Miracle-dz/UniFAR-FTUs huggingface dataset:
Antisense Oligonucleotide-Based Rescue of Aberrant Splicing Defects Caused by 15 Pathogenic Variants in ABCA4

The discovery of novel intronic variants in the ABCA4 locus has contributed significantly to solving the missing heritability in Stargardt disease (STGD1). The increasing number of variants affecting pre-mRNA splicing makes ABCA4 a suitable candidate for antisense oligonucleotide (AON)-based splicing modulation therapies. In this study, AON-based splicing modulation was assessed for 15 recently described intronic variants (three near-exon and 12 deep-intronic variants). In total, 26 AONs were designed and tested in vitro using a midigene-based splice system. Overall, partial or complete splicing correction was observed for two variants causing exon elongation and all variants causing pseudoexon inclusion. Together, our results confirm the high potential of AONs for the development of future RNA therapies to correct splicing defects causing STGD1.
Novel Single Inhibitor of HDAC6/8 and Dual Inhibitor of PI3K/HDAC6 as Potential Alternative Treatments for Prostate Cancer

Background: Prostate cancer is the second most frequently diagnosed malignancy worldwide. Here, the cytotoxic and antimetastatic effects of a new HDAC6/8 inhibitor, LASSBio-1911, and a new dual-PI3K/HDAC6 inhibitor, LASSBio-2208, were evaluated against PC3 prostate cancer cell line. Methods: A MTT assay was used to assess the cell viability. Annexin V/propidium iodide (PI) was used to detect apoptotic cell death and to analyze the cell cycle distribution. Interleukin 6 (IL-6) levels were measured by ELISA. A cell scratch assay was performed to assess cell migration, and the expression of proteins was estimated by Western blotting. Results: LASSBio-1911 and LASSBio-2208 exert cytotoxic effects against PC3 cells. However, LASSBio-2208 was demonstrated to be more potent than LASSBio-1911. The apoptosis assays showed that both compounds trigger apoptotic processes and cause the arrest of cells in the G2/M phase of the cell cycle. The Western blot analysis revealed that LASSBio-2208 significantly decreased the expression of p-JNK and JAK2. However, both compounds reduced the expression of p-STAT3, IL-6 secretion, and cell migration. Conclusions: LASSBio-1911 and LASSBio-2208 demonstrated significant activity in reducing cell viability and migration. These compounds can be further used as prototypes for the development of new potential anticancer alternative treatments.
Shape Prior Guided Instance Disparity Estimation for 3D Object Detection

In this paper, we propose a novel system named Disp R-CNN for 3D object detection from stereo images. Many recent works solve this problem by first recovering point clouds with disparity estimation and then apply a 3D detector. The disparity map is computed for the entire image, which is costly and fails to leverage category-specific prior. In contrast, we design an instance disparity estimation network (iDispNet) that predicts disparity only for pixels on objects of interest and learns a category-specific shape prior for more accurate disparity estimation. To address the challenge from scarcity of disparity annotation in training, we propose to use a statistical shape model to generate dense disparity pseudo-ground-truth without the need of LiDAR point clouds, which makes our system more widely applicable. Experiments on the KITTI dataset show that, when LiDAR ground-truth is not used at training time, Disp R-CNN outperforms previous state-of-the-art methods based on stereo input by 20 percent in terms of average precision for all categories. The code and pseudo-ground-truth data are available at the project page: https://github.com/zju3dv/disprcnn.
Phthalate Exposures in the Neonatal Intensive Care Unit

