distinct nanoclusters, with active integrin nanoclusters being more organized. This unexpected segregation indicates synchronization of integrin activities within nanoclusters, implying the existence of a coordinate mechanism of integrin activity regulation.
High School Students' Views on the PBL Activities Supported via Flipped Classroom and LEGO Practices

The purpose of this study was to investigate the high school students’ views on instructions based on Flipped Classroom Model (FC) and LEGO applications. The case study, which is one of the qualitative research methods, was used within the scope of the study, the duration of which was 7 weeks. In order to choose the research group of the study, one of the purposeful sampling methods, criterion sampling, was used. In this context, the study was conducted with 35 10th grade high school students from two different classes. EGA (ExperimentalGroupA) consisted of 18 students while EGB (ExperimentalGroupB) consisted of 17 students. Within the scope of the study, algorithm instruction with FC and LEGO applications was conducted on EGA and LEGO applications and algorithm instruction in classroom were conducted on EGB. In accordance with the study, processes of focus group discussions and gathering data through observation were carried out. For the analysis of the data that was gathered, content analysis was performed and NVivo 8 was used. In the end of the study, the students were observed to be having great prejudices and reported negative views in the beginning of the study. Upon the initiation of the study, the prejudices and negative opinions were observed to be replaced by positive opinions. Students mentioned a great deal of educational benefits of the study. They stated that with the study, their motivation and interest in the lesson increased thanks to the implementations. Additionally in the group work, students said that they cooperated, exchanged ideas, shared tasks, took responsibility and socialized with their friends. About FC, students gave positive feedback on the communication opportunities of the atmosphere and they stated that they could repeatedly go beyond the class hours with FC, hence came prepared and saved time. Also students stated that FC atmosphere improved opportunities for teacher-student communication.