Miracle-dz/UniFAR-FTUs huggingface dataset:
Correlation the between the regulation of miRNA-1 in c-Met-induced EMT and cervical cancer progression

Cervical cancer is a common malignant tumor of the female reproductive system. Despite advances in cervical cancer therapy, tumor recurrence and metastasis remain the leading cause of mortality for patients with cervical cancer. Therefore, the investigation of tumorigenesis and progression, and the search for novel therapeutic targets, has been the primary focus in cervical cancer research. The aims of the present study were: i) To analyze the alterations in c-Met, E-cadherin and microRNA (miRNA)-1 expression levels in cervical cancer tissues; ii) to assess the correlation between the above genes and the pathological characteristics of the cancer tissues; and iii) to examine the potential mechanism through which miRNA-1 may regulate c-Met-induced epithelial-mesenchymal transition to promote the development of cervical cancer. In cervical cancer tissues, c-Met was more highly expressed, while E-cadherin exhibited lower expression levels compared with the adjacent tissues. The 24-month follow-up reported that a lower c-Met expression level was correlated with higher E-cadherin expression levels and a longer survival rate. The miRNA-1 expression level in cancer tissues was 0.41±0.07 times lower compared with the adjacent tissues (P<0.01). A low miRNA expression level was correlated with a low survival rate of patients. In vitro, miRNA-1 inhibited the proliferation and migration of cervical cancer cell lines by downregulating c-Met mRNA. When miRNA-1 expression was downregulated in cervical cancer tissues, the inhibition of c-Met expression was reversed. The upregulation of c-Met expression levels was able to inhibit E-cadherin expression, which triggered the proliferation, migration and infiltration of cancer cells, and thus reduced patient survival rates.
Analysis of Internal Knee Forces Allows for the Prediction of Rupture Events in a Clinically Relevant Model of Anterior Cruciate Ligament Injuries

Background: A recently developed mechanical impact simulator induced an anterior cruciate ligament (ACL) rupture via the application of a combination of inverse dynamics–based knee abduction moment (KAM), anterior tibial shear force (ATS), and internal tibial rotation moment with impulsive compression in a cohort of cadaveric limbs. However, there remains an opportunity to further define the interaction of internal forces and moments at the knee and their respective influence on injury events. Purpose: To identify the influence of internal knee loads on an ACL injury event using a cadaveric impact simulator. Study Design: Controlled laboratory study. Methods: Drop-landing simulations were performed and analyzed on 30 fresh-frozen cadaveric knees with a validated mechanical impact simulator. Internal forces and moments at the knee joint center were calculated using data from a 6-axis load cell recorded on the femur during testing. Kinetic data from a total of 1083 trials that included 30 ACL injury trials were used as inputs for principal component (PC) analysis to identify the most critical features of loading waveforms. Logistic regression analysis with a stepwise selection was used to select the PCs that predicted an ACL injury. Injurious waveforms were reconstructed with selected PCs in logistic regression analysis. Results: A total of 3 PCs were selected in logistic regression analysis that developed a significant model (P < .001). The external loading of KAM was highly correlated with PC1 (ρ < –0.8; P < .001), which explained the majority (>69%) of the injurious waveforms reconstructed with the 3 selected PCs. The injurious waveforms demonstrated a larger internal knee adduction moment and lateral tibial force. After the ACL was ruptured, decreased posterior tibial force was observed in injury trials. Conclusion: These findings give us a better understanding of ACL injury mechanisms using 6-axis kinetics from an in vitro simulator. An ACL rupture was correlated with an internal knee adduction moment (external KAM) and was augmented by ATS and lateral tibial force induced by an impact, which distorted the ACL insertion orientation. Clinical Relevance: The ACL injury mechanism explained in this study may help target injury prevention programs to decrease injurious knee loading (KAM, ATS, and lateral tibial force) during landing tasks.
Predictive and prognostic value of phosphorylated c-KIT and PDGFRA in advanced non-small cell lung cancer harboring ALK fusion