Background: Di-2-ethylhexyl phthalate (DEHP), a phthalate compound found in medical devices, may cause toxic effects in premature infants. In this study, the objective is to quantify DEHP exposures from various intravenous and respiratory therapy devices, and to use these values to predict typical exposure for an infant in a neonatal unit. Methods: Common IV products used on infants are directed through various types of IV tubing (IVT) and analyzed for DEHP content. DEHP exposure for infants receiving respiratory therapy was determined indirectly through analysis of urine DEHP metabolites. By deriving these values for DEHP we calculated the daily exposure to DEHP from common IV fluids (IVF) and respiratory devices during hospitalization in a neonatal unit. Results: IVF labeled DEHP-positive showed very high concentrations of DEHP, but when passed through IVT, substantial amounts were adsorbed. DEHP was undetectable with all DEHP-negative IVF tests, except when passed through DEHP-positive IVT. The DEHP leached from most respiratory devices was relatively modest, except that detected from bubble CPAP. In 14 very low birthweight infants, the mean DEHP exposure was 182,369 mcg/kg over 81.2 days of the initial hospitalization. Ninety-eight percent of the exposure was from respiratory devices, with bubble CPAP accounting for 95% of the total DEHP exposure in these infants. Conclusions: The DEHP exposure in our neonatal unit can be reduced markedly by avoiding or modifying bubble CPAP equipment and avoiding IV tubing containing DEHP.
Improving Patient Flow and Decreasing Patient Length of Stay in the Pediatric Emergency Department Through Implementation of a Fast Track

Increased utilization of the emergency department (ED) for low acuity concerns saturates EDs, leading to overcrowding. As the ED becomes crowded, the quality of care threatens patient safety and increases length of stay. To improve the efficiency of evaluation and discharge of low acuity patients in the pediatric ED, a performance improvement project was implemented to develop a Fast Track. An interdisciplinary team developed the process of Fast Track, as well as guidelines for low acuity patients who would be evaluated in the designated area by an advanced practice provider and registered nurse team. Within 14 months of operating, length of stay of low acuity patients triaged an emergency severity illness score of 4 or 5 dropped 36% (from 144 to 92 min). Pediatric patients who present to the ED with low acuity concerns can be effectively and efficiently cared for in a timely fashion in a pediatric ED Fast Track.
Wastes from Agricultural Silage Film Recycling Line as a Potential Polymer Materials

The recycling of plastics is currently one of the most significant industrial challenges. Due to the enormous amounts of plastic wastes generated by various industry branches, it is essential to look for potential methods for their utilization. In the presented work, we investigated the recycling potential of wastes originated from the agricultural films recycling line. Their structure and properties were analyzed, and they were modified with 2.5 wt % of commercially available compatibilizers. The mechanical and thermal performance of modified wastes were evaluated by tensile tests, thermogravimetric analysis, and differential scanning calorimetry. It was found that incorporation of such a small amount of modifiers may overcome the drawbacks caused by the presence of impurities. The incorporation of maleic anhydride-grafted compounds enhanced the tensile strength of wastes by 13–25%. The use of more ductile compatibilizers—ethylene-vinyl acetate and paraffin increased the elongation at break by 55–64%. The presence of compatibilizers also reduced the stiffness of materials resulting from the presence of solid particles. It was particularly emphasized for styrene-ethylene-butadiene-styrene and ethylene-vinyl acetate copolymers, which caused up to a 20% drop of Young’s modulus. Such effects may facilitate the further applications of analyzed wastes, e.g., in polymer film production. Thermal performance was only slightly affected by compatibilization. It caused a slight reduction in polyethylene melting temperatures (up to 2.8 °C) and crystallinity degree (up to 16%). For more contaminated materials, the addition of compatibilizers caused a minor reduction in the decomposition onset (up to 6 °C). At the same time, for the waste after three washing cycles, thermal stability was improved. Moreover, depending on the desired properties and application, materials do not have to go through the whole recycling line, simplifying the process, reducing energy and water consumption. The presented results indicate that it is possible to efficiently use the materials, which do not have to undergo the whole recycling process. Despite the presence of impurities, they could be applied in the manufacturing of products which do not require exceptional mechanical performance.
What Is the Community Pharmacists’ Role in Supporting Older Australians with Palliative Care Needs?

