Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictors of persistent disease activity and long quiescence in systemic lupus erythematosus: results from the Hopkins Lupus Cohort

Objectives The aim of this study is to identify prognostic factors of persistent disease activity and long quiescence in systemic lupus erythematosus (SLE). Methods Patients enrolled in the Hopkins Lupus Cohort from 1987 to 2012, who attended at least three visits per year during 3 consecutive years following baseline and had available information on disease activity were included. Patterns of SLE disease activity over the 3-year period were defined as: persistent long quiescent (pLQ), persistent relapsing-remitting (pRR), persistent chronic active (pCA) and mixed based on Modified SLE Disease Activity Index (M-SLEDAI). Possible predictors of pCA (vs pLQ, pRR and mixed) and pLQ (vs pCA, pRR and mixed) were identified by univariate and multivariate logistic regression analyses. Results 916 patients were included. In the multivariate analysis, use of hydroxychloroquine (OR: 0.45, 95% CI 0.22 to 0.92, p=0.03), African American ethnicity (OR: 2.36, 95% CI 1.15 to 4.85, p=0.02) and baseline SLEDAI (OR: 1.10, 95% CI 1.03 to 1.17, p=0.005) remained significant predictors of pCA. Higher education (>12 years; OR. 2.07, 95% CI 1.07 to 4.03, p=0.03) and lower baseline SLEDAI (OR: 0.67, 95% CI 0.56 to 0.82, p<0.001) were significant predictors of pLQ, while African American (OR: 0.38, 95% CI 0.17 to 0.83, p=0.02) and female patients (OR: 0.26, 95% CI 0.12 to 0.57, p<0.001) were less likely to achieve pLQ. Conclusion African American ethnicity and high disease activity at baseline predict chronic activity in SLE, regardless of treatment, years of education and income. Higher education, low disease activity at baseline and male sex predict long quiescence. The use of hydroxychloroquine is independently associated with a lower risk of chronically active disease.
NF-κB p65 dimerization and DNA-binding is important for inflammatory gene expression

Increasing evidence shows that many transcription factors execute important biologic functions independent from their DNA‐binding capacity. The NF‐κB p65 (RELA) subunit is a central regulator of innate immunity. Here, we investigated the relative functional contribution of p65 DNA‐binding and dimerization in p65‐deficient human and murine cells reconstituted with single amino acid mutants preventing either DNA‐binding (p65 E/I) or dimerization (p65 FL/DD). DNA‐binding of p65 was required for RelB‐dependent stabilization of the NF‐κB p10O protein. The antiapoptotic function of p65 and expression of the majority of TNF‐α–induced genes were dependent on p65′s ability to bind DNA and to dimerize. Chromatin immunoprecipitation with massively parallel DNA sequencing experiments revealed that impaired DNA‐binding and dimerization strongly diminish the chromatin association of p65. However, there were also p65‐independent TNF‐α‐inducible genes and a subgroup of p65 binding sites still allowed some residual chromatin association of the mutants. These sites were enriched in activator protein 1 (AP‐1) binding motifs and showed increased chromatin accessibility and basal transcription. This suggests a mechanism of assisted p65 chromatin association that can be in part facilitated by chromatin priming and cooperativity with other transcription factors such as AP‐1. —Riedlinger, T. , Liefke, R. , Meier‐Soelch, J., Jurida, L. , Nist, A. , Stiewe, T. , Kracht, M. , Schmitz, M. L. NF‐κB p65 dimerization and DNA‐binding is important for inflammatory gene expression. FASEB J. 33, 4188–4202 (2019). www.fasebj. org
To test or not: occurrence of sickle cell trait and assessment of the awareness toward its screening among patients attending Magale Health Center IV, Namisindwa District, Eastern Uganda

