Miracle-dz/UniFAR-FTUs huggingface dataset:
Target Discovery in Ralstonia solanacearum Through an Activity-Based Protein Profiling Technique based on Bioactive Oxadiazole Sulfones.

Ralstonia solanacearum is an extremely destructive and rebellious phytopathogen that can cause bacterial wilt diseases in more than 200 plant species. To explore and discover the potential targets in R. solanacearum for the purpose of developing new agrochemicals targeting this infection, here, we exploited a typical activity-based protein profiling (ABPP) technique for target discovery in R. solanacearum based on an activity-based probe 1 derived from bioactive oxadiazole sulfones. A total of 65 specific targets were identified with high confidence through a quantitative chemical proteomic approach. Three representative proteins (glycine cleavage system H protein, thiol peroxidase, and dihydrolipoamide S-succinyltransferase) were validated as the targets by using the immunoblotting analysis with their respective antibodies. Additionally, the in vitro interaction between the recombinant thiol peroxidase and probe 1 further confirmed that this protein was a target of oxadiazole sulfones. We anticipated that these discovered protein targets in R. solanacearum can stimulate the discovery and development of novel agrochemicals targeting bacterial infections caused by R. solanacearum.
Evolution of neurocritical care.

DOI:10.1097/MCC.0000000000000712 as ‘standard of care’ 20 years ago or even five years ago is now very different in 2020. In particular, neocritical care that focuses on the care of critically ill patients with acute brain and nervous system disorders has grown significantly. In 2000, there were few if any dedicated neurocritical care units (NCCU). Today, data from PRINCE, a multicenter, international, point-prevalence, cross-sectional, prospective, observational, noninterventional study suggests that over two-thirds of patients with neurocritical disorders are managed in dedicated in NCCUs although there remains significant geographic variability [1]. This is important as accumulating data suggests outcomes are improved when appropriate patients are admitted to a dedicated NCCU [2]. The reasons for this association between improved outcome and NCCUs are uncertain but in part are likely associated with advances in technology, diagnostic tools, and care; better understanding of pathophysiology and organization of care. In this edition of Current Opinion in Critical Care (COCC), we have chosen to review ten topics that include prehospital care, diagnosis and monitoring, surgery, pharmacology, and ICU care that until recently were nonexistent, not – feasible or not well appreciated. First, mobile stroke units (MSUs) are described. The MSU concept was first introduced in 2003 but it is only in recent years that MSUs have proliferated with a clear realization that ‘time is brain,’ and with advances in information technology and portable CT scanners. This concept is still evolving and rather than only help in stroke care may gradually morph into a neuro-ER or ICU that is taken to the patient for all types of acute brain injuries [3,4]. Second, in daily practice, the challenge for intensivists is to identify patients who are at risk for secondary injury, determine disease severity, and distinguish responders from nonresponders to therapy. Biomarkers can help answer these challenges, for example, troponin in cardiac disease. Although biomarkers have been used for many years in brain injury interest in their use has increased since the FDA-approved biomarkers (UCH-L1 and GFAP) in early 2018 to help evaluate mild traumatic brain injury (TBI). In addition, the recent advent of
Ultrathin, Biocompatible, and Flexible Pressure Sensor with a Wide Pressure Range and Its Biomedical Application.

In this research, an ultrathin, biocompatible and flexible pressure sensor with a wide pressure range has been developed and applied toward biomedical applications. The pressure sensing mechanism is based upon the variation of contact resistance between an electrode and a three-dimensional microstructured polyimide/carbon nanotube (PI/CNT) composite film. The sensor has a thickness of about 31.3 µm, a maximum sensitivity of 41.0 MPa-1, and a sensing range of 10-500 kPa. Also, in-situ temperature measurement by the integrated resistive temperature detector (RTD) enables data correction in varying temperature conditions. In order to show the advantage of the fabricated sensor, it is attached on the human body and the radiofrequency ablation (RFA) needle with small the radius of curvature. In these experiments, the proposed pressure sensor measures the subtle pressure level (pulse pressure) and high pressure level (fingertip pressure) without losing conformal contact with the skin. In addition, when the pressure sensor integrated RFA needle is inserted into a bovine liver, it successfully detects the occurrence of the steam popping phenomenon.
A Focus Group Study about Oral Drug Administration Practices at Hospital Wards—Aspects to Consider in Drug Development of Age-Appropriate Formulations for Children