As the population ages, the number of older populations globally requiring palliative care is rapidly growing, requiring services of multidisciplinary teams—including community pharmacists. The aim of this study is to describe the community pharmacists’ perceived role in providing services to community dwelling older Australians receiving palliative care. Utilising an eight-domain End of Life Directions for Aged Care (ELDAC) care model, a national cross-sectional questionnaire was designed and undertaken online with Australian community pharmacists. Respondents were asked questions relating to socio-demographic characteristics, practice characteristics, and scope of services provided. Of the 62 pharmacists who responded to the questionnaire, 51 were included in the final data analysis and reporting. Pharmacists working in dispensing roles made up about half of the respondents, while the remainder worked in settings such as general practice, residential aged care, or providing medication review services. Pharmacists can identify patients with indicators of poor life expectancy and mostly work with older Australians daily. Dispensing and non-dispensing pharmacists offer a range of services that complement each other. Organisations caring for the aged should consider the role of the pharmacist, in caring for people with palliative care needs, along with their carers.
Effects of Pokémon GO on Physical Activity and Psychological and Social Outcomes: A Systematic Review

Augmented reality (AR) mobile game, Pokémon GO, leverages gamification and location tracking technology to encourage players to walk in different places to catch Pokémon characters in real-world settings. The systematic review sought to explore the impact Pokémon GO has on players’ physical activity (PA), and psychological and social outcomes. Six research databases (PubMed, SPORTDiscus, PsycInfo, Web of Science, Science Direct, and Scopus) were used. Study inclusion criteria were: (1) quantitative research published in English; (2) examined the relationships between or impact of Pokémon GO on PA, psychological, and/or social outcomes; and (3) included participants played or exposed to Pokémon GO. Thirty-six studies were included with a total sample of 38,724 participants. Players had significantly greater PA than non-players in terms of daily steps and number of days spent in moderate PA. Pokémon GO game also improved players’ social interactions and their mood/affects. Selective attention and concentration improved in adolescents and memory improved in young adults after playing the game. Findings suggest playing Pokémon GO could promote meaningful improvements in walking behavior, as well as psychological and social well-being. More multidimensional research with randomized controlled trial design is needed to identify factors that influence adoption and sustainability of Pokémon GO playing.
The Impact of Intolerance of Uncertainty on Negative Emotions in COVID-19: Mediation by Pandemic-Focused Time and Moderation by Perceived Efficacy

The COVID-19 global pandemic has resulted in a large number of people suffering from emotional problems. However, the mechanisms by which intolerance of uncertainty (IU) affects negative emotions during the COVID-19 pandemic remain unclear. This study aimed to explore the mediating role of pandemic-focused time and the moderating role of perceived efficacy in the association between IU and negative emotions during the COVID-19 pandemic based on the uncertainty-time-efficacy-emotion model (UTEE). 1131 participants were recruited to complete measures of COVID-19 IU, pandemic-focused time, perceived efficacy, negative emotions and demographic variables during the COVID-19 pandemic. The results showed that COVID-19 IU was significantly and positively associated with negative emotions, and this link could be mediated by pandemic-focused time. Moreover, the direct effect of COVID-19 IU on negative emotions was moderated by perceived efficacy. Specifically, the direct effect of COVID-19 IU on negative emotions was much stronger for individuals with lower levels of perceived efficacy. The current study further extended the previous integrative uncertainty tolerance model. Furthermore, the study suggested that policy makers and mental health professionals should reduce the general public’s negative emotions during the pandemic through effective interventions such as adjusting COVID-19 IU, shortening pandemic-focused time and enhancing perceived efficacy.
Anticholinesterase Activities of Different Solvent Extracts of Brewer’s Spent Grain

Cholinesterases, involved in acetylcholine catabolism in the central and peripheral nervous system, have been strongly linked with neurodegenerative diseases. Current therapeutic approaches using synthetic drugs present several side effects. Hence, there is an increasing research interest in naturally-occurring dietary polyphenols, which are also considered efficacious. Food processing by-products such as brewer’s spent grain (BSG) would be a potential bio-source of polyphenols. In this study, polyphenol-rich BSG extracts using 60% acetone and 0.75% NaOH solutions were generated, which were further subjected to liquid–liquid partitioning using various organic solvents. The water-partitioned fractions of the saponified extracts had the highest total polyphenol content (6.2 ± 2.8 mgGAE/g dw) as determined by Folin–Ciocalteu reagent, while the LC-MS/MS showed ethyl acetate fraction with the highest phenolics (2.9 ± 0.3 mg/g BSG dw). The best inhibitions of acetyl- (37.9 ± 2.9%) and butyryl- (53.6 ± 7.7%) cholinesterases were shown by the diethyl ether fraction of the saponified extract. This fraction contained the highest sum of quantified phenolics (99 ± 21.2 µg/mg of extract), and with significant (p < 0.01) inhibitory contribution of decarboxylated-diferulic acid. Amongst the standards, caffeic acid presented the highest inhibition for both cholinesterases, 25.5 ± 0.2% for acetyl- and 52.3 ± 0.8% for butyryl-cholinesterase, respectively, whilst the blends insignificantly inhibited both cholinesterases. The results showed that polyphenol-rich BSG fractions have potentials as natural anti-cholinesterase agents.
HIV Pre-exposure Prophylaxis (PrEP): Knowledge, attitudes and counseling practices among physicians in Germany – A cross-sectional survey

