Miracle-dz/UniFAR-FTUs huggingface dataset:
Contemporary balloon aortic valvuloplasty: Changing indications and refined technique

Even if un to improve long‐term prognosis, balloon aortic valvuloplasty (BAV) may be useful in selected patients with symptomatic severe aortic stenosis either as a bridge to surgical or transcatheter valve replacement (aortic valve replacement [AVR] or transcatheter aortic valve implantation [TAVI]) or as a triage strategy for patients with uncertain indications. International guidelines recommend BAV as: a “bridge” to AVR/TAVI, a “trial” in patients with undetermined symptoms, or a “bridge‐to‐decision” in case of comorbidities. However, in clinical practice, BAV is also used as a palliative measure to improve hemodynamics and quality of life in many patients who are excluded from AVR/TAVI. Finally, BAV is often performed during TAVI to facilitate prosthesis delivery, optimize frame expansion, or for bioprosthetic valve fracture in selected valve‐in‐valve procedures. Technical innovations, which allow for a mini‐invasive approach via transradial access and pacing delivered through the wire, have led to a decrease in complications over time. This review focuses on contemporary BAV with a specific emphasis on new indications, innovative techniques, and specific complex patient subgroups.
Permanent Pro-Tumorigenic Shift in Adipose Tissue-Derived Mesenchymal Stromal Cells Induced by Breast Malignancy

During cancer progression, breast tumor cells interact with adjacent adipose tissue, which has been shown to be engaged in cancer aggressiveness. However, the tumor-directed changes in adipose tissue-resident stromal cells affected by the tumor–stroma communication are still poorly understood. The acquired changes might remain in the tissue even after tumor removal and may contribute to tumor relapse. We investigated functional properties (migratory capacity, expression and secretion profile) of mesenchymal stromal cells isolated from healthy (n = 9) and tumor-distant breast adipose tissue (n = 32). Cancer patient-derived mesenchymal stromal cells (MSCs) (MSC-CA) exhibited a significantly disarranged secretion profile and proliferation potential. Co-culture with MDA-MB-231, T47D and JIMT-1, representing different subtypes of breast cancer, was used to analyze the effect of MSCs on proliferation, invasion and tumorigenicity. The MSC-CA enhanced tumorigenicity and altered xenograft composition in immunodeficient mice. Histological analysis revealed collective cell invasion with a specific invasive front of EMT-positive tumor cells as well as invasion of cancer cells to the nerve-surrounding space. This study identifies that adipose tissue-derived mesenchymal stromal cells are primed and permanently altered by tumor presence in breast tissue and have the potential to increase tumor cell invasive ability through the activation of epithelial-to-mesenchymal transition in tumor cells.
Finite element analysis of a one-piece zirconia implant in anterior single tooth implant applications

This study evaluated the von Mises stress (MPa) and equivalent strain occurring around monolithic yttria-zirconia (Zir) implant using three clinically simulated finite element analysis (FEA) models for a missing maxillary central incisor. Two unidentified patients’ cone-beam computed tomography (CBCT) datasets with and without right maxillary central incisor were used to create the FEA models. Three different FEA models were made with bone structures that represent a healed socket (HS), reduced bone width edentulous site (RB), and immediate extraction socket with graft (EG). A one-piece abutment-implant fixture mimicking Straumann Standard Plus tissue level RN 4.1 X 11.8mm, for titanium alloy (Ti) and Zir were modeled. 178 N oblique load and 200 N vertical load were used to simulate occlusal loading. Von Mises stress and equivalent strain values for around each implant model were measured. Within the HS and RB models the labial-cervical region in the cortical bone exhibited highest stress, with Zir having statistically significant lower stress-strain means than Ti in both labial and palatal aspects. For the EG model the labial-cervical area had no statistically significant difference between Ti and Zir; however, Zir performed better than Ti against the graft. FEA models suggest that Ti, a more elastic material than Zir, contributes to the transduction of more overall forces to the socket compared to Zir. Thus, compared to Ti implants, Zir implants may be less prone to peri-implant bone overloading and subsequent bone loss in high stress areas especially in the labial-cervical region of the cortical bone. Zir implants respond to occlusal loading differently than Ti implants. Zir implants may be more favorable in non-grafted edentulous or immediate extraction with grafting.
LINC00662 triggers malignant progression of chordoma by the activation of RNF144B via targeting miR-16-5p.

