Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of topical Citrullus colocynthis (bitter apple) extract oil in chemotherapy‐induced peripheral neuropathy: A pilot double‐blind randomized placebo‐controlled clinical trial

Chemotherapy‐induced peripheral neuropathy (CIPN) is one of the most common complications in patients with cancer. Citrullus colocynthis (bitter apple) has been used in traditional Persian medicine as an effective pain relief, especially for neuralgia. We designed a pilot clinical trial to evaluate the safety and efficacy of topical C. colocynthis oil in management of CIPN in breast cancer patients. Thirty‐four cancer patients with CIPN were randomly enrolled in two arms of a randomized, double‐blind, placebo‐controlled clinical trial. The patients were treated by topical C. colocynthis oil or placebo, two times per day for 2 months. Functional Assessment of Cancer Therapy/Gynecologic Oncology Group (FACT/GOG)‐Neurotoxicity (Ntx) score was set as the primary outcome measure. No significant improvement was observed in the total score of FACT/GOG‐Ntx scale (2.40 ± 1.90 vs. 1.05 ± 1.36, p = .879) in drug and placebo groups, respectively. There was also no significant improvement in the mean scores of FACT/GOG‐Ntx in the sensory, motor, hearing, and functional domains in the two study groups. According to the results of this preliminary study, topical C. colocynthis oil failed to improve the symptoms of CIPN compared with placebo.
Microglial subtypes: diversity within the microglial community

Microglia are brain‐resident macrophages forming the first active immune barrier in the central nervous system. They fulfill multiple functions across development and adulthood and under disease conditions. Current understanding revolves around microglia acquiring distinct phenotypes upon exposure to extrinsic cues in their environment. However, emerging evidence suggests that microglia display differences in their functions that are not exclusively driven by their milieu, rather by the unique properties these cells possess. This microglial intrinsic heterogeneity has been largely overlooked, favoring the prevailing view that microglia are a single‐cell type endowed with spectacular plasticity, allowing them to acquire multiple phenotypes and thereby fulfill their numerous functions in health and disease. Here, we review the evidence that microglia might form a community of cells in which each member (or “subtype”) displays intrinsic properties and performs unique functions. Distinctive features and functional implications of several microglial subtypes are considered, across contexts of health and disease. Finally, we suggest that microglial subtype categorization shall be based on function and we propose ways for studying them. Hence, we advocate that plasticity (reaction states) and diversity (subtypes) should both be considered when studying the multitasking microglia.
Anti-inflammatory and anti-Candida effects of Brazilian organic propolis, a promising source of bioactive molecules and functional food.

Brazilian organic propolis (BOP) is an unexplored Brazilian propolis that is produced organically and certified according to international legislation. Our results showed that BOP has strong anti-inflammatory effects and acts by reducing NF-кB activation, TNF-α release and neutrophil migration. In addition, BOP6 exhibited antifungal activity on planktonic and biofilm cultures of Candida albicans, C. glabrata, C. tropicalis, C. krusei and C. parapsisolis, and it reduced in vitro yeast cell adhesion to human keratinocytes at sub-inhibitory concentrations. BOP demonstrated significantly low toxicity in Galleria melonella larvae at antifungal doses. Lastly, a chemical analysis revealed the presence of caffeoyltartaric acid, 3,4-Dicaffeoylquinic acid, quercetin, gibberellin A7, A9 and A20 in BOP, which may be responsible for the biological properties observed. Thus, our data indicate that BOP is a promising source of anti-inflammatory and antifungal molecules that may be used as a functional food.
A Novel Adenosine Kinase from Bombyx mori: Enzymatic Activity, Structure, and Biological Function

Adenosine kinase (ADK) is the first enzyme in the adenosine remediation pathway that catalyzes adenosine phosphorylation into adenosine monophosphate, thus regulating adenosine homeostasis in cells. To obtain new insights into ADK from Bombyx mori (BmADK), we obtained recombinant BmADK, and analyzed its activity, structure, and function. Gel-filtration showed BmADK was a monomer with molecular weight of approximately 38 kDa. Circular dichroism spectra indicated BmADK had 36.8% α-helix and 29.9% β-strand structures, respectively. The structure of BmADK was stable in pH 5.0–11.0, and not affected under 30 °C. The melting temperature and the enthalpy and entropy changes in the thermal transition of BmADK were 46.51 ± 0.50 °C, 253.43 ± 0.20 KJ/mol, and 0.79 ± 0.01 KJ/(mol·K), respectively. Site-directed mutagenesis demonstrated G68, S201, E229, and D303 were key amino acids for BmADK structure and activity. In particular, S201A mutation significantly increased the α-helix content of BmADK and its activity. BmADK was located in the cytoplasm and highly expressed in the silk gland during the pre-pupal stage. RNA interference revealed the downregulation of BmADK decreased ATG-8, Caspase-9, Ec-R, E74A, and Br-C expression, indicating it was likely involved in 20E signaling, apoptosis, and autophagy to regulate silk gland degeneration and silkworm metamorphosis. Our study greatly expanded the knowledge on the activity, structure, and role of ADK.
Psychological status and disease activity were major predictors of body image disturbances in patients with Sjögren’s syndrome

