Miracle-dz/UniFAR-FTUs huggingface dataset:
IoT-RECSM—Resource-Constrained Smart Service Migration Framework for IoT Edge Computing Environment

The edge-based computing paradigm (ECP) becomes one of the most innovative modes of processing distributed Interneit of Things (IoT) sensor data. However, the edge nodes in ECP are usually resource-constrained. When more services are executed on an edge node, the resources required by these services may exceed the edge node’s, so as to fail to maintain the normal running of the edge node. In order to solve this problem, this paper proposes a resource-constrained smart service migration framework for edge computing environment in IoT (IoT-RECSM) and a dynamic edge service migration algorithm. Based on this algorithm, the framework can dynamically migrate services of resource-critical edge nodes to resource-rich nodes. In the framework, four abstract models are presented to quantificationally evaluate the resource usage of edge nodes and the resource consumption of edge service in real-time. Finally, an edge smart services migration prototype system is implemented to simulate the edge service migration in IoT environment. Based on the system, an IoT case including 10 edge nodes is simulated to evaluate the proposed approach. According to the experiment results, service migration among edge nodes not only maintains the stability of service execution on edge nodes, but also reduces the sensor data traffic between edge nodes and cloud center.
Genetic correction of Werner syndrome gene reveals impaired pro‐angiogenic function and HGF insufficiency in mesenchymal stem cells

WRN mutation causes a premature aging disease called Werner syndrome (WS). However, the mechanism by which WRN loss leads to progeroid features evident with impaired tissue repair and regeneration remains unclear. To determine this mechanism, we performed gene editing in reprogrammed induced pluripotent stem cells (iPSCs) derived from WS fibroblasts. Gene correction restored the expression of WRN. WRN+/+ mesenchymal stem cells (MSCs) exhibited improved pro‐angiogenesis. An analysis of paracrine factors revealed that hepatocyte growth factor (HGF) was downregulated in WRN−/− MSCs. HGF insufficiency resulted in poor angiogenesis and cutaneous wound healing. Furthermore, HGF was partially regulated by PI3K/AKT signaling, which was desensitized in WRN−/− MSCs. Consistently, the inhibition of the PI3K/AKT pathway in WRN+/+ MSC resulted in reduced angiogenesis and poor wound healing. Our findings indicate that the impairment in the pro‐angiogenic function of WS‐MSCs is due to HGF insufficiency and PI3K/AKT dysregulation, suggesting trophic disruption between stromal and epithelial cells as a mechanism for WS pathogenesis.
How to Relax in Stressful Situations: A Smart Stress Reduction System

Stress is an inescapable element of the modern age. Instances of untreated stress may lead to a reduction in the individual’s health, well-being and socio-economic situation. Stress management application development for wearable smart devices is a growing market. The use of wearable smart devices and biofeedback for individualized real-life stress reduction interventions has received less attention. By using our unobtrusive automatic stress detection system for use with consumer-grade smart bands, we first detected stress levels. When a high stress level is detected, our system suggests the most appropriate relaxation method by analyzing the physical activity-based contextual information. In more restricted contexts, physical activity is lower and mobile relaxation methods might be more appropriate, whereas in free contexts traditional methods might be useful. We further compared traditional and mobile relaxation methods by using our stress level detection system during an eight day EU project training event involving 15 early stage researchers (mean age 28; gender 9 Male, 6 Female). Participants’ daily stress levels were monitored and a range of traditional and mobile stress management techniques was applied. On day eight, participants were exposed to a ‘stressful’ event by being required to give an oral presentation. Insights about the success of both traditional and mobile relaxation methods by using the physiological signals and collected self-reports were provided.
Cortical processing of chemosensory and hedonic features of taste in active licking mice

In the last two decades, a considerable amount of work has been devoted to investigating the neural processing and dynamics of the primary taste cortex of rats. Surprisingly, much less information is available on cortical taste electrophysiology in awake mice, an animal model that is taking a more prominent role in taste research. Here we present electrophysiological evidence demonstrating how the gustatory cortex (GC) encodes information pertaining the basic taste qualities (sweet, salty, sour, and bitter) when stimuli are actively sampled through licking, the stereotyped behavior by which mice control the access of fluids in the mouth. Mice were trained to receive each stimulus on a fixed ratio schedule in which they had to lick a dry spout six times to receive a tastant on the seventh lick. Electrophysiological recordings confirmed that GC neurons encode both chemosensory and hedonic aspects of actively sampled tastants. In addition, our data revealed two other main findings; GC neurons encoded information about taste identity in as little as 120 ms. Consistent with the ability of GC neurons to rapidly encode taste information, nearly half of the recorded neurons exhibited spiking activity that was entrained to licking at rates up to 8 Hz. Overall, our results highlight how the GC of mice processes tastants when they are actively sensed through licking, reaffirming and expanding our knowledge on cortical taste processing. NEW & NOTEWORTHY Relatively little information is available on the neural dynamics of taste processing in the mouse gustatory cortex (GC). In this study we investigate how the GC encodes information of the qualities and hedonics of a broad panel of gustatory stimuli when tastants are actively sampled through licking. Our results show that the GC neurons broadly encode taste qualities but also process taste hedonics and licking information in a temporally dynamic manner.
Green Nut Oil or DHA Supplementation Restored Decreased Distribution Levels of DHA Containing Phosphatidylcholines in the Brain of a Mouse Model of Dementia

Dementia is a major public health concern nowadays. Reduced levels of brain docosahexaenoic acid (DHA) and DHA-phosphatidylcholines (DHA-PCs) in dementia patients were reported previously. Recently, we have reported that supplementation of green nut oil (GNO) or DHA improves memory function and distribution levels of brain DHA in senescence accelerated mice P8 (SAMP8). GNO is extracted from Plukenetia volubilis seeds, and SAMP8 is a well-known model mouse of dementia. In this current study, we examined the results of GNO or DHA supplementation in the distribution levels of brain DHA-PCs in same model mouse of dementia using desorption electrospray ionization (DESI) mass spectrometry imaging (MSI). We observed significantly decreased distribution of brain DHA-PCs, PC (16:0_22:6), and PC (18:0_22:6) in SAMP8 mice compared to wild type mice, and GNO or DHA treatment restored the decreased distribution levels of PC (16:0_22:6) and PC (18:0_22:6) in the brain of SAMP8 mice. These results indicate that GNO or DHA supplementation can ameliorate the decreased distribution of brain DHA-PCs in dementia, and could be potentially used for the prevention and treatment of dementia.
Palliative Care in a Death-Denying Culture: Exploring Barriers to Timely Palliative Efforts for Heart Failure Patients in the Primary Care Setting

Context: Heart failure (HF) is a complex, life-limiting disease that is prevalent and burdensome. All major cardiology societies and international clinical practice guidelines recommend the integration of palliative care (PC) interventions alongside usual HF management. Objectives: The purpose of this review of the literature was to evaluate the various barriers to the early initiation of PC for HF patients in the primary care setting. Methods: An integrative literature review was conducted in order to assess and incorporate the diverse sources of literature available. An EBSCO search identified relevant articles in the following databases: Medline complete, Academic Search Premier, CINAHL, PsycINFO, Cochrane Library, and SocINDEX. The search was limited to full text, peer reviewed, English only, and published between 2010 and 2019. Results: Barriers to the integration of PC for HF patients include poor communication between provider/patient and interdisciplinary providers, the misperception and miseducation of what PC is and how it can be incorporated into patient care, the unpredictable disease trajectory of HF, and the limited time allowed for patient care in the primary care setting. Conclusion: The results of this review highlight a lack of communication, time, and knowledge as barriers to delivering PC. Primary care providers caring for patients with HF need to establish an Annual Heart Failure Review to meticulously evaluate symptoms and allow the time for communication involving prognosis, utilize a PC referral screening tool such as the Needs Assessment Tool: Progressive Disease-Heart Failure, and thoroughly understand the benefits and appropriate integration of PC.
MiR193a Modulation and Podocyte Phenotype †

Apolipoprotein L1 (APOL1)-miR193a axis has been reported to play a role in the maintenance of podocyte homeostasis. In the present study, we analyzed transcription factors relevant to miR193a in human podocytes and their effects on podocytes’ molecular phenotype. The motif scan of the miR193a gene provided information about transcription factors, including YY1, WT1, Sox2, and VDR-RXR heterodimer, which could potentially bind to the miR193a promoter region to regulate miR193a expression. All structure models of these transcription factors and the tertiary structures of the miR193a promoter region were generated and refined using computational tools. The DNA-protein complexes of the miR193a promoter region and transcription factors were created using a docking approach. To determine the modulatory role of miR193a on APOL1 mRNA, the structural components of APOL1 3’ UTR and miR193a-5p were studied. Molecular Dynamic (MD) simulations validated interactions between miR193a and YY1/WT1/Sox2/VDR/APOL1 3′ UTR region. Undifferentiated podocytes (UPDs) displayed enhanced miR193a, YY1, and Sox2 but attenuated WT1, VDR, and APOL1 expressions, whereas differentiated podocytes (DPDs) exhibited attenuated miR193a, YY1, and Sox2 but increased WT1, VDR, APOL1 expressions. Inhibition of miR193a in UPDs enhanced the expression of APOL1 as well as of podocyte molecular markers; on the other hand, DPD-transfected with miR193a plasmid showed downing of APOL1 as well as podocyte molecular markers suggesting a causal relationship between miR193a and podocyte molecular markers. Silencing of YY1 and Sox2 in UPDs decreased the expression of miR193a but increased the expression of VDR, and CD2AP (a marker of DPDs); in contrast, silencing of WT1 and VDR in DPDs enhanced the expression of miR193a, YY1, and Sox2. Since miR193a-downing by Vitamin D receptor (VDR) agonist not only enhanced the mRNA expression of APOL1 but also of podocyte differentiating markers, suggest that down-regulation of miR193a could be used to enhance the expression of podocyte differentiating markers as a therapeutic strategy.
Economic Implications of Chinese Diagnosis-Related Group–Based Payment Systems for Critically Ill Patients in ICUs

Supplemental Digital Content is available in the text. Objectives: To evaluate the economic implications of payments based on Chinese diagnosis-related groups for critically ill patients in ICUs in terms of total hospital expenditure, out-of-pocket payments, and length of stay. Design: A pre-post comparison of patient cohorts admitted to ICUs 1 year before and 1 year after Chinese diagnosis-related group reform was undertaken. Demographic characteristics, clinical data, and medical expenditures were collated from a health insurance database. Setting: Twenty-two public hospitals in Sanming, Southern China. Patients: All patients admitted to ICUs from January 1, 2017, to December 31, 2018. Intervention: The implementation of Chinese diagnosis-related group–based payments on January 1, 2018. Measurements and Main Results: Economic variables (total expenditures, out-of-pocket payments, and length of stay) were calculated for each patient from the day of hospital admission to the day of hospital discharge. Adjusted mean out-of-pocket payment estimates were 29.46% (p < 0.001) lower following reform. Adjusted mean out-of-pocket payments fell by 41.32% for patients in neonatal ICU, whereas there were no significant decreases in out-of-pocket payments for patients in PICU and adult ICU. Furthermore, adjusted mean out-of-pocket payments decreased by 55.74% in secondary hospitals, but there was no significant change in tertiary hospitals after Chinese diagnosis-related group reform. No significant changes were found in total expenditures and length of stay. Conclusions: Chinese diagnosis-related group policy provided an opportunity for critically ill patients in ICUs to achieve at least short-term financial benefits in reducing out-of-pocket payments, without affecting the total expenditures and length of stay. Chinese diagnosis-related group–based payment significantly relieved financial burdens for patients with lower illness severities, such as patients in neonatal ICU. The results of this study can offer significant insights for policymakers in reducing the financial burden on critically ill patients, both in China and in other countries with similar systems.
Efficacy and Safety of Polaprezinc (Zinc Compound) on Zinc Deficiency: A Systematic Review and Dose–Response Meta-Analysis of Randomized Clinical Trials Using Individual Patient Data

Zinc intake is recommended for zinc deficiency. In clinical practice, polaprezinc has been used as a zinc replacement therapy for zinc deficiency. However, the efficacy of polaprezinc has not been established. To confirm the efficacy on zinc deficiency of polaprezinc and provide additional information on an appropriate regimen, we conducted a systematic review using individual patient data (IPD). We searched PubMed, the Japanese database Ichushi, and the database owned by the marketing authorization holder of polaprezinc. Randomized placebo-controlled trials that reported the serum zinc concentration were eligible. The mean difference of the change from baseline in serum zinc concentration was estimated using a fixed-effects model. The linear dose–response relationship and the subgroup effects were also assessed. Out of 54 unique randomized clinical trials (RCTs), four studies met the eligibility criteria, and we could access IPD for all of them. All three doses of polaprezinc (75 mg, 150 mg, and 300 mg) and the placebo group were examined. The dose-combined overall polaprezinc increased the change from baseline by a mean of 9.08 µg/dL (95% confidence interval: 5.46, 12.70; heterogeneity: I2 = 0.61%) compared to the placebo. A significant dose–response relationship was confirmed (p < 0.001). Baseline serum zinc concentration was considered an effect modifier in polaprezinc 300 mg. All doses of polaprezinc were tolerable, but a dose–response relationship with adverse events (AEs) was observed in gastrointestinal disorders. The dose of 300 mg may be useful among patients with baseline serum zinc concentration of less than 70 µg/dL, and 150 mg for 70 µg/dL or more.
Multimeric antibodies with increased valency surpassing functional affinity and potency thresholds using novel formats

ABSTRACT The success of therapeutic antibodies is largely attributed for their exquisite specificity, homogeneity, and functionality. There is, however, a need to engineer antibodies to extend and enhance their potency. One parameter is functional affinity augmentation, since antibodies matured in vivo have a natural affinity threshold. Generation of multivalent antibodies is one option capable of surpassing this affinity threshold through increased avidity. In this study, we present a novel platform consisting of an array of multivalent antibody formats, termed Quads, generated using the self-assembling tetramerization domain from p53. We demonstrate the versatility of this tetramerization domain by engineering anti-tumor necrosis factor (TNF) Quads that exhibit major increases in binding potency and in neutralizing TNF-mediated cytotoxicity compared to parental anti-TNF molecules. Further, Quads are amenable to fusion with different binding domains, allowing generation of novel multivalent monospecific and bispecific formats. Quads are thus a novel group of molecules that can be engineered to yield potential therapeutics with novel modalities and potencies.
Machine Learning Approaches for Quality Assessment of Protein Structures

Protein structures play a very important role in biomedical research, especially in drug discovery and design, which require accurate protein structures in advance. However, experimental determinations of protein structure are prohibitively costly and time-consuming, and computational predictions of protein structures have not been perfected. Methods that assess the quality of protein models can help in selecting the most accurate candidates for further work. Driven by this demand, many structural bioinformatics laboratories have developed methods for estimating model accuracy (EMA). In recent years, EMA by machine learning (ML) have consistently ranked among the top-performing methods in the community-wide CASP challenge. Accordingly, we systematically review all the major ML-based EMA methods developed within the past ten years. The methods are grouped by their employed ML approach—support vector machine, artificial neural networks, ensemble learning, or Bayesian learning—and their significances are discussed from a methodology viewpoint. To orient the reader, we also briefly describe the background of EMA, including the CASP challenge and its evaluation metrics, and introduce the major ML/DL techniques. Overall, this review provides an introductory guide to modern research on protein quality assessment and directions for future research in this area.
Local Consolidation Therapy versus Observation for Oligometastatic Non Small Cell Lung Cancer Patients: Phase II Randomized Trial

