Europe PMC in 2023.

Europe PMC (https://europepmc.org/) is an open access database of life science journal articles and preprints, which contains over 42 million abstracts and over 9 million full text articles accessible via the website, APIs and bulk download. This publication outlines new developments to the Europe PMC platform since the last database update in 2020 (1) and focuses on five main areas. (i) Improving discoverability, reproducibility and trust in preprints by indexing new preprint content, enriching preprint metadata and identifying withdrawn and removed preprints. (ii) Enhancing support for text and data mining by expanding the types of annotations provided and developing the Europe PMC Annotations Corpus, which can be used to train machine learning models to increase their accuracy and precision. (iii) Developing the Article Status Monitor tool and email alerts, to notify users about new articles and updates to existing records. (iv) Positioning Europe PMC as an open scholarly infrastructure through increasing the portion of open source core software, improving sustainability and accessibility of the service.

Sex matters: The MouseX DW-ALLEN Atlas for mice diffusion-weighted MR imaging.

Overcoming sex bias in preclinical research requires not only including animals of both sexes in the experiments, but also developing proper tools to handle such data. Recent work revealed sensitivity of diffusion-weighted MRI to glia morphological changes in response to inflammatory stimuli, opening up exciting possibilities to characterize inflammation in a variety of preclinical models of pathologies, the great majority of them available in mice. However, there are limited resources dedicated to mouse imaging, like those required for the data processing and analysis. To fill this gap, we build a mouse MRI template of both structural and diffusion contrasts, with anatomical annotation according to the Allen Mouse Brain Atlas, the most detailed public resource for mouse brain investigation. To achieve a standardized resource, we use a large cohort of animals in vivo, and include animals of both sexes. To prove the utility of this resource to integrate imaging and molecular data, we demonstrate significant association between the mean diffusivity from MRI and gene expression-based glia density. To demonstrate the need of equitable sex representation, we compared across sexes the warp fields needed to match a male-based template, and our template built with both sexes. Then, we use both templates for analysing mice imaging data obtained in animals of different ages, demonstrating that using a male-based template creates spurious significant sex effects, not present otherwise. All in all, our MouseX DW-ALLEN Atlas will be a widely useful resource getting us one step closer to equitable healthcare.

Antibacterial and wound healing potential of biosynthesized zinc oxide nanoparticles against carbapenem-resistant Acinetobacter baumannii: an in vitro and in vivo study.

Carbapenem-resistant Acinetobacter baumannii denotes a significant menace to public health, and it mandates an urgent development of new effective medications. Here, we aimed to estimate the efficiency of the zinc oxide nanoparticles (ZnO NP) biosynthesized from Arthrospira maxima (Spirulina) both in vitro and in vivo. Carbapenem-resistant A. baumannii isolates were collected, identified, tested for their antibiotic susceptibility, and then subjected to PCR to detect carbapenemase-producing genes. The most predominant carbapenemase resistance gene was blaKPC. The biosynthesized ZnO NP were characterized using UV, FTIR, XRD, SEM, and TEM. The prepared ZnO NP was then tested against A. baumannii isolates to determine the minimum inhibitory concentration (MIC), which ranged from 250 to 1000 µg/ml. Burn wound was persuaded in twenty rats and inoculated with carbapenem-resistant A. baumannii isolate. Rats were allocated into four groups: a negative control group, a positive control group treated with topical 0.9% saline, a test treatment group that received topical ZnO NP, and a standard treatment group. All groups received treatment for 15 consecutive days and then euthanized. Skin samples were harvested and then subjected to histopathological and immunochemical investigations. ZnO NP revealed a comparable antibacterial activity to colistin as it revealed a lower level of fibrosis, mature surface epithelization with keratinization, and restoration of the normal skin architecture. In addition, it significantly decreased the immunoreactivity of the studied inflammatory markers. Thus, ZnO NP synthesized by A. maxima could be considered a promising, safe, and biocompatible alternative to traditional antibiotics in the therapy of carbapenem-resistant A. baumannii infections.

Repetitive deep TMS in alcohol dependent patients halts progression of white matter changes in early abstinence.