ABSTRACT Sjögren’s syndrome (SS) often leads to disease-related body defects and functional impairments, which may result in the body image disturbances (BID) of patients. The aim of this study was to investigate the severity and predictors of BID among SS patients. Two hundred and thirty-one SS patients [mean (IQR) age: 51 (42–58); females: 94.4%] and 224 age and sex-matched healthy controls were included in this cross-sectional study. Questionnaires were applied: body image disturbance questionnaire (BIDQ), the hospital anxiety and depression scale (HADS), fatigue severity scale (FSS), the 10-cm pain Visual Analog Scale (VAS), the oral health impact profile-14 (OHIP-14), the ocular surface disease index (OSDI), the social support rate scale (SSRS). Independent sample t-test, Mann–Whitney U-test, Chi-square test, spearman rank correlation, and stepwise linear regression were performed by SPSS version 20.0 to analyze these data. In 231 SS patients, the mean of the overall BIDQ score was 1.80 ± 1.21, and SS patients had significantly higher scores in each domain of BIDQ compared with healthy controls (p < 0.05). The stepwise multiple linear regression analysis revealed that high BIDQ score was predicted by severe anxiety (β = 0.081; p < 0.001), high disease activity (β = 0.038; p < 0.001) and poor oral health (β = 0.017; p = 0.007) in SS patients. Patients with SS suffer from severe BID and it is necessary for rheumatologists to pay more attention to SS patients’ body image disturbance, especially those with high disease activity, severe anxiety, and poor oral health to improve patients’ quality of life.
Continuous Meter-Scale Synthesis of Weavable Tunicate Cellulose/Carbon Nanotube Fibers for High-Performance Wearable Sensors.

Weavable sensing fibers with superior mechanical strengths and sensing functionality are crucial for the realization of wearable textile sensors. However, in the fabrication of previously reported wearable sensing fibers, additional processes such as reduction, doping, and coating were essential to satisfy both requirements. The sensing fibers should be continuously synthesized in a scalable process for commercial applications with high reliability and productivity, which was challenging. In this study, we firstly synthesize mass-producible wearable sensing fibers with good mechanical properties and sensing functionality without additional processes by incorporating carbon nanotubes (CNTs) into distinct nanocellulose. Nanocellulose extracted from tunicate (TCNF) is homogeneously composited with single-walled CNTs and composite fibers (TCNF/CNT) are continuously produced in aligned directions by wet spinning facilitating liquid-crystal properties. The TCNF/CNT fibers exhibit a superior gas (NO2) sensing performance with high selectivity and sensitivity (parts-per-billion detection). In addition, the TCNF/CNT fibers can endure complex and harsh distortions maintaining their intrinsic sensing properties and can be perfectly integrated with conventional fabrics using a direct weaving process. Our meter-scale scalable synthesis of functional composite fibers is expected to provide a mass production platform of versatile wearable sensors.
Antibiotic- and Fluid-Focused Bundles Potentially Improve Sepsis Management, but High-Quality Evidence Is Lacking for the Specificity Required in the Centers for Medicare and Medicaid Service's Sepsis Bundle (SEP-1).

