Miracle-dz/UniFAR-FTUs huggingface dataset:
S100A8/A9 proteins mediate neutrophilic inflammation and lung pathology during tuberculosis.

RATIONALE A hallmark of pulmonary tuberculosis (TB) is the formation of granulomas. However, the immune factors that drive the formation of a protective granuloma during latent TB, and the factors that drive the formation of inflammatory granulomas during active TB, are not well defined. OBJECTIVES The objective of this study was to identify the underlying immune mechanisms involved in formation of inflammatory granulomas seen during active TB. METHODS The immune mediators involved in inflammatory granuloma formation during TB were assessed using human samples and experimental models of Mycobacterium tuberculosis infection, using molecular and immunologic techniques. MEASUREMENTS AND MAIN RESULTS We demonstrate that in human patients with active TB and in nonhuman primate models of M. tuberculosis infection, neutrophils producing S100 proteins are dominant within the inflammatory lung granulomas seen during active TB. Using the mouse model of TB, we demonstrate that the exacerbated lung inflammation seen as a result of neutrophilic accumulation is dependent on S100A8/A9 proteins. S100A8/A9 proteins promote neutrophil accumulation by inducing production of proinflammatory chemokines and cytokines, and influencing leukocyte trafficking. Importantly, serum levels of S100A8/A9 proteins along with neutrophil-associated chemokines, such as keratinocyte chemoattractant, can be used as potential surrogate biomarkers to assess lung inflammation and disease severity in human TB. CONCLUSIONS Our results thus show a major pathologic role for S100A8/A9 proteins in mediating neutrophil accumulation and inflammation associated with TB. Thus, targeting specific molecules, such as S100A8/A9 proteins, has the potential to decrease lung tissue damage without impacting protective immunity against TB.
Stenotrophobium rhamnosiphilum gen. nov., sp. nov., isolated from a glacier, proposal of Steroidobacteraceae fam. nov. in Nevskiales and emended description of the family Nevskiaceae.

A Gram-stain-negative strain, designated GT1R17T, was isolated from an ervoconite sample collected from Gawalong glacier in the Tibet Autonomous Region, PR China. Strain GT1R17T was catalase- and oxidase-positive, and grew optimally at 20-25°C and pH 7.0. The highest level of 16S rRNA gene sequence similarities were found to members of the genera Nevskia(92.27-93.15 %) and Hydrocarboniphaga(91.92-92.96 %). Phylogenetic analyses based on 16S rRNA gene sequences and genomic data revealed that the strain GT1R17T belonged to the family Nevskiaceae, but could not be assigned to any known genera. The genomic DNA G+C content was 54.4 mol%. The major fatty acids were summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), summed feature 8 (C18 : 1 ω7c and/or C18 : 1ω6c), C16 : 0, iso-C16 : 0 and summed feature 2 (C14 : 0 3OH and/or iso-C16 : 1 I). The polar lipids were phosphatidylglycerol, phosphatidylethanolamine and one unidentified lipid. The ubiquinone was Q-8. On the basis of the phenotypic, chemotaxonomic, genotypic and phylogenetic data, a novel species of a new genus,Stenotrophobiumrhamnosiphilum gen. nov., sp. nov. within the family Nevskiaceae, is proposed, with GT1R17T (=CGMCC 1.16137T=NBRC 113346T) as the type strain. In addition, phylogenetic analyses revealed that Steroidobacter and Povalibacter formed an independent clade in the order Nevskiales and were away from the families Nevskiaceae, Algiphilaceae and Salinisphaeraceae. Therefore, we propose to remove Steroidobacter and Povalibacter from the family Nevskiaceae and propose a new family Steroidobacteraceae in the order Nevskiales.
Effects of Phoenix dactylifera Ajwa on Infection, Hospitalization, and Survival Among Pediatric Cancer Patients in a University Hospital: A Nonrandomized Controlled Trial