AIM: Alcohol use disorder (AUD) is the most prevalent form of addiction, with a great burden on society and limited treatment options. A recent clinical trial reported significant clinical benefits of deep transcranial magnetic stimulations (Deep TMS) targeting midline frontocortical areas. However, the underlying biological substrate remained elusive. Here, we report the effect of Deep TMS on the microstructure of white matter. METHODS: A total of 37 (14 females) AUD treatment-seeking patients were randomized to sham or active Deep TMS. Twenty (six females) age-matched healthy controls were included. White matter integrity was evaluated by fractional anisotropy (FA). Secondary measures included brain functional connectivity and self-reports of craving and drinking units in the 3 months of follow-up period. RESULTS: White matter integrity was compromised in patients with AUD relative to healthy controls, as reflected by the widespread reduction in FA. This alteration progressed during early abstinence (3 weeks) in the absence of Deep TMS. However, stimulation of midline frontocortical areas arrested the progression of FA changes in association with decreased craving and relapse scores. Reconstruction of axonal tracts from white-matter regions showing preserved FA values identified cortical regions in the posterior cingulate and dorsomedial prefrontal cortices where functional connectivity was persistently modulated. These effects were absent in the sham-stimulated group. CONCLUSIONS: By integrating brain structure and function to characterize the alcohol-dependent brain, this study provides mechanistic insights into the TMS effect, pointing to myelin plasticity as a possible mediator.

Unveiling the Antiviral Efficacy of Forskolin: A Multifaceted In Vitro and In Silico Approach.

Coleus forskohlii (Willd.) Briq. is a medicinal herb of the Lamiaceae family. It is native to India and widely present in the tropical and sub-tropical regions of Egypt, China, Ethiopia, and Pakistan. The roots of C. forskohlii are edible, rich with pharmaceutically bioactive compounds, and traditionally reported to treat a variety of diseases, including inflammation, respiratory disorders, obesity, and viral ailments. Notably, the emergence of viral diseases is expected to quickly spread; consequently, these data impose a need for various approaches to develop broad active therapeutics for utilization in the management of future viral infectious outbreaks. In this study, the naturally occurring labdane diterpenoid derivative, Forskolin, was obtained from Coleus forskohlii. Additionally, we evaluated the antiviral potential of Forskolin towards three viruses, namely the herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), hepatitis A virus (HAV), and coxsackievirus B4 (COX-B4). We observed that Forskolin displayed antiviral activity against HAV, COX-B4, HSV-1, and HSV-2 with IC50 values of 62.9, 73.1, 99.0, and 106.0 µg/mL, respectively. Furthermore, we explored the Forskolin's potential antiviral target using PharmMapper, a pharmacophore-based virtual screening platform. Forskolin's modeled structure was analyzed to identify potential protein targets linked to its antiviral activity, with results ranked based on Fit scores. Cathepsin L (PDB ID: 3BC3) emerged as a top-scoring hit, prompting further exploration through molecular docking and MD simulations. Our analysis revealed that Forskolin's binding mode within Cathepsin L's active site, characterized by stable hydrogen bonding and hydrophobic interactions, mirrors that of a co-crystallized inhibitor. These findings, supported by consistent RMSD profiles and similar binding free energies, suggest Forskolin's potential in inhibiting Cathepsin L, highlighting its promise as an antiviral agent.

Unravelling the Antimicrobial, Antibiofilm, Suppressing Fibronectin Binding Protein A (fnba) and cna Virulence Genes, Anti-Inflammatory and Antioxidant Potential of Biosynthesized Solanum lycopersicum Silver Nanoparticles.

