Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic mutation of familial dilated cardiomyopathy based on next-generation semiconductor sequencing

Dilated cardiomyopathy (DCM) is a complex myocardial disease of multifactorial etiologies, including enlarged cardiac chambers and contractile dysfunction. It has been suggested that the inheritance of DCM-associated mutations predominates its onset. Therefore, the present study investigated the pathogenesis of DCM via pedigree analysis and genetic diagnosis by massive whole-exome screening, and targeted exon capture. To study the familial gene-phenotype association, the exon and splice sites of 325 hereditary disease-associated genes in the proband with familial dilated cardiomyopathy (FDC), including 61 cardiac disease-associated genes, such as the lamins A/C (LMNA), were analyzed by ultra-high multiplex polymerase chain reaction and the Ion AmpliSeq™ Inherited Disease Panel. The present study also conducted Sanger DNA Sequencing for family members with global minor allele frequencies <1% to verify potential pathogenic mutation sites. A total of three rare missense mutations were detected, including heterozygous c.244G>A in LMNA, c.546C>G in potassium voltage-gated channel subfamily KQT (KCNQ4) and c.1276G>A in EYA transcriptional coactivator and phosphatase 1 (EYA1), indicating a glutamic acid to lysine substitution at amino acid 82 (p.E82K) in LMNA, a p.F182L in KCNQ4 (a mutation associated with pathogenic deafness) and p.G426S in EYA1 (associated with Branchiootorenal syndrome 1 and Branchiootic syndrome 1 pathogenesis). In the present study, a carrier with slight hearing impairment was detected in the family analyzed; however, no patients with deafness or branchiootorenal syndrome were observed. LMNA p.E82K revealed SIFT and PolyPhen-2 scores of 0 and 1, respectively. In the second generation, 3 patients with DCM underwent permanent pacemaker implantation due to sick sinus syndrome, atrioventricular block and unstable cardiac electrophysiology. The present study suggested that LMNA p.E82K may contribute to the pathogenesis of FDC and concomitant atrioventricular block. At present, only three families with DCM resulting from similar mutations have been reported. The present study demonstrated the strong pathogenic effects of LMNA p.E82K on DCM.
Quantitative screening of serum protein biomarkers by reverse phase protein arrays

Screening biomarkers in serum samples for different diseases has always been of great interest because it presents an early, reliable, and, most importantly, noninvasive means of diagnosis and prognosis. Reverse phase protein arrays (RPPAs) are a high-throughput platform that can measure single or limited sets of proteins from thousands of patients' samples in parallel. They have been widely used for detection of signaling molecules involved in diseases, especially cancers, and related regulation pathways in cell lysates. However, this approach has been difficult to adapt to serum samples. Previously, we developed a sensitive method called the enhanced protein array to quantitatively measure serum protein levels from large numbers of patient samples. Here, we further refine the technology on several fronts: 1. simplifying the experimental procedure; 2. optimizing multiple parameters to make the assay more robust, including the support matrix, signal reporting method, background control, and antibody validation; and 3. establishing a method for more accurate quantification. Using this technology, we quantitatively measured the expression levels of 10 proteins: alpha-fetoprotein (AFP), beta 2 microglobulin (B2M), Carcinoma Antigen 15-3(CA15-3), Carcinoembryonic antigen (CEA), golgi protein 73 (GP73), Growth differentiation factor 15 (GDF15), Human Epididymis Protein 4 (HE4), Insulin Like Growth Factor Binding Protein 2 (IGFBP2), osteopontin (OPN) and Beta-type platelet-derived growth factor receptor (PDGFRB) from serum samples of 132 hepatocellular carcinoma (HCC) patients and 78 healthy volunteers. We found that 6 protein expression levels are significantly increased in HCC patients. Statistical and bioinformatical analysis has revealed decent accuracy rates of individual proteins, ranging from 0.617 (B2M) to 0.908 (AFP) as diagnostic biomarkers to distinguish HCC from healthy controls. The combination of these 6 proteins as a specific HCC signature yielded a higher accuracy of 0.923 using linear discriminant analysis (LDA), logistic regression (LR), random forest (RF) and support vector machine (SVM) predictive model analyses. Our work reveals promise for using reverse phase protein arrays for biomarker discovery and validation in serum samples.
Multicultural Transitions: Caregiver Presence and Language-Concordance at Discharge