Oral drug administration to pediatric patients is characterized by a lack of age-appropriate drug products and the off-label use of medicines. However, drug administration practices at hospital wards is a scarcely studied subject. The aim of this study was to explore the oral drug administration practices at pediatric hospital wards, with a focus on experiences and challenges faced, methods used to mitigate existing problems, drug manipulation habits, perceptions about oral dosage forms and future needs of oral dosage forms for children. This was a qualitative study consisting of focus group discussions with physicians, nurses and clinical pharmacists in a tertiary university hospital with the objective of bringing forward a holistic view on this research topic. These healthcare professionals recognized different administration challenges that were classified as either dosage form-related or patient-related ones. A lack of depot formulations developed especially for children as well as oral pediatric dosage forms of drug substances currently available as intravenous dosage forms was recognized. The preferred oral dosage forms were oral liquids and orodispersible tablets. Patient-centered drug administration practices including factors facilitating drug administration both at hospital wards and at home after patient discharge were identified. Among all healthcare professionals, the efficient cooperation in drug prescribing and administration as well as in educating the child’s caregivers in correct administration techniques before discharge and improving the overall discharge process of patients was emphasized. This study complements the prevalent understanding that new dosage forms for children of varying ages and stages of development are still needed. It also brings a holistic view on different aspects of oral drug administration to pediatric patients and overall patient-centered drug administration practices.
Evaluation on the nutrition intervention effect of WeiWei Nutrients tablet among rural Miao minority preschooler's

A nutrition survey among 162 rural Miao minority preschooler's Were conducted,and grouped nutritional intervention were conducted through Intake of Wei Wei nutrients tablets and blank control.The result revealed that The energy and protein intake among Miao preschooler has met Recommended Dietary Allowance (RDA),but the intake of Calcium,Zinc,Vitamin B2 and Vitamin A are inadequate,the dietary structure is unreasonable.The prevalence Of anemia is high.The Wei Wei nutrient tablets has remarkable effect in reducing The incidence of anemia,several suggestion was put forward to improve the nutrition and health status among preschooler.
Impact of flavivirus vaccine-induced immunity on primary Zika virus antibody response in humans

Background Zika virus has recently spread to South- and Central America, causing congenital birth defects and neurological complications. Many people at risk are flavivirus pre-immune due to prior infections with other flaviviruses (e.g. dengue virus) or flavivirus vaccinations. Since pre-existing cross-reactive immunity can potentially modulate antibody responses to Zika virus infection and may affect the outcome of disease, we analyzed fine-specificity as well as virus-neutralizing and infection-enhancing activities of antibodies induced by a primary Zika virus infection in flavivirus-naïve as well as yellow fever- and/or tick-borne encephalitis-vaccinated individuals. Methodology Antibodies in sera from convalescent Zika patients with and without vaccine-induced immunity were assessed by ELISA with respect to Zika virus-specificity and flavivirus cross-reactivity. Functional analyses included virus neutralization and infection-enhancement. The contribution of IgM and cross-reactive antibodies to these properties was determined by depletion experiments. Principal findings Pre-existing flavivirus immunity had a strong influence on the antibody response in primary Zika virus infections, resulting in higher titers of broadly flavivirus cross-reactive antibodies and slightly lower levels of Zika virus-specific IgM. Antibody-dependent enhancement (ADE) of Zika virus was mediated by sub-neutralizing concentrations of specific IgG but not by cross-reactive antibodies. This effect was potently counteracted by the presence of neutralizing IgM. Broadly cross-reactive antibodies were able to both neutralize and enhance infection of dengue virus but not Zika virus, indicating a different exposure of conserved sequence elements in the two viruses. Conclusions Our data point to an important role of flavivirus-specific IgM during the transient early stages of infection, by contributing substantially to neutralization and by counteracting ADE. In addition, our results highlight structural differences between strains of Zika and dengue viruses that are used for analyzing infection-enhancement by cross-reactive antibodies. These findings underscore the possible impact of specific antibody patterns on flavivirus disease and vaccination efficacy.
Characterisation of cyclic alternating pattern during sleep in older men and women using large population studies.