This nonrandomized controlled trial determined the effects of Phoenix dactylifera palm date (Ajwa) intake on the number of infections and hospitalizations associated with fever, neutropenia, and mortality of pediatric cancer patients admitted between 2008 and 2017 to King Abdulaziz University Hospital (Jeddah, Saudi Arabia). Patients were eligible to be enrolled if they fulfilled the inclusion criteria, were not allergic to Ajwa, and were not enrolled in another study. Of 200 screened patients, 56 were included and 144 were excluded. Of the 56, 26 agreed to take Ajwa, and 30 served as controls. Both groups were assessed based on infection rates, frequency of hospital admissions for fever and neutropenia, and mortality rate. Background information regarding demographics, clinicopathological data, and treatment options was documented. Supplementation of Ajwa significantly reduced hospital admissions (for fever-associated neutropenia) and infections (P = .009 and P < .001, respectively). Off-treatment did not significantly differ between the Ajwa and control groups. The Ajwa group had a better survival rate in comparison to the non-Ajwa group (stratified log-rank P = .005), where the main cause of death of patients in the non-Ajwa group was disease progression associated with infections (77%). In summary, Ajwa intake during the standard treatment of pediatric cancer patients improved their treatment outcome.
Protective effect of melatonin and agomelatine on adriamycin-induced nephrotoxicity in rat model: a renal scintigraphy and biochemical study.

OBJECTIVE We aimed to determine the possible protective effects of melatonin and agomelatine on an animal model of adriamycin nephrotoxicity by 99mTc DMSA renal scintigraphy and biochemical methods. METHODS Ten weeks old 49 male Wistar rats were randomly separated into seven groups; namely control (CON), adriamycin (ADR), melatonin (MEL), agomelatine (AGO), melatonin + adriamycin (MEL+ADR), agomelatine + adriamycin (AGO+ADR) and melatonin + agomelatine + adriamycin (MEL+AGO+ADR) groups. Nephrotoxicity was induced by a three-dose of 18 mg/kg adriamycin, i.p. at a 24 h interval on the 5th, 6th and 7th days. A dose of melatonin and agomelatine (40 mg/kg/i.p, the same doses) were injected for 7 days before and after the injected of ADR (18 mg/kg, i.p.), respectively. On the 8th day of the experiment, all animals were evaluated and scintigraphic and biochemical parameters were assessed, respectively. RESULTS ADR significantly increased blood urea nitrogen (1040 %) and plasma creatinine (1020 %), and decreased 99mTc DMSA uptake levels (59 %) compared to the control (p < 0.001). Pretreatment with MEL, AGO, MEL+AGO mitigated these abnormalities produced by ADR in the kidney (p < 0.001). CONCLUSION 99mTc DMSA for the early determination of ADR-induced nephrotoxicity had an important role. Also, a significant correlation was found between biochemical and scintigraphy parameters. Adriamycin caused significant damages to kidneys that were reduced with MEL and AGO (Tab. 2, Fig. 3, Ref. 39).
Rhodoptilometrin, a Crinoid-Derived Anthraquinone, Induces Cell Regeneration by Promoting Wound Healing and Oxidative Phosphorylation in Human Gingival Fibroblast Cells

Gingival recession (GR) potentially leads to the exposure of tooth root to the oral cavity microenvironment and increases susceptibility to dental caries, dentin hypersensitivity, and other dental diseases. Even though many etiological factors were reported, the specific mechanism of GR is yet to be elucidated. Given the species richness concerning marine biodiversity, it could be a treasure trove for drug discovery. In this study, we demonstrate the effects of a marine compound, (+)-rhodoptilometrin from crinoid, on gingival cell migration, wound healing, and oxidative phosphorylation (OXPHOS). Experimental results showed that (+)-rhodoptilometrin can significantly increase wound healing, migration, and proliferation of human gingival fibroblast cells, and it does not have effects on oral mucosa fibroblast cells. In addition, (+)-rhodoptilometrin increases the gene and protein expression levels of focal adhesion kinase (FAK), fibronectin, and type I collagen, changes the intracellular distribution of FAK and F-actin, and increases OXPHOS and the expression levels of complexes I~V in the mitochondria. Based on our results, we believe that (+)-rhodoptilometrin might increase FAK expression and promote mitochondrial function to affect cell migration and promote gingival regeneration. Therefore, (+)-rhodoptilometrin may be a promising therapeutic agent for GR.
Therapeutic Challenges and Prognosis of Descemet's Membrane Endothelial Keratoplasty in Herpes Simplex Eye Disease