Secondary KIT gene amplification leads to tyrosine kinase inhibitor resistance in anaplastic lymphoma kinase (ALK) fusion-positive advanced non-small cell lung cancer (NSCLC). The presence of the 4q12 amplicon causes the activation of downstream mast/stem cell growth factor receptor Kit (c-Kit) or platelet-derived growth factor receptor α (PDGFRA) signaling pathways. Therefore, in the present study, the association between the functional proteins phosphorylated c-Kit (p-c-Kit) and phosphorylated PDGFRA (p-PDGFRA) and the prognosis of ALK fusion NSCLC was investigated. Advanced stage NSCLC samples with ALK fusion were tested for their p-c-Kit and p-PDGFRA content by immunohistochemical staining, and for its association with crizotinib efficacy and the survival of the patients. Of 64 eligible ALK-positive patients with NSCLC, 30 (46.9%) were p-c-Kit-positive and 10 (15.7%) were p-PDGFRA-positive. Brain metastases were more common in ALK-positive cases that were p-PDGFRA-positive compared with those who were p-PDGFRA-negative. ALK-positive patients treated with crizotinib, who exhibited high levels of p-c-Kit had significantly lower progression-free survival times than those with low levels. In addition, the patients with high levels of p-c-Kit exhibited lower overall survival times than those with low levels. Furthermore, multivariate analysis indicated that high levels of p-c-Kit in patients with ALK fusion was the only significant predictive factor for crizotinib efficacy and was a prognostic factor for poor overall survival time. However, no statistically significant difference was observed in the survival of patients with different p-PDGFRA levels. p-PDGFRA was more frequently expressed in the ALK-positive cases with brain metastasis. c-Kit signaling activation may be associated with poor efficacy of crizotinib and poor prognosis in advanced ALK fusion NSCLC.
Prognostic value of KRAS/TP53/PIK3CA in non-small cell lung cancer

The present study explored the association between KRAS proto-oncogene GTPase (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) and tumor protein p53 (TP53) mutations, and the clinical features and survival prognosis in 50 patients with non-small cell lung cancer (NSCLC). The most common concurrent single gene mutation was TP53, followed by KRAS and PIK3CA. Co-existing mutations were found in 17 patients. KRAS, PIK3CA and TP53 mutations were associated with carbohydrate antigen 19-9 expression, invasive growth, vacuolar signs and margin lobulation on chest CT. The incidence of distant metastasis (bone and adrenal) with KRAS and TP53 mutations was greater than that of local metastasis (pleura). Patients with the wild-type genes experienced longer progression-free survival (PFS) times than those with KRAS, TP53, KRAS/TP53 or PIK3CA/TP53 mutations. Patients with KRAS/TP53 or PIK3CA/TP53 mutations experienced shorter PFS times than those with a single KRAS or TP53 mutation. KRAS, PIK3CA and TP53 mutations were associated with distant metastases and a poor prognosis. Patients with NSCLC should receive routine KRAS, PIK3CA and TP53 gene sequencing to determine mutations for the analysis of clinical characteristics and prognosis.
Precision prevention: A focused response to shifting paradigms in healthcare

Human health and disease are defined at the intersection of molecules, environment, and lifestyle, which combined determine phenotypic outcomes. To date, most clinical applications in the precision medicine space have focused on DNA, with lesser attention given to the biology encoded by RNA molecules, or the complexity of biological regulation at the level of proteins and metabolites. The totality of this information must be integrated in ways that allow for implementation of knowledge-based health promotion and prevention strategies that can help address current limitations in healthcare delivery. This review describes recent advances in the development of diagnostic tools for early detection and stratification of individuals suffering from chronic obstructive pulmonary disease and their heightened risk for the development of lung malignancies. Impact statement The study of LINE-1 retroelements and their role in the pathogenesis of diseases of the lung such as COPD and lung cancer may provide valuable diagnostic and therapeutic tools to identify pre-emptively individuals at risk of pulmonary disease progression. Limited information is presently available on the role of LINE-1 in the regulation of disease phenotypes and the development of novel therapeutics designed to curtail LINE-1-mediated pathogenesis. Successful implementation of precision prevention strategies may help to spare those impacted by obstructive pulmonary disease from continued deterioration, while realizing significant cost savings and improved quality of healthcare.
Biatoraalnetorum (Ramalinaceae, Lecanorales), a new lichen species from western North America