Purpose To evaluate the occurrence of sickle cell trait (SCT), assess patient awareness and evaluate the performance of a sickle cell hemoglobin-S (dithionate-qualitative solubility) point-of-care test among patients seeking care at Magale Health Center IV, Namisindwa District, Eastern Uganda. Materials and methods We conducted a cross sectional study, in which we consecutively enrolled participants aged ≥18 years at Magale Health Center IV. Four milliliters of EDTA blood were collected by venipuncture and screened for SCT using solubility testing, and confirmed with hemoglobin (Hb) electrophoresis at Central Public Health Laboratory (CPHL), Kampala, Uganda. A structured questionnaire was used to assess participants’ awareness of SCT. Data were presented as proportion, and measurements of diagnostic test performance were calculated. Results We enrolled 242 participants, of these 58.7% (N = 142) were females. Their mean age was 26.4 years (range 18–49). Of the 242 participants, 11, who represent 4.5% (95% CI: 3.3–5.9), tested positive. The sensitivity, specificity, positive predictive value and negative predictive value of the rapid sickle cell test were 63.64%, 100%, 100% and 98.30%, respectively. There was knowledge gap regarding sickle cell awareness. Conclusion The occurrence of SCT was high, and the point-of-care test showed a high diagnostic reliability. The risk of SCT is associated with genetic predisposition as indicated by Hb electrophoresis. Community sensitization is key to avert the associated risk of Hb defects.
Increased cryo-survival rate in ejaculated human sperm from infertile men following pre-freeze in vitro myo-inositol supplementation

Objective To investigate the effects of in vitro myo-inositol (Myo-Ins) supplementation of cryopreserved human semen on the cryo-survival rate (CSR). Methods Semen samples were obtained from 41 infertile men. Following routine semen analysis, each sample was divided into two equal aliquots (0.5 mL each). One aliquot was treated with 1 mg of Myo-Ins dissolved in 10 µL of sperm preparation medium. The second aliquot was treated with 10 µL of the same medium (control). Both aliquots were incubated for 20 minutes prior to freezing to slow the freezing process. The frozen samples were examined for post-thaw percentages of total motility (TM), progressive motility (PM), and the CSR, defined as the percentage of post-thaw TM divided by the percentage of pre-freeze TM and multiplied in 100. The results were expressed as median and interquartile range (25th and 75th percentiles). Results The pre-freeze TM (50% [30%–50%]) and PM (35% [20%–35%]) were significantly higher than the post-thaw TM and PM in the Myo-Ins group (15% [10%–35%] and 10% [5%–20%]; p<0.001 and p<0.001, respectively) and the control group (10% [6%–30%] and 5% [3%–15%]; p<0.001 and p<0.001, respectively). The CSR of the 41 semen aliquots supplemented with Myo-Ins (40% [25%–70%]) was significantly higher than that of the control samples (30% [13%–58%], p=0.041). The CSR of the 26 abnormal semen samples that were supplemented with Myo-Ins (38% [20%–50%]) was significantly higher than that of the control samples (23% [12%–30%], p=0.031). Conclusion In vitro Myo-Ins supplementation of ejaculated human sperm from infertile men resulted in a significant increase in the CSR in samples with abnormal pre-freeze sperm parameters.
Comparison of Primary Midline Closure, Limberg Flap, and Karydakis Flap Techniques in Pilonidal Sinus Surgery

Background Pilonidal sinus (PS) is a common disease of the sacrococcygeal-natal region. There are many treatment options, but there is still no consensus on the ideal treatment. We compared the results of our PS patients who were treated with primary midline closure (PMC), Limberg flap repair (LFR), and Karydakis flap (KF). Material/Methods The data for 924 PS patients from 2013 to 2017 were retrospectively examined. Demographic data, surgical procedures, schedules, and recurrence rates were examined. Results The mean age was 28.4 years (14–77 years), 82.5% were male (n=762), and 17.5% were female (n=162). PMC was performed on 53.7% (n=496) of the patients, 32.5% (n=300) received LFR, and 13.9% (n=128) underwent KF. PMC was the first choice among females but LFR was the first choice in recurrent patients. The recurrence rate was 10.8% in the PMC group, 8% in the LFR group, and 3.1% in the KF group. In Short Form Survey-36 (SF-36) scores, the best cosmetic outcomes were observed in cases of PMC (p<0.05). Overall, wound dehiscence (WD) was observed in 7.5%, surgical site infection (SSI) in 2.4%, and seroma in 8.5% of all patients. The KF group had the lowest complication rates (p<0.01). Conclusions According to the results of this study, the reason for preferring PMC among women is cosmetic concerns. PMC still remains important for treatment, but it should be noted that the recurrence rates due to inadequate excision are mostly observed in cases of PMC. Considering their low recurrence rates, LFR or KF should be considered first. When low recurrence rates, patient comfort, and cosmetic results are evaluated together, KF in particular emerges as a method preferred by physicians and patients.
Metaanalysis of 68Ga-PSMA-11 PET Accuracy for the Detection of Prostate Cancer Validated by Histopathology