Background and Objectives: Urinary tract infections [UTIs] are considered the third most known risk of infection in human health around the world. There is increasing appreciation for the pathogenicity of Gram-positive and Gram-negative strains in UTIs, aside from fungal infection, as they have numerous virulence factors. Materials and Methods: In this study, fifty urine samples were collected from patients suffering from UTI. Among the isolates of UTI microbes, six isolates were described as MDR isolates after an antibiotic susceptibility test carried out using ten different antibiotics. An alternative treatment for microbial elimination involved the use of biosynthesized silver nanoparticles (AgNPs) derived from Solanum lycopersicum [S. cumin]. Results: The sizes and shapes of AgNPs were characterized through TEM imaging, which showed spherical particles in a size range of 35-80 nm, of which the average size was 53 nm. Additionally, the silver nanoparticles (AgNPs) demonstrated inhibitory activity against Staphylococcus aureus (OR648079), exhibiting a 31 mm zone of inhibition at a minimum inhibitory concentration (MIC) of 4 mg/mL and a minimum bactericidal concentration (MBC) of 8 mg/mL. This was followed by Aspergillus niger (OR648075), which showed a 30 mm inhibition zone at an MIC of 16 mg/mL and a minimum fungicidal concentration (MFC) of 32 mg/mL. Then, Enterococcus faecalis (OR648078), Klebsiella pneumoniae (OR648081), and Acinetobacter baumannii (OR648080) each displayed a 29 mm zone of inhibition at an MIC of 8 mg/mL and an MBC of 16 mg/mL. The least inhibition was observed against Candida auris (OR648076), with a 25 mm inhibition zone at an MIC of 16 mg/mL and an MFC of 32 mg/mL. Furthermore, AgNPs at different concentrations removed DPPH and H2O2 at an IC50 value of 13.54 µg/mL. Also, AgNPs at 3 mg/mL showed remarkable DNA fragmentation in all bacterial strains except Enterococcus faecalis. The phytochemical analysis showed the presence of different active organic components in the plant extract, which concluded that rutin was 88.3 mg/g, garlic acid was 70.4 mg/g, and tannic acid was 23.7 mg/g. Finally, AgNPs concentrations in the range of 3-6 mg/mL showed decreased expression of two of the fundamental genes necessary for biofilm formation within Staphylococcus aureus, fnbA (6 folds), and Cna (12.5 folds) when compared with the RecA gene, which decreased by one-fold when compared with the control sample. These two genes were submitted with NCBI accession numbers [OR682119] and [OR682118], respectively. Conclusions: The findings from this study indicate that biosynthesized AgNPs from Solanum lycopersicum exhibit promising antimicrobial and antioxidant properties against UTI pathogens, including strains resistant to multiple antibiotics. This suggests their potential as an effective alternative treatment for UTIs. Further research is warranted to fully understand the mechanisms of action and to explore the therapeutic applications of these nanoparticles in combating UTIs.

Bioinspired Graphene Oxide-Magnetite Nanocomposite Coatings as Protective Superhydrophobic Antifouling Surfaces.

Antifouling (AF) nanocoatings made of polydimethylsiloxane (PDMS) are more cost-efficient and eco-friendly substitutes for the already outlawed tributyltin-based coatings. Here, a catalytic hydrosilation approach was used to construct a design inspired by composite mosquito eyes from non-toxic PDMS nanocomposites filled with graphene oxide (GO) nanosheets decorated with magnetite nanospheres (GO-Fe3O4 nanospheres). Various GO-Fe3O4 hybrid nanofillers were dispersed into the PDMS resin through a solution casting method to evaluate the structure-property relationship. A simple coprecipitation procedure was used to fabricate magnetite nanospheres with an average diameter of 30-50 nm, a single crystal structure, and a predominant (311) lattice plane. The uniform bioinspired superhydrophobic PDMS/GO-Fe3O4 nanocomposite surface produced had a micro-/nano-roughness, low surface-free energy (SFE), and high fouling release (FR) efficiency. It exhibited several advantages including simplicity, ease of large-area fabrication, and a simultaneous offering of dual micro-/nano-scale structures simply via a one-step solution casting process for a wide variety of materials. The superhydrophobicity, SFE, and rough topology have been studied as surface properties of the unfilled silicone and the bioinspired PDMS/GO-Fe3O4 nanocomposites. The coatings' physical, mechanical, and anticorrosive features were also taken into account. Several microorganisms were employed to examine the fouling resistance of the coated specimens for 1 month. Good dispersion of GO-Fe3O4 hybrid fillