Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of antibody-mediated complement-dependent cytotoxicity by modulating the intrinsic affinity and binding valency of IgG for target antigen

ABSTRACT Complement-dependent cytotoxicity (CDC) is a potent effector mechanism, engaging both innate and adaptive immunity. Although strategies to improve the CDC activity of antibody therapeutics have primarily focused on enhancing the interaction between the antibody crystallizable fragment (Fc) and the first subcomponent of the C1 complement complex (C1q), the relative importance of intrinsic affinity and binding valency of an antibody to the target antigen is poorly understood. Here we show that antibody binding affinity to a cell surface target antigen evidently affects the extent and efficacy of antibody-mediated complement activation. We further report the fundamental role of antibody binding valency in the capacity to recruit C1q and regulate CDC. More specifically, an array of affinity-modulated variants and functionally monovalent bispecific derivatives of high-affinity anti-epidermal growth factor receptor (EGFR) and anti-human epidermal growth factor receptor 2 (HER2) therapeutic immunoglobulin Gs (IgGs), previously reported to be deficient in mediating complement activation, were tested for their ability to bind C1q by biolayer interferometry using antigen-loaded biosensors and to exert CDC against a panel of EGFR and HER2 tumor cells of various histological origins. Significantly, affinity-reduced variants or monovalent derivatives, but not their high-affinity bivalent IgG counterparts, induced near-complete cell cytotoxicity in tumor cell lines that had formerly been shown to be resistant to complement-mediated attack. Our findings suggest that monovalent target engagement may contribute to an optimal geometrical positioning of the antibody Fc to engage C1q and deploy the complement pathway.
Silver Nanoparticle Conjugated Star PCL-b-AMPs Copolymer as Nanocomposite Exhibits Efficient Antibacterial Properties.

The traditional antibiotics have specific intracellular targets and disinfect in chemical ways, and the drug-resistance induced by the antibiotics has grown into an emerging threat. It is an urgent to call for novel strategies and antibacterial materials to control this situation. Herein, we report a class of silver-decorated nanocomposite AgNPs@PCL-b-AMPs as potent nano-antibiotic, constructed by ring-opening polymerization of the monomers ε-caprolactone, Z-Lys-N-carboxyanhydrides (NCAs) and Phe-NCAs, then decorated with AgNPs, and characterized by SEM, TEM and DLS. The biological assays revealed that the nanocomposite possessed strong antibacterial efficacy against both Gram-positive and Gram-negative bacteria including clinic isolated bacteria MRSA, VRE, P. aeruginosa, and K. pneumonia, exhibiting a MIC value range in 2-8 μg/mL. Importantly, the S. aureus and P. aeruginosa treated with the nanocomposite didn't show drug-resistance even after 21th passages. Also, in vivo anti-infective assays showed that the nanocomposite was able to effectively kill bacteria in the infected viscera of mice. The study of the sterilization mechanism showed that the nanocomposite exhibited a multimodal antimicrobial mechanism, including irreversibly damaged the membrane structure, made the leakage of intracellular ions and subsequently induced generation of the reactive oxygen species (ROS), ultimately sterilized bacteria. The nanocomposite exhibit effective broad-spectrum antibacterial property and show low toxicity to the mammalian cells /animal. Overall, the AgNPs@PCL-b-AMPs gained in this work show great potential as a highly promising antibacterial material for biomedical applications including drug-resistant bacterial infection.
Draft Genome Sequences of Bacillus sp. Strains RM1(2019), RM2(2019), RM9(2019), RM11(2019), and RM15(2019), Isolated from Temperate Soils in the Hudson River Valley of New York

We report the draft genome sequences of five novel Bacillus strains isolated from temperate soils in Annandale-on-Hudson, NY. Strains RM1(2019), RM9(2019), and RM15(2019) were identified as Bacillus toyonensis, while RM11(2019) was identified as Bacillus thuringiensis. The draft genome of strain RM2(2019) was unclassified and likely represents a new species. ABSTRACT We report the draft genome sequences of five novel Bacillus strains isolated from temperate soils in Annandale-on-Hudson, NY. Strains RM1(2019), RM9(2019), and RM15(2019) were identified as Bacillus toyonensis, while RM11(2019) was identified as Bacillus thuringiensis. The draft genome of strain RM2(2019) was unclassified and likely represents a new species.
Primary Care Prescriptions of Potentially Nephrotoxic Medications in Children with CKD.

BACKGROUND AND OBJECTIVES Pediatric CKD management focuses on limiting kidney injury, including avoiding nephrotoxic medications. Nephrotoxic medication prescription practices for children with CKD are unknown. Our objective was to determine the prevalence and rates of primary care prescriptions for potentially nephrotoxic medications in children with CKD versus without CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a retrospective, matched population-based cohort study of patients aged <18 years, registered at a general practice participating in the UK Clinical Practice Research Datalink (CPRD) from 1997 to 2017. Children with a clinical code indicating an incident diagnosis of CKD were matched 1:4 to patients without CKD on CKD diagnosis date, sex, age, CPRD practice, and number of general practitioner visits in the year before cohort entry. We calculated the prevalence and the rate of potentially nephrotoxic medication prescriptions throughout the follow-up period in patients with versus without CKD. Primary analyses included the following medication classes: aminoglycosides, antivirals, nonsteroidal anti-inflammatory drugs, salicylates, proton pump inhibitors, and immunomodulators. Secondary analyses used an expanded nephrotoxicity definition that also included, among others, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Adjusted prescription rates were calculated using multivariable binomial regression. RESULTS From 1,535,816 eligible patients, we identified 1018 incident CKD and 4072 non-CKD matches (mean age, 9.8 years [range, 1.1-17.9 years]; 52% male; mean follow-up time, 3.3 years). Overall, 26% of patients with and 15% of patients without CKD were prescribed one or more potentially nephrotoxic medication during follow-up. The overall rate of nephrotoxic medication prescriptions was 71 (95% confidence interval [95% CI], 55 to 93) prescriptions per 100 person-years in patients with CKD and eight (95% CI, 7 to 9) prescriptions per 100 person-years in patients without CKD (adjusted rate ratio, 4.1; 95% CI, 2.7 to 6.1). CONCLUSIONS Potentially nephrotoxic medications are prescribed at high rates to children with CKD.
A Meta-analysis of Narrative Game-based Interventions for Promoting Healthy Behaviors

Health interventions that use serious games have become increasingly popular. However, many of these games have been designed with few immersive game features which would improve users’ engagement with the persuasive messages. To address this issue, researchers have incorporated narrative elements in games to facilitate message processing and enhance behavioral change. There have been theoretical debates about whether narratives benefit these interventions; empirical evidences for their effects are slightly mixed. This meta-analysis provides a deeper understanding of the overall impact of narrative game-based interventions on health-related behaviors and their psychological determinants. Combining the results from 22 studies, this meta-analysis found that narrative game-based interventions were effective in changing behaviors, knowledge, self-efficacy, and enjoyment. These effects were moderated by factors such as the genre of the game, the genre of the story, group play, and participant age. Implications of the findings and suggestions for future design of narrative game-based interventions were discussed.
The well-being profile (WB-Pro): Creating a theoretically based multidimensional measure of well-being to advance theory, research, policy, and practice.

There is no universally agreed definition of well-being as a subjective experience, but Huppert and So (2013) adopted and systematically applied the definition of well-being as positive mental health-the opposite of the common mental disorders described in standard mental health classifications (e.g., Diagnostic and Statistical Manual of Mental Disorders). We extended their theoretical approach to include multi-item scales, using 2 waves of nationally representative U.S. adult samples to develop, test, and validate our multidimensional measure of well-being (WB-Pro). This resulted in a good-fitting a priori (48-item, 15-factor) model that was invariant over time, education, gender, and age; showed good reliability (coefficient αs .81-.93), test-retest correlation (.73-.85; M = .80), and convergent/discriminant validity based on a multitrait-multimethod analysis, and relations with demographic variables, selected psychological measures, and other multidimensional and purportedly unidimensional well-being measures. Further, we found that items from 2 widely used, purportedly unidimensional well-being measures loaded on different WB-Pro factors consistent with a priori predictions based on the WB-Pro factor structure, thereby calling into question their claimed unidimensionality and theoretical rationale. Because some applications require a short global measure, we used a machine-learning algorithm to construct 2 global well-being short versions (five- and 15-item forms) and tested these formative measures in relation to the full-form and validity criteria (to download short and long versions see https://ippe.acu.edu.au/research/research-instruments/wb-pro). The WB-Pro appears to be one of the most comprehensive measures of subjective well-being, based on a sound conceptual model and empirical support, with broad applicability for research and practice, as well as providing a framework for evaluating the breadth of other well-being measures. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Robust Real-Time Embedded EMG Recognition Framework Using Temporal Convolutional Networks on a Multicore IoT Processor

Hand movement classification via surface electromyographic (sEMG) signal is a well-established approach for advanced Human-Computer Interaction. However, sEMG movement recognition has to deal with the long-term reliability of sEMG-based control, limited by the variability affecting the sEMG signal. Embedded solutions are affected by a recognition accuracy drop over time that makes them unsuitable for reliable gesture controller design. In this paper, we present a complete wearable-class embedded system for robust sEMG-based gesture recognition, based on Temporal Convolutional Networks (TCNs). Firstly, we developed a novel TCN topology (TEMPONet), and we tested our solution on a benchmark dataset (Ninapro), achieving 49.6% average accuracy, 7.8%, better than current State-Of-the-Art (SoA). Moreover, we designed an energy-efficient embedded platform based on GAP8, a novel 8-core IoT processor. Using our embedded platform, we collected a second 20-sessions dataset to validate the system on a setup which is representative of the final deployment. We obtain 93.7% average accuracy with the TCN, comparable with a SoA SVM approach (91.1%). Finally, we profiled the performance of the network implemented on GAP8 by using an 8-bit quantization strategy to fit the memory constraint of the processor. We reach a $\mathbf {4\times }$ lower memory footprint (460 kB) with a performance degradation of only 3% accuracy. We detailed the execution on the GAP8 platform, showing that the quantized network executes a single classification in 12.84 ms with a power envelope of 0.9 mJ, making it suitable for a long-lifetime wearable deployment.
The crystal structure of the mycobacterial trehalose monomycolate transport factor A, TtfA, reveals an atypical fold

Trehalose monomycolate (TMM) represents an essential element of the mycobacterial envelope. While synthesized in the cytoplasm, TMM is transported across the inner membrane by MmpL3 but, little is known regarding the MmpL3 partners involved in this process. Recently, the TMM transport factor A (TtfA) was found to form a complex with MmpL3 and to participate in TMM transport, although its biological role remains to be established. Herein, we report the crystal structure of the Mycobacterium smegmatis TtfA core domain. The phylogenetic distribution of TtfA homologues in non‐mycolate containing bacteria suggests that TtfA may exert additional functions.
Orphenadrine in treatment of muscle cramps in cirrhotic patients: a randomized study

Supplemental Digital Content is available in the text. Objective Many patients of liver cirrhosis are complaining of muscle cramps, which are annoying to them. There is no effective treatment for muscle cramps in cirrhotic patients till now. This study purposed to evaluate efficacy and safety of orphenadrine in the treatment of muscle cramps in cirrhotic patients. Methods One hundred and twenty four patients who had muscle cramps three or more times weekly were included. They were divided into two arms: 62 patients administrated orphenadrine and 62 administrated placebo. They were followed up till 2 weeks after the end of therapy. Muscle cramps were evaluated using questionnaire as regards severity, duration, and frequency. Also, side effects of orphenadrine were recorded. Results Frequency, duration of muscle cramps, and pain score improved significantly after 1 month of orphenadrine therapy in comparison to placebo. Few side effects were recorded in the form of dry mouth, drowsiness, and nausea. Conclusion Orphenadrine is considered as promising safe drug for treatment of muscle cramps associated with liver cirrhosis.
Comparison of three office blood pressure measurement techniques and their effect on hypertension prevalence in the general population.