68Ga-PSMA-11 PET is used to stage patients with prostate cancer. We performed an updated metaanalysis that separates imaging at the time of diagnosis and at the time of biochemical recurrence and focuses on pathology correlation in both populations. Methods: We searched the MEDLINE and EMBASE databases using the PRISMA statement. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool 2. In total, 1,811 studies were screened, 58 were analyzed, 41 were included for qualitative synthesis, and 29 were included for quantitative analysis. A random-effect model and a hierarchical summary receiver-operating-characteristic model were used to summarize the sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy for pelvic lymph nodes in initial staging compared with pathology at prostatectomy and the PPV for lesions with pathologic correlation in those with biochemical recurrence. We also summarized the detection rate of 68Ga-PSMA-11 in those with biochemical recurrence stratified by prostate-specific antigen (PSA) at the time of imaging. Results: The metaanalysis of 68Ga-PSMA-11 at initial staging demonstrated a sensitivity and specificity of 0.74 (95% confidence interval [95% CI], 0.51–0.89) and 0.96 (95% CI, 0.85–0.99), respectively, using nodal pathology at prostatectomy as a gold standard. At biochemical recurrence, the PPV was 0.99 (95% CI, 0.96–1.00). The detection rate was 0.63 (95% CI, 0.55–0.70), with a PSA of less than 2.0 and 0.94 (95% CI, 0.91–0.96) with a PSA of more than 2.0. Conclusion: 68Ga-PSMA-11 performed well for the localization of metastatic prostate cancer at initial staging and at the time of biochemical recurrence.
Inhibitors of energy metabolism interfere with antibiotic-induced death in mycobacteria

Energy metabolism has recently gained interest as a target space for antibiotic drug development in mycobacteria. Of particular importance is bedaquiline (Sirturo), which kills mycobacteria by inhibiting the F1F0 ATP synthase. Other components of the electron transport chain such as the NADH dehydrogenases (NDH-2 and NdhA) and the terminal respiratory oxidase bc1:aa3 are also susceptible to chemical inhibition. Because antituberculosis drugs are prescribed as part of combination therapies, the interaction between novel drugs targeting energy metabolism and classical first and second line antibiotics must be considered to maximize treatment efficiency. Here, we show that subinhibitory concentration of drugs targeting the F1F0 ATP synthase and the cytochrome bc1:aa3, as well as energy uncouplers, interfere with the bactericidal potency of isoniazid and moxifloxacin. Isoniazid- and moxifloxacin-induced mycobacterial death correlated with a transient increase in intracellular ATP that was dissipated by co-incubation with energy metabolism inhibitors. Although oxidative phosphorylation is a promising target space for drug development, a better understanding of the link between energy metabolism and antibiotic-induced mycobacterial death is essential to develop potent drug combinations for the treatment of tuberculosis.
Multiple color patches and parasites in Sceloporus occidentalis: differential relationships by sex and infection

Abstract Parasites generally have a negative influence on the color expression of their hosts. Sexual selection theory predicts resistant high-quality individuals should show intense coloration, whereas susceptible low-quality individuals would show poor coloration. However, intensely colored males of different species of Old and New World lizards were more often infected by hemoparasites. These results suggest that high-quality males, with intense coloration, would suffer higher susceptibility to hemoparasites. This hypothesis remains poorly understood and contradicts general theories on sexual selection. We surveyed a population of Sceloporus occidentalis for parasites and found infections by the parasite genera Lankesterella and Acroeimeria. In this population, both males and females express ventral blue and yellow color patches. Lankesterella was almost exclusively infecting males. The body size of the males significantly predicted the coloration of both blue and yellow patches. Larger males showed darker (lower lightness) blue ventral patches and more saturated yellow patches that were also orange-skewed. Moreover, these males were more often infected by Lankesterella than smaller males. The intestinal parasite Acroeimeria infected both males and females. The infection by intestinal parasites of the genus Acroeimeria was the best predictor for the chroma in the blue patch of the males and for hue in the yellow patch of the females. Those males infected by Acroeimeria expressed blue patches with significantly lower chroma than the uninfected males. However, the hue of the yellow patch was not significantly different between infected and uninfected females. These results suggest a different effect of Lankesterella and Acroeimeria on the lizards. On the one hand, the intense coloration of male lizards infected by Lankesterella suggested high-quality male lizards may tolerate it. On the other hand, the low chroma of the blue coloration of the infected males suggested that this coloration could honestly express the infection by Acroeimeria.
Resveratrol protects against isoproterenol induced myocardial infarction in rats through VEGF-B/AMPK/eNOS/NO signalling pathway

Abstract According to our previous results, resveratrol (RSV, 3, 5, 4-trihydroxystilbene), a naturally polyphenolic phytoalexin, could attenuate myocardial ischemia/reperfusion injury through up-regulation of vascular endothelial growth factor B (VEGF-B) in isolated rat heart or H9c2 cells. However, the molecular mechanism remains unclear. In this study, we investigated the protective effect of RSV on myocardial infarction (MI) in rats and further explored the underlying signal pathway after VEGF-B. Rats received RSV or normal saline by intragastric administration for 7 consecutive days and followed by subcutaneously isoproterenol (ISO) or normal saline injections for another 2 days. We found that RSV pretreatment prevented the unfavourable changes in HW/BW, HW/TL, infarct size, and cell apoptosis in ISO-treated rats. Moreover, superoxide and malondialdehyde (MDA) production were significantly reduced and superoxide dismutase (SOD) was increased by RSV in ISO-treated rats. Furthermore, it showed that RSV pretreatment increased VEGF-B, p-eNOS and p-AMPK expression, and NO production in ISO-treated rats. Using Neonatal Rat Ventricular Myocytes (NRVM), we found that VEGF-B siRNA could abolish the cardio-protective effect of RSV. The enhanced ratios of eNOS phosphorylation to eNOS expression induced by RSV were markedly reversed by VEGF-B siRNA in NRVM also. Meantime, we found that the effect of VEGF-B knock-down on eNOS activation was rescued by AMPK activator AICAR. L-NAME, a NOS inhibitor, could inhibit RSV enhanced eNOS phosphorylation but had no effect on VEGF-B expression in NRVM or in rats. Collectively, our results indicate that RSV exerts cardio-protection from ISO-induced myocardial infarction through VEGF-B/AMPK/eNOS/NO signalling pathway.
The Multidisciplinary Approach to Alzheimer's Disease and Dementia. A Narrative Review of Non-Pharmacological Treatment

Background: Alzheimer's disease (AD) and dementia are chronic diseases with progressive deterioration of cognition, function, and behavior leading to severe disability and death. The prevalence of AD and dementia is constantly increasing because of the progressive aging of the population. These conditions represent a considerable challenge to patients, their family and caregivers, and the health system, because of the considerable need for resources allocation. There is no disease modifying intervention for AD and dementia, and the symptomatic pharmacological treatments has limited efficacy and considerable side effects. Non-pharmacological treatment (NPT), which includes a wide range of approaches and techniques, may play a role in the treatment of AD and dementia. Aim: To review, with a narrative approach, current evidence on main NPTs for AD and dementia. Methods: PubMed and the Cochrane database of systematic reviews were searched for studies written in English and published from 2000 to 2018. The bibliography of the main articles was checked to detect other relevant papers. Results: The role of NPT has been largely explored in AD and dementia. The main NPT types, which were reviewed here, include exercise and motor rehabilitation, cognitive rehabilitation, NPT for behavioral and psychological symptoms of dementia, occupational therapy, psychological therapy, complementary and alternative medicine, and new technologies, including information and communication technologies, assistive technology and domotics, virtual reality, gaming, and telemedicine. We also summarized the role of NPT to address caregivers' burden. Conclusions: Although NPT is often applied in the multidisciplinary approach to AD and dementia, supporting evidence for their use is still preliminary. Some studies showed statistically significant effect of NPT on some outcomes, but their clinical significance is uncertain. Well-designed randomized controlled trials with innovative designs are needed to explore the efficacy of NPT in AD and dementia. Further studies are required to offer robust neurobiological grounds for the effect of NPT, and to examine its cost-efficacy profile in patients with dementia.
Language, Identity and the Cultural Context of Names in Selected Nigerian Novels