STUDY OBJECTIVES To assess the microstructural architecture of non-rapid eye movement (NREM) sleep known as cyclic alternating pattern (CAP) in relation to the age, gender, subjective sleep quality and the degree of sleep disruption in large community-based cohort studies of older people. METHODS We applied a high performance automated CAP detection system to characterise CAP in 2,811 men from the Osteoporotic Fractures in Men Sleep Study (MrOS) and 426 women from the Study of Osteoporotic Fractures Sleep Study (SOF). CAP was assessed with respect to age and gender and correlated to obstructive apnea-hypopnea index (OAHI), arousal index (AI-NREM) and periodic limb movements in sleep index (PLMSI). Further, we evaluated CAP across levels of subjective sleep quality measures using analysis of covariance. RESULTS Age was significantly associated with the number of CAP sequences during NREM sleep (MrOS: p = 0.013, SOF = 0.051). CAP correlated significantly with AI-NREM (MrOS: ρ = 0.30, SOF: ρ = 0.29). CAP rate, especially the A2+A3 index, was inversely related to subjectively reported quality of sleep, independent of age and sleep disturbance measures. Women experienced significantly fewer A1-phases compared to men, in particular in slow wave sleep (N3). CONCLUSIONS We demonstrate that automated CAP analysis of large-scaled databases can lead to new findings on CAP and its subcomponents. We show that sleep disturbance indices are associated with CAP rate. Further, CAP rate is significantly linked to subjectively reported sleep quality, independent from traditionally scored markers of sleep fragmentation. Finally, men and women show differences in the micro-architecture of sleep as identified by CAP, despite similar macro-architecture.
Quirks of dye nomenclature. 14. Madder: queen of red dyes

ABSTRACT The long history of madder as a source of red dyes and pigments is presented. The variety of plant sources and the range of anthraquinone components discovered over a long period are addressed. Topics such as analysis, industrial uses, biological staining, red bone staining in live animals and toxicity are outlined briefly. The contributions of many chemists are acknowledged.
Identification of Cancer Stem Cell Subpopulations in Head and Neck Metastatic Malignant Melanoma

Cancer stem cells (CSCs) have been identified in many cancer types. This study identified and characterized CSCs in head and neck metastatic malignant melanoma (HNmMM) to regional lymph nodes using induced pluripotent stem cell (iPSC) markers. Immunohistochemical (IHC) staining performed on 20 HNmMM tissue samples demonstrated expression of iPSC markers OCT4, SOX2, KLF4, and c-MYC in all samples, while NANOG was expressed at low levels in two samples. Immunofluorescence (IF) staining demonstrated an OCT4+/SOX2+/KLF4+/c-MYC+ CSC subpopulation within the tumor nests (TNs) and another within the peritumoral stroma (PTS) of HNmMM tissues. IF also showed expression of NANOG by some OCT4+/SOX2+/KLF4+/c-MYC+ cells within the TNs in an HNmMM tissue sample that expressed NANOG on IHC staining. In situ hybridization (n = 6) and reverse-transcription quantitative polymerase chain reaction (n = 5) on the HNmMM samples confirmed expression of all five iPSC markers. Western blotting of primary cell lines derived from four of the 20 HNmMM tissue samples showed expression of SOX2, KLF4, and c-MYC but not OCT4 and NANOG, and three of these cell lines formed tumorspheres in vitro. We demonstrate the presence of two putative CSC subpopulations within HNmMM, which may be a novel therapeutic target in the treatment of this aggressive cancer.
LPS‐induced inflammation desensitizes hepatocytes to Fas‐induced apoptosis through Stat3 activation—The effect can be reversed by ruxolitinib

