Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptome profiling reveals that VNPP433‐3β, the lead next‐generation galeterone analog inhibits prostate cancer stem cells by downregulating epithelial–mesenchymal transition and stem cell markers

Cancer stem cells (CSCs) virtually present in all tumors albeit in small numbers are primarily responsible for driving cancer progression, metastasis, drug resistance, and recurrence. Prostate cancer (PCa) is the second most frequent cancer in men worldwide, and castration resistant prostate cancer (CRPC) remains a major challenge despite the tremendous advancements in medicine. Currently, none of the available treatment options are effective in treating CRPC. We earlier reported that VNPP433‐3β, the lead next‐generation galeterone analog is effective in treating preclinical in vivo models of CRPC. In this study using RNA‐seq, cytological, and biochemical methods, we report that VNPP433‐3β inhibits prostate CSCs by targeting key pathways critical to stemness and epithelial–mesenchymal transition. VNPP433‐3β inhibits CSCs in PCa, presumably by degrading the androgen receptor (AR) thereby decreasing the AR‐mediated transcription of several stem cell markers including BMI1 and KLF4. Transcriptome analyses by RNA‐seq, Ingenuity Pathway Analysis, and Gene Set Enrichment Analysis demonstrate that VNPP433‐3β inhibits transcription of several genes and functional pathways critical to the prostate CSCs thereby inhibiting CSCs in PCa besides targeting the bulk of the tumor.
Learning-Based Intrinsic Reflectional Symmetry Detection

Reflectional symmetry is a ubiquitous pattern in nature. Previous works usually solve this problem by voting or sampling, suffering from high computational cost and randomness. In this article, we propose a learning-based approach to intrinsic reflectional symmetry detection. Instead of directly finding symmetric point pairs, we parametrize this self-isometry using a functional map matrix, which can be easily computed given the signs of Laplacian eigenfunctions under the symmetric mapping. Therefore, we manually label the eigenfunction signs for a variety of shapes and train a novel neural network to predict the sign of each eigenfunction under symmetry. Our network aims at learning the global property of functions and consequently converts the problem defined on the manifold to the functional domain. By disentangling the prediction of the matrix into separated bases, our method generalizes well to new shapes and is invariant under perturbation of eigenfunctions. Through extensive experiments, we demonstrate the robustness of our method in challenging cases, including different topology and incomplete shapes with holes. By avoiding random sampling, our learning-based algorithm is over 20 times faster than state-of-the-art methods, and meanwhile, is more robust, achieving higher correspondence accuracy in commonly used metrics.
Multidirectional activity of bakuchiol against cellular mechanisms of facial ageing ‐ Experimental evidence for a holistic treatment approach

Skin ageing is a multifactorial process involving formation of reactive oxygen species, consecutive inflammation with reduced epidermal and dermal cell viability and resulting damage to the extracellular matrix. Effective dermocosmetic treatment modalities should ideally address these hallmarks in a holistic approach. Here, we determined the corresponding activity profile of bakuchiol, a plant‐derived meroterpene, in an array of in vitro, ex vivo and in vivo studies and compared it to retinol, currently considered as gold standard in topical antiageing cosmetics.
Older immigrant adults experiences with social isolation: a qualitative interpretive meta synthesis

Abstract Objectives: Older immigrants totaled 7.3 million in 2018, representing 13.9 percent of the population of seniors in the U.S. While this population is found to contribute significantly to society, along with new opportunities comes circumstantial challenges. Of these, one of the most salient issues for foreign-born older adults is social isolation. Additionally, this population may be at an increased risk for social isolation with poor mental health because migrating to a new country might result in resettlement challenges. Despite these concerns, less is known about the consequences of social isolation among older immigrant adults. Hence, this study seeks to explore consequences of social isolation among older immigrants, as well as interventions to combat isolation. Methods: Guided by the Population Interest Context (PICO) framework and the Qualitative Interpretive Meta-Synthesis (QIMS) guidelines. Results: The final sample of seven full text articles were published between 2011 and 2021, totaling 286 participants with ages ranging from 61 to 93 years old. Findings from the study indicated that older immigrants are at risk of social isolation and loneliness because they have fewer social connections due to leaving behind their familiar social group in the home country, encounter linguistic challenges that negatively contribute to greater social isolation and poor mental health. Despite these difficulties older immigrants reported various social interventions, access to senior centers, community programs and services to be of greater importance in building social networks. Conclusion: Authors discuss opportunities for future research, such as exploring evidence-based studies on interventions for social isolation and loneliness of older immigrant populations.
A multidisciplinary perspective on physician-assisted dying in primary care in The Netherlands: A narrative interview study

