Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted urine proteomics in lupus nephritis – a meta-analysis

ABSTRACT Background Proteomic approaches are central in biomarker discovery. While mass-spectrometry-based techniques are widely used, novel targeted proteomic platforms have enabled the high-throughput detection of low-abundance proteins in an affinity-based manner. Urine has gained growing attention as an ideal biofluid for monitoring renal disease including lupus nephritis (LN). Methods Pubmed was screened for targeted proteomic studies of LN urine interrogating ≥1000 proteins. Data from the primary studies were combined and a meta-analysis was performed. Shared proteins elevated in active LN across studies were identified, and relevant pathways were elucidated using ingenuity pathway and gene ontology analysis. Urine proteomic data was cross-referenced against renal single-cell RNAseq data from LN kidneys. Results Two high-throughput targeted proteomic platforms with capacity to interrogate ≥1000 proteins have been used to investigate LN urine. Twenty-three urine proteins were significantly elevated in both studies, including 10 chemokines, and proteins implicated in angiogenesis, and extracellular matrix turnover. Of these, Cathepsin S, CXCL10, FasL, ferritin, macrophage migration inhibitory factor (MIF), and resistin were also significantly elevated within LN kidneys. Conclusion Targeted urinary proteomics have uncovered multiple novel biomarkers for LN. Further validation in prospective cohorts and mechanistic studies are warranted to establish their clinical utility.
Adsorption of miR-218 by lncRNA HOTAIR regulates PDE7A and affects glioma cell proliferation, invasion, and apoptosis.

OBJECTIVE To evaluate the role of targeted adsorption of miR-218 by long-chain non-coding RNAHOTAIR to regulate PDE7A on glioma cell proliferation, invasion, and apoptosis. METHODS The expressions of lncRNA HOTAIR, miR-218, and PDE7A in glioma tissues and normal parcancer tissues, NHA and glioma cell lines were determined, and correlations among the three genes were analyzed. The subcellular localization of lncRNA HOTAIR was determined by fluorescent in situ hybridization. Dual-luciferase reporter assay was used to validate the targeted relationship between lncRNA HOTAIR/miR-218/PDE7A. Glioma cells were grouped to receive intervention of lncRNA HOTAIR or miR-218. MTT, transwell, and flow cytometry were performed to determine the proliferation, invasion, and apoptosis of cells. RESULTS Compared with the normal tissues and cells, the expression of lncRNA HOTAIR was increased while miR-218 was suppressed in glioma tissues samples and cells (all P<0.05). Inhibition of lncRNA HOTAIR expression, was able to induce apoptosis and suppress the proliferation and invasion of cells (all P<0.05). LncRNA HOTAIR is mainly localized in the cytoplasm, and is able to adsorb miR-218 as ceRNA. The effect of knockdown of HOTAIR on glioma cells could be partially rescued by miR-218 inhibitor. The expression of PDE7A was enhanced in glioma tissues and cells compared to normal tissues and cells (all P<0.05), which positively correlated with the expression of HOTAIR (r=0.546, P<0.05) and negatively correlated with the expression of miR-218 (r=0.363, P<0.05). The targeted relationship between miR-218 and PDE7A was validated: Overexpression of miR-218 was able to suppress the proliferation and invasion of glioma cells and restrain apoptosis compared to the miR-NC group (all P<0.05). The effect of miR-218 on glioma cells could be partially rescued by PDE7A. CONCLUSION lncRNA HOTAIR can adsorb miR-218 to regulate expression of PDE7A and promote the malignant biologic behavior of glioma cells.
Short-term blood pressure variability, arterial stiffness, and cardiovascular events: results from the Bordeaux cohort

