Miracle-dz/UniFAR-FTUs huggingface dataset:
Preliminary Assessment of Microbial Community Structure of Wind-Tidal Flats in the Laguna Madre, Texas, USA

Aside from two samples collected nearly 50 years ago, little is known about the microbial composition of wind tidal flats in the hypersaline Laguna Madre, Texas. These mats account for ~42% of the lagoon’s area. These microbial communities were sampled at four locations that historically had mats in the Laguna Madre, including Laguna Madre Field Station (LMFS), Nighthawk Bay (NH), and two locations in Kenedy Ranch (KRN and KRS). Amplicon sequencing of 16S genes determined the presence of 51 prokaryotic phyla dominated by Bacteroidota, Chloroflexi, Cyanobacteria, Desulfobacteria, Firmicutes, Halobacteria, and Proteobacteria. The microbial community structure of NH and KR is significantly different to LMFS, in which Bacteroidota and Proteobacteria were most abundant. Twenty-three cyanobacterial taxa were identified via genomic analysis, whereas 45 cyanobacterial taxa were identified using morphological analysis, containing large filamentous forms on the surface, and smaller, motile filamentous and coccoid forms in subsurface mat layers. Sample sites were dominated by species in Oscillatoriaceae (i.e., Lyngbya) and Coleofasciculaceae (i.e., Coleofasciculus). Most cyanobacterial sequences (~35%) could not be assigned to any established taxa at the family/genus level, given the limited knowledge of hypersaline cyanobacteria. A total of 73 cyanobacterial bioactive metabolites were identified using ultra performance liquid chromatography-Orbitrap MS analysis from these commu nities. Laguna Madre seems unique compared to other sabkhas in terms of its microbiology.
Identification of 6-(piperazin-1-yl)-1,3,5-triazine as a chemical scaffold with broad anti-schistosomal activities

Background: Schistosomiasis, caused by infection with blood fluke schistosomes, is a neglected tropical disease of considerable importance in resource-poor communities throughout the developing world. In the absence of an immunoprophylactic vaccine and due to over-reliance on a single chemotherapy (praziquantel), schistosomiasis control is at risk should drug insensitive schistosomes develop. In this context, application of in silico virtual screening on validated schistosome targets has proven successful in the identification of novel small molecules with anti-schistosomal activity. Methods: Focusing on the Schistosoma mansoni histone methylation machinery, we herein have used RNA interference (RNAi), ELISA-mediated detection of H3K4 methylation, homology modelling and in silico virtual screening to identify a small collection of small molecules for anti-schistosomal testing. A combination of low to high-throughput whole organism assays were subsequently used to assess these compounds’ activities on miracidia to sporocyst transformation, schistosomula phenotype/motility metrics and adult worm motility/oviposition readouts. Results: RNAi-mediated knockdown of smp_138030/smmll-1 (encoding a histone methyltransferase, HMT) in adult worms (~60%) reduced parasite motility and egg production. Moreover, in silico docking of compounds into Smp_138030/SmMLL-1’s homology model highlighted competitive substrate pocket inhibitors, some of which demonstrated significant activity on miracidia, schistosomula and adult worm lifecycle stages together with variable effects on HepG2 cells. Particularly, the effect of compounds containing a 6-(piperazin-1-yl)-1,3,5-triazine core on adult schistosomes recapitulated the results of the smp_138030/smmll-1 RNAi screens. Conclusions: The biological data and the structure-activity relationship presented in this study define the 6-(piperazin-1-yl)-1,3,5-triazine core as a promising starting point in ongoing efforts to develop new urgently needed schistosomicides.
The Incidence of Chronic Mesenteric Ischemia in the Well-Defined Region of a Dutch Mesenteric Ischemia Expert Center

