Miracle-dz/UniFAR-FTUs huggingface dataset:
Roles of Non-Coding RNAs as Novel Diagnostic Biomarkers in Parkinson’s Disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting 5%of the elderly population. Currently, the diagnosis of PD is mainly based on clinical features and no definitive diagnostic biomarkers have been identified. The discovery of biomarkers at the earliest stages of PD is of extreme interest. This review focuses on the current findings in the field of circulating non-coding RNAs in PD. We briefly describe the more established circulating biomarkers in PD and provide a more thorough review of non-coding RNAs, in particular microRNAs, long non-coding RNAs and circular RNAs, differentially expressed in PD, highlighting their potential for being considered as biomarkers for diagnosis. Together, these studies hold promise for the use of peripheral biomarkers for the diagnosis of PD.
The Excess Costs of Dementia: A Systematic Review and Meta-Analysis.

BACKGROUND Dementia is one of the costliest diseases for health care systems with growing importance for policy makers. OBJECTIVE The aim of this study is to systematically review the current literature of excess cost studies for dementia and to analyze excess costs in a meta-analysis. METHODS A systematic literature search was conducted in PubMed, EconLit, NHS-EED, and Cochrane Library. 22 studies were included and assigned to one of three subgroups according to the time period that they analyzed during disease progression: the time of diagnosis, the time between diagnosis and death, and the time prior to death. Excess costs were analyzed using the ratio of means (ROM) and meta-analysis was performed by pooling ROMs in a random effects model. RESULTS Total costs were significantly higher for demented persons compared to non-demented persons at the time of diagnosis (ROM: 2.08 [1.71, 2.54], p < 0.00001, I2 = 98%) and in the time period between diagnosis and death (ROM: 2.19 [1.97, 2.44], p < 0.00001, I2 = 100%). The ROM was highest for professional home care (ROM: 4.96 [2.62, 9.40], p < 0.0001, I2 = 88%) and for nursing facilities (ROM: 4.02 [2.53, 6.40], p < 0.00001, I2 = 100%) for the time period between diagnosis and death. CONCLUSION This meta-analysis is the first to assess excess costs of dementia by the ROM method on a global scale. We conclude that our findings demonstrate that costs of dementia constitute a substantial economic burden.
LncRNA AFAP1-AS1/miR-27b-3p/VEGF-C axis modulates stemness characteristics in cervical cancer cells

Abstract Background: Long non-coding RNA (lncRNA) actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs (miRs) to play cancer-promoting roles in cancer stem cells. However, the regulatory mechanism of AFAP1-AS1 in cervical cancer (CC) stem cells is unknown. The present study aimed to provide a new therapeutic target for the clinical treatment of CC. Methods: Hyaluronic acid receptor cluster of differentiation 44 variant exon 6 (CD44v6)(+) CC cells were isolated by flow cytometry (FCM). Small interfering RNAs of AFAP1-AS1 (siAFAP1-AS1) were transfected into the (CD44v6)(+) cells. The levels of AFAP1-AS1 were measured by quantitative real-time PCR (qRT-PCR). Sphere formation assay, cell cycle analysis, and Western blotting were used to detect the effect of siAFAP1-AS1. RNA pull-down and luciferase reporter assay were used to verify the relationship between miR-27b-3p and AFAP1-AS1 or vascular endothelial growth factor (VEGF)-C. Results: CD44v6(+) CC cells had remarkable stemness and a high level of AFAP1-AS1. However, AFAP1-AS1 knockdown with siAFAP1-AS1 suppressed the cell cycle transition of G(1)/S phase and inhibited self-renewal of CD44v6(+) CC cells, the levels of the stemness markers octamer-binding transcription factor 4 (OCT4), osteopontin (OPN), and cluster of differentiation 133 (CD133), and the epithelial-mesenchymal transition (EMT)-related proteins Twist1, matrix metalloprotease (MMP)-9, and VEGF-C. In the mechanism study, miR-27b-3p/VEGF-C signaling was demonstrated to be a key downstream of AFAP1-AS1 in the CD44v6(+) CC cells. Conclusions: LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C.
A RI EL: VOLUME CODING FOR SENTENCE GENERATION COMPARISONS