Abstract Biatoraalnetorum S. Ekman & Tønsberg, a lichenised ascomycete in the family Ramalinaceae (Lecanorales, Lecanoromycetes), is described as new to science. It is distinct from other species of Biatora in the combination of mainly three-septate ascospores, a crustose thallus forming distinctly delimited soralia that develop by disintegration of convex pustules and the production of atranorin in the thallus and apothecia. The species is known from the Pacific Northwest of North America, where it inhabits the smooth bark of Alnusalnobetulasubsp.sinuata and A.rubra. Biatoraalnetorum is also a new host for the lichenicolous ascomycete Sclerococcumtoensbergii Diederich.
Low-Cost Tracking Systems Allow Fine Biomechanical Evaluation of Upper-Limb Daily-Life Gestures in Healthy People and Post-Stroke Patients

Since the release of the first Kinect in 2011, low-cost technologies for upper-limb evaluation has been employed frequently for rehabilitation purposes. However, a limited number of studies have assessed the potential of the Kinect V2 for motor evaluations. In this paper, a simple biomechanical protocol has been developed, in order to assess the performances of healthy people and patients, during daily-life reaching movements, with focus on some of the patients’ common compensatory strategies. The assessment considers shoulder range of motion, elbow range of motion, trunk compensatory strategies, and movement smoothness. Seventy-seven healthy people and twenty post-stroke patients participated to test the biomechanical assessment. The testing protocol included four different experimental conditions: (1) dominant limb and (2) non-dominant limb of 77 healthy people, and (3) the more impaired limb of 20 post-stroke hemiparetic patients, and (4) the less-impaired limb of 11 patients (subgroup of the original 20). Biomechanical performances of the four groups were compared. Results showed that the dominant and non-dominant limbs of healthy people had comparable performances (p > 0.05). On the contrary, condition (3) showed statistically significant differences between the healthy dominant/non-dominant limb and the less-affected limb in hemiparetic patients, for all parameters of assessment (p < 0.001). In some cases, the less-affected limb of the patients also showed statistical differences (p < 0.05), with respect to the healthy people. Such results suggest that Kinect V2 has the potential for being employed at home, laboratory or clinical environment, for the evaluation of patients’ motor performances.
Blue Electroluminescent Al2O3/Tm2O3 Nanolaminate Films Fabricated by Atomic Layer Deposition on Silicon

Realization of a silicon-based light source is of significant importance for the future development of optoelectronics and telecommunications. Here, nanolaminate Al2O3/Tm2O3 films are fabricated on silicon utilizing atomic layer deposition, and intense blue electroluminescence (EL) from Tm3+ ions is achieved in the metal-oxide-semiconductor structured luminescent devices based on them. Precise control of the nanolaminates enables the study on the influence of the Tm dopant layers and the distance between every Tm2O3 layer on the EL performance. The 456 nm blue EL from Tm3+ ions shows a maximum power density of 0.15 mW/cm2. The EL intensities and decay lifetime decrease with excessive Tm dopant cycles due to the reduction of optically active Tm3+ ions. Cross-relaxation among adjacent Tm2O3 dopant layers reduces the blue EL intensity and the decay lifetime, which strongly depends on the Al2O3 sublayer thickness, with a critical value of ~3 nm. The EL is attributed to the impact excitation of the Tm3+ ions by hot electrons in Al2O3 matrix via Poole–Frenkel mechanism.
Self-efficacy and Satisfaction With Teaching in Online Courses

Background Growth of online education has increased the demand for satisfied educators with perceived self-efficacy in online teaching. Teaching self-efficacy is an indicator of the belief that one can make a difference in student learning outcomes. Purpose The aim of this study was to examine the level of teaching self-efficacy and satisfaction of online nursing faculty. Methods This study used a descriptive cross-sectional survey design. Faculty satisfaction was measured by the Online Instructor Satisfaction Measure, and self-efficacy for online teaching was measured by the Michigan Nurse Educator's Sense of Efficacy for Online Teaching instrument. Results The sample included 100 faculty in multiple schools of nursing who taught at least 1 online course in RN to BSN or graduate nursing programs. Overall, participants had relatively high levels of online teaching self-efficacy and satisfaction. Conclusions Teacher self-efficacy can be facilitated through faculty development and increased experience teaching online.
Decreasing frequency and improved outcomes of hepatitis C‐related liver transplantation in the era of direct‐acting antivirals – a retrospective cohort study