Purpose: To describe the functional outcome, postoperative complications, and complication management of Descemet's membrane endothelial keratoplasty (DMEK) in corneal decompensation secondary to Herpes simplex eye disease (HED). Methods: This retrospective interventional case series included 17 eyes that received DMEK for endothelial decompensation secondary to HED. Complete ophthalmological examination, including corrected-distance visual acuity (CDVA), anterior segment slit-lamp, and optical coherence tomography assessment, were performed preoperatively and postoperatively at regular follow-up intervals. Visual outcome and complication rates were compared with those of 72 consecutive eyes that received DMEK for Fuchs endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) during the same period. Results: Mean follow-up time was 11.1 ± 5.9 months (range 6–27). CDVA improved from 1.16 ± 0.46 logMAR to 0.62 ± 0.44 logMAR (P = 0.001). Corneal pachymetry significantly decreased from 695 ± 53 &mgr;m at day 1 to 569 ± 88 &mgr;m at 2 months (P < 0.001). Postoperative complications occurred in 12 eyes, including primary graft failure (12%), endotheliitis (29%), corneal ulcers (35%), and cystoid macular edema (18%). Most complications occurred shortly after surgery, with a median delay of 2.5 months. In comparison, the complication rates for DMEK in FECD and PBK were significantly lower (no graft failure, P = 0.005; no endotheliitis, P < 0.001; no corneal ulcers, P < 0.001 and 3% cystoid macular edema, P = 0.046). Conclusions: DMEK surgery significantly improved CDVA in patients with endothelial decompensation due to HED. The rate of postoperative complications was higher than for FECD and PBK. Close follow-up is mandatory and the rate of postoperative inflammatory events suggests that patients should be kept on high doses of oral valacyclovir.
Effect of Dapagliflozin Treatment on the Expression of Renal Sodium Transporters/Channels on High-Fat Diet Diabetic Mice

Background: Inhibition of the Na+/glucose co-transporter 2 is a new therapeutic strategy for diabetes. It is unclear how proximal loss of Na+ (and glucose) affects the subsequent Na+ transporters in the proximal tubule (PT), thick ascending limb of loop of Henle (TAL), distal convoluted tubule (DCT) and collecting duct (CD). Methods: Mice on a high fat diet were administered 3 doses streptozotocin 6 days prior to oral dapagliflozin administration or vehicle for 18 days. A control group of lean mice were also included. Body weight and glucose were recorded at regular intervals during treatment. Renal Na+ transporters expression in nephron segments were analyzed by RT-qPCR and Western blot. Results: Dapagliflozin treatment resulted in a significant reduction in body weight and blood glucose compared to vehicle-treated controls. mRNA results showed that Na+-hydrogen antiporter 3 (NHE3), Na+/phosphate cotransporter (NaPi-2a) and epithelial Na+ channel expression was increased, Ncx1, ENaCβ and ENaCγ expression declined (p all < 0.05), respectively, in dapagliflozin-treated mice when compared with saline vehicle mice. Na-K-2Cl cotransporters and Na-Cl cotransporter mRNA expression was not affected by dapagliflozin treatment. Na+/K+-ATPase (Atp1b1) expression was also increased significantly by dapagliflozin treatment, but it did not affect Atp1a1 and glucose transporter 2 expression. Western blot analysis showed that NaPi-2a, NHE3 and ATP1b1 expression was upregulated in dapagliflozin-treated diabetic mice when compared with saline vehicle mice (p < 0.05). Conclusion: Our findings suggest that dapagliflozin treatment augments compensatory changes in the renal PT in diabetic mice.
Visiting Newton's atelier before the Principia, 1679–1684

ABSTRACT The worksheets that presumably contained Newton's early development of the fundamental concepts in his Principia have been lost. A plausible reconstruction of this development is presented based on Newton's exchange of letters with Robert Hooke in 1679, with Edmund Halley in 1686, and on some clues in the diagram associated with Proposition 1 in Book 1 of the Principia that have been ignored in the past. A graphical construction associated with this proposition leads to a rapidly convergent method to obtain orbits for central forces, which elucidates how Newton may have have been led to formulate some of his most fundamental propositions in the Principia.
Erratum to cannabis in palliative care: current challenges and practical recommendations.

Department of Family Medicine, Department of Oncology, McGill University, Montreal, Canada; Clinique Santé Cannabis, Montreal, Canada; Department of Rehabilitation Medicine, Department of Geography, University of Washington, Seattle, WA, USA; College of Nursing, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Family Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada; Pharmacy Department, CHUM (Centre Hospitalier de l'Université de Montréal), Montreal, Canada Correspondence to: Claude Cyr, MD. Clinique La Cité Médicale de Montréal, 3500 Boulevard DeMaisonneuve west, suite 1520, Montreal, QC, H3Z 3C1, Canada. Email: claudecyrmd@gmail.com.
The Late Endosomal Pathway Regulates the Ciliary Targeting of Tetraspanin Protein Peripherin 2