Mapping sequences of discrete data to a point in a continuous space makes it difficult to retrieve those sequences via random sampling. Mapping the input to a volume would make it easier to retrieve at test time, and that is the strategy followed by the family of approaches based on Variational Autoencoder. However the fact that they are at the same time optimizing for prediction and for smoothness of representation, forces them to trade-off between the two. We benchmark the performance of some of the standard methods in deep learning to generate sentences by uniformly sampling a continuous space. We do it by proposing AriEL, that constructs volumes in a continuous space, without the need of encouraging the creation of volumes through the loss function. We first benchmark on a toy grammar, that allows to automatically evaluate the language learned and generated by the models. Then, we benchmark on a real dataset of human dialogues. Our results indicate that the random access to the stored information can be significantly improved, since our method AriEL is able to generate a wider variety of correct language by randomly sampling the latent space. VAE follows in performance for the toy dataset while, AE and Transformer follow for the real dataset. This partially supports the hypothesis that encoding information into volumes instead of into points, leads to improved retrieval of learned information with random sampling. We hope this analysis can clarify directions to lead to better generators.
Effects of Wi‐Fi Radiofrequency Radiation on Carbapenem‐Resistant Klebsiella pneumoniae

The hazardous consequences of electromagnetic field (EMF) exposure represent a public health concern. Common sources of EMF include smartphones and wireless fidelity (Wi‐Fi). The aim of our study is to assess whether exposure to Wi‐Fi radiofrequency radiation influences the pathogenic traits of carbapenem‐resistant Klebsiella pneumoniae. The susceptibility to antibiotics was evaluated by the determination of minimum inhibitory concentrations (MIC). In this study, K. pneumoniae showed a non‐linear response to treatments with Colistin and Gentamycin following different Wi‐Fi exposure periods. Transmission electron microscopy revealed morphological changes in the bacterial cell membrane within 24 h of Wi‐Fi exposure. Crystal violet quantification and quantitative real‐time polymerase chain reaction showed that the ability to form biofilms was greater in Wi‐Fi exposed K. pnemoniae when compared to control. Moreover, higher levels of bcsA, mrkA, and luxS messenger RNAs were observed. Our data suggest that Wi‐Fi exposure can influence bacteria in a stressful way, leading to an alteration in their antibiotic susceptibility, morphological changes, and cumulative biofilm formation. © 2021 Bioelectromagnetics Society.
Automated detection of substance use information from electronic health records for a pediatric population

Abstract Objective Substance use screening in adolescence is unstandardized and often documented in clinical notes, rather than in structured electronic health records (EHRs). The objective of this study was to integrate logic rules with state-of-the-art natural language processing (NLP) and machine learning technologies to detect substance use information from both structured and unstructured EHR data. Materials and Methods Pediatric patients (10-20 years of age) with any encounter between July 1, 2012, and October 31, 2017, were included (n = 3890 patients; 19 478 encounters). EHR data were extracted at each encounter, manually reviewed for substance use (alcohol, tobacco, marijuana, opiate, any use), and coded as lifetime use, current use, or family use. Logic rules mapped structured EHR indicators to screening results. A knowledge-based NLP system and a deep learning model detected substance use information from unstructured clinical narratives. System performance was evaluated using positive predictive value, sensitivity, negative predictive value, specificity, and area under the receiver-operating characteristic curve (AUC). Results The dataset included 17 235 structured indicators and 27 141 clinical narratives. Manual review of clinical narratives captured 94.0% of positive screening results, while structured EHR data captured 22.0%. Logic rules detected screening results from structured data with 1.0 and 0.99 for sensitivity and specificity, respectively. The knowledge-based system detected substance use information from clinical narratives with 0.86, 0.79, and 0.88 for AUC, sensitivity, and specificity, respectively. The deep learning model further improved detection capacity, achieving 0.88, 0.81, and 0.85 for AUC, sensitivity, and specificity, respectively. Finally, integrating predictions from structured and unstructured data achieved high detection capacity across all cases (0.96, 0.85, and 0.87 for AUC, sensitivity, and specificity, respectively). Conclusions It is feasible to detect substance use screening and results among pediatric patients using logic rules, NLP, and machine learning technologies.
Calcium ions promote membrane fusion by forming negative-curvature inducing clusters on specific anionic lipids