Introduction: Patients with low health literacy (HL) and minority patients encounter many challenges during hospital to community transitions. We assessed care transitions of minority patients with various HL levels and tested whether presence of caregivers and provision of language-concordant care are associated with better care transitions. Methods: A prospective cohort study of 598 internal medicine patients, Hebrew, Russian, or Arabic native speakers, at a tertiary medical center in central Israel, from 2013 to 2014. HL was assessed at baseline with the Brief Health Literacy Screen. A follow-up telephone survey was used to administer the Care Transition Measure [CTM] and to assess, caregiver presence and patient–provider language-concordance at discharge. Results: Patients with low HL and without language-concordance or caregiver presence had the lowest CTM scores (33.1, range 0–100). When language-concordance and caregivers were available, CTM scores did not differ between the medium-high and low HL groups (68.7 and 66.9, respectively, p = 0.118). The adjusted analysis, showed that language-concordance and caregiver presence during discharge moderate the relationship between HL and patients’ care transition experience (p < 0.001). Conclusions: Language-concordance care and caregiver presence are associated with higher patients’ ratings of the transitional-care experience among patients with low HL levels and among minorities.
Circulating Epithelial Cell Characterization and Correlation with Remission and Survival in Patients with Thyroid Cancer.

BACKGROUND Thyroid cancer is the most common endocrine tumor and generally has relatively good clinical outcomes. However, 15-20% of patients ultimately develop recurrence or disease-related death. The appropriate prognostic factors for thyroid cancer are still elusive. This study evaluated whether the number of circulating tumor cells/circulating epithelial cells (CECs) expressing either epithelial cell adhesion molecule (EpCAM), podoplanin (PDPN), or thyrotropin receptor (TSHR) is related to remission and disease-specific mortality (DSM) of patients with thyroid cancer. METHODS Blood samples were collected from patients (n = 128) after thyroidectomy or radioactive iodide therapy. CECs were enriched by lysis of red blood cells and depletion of leukocytes. Subtyping and quantification of the enriched cells were performed with immunofluorescence staining using antibodies against EpCAM, TSHR, and PDPN, respectively. Whether the number of a specific subtype of CECs is related to remission and DSM of patients was determined by univariate and multivariate analyses. RESULTS The EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs counts for patients in the non-remission group (n = 43) were significantly higher when compared to the remission group (n = 85; p < 0.001). Receiver operating characteristic analysis showed that the number of EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was able to distinguish the status of remission from non-remission. The cutoff point for EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was 40, 47, and 14 (cells/mL), with the accuracy of the assay equivalent to 80.4%, 76.6%, and 77.3%, respectively. On the other hand, the number of EpCAM+-CECs (p < 0.001), PDPN+-CECs (p = 0.013), and TSHR+-CECs (p < 0.001) for patients in the DSM group (n = 17) was significantly higher when compared to the patients who survived (n = 111). Receiver operating characteristic analysis showed that EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs counts were able to distinguish mortality from survival status. The cutoff point for EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was 27, 25, and 9 (cells/mL), with the accuracy of the assay equivalent to 69.5%, 67.2%, and 68.5%, respectively. CONCLUSIONS CEC testing is a useful tool for analysis of overall survival and remission status of patients with thyroid cancer. Implementation of CEC testing into routine clinical test may be worthy to consider for patient clinical care.
Preclinical studies reveal that LSD1 inhibition results in tumor growth arrest in lung adenocarcinoma independently of driver mutations