Abstract Most research on physician-assisted dying (PAD) in the Netherlands focuses on general practitioners (GPs). Less is known about the perspectives of other professionals. We performed narrative interviews with 10 professionals other than GPs to explore their perspectives on PAD in primary care. The results provide insight into PAD as an enacted practice involving many different actors, considerations, and expectations and into the intertwinement between PAD and palliative sedation. The study shows how a multidisciplinary perspective to PAD provides new avenues for practice, research, and ethics. It poses the question whether PAD can and should be considered merely a physicians’ concern.
ACSM-AMSSM Call to Action: Adapting Preparticipation Cardiovascular Screening to the COVID-19 Pandemic.

ABSTRACT Preparticipation cardiovascular screening, designed to identify cardiovascular pathology responsible for sudden unexpected death, is recommended by all major professional medical organizations overseeing the clinical care of competitive athletes. Data from several large, prospective, cohort studies indicate that cardiac imaging findings consistent with inflammatory heart disease following COVID-19 infection are more common than most forms of heart disease associated with sudden death during exercise. This call-to-action document is intended to provide recommendations about how routine preparticipation cardiovascular screening for young competitive athletes - which has the capacity to detect both COVID-19 cardiovascular complications and pathology unrelated to infection - should be altered to account for recent scientific advances.
A Facebook-Delivered Weight Loss Intervention Using Open Enrollment: Randomized Pilot Feasibility Trial

Background Behavioral weight loss programs typically enroll 12-40 people into groups that then suffer from declining engagement over time. Web-based patient communities, on the other hand, typically offer no limits on capacity and membership is fluid. This model may be useful for boosting engagement in behavioral weight loss interventions, which could lead to better outcomes. Objective In this study, we aimed to examine the feasibility and acceptability of continuously enrolling participants into a Facebook-delivered weight loss intervention for the first 8 of 16 weeks relative to the same intervention where no new participants were enrolled after randomization. Methods We conducted a randomized pilot trial to compare a Facebook weight loss group that used open enrollment with a group that used closed enrollment on feasibility and acceptability in adults with BMI 27-45 kg/m2. The feasibility outcomes included retention, engagement, and diet tracking adherence. We described the percentage loss of ≥5% weight in both groups as an exploratory outcome. We also explored the relationship between total volume of activity in the group and weight loss. The participants provided feedback via web-based surveys and focus groups. Results Randomized participants (68/80, 85% women) were on average, aged 40.2 (SD 11.2) years with a mean BMI of 34.4 (SD 4.98) kg/m2. We enrolled an additional 54 participants (50/54, 93% female) in the open enrollment condition between weeks 1 and 8, resulting in a total group size of 94. Retention was 88% and 98% under the open and closed conditions, respectively. Randomized participants across conditions did not differ in engagement (P=.72), or diet tracking adherence (P=.42). Participant feedback in both conditions revealed that sense of community was what they liked most about the program and not enough individualized feedback was what they liked the least. Weight loss of ≥5% was achieved by 30% (12/40) of the participants randomized to the open enrollment condition and 18% (7/40) of the participants in the closed enrollment condition. Exploratory analyses revealed that the open condition (median 385, IQR 228-536.5) had a greater volume of engagement than the closed condition (median 215, IQR 145.5-292; P=.007). Furthermore, an increase of 100 in the total volume of engagement in the Facebook group each week was associated with an additional 0.1% weekly weight loss among the randomized participants (P=.02), which was independent of time, individual participant engagement, and sociodemographic characteristics. Conclusions Open enrollment was as feasible and acceptable as closed enrollment. A greater volume of engagement in the Facebook group was associated with weight loss, suggesting that larger groups that produce more engagement overall may be beneficial. Future research should examine the efficacy of the open enrollment approach for weight loss in a fully powered randomized trial. Trial Registration ClinicalTrials.gov NCT02656680; https://clinicaltrials.gov/ct2/show/NCT02656680
Synchronous Spatiotemporal Graph Transformer: A New Framework for Traffic Data Prediction