Supplemental Digital Content is available in the text Objective: Short-term blood pressure variability derived from 24-h ambulatory monitoring is associated with poor cardiovascular prognosis. However, previous analyses of this have clearly been influenced by clinical cofounders, particularly blood pressure (BP) level. Arterial stiffness is a powerful marker of cardiovascular risk, which may influence BP variability. In this study, we assessed the prognostic value of BP variability based on 24-h ambulatory measurements and adjusted for arterial stiffness. Methods: Population: Bordeaux cohort of hypertensive patients. Inclusion criteria were 24-h ambulatory BP monitoring at baseline with measurements every 15’ day and night, determination of wake-up time and bedtime, and assessment of arterial stiffness with monitoring of Korotkoff sound arrival time. A total of 969 patients (age 54 ± 14 years) with an average follow up of 120 ± 78 months and 178 cardiovascular recorded events were included. Results: In univariate survival analyses, the standard deviations of day, night, and 24-h SBP were associated with the occurrence of cardiovascular events. The standard deviation of night-time SBP showed the strongest association with the outcome variable and was entered into multivariate analyses. In multivariate analyses, night-time SBP variability remained significantly associated with the occurrence of cardiovascular events after adjusting for major cardiovascular risk factors, 24-h SBP, and arterial stiffness. BP variability and arterial stiffness showed no significant association. Conclusion: Our results suggest that variability of night-time SBP is an important marker of the risk of cardiovascular events in hypertensive patients, independently of average 24-h BP and arterial stiffness.
Secukinumab real world drug retention compared to TNF-alpha inhibitors in psoriatic arthritis.

OBJECTIVES To prospectively study real-world efficacy and safety of secukinumab in psoriatic arthritis (PsA) patients from the Israeli registry of inflammatory diseases. METHODS PsA patients fulfilling the CASPAR criteria were included in the analysis from 2010 to 2019. The primary endpoint was secukinumab drug retention compared to other TNF-α inhibitors (TNFi). Bivariate and multivariate analyses were made by Cox regression analysis. Drug retention according to treatment line was examined with Kaplan-Meier curves. RESULTS Included were 404 PsA patients who had 709 treatment courses during the study period. Ninety patients had been treated with secukinumab (22%). The secukinumab-treated patients were significantly older and their disease duration was longer. Secukinumab was less likely to be the first line of treatment compared to TNFi. Secukinumab had a drug retention comparable to TNFi, and a better drug retention than TNFi among biologic-experienced patients. Neither methotrexate combination nor body mass index affected the inefficacy event rate. Secukinumab had a similar rate of adverse events as TNFi. CONCLUSIONS This multicentre real-world study demonstrated that secukinumab had a drug retention comparable to TNFi. Secukinumab had a better drug retention than TNFi among biologic-experienced patients. IL-17 inhibition is an effective mechanism of action to treat PsA in real life.
Beyond the ‘purple drank’: Study of promethazine abuse according to the European Medicines Agency adverse drug reaction reports

Background: Promethazine is a medicinal product, available on its own or in combination with other ingredients including dextromethorphan, paracetamol and/or expectorants. Anecdotal reports have however indicated that promethazine may have a misuse potential, especially in adolescents. Objective: We here aimed at studying how this phenomenon has been reported to the European Monitoring Agency Adverse Drug Reactions database. Methods: After a formal request to the European Monitoring Agency, the promethazine-specific dataset has been studied, performing a descriptive analysis of misuse/abuse/dependence-related adverse drug reaction reports. The study was approved by the University of Hertfordshire (LMS/PGR/UH/03234). Results: The analysis of promethazine data showed increasing levels of misuse/abuse/ dependence issues over time (2003–2019). Out of a total number of 1543 cases of adverse drug reactions, the abuse/misuse/dependence-related cases reported were 557, with ‘drug abuse’ (300/557: 53.8%) and ‘intentional product misuse’ (117/557: 21.0%). being the most represented adverse drug reactions. A high number of fatalities were described (310/557: 55.6%), mostly recorded as ‘drug toxicity/drug abuse’ cases, with opiates/opioids having been the most commonly reported concomitant drugs used. Conclusion: Anecdotal promethazine misuse/abuse reports have been confirmed by European Monitoring Agency data. Promethazine misuse/abuse appears to be an alarming issue, being associated with drug-related fatalities. Thus, healthcare professionals should be warned about a possible misuse of promethazine and be vigilant, as in some countries medicinal products containing promethazine can be purchased over the counter. Since promethazine is often available in association with opioids, its abuse may be considered a public health issue, with huge implications for clinical practice.
Small‐scale field evaluation of the entomological efficacy and the residual activity of Fludora® Fusion WP‐SB indoor residual spraying against Anopheles culicifacies s.l. in Gujarat, India

To evaluate the entomological efficacy and the residual activity of indoor residual spraying with Fludora® Fusion 562.5 WP‐SB, a combination formulation containing clothianidin, a neonicotinoid and deltamethrin, a pyrethroid, against the main rural malaria vector, Anopheles culicifacies s.l. , in India in a small‐scale trial.
COVID‐19‐associated oxidative damage to red blood cells