Vesicles enriched in certain negatively charged lipids, such as phosphatidylserine and PIP2, are known to undergo fusion in the presence of calcium ions without assistance from protein assemblies. Other lipids do not exhibit this propensity, even if they are negatively charged. Using our recently developed methodology, we extract elastic properties of a representative set of lipids. This allows us to trace the origin of lipid-calcium selectivity in membrane fusion to the formation of lipid clusters with long-range correlations that induce negative curvature on the membrane surface. Furthermore, the clusters generate lateral tension in the headgroup region at the membrane surface, concomitantly increasing its Gaussian bending modulus. Finally, calcium binding also reduces the orientational polarization of water around the membrane headgroups, potentially reducing the hydration force acting between membranes. Binding calcium only weakly increases membrane bending rigidity and tilt moduli, in agreement with experiments. We show how the combined effects of calcium binding to membranes lower the barriers along the fusion pathway that lead to the formation of the fusion stalk as well as the fusion pore.
Prospective Trial of Near-Infrared Spectroscopy for Continuous Noninvasive Monitoring of Free Fibular Flaps

Introduction Some free flaps develop postoperative vessel thrombosis, which influences the flap survival rate. Early discovery and identification of vascular crisis are critical to the success rate of flap salvage. The primary aims of this study were to determine the features of postoperative blood supply changes in fibular flaps with normal and abnormal blood flow, using near-infrared spectroscopy (NIRS), to monitor oxygenation and blood flow, and to characterize the probable risk factors for vascular crisis. Methods Sixty-three consecutive patients undergoing reconstruction of unilateral mandibular defects with free fibular flaps at the Peking University School of Stomatology were included. Patients were divided into 2 groups, A (n = 38) and B (n = 25); fibular flaps in group A underwent continuous NIRS monitoring from immediately postoperatively until 7 days postoperatively (approximately 150 hours), whereas fibular flaps and opposite mandibles in group B underwent intermittent monitoring: once every 4 hours during the first 24 hours postoperatively and once every 12 hours from 24 to 168 hours postoperatively. Results Six fibular flaps developed vascular thromboses: 4 were venous thromboses and 2 were arterial thromboses; 5 were rescued after exploration. Of 6 regional oxygen saturation (rSO2) values in the continuous monitoring group, 4 showed no significant differences at any time point compared with the intermittent monitoring group (P > 0.05). The rSO2 of the fibular flap was significantly different from that in the opposite mandible in the first 36 hours postoperatively (P < 0.05). This difference decreased over time. During the initial period of venous thrombosis, rSO2, deoxyhemoglobin, and oxygenated hemoglobin all rose slightly, then showed simultaneous rapid reduction. However, the magnitude of reduction was smaller for deoxyhemoglobin than for oxygenated hemoglobin. Conclusions Near-infrared spectroscopy can be used for noninvasive and reliable assessment of oxygenation and blood flow in free flaps through continuous, real-time monitoring. It is also portable, inexpensive, and simple to operate. In addition, the detection depth of NIRS is up to 2.0 cm, so it can be used to monitor buried flaps with depths <2.0 cm.
Piezo1-Mediated Mechanotransduction Promotes Cardiac Hypertrophy by Impairing Calcium Homeostasis to Activate Calpain/Calcineurin Signaling

Supplemental Digital Content is available in the text. Hemodynamic overload induces pathological cardiac hypertrophy, which is an independent risk factor for intractable heart failure in long run. Beyond neurohumoral regulation, mechanotransduction has been recently recognized as a major regulator of cardiac hypertrophy under a myriad of conditions. However, the identification and molecular features of mechanotransducer on cardiomyocytes are largely sparse. For the first time, we identified Piezo1 (Piezo type mechanosensitive ion channel component 1), a novel mechanosensitive ion channel with preference to Ca2+ was remarkably upregulated under pressure overload and enriched near T-tubule and intercalated disc of cardiomyocyte. By applying cardiac conditional Piezo1 knockout mice (Piezo1fl/flMyh6Cre+, Piezo1Cko) undergoing transverse aortic constriction, we demonstrated that Piezo1 was required for the development of cardiac hypertrophy and subsequent adverse remodeling. Activation of Piezo1 by external mechanical stretch or agonist Yoda1 lead to the enlargement of cardiomyocytes in vitro, which was blocked by Piezo1 silencing or Yoda1 analog Dooku1 or Piezo1 inhibitor GsMTx4. Mechanistically, Piezo1 perturbed calcium homeostasis, mediating extracellular Ca2+ influx and intracellular Ca2+ overload, thereby increased the activation of Ca2+-dependent signaling, calcineurin, and calpain. Inhibition of calcineurin or calpain could abolished Yoda1 induced upregulation of hypertrophy markers and the hypertrophic growth of cardiomyocytes in vitro. From a comprehensive view of the cardiac transcriptome, most of Piezo1 affected genes were highly enriched in muscle cell physiology, tight junction, and corresponding signaling. This study characterizes an undefined role of Piezo1 in pressure overload induced cardiac hypertrophy. It may partially decipher the differential role of calcium under pathophysiological condition, implying a promising therapeutic target for cardiac dysfunction.
Analyzing security issues of android mobile health and medical applications

OBJECTIVE We conduct a first large-scale analysis of mobile health (mHealth) apps available on Google Play with the goal of providing a comprehensive view of mHealth apps' security features and gauging the associated risks for mHealth users and their data. MATERIALS AND METHODS We designed an app collection platform that discovered and downloaded more than 20 000 mHealth apps from the Medical and Health & Fitness categories on Google Play. We performed a suite of app code and traffic measurements to highlight a range of app security flaws: certificate security, sensitive or unnecessary permission requests, malware presence, communication security, and security-related concerns raised in user reviews. RESULTS Compared to baseline non-mHealth apps, mHealth apps generally adopt more reliable signing mechanisms and request fewer dangerous permissions. However, significant fractions of mHealth apps expose users to serious security risks. Specifically, 1.8% of mHealth apps package suspicious codes (eg, trojans), 45.0% rely on unencrypted communication, and as much as 23.0% of personal data (eg, location information and passwords) is sent on unsecured traffic. An analysis of the app reviews reveals that mHealth app users are largely unaware of the surfaced security issues. CONCLUSION Despite being better aligned with security best practices than non-mHealth apps, mHealth apps are still far from ensuring robust security guarantees. App users, clinicians, technology developers, and policy makers alike should be cognizant of the uncovered security issues and weigh them carefully against the benefits of mHealth apps.
Thermodynamic Performance Investigation of a Small-Scale Solar Compression-Assisted Multi-Ejector Indoor Air Conditioning System for Hot Climate Conditions

In year-round hot climatic conditions, conventional air conditioning systems consume significant amounts of electricity primarily generated by conventional power plants. A compression-assisted, multi-ejector space cooling system driven by low-grade solar thermal energy is investigated in terms of energy and exergy performance, using a real gas property-based ejector model for a 36 kW-scale air conditioning application, exposed to annually high outdoor temperatures (i.e., up to 42 °C), for four working fluids (R11, R141b, R245fa, R600a). Using R245fa, the multi-ejector system effectively triples the operating condenser temperature range of a single ejector system to cover the range of annual outdoor conditions, while compression boosting reduces the generator heat input requirement and improves the overall refrigeration coefficient of performance (COP) by factors of ~3–8 at medium- to high-bound condenser temperatures, relative to simple ejector cycles. The system solar fraction varies from ~0.2 to 0.9 in summer and winter, respectively, with annual average mechanical and overall COPs of 24.5 and 0.21, respectively. Exergy destruction primarily takes place in the ejector assembly, but ejector exergy efficiency improves with compression boosting. The system could reduce annual electric cooling loads by over 40% compared with a conventional local split air conditioner, with corresponding savings in electricity expenditure and GHG emissions.
Use of non-cancer drugs and survival among patients with pancreatic adenocarcinoma: a nationwide registry-based study in Norway