Benefit of direct‐acting antivirals (DAA) for hepatitis C virus (HCV) on clinical outcomes is unclear. We examined temporal trends in liver transplant (LT) listings, receipt of LT, re‐LT, and survival between pre‐DAA (2009–2012) and DAA era (2013–2016) using UNOS database. Of 32 319 first adult LT, 15 049 (47%) were performed for HCV. Trends on listing, first LT, and of re‐LT for HCV showed 23%, 20%, and 21% decrease in DAA compared to pre‐DAA era (P < 0.0001). One‐year liver graft and patient survival among HCV LT improved in DAA era (90% vs. 86% and 92% vs. 88%, respectively, P < 0.0001). Non‐HCV LT showed no improvement in survival (89% vs. 89% and 92% vs. 92.4%, P = NS). On cox regression, compared to non‐HCV LTs in DAA era, LT for HCV in pre‐DAA era had worse patient survival (HR 1.56 [1.04–2.35]). The outcome was similar when compared to LTs for HCV in DAA era and for non‐HCV in pre‐DAA era. Burden of HCV‐related LT waitlist and LT is declining in DAA era, with improved post‐transplant outcomes, more so in later than earlier DAA era. Our findings negate recent Cochrane meta‐analysis on DAA therapy and encourage studies to examine HCV clinical outcomes outside LT setting.
Hyperendemic Chlamydia trachomatis sexually transmitted infections among females represent a high burden of asymptomatic disease and health disparity among Pacific Islanders in Fiji

Background Chlamydia trachomatis is the most common bacterial sexually transmitted infection worldwide with some of the highest prevalence rates among Pacific Island Countries where syndromic management is practiced. However, little is known about the true prevalence and risk indicators for infection among neglected populations in these countries that suffer from health disparities. Methodology/Principal findings Consecutive sampling was used to enroll sexually active females, aged 18–40 years, attending 12 Fijian Ministry of Health and Medical Services Health Centers and outreach locations from February to December, 2018. A Behavioral Surveillance Survey was administered to assess risk indicators for infection. Signs and symptoms were recorded, and vaginal swabs were tested for C. trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Candida and bacterial vaginosis. Bivariate and multivariate logistic regression analyses were performed using R-Studio. Of 577 participants, 103 (17.85%) were infected with C. trachomatis of whom 80% were asymptomatic and only 11 met criteria for syndromic management; 38.8% of infected women were 18–24 years old with a prevalence of 30.5%. 91.7% of participants intermittently or did not use condoms. C. trachomatis infection was associated with iTaukei ethnicity (OR 21.41 [95% CI: 6.38–133.53]); two lifetime partners (OR 2.12 [95% CI: 1.08–4.18]); and N. gonorrhoeae co-infection (OR 9.56 [95% CI: 3.67–28.15]) in multivariate analyses. Conclusions A disproportionately high burden of C. trachomatis is present among young asymptomatic women in Fiji of iTaukei ethnicity despite the low number of lifetime partners. Syndromic management and lack of barrier contraceptives contribute to hyperendemic levels. Strategic STI education and screening of at-risk adolescents, young women, and their partner(s) with appropriate treatment are urgently needed to control the epidemic.
Novel Organ Perfusion and Preservation Strategies in Transplantation – Where Are We Going in the United Kingdom?

Supplemental Digital Content is available in the text. This review article focuses on current clinical outcomes with novel perfusion strategies in organ transplantation. Broadly, these approaches can be divided into in situ regional perfusion in the donor and ex situ machine perfusion of individual organs. In both settings, hypothermic and normothermic techniques are in clinical use. Evidence from full text articles, abstracts, and data presented at scientific meetings has been considered. Animal studies have been excluded. The review focuses on kidney, liver, pancreas, heart, and lungs. The level of evidence ranges from quasi-experimental work in human pancreas to multiple meta-analyses of Randomized Controlled Trials for hypothermic machine perfusion of kidneys. The data in this review were presented to experts in organ perfusion and preservation at the National Health Service Blood and Transplant Preservation and Perfusion Future Strategy Summit in London in October 2018. The outcomes of the meeting are discussed in the review after due consideration of the available evidence base.
VEGFR2 Blockade Improves Renal Damage in an Experimental Model of Type 2 Diabetic Nephropathy