Background and Objective: Based on retrospective trials, most progression sites after first line systemic therapy for metastatic non small cell lung cancer (NSCLC) were the primary disease sites rather than new sites. Therefore we conducted phase II randomized study to determine whether oligometastatic NSCLC without disease progression after first line chemotherapy, have prolonged progression free survival when treated with local consolidation therapy of residual disease followed by surveillance compared with no local consolidation therapy (observation). Patients and Methods: Forty eight eligible patients were randomized to either immediate or no local consolidation radiotherapy. 26 patients of immediate local consolidation radiotherapy received 3 D-conformal radiation therapy to primary tumor site and metastatic sites of disease. 22 patients were followed up by observation. Results: Patients in local consolidation arm had significantly better progression free survival (PFS) compared with patients in observation group. Median PFS was 9.5 months (95% CI 7.8 - 11.08) in local consolidation arm and 4.5 months (95%CI 3.9 - 5.7) in observation arm. Patients in local consolidation arm had longer median time to appearance of new metastatic sites (10 months CI 9.3 - 12.6) than those patients in observation arm (4.5 months CI 4.2 - 6.9). Median overall survival (OS) of patients in local consolidation arm was 12 months (95% CI 12.1 - 18.01) and in observation arm 10 months (95% CI 8.7 - 13.8). One year OS rate was 42.3% in local consolidation arm and 31.8% in observation arm; 2 year OS rate was 23.1% in local consolidation arm and only 4.5% in observation arm. Conclusion: Local consolidation radiotherapy is simple, safe, efficient, and not expensive treatment for oligometastatic non small cell lung cancer after upfront chemotherapy. Local consolidation radiotherapy achieved significantly prolonged progression free survival and delayed appearance of new metastatic sites. Phase III studies are recommended to test benefit of local consolidation radiotherapy to gain prolonged progression free survival and overall survival. Also, define optimal patients’ subgroups that are more likely to benefit of local consolidation radiotherapy.
Intraoperative aberrometry in cataract surgery with topical versus peribulbar anesthesia

Purpose: To study the effect of choice of anesthesia on the refractive outcomes of intraoperative aberrometry (IA) for intraocular lens power calculation in cataract surgeries. Methods: This prospective, interventional nonrandomized cohort study was conducted at a tertiary care hospital between March and August 2018. A total of 178 patients with age-related cataract were allocated into two groups. Group 1 received peribulbar anesthesia using a mixture of xylocaine 2% + adrenaline 0.125 mg/ml + hyaluronidase 15 IU/ml with a 23G, 32 mm needle, while Group 2 received topical anesthesia with proparacaine hydrochloride 0.05% drops. Intraoperative aphakic measurements and IOL power calculations were obtained in all patients with the optiwave refractive analysis (ORA) system. Analysis was performed to compare the baseline parameters and postoperative manifest refraction at month 1. Results: A total of 89 patients were included in group 1 and 89 in group 2. At baseline, the axial lengths (P = 0.66) and mean keratometry (P = 0.91) were comparable. The quality measure of captured wavefront data was comparable (0.25) between the groups. Also, the postoperative mean refractive spherical equivalents were comparable between the two groups (P = 0.98) at one month. Conclusion: IA can be utilized well for cataract surgeries performed under local anesthesia with good quality of captured wavefront, provided the eye can be aligned in centre with the fixation light of ORA.
CXCL12 is required for stirrup‐shaped stapes formation during mammalian middle ear development

The mammalian middle ear comprises a chain of three ossicles—the malleus, incus, and stapes—each of which has a unique morphology for efficiently transmitting sound information. In particular, the stapes, which is attached to the inner ear, is stirrup‐shaped with a head and base connected by two crural arches, forming the stapedial foramen, through which the stapedial artery passes. However, how the stapes acquires this critical stirrup shape for association with the stapedial artery during development is not clear.
Sulfated vizantin inhibits biofilm maturation by Streptococcus mutans

Streptococcus mutans is the main pathogen of dental caries and adheres to the tooth surface via soluble and insoluble glucans produced by the bacterial glucosyltransferase enzyme. Thus, the S. mutans glucosyltransferase is an important virulence factor for this cariogenic bacterium. Sulfated vizantin effectively inhibits biofilm formation by S. mutans without affecting its growth. In this study, less S. mutans biofilm formation occurred on hydroxyapatite discs coated with sulfated vizantin than on noncoated discs. Sulfated vizantin showed no cytotoxicity against the human gingival cell line Ca9‐22. Sulfated vizantin dose‐dependently inhibited the extracellular release of cell‐free glucosyltransferase from S. mutans and enhanced the accumulation of cell‐associated glucosyltransferase, compared with that observed with untreated bacteria. Sulfated vizantin disrupted the localization balance between cell‐associated glucosyltransferase and cell‐free glucosyltransferase, resulting in inhibited biofilm maturation. These results indicate that sulfated vizantin can potentially serve as a novel agent for preventing dental caries.