OBJECTIVES There is an ongoing controversy about the magnitude of the difference between unattended automated office blood pressure (AOBP) and conventional office blood pressure (BP). The aim of our study was to compare unattended AOBP with both auscultatory BP and oscillometric attended AOBP in an epidemiological setting. METHODS In 2588 participants of the Czech post-MoNItoring of CArdiovascular Disease study (a randomly selected 1% representative population sample aged 25-64 years, mean age 48 ± 11 years, 47.5% males), BP was measured using an AOBP device unattended, auscultatory mercury sphygmomanometer and an oscillometric attended AOBP device. RESULTS On average, auscultatory BP was 10.6/5.6 mmHg higher than unattended AOBP. Similarly, oscillometric attended AOBP was 9.9/3.4 mmHg higher than unattended AOBP, while the mean difference between attended oscillometric AOBP and auscultatory BP was 0.8/2.1 mmHg. Unattended systolic AOBP of 127 mmHg corresponded to SBP of 140 mmHg measured by a conventional sphygmomanometer. The prevalence of hypertension varied depending on the measurement technique and ranged from 31.5 to 40.1%. Reasonable agreement in hypertension diagnosis was observed with unattended AOBP cut-off at least 130/85 mmHg when compared with both auscultatory (McNemar P = 0.07, kappa 0.819) and attended oscillometric AOBP (McNemar P = 0.46, kappa 0.852) thresholds of at least 140/90 mmHg. CONCLUSION Unattended automated office SBP is on average 10 mmHg lower than the office auscultatory or attended AOBP values. In epidemiological settings, a threshold of unattended AOBP at least 130/85 mmHg should make comparison of hypertension prevalence possible with studies using auscultatory techniques and cut-off values of 140/90 mmHg.
Role for the membrane estrogen receptor alpha in the sexual differentiation of the brain

Estrogens exert pleiotropic effects on multiple physiological and behavioral responses. Male and female sexual behavior in rodents constitutes some of the best‐characterized responses activated by estrogens in adulthood and largely depend on ERα. Evidence exists that nucleus‐ and membrane‐initiated estrogen signaling cooperate to orchestrate the activation of these behaviors both in short‐ and long‐term. However, questions remain regarding the mechanism(s) and receptor(s) involved in the early brain programming during development to organize the circuits underlying sexually differentiated responses. Taking advantage of a mouse model harboring a mutation of the ERα palmitoylation site, which prevents membrane ERα signaling (mERα; ERα‐C451A), this study investigated the role of mERα on the expression of male and female sexual behavior and neuronal populations that differ between sexes. The results revealed no genotype effect on the expression of female sexual behavior, while male sexual behavior was significantly reduced, but not abolished, in males homozygous for the mutation. Similarly, the number of kisspeptin‐ (Kp‐ir) and calbindin‐immunoreactive (Cb‐ir) neurons in the anteroventral periventricular nucleus (AVPv) and the sexually dimorphic nucleus of the preoptic area (SDN‐POA), respectively, were not different between genotypes in females. In contrast, homozygous males showed increased numbers of Kp‐ir and decreased numbers of Cb‐ir neurons compared to wild‐types, thus leading to an intermediate phenotype between females and wild‐type males. Importantly, females neonatally treated with estrogens exhibited the same neurochemical phenotype as their corresponding genotype among males. Together, these data provide evidence that mERα is involved in the perinatal programming of the male brain.
Junior doctors’ experience of interprofessional shadowing in a palliative care setting

ABSTRACT Interprofessional shadowing, whereby medical students take on the role of another profession, is an effective interprofessional education (IPE) method to promote interprofessional teamwork. Palliative care is an ideal setting for IPE as multidisciplinary teams work together to deliver holistic patient care. This brief report explores junior doctors’ experiences in shadowing nurses to provide care to patients in a hospice setting in New Zealand. We conducted semi-structured interviews with six participants to find out the impact that this shadowing experience had on their professional development and feasibility of incorporating this activity into the undergraduate medical curriculum. Inductive thematic analysis revealed that shadowing a nurse for two days increased participants’ awareness of the nursing role and gave them the opportunity to develop a personal relationship with their patients, both of which made participants actively reflect on the value of IPE and the way they practice medicine. Participants considered the palliative care setting as conducive to IPE and saw the value of incorporating interprofessional shadowing into the undergraduate medical curriculum.
Habenular connections with the dopaminergic and serotonergic system and their role in stress‐related psychiatric disorders