INTRODUCTION: This study aimed to determine the incidence of chronic mesenteric ischemia (CMI) and to examine the influence of the etiological cause, location, and severity of a mesenteric artery stenosis on the probability of having CMI. METHODS: A prospective database, containing the details of all patients with suspected CMI referred to a renowned CMI expert center, was used. Patients residing within the expert centers' well-defined region, between January 2014 and October 2019, were included. CMI was diagnosed when patients experienced sustained symptom improvement after treatment. RESULTS: This study included 358 patients, 75 had a ≥50% atherosclerotic stenosis of 1 vessel (CMI 16%), 96 of 2 or 3 vessels (CMI 81%), 81 celiac artery compression (CMI 25%), and 84 no stenosis (CMI 12%). In total, 138 patients were diagnosed with CMI, rendering a mean incidence of 9.2 (95% confidence interval [CI] 6.2–13.7) per 100,000 inhabitants. Atherosclerotic CMI was most common, with a mean incidence of 7.2 (95% CI 4.6–11.3), followed by median arcuate ligament syndrome 1.3 (95% CI 0.5–3.6) and chronic nonocclusive mesenteric ischemia 0.6 (95% CI 0.2–2.6). The incidence of CMI was highest in female patients (female patients 12.0 [95% CI 7.3–19.6] vs male patients 6.5 [95% CI 3.4–12.5]) and increased with age. CMI was more prevalent in the presence of a ≥70% atherosclerotic single-vessel stenosis of the superior mesenteric artery (40.6%) than the celiac artery (5.6%). DISCUSSION: The incidence of CMI is higher than previously believed and increases with age. Probability of CMI seems highest in suspected CMI patients with multivessel disease or a ≥70% atherosclerotic single-vessel superior mesenteric artery stenosis.
Does the Modality Used in Health Coaching Matter? A Systematic Review of Health Coaching Outcomes

Objective The purpose of this review was to evaluate the modalities (e.g., face-to-face, telephone or electronic) of pharmacist health coaching providing the greatest improvement in patient outcomes, to enable a more comprehensive evaluation to be done and quality decision-making around health coaching modalities to be undertaken by pharmacists. Methods This systematic review followed the PRISMA guidelines. CINHAL, EMBASE, PubMed, PsychINFO and SCOPUS were searched (2000–2019). Included articles were reviewed for the modality used to health coach, the training provided, and the outcomes. Results Twelve papers met the eligibility criteria. A majority of studies included involved a combination of modalities of pharmacist health coaching. Four papers referred to face-to-face sessions, and one study used telephone coaching. In each paper, coaching led to an improvement in clinical and non-clinical health outcomes. Conclusion The training provided to health coaches varied and in some cases was not reported. Inconsistencies in reports led to difficulties when comparing study outcomes. Therefore, conclusions about the modality providing the greatest improvement in patient outcomes and the most pragmatic health coaching modality are not possible. Studies that document the training, the modality, the outcomes and the cost benefits of coaching by pharmacists are warranted to enable a more comprehensive evaluation to be done and quality decision-making around health coaching modalities to be undertaken by pharmacists.
Schwann Cell Autocrine and Paracrine Regulatory Mechanisms, Mediated by Allopregnanolone and BDNF, Modulate PKCε in Peripheral Sensory Neurons

Protein kinase type C-ε (PKCε) plays important roles in the sensitization of primary afferent nociceptors, such as ion channel phosphorylation, that in turn promotes mechanical hyperalgesia and pain chronification. In these neurons, PKCε is modulated through the local release of mediators by the surrounding Schwann cells (SCs). The progesterone metabolite allopregnanolone (ALLO) is endogenously synthesized by SCs, whereas it has proven to be a crucial mediator of neuron-glia interaction in peripheral nerve fibers. Biomolecular and pharmacological studies on rat primary SCs and dorsal root ganglia (DRG) neuronal cultures were aimed at investigating the hypothesis that ALLO modulates neuronal PKCε, playing a role in peripheral nociception. We found that SCs tonically release ALLO, which, in turn, autocrinally upregulated the synthesis of the growth factor brain-derived neurotrophic factor (BDNF). Subsequently, glial BDNF paracrinally activates PKCε via trkB in DRG sensory neurons. Herein, we report a novel mechanism of SCs-neuron cross-talk in the peripheral nervous system, highlighting a key role of ALLO and BDNF in nociceptor sensitization. These findings emphasize promising targets for inhibiting the development and chronification of neuropathic pain.
Genome-Wide Analysis Reveals Transcription Factors Regulated by Spider-Mite Feeding in Cucumber (Cucumis sativus)