Peripherin 2 (PRPH2) is a tetraspanin protein concentrated in the light-sensing cilium (called the outer segment) of the vertebrate photoreceptor. The mechanism underlying the ciliary targeting of PRPH2 and the etiology of cone dystrophy caused by PRPH2 mutations remain elusive. Here we show that the late endosome (LE) is the main waystation that critically sorts newly synthesized PRPH2 to the cilium. PRPH2 is expressed in the luminal membrane of the LE. We delineate multiple C-terminal motifs of PRPH2 that distinctively regulate its LE and ciliary targeting through ubiquitination and binding to ESCRT (Endosomal Sorting Complexes Required for Transport) component Hrs. Using the newly developed TetOn-inducible system in transfected male and female mouse cones in vivo, we show that the entry of nascent PRPH2 into the cone outer segment can be blocked by either cone dystrophy-causing C-terminal mutations of PRPH2, or by short-term perturbation of the LE or recycling endosomal traffic. These findings open new avenues of research to explore the biological role of the LE in the biosynthetic pathway and the etiology of cone dystrophy caused by PRPH2 mutations and/or malfunctions of the LE. SIGNIFICANCE STATEMENT Peripherin 2 (PRPH2) is a tetraspanin protein abundantly expressed in the light-sensing cilium, the outer segment, of the vertebrate photoreceptor. The mechanism underlying the ciliary transport of PRPH2 is unclear. The present study reveals a novel ciliary targeting pathway, in which the newly synthesized PRPH2 is first targeted to the lumen of the late endosome (LE) en route to the cilia. We deciphered the protein motifs and the machinery that regulates the LE trafficking of PRPH2. Using a novel TetOn-inducible system in transfected mouse cones, we showed that the LE pathway of PRPH2 is critical for its outer segment expression. A cone dystrophy-causing mutation impairs the LE and ciliary targeting of PRPH2, implicating the relevance of LE to cone/macular degenerative diseases.
Remote Control System for Battery-Assisted Devices with 16 nW Standby Consumption

One of the biggest impacts of the vision ‘Internet of Things’ is the massive number of connected devices, where billions of nodes will exchange data, information and commands. While wireless systems offer advantages such as increased flexibility, they also introduce one major challenge: how to power each individual node. In many cases, there is no way around the use of batteries. To minimize the environmental impact, increasing the battery’s longevity is the most important factor. This paper introduces a wireless battery-assisted node that has a drastically reduced energy consumption in the standby mode. The state (on/off) will be changed by harvesting a radiofrequency signal. A latching switch connects or disconnects the load—for example, a microcontroller—and the battery. The switch is connected to a charge pump which converts an AC (alternating current) signal into a usable DC (direct current) control signal. An antenna is mounted to the charge pump via a matching network. An electromagnetic wave is emitted by a remote control switch that switches the system on and off. The used frequency is 868 MHz and therefore in the UHF RFID (ultra high frequency radio frequency identification) band. The measurement results show that the wireless node consumes less than 16nW in the standby mode. The remote controlling is possible from a distance of more than 12m. The presented system can be integrated in further work on a UHF RFID tag. Thus, the existing protocol standard can be used to identify the object to be switched. By custom commands, the switching request can be transmitted from the remote control (UHF RFID reader) to the switching node.
Predictors of postconcussive symptoms 3 months after mild traumatic brain injury.

OBJECTIVE There is continuing controversy regarding predictors of poor outcome following mild traumatic brain injury (mTBI). This study aimed to prospectively examine the influence of preinjury factors, injury-related factors, and postinjury factors on outcome following mTBI. METHOD Participants were 123 patients with mTBI and 100 trauma patient controls recruited and assessed in the emergency department and followed up 1 week and 3 months postinjury. Outcome was measured in terms of reported postconcussional symptoms. Measures included the ImPACT Post-Concussional Symptom Scale and cognitive concussion battery, including Attention, Verbal and Visual memory, Processing Speed and Reaction Time modules, pre- and postinjury SF-36 and MINI Psychiatric status ratings, VAS Pain Inventory, Hospital Anxiety and Depression Scale, PTSD Checklist-Specific, and Revised Social Readjustment Scale. RESULTS Presence of mTBI predicted postconcussional symptoms 1 week postinjury, along with being female and premorbid psychiatric history, with elevated HADS anxiety a concurrent indicator. However, at 3 months, preinjury physical or psychiatric problems but not mTBI most strongly predicted continuing symptoms, with concurrent indicators including HADS anxiety, PTSD symptoms, other life stressors and pain. HADS anxiety and age predicted 3-month PCS in the mTBI group, whereas PTSD symptoms and other life stressors were most significant for the controls. Cognitive measures were not predictive of PCS at 1 week or 3 months. CONCLUSIONS Given the evident influence of both premorbid and concurrent psychiatric problems, especially anxiety, on postinjury symptoms, managing the anxiety response in vulnerable individuals with mTBI may be important to minimize ongoing sequelae.
Psychophysiological treatment outcomes: Corticotropin-releasing factor type 1 receptor antagonist increases inhibition of fear-potentiated startle in PTSD patients.