OBJECTIVE To address three controversial components in the Centers for Medicare and Medicaid Service's sepsis bundle for performance measure (SEP-1): antibiotics within 3 hours, a 30 mL/kg fluid infusion for all hypotensive patients, and repeat lactate measurements within 6 hours if initially elevated. We hypothesized that antibiotic- and fluid-focused bundles like SEP-1 would probably show benefit, but evidence supporting specific antibiotic timing, fluid dosing, or serial lactate requirements would not be concordant. Therefore, we performed a meta-analysis of studies of sepsis bundles like SEP-1. DATA SOURCES PubMed, Embase, ClinicalTrials.gov through March 15, 2018. STUDY SELECTION Studies comparing survival in septic adults receiving versus not receiving antibiotic- and fluid-focused bundles. DATA EXTRACTION Two investigators (D.J.P., P.Q.E.). DATA SYNTHESIS Seventeen observational studies (11,303 controls and 4,977 bundle subjects) met inclusion criteria. Bundles were associated with increased odds ratios of survival (odds ratio [95% CI]) in 15 studies with substantial heterogeneity (I = 61%; p < 0.01). Survival benefits were consistent in the five largest (1,697-12,486 patients per study) (1.20 [1.11-1.30]; I = 0%) and six medium-sized studies (167-1,029) (2.03 [1.52-2.71]; I = 8%) but not the six smallest (64-137) (1.25 [0.42-3.66]; I = 57%). Bundles were associated with similarly increased survival benefits whether requiring antibiotics within 1 hour (n = 7 studies) versus 3 hours (n = 8) versus no specified time (n = 2); or 30 mL/kg fluid (n = 7) versus another volume (≥ 2 L, n = 1; ≥ 20 mL/kg, n = 2; 1.5-2 L or 500 mL, n = 1 each; none specified, n = 4) (p = 0.19 for each comparison). In the only study employing serial lactate measurements, survival was not increased versus others. No study had a low risk of bias or assessed potential adverse bundle effects. CONCLUSIONS Available studies support the notion that antibiotic- and fluid-focused sepsis bundles like SEP-1 improve survival but do not demonstrate the superiority of any specific antibiotic time or fluid volume or of serial lactate measurements. Until strong reproducible evidence demonstrates the safety and benefit of any fixed requirement for these interventions, the present findings support the revision of SEP-1 to allow flexibility in treatment according to physician judgment.
Very early cognitive screening and return to work after stroke

ABSTRACT Background: Stroke is a common cause of long-term disability worldwide, and an increasing number of persons affected by stroke are of working age. In addition to physical impairments, a majority of patients reportedly suffer cognitive impairments after stroke. Reduced cognitive function may hinder poststroke return to work (RTW); however, most studies of this relationship have assessed cognitive function months after the stroke. Objectives: The current study aims to investigate the degree of post-stroke RTW, and whether very early cognitive function screening can predict RTW after a stroke. Methods: This study included 145 persons treated for stroke at 18–63 years of age at a large university hospital in Sweden between 2011 and 2016. Data were retrieved from the GOTVED database. Within 36–48 h after hospital admission, cognitive function was screened using the Montreal Cognitive Assessment (MoCA). Full and partial RTW were assessed based on the Swedish Social Insurance Agency’s register. Logistic regression was performed to analyze the potential predictors of RTW at 6 months and 18 months. Results: Neither global cognitive function nor executive function at 36–48 h after stroke predicted any degree of RTW at 6 or 18 months. Male sex, lower stroke severity, and not being on sick leave prior to stroke were significant predictors of RTW. Conclusions: Screening for cognitive impairments at 36–48-h post stroke is apparently too early for predicting RTW, and thus cannot be the sole basis for discharge planning after stroke. Additional research is needed to further analyze cognitive function early after stroke and RTW.
Physician Judgment and Circulating Biomarkers Predict 28-Day Mortality in Emergency Department Patients.

OBJECTIVES To determine whether biomarkers of endothelial activation and inflammation provide added value for prediction of in-hospital mortality within 28 days when combined with physician judgment in critically ill emergency department patients. DESIGN Prospective, observational study. SETTING Two urban, academic emergency departments, with ≈80,000 combined annual visits, between June 2016 and December 2017. PATIENTS Admitted patients, greater than 17 years old, with two systemic inflammatory response syndrome criteria and organ dysfunction, systolic blood pressure less than 90 mm Hg, or lactate greater than 4.0 mmol/L. Patients with trauma, intracranial hemorrhage known prior to arrival, or without available blood samples were excluded. INTERVENTIONS Emergency department physicians reported likelihood of in-hospital mortality (0-100%) by survey at hospital admission. Remnant EDTA blood samples, drawn during the emergency department stay, were used to measure angiopoietin-1, angiopoietin-2, tumor necrosis factor receptor-1, interleukin-6, and interleukin-8. MEASUREMENTS AND MAIN RESULTS We screened 421 patients and enrolled 314. The primary outcome of in-hospital mortality within 28 days occurred in 31 (9.9%). When predicting the primary outcome, the best biomarker model included angiopoietin-2 and interleukin-6 and performed moderately well (area under the curve, 0.72; 95% CI, 0.69-0.75), as did physician judgment (area under the curve, 0.78; 95% CI, 0.74-0.82). Combining physician judgment and biomarker models improved performance (area under the curve, 0.85; 95% CI, 0.82-0.87), with area under the curve change of 0.06 (95% CI, 0.04-0.09; p < 0.01) compared with physician judgment alone. CONCLUSIONS Predicting in-hospital mortality within 28 days among critically ill emergency department patients may be improved by including biomarkers of endothelial activation and inflammation in combination with emergency department physician judgment.
Spinal Cord Ependymomas With MYCN Amplification Show Aggressive Clinical Behavior.