Names are a reflection of a people's language and culture hence novelists often adopt names to capture their sociocultural background, the society in which their texts are set, or the background of their fictional characters. Using the framework of Anthroponomastics which leans on linguistic anthropology, this study examines names in four selected Nigerian novels, namely Chinua Achebe's Things Fall Apart and Anthills of the Savannah, and Chimamanda Adichie's Purple Hibiscus and Half of a Yellow Sun. The analysis of the names extracted from the novels shows that in names, language and culture intertwine to bequeath an identity to the named person. This identity may mirror the expected character, roles or the circumstances surrounding the conception and birth of the named one, or may generally reflect the worldview of his/her society. The meaning of names is contextual and derives from a society’s cultural and sociolinguistic reservoir which is accessible to members whenever they need names that capture their intended meaning. The names in the novels also indicate the individual and the group identity of the bearers and their society, but expressed through language and they often have multi-faceted meanings.
Electrospun nanofiber blend with improved mechanical and biological performance

Background Here, electrospun fibers based on a blend of polycaprolactone (PCL), poly(ethylene glycol) (PEG), and gelatin methacryloyl (GelMA) were developed. The careful choice of this polymer combination allowed for the preparation of a biomaterial that preserved the mechanical strength of PCL, while at the same time improving the hydrophilicity of the blended material and human osteoblast maturation. Methods The morphology, chemical structure, wettability, and mechanical properties before and after UV photocrosslinking were evaluated. Furthermore, human osteoblasts (hFOB) were cultivated for up to 21 days on the scaffolds, and their potential to upregulate cell proliferation, alkaline phosphatase (ALP) activity, and calcium deposition were investigated. Results Contact angle measurement results showed that the developed scaffolds presented hydrophilic properties after PEG and GelMA incorporation before (25°) and after UV photocross-linking (69°) compared to pure PCL (149°). PCL:PEG:GelMA-UV displayed a slight increase in mechanical strength (elastic modulus ~37 MPa) over PCL alone (~33 MPa). Normally, an increase in strength of fibers leads to a decrease in elongation at break, due to the material becoming less deformable and stiffer, thus leading to breaks at low strain. This behavior was observed by comparing PCL (elongation at break ~106%) and PCL:PEG:GelMA-UV (~50%). Moreover, increases in ALP activity (10-fold at day 14) and calcium deposition (1.3-fold at day 21) by hFOBs were detected after PEG and GelMA incorporation after UV photocross-linking compared to pure PCL. Ultrathin and hydrophilic fibers were obtained after PEG and GelMA incorporation after UV photocrosslinking, but the strength of PCL was maintained. Interestingly, those ultrathin fiber characteristics improved hFOB functions. Conclusion These findings appear promising for the use of these electrospun scaffolds, based on the combination of polymers used here for numerous orthopedic applications.
Original vs. non‐original abutments for screw‐retained single implant crowns: An in vitro evaluation of internal fit, mechanical behaviour and screw loosening

OBJECTIVES To assess the internal accuracy, mechanical behaviour under static load and screw loosening before and after cyclic loading of implant-supported crowns restored with original components or with two compatible non-original brands. MATERIALS AND METHODS Sixty-three dental implants were divided into three groups (n = 21 each): Group 1 used original components, and groups 2 and 3 used non-original components. Internal accuracy was measured throughout a cross section of the sample groups (n = 8) using scanning electron microscopy (SEM) to evaluate the fit for implant-abutments, implant-crowns and crown-abutments. To evaluate load-bearing capacity, eight samples from each group were loaded until fracture according to ISO Norm 14801. The removal torque value (RTV) was evaluated in the screws connecting the crown with the abutment and the abutment with the implant before and after cyclic loading (2 x 106 cycles) in five samples from each group. The data were analysed using the Kruskal-Wallis test (p < 0.05). RESULTS Statistically significant differences were found among the mean crown-abutment gaps measured in Group 1 (9.3 μm), Group 2 (45.4 μm) and Group 3 (44.9 μm). Higher values for mean load-bearing capacity were found in Group 1 (1,098 N) than in groups 2 and 3 (1,057 and 973 N, respectively); however, these differences were not statistically significant. Original abutment-implant screws exhibited lower percentages of torque reduction than the non-originals. CONCLUSIONS Enhanced fit is expected when original components are used. The original abutments exhibited lower percentages of torque reduction after cyclic loading than non-originals.