Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety, tolerance, pharmacokinetic and pharmacodynamic properties of thrombopoietin mimetic peptide for injection in Chinese healthy volunteers: a randomized, placebo-controlled, double-blind study

Abstract The thrombopoietin mimetic peptide for injection is a second-generation thrombopoietin receptor agonist (TPO-RA) used in the treatment of patients with immune thrombocytopenia. The aim of the present study was to assess the safety, tolerance, pharmacokinetic and pharmacodynamic properties of thrombopoietin mimetic peptide for injection in Chinese healthy volunteers. A randomized, placebo-controlled, double-blind, dose-escalation study was conducted in healthy Chinese subjects aged 18–50 years. Thirty subjects received single subcutaneous injection of 0.3 μg/kg, 1.0 μg/kg, 2.0 μg/kg thrombopoietin mimetic peptide or placebo. Thrombopoietin mimetic peptide was safe and well tolerated at doses of 0.3–2.0 μg/kg. There was no significant change in mean platelet count (PLT) from baseline at the 0.3 μg/kg or placebo groups. The mean PLT of subjects in the 1.0 μg/kg and 2.0 μg/kg groups peaked at day 12 (± 1), began to decline around day 17, and returned to the baseline level at day 28 (± 1). Platelet aggregation rates of the three dose groups showed no significant change before and after administration. Serum concentrations of thrombopoietin mimetic peptide in all subjects were below the quantization limit. This was the first study to demonstrate that subcutaneous injection of thrombopoietin mimetic peptide at doses of 0.3–2.0 μg/kg was safe and well tolerated in Chinese healthy subjects. As a second-generation TPO-RA, thrombopoietin mimetic peptide is effective at improving PLT after single subcutaneous injection at dose of ≥1 μg/kg. P lain l anguage s ummary What is the context? ● Immune thrombocytopenia (ITP) is a rare, serious autoimmune disorder characterized by low platelet count (PLT) without an alternate cause. The treatment goal of ITP is to increase the platelet count to a safe level that can stop active bleeding and reduce the risks of future bleeding. ● Thrombopoietin receptor agonists (TPO-RAs, e.g. eltrombopag, avatrombopag, hetrombopag, and romiplostim) have shown high response rates in stimulating platelet production and reducing the risk of bleeding. TPO-RAs provide ITP patients with well-tolerated, long-term treatment choices. What is new? ● The thrombopoietin mimetic peptide for injection is a new TPO-RAs developed by Shandong Quangang Pharmaceutical Co., Ltd. (China). ● This study showed that thrombopoietin mimetic peptide is effective at improving PLT after a single subcutaneous injection. ● The thrombopoietin mimetic peptide is safe and well-tolerated in Chinese healthy subjects. What is the impact? ● This study provides evidence for the further development potential of the thrombopoietin mimetic peptide.
Açaí (Euterpe Oleraceae Mart.) Seeds Regulate NF-κB and Nrf2/ARE Pathways Protecting Lung against Acute and Chronic Inflammation.

BACKGROUND/AIMS Respiratory diseases are the world's biggest cause of mortality and disability. Specific nutrients have been proposed to positively affect disease progression as novel therapy alternatives to glucocorticosteroids. There has been a lot of attention in the possible health advantages of dietary assumption of Açai Seeds, popular native fruit found in the Amazon region which is rich in bioactive compounds. Until today nobody investigated the beneficial property of Açai Seeds administration in lung disease. METHODS In our study we use two model of lung disease: for acute lung disease we use an intrapleural injection of Carrageenan; for chronic disease we used an intratracheal instillation of bleomycin. Açai Seeds was administered orally dissolved in saline. RESULTS We found that Açai Seeds was able to reduce histological alteration, cells infiltration, pro inflammatory cytokine release, inflammation, and oxidative stress in both acute and chronic model of lung disease. CONCLUSION Our data clearly demonstrate for the first time that Açai Seeds administration was useful against lung disease by the reduction of NF-κB nuclear translocation and by the stimulation of Nrf2/ARE pathways promoting the physiological antioxidant defense.
Out-of-plane electret-based MEMS energy harvester with the combined nonlinear effect from electrostatic force and a mechanical elastic stopper