A 9-year-old Afro-Caribbean boy presented with fever, abdominal pain and collapse. Physical examination was normal, as were chest X-ray and computed tomography of his head. Urinalysis showed microscopic haematuria and proteinuria. A reverse transcription polymerase chain reaction (RT-PCR) was positive for SARS-CoV-2 RNA. His full blood count on presentation showed a haemoglobin concentration of 99 g/l, a mean cell volume (MCV) of 59.7 fl, a reticulocyte count of 89 9 10/l, a white cell count of 8.4 9 10/l and a platelet count of 137 9 10/l. Lactate dehydrogenase (LDH) was elevated at 657 iu/l with an elevated bilirubin of 42 lmol/l and an alanine transaminase of 195 iu/l. A direct Coombs test was negative and the result of a glucose-6-phosphate-dehydrogenase assay was 17.8 iu/g Hb (normal range 8.8–12.8). High performance liquid chromatography showed a haemoglobin A2 of 6.1% suggesting a diagnosis of b thalassaemia trait. Blood film examination (image) showed evidence of oxidative haemolysis with numerous blister and hemighost cells (long arrows), keratocytes (short arrows), irregularly contracted cells and echinocytes. The patient had received no drugs known to cause oxidative haemolysis. The sample was referred to the regional genetics laboratory for further evaluation of possible enzymopathies by Next-Generation Sequencing. This showed a heterozygous pathogenic variant of HBB, Hb Monroe, which has the phenotype of b thalassaemia with no G6PD mutation or evidence of other cause for the profound blood film changes. Due to a rising LDH of 1370 iu/l and development of heart block, together with an elevated troponin of 884 ng/l, the patient was referred to the regional paediatric cardiac unit for further management and evaluation for a possible Kawasaki disease-type disorder. He made a full recovery following intravenous methylprednisolone and intravenous immunoglobulin.
First reported adult patient with retinal dystrophy and leukodystrophy caused by a novel ACBD5 variant: A case report and review of literature

Peroxisomes play an essential role in lipid metabolism via interaction with other intracellular organelles. The information about the role of the Acyl‐CoA‐binding domain containing‐protein 5 (ACBD5) in these interactions in human cells is emerging. Moreover, a few patients with retinal dystrophy and leukodystrophy caused by pathogenic variants in ACBD5 have been recently introduced. Here, we present a 36‐year‐old female with retinal dystrophy, leukodystrophy, and psychomotor regression due to a novel homozygous variant in ACBD5. Our study adds to the growing knowledge of this peroxisomal disorder by providing phenotypic details of the first adult patient.
Effects of Complete Bladder Cuff Removal on Oncological Outcomes Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma

Purpose This study aimed to evaluate the effects of bladder cuff method on oncological outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma. Materials and Methods The records of 1,095 patients treated with RNU performed at our hospital between 1994 and 2018 were retrospectively reviewed; 856 patients with no bladder tumor history were enrolled in the present study. The management of bladder cuff was divided into two categories: extravesical ligation (EL) or transvesical resection (TR). Survival was analyzed using the Kaplan-Meier method and Cox regression analyses were performed to determine which factors were associated with intravesical recurrence (IVR)–free survival (IVRFS), cancer-specific survival (CSS), and overall survival (OS). Results The mean patient age was 64.8 years and the median follow-up was 37.7 months. Among the 865 patients, 477 (55.7%) underwent the TR and 379 (44.3%) the EL. Significantly higher IVRFS (p=0.001) and OS (p=0.013) were observed in the TR group. In multivariable analysis, IVR, CSS, and OS were independently associated with the EL. Among 379 patients treated with the EL, eight underwent remnant ureterectomy. Based on radical cystectomy–free survival, significant difference was not observed between the two groups. However, significantly higher IVRFS was observed in the TR group when the tumor was located in the renal pelvis. Conclusion Intramural complete excision of the distal ureter during RNU should be the gold standard approach compared with EL for the management of distal ureter in terms of oncological outcomes.
Toxoplasma gondii infection and the risk of adult glioma in two prospective studies