Modeling the spatiotemporal relationship (STR) of traffic data is important yet challenging for existing graph networks. These methods usually capture features separately in temporal and spatial dimensions or represent the spatiotemporal data by adopting multiple local spatial–temporal graphs. The first kind of method mentioned above is difficult to capture potential temporal–spatial relationships, while the other is limited for long-term feature extraction due to its local receptive field. To handle these issues, the Synchronous Spatio-Temporal grAph Transformer (S2TAT) network is proposed for efficiently modeling the traffic data. The contributions of our method include the following: 1) the nonlocal STR can be synchronously modeled by our integrated attention mechanism and graph convolution in the proposed S2TAT block; 2) the timewise graph convolution and multihead mechanism designed can handle the heterogeneity of data; and 3) we introduce a novel attention-based strategy in the output module, being able to capture more valuable historical information to overcome the shortcoming of conventional average aggregation. Extensive experiments are conducted on PeMS datasets that demonstrate the efficacy of the S2TAT by achieving a top-one accuracy but less computational cost by comparing with the state of the art.
Assessment of Sleep Duration and Number of Awakenings Based on Ankle and Wrist Actigraphy in Medical Hospitalized Older Patients

Background Most studies performed in the hospital assess sleep using self-reports; few rely on actigraphy. Although wrist actigraphy is commonly used for sleep assessment in field studies, in-hospital assessment may be challenging and cumbersome because other more necessary monitoring devices are often attached to patients’ upper limbs; these may affect interpretation of wrist activity data. Placement on the ankle may be a viable solution. Objective To compare total sleep time (TST) and number of awakenings (NOA) using concomitant wrist and ankle actigraphy, as well as self-reports in a sample of older adult patients hospitalized in medical units. Methods This was a prospective observational study. Objective sleep data were collected using ankle and wrist actigraphy, and subjective data using sleep diary. Repeated measures mixed model analysis was performed, adjusting for age, gender, sleep medications, symptoms severity, interaction between types of measure, and night number. Results Twenty-one older adults (65+) wore ankle and wrist actigraphy devices and subjectively estimated sleep parameters for an average of (2.15 ± 1.01) nights, with 40 nights available for analysis. TST was lower for wrist than ankle actigraphy (F(2,87) = 7.92, p = . 0007). Neither differed from self-reports. NOA differed between all types of measure (ankle, 8.58 ± 6.66; wrist, 15.49 ± 7.47; self-report, 1.81 ± 1.83; F(2,85) = 47.66, p < . 001). No significant within-subject variations and no interaction between devices and repeated measures were found. Conclusions Despite differences between ankle and wrist assessments, all three methods provided consistent TST estimation within participants. Findings provide preliminary support for the use of ankle actigraphy for sleep assessment in hospital settings.
WIDE BAND DUAL FREQUENCY CIRCULAR SLOT ANTEENA WITH RECTANGULAR STUB AT X AND KU

The paper presents design and study of the performance of simple circular slot antenna, fed by microstrip line. The dual frequency response having center frequency of 10.58 GHz is observed by using 0.2m. m wide rectangular stub connected with microstrip line. The effect of bandwidth enhancement studies on the return loss performance (-10db) by changing the substrate thickness and substrate material is also being carried out.
Macrophage activation syndrome in rheumatic disease: Clinical characteristics and prognosis of 20 adult patients