This paper presents the fabrication, modeling and characterization of an out-of-plane electret-based vibrational energy harvester (e-VEH) that has both positive and negative charged electret plates integrated into a single seismic mass system. Strong electrostatic spring-softening effect is induced due to the electric field provided by the double-charged electret plates. An elastic stopper is introduced for reliability concern by limiting the motion of seismic mass and meanwhile serves as a functional element to realize spring-hardening effect. The device has an overall volume of about 0.14 cm3 and is fabricated based on MEMS compatible silicon micromachining technology. When subject to weak excitations, the device exhibits an approximately linear frequency response but changes to a significantly larger broadband when strongly excited due to the combined nonlinear effect from electrostatic force and a mechanical elastic stopper. At a high excitation level of 0.48 g, the experimental results show that the device has 3 dB bandwidths of 3.7 Hz for frequency-up sweep and 2.8 Hz for frequency-down sweep, respectively, which demonstrate a large enhancement compared to the linear response (1.3 Hz). An optimal output power of 0.95 μW is also achieved with a low resonance of 95 Hz. This corresponds to a normalized power density of 37.4 μW cm−3 g−2.
Anxiety sensitivity in relation to post-traumatic stress disorder symptom clusters among young adults with probable post-traumatic stress disorder

ABSTRACT Despite the promise of past research on anxiety sensitivity (AS) and posttraumatic stress, extant work is limited, given (1) most studies consist of non-Hispanic White and middle-aged samples, (2) few have demonstrated incremental validity to general emotional traits and social determinants of health, and (3) limited work has characterized how AS relates to specific Posttraumatic Stress Disorder (PTSD) symptom clusters among those with (probable) PTSD. The current study evaluated the role of AS in relation to PTSD symptom clusters among a racially/ethnically diverse sample of young adults with probable PTSD. Participants included young adults who met the clinical cut-off for probable PTSD per the Posttraumatic Diagnostic Scale. Results indicated that AS was significantly related to overall posttraumatic stress symptom severity; the effect was evident after adjusting for a range of covariates including neuroticism and subjective social status. AS also was incrementally associated with arousal and hyperreactivity, changes in mood and cognition, and intrusion PTSD symptom clusters. In contrast to expectation, no effect for AS was evident for the avoidance PTSD symptom cluster. The current data uniquely add to the existing AS PTSD literature by showcasing distinct symptom cluster patterns among a racially/ethnically diverse sample of young adults with probable PTSD.
Minimally Invasive Diaphragm Plication for Acquired Unilateral Diaphragm Paralysis: A Systematic Review

Objective: Diaphragm paralysis is a relatively uncommon entity that can be both congenital and acquired in nature. While commonly asymptomatic, it can also cause a significant decrease in pulmonary function and reserve, particularly in patients with underlying pulmonary diseases. Our aim was to summarize the current literature regarding the minimally invasive techniques used in the surgical correction of acquired diaphragm paralysis via traditional and robotic minimally invasive approaches. Methods: We conducted a systematic review of available literature using the Cochrane methodology and reported findings according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Results: A total of 6,561 citations were identified through initial database and reference searches, of which 90 articles met the inclusion criteria for review. After further assessment, 33 appropriate full-text studies were selected for the review. Of the selected publications, the majority represented case reports and single-center retrospective studies with level of evidence 4. Only 1 level 2b study (individual cohort study) was identified, comparing minimally invasive and open approaches. Conclusions: Each of the minimally invasive approaches has its unique benefits and disadvantages, which are summarized and delineated in this article. Ultimately, no preferred method of diaphragm plication for diaphragm paralysis can be recommended at this time based on clinical data. The choice of procedure and surgical approach continues to be selected based on the surgeon's experience and preference.
Architectural design and development of an upper-limb rehabilitation device: a modular synthesis approach