Abstract Background The prognosis of pancreatic cancer is poor and new treatment strategies are urgently needed. To identify non-cancer drugs that could be re-purposed for cancer, we investigated the association between the use of selected drugs and cancer-specific mortality in a nationwide cohort of pancreatic cancer patients. Material and methods The study is based on linkage between the Cancer Registry of Norway and the Norwegian Prescription Database, comprising 2614 pancreatic cancer patients diagnosed between 2007 and 2014. We evaluated the association between use at diagnosis of a pre-defined list of non-cancer drugs, including metformin, antihypertensives, and statins, and pancreatic cancer-specific mortality, using Cox regression. Patients were defined as users of a particular drug if it was prescribed before diagnosis, and the prescription covered the date of diagnosis. Results In total, 2096 (80.2%) patients died from pancreatic cancer; median survival was 6 months. Statin users (n = 621) had lower mortality (hazard ratio (HR): 0.86; 95% confidence interval (CI) 0.76–0.97) compared to non-users (n = 1993). This association was more pronounced (P-heterogeneity 0.062) in users of hydrophilic (n = 37, HR: 0.61; 95% CI 0.42–0.90) than lipophilic (n = 587, HR: 0.87; 95% CI 0.78–0.98) statins. An indication for lower mortality (HR: 0.85; 95% CI 0.69–1.05) was observed in users of non-selective beta-blockers (n = 113) compared to non-users (n = 2501). Notably, when compared to users of other antihypertensives (n = 643), users of non-selective beta-blockers (n = 40) had lower mortality (HR 0.67; 95% CI 0.47–0.96). The use of other drugs, including selective beta-blockers and metformin, was not associated with mortality. Conclusion The findings suggest an association between the use of statins and non-selective beta-blockers and reduced pancreatic cancer mortality, and add to the literature supporting the design of randomised clinical trials to evaluate those drugs in the management of pancreatic cancer.
Identification of key genes in allergic rhinitis by bioinformatics analysis

Objective This study aimed to explore the potential molecular mechanism of allergic rhinitis (AR) and identify gene signatures by analyzing microarray data using bioinformatics methods. Methods The dataset GSE19187 was used to screen differentially expressed genes (DEGs) between samples from patients with AR and healthy controls. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied for the DEGs. Subsequently, a protein–protein interaction (PPI) network was constructed to identify hub genes. GSE44037 and GSE43523 datasets were screened to validate critical genes. Results A total of 156 DEGs were identified. GO analysis verified that the DEGs were enriched in antigen processing and presentation, the immune response, and antigen binding. KEGG analysis demonstrated that the DEGs were enriched in Staphylococcus aureus infection, rheumatoid arthritis, and allograft rejection. PPI network and module analysis predicted seven hub genes, of which six (CD44, HLA-DPA1, HLA-DRB1, HLA-DRB5, MUC5B, and CD274) were identified in the validation dataset. Conclusions Our findings suggest that hub genes play important roles in the development of AR.
The economic burden of mental disorders among adults in Singapore: evidence from the 2016 Singapore Mental Health Study

Abstract Background Little is known about the economic burden of mental disorders in multiethnic Asian populations. Aims The study aimed to estimate the economic cost of mental disorders in Singapore using data from the second Singapore Mental Health Study (SMHS 2016). Method The SMHS 2016 is a nationally representative survey of the Singapore Resident population aged 18 years and above. Data on mental disorders and healthcare resource utilization were obtained from the World Mental Health Composite International Diagnostic Interview and the adapted version of the Client Service Receipt Inventory. Results The costs of visits to a restructured hospital doctor, other private health workers, accident and emergency, and intermediate and long-term care services and productivity losses tend to be much higher in those with mental disorders than those without mental disorders. The average annual excess cost associated with mental disorders per person was estimated to be S$3938.9 (95% CI, S$-100.8–S$7978.7). Extrapolation of these excess costs to the population suggests that the incremental costs of mental disorders in Singapore is about S$1.7 billion per year. Conclusion This study provides evidence of the substantial burden of mental disorders on Singaporean society – both in terms of direct medical costs and loss of productivity costs.