The absence of optimal treatments for Diabetic Nephropathy (DN) highlights the importance of the search for novel therapeutic targets. The vascular endothelial growth factor receptor 2 (VEGFR2) pathway is activated in experimental and human DN, but the effects of its blockade in experimental models of DN is still controversial. Here, we test the effects of a therapeutic anti-VEGFR2 treatment, using a VEGFR2 kinase inhibitor, on the progression of renal damage in the BTBR ob/ob (leptin deficiency mutation) mice. This experimental diabetic model develops histological characteristics mimicking the key features of advanced human DN. A VEGFR2 pathway-activation blockade using the VEGFR2 kinase inhibitor SU5416, starting after kidney disease development, improves renal function, glomerular damage (mesangial matrix expansion and basement membrane thickening), tubulointerstitial inflammation and tubular atrophy, compared to untreated diabetic mice. The downstream mechanisms involved in these beneficial effects of VEGFR2 blockade include gene expression restoration of podocyte markers and downregulation of renal injury biomarkers and pro-inflammatory mediators. Several ligands can activate VEGFR2, including the canonical ligands VEGFs and GREMLIN. Activation of a GREMLIN/VEGFR2 pathway, but not other ligands, is correlated with renal damage progression in BTBR ob/ob diabetic mice. RNA sequencing analysis of GREMLIN-regulated genes confirm the modulation of proinflammatory genes and related-molecular pathways. Overall, these data show that a GREMLIN/VEGFR2 pathway activation is involved in diabetic kidney disease and could potentially be a novel therapeutic target in this clinical condition.
Driver mutations in acute myeloid leukemia.

PURPOSE OF REVIEW The mutational landscape of acute myeloid leukemia (AML) has revised diagnostic, prognostic, and therapeutic schemata over the past decade. Recurrently mutated AML genes have functional consequences beyond typical oncogene-driven growth and loss of tumor suppresser function. RECENT FINDINGS Large-scale genomic sequencing efforts have mapped the complexity of AML and trials of mutation-based targeted therapy has led to several FDA-approved drugs for mutant-specific AML. However, many recurrent mutations have been identified across a spectrum from clonal hematopoiesis to myelodysplasia to overt AML, such as effectors of DNA methylation, chromatin modifiers, and spliceosomal machinery. The functional effects of these mutations are the basis for substantial discovery. SUMMARY Understanding the molecular and pathophysiologic functions of key genes that exert leukemogenic potential is essential towards translating these findings into better treatment for AML.
Diabetic Neuropathy Is a Substantial Burden in People With Type 1 Diabetes and Is Strongly Associated With Socioeconomic Disadvantage: A Population-Representative Study From Scotland

OBJECTIVE To assess the contemporaneous prevalence of diabetic peripheral neuropathy (DPN) in people with type 1 diabetes (T1D) in Scotland and study its cross-sectional association with risk factors and other diabetic complications. RESEARCH DESIGN AND METHODS We analyzed data from a large representative sample of adults with T1D (N = 5,558). We assessed the presence of symptomatic neuropathy using the dichotomized (≥4) Michigan Neuropathy Screening Instrument Patient Questionnaire score. Logistic regression models were used to investigate associations between DPN and risk factors, as well as with other complications. RESULTS The burden of DPN is substantial with 13% prevalence overall. Adjusting for attained age, diabetes duration, and sex, the odds of DPN increased mainly with waist-to-hip ratio, lipids, poor glycemic control (odds ratio 1.51 [95% CI 1.21–1.89] for levels of 75 vs. 53 mmol/mol), ever versus never smoking (1.67 [1.37–2.03]), and worse renal function (1.96 [1.03–3.74] for estimated glomerular filtration rate levels <30 vs. ≥90 mL/min/1.73 m2). The odds significantly decreased with higher HDL cholesterol (0.77 [0.66–0.89] per mmol/L). Living in more deprived areas was associated with DPN (2.17 [1.78–2.65]) for more versus less deprived areas adjusted for other risk factors. Finally, individuals with prevalent DPN were much more likely than others to have other diabetes complications. CONCLUSIONS Diabetic neuropathy remains substantial, particularly affecting those in the most socioeconomically deprived groups. Those with clinically manifest neuropathy also have a higher burden of other complications and elevated levels of modifiable risk factors. These data suggest that there is considerable scope to reduce neuropathy rates and narrow the socioeconomic differential by better risk factor control.