Abstract Purpose Enormous assistance is required during rehabilitation activities, which might result in a variety of complications if performed manually. To solve this issue, several solutions in the form of assistive devices have been presented recently. Another issue highlighted is the lack of kinematic compatibility in low degrees-of-freedom (dof) systems. The proposed approach of developing a human-motion-oriented rehabilitation device deals with the problem through hybrid architectures. A novel modular synthesis approach is used for the purpose to induce generality in the design process. Materials and methods Using a modular strategy, three planar hybrid configurations are generated for two-dof mechanisms for supporting flexion/extension motion. Three such architectures are optimally synthesised and kinematically analysed over the entire workspace. A Genetic Algorithm (GA) is used to synthesise the architecture parameters optimally. Moreover, the outcomes are evaluated against a set of seven poses and posture locations of the wrist to choose the most suitable configuration among the others. Subsequently, kinematic compatibility is analysed for the coupled system – formed by the selected architecture and the human arm – while wearing the proposed mechanism. Results According to the findings of optimal synthesis, workspace and singularity analysis, configuration-III is capable of achieving the optimal postures for all task space locations (TSLs). Further, the work modifies the design by attaching additional three revolute passive joints for correcting misalignment concerns using coupled mobility analysis. Conclusion The modular strategy for hybrid architectures and the subsequent mobility analysis provides an algorithmic framework for synthesising a task-based rehabilitation device. IMPLICATIONS OF REHABILITATION Manual physiotherapy is reported as repeated task, expensive and time-consuming, and considered stressful for the therapist or assistants to provide one-on-one physiotherapy to each patient in the traditional method. Robotic rehabilitation is, therefore, a viable option. In the several reported works on robotic rehabilitation exoskeletons, misalignment of the exoskeleton and the human motion is considered an open challenge. Normally, it is being managed through large number of degrees of freedom, which is certainly expensive and complex in control. The proposed approach of developing a human-motion-oriented rehabilitation device deals with the problem through hybrid architectures and modular strategy to develop them. While focusing upon the emulation of natural human motion trajectory, the compatibility of orthotic joint and human joint motion needs attention. As biological joint possesses complex kinematic characteristics, closed-loops are used in the design. Overall, a complete framework of a cost effective low-dof rehabilitation device is proposed and detailed through coupled analysis.
Exodus: sequencing-based pipeline for quantification of pooled variants

Abstract Summary Next-Generation Sequencing is widely used as a tool for identifying and quantifying microorganisms pooled together in either natural or designed samples. However, a prominent obstacle is achieving correct quantification when the pooled microbes are genetically related. In such cases, the outcome mostly depends on the method used for assigning reads to the individual targets. To address this challenge, we have developed Exodus—a reference-based Python algorithm for quantification of genomes, including those that are highly similar, when they are sequenced together in a single mix. To test Exodus’ performance, we generated both empirical and in silico next-generation sequencing data of mixed genomes. When applying Exodus to these data, we observed median error rates varying between 0% and 0.21% as a function of the complexity of the mix. Importantly, no false negatives were recorded, demonstrating that Exodus’ likelihood of missing an existing genome is very low, even if the genome’s relative abundance is low and similar genomes are present in the same mix. Taken together, these data position Exodus as a reliable tool for identifying and quantifying genomes in mixed samples. Exodus is open source and free to use at: https://github.com/ilyavs/exodus. Availability and implementation Exodus is implemented in Python within a Snakemake framework. It is available on GitHub alongside a docker containing the required dependencies: https://github.com/ilyavs/exodus. The data underlying this article will be shared on reasonable request to the corresponding author. Supplementary information Supplementary data are available at Bioinformatics online.
Reduced mismatch negativity in children and adolescents with autism spectrum disorder is associated with their impaired adaptive functioning