Lung adenocarcinoma (LUAD) is the most prevalent subtype of non‐small cell lung cancer. Despite the development of novel targeted and immune therapies, the 5‐year survival rate is still only 21%, indicating the need for more efficient treatment regimens. Lysine‐specific demethylase 1 (LSD1) is an epigenetic eraser that modifies histone 3 methylation status, and is highly overexpressed in LUAD. Using representative human cell culture systems and two autochthonous transgenic mouse models, we investigated inhibition of LSD1 as a novel therapeutic option for treating LUAD. The reversible LSD1 inhibitor HCI‐2509 significantly reduced cell growth with an IC50 of 0.3–5 μmin vitro, which was linked to an enhancement of histone 3 lysine methylation. Most importantly, growth arrest, as well as inhibition of the invasion capacities, was independent of the underlying driver mutations. Subsequent expression profiling revealed that the cell cycle and replication machinery were prominently affected after LSD1 inhibition. In addition, our data provide evidence that LSD1 blockade significantly interferes with EGFR downstream signaling. Finally, our in vitro results were confirmed by preclinical therapeutic approaches, including the use of two autochthonous transgenic LUAD mouse models driven by either EGFR or KRAS mutations. Importantly, LSD1 inhibition resulted in significantly lower tumor formation and a strong reduction in tumor progression, which were independent of the underlying mutational background of the mouse models. Hence, our findings provide substantial evidence indicating that tumor growth of LUAD can be markedly decreased by HCI‐2509 treatment, suggesting its use as a single agent maintenance therapy or combined therapeutical application in novel concerted drug approaches.
Effective Guided Image Filtering for Contrast Enhancement

Although the guided image filtering (GIF) has an excellent edge-preserving property, it is prone to suffer from the halo artifacts near the edges. Weighted GIF and gradient-domain GIF try to address the problem by incorporating an edge-aware weighting into GIF. However, they are very sensitive to the regularization parameter and the halo artifacts will become serious as the regularization parameter increases. Moreover, noise in the background is often amplified because of the fixed amplification factor for the detail layer. In this letter, an effective GIF is proposed for better contrast enhancement. First, the average of local variances for all pixels is incorporated into the cost function of GIF for preserving the edges accurately in the base layer. Second, the amplification factor for the detail layer is calculated in a content-adaptive way for suppressing the noise while boosting the fine details. Experimental results show that the proposed filter is more robust to the regularization parameter and can produce visually pleasing output images. Compared to GIF and its related filters, halo artifacts and noise are reduced or attenuated by the proposed filter significantly.
Design and Characterization of Tri-Axis Soft Inductive Tactile Sensors

Tactile sensors are essential for robotic systems to safely and effectively interact with the environment and humans. In particular, tri-axis tactile sensors are crucial for dexterous robotic manipulations by providing shear force, slip, or contact angle information. The soft inductive tactile sensor (SITS) is a new type of tactile sensor that measures inductance variations caused by eddy-current effect. In this paper, we present a soft tri-axis tactile sensor using the configuration of four planar coils and a single conductive film with a hyperelastic material in between them. The working principle is explained and the design methods are outlined. A 3-D finite-element model was developed to characterize the tri-axis SITS and to optimize the target design through parameter study. Prototypes were fabricated, characterized, and calibrated, and a force measurement resolution of 0.3 mN is achieved in each axis. Demonstrations show that the sensor can clearly measure light touch (a few mN normal force) and shear force pulses (10–30 mN) produced by a serrated leaf when it is moved across the sensor surface. The presented sensor is low cost, high performance, robust, durable, and easily customizable for a variety of robotic and healthcare applications.
Insights into endotoxin-mediated lung inflammation and future treatment strategies

ABSTRACT Introduction: Airway inflammatory disorders are prevalent diseases in need of better management and new therapeutics. Immunotherapies offer a solution to the problem of corticosteroid resistance. Areas covered: The current review focuses on lipopolysaccharide (Gram-negative bacterial endotoxin)-mediated inflammation in the lung and the animal models used to study related diseases. Endotoxin-induced lung pathology is usually initiated by antigen presenting cells (APC). We will discuss different subsets of APC including lung dendritic cells and macrophages, and their role in responding to endotoxin and environmental challenges. Expert commentary: The pharmacotherapeutic considerations to combat airway inflammation should cost-effectively improve quality of life with sustainable and safe strategies. Selectively targeting APCs in the lung offer the potential for a promising new strategy for the better management and treatment of inflammatory lung disease.
Evaluation of bilosomes as nanocarriers for transdermal delivery of tizanidine hydrochloride: in vitro and ex vivo optimization