Toxoplasma gondii (T gondii) is a common parasite that shows affinity to neural tissue and may lead to the formation of cysts in the brain. Previous epidemiologic studies have suggested an association between glioma and increased prevalence of T gondii infection, but prospective studies are lacking. Therefore, we examined the association between prediagnostic T gondii antibodies and risk of glioma in two prospective cohorts using a nested case‐control study design. Cases and matched controls were selected from the American Cancer Society's Cancer Prevention Study‐II Nutrition Cohort (CPSII‐NC) (n = 37 cases and 74 controls) and the Norwegian Cancer Registry's Janus Serum Bank (Janus) (n = 323 cases and 323 controls). Blood samples collected prior to diagnosis were analyzed for antibodies to two T gondii surface antigens (p22 and sag‐1), with individuals considered seropositive if antibodies to either antigen were detected. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for each cohort. In both cohorts, a suggestive increase in glioma risk was observed among those infected with T gondii (OR: 2.70; 95% CI: 0.96‐7.62 for CPSII‐NC; OR: 1.32, 95% CI: 0.85‐2.07 for Janus), particularly among participants with high antibody titers specific to the sag‐1 antigen (CPSII‐NC OR: 3.35, 95% CI: 0.99‐11.38; Janus OR: 1.79, 95% CI: 1.02‐3.14). Our findings provide the first prospective evidence of an association between T gondii infection and risk of glioma. Further studies with larger case numbers are needed to confirm a potential etiologic role for T gondii in glioma.
Soil‐gas diffusivity in large soil monoliths

The variability of gas diffusion in soil is not well known, but is important for assessing greenhouse gas emissions, soil decontamination, oxidation in soil and plant and root respiration. The goal of this study was to assess small‐scale variability of the relative soil‐gas diffusivity (Ds / Do, msoil air) using large intact soil monoliths and to compare Ds / Do calculation methods. Neon (Ne) was maintained constant at the lower boundary of three monoliths of two soils (a sand and an organic soil). Ne concentration was measured at large spatial and temporal frequencies. Calculation methods included the use of average concentration, and average Ds / Do per horizon, per section, or for the entire soil profile. Considering all sections of the monoliths, Ds / Do varied from 3.5 × 10−3 to 1.2 × 10−1 for the Ap horizon and from 4.8 × 10−3 to 8.3 × 10−1 for the Bf horizon in the sand and from 1.0 × 10−3 to 7.9 × 10−3 for the Ohp horizon and from 2.4 × 10−4 to 7.7 × 10−2 for the Of horizon in the organic soil. For the entire soil profile, variations in Ds / Do between monoliths reached 125% in the sand and 56% in the organic soil. The Ds / Do calculation method influenced the apparent variability (CV) of Ds / Do and, to a lesser extent, Ds / Do values of the overall soil profile. Differences in Ds / Do between monoliths could not be explained solely by the variability of total soil porosity and air‐filled porosity. Soil macroporosity (cracks and earthworm burrows) and layering greatly influenced variability of gas movement. Thus, the choice of sampling procedure, calculation method and modelling must be governed by the scale of the processes of interest and soil variability attributes.
Temporal regulation of tumor growth in nocturnal mammals: In vivo studies and chemotherapeutical potential

Tumors of the nervous system including glioblastoma multiforme (GBM) are the most frequent and aggressive form of brain tumors; however, little is known about the impact of the circadian timing system on the formation, growth, and treatment of these tumors. We investigated day/night differences in tumor growth after injection of A530 glioma cells isolated from malignant peripheral nerve sheath tumor (MPNSTs) of NPcis (Trp53+/−; Nf1+/−) mice. Synchronized A530 cell cultures expressing typical glial markers were injected at the beginning of the day or night into the sciatic nerve zone of C57BL/6 mice subject to a 12:12 hours light/dark (LD) cycle or after being released to constant darkness (DD). Tumors generated in animals injected early at night in the LD cycle or in DD showed higher growth rates than in animals injected diurnally. No differences were found when animals were injected at the same time with cultures synchronized 12 hours apart. Similar experiments performed with B16 melanoma cells showed higher tumor growth rates in animals injected at the beginning of the night compared to those injected in the daytime. A higher tumor growth rate than that in controls was observed when mice were injected with knocked‐down clock gene Bmal1 cells. Finally, when we compared day/night administration of different doses of the proteasome inhibitor Bortezomib (0.5‐1.5 mg/kg) in tumor‐bearing animals, we found that low‐dose chemotherapy displayed higher efficacy when administered at night. Results suggest the existence of a precise temporal control of tumor growth and of drug efficacy in which the host state and susceptibility are critical.
Pharmacological Interventions for the Prevention of Fetal Growth Restriction: A Systematic Review and Network Meta‐Analysis