OBJECTIVE Chordoma is a rare malignant tumor difficult to diagnose and treat. Long non-coding RNAs acting as novel biomarkers are frequently reported in numerous cancers. The purpose of this study was to investigate the role of long intergenic non-coding RNA 00662 (LINC00662) and its associated action mechanisms in chordoma. MATERIALS AND METHODS The expression of LINC00662, Ring finger protein 144B (RNF144B), and microRNA-16-5p (miR-16-5p) was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The protein levels of RNF144B, cell proliferation markers (Cyclin D1 and Ki67), epithelial-mesenchymal transition (EMT) markers (E-cadherin, Vimentin and N-cadherin), and glycolysis markers [glucose transporter 1 (GLUT1), hexokinase II (HK2), and lactic dehydrogenase A (LDHA)] were determined by Western blot. Cell proliferation, the number of colonies, migration, and invasion were investigated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, and transwell assays, respectively. Glycolysis progress was evaluated by the glycolysis stress test, glucose consumption, lactate production, and ATP production. The relationship between miR-16-5p and LINC00662 or RNF144B was predicted by the online bioinformatics tool starBase and verified by Dual-Luciferase reporter assay. Xenograft tumor model was established to monitor the role of LINC00662 in vivo. RESULTS LINC00662 and RNF144B were aberrantly upregulated in chordoma tissues. Knockdown of LINC00662 or RNF144B impeded proliferation, colony formation, invasion, migration, EMT, and glycolysis in chordoma cells. Besides, RNF144B overexpression reversed the role of LINC00662 knockdown. It was confirmed that miR-16-5p was a target of LINC00662, and miR-16-5p could target RNF144B. The relationship between LINC00662 and RNF144B was established by miR-16-5p. In addition, LINC00662 stable knockdown inhibited tumor growth in vivo. CONCLUSIONS LINC00662 participated in the malignant progression of chordoma by the promotion of RNF144B by acting as a sponge of miR-16-5p, suggesting that LINC00662 was a promising therapeutic target for chordoma.
Patients’ preferences of cutaneous leishmaniasis treatment outcomes: Findings from an international qualitative study

Background Cutaneous leishmaniasis (CL) is a disease that often affects exposed skin areas and may heal leaving lifelong scars. Patients’ expectations from treatment are rarely considered in drug development for CL. An initiative aiming to address shortcomings in clinical trial design and conduct for CL treatments involving the researchers’ community is on-going. This manuscript presents patient-preferred outcomes for CL and an assessment on how to consider these in the conduct of future trials. Methodology/Principal findings We report preferred treatment outcomes by 74 patients with confirmed CL in endemic regions of Brazil, Burkina Faso, Colombia, Iran, Morocco, Peru and Tunisia during individual in-depth interviews. Beyond outcomes customarily considered in trials (such as lesion appearance and adverse events), patients talked about a large number of outcomes related to quality of life, such as pain, scar formation, and others affecting their work and daily activities. They also reported fears around getting rid of the parasite, disease recurrence, and possible sequelae. Conclusions/Significance The study results provide a rich insight into important outcomes for CL treatments, as well as related topics, from the perspective of a diverse patient population. Among the outcomes identified, we argue that those related to quality of life as well as recurrence should be included to a greater extent for assessment in clinical trials, and discuss the suitability of measurement instruments such as the Dermatology Quality of Life Index (DLQI). Interviews also point out the potential need to address concerns related to parasitological cure or scar formation, such as social stigmatization and disability. In addition, patients should be given information in order to clarify reported misconceptions. This study therefore suggests a methodology for consulting CL patients on outcomes as elements of clinical trial design, and how to incorporate these outcomes in trials. It also discusses how reported outcomes could be addressed in clinical care.
Notch Signaling in Skeletal Development, Homeostasis and Pathogenesis