Adult spinal cord ependymomas are typically low grade and have a relatively favorable clinical course following gross total resection. We report 4 cases of anaplastic spinal cord ependymoma with MYCN amplification, an exceptionally rare finding. All cases occurred in the spinal cord of adolescent and young adult women and had morphological and immunohistochemical features of anaplastic ependymomas (World Health Organization grade III). Chromosomal microarray analysis demonstrated amplification of 2p24 (including MYCN) in all cases. One patient died 6 months after surgery. Another patient recently had removal of metastatic nodules in the thoracic region, following gross total resection and adjuvant radiation therapy of a lumbar ependymoma 1 year previously. One patient responded well after chemotherapy but died after multiple relapses 82 months after diagnosis. We found MYCN amplification reported in 2 other ependymomas, both anaplastic and arising in the spinal cord of adult females (Brain Pathol 2001;11:133-43). One patient had multiple recurrences in the spinal cord and an intracranial metastasis. Although MYCN amplification is rare in ependymomas, the current and previously reported cases suggest that this is associated with higher-grade histology, spinal location, and often unfavorable prognosis. The clinical significance and therapeutic implications of MYCN amplification in ependymomas require further evaluation.
Transcriptome analysis reveals new insights into MdBAK1-mediated plant growth in Malus domestica.

BAK1 effects on plant stress responses have been well documented, but little is known regarding its effects on plant growth. In this study, we functionally characterized MdBAK1. Overexpressing MdBAK1 in Arabidopsis thaliana and apple trees promoted growth. Longitudinal stem cells were longer in transgenic plants than in wild-type plants. The size and number of cells and the area of the transverse stem were greater in the transgenic lines than in the wild-type plants. Moreover, transgenic A. thaliana and apple plants were more sensitive to an exogenous brassinosteroid. A transcriptome analysis of wild-type and transgenic apple revealed that MdBAK1 overexpression activated the brassinosteroid and ethylene signals, xylem production, and stress responses. Trend and Venn analyses indicated that carbohydrate, energy, and hormone metabolic activities were greater in transgenic plants during different periods. Moreover, a weighted gene co-expression network analysis proved that carbohydrate, hormone, and xylem metabolism as well as cell growth may be critical for MdBAK1-mediated apple tree growth and development. Compared with the corresponding levels in wild-type plants, the endogenous brassinosteroid, cytokinin, starch, sucrose, trehalose, glucose, fructose, and total sugar contents were considerably different in transgenic plants. Our results imply that MdBAK1 helps to regulate growth of apple tree through the above-mentioned pathways. These findings provide new information regarding the effects of MdBAK1 on plant growth and development.
Metagenome-Assembled Genome Sequence of Phormidium sp. Strain SL48-SHIP, Isolated from the Microbial Mat of Salt Lake Number 48 (Novosibirsk Region, Russia)

The Phormidium sp. strain SL48-SHIP genome was obtained from metagenomics sequencing of the microbial mat of Salt Lake No. 48 (54.201806 N, 78.179194 E; Novosibirsk Region, Russia). The sequenced and annotated genome is 4,384,607 bp and encodes 3,807 genes. ABSTRACT The Phormidium sp. strain SL48-SHIP genome was obtained from metagenomics sequencing of the microbial mat of Salt Lake No. 48 (54.201806 N, 78.179194 E; Novosibirsk Region, Russia). The sequenced and annotated genome is 4,384,607 bp and encodes 3,807 genes.
A molecular triage process mediated by RING finger protein 126 and BCL2-associated athanogene 6 regulates degradation of G0/G1 switch gene 2