To gain insight into the regulatory networks that underlie the induced defense in cucumber against spider mites, genes encoding transcription factors (TFs) were identified in the cucumber (Cucumis sativus) genome and their regulation by two-spotted spider mite (Tetranychus urticae) herbivory was analyzed using RNA-seq. Of the total 1212 annotated TF genes in the cucumber genome, 119 were differentially regulated upon spider-mite herbivory during a period of 3 days. These TF genes belong to different categories but the MYB, bHLH, AP2/ERF and WRKY families had the highest relative numbers of differentially expressed genes. Correlation analysis of the expression of TF genes with defense-associated genes during herbivory and pathogen infestation, and in different organs resulted in the putative identification of regulators of herbivore-induced terpenoid and green-leaf-volatile biosynthesis. Analysis of the cis-acting regulatory elements (CAREs) present in the promoter regions of the genes responsive to spider-mite feeding revealed potential TF regulators. This study describes the TF genes in cucumber that are potentially involved in the regulation of induced defense against herbivory by spider mites.
An Improved Physical-Stochastic Model for Simulating Electrical Tree Propagation in Solid Polymeric Dielectrics

The dielectric breakdown of solid polymeric materials is due to the inception and propagation of electrical trees inside them. The remaining useful life of the solid dielectrics could be determined using propagation simulations correlated with non-intrusive measurements such as partial discharges (PD). This paper presents a brief review of the different models for simulating electrical tree propagation in solid dielectrics. A novel improved physical-stochastic model is proposed, which allows quantitatively and qualitatively analyzing the electrical tree propagation process in polymeric dielectrics. Simulation results exhibit good agreement with measurements presented in the literature. It is concluded that the model allows adequately predicting the tree propagation behavior and additional experimental analyses are required in order to improve the model accuracy.
The State of Art of Regenerative Therapy in Cardiovascular Ischemic Disease: Biology, Signaling Pathways, and Epigenetics of Endothelial Progenitor Cells

Ischemic heart disease is currently a major cause of mortality and morbidity worldwide. Nevertheless, the actual therapeutic scenario does not target myocardial cell regeneration and consequently, the progression toward the late stage of chronic heart failure is common. Endothelial progenitor cells (EPCs) are bone marrow-derived stem cells that contribute to the homeostasis of the endothelial wall in acute and chronic ischemic disease. Calcium modulation and other molecular pathways (NOTCH, VEGFR, and CXCR4) contribute to EPC proliferation and differentiation. The present review provides a summary of EPC biology with a particular focus on the regulatory pathways of EPCs and describes promising applications for cardiovascular cell therapy.
Ultrasound-Attenuated Microorganisms Inoculated in Vegetable Beverages: Effect of Strains, Temperature, Ultrasound and Storage Conditions on the Performances of the Treatment

Four microorganisms (Lactobacillus acidophilus LA5, Bifidobacterium animalis subsp. lactis DSM 10140 and Lactiplantibacillus plantarum c16 and c19) were attenuated through ultrasound (US) treatments (40% of power for 2, 4 and 6 min; and 60% for 2 min; pulses were set at 2 s) inoculated in rice–oats–almond–soy-based beverages and stored at 4 °C for eight days. All strains were able to survive throughout the storage independently by the food matrix. Concerning the effect on acidification, the results were analyzed through multifactorial analysis of variance (MANOVA) and the key-findings of this were: (i) The treatment with 40% of power for 6 min was the most efficient at delaying acidification; (ii) Lb. acidophilus LA5 showed the best capacity to delay acidification; (iii) in the soy-based beverage a lower acidification was found. In a second step, L. plantarum c16 and c19 were attenuated, inoculated in rice beverage, stored under a thermal abuse (for 4 and 24 h) and then at 4, 15 and 20 °C. The results showed that only when US were combined with refrigeration temperatures were they efficient at delaying acidification. Thus, a perspective for attenuation could be the optimization of the treatment to design an effective way to counteract acidification also under a thermal abuse.
High fat-fed GPR55 null mice display impaired glucose tolerance without concomitant changes in energy balance or insulin sensitivity but are less responsive to the effects of the cannabinoids rimonabant or Δ(9)-tetrahydrocannabivarin on weight gain