The prevention of fetal growth restriction (FGR) is challenging in clinical practice. To date, no meta‐analysis summarized evidence on the relative benefits and harms of pharmacological interventions for FGR prevention. We performed a systematic review and network meta‐analysis (NetMA), searching PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until November 2019. We included clinical trials and observational studies on singleton gestating women evaluating antiplatelet, anticoagulant, or other treatments, compared between each other or with controls (placebo or no treatment), and considering the pregnancy outcome FGR (primary outcome of the NetMA). Secondary efficacy outcomes included preterm birth, placental abruption, and fetal or neonatal death. Safety outcomes included bleeding and thrombocytopenia. Network meta‐analyses using a frequentist framework were conducted to derive odds ratios (ORs) and 95% confidence intervals (CIs). Of 18,780 citations, we included 30 studies on 4,326 patients. Low molecular weight heparin (LMWH), alone or associated with low‐dose aspirin (LDA), appeared more efficacious than controls in preventing FGR (OR 2.00, 95% CI 1.27–3.16 and OR 2.67, 95% CI 1.21–5.89 for controls vs. LMWH and LDA + LMWH, respectively). No difference between active treatments emerged in terms of FGR prevention, but estimates for treatments other than LMWH +/‐ LDA were imprecise. Only the confidence in the evidence regarding LMWH vs. controls was judged as moderate, according to the Confidence in Network Meta‐Analysis framework. No treatment was associated with an increased risk of bleeding, although estimates were precise enough only for LMWH. These results should inform clinicians on the benefits of active pharmacological prophylaxis for FGR prevention.
Effects of cadmium on mineral nutrient concentrations in plants differing in tolerance for cadmium

Abstract The effects of 3 d treatments with 0.3 and 1.0 mg‐L‐1 of cadmium (Cd) on selected mineral nutrient composition in plants differing in tolerance for Cd were studied. The concentrations of potassium (K) decreased in Cd‐sensitive kidney bean and pea and that of manganese (Mn) decreased in the semi‐resistant rice and maize plants with increasing application of Cd in the culture solution. Copper (Cu) content increased in the roots of the plants above, but no changes in Cu contents were observed in the Cd resistant cucumber and pumpkin plants. Calcium (Ca), magnesium (Mg), and zinc (Zn) did not show any clear tendency with Cd applications in any of the plants examined. Water absorption by kidney bean was reduced by Cd, but that of rice and cucumber was not. Permeability of the plasma membrane of root cells may be affected by Cd, whereas absorption of some of the elements and water may be prevented.
Self-Cross-Linked Hyaluronic Acid Hydrogel in Endonasal Endoscopic Dacryocystorhinostomy: A Randomized, Controlled Trial

Supplemental Digital Content is available in the text Purpose: To investigate whether self-cross-linked HA hydrogel fill stimulates wound mucosal regeneration and its epithelialization around the ostia to improve long-term ostial patency in endonasal endoscopic dacryocystorhinostomy (En-DCR). Methods: One hundred and ninety-two patients with unilateral primary chronic dacryocystitis (PCD) were randomized divided into 2 groups: group A (the HA hydrogel group) and group B (the control group). All patients underwent En-DCR. The HA hydrogel group received HA hydrogel filling the ostium at the end of the surgery and the control group received no treatment. The mucosal epithelialization of the wound, the formation of granulation, the formation of scars, and the success rate of ostial patency were compared. Results: Our study included 82 patients in group A and 79 patients in group B. At the 2-week follow up, 74 patients (90.2%) in the group A had a healed ostium with a lining of intact epithelial mucosa. It was higher when compared with 56 patients (70.9%) in group B (X2 = 9.698, P < 0.05). At the 12-month follow up, Granulation were present in 7.3% of patients in group A which was significantly lower than the 19.0% of patients in group B (X2 = 4.831, P < 0.05). No statistical difference was found with scars formation between 2 groups (X2 = 1.607, P = 0.205). The success rate of ostial patency was 89.0% (73/82) in group A and 77.2% (61/79) in group B. The success rate was much higher in group A than group B (X2 = 4.02, P < 0.05). Conclusion: Self-cross-linked HA hydrogel may enhance the success rate of En-DCR for PCD by promoting mucosal epithelial healing and preventing excessive granulation.