Children and adolescents on the autism spectrum display sensory disturbances, rigid and repetitive behavior, social communication problems and a high prevalence of impaired adaptive functioning. Autism is associated with slowed behavioral and neural habituation to repeated sensory input and decreased responses to sensory deviations. Mismatch negativity (MMN) reflects a pre‐attentive difference in the neural response to sensory deviations relative to regularities and studies overall suggest that children and adolescents with autism tend to have smaller MMN. However, it remains unclear whether reduced MMN in autism is coupled to severity of specific autistic symptoms or more generally to lower level of adaptive functioning. To address these questions, the present study used electroencephalography (EEG) to assess whether auditory MMN in 59 children and adolescents with autism aged 7–14 years compared to 59 typically developing children and adolescents were related to specific autistic symptoms or level in adaptive functioning. As hypothesized, the autism group had a lower MMN amplitude than controls. Smaller MMN amplitudes were specifically associated with lower adaptive functioning in the autistic subjects but not in controls while no apparent relationships were observed with autistic‐like social interaction and communication problems, atypical language, rigidity, stereotypy or sensory sensitivity symptoms. Our findings indicate that a blunted response to changes in sensory input may underlie or contribute to the generalized difficulties with adapting to daily life circumstances seen in children and adolescents with autism.
A mechanistic model of snakebite as a zoonosis: Envenoming incidence is driven by snake ecology, socioeconomics and its impacts on snakes

Snakebite is the only WHO-listed, not infectious neglected tropical disease (NTD), although its eco-epidemiology is similar to that of zoonotic infections: envenoming occurs after a vertebrate host contacts a human. Accordingly, snakebite risk represents the interaction between snake and human factors, but their quantification has been limited by data availability. Models of infectious disease transmission are instrumental for the mitigation of NTDs and zoonoses. Here, we represented snake-human interactions with disease transmission models to approximate geospatial estimates of snakebite incidence in Sri Lanka, a global hotspot. Snakebites and envenomings are described by the product of snake and human abundance, mirroring directly transmitted zoonoses. We found that human-snake contact rates vary according to land cover (surrogate of occupation and socioeconomic status), the impacts of humans and climate on snake abundance, and by snake species. Our findings show that modelling snakebite as zoonosis provides a mechanistic eco-epidemiological basis to understand snakebites, and the possible implications of global environmental and demographic change for the burden of snakebite.
LncRNA OIP5-AS1 inhibits the lipopolysaccharide-induced inflammatory response and promotes osteogenic differentiation of human periodontal ligament cells by sponging miR-92a-3p

ABSTRACT Periodontitis is a chronic infectious disease that affects the oral health of adults. Long non-coding RNA OIP5 antisense RNA 1 (OIP5-AS1) has been reported to downregulated in the periodontal tissue of patients with periodontitis. Therefore, the study sought to look at the possible functions of OIP5-AS1 in periodontitis and the associated underlying mechanisms. In the present study, the expression level of OIP5-AS1 and microRNA-92a-3p were analyzed using reverse transcription-quantitative PCR. The levels of osteogenic proteins were determined using western blotting and inflammatory cytokines and oxidative stress were also examined. The proliferation of human periodontal ligament stem cells (hPDLSCs) was evaluated using MTT assays. Assay of osteogenic differentiation was undertaken by means of Alkaline phosphatase staining. The possible association between OIP5-AS1 and miR-92a-3p was determined applying dual-luciferase reporter assays and verified by RNA immunoprecipitation assay. We found that OIP5-AS1 was expressed at low levels in lipopolysaccharide (LPS)-stimulated hPDLSCs. OIP5-AS1 overexpression promoted proliferation and osteogenic differentiation ability and reduced LPS-induced inflammation in hPDLSCs. Furthermore, OIP5-AS1 directly targeted and reduced miR-92a-3p expression. The overexpression of miR-92a-3p partly abolished the effects of OIP5-AS1 on LPS-induced cell proliferation and osteogenic differentiation as well as inflammation in hPDLSCs. Collectively, the results indicated that OIP5-AS1 overexpression inhibited the LPS-induced inflammatory response and promoted the osteogenic differentiation of hPDLSCs by sponging miR-92a-3p. Thus, OIP5-AS1 is probably an essential objective for research during periodontitis treatment. Graphical abstract
‘There Were Moments We Wished She Could Just Die’: The Highly Gendered Burden of Nodding Syndrome in Northern Uganda