Background The insulin-sensitizing phytocannabinoid, Δ(9)-tetrahydrocannabivarin (THCV) can signal partly via G-protein coupled receptor-55 (GPR55 behaving as either an agonist or an antagonist depending on the assay). The cannabinoid receptor type 1 (CB1R) inverse agonist rimonabant is also a GPR55 agonist under some conditions. Previous studies have shown varied effects of deletion of GPR55 on energy balance and glucose homeostasis in mice. The contribution of signalling via GPR55 to the metabolic effects of THCV and rimonabant has been little studied. Methods In a preliminary experiment, energy balance and glucose homeostasis were studied in GPR55 knockout and wild-type mice fed on both standard chow (to 20 weeks of age) and high fat diets (from 6 to 15 weeks of age). In the main experiment, all mice were fed on the high fat diet (from 6 to 14 weeks of age). In addition to replicating the preliminary experiment, the effects of once daily administration of THCV (15 mg kg−1 po) and rimonabant (10 mg kg−1 po) were compared in the two genotypes. Results There was no effect of genotype on absolute body weight or weight gain, body composition measured by either dual-energy X-ray absorptiometry or Nuclear Magnetic Resonance (NMR), fat pad weights, food intake, energy expenditure, locomotor activity, glucose tolerance or insulin tolerance in mice fed on chow. When the mice were fed a high fat diet, there was again no effect of genotype on these various aspects of energy balance. However, in both experiments, glucose tolerance was worse in the knockout than the wild-type mice. Genotype did not affect insulin tolerance in either experiment. Weight loss in rimonabant- and THCV-treated mice was lower in knockout than in wild-type mice, but surprisingly there was no detectable effect of genotype on the effects of the drugs on any aspect of glucose homeostasis after taking into account the effect of genotype in vehicle-treated mice. Conclusions Our two experiments differ from those reported by others in finding impaired glucose tolerance in GPR55 knockout mice in the absence of any effect on body weight, body composition, locomotor activity or energy expenditure. Nor could we detect any effect of genotype on insulin tolerance, so the possibility that GPR55 regulates glucose-stimulated insulin secretion merits further investigation. By contrast with the genotype effect in untreated mice, we found that THCV and rimonabant reduced weight gain, and this effect was in part mediated by GPR55.
Effects of elephant activities on forest plantations in the Kilimanjaro forest-game reserve in northern Tanzania

A study of the effects of elephant activities on forest plantations was conducted between December 1971 and May 1972 in the Kilimanjaro Forest-Game Reserve. Faecal counts in the forest gave an estimate of elephant population density of 0.67 km-2 and a total population of 1197 ? 259. Trees damaged by elephants were enumerated in a total of 180 quadrats of (50 x 50) m each, covering an area of 45 ha. Out of 175450 trees enumerated an estimated 42565 or 24.3 % sustained damage from elephants. Pinus patula Schiede and Deppe suffered most damage of four exotic tree species studied. Damage by uprooting and breaking was higher in young than in old trees. Girdling accounted for over 75 % of the damage; more in young trees. Browsing resulted in stunted growth of young trees. Damage to tree plantations was severe in areas where weeding, pruning and thinning were late, or in areas where patches of bush were left uncleared between the compartments. Damage was also more severe in the dry season than in the rainy season. Trees were examined for secondary damage by borers or fungi, but no evidence was found. Recommendations for control and regulation of game populations in the reserve are suggested.
Causes of false-negative rapid diagnostic tests for symptomatic malaria in the DRC

Background The majority of Plasmodium falciparum malaria diagnoses in Africa are made using rapid diagnostic tests (RDTs) that detect histidine-rich protein 2. Increasing reports of false-negative RDT results due to parasites with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3) raise concern about existing malaria diagnostic strategies. We previously identified pfhrp2-negative parasites among asymptomatic children in the Democratic Republic of the Congo (DRC), but their impact on diagnosis of symptomatic malaria is unknown. Methods We performed a cross-sectional study of false-negative RDTs in symptomatic subjects in 2017. Parasites were characterized by microscopy; RDT; pfhrp2/3 genotyping and species-specific PCR assays; a multiplex bead-based immunoassay; and/or whole-genome sequencing. Results Among 3,627 symptomatic subjects, we identified 427 (11.8%) RDT-/microscopy+ cases. Parasites from eight (0.2%) samples were initially classified as putative pfhrp2/3 deletions by PCR, but antigen testing and whole-genome sequencing confirmed the presence of intact genes. Malaria prevalence was high (57%) and non-falciparum co-infection common (15%). HRP2-based RDT performance was satisfactory and superior to microscopy. Conclusions Symptomatic malaria due to pfhrp2/3-deleted P. falciparum was not observed in the DRC. Ongoing HRP2-based RDT use is appropriate for the detection of falciparum malaria in the DRC.
A Clinical Study on the Use of Intraventricular Polymyxin B Supplemented by Continuous External Ventricular Drainage in the Treatment of Drug-Resistant Gram-Negative Bacilli Intracranial Infection