After exposure to a traumatic event, a subset of people develop post-traumatic stress disorder (PTSD). One of the key deficits in PTSD is regulation of fear, and impaired inhibition of fear-potentiated startle (FPS) has been identified as a potential physiological biomarker specific to PTSD. As part of a larger clinical trial, this study investigated the effects of a CRF receptor 1 antagonist, GSK561679, on inhibition of fear-potentiated startle during a conditional discrimination fear-conditioning paradigm, termed AX+/BX-. Prior research using this paradigm has demonstrated deficits in inhibition of conditioned fear in several PTSD populations. The randomized, double-blind, placebo-controlled clinical trial compared fear inhibition between female PTSD participants taking 350 mg/day GSK561679 (n = 47 pre- and 29 post-treatment) and patients taking a placebo pill (n = 52 pre- and 30 post-treatment) daily for 6 weeks. There was no significant difference between the two groups in their acquisition of fear or discrimination between threat and safety cues, and no pre-post-treatment effect on these measures. However, there was a significant effect of treatment on inhibition of FPS during the AB trials in the AX+/BX- transfer test (p < 0.05). While all PTSD participants showed typical impairments in fear inhibition prior to treatment, GSK561679 enhanced fear inhibition post-treatment, independent of clinical effects. The current study suggests that CRF receptor 1 antagonism may have specific effects within neural circuitry mediating fear inhibition responses, but not overall symptom presentation, in PTSD.
Parenting children with intellectual disability: linking maternal insightfulness to sensitivity.

BACKGROUND This study examined mothers' representation of their children's inner world - maternal insightfulness - and its link to sensitive maternal behaviour. We aimed to understand some of the parental processes that underlie parenting children with intellectual disability (ID). METHODS The sample included 38 mothers and their children with non-specific ID aged 2.5 to 5.5 years. Children had developmental quotient scores of M = 56.29, SD = 9.65 and adaptive behaviour scores of M = 60.72, SD = 10.43. We hypothesised that mothers who were insightful show more sensitive behaviour when interacting with their children than non-insightful mothers do. Maternal insightfulness was assessed using the insightfulness interview, and maternal sensitive behaviour during mother-child interaction was assessed using the emotional availability observation scales. RESULTS Forty-one per cent of the mothers showed positive insightfulness regarding their children's inner world. These mothers showed higher levels of sensitive behaviour than did the non-insightful mothers. The insightfulness-sensitivity link was not associated with any of the mothers' or the children's characteristics, including the level of developmental quotient, suggesting that these parental constructs are not simply a reflection of the level of the children's developmental delay. CONCLUSIONS Better understanding of the mechanism of parenthood, including the insightfulness-sensitivity link, may help personalise the support provided to parents of children with ID. The associations between maternal insightfulness and sensitivity imply that promoting maternal insightfulness may enhance mothers' sensitivity towards their children.
Field performance of the INSTI HIV‐1/‐2 antibody test in two South African antenatal clinics

This was a prospective study that assessed field performance of the INSTI HIV‐1/‐2 antibody test (INSTI test) in two antenatal clinics in South Africa (SA). INSTI test was evaluated against rapid tests used at these clinics, and pooled nucleic acid amplification testing (NAAT) performed for individuals with negative rapid tests. Three hundred and eighty‐six pregnant women were enrolled; 334 (86.5%) with negative results on the screening rapid test, and 52 (13.5%; 95% confidence interval [CI]: 10.2–17.3%) with positive results on screening and confirmatory rapid tests. INSTI test yielded the same results as other rapid tests in all participants, thus showing a 100% sensitivity (95% CI: 93.2–100.0%) and specificity (95% CI: 98.9–100.0%). Pooled NAAT was performed for 290 participants who had negative rapid tests, and yielded negative results in all pools. These data show excellent field performance of the INSTI test, and highlight that this test can be implementedat SA clinics.