Skeletal development is a complex process which requires the tight regulation of gene activation and suppression in response to local signaling pathways. Among these pathways, Notch signaling is implicated in governing cell fate determination, proliferation, differentiation and apoptosis of skeletal cells-osteoblasts, osteoclasts, osteocytes and chondrocytes. Moreover, human genetic mutations in Notch components emphasize the critical roles of Notch signaling in skeletal development and homeostasis. In this review, we focus on the physiological roles of Notch signaling in skeletogenesis, postnatal bone and cartilage homeostasis and fracture repair. We also discuss the pathological gain- and loss-of-function of Notch signaling in bone and cartilage, resulting in osteosarcoma and age-related degenerative diseases, such as osteoporosis and osteoarthritis. Understanding the physiological and pathological function of Notch signaling in skeletal tissues using animal models and human genetics will provide new insights into disease pathogenesis and offer novel approaches for the treatment of bone/cartilage diseases.
Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury

Human breast milk is the optimal source of nutrition for infant growth and development. Breast milk fats and their downstream derivatives of fatty acids and fatty acid-derived terminal mediators not only provide an energy source but also are important regulators of development, immune function, and metabolism. The composition of the lipids and fatty acids determines the nutritional and physicochemical properties of human milk fat. Essential fatty acids, including long-chain polyunsaturated fatty acids (LCPUFAs) and specialized pro-resolving mediators, are critical for growth, organogenesis, and regulation of inflammation. Combined data including in vitro, in vivo, and human cohort studies support the beneficial effects of human breast milk in intestinal development and in reducing the risk of intestinal injury. Human milk has been shown to reduce the occurrence of necrotizing enterocolitis (NEC), a common gastrointestinal disease in preterm infants. Preterm infants fed human breast milk are less likely to develop NEC compared to preterm infants receiving infant formula. Intestinal development and its physiological functions are highly adaptive to changes in nutritional status influencing the susceptibility towards intestinal injury in response to pathological challenges. In this review, we focus on lipids and fatty acids present in breast milk and their impact on neonatal gut development and the risk of disease.
Early weight gain predicts treatment response in adolescents with anorexia nervosa enrolled in a family-based partial hospitalization program.

OBJECTIVE Improved treatment outcome in family-based treatment (FBT) for anorexia nervosa (AN) is predicted by weight gain occurring early in the course of treatment (i.e., about 4 lbs by week 4). Although prior work suggests that early weight gain in higher levels of care (e.g., partial hospitalization programs [PHP]) predicts weight restoration at discharge, no study has examined the specific rate of gain within FBT-informed PHP programs that best predicts treatment response. METHOD This study examined rate of weight gain in pounds and percent expected body weight (EBW) that predicts positive outcome in 70 patients (M age = 15.49 years, SD = 2.56) with AN who were enrolled in a family-based PHP. RESULTS Receiver operator characteristic analyses demonstrated that changes in %EBW during weeks 2-5 were more useful than changes in weight in predicting positive outcome. Gaining at least 8.9 pounds or over 8% of EBW in the first 4 weeks of treatment significantly predicted positive outcome. DISCUSSION Findings suggest that positive outcome in an FBT-informed PHP is predicted by rapid weight gain in the initial weeks of treatment. Research is needed to identify specific family and patient characteristics that facilitate weight gain and to develop corresponding interventions to improve outcome.
Antifungal susceptibility of Candida species to copper oxide nanoparticles on polycaprolactone fibers (PCL-CuONPs)