Purpose To investigate the clinical effect of ventricular polymyxin B supplemented by continuous external ventricular drainage in the treatment of intracranial infection with multidrug-resistant (MDR) or extensively drug-resistant (XDR) Gram-negative (G-) bacilli following neurosurgery. Patients and Methods A retrospective analysis was performed on 28 patients who had G-bacilli intracranial infection following neurosurgery in our department between January 2017 and December 2019. The patients were treated with intraventricular polymyxin B supplemented by continuous external ventricular drainage. The clinical characteristics, treatment process, cerebrospinal-fluid-related indicators, results and prognosis were analysed. Results All of 28 patients developed an infection subsequent to neurosurgery, and cerebrospinal fluid (CSF) cultures demonstrated MDR/XDR G- bacilli, including Acinetobacter baumannii in 14 cases, Klebsiella pneumoniae in 9 cases, Pseudomonas aeruginosa in 3 cases, and Enterobacter cloacae in 2 cases. The ventricular drainage tube remained unobstructed in all patients during treatment, and intraventricular polymyxin B combined with intravenous antibiotics were administered each day. The duration of treatment with intraventricular polymyxin B was 14.96±4.28 days, and the time required to obtain a negative CSF culture was 8.23±4.02 days. The bacterial clearance rate from cerebrospinal fluid was 92.9% (26/28), and the clinical cure rate was 82.1% (23/28). Among them, 18 patients underwent ventriculoperitoneal shunt insertion for hydrocephalus 82.5 (59.5,114.75) days after the infection was cured, and the mortality rate was 17.6% (5/28). There was no significant change in patient blood creatinine levels before and after treatment. Cured patients were followed up for 4 months to 3 years, and no recurrences were observed. Conclusion Treatment of intracranial infection with MDR/XDR G- bacilli using early intraventricular polymyxin B supplemented by continuous external ventricular drainage treatment may be a safe and effective treatment strategy.
Lysophosphatidic Acid Receptor 5 Contributes to Imiquimod-Induced Psoriasis-Like Lesions through NLRP3 Inflammasome Activation in Macrophages

The pathogenesis of psoriasis, an immune-mediated chronic skin barrier disease, is not fully understood yet. Here, we identified lysophosphatidic acid (LPA) receptor 5 (LPA5)-mediated signaling as a novel pathogenic factor in psoriasis using an imiquimod-induced psoriasis mouse model. Amounts of most LPA species were markedly elevated in injured skin of psoriasis mice, along with LPA5 upregulation in injured skin. Suppressing the activity of LPA5 with TCLPA5, a selective LPA5 antagonist, improved psoriasis symptoms, including ear thickening, skin erythema, and skin scaling in imiquimod-challenged mice. TCLPA5 administration attenuated dermal infiltration of macrophages that were found as the major cell type for LPA5 upregulation in psoriasis lesions. Notably, TCLPA5 administration attenuated the upregulation of macrophage NLRP3 in injured skin of mice with imiquimod-induced psoriasis. This critical role of LPA5 in macrophage NLRP3 was further addressed using lipopolysaccharide-primed bone marrow-derived macrophages. LPA exposure activated NLRP3 inflammasome in lipopolysaccharide-primed cells, which was evidenced by NLRP3 upregulation, caspase-1 activation, and IL-1β maturation/secretion. This LPA-driven NLRP3 inflammasome activation in lipopolysaccharide-primed cells was significantly attenuated upon LPA5 knockdown. Overall, our findings establish a pathogenic role of LPA5 in psoriasis along with an underlying mechanism, further suggesting LPA5 antagonism as a potential strategy to treat psoriasis.