Nodding Syndrome (NS) occurs within a wide spectrum of epilepsies seen in onchocerciasis endemic areas of sub-Saharan Africa. It has debilitating consequences on affected individuals and increases the socio-economic, physical and psychological burden on care-givers and their households, diminishing their standing within the community. Social science research on the disproportionate burden of the disease on females is limited. Based on ethnographic research over 3 years in northern Uganda, we explored the burden of being ill and care-giving for persons with NS from a gendered perspective. We found that NS-affected females were at greater risk of physical and psychological abuse, sexual violence, unwanted pregnancies, sexually transmitted infections and stigma, in a context of deteriorating socio-economic conditions. Primary care-givers of the NS-affected, mostly women, struggled to make ends meet and were subjected to stigma and abandonment. Targeted interventions, including legal protection for affected females, stigma reduction, and psycho-social and financial support are needed.
The FLT3 Y842D mutation may be highly sensitive to midostaurin: a case report

A Y842D mutation within the activation loop of fms-like tyrosine kinase 3 (FLT3) has been shown to confer strong resistance to sorafenib in vitro. Whether this type of mutation exerts clinically significant effects in patients with acute myeloid leukaemia (AML) remains unclear. Here, a novel Y842D activating mutation within the kinase domain of FLT3, in a pregnant patient with de novo hyperleucocyte acute myeloid leukaemia, is described. Following induction failure with standard dose idarubicin and cytarabine (IA), the patient received re-induction combined with midostaurin, a promising agent targeting mutant-FLT3, and IA regimen. Fortunately, morphological remission was achieved. During the period of midostaurin treatment, the patient exhibited a symptom that was characteristic of differentiation syndrome, which disappeared following treatment with methylprednisolone. The present case revealed that Y842D, an uncommon activating mutation in the activation loop of FLT3, may be a midostaurin-sensitive mutation type in patients with acute myeloid leukaemia.
Assessing EHR Data for Use in Clinical Improvement and Research

ABSTRACT: Data from electronic health records (EHRs) are becoming accessible for use in clinical improvement projects and nursing research. But the data quality may not meet clinicians' and researchers' needs. EHR data, which are primarily collected to document clinical care, invariably contain errors and omissions. This article introduces nurses to the secondary analysis of EHR data, first outlining the steps in data acquisition and then describing a theory-based process for evaluating data quality and cleaning the data. This process involves methodically examining the data using six data quality dimensions—completeness, correctness, concordance, plausibility, currency, and relevance—and helps the clinician or researcher to determine whether data for each variable are fit for use. Two case studies offer examples of problems that can arise and their solutions. This article introduces nurses to the secondary analysis of electronic health record (EHR) data, first outlining the steps in data acquisition and then describing a theory-based process for evaluating data quality and cleaning the data.
Comparison of executive dysfunction, proinflammatory cytokines, and appetite hormones between first-episode and multiple-episode bipolar disorders

Abstract Background Evidence has demonstrated associations of bipolar disorder (BD) with cognitive impairment, dysregulated proinflammatory cytokines, and appetite hormones. Aim To compare executive dysfunction, proinflammatory cytokines, and appetite hormones between patients with first-episode and multiple-episode BDs. Methods This cross-sectional study included young adults aged 18 to 39 years who were diagnosed as having type 1 BD in the first or recurrent episode and a group of age-/sex-matched healthy controls. Data regarding patient characteristics, clinical symptoms, cytokines (C-reactive protein [CRP], interleukin-6, and tumor necrosis factor [TNF]-α), appetite hormones (leptin, adiponectin, ghrelin, and insulin), and executive function evaluated using the Wisconsin Card Sorting Test (WCST) were collected. Results A total of 112 participants (38 patients in the multiple-episode BD group, 31 patients in the first-episode BD group, and 43 in the control group) were included. Multivariate analysis revealed that patients in the multiple-episode BD group performed significantly worse in the WCST (P < .05) and had higher levels of ghrelin (P = .002), and lower levels of CRP (P = .040) than those in the first-episode BD group. Patients with BD had significantly higher TNF-α and ghrelin levels compared with the healthy controls. No significant associations of CRP, TNF-α, and ghrelin levels with executive function were observed. Conclusions Profiles in proinflammatory cytokines and appetite hormones as well as executive function significantly differed between patients with first-episode and multiple-episode BDs and controls, which may suggest their potential roles in the clinical stages and pathophysiology of type 1 BD.