Objectives Macrophage activation syndrome (MAS) is a hyperinflammatory condition that is known to be secondary hemophagocytic lymphohistiocytosis (HLH) in patients with rheumatic disease. The aim of study was to evaluate the clinical manifestations and outcomes in patients with MAS with rheumatic disease. Materials and methods We performed a retrospective study of 20 adult patients who were diagnosed with MAS from 2012 to 2020. MAS was classified according to the HLH-2004 criteria. Patients’ information, including clinical features, laboratory findings, and treatment regimens, was collected, and the overall survival rate was estimated by the Kaplan–Meier method. Results Twenty patients (18 women, 35.6 ± 18.3 years) who met the HLH-2004 criteria also fulfilled the 2016 EULAR/ACR/PRINTO classification criteria for MAS, and HScore was higher than 169 (mean, 241.1). Fourteen patients with systemic lupus erythematosus and 6 patients with adult-onset Still’s disease were included. All patients were treated initially with corticosteroids, and 16 patients required additional immunosuppressants. The overall survival at 3 and 6 months was 75.2% and 64.3%. In survivors, renal impairment was less common (7.7% versus 71.4%, p = 0.007), the levels of AST (364.0 versus 81.0 IU/L, p = 0.019) and LDH (1346.0 versus 343.0IU/L, p = 0.014), and platelet count (90.0 versus 43.0 × 109/L, p = 0.02) were higher in compared to non-survivors. Nine patients had opportunistic infections, five of whom died during admission. Conclusion The mortality of patients with MAS associated with rheumatic disease remains high. Renal impairment, levels of AST and LDH, and platelet count might be associated with prognosis.
Metagenomic Sequencing with Strain-Level Resolution Implicates Metagenomic Sequencing with Strain-Level Resolution Implicates Uropathogenic E. coli in Necrotizing Enterocolitis and Mortality in Uropathogenic E. coli in Necrotizing Enterocolitis and Mortality in Preterm Infants Preterm Infants

identify We a large-scale deep shotgun metagenomic sequence analysis of the early intestinal microbiome of 144 preterm and 22 term infants. Using a pan-genomic approach to functionally subtype the , we identify genes associated with NEC that by We analyzed deep shotgun metagenomic sequencing of fecal samples collected from 144 preterm infants in 3 neonatal intensive care units and 22 term infants. We applied an assembly-free, pangenome-based computational analysis to determine the E. coli -speciﬁc gene content of strains within the infant micro-biomes. Accessory genes involved in iron acquisition, phosphotransferase systems (PTSs), and D-serine metabolism were characteristic of strains associated with NEC risk. Additional analysis characterized the risk strains as uropathogenic E. coli (UPEC) (Flores-Mireles et al., 2015; Wiles et al., 2008; Zhang and Foxman, 2003). We present evidence that (i) colonization by UPEC is a risk factor for development of NEC and (ii) UPEC correlated with death as an outcome. These ﬁndings suggest an association between UPEC and NEC and provide a founda-tion for advancing the epidemiology of NEC. In our patient population, we identify carriage of uropathogenic subtypes of E. coli as a signiﬁcant contributor to risk of NEC.
ImmunogenicityAllergenic Activity and Preserve Grass Pollen Allergen, Phl p 6, to Reduce Genetic Engineering of the Major Timothy

On the basis of IgE epitope mapping data, we have produced three allergen fragments comprising aa 1–33, 1–57, and 31–110 of the major timothy grass pollen allergen Phl p 6 aa1–110 by expression in Escherichia coli and chemical synthesis. Circular dichroism analysis showed that the puriﬁed fragments lack the typical (cid:1) -helical fold of the complete allergen. Superposition of the sequences of the fragments onto the three-dimensional allergen structure indicated that the removal of only one of the four helices had led to the destabilization of the (cid:1) helical structure of Phl p 6. The lack of structural fold was accompanied by a strong reduction of IgE reactivity and allergenic activity of the three fragments as determined by basophil histamine release in allergic patients. Each of the three Phl p 6 fragments adsorbed to CFA induced Phl p 6-speciﬁc IgG Abs in rabbits. However, immunization of mice with fragments adsorbed to an adjuvant allowed for human use (AluGel-S) showed that only the Phl p 6 aa 31–110 induced Phl p 6-speciﬁc IgG Abs. Anti-Phl p 6 IgG Abs induced by vaccination with Phl p 6 aa31–110 inhibited patients’ IgE reactivity to the wild-type allergen as well as Phl p 6-induced basophil degranulation. Our results are of importance for the design of hypoallergenic allergy vaccines. They show that it has to be demonstrated that the hypoallergenic derivative induces a robust
Hippocampal c-Jun-N-terminal kinases serve as negative Hippocampal c-Jun-N-terminal kinases serve as negative regulators of associative learning regulators of associative learning us know how access to this document benefits you.