The habenula (Hb) is a phylogenetically old epithalamic structure differentiated into two nuclear complexes, the medial (MHb) and lateral habenula (LHb). After decades of search for a great unifying function, interest in the Hb resurged when it was demonstrated that LHb plays a major role in the encoding of aversive stimuli ranging from noxious stimuli to the loss of predicted rewards. Consistent with a role as an anti‐reward center, aberrant LHb activity has now been identified as a key factor in the pathogenesis of major depressive disorder. Moreover, both MHb and LHb emerged as new players in the reward circuitry by primarily mediating the aversive properties of distinct drugs of abuse. Anatomically, the Hb serves as a bridge that links basal forebrain structures with monoaminergic nuclei in the mid‐ and hindbrain. So far, research on Hb has focused on the role of the LHb in regulating midbrain dopamine release. However, LHb/MHb are also interconnected with the dorsal (DR) and median (MnR) raphe nucleus. Hence, it is conceivable that some of the habenular functions are at least partly mediated by the complex network that links MHb/LHb with pontomesencephalic monoaminergic nuclei. Here, we summarize research about the topography and transmitter phenotype of the reciprocal connections between the LHb and ventral tegmental area‐nigra complex, as well as those between the LHb and DR/MnR. Indirect MHb outputs via interpeduncular nucleus to state‐setting neuromodulatory networks will also be commented. Finally, we discuss the role of specific LHb‐VTA and LHb/MHb‐raphe circuits in anxiety and depression.
Metabolomics Profiling and AKR Characterization During Paurometabolous Development of Corythucha ciliata (Hemiptera: Tingidae)

Abstract The sycamore lace bug, Corythucha ciliata (Say) is an invasive pest infesting trees of the genus Platanus. Both adults and nymphs damage the foliage of sycamore trees. Nymphs cannot survive in low temperatures; however, the sycamore lace bug overwinters as adults. In this study, we analyzed the metabolite profiles of this pest to determine significantly regulated metabolites during paurometabolous development from nymphs to adults. The identification of metabolites is essential to convert analytical data into meaningful biological knowledge. A total of 62 metabolites were identified using GC-MS. Among them, 29 different metabolites showed differences in content among nymphs, adult females (AF), and adult males (AM). Five of the 29 metabolites, including caffeic acid, D-glucose, D-mannose, glycerol and aminooxyacetic acid, were significantly increased and nine of them were significantly decreased during the developmental stages from nymph to adult. In addition, we identified three novel aldo-keto reductase (AKR) genes that may play a significant role in the control of glycerol biosynthesis. Moreover, the characteristics and expression levels of these genes were analyzed. This study will provide us with the necessary information to improve our understanding of the changes in metabolites in C. ciliata during paurometabolous development.
Discriminative Canonical Pattern Matching for Single-Trial Classification of ERP Components

Event-related potentials (ERPs) are one of the most popular control signals for brain–computer interfaces (BCIs). However, they are very weak and sensitive to the experimental settings including paradigms, stimulation parameters and even surrounding environments, resulting in a diversity of ERP patterns across different BCI experiments. It's still a challenge to develop a general decoding algorithm that can adapt to the ERP diversities of different BCI datasets with small training sets. This study compared a recently developed algorithm, i.e., discriminative canonical pattern matching (DCPM), with seven ERP-BCI classification methods, i.e., linear discriminant analysis (LDA), stepwise LDA, bayesian LDA, shrinkage LDA, spatial-temporal discriminant analysis (STDA), xDAWN and EEGNet for the single-trial classification of two private EEG datasets and three public EEG datasets with small training sets. The feature ERPs of the five datasets included P300, motion visual evoked potential (mVEP), and miniature asymmetric visual evoked potential (aVEP). Study results showed that the DCPM outperformed other classifiers for all of the tested datasets, suggesting the DCPM is a robust classification algorithm for assessing a wide range of ERP components.