The integration of metallic or ceramic nanoparticles in polymer matrices has improved the antimicrobial and antifungal behavior, resulting in the search for composites with increased bactericidal and antimycotic properties. A polycaprolactone fibers with copper oxide nanoparticles was prepared. Polycaprolactone-copper fibers (PCL- CuONPs) were prepared into two major steps in situ method: (a) Synthesis of CuO particles, then (b) incorporation of polycaprolactone to electrospun process. The first step is the reduction of Cu+2 ions by gallic acid in N,N-dimethylformamide and tetrahydrofuran solution with the simple addition of polycaprolactone in the solution for the second electrospun step. Raman spectra provide information about the nature of the copper oxide synthesized. There are three Raman peaks in the sample, at 294 and 581 cm-1 and a very broad band from 400 to 600 cm-1 which are characteristics bands for CuO. Scanning electron microscopy (TEM) revealed copper oxide nanoparticles with semispherical shapes with diameter 35 ±11 nm. Dynamic light scattering (DLS) analysis showed uniform CuONPs in a range of 88±11 nm. Scanning electron microscopy (SEM) of PCL-CuONps reveled fibers with diameters ranging from 925 to 1080 nm were successfully obtained by electrospinning technique. Orientation, morphology and diameter were influenced by the increment on CuONPs concentration, with the smaller diameter present in samples prepared from low concentrated solutions. The antimycotic applicability of the composite was evaluated to determine the antifungal activity in three species of the genus Candida (Candida albicans, Candida glabrata and Candida tropicalis). PCL-CuONPs exhibit a considerable antifungal effect on all species tested. The preparation of PCL-CuONPs was simple, fast and low-cost for practical application as an antifungal dressing.
The Impact of Environmental Conditions on Urban Eco-Sustainable Total Factor Productivity: A Case Study of 21 Cities in Guangdong Province, China

Environmental protection has attracted much attention. This study first describes the status of the ecological environment and then uses data envelopment analysis and the system the system generalized method of moments (GMM) model to study the relationship between the environmental status and ecological sustainable total factor productivity (ESTFP) in 21 prefecture-level cities of Guangdong Province. The main conclusions of this study are as follows. (1) The ecological index (EI), which reflects the ecological environment, shows a general trend of first decreasing and then rising. The average EI value decreased from 80.95 in 2008 to 68.71 in 2011 and then gradually increased to 74.76 in 2017. (2) The ecological sustainable total factor productivity (ESTFP = 0.960), including the two additional dimensions of the urban resource consumption index (URCI) and urban pollution discharge index (UPDI), is better than the traditional total factor productivity (TFP = 0.954). (3) The EI has a highly significant positive promoting effect on ESTFP at a significance level of 1%. The methods and results from this research provide an important scientific reference for the research on urban production efficiency and sustainable urban development in China.
Recovery of serum testosterone following neoadjuvant androgen deprivation therapy in Japanese prostate cancer patients treated with low-dose rate brachytherapy

Abstract Objective To investigate the time course of total testosterone (TT) recovery after cessation of androgen deprivation therapy (ADT) in Japanese patients treated with brachytherapy. Methods In total, 125 patients with prostate cancer received 6 months of neoadjuvant ADT (nADT) followed by low-dose rate (LDR) brachytherapy. TT was measured every 3 months after cessation of nADT, and some predictive factors affecting TT recovery were analyzed. Results The cumulative incidence rates of TT recovery to normal levels (TT ≥ 3.0 ng/mL) after 12 and 24 months cessation were 49.6% and 81.6%, respectively. The median interval to recover to normal TT was 15 months. In multivariate analysis, the use of a gonadotropin-releasing hormone (GnRH) antagonist as nADT significantly earlier improved to recovery to normal TT level (p = 0.046). Conversely, higher body mass index (BMI) and hypertension significantly prolonged TT recovery to normal (p = 0.026 and p = 0.026, respectively). Conclusions Approximately one-fifth of patients still had low TT levels 2 years after the cessation of 6 months nADT before LDR brachytherapy. Use of a GnRH agonist, higher BMI, and hypertension were the predictive factors for slower TT recovery to normal TT levels after the cessation of nADT.
Integrated bioinformatics analysis of the crucial candidate genes and pathways associated with glucocorticoid resistance in acute lymphoblastic leukemia