In the adult mouse, signaling through c-Jun N-terminal kinases (JNKs) links exposure to acute stress to various physiological responses. Inflammatorycytokines,braininjuryandischemicinsult,orexposuretopsychologicalacutestressorsinduceactivationofhippocampalJNKs.HerewereportthatexposuretoacutestresscausedactivationofJNKsinthehippocampalCA1andCA3subfields,andimpairedcontextualfearconditioning.Conversely,intrahippocampalinjectionofJNKsinhibitorssp600125(30 (cid:1) M ) or D -JNKI1 (8 (cid:1) M ) reduced activity of hippocampal JNKs and rescued stress-induced deficits in contextual fear. In addition, intrahippocampal administration of anisomycin (100 (cid:1) g/ (cid:1) l), a potent JNKs activator, mimicked memory-impairing effects of stress on contextual fear. This anisomycin-induced amnesia was abolished after cotreatment with JNKs selective inhibitor sp600125 without affecting anisomycin’s ability to effectivelyinhibitproteinsynthesisasmeasuredbyc-Fosimmunoreactivity.WealsodemonstratedmilderandtransientactivationoftheJNKspathwayintheCA1subfieldofthehippocampusduringcontextualfearconditioningandanenhancementofcontextualfearafterpharmacologicalinhibitionofJNKsunderbaselineconditions. Finally,usingcombinedbiochemicalandtransgenicapproacheswithmutantmicelackingdifferentmembersoftheJNKfamily( Jnk1, Jnk2, and Jnk3 ), we provided evidence that JNK2 and JNK3 are critically involvedinstress-induceddeficitofcontextualfear,whileJNK1mainlyregulatesbaselinelearninginthisbehavioraltask.Together,theseresultssupportthepossibilitythathippocampalJNKsserveasacriticalmolecularregulatorintheformationofcontextualfear.
Adaptive sliding mode fuzzy control of planar inverted pendulum

A dynamical model of the planar inverted pendulum is developed by using Lagrange equations. By the linearization of the model at its equilibrium yields, the decoupled linear systems of the inverted pendulum in two perpendicular control directions are obtained. Both of the two systems consist of two coupled subsystems including positioning subsystem of the base cart and balancing system of the pole. For each direction, the adaptive sliding mode fuzzy control approach is developed. Finally, the circular motion of the base cart is implemented and the pole is kept balance. A motion experiment shows the effectiveness of the adaptive sliding mode fuzzy control strategy.
Leading to Functional ImpairmentLymphocytes Oxidative Damage in Human T Methamphetamine Causes Mitrochondrial

Methamphetamine (METH) abuse is known to be associated with an inordinate rate of infections. Although many studies have described the association of METH exposure and immunosuppression, so far the underlying mechanism still remains elusive. In this study, we present evidence that METH exposure resulted in mitochondrial oxidative damage and caused dysfunction of primary human T cells. METH treatment of T lymphocytes led to a rise in intracellular calcium levels that enhanced the generation of reactive oxygen species. TCR-CD28 linked calcium mobilization and subsequent uptake by mitochondria in METH-treated T cells correlated with an increase in mitochondrion-derived superoxide. Exposure to METH-induced mitochondrial dysfunction in the form of marked decrease in mitochondrial membrane potential, increased mitochondrial mass, enhanced protein nitrosylation and diminished protein levels of complexes I, III, and IV of the electron transport chain. These changes paralleled reduced IL-2 secretion and T cell proliferative responses after TCR-CD28 stimulation indicating impaired T cell function. Furthermore, antioxidants attenuated METH-induced mitochondrial damage by preserving the protein levels of mitochondrial complexes I, III, and IV. Altogether, our data indicate that METH can cause T cell dysfunction via induction of oxidative stress and mitochondrial injury as underlying mechanism of immune impairment secondary to METH abuse. The Journal of Immunology , 2010, 185: 2867–2876.
Selected problems of assessment of suitability of rural areas for investment activities on an example an optimal location for production plant.

Rural areas are increasingly often becoming attractive to investors. One obvious reason is the limited total area of land allocated to development in towns. Moreover, land parcels available for development in nonurbanised surroundings are less expensive. Rural areas lying in the proximity of towns are particularly appealing. However, the choice of a location that will satisfy the expectations of both the investor and future users of a planned building development depends on a number of factors, some of which can generate many problems. Thus, decision support methods can be useful when making a decision about the location of a building investment. This article contains a case of an analysis of available locations for the development of an industrial project in a rural area, which was conducted with two methods: multi-criteria analysis and graphic method.