Abstract Bilosomes were developed in order to investigate their efficacy as nanocarriers for transdermal delivery of Tizanidine HCl (TZN), a skeletal muscle relaxant with low oral bioavailability. Full factorial experimental design consisting of 27 combinations was generated to study the effects of surfactant type, surfactant-to-cholesterol ratio and the amount of bile salt on the entrapment efficiency (EE), the vesicle size (VS) and in vitro dissolution of the TZN-loaded bilosomes. The permeation through the stratum cornea was optimized with the vertical diffusion assembly using excised rat skin. The permeation parameters of the selected bilosomes were compared to the unformulated drug and it was shown that TZN-B24 exhibited the highest enhancement ratio (ER = 8.8). The optimal formula (TZN-B24) consisting of span 60 in a ratio with cholesterol of 1:1 and 20 mg of bile salt was obtained by employing the desirability function of Design-Expert® software. The mathematical model used for the optimization was validated by comparing the predicted values of the EE (82.3%) and the VS (165.8 nm) with the experimental values of EE = 84.42% and of VS = 161.95 nm. TZN-B24 displayed high zeta potential which contributed to its good stability. It was evident from the results of this study that incorporating TZN in bilosomes improved significantly its permeation through the skin barrier and thus bilosomes can offer a potential nanoplatform using the transdermal route to improve the bioavailability of the drug.
Does Getting Stigma Under the Skin Make It Thinner? Emotion Regulation as a Stress-Contingent Mediator of Stigma and Mental Health

Emotion regulation deficits may link stigma to poor mental health, yet authors of existing studies have relied on self-reported stigma and have not considered contextual factors. In the present research, we examined associations among cultural stigma (i.e., objective devaluation of one’s stigmatized status), emotion regulation deficits, and poor mental health. In Study 1, we created an index of cultural stigma by asking members of the general public and stigma experts to indicate desired social distance toward 93 stigmatized attributes. In Study 2, emotion regulation deficits mediated the association between cultural stigma and adverse mental health outcomes, including depressive symptoms and alcohol use problems, among individuals endorsing diverse stigmatized identities. The indirect effect of cultural stigma, via emotion regulation, on these outcomes was stronger among those reporting more life stress. These findings highlight the adverse impact of cultural stigma on mental health and its role in potentiating stigmatized individuals’ susceptibility to general life stress.
The p33 protein of Citrus tristeza virus affects viral pathogenicity by modulating a host immune response.

Accumulation of reactive oxygen species (ROS) is a general plant basal defense strategy against viruses. In this study, we show that infection by Citrus tristeza virus (CTV) triggered ROS burst in Nicotiana benthamiana and in the natural citrus host, the extent of which was virus-dose dependent. Using Agrobacterium-mediated expression of CTV-encoded proteins in N. benthamiana, we found that p33, a unique viral protein, contributed to the induction of ROS accumulation and programmed cell death. The role of p33 in CTV pathogenicity was assessed based on gene knockout and complementation in N. benthamiana. In the citrus-CTV pathosystem, deletion of the p33 open reading frame in a CTV variant resulted in a significant decrease in ROS production, compared to that of the wild type CTV, which correlated with invasion of the mutant virus into the immature xylem tracheid cells and abnormal differentiation of the vascular system. By contrast, the wild type CTV exhibited phloem-limited distribution with a minor effect on the vasculature. We conclude that the p33 protein is a CTV effector that negatively affects virus pathogenicity and suggest that N. benthamiana recognizes p33 to activate the host immune response to restrict CTV into the phloem tissue and minimize the disease syndrome.
Sexual Orientation and Depressive Symptoms Among High School Students in Jiangxi Province