Glucocorticoids (GC) are the foundation of the chemotherapy regimen in acute lymphoblastic leukemia (ALL). However, resistance to GC is observed more frequently than resistance to other chemotherapy agents in patients with ALL relapse. Moreover, the mechanism underlying the development of GC resistance in ALL has not yet been fully uncovered. In this study, we used bioinformatic analysis methods to integrate the candidate genes and pathways participating in GC resistance in ALL and subsequently verified the bioinformatics findings with in vitro cell experiments. Ninety‐nine significant common differentially expressed genes (DEGs) associated with GC resistance were determined by integrating two gene profile datasets, including GC‐sensitive and ‐resistant samples. Using Kyoto Encyclopedia of Genes and Genomes (KEGG) and REACTOME pathways analysis, the signaling pathways in which DEGs were significantly enriched were clustered. The GC resistance‐related biologically functional interactions were visualized as DEG‐associated Protein–Protein Interaction (PPI) network complexes, with 98 nodes and 127 edges. MYC, a node which displayed the highest connectivity in all edges, was highlighted as the core gene in the PPI network. Increased C‐MYC expression was observed in adriamycin‐resistant BALL‐1/ADR cells, which we demonstrated was also resistant to dexamethasone. These results outlined a panorama in which the solitary and scattered experimental results were integrated and expanded. The potential promising target of the candidate pathways and genes involved in GC resistance of ALL was concomitantly revealed.
Association of Formal and Informal Social Support With Health-Related Quality of Life Among Chinese Rural Elders

Objectives: To explore the association of formal and informal social support with health-related quality of life (HRQOL) among Chinese rural elders and further investigate the influence of quantity and quality of social support on their HRQOL. Methods: The sample of 4189 Chinese rural elders over 60 years old was acquired from the 2015 China Health and Retirement Longitudinal Study (CHARLS). The HRQOL was evaluated by EQ-5D-3L questionnaire. The social support assessment was mainly based on the social support rating scale (SSRS), and Tobit regression analysis was used to explore the impact of social support on HRQOL. Results: The average EQ-5D index score (0 to 1) of the Chinese rural elders was 0.78 ± 0.16. Participants who were male or with better education were found to have higher scores. Those elders living alone, suffering from chronic diseases or disabled acquired lower scores. As for formal social support, higher medical or pension insurance and more social activities statistically significantly possessed higher scores. As for informal social support, higher number of offspring had a significant association with lower scores, while more contact with children and financial support from family were shown to be statistically significantly associated with higher scores after controlling for sociodemographic characteristics. The quality of social support is more important than its quantity. An interesting finding was that the EQ-5D index scores did not support the Chinese traditional belief that ‘the more children, the more blessings’. Conclusions: The EQ-5D index scores of the rural elders in China is above the median level based on the scores of EQ-5D. Social support is significantly associated with elderly peoples’ quality of life. The results would be significant for accurately improving the life quality of Chinese rural elders from the perspective of social support.
CBD (Cannabidiol) Product Attitudes, Knowledge, and Use Among Young Adults

Abstract Background: Cannabidiol (CBD), a non-psychoactive component of cannabis is marketed as a potential treatment for many conditions and widely available to purchase as a dietary supplement. In 2017, sales of CBD exceeded 820 million dollars despite many unconfirmed health claims, murky legality, and limited product efficacy and safety testing. Purpose/Objectives: This study aims to explore cannabidiol (CBD) knowledge, attitudes, and use among young adults. Methods: The anonymous 36-item survey developed using Qualtrics was distributed via social media from November 2018 to January 2019 with 340 respondents. Results: Of the 340 respondents, 242 reported they had heard of CBD, and 135 reported using CBD products. CBD users were primarily white, female, without children, made less than $25,000 per year, and unmarried. Most commonly used CBD products were edibles (56.30%), tinctures (54.07%), and vape (38.52%). Top reasons for use included stress relief (65.39%), relaxation (54.81%), and sleep improvement (42.22%). Many respondents reported using guesswork to determine dosage, and over half of respondents reported at least one unanticipated side effect. Conclusions/Importance: This study revealed that many users are not responsibly using CBD products, many believe CBD products provide health benefits that are not yet scientifically proven, and they are not knowledgeable about legal and regulatory issues. Until CBD use is more thoroughly researched and has more comprehensive regulation, public health professionals should address alternative stress and anxiety treatment methods.