Recent studies have established a concept of tumour necrosis factor‐α (TNF‐α)/Fas signalling crosstalk, highlighting TNF‐α as a critical cytokine in sensitizing hepatocytes to death induced by Fas activation. However, in the exact inflammatory response, besides TNF‐α, many other mediators, that might modulate apoptotic response differentially, are released. To resolve the issue, we studied the effects of lipopolysaccharide (LPS), one of the crucial inductors of inflammation in the liver, on apoptotic outcome. We show that LPS‐induced inflammation diminishes the sensitivity of hepatocytes to Fas stimulus in vivo at caspase‐8 level. Analysis of molecular mechanisms revealed an increased expression of various pro‐inflammatory cytokines in non‐parenchymal liver cells and hepatocyte‐specific increase in Bcl‐xL, associated with signal transducer and activator of transcription 3 (Stat3) phosphorylation. Pre‐treatment with ruxolitinib, a selective Janus kinase (JAK) 1/2 inhibitor, prevented the LPS‐induced Stat3 phosphorylation and restored the sensitivity of hepatocytes to Fas‐mediated apoptosis. Furthermore, ruxolitinib pre‐treatment diminished the LPS‐induced Bcl‐xL up‐regulation without an inhibitory effect on LPS‐induced expression of pro‐inflammatory cytokines. In summary, although the reports are showing that the effects of isolated pro‐inflammatory mediators, such as TNF‐α or neutrophils, are pro‐apoptotic, the overall effect of inflammatory milieu on hepatocytes in vivo is Stat3‐dependent desensitization to Fas‐mediated apoptosis.
Effects of Two Passive Back-Support Exoskeletons on Muscle Activity, Energy Expenditure, and Subjective Assessments During Repetitive Lifting

Objective The aim of this study was to explore the efficacy of two different passive back-support exoskeleton (BSE) designs during repetitive lifting in different postures. Background Although BSEs have been proposed as a potential intervention for reducing physical demands, limited information is available about the impacts of different exoskeleton designs in diverse work scenarios. Method Eighteen participants (gender-balanced) performed lab-based simulations of repetitive lifting tasks. These tasks were performed in 12 different conditions, involving two BSEs and a control condition, two levels of lifting symmetry (symmetric and asymmetric), and two postures (standing and kneeling). Outcome measures described muscle activity and energy expenditure, along with perceived discomfort, balance, and usability. Results Using both BSEs significantly reduced peak activity of the trunk extensor muscles (by ~10%–28%) and energy expenditure (by ~4%–13%) in all conditions tested. Such reductions, though, were task dependent and differed between the two BSEs. In most of the tested conditions, using BSEs positively affected subjective responses regarding perceived exertion and usability. Conclusion Our results suggest that the beneficial effects of a BSE are task specific and depend on the specific BSE design approach. More work is needed, though, to better characterize this task specificity and to determine the generalizability of BSE effects on objective and subjective outcomes for a wider range of conditions and users. Application Our results provide new evidence to guide the selection and application of passive BSE designs in diverse lifting tasks.
Proton magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations

1H‐MR spectroscopy of skeletal muscle provides insight into metabolism that is not available noninvasively by other methods. The recommendations given in this article are intended to guide those who have basic experience in general MRS to the special application of 1H‐MRS in skeletal muscle. The highly organized structure of skeletal muscle leads to effects that change spectral features far beyond simple peak heights, depending on the type and orientation of the muscle. Specific recommendations are given for the acquisition of three particular metabolites (intramyocellular lipids, carnosine and acetylcarnitine) and for preconditioning of experiments and instructions to study volunteers.
Efficacy of a behavior change program on cardiovascular parameters in patients with hypertension: a randomized controlled trial