Research in western countries has shown that adolescents who self-identify as lesbian, gay, or bisexual (LGB) are at increased risk for depression, but little is known about this relationship among adolescents in China. A school-based cross-sectional survey was conducted among 1816 high school students in Jiangxi province. Logistic regression was used to explore the relationship between sexual orientation and depressive symptoms. Approximately 4% of participants self-identified as LGB, and 14% reported being unsure of their sexual identity. After controlling for potential confounding factors, students who self-identified as LGB had significantly higher odds of depressive symptoms compared with heterosexual students: adjusted odds ratio = 6.16 (2.13-17.83) and adjusted odds ratio = 2.29 (1.13-4.63) for males and females, respectively. Culturally appropriate programs and policies that support LGB students and address discrimination and victimization are needed to improve the mental health of Chinese LGB youth.
In-route task selection in crowdsourcing

We consider a spatial crowdsourcing scenario where (1) a worker is traveling on a preferred/typical path within a road network where (2) there is a set of tasks, each associated with a positive reward, available to be performed and (3) that the worker is willing to possibly deviate from his/her preferred path to perform tasks as long as (4) he/she travels at most a total given distance/time. We name this the In-Route Task Selection (IRTS) problem and investigate it using the skyline paradigm in order to obtain a set of diverse solutions yielding good combinations of detour and reward. Given the NP-hardness of the IRTS problem we present a heuristic approach that produces solutions with good values of precision and recall for problems of realistic sizes within practical query processing time.
Nintedanib plus Sildenafil in Patients with Idiopathic Pulmonary Fibrosis

Background Nintedanib is an approved treatment for idiopathic pulmonary fibrosis (IPF). A subgroup analysis of a previously published trial suggested that sildenafil may provide benefits regarding oxygenation, gas exchange as measured by the diffusion capacity of the lungs for carbon monoxide (DlCO), symptoms, and quality of life in patients with IPF and severely decreased DlCO. That idea was tested in this trial. Methods We randomly assigned, in a 1:1 ratio, patients with IPF and a DlCO of 35% or less of the predicted value to receive nintedanib at a dose of 150 mg twice daily plus sildenafil at a dose of 20 mg three times daily (nintedanib‐plus‐sildenafil group) or nintedanib at a dose of 150 mg twice daily plus placebo three times daily (nintedanib group) for 24 weeks. The primary end point was the change from baseline in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 12 (the total score ranges from 0 to 100, with higher scores indicating worse health‐related quality of life). Secondary end points included measures of dyspnea and safety. Results A total of 274 patients underwent randomization. There was no significant difference in the adjusted mean change from baseline in the SGRQ total score at week 12 between the nintedanib‐plus‐sildenafil group and the nintedanib group (‐1.28 points and ‐0.77 points, respectively; P=0.72). A benefit from sildenafil treatment was not observed with regard to dyspnea as measured with the use of the University of California, San Diego, Shortness of Breath Questionnaire. No new safety signals were observed, as compared with previous trials. Conclusions In patients with IPF and a DlCO of 35% or less of the predicted value, nintedanib plus sildenafil did not provide a significant benefit as compared with nintedanib alone. No new safety signals were identified with either treatment regimen in this population of patients. (Funded by Boehringer Ingelheim; INSTAGE ClinicalTrials.gov number, NCT02802345.)
RECLAIMING Data: Overcoming App Identification Barriers for Exercising Data Protection Rights

Data protection regulations generally afford individuals certain rights over their personal data, including the rights to access, rectify, and delete the data held on them. Exercising such rights naturally requires those with data management obligations (service providers) to be able to match an individual with their data. However, many mobile apps collect personal data, without requiring user registration or collecting details of a user's identity (email address, names, phone number, and so forth). As a result, a user's ability to exercise their rights will be hindered without means for an individual to link themselves with this 'nameless' data. Current approaches often involve those seeking to exercise their legal rights having to give the app's provider more personal information, or even to register for a service; both of which seem contrary to the spirit of data protection law. This paper explores these concerns, and indicates simple means for facilitating data subject rights through both application and mobile platform (OS) design.