Oxidative phosphorylation generates most of the ATP in respiring cells. ATP is an essential energy source, especially in cardiomyocytes because of their continuous contraction and relaxation. Previously, we reported that G0/G1 switch gene 2 (G0S2) positively regulates mitochondrial ATP production by interacting with FOF1-ATP synthase. G0S2 overexpression mitigates ATP decline in cardiomyocytes and strongly increases their hypoxic tolerance during ischemia. Here, we show that G0S2 protein undergoes proteasomal degradation via a cytosolic molecular triage system and that inhibiting this process increases mitochondrial ATP production in hypoxia. First, we performed screening with a library of siRNAs targeting ubiquitin-related genes and identified RING finger protein 126 (RNF126) as an E3 ligase involved in G0S2 degradation. RNF126-deficient cells exhibited prolonged G0S2 protein turnover and reduced G0S2 ubiquitination. BCL2-associated athanogene 6 (BAG6), involved in the molecular triage of nascent membrane proteins, enhanced RNF126-mediated G0S2 ubiquitination both in vitro and in vivo. Next, we found that Glu-44 in the hydrophobic region of G0S2 acts as a degron necessary for G0S2 polyubiquitination and proteasomal degradation. Because this degron was required for an interaction of G0S2 with BAG6, an alanine-replaced G0S2 mutant (E44A) escaped degradation. In primary cultured cardiomyocytes, both overexpression of the G0S2 E44A mutant and RNF126 knockdown effectively attenuated ATP decline under hypoxic conditions. We conclude that the RNF126/BAG6 complex contributes to G0S2 degradation and that interventions to prevent G0S2 degradation may offer a therapeutic strategy for managing ischemic diseases.
Dysregulation of the histone demethylase KDM6B in alcohol dependence is associated with epigenetic regulation of inflammatory signaling pathways

Epigenetic enzymes oversee long‐term changes in gene expression by integrating genetic and environmental cues. While there are hundreds of enzymes that control histone and DNA modifications, their potential roles in substance abuse and alcohol dependence remain underexplored. A few recent studies have suggested that epigenetic processes could underlie transcriptomic and behavioral hallmarks of alcohol addiction. In the present study, we sought to identify epigenetic enzymes in the brain that are dysregulated during protracted abstinence as a consequence of chronic and intermittent alcohol exposure. Through quantitative mRNA expression analysis of over 100 epigenetic enzymes, we identified 11 that are significantly altered in alcohol‐dependent rats compared with controls. Follow‐up studies of one of these enzymes, the histone demethylase KDM6B, showed that this enzyme exhibits region‐specific dysregulation in the prefrontal cortex and nucleus accumbens of alcohol‐dependent rats. KDM6B was also upregulated in the human alcoholic brain. Upregulation of KDM6B protein in alcohol‐dependent rats was accompanied by a decrease of trimethylation levels at histone H3, lysine 27 (H3K27me3), consistent with the known demethylase specificity of KDM6B. Subsequent epigenetic (chromatin immunoprecipitation [ChIP]–sequencing) analysis showed that alcohol‐induced changes in H3K27me3 were significantly enriched at genes in the IL‐6 signaling pathway, consistent with the well‐characterized role of KDM6B in modulation of inflammatory responses. Knockdown of KDM6B in cultured microglial cells diminished IL‐6 induction in response to an inflammatory stimulus. Our findings implicate a novel KDM6B‐mediated epigenetic signaling pathway integrated with inflammatory signaling pathways that are known to underlie the development of alcohol addiction.
Healing physiology following delayed surgery for femoral midshaft fracture caused by high-energy injury: an in vivo study in dogs

Objective An experimental model of severe soft tissue damage was designed to simulate high-energy fracture and observe the fracture healing process following early surgery and surgery delayed by 1 week. Methods Forty dogs were randomized to Group A (immediate surgery) and B (delayed surgery). The femur was broken, and the two ends were forcefully stabbed to damage the surrounding soft tissues. The fracture was repaired using a custom six-hole steel plate. Four dogs were killed on day 3 and weeks 1, 2, 4, and 8 following bone fracture. Soft tissue and bone were examined by light and electron microscopy. Results In Group A, no callus was present at 1, 2, 4, and 8 weeks following fracture, resulting in atrophic nonunion. In Group B, visible weak external callus was present 1 week following fracture, and good external callus growth was present at 2, 4, and 8 weeks, leading to callus healing. Conclusion These findings suggest that the first week is critical for fracture healing. Absence of callus in the early stage is indicative of absence of callus growth throughout the entire healing process, while the presence of callus in the early stage is indicative of vigorous callus growth thereafter.