ABSTRACT Objective To investigate the efficacy of a behavior change program named Vida Ativa Melhorando a Saúde on cardiovascular parameters in hypertensive patients. Methods Ninety hypertensive patients aged over 40 years were randomly allocated to one of two groups: Vida Ativa Melhorando a Saúde or Control (n=45 respectively). Patients in the Vida Ativa Melhorando a Saúde group took part in a behavior change program aimed to encourage changes in physical activity levels and eating habits, according to the Social Cognitive Theory. The program consisted of 90-minute weekly group meetings conducted by a physical therapist and a dietitian. One chapter of the educational material (workbook) provided was discussed per meeting. Participants in the Control Group attended a single educative lecture on lifestyle changes. Brachial and central blood pressure, arterial stiffness and endothelial function parameters were measured pre- and post-intervention. Results Vida Ativa Melhorando a Saúde led to reduction of brachial (131.3±15.8mmHg to 125.1±17.3mmHg; p<0.01) and central (123.6±16.3mmHg to 119.0±20.6mmHg; p=0.02) systolic and brachial diastolic (123.6±16.3mmHg to 119.0±20.6mmHg; p<0.01) blood pressure values, and improvement of post-occlusive reactive hyperemia (from 5.7±2.5mL·100mL−1 to 6.5±2.1mL·100mL−1 tissue·min−1; p=0.04). No changes in body composition, heart rate and arterial stiffness parameters were detected in both groups (p>0.05). Conclusion Vida Ativa Melhorando a Saúde program improved blood pressure and microvascular reactivity in hypertensive patients. Trial registration: ClinicalTrials.gov: NCT02257268
Comparison of Biologics and Oral Treatments for Plaque Psoriasis: A Meta-analysis.

Importance The clinical benefits of novel treatments for moderate to severe psoriasis are well established, but wide variations exist in patient response across different therapies. In the absence of head-to-head randomized trials, meta-analyses synthesizing data from multiple studies are needed to assess comparative efficacy among psoriasis treatments. Objective To estimate the relative short-term and long-term efficacy of biologics and oral agents for the treatment of moderate to severe psoriasis. Data Sources A systematic literature review was conducted on December 4, 2017, and updated on September 17, 2018. The Embase, MEDLINE, and Cochrane Central Register databases were included. Study Selection Phase 2, 3, or 4 randomized clinical trials of treatments licensed by the US Food and Drug Administration and the European Medicines Agency for adults with moderate to severe psoriasis with data on Psoriasis Area and Severity Index assessment of 75%, 90%, and 100% reductions (PASI 75, 90, and 100) at 10 to 16 weeks (short-term efficacy) or 44 to 60 weeks (long-term efficacy) from baseline. Data Extraction and Synthesis Data were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. A bayesian network meta-analysis was conducted to estimate short-term PASI response rates; to account for variation across trials, an ordinal model that adjusted for reference arm response was implemented. The long-term PASI rates were estimated via a traditional meta-analysis. Main Outcomes and Measures PASI 75, 90, and 100 response rates at 10 to 16 weeks and 44 to 60 weeks from baseline. Results Sixty trials meeting all inclusion criteria were included. At weeks 10 to 16, the highest PASI 90 rates were seen with risankizumab-rzaa (71.6%; 95% credible interval [CrI], 67.5%-75.4%), brodalumab (70.8%; 95% CrI, 66.8%-74.6%), ixekizumab (70.6%; 95% CrI, 66.8%-74.6%), and guselkumab (67.3%; 62.5%-71.9%). At weeks 44 to 60, the treatments with the highest PASI 90 rates were risankizumab-rzaa (79.4%, 95% CI, 75.5%-82.9%), guselkumab (76.5%; 95% CI, 72.1%-80.5%), brodalumab (74.0%; 95% CI, 69.3%-78.1%), and ixekizumab (73.9%; 95% CI, 69.9%-77.5%). Findings were consistent for short-term and long-term PASI 75 and 100 responses. Conclusions and Relevance This study provides an assessment of the comparative efficacy among treatments for moderate to severe plaque psoriasis. The meta-analysis suggests that brodalumab, guselkumab, ixekizumab, and risankizumab-rzaa were associated with the highest PASI response rates in both short-term and long-term therapy.