Background German statutory health insurance began covering the costs associated with HIV PrEP in September 2019; however, to bill for PrEP services, physicians in Germany must either be certified as HIV-specialists according to a nationwide quality assurance agreement, or, if they are non-HIV-specialists, have completed substantial further training in HIV/PrEP care. Given the insufficient implementation of PrEP, the aim of our study was to explore the potential to increase the number of non-HIV-specialists providing PrEP-related services. Methods We conducted an anonymous survey among a random sample of internists, general practitioners, dermatologists and urologists throughout Germany using a self-developed questionnaire. We calculated a knowledge score and an attitudes score from individual items in these two domains. Both scores ranged from 0–20, with high values representing good knowledge or positive attitudes. We also asked participants about the proportion of PrEP advice they provided proactively to men who have sex with men (MSM) and trans-persons who met the criteria to be offered PrEP. Results 154 physicians completed the questionnaire. Self-assessed knowledge among HIV-specialists was greater than among non-HIV-specialists [Median knowledge score: 20.0 (IQR = 0.0) vs. 4.0 (IQR = 11.0), p<0.001]. Likewise, attitudes towards PrEP were more positive among HIV-specialists than non-HIV-specialists [Median attitudes score: 18.0 (IQR = 3.0) vs. 13.0 (IQR = 5.25), p<0.001]. The proportion of proactive advice on PrEP provided to at-risk MSM and trans-persons by HIV-specialists [Median: 30.0% (IQR = 63.5%)] was higher than that provided by non-HIV-specialists [Median: 0.0% (IQR = 11.3%), p<0.001]. However, the results of our multiple regression suggest the only independent predictor of proactive PrEP advice was the knowledge score, and not whether physicians were HIV-specialists or non-HIV-specialists. Conclusions These findings point to opportunities to improve PrEP implementation in individuals at risk of acquiring HIV. Targeted training, particularly for non-HIV-specialists, and the provision of patient-centered information material could help improve care, especially in rural areas.
Associations between Physical Activity, Sunshine Duration and Osteoporosis According to Obesity and Other Lifestyle Factors: A Nested Case–Control Study

(1) Background: The purpose of the study was to evaluate the associations between physical activity (PA), sunshine duration (SD) and the occurrence of osteoporosis according to lifestyle status. (2) Methods: Data from the Korean National Health Insurance Service–National Sample Cohort (NHIS-NSC) collected from 2009 to 2015 were used. Osteoporosis (n = 19,351) and control (n = 38,702) participants were matched in a 1:2 ratio according to age, sex, income, and region of residence. PA was classified as moderate- to high-intensity PA (MHPA) or low-intensity PA (LPA) based on the International Physical Activity Questionnaire (IPAQ). SD was classified as short (≤6 h) or long (>6 h). Conditional logistic regression was used to calculate the odds ratios (ORs) with 95% confidence intervals (CIs) of MHPA and long SD for the occurrence of osteoporosis. Subgroup analyses were performed according to SD (or PA), obesity, smoking, and alcohol consumption. (3) The adjusted OR of MHPA for osteoporosis was 0.90 (95% CI = 0.87–0.94). The results were consistent in the age/sex, SD, obesity, smoking, and alcohol consumption subgroups, but not the <60-year-old male and underweight subgroups. The adjusted OR of long SD for osteoporosis was 0.96 (95% CI = 0.93–1.00). The findings were consistent in the <60-year-old female, obese, nonsmoker, and <1 time a week alcohol consumption subgroups. (4) Conclusions: We suggest that both higher intensity of PA and long SD could decrease the risk of osteoporosis. Specifically, PA could decrease the risk of osteoporosis in individuals with most characteristics except male sex or underweight. Long SD could decrease the risk of osteoporosis in young females, obese individuals, nonsmokers, and individuals with lower alcohol consumption.
The Emerging Role of Immunotherapy in Intrahepatic Cholangiocarcinoma

Biliary tract cancer, and intrahepatic cholangiocarcinoma (iCC) in particular, represents a rather uncommon, highly aggressive malignancy with unfavorable prognosis. Therapeutic options remain scarce, with platinum-based chemotherapy is being considered as the gold standard for the management of advanced disease. Comprehensive molecular profiling of tumor tissue biopsies, utilizing multi-omics approaches, enabled the identification of iCC’s intratumor heterogeneity and paved the way for the introduction of novel targeted therapies under the scope of precision medicine. Yet, the unmet need for optimal care of patients with chemo-refractory disease or without targetable mutations still exists. Immunotherapy has provided a paradigm shift in cancer care over the past decade. Currently, immunotherapeutic strategies for the management of iCC are under intense research. Intrinsic factors of the tumor, including programmed death-ligand 1 (PD-L1) expression and mismatch repair (MMR) status, are simply the tip of the proverbial iceberg with regard to resistance to immunotherapy. Acknowledging the significance of the tumor microenvironment (TME) in both cancer growth and drug response, we broadly discuss about its diverse immune components. We further review the emerging role of immunotherapy in this rare disease, summarizing the results of completed and ongoing phase I–III clinical trials, expounding current challenges and future directions.
Understanding the Health Behavior Decision-Making Process with Situational Theory of Problem Solving in Online Health Communities: The Effects of Health Beliefs, Message Credibility, and Communication Behaviors on Health Behavioral Intention

Online health communities (OHCs) offer users the opportunity to share and seek health information through these platforms, which in turn influence users’ health decisions. Understanding what factors influence people’s health decision-making process is essential for not only the design of the OHC, but also for commercial health business who are promoting their products to patients. Previous studies explored the health decision-making process from many factors, but lacked a comprehensive model with a theoretical model. The aim of this paper is to propose a research model from the situational theory of problem solving in relation to forecasting health behaviors in OHCs. An online questionnaire was developed to collect data from 321 members of online health communities (HPV Tieba and HPV vaccina Tieba) who have not received an HPV vaccination. The partial least squares structural equation modeling (PLS-SEM) method was employed for the data analysis. Findings showed that information selection and acquisition is able to forecast HPV vaccination intentions, perceived seriousness and perceived susceptibility can directly impact HPV vaccination intention and have an indirect impact by information selection and acquisition, and perceived message credibility indirectly affected HPV vaccination intention via information selection. The current paper supports health motivations analysis in OHCs, with potential to assist users’ health-related decision-making.
Eco-Friendly Dye-Sensitized Solar Cells Based on Water-Electrolytes and Chlorophyll

Organic solvents used for electrolytes of dye-sensitized solar cells (DSSCs) are generally not only toxic and explosive but also prone to leakage due to volatility and low surface tension. The representative dyes of DSSCs are ruthenium-complex molecules, which are expensive and require a complicated synthesis process. In this paper, the eco-friendly DSSCs were presented based on water-based electrolytes and a commercially available organic dye. The effect of aging time after the device fabrication and the electrolyte composition on the photovoltaic performance of the eco-friendly DSSCs were investigated. Plasma treatment of TiO2 was adopted to improve the dye adsorption as well as the wettability of the water-based electrolytes on TiO2. It turned out that the plasma treatment was an effective way of improving the photovoltaic performance of the eco-friendly DSSCs by increasing the efficiency by 3.4 times. For more eco-friendly DSSCs, the organic-synthetic dye was replaced by chlorophyll extracted from spinach. With the plasma treatment, the efficiency of the eco-friendly DSSCs based on water-electrolytes and chlorophyll was comparable to those of the previously reported chlorophyll-based DSSCs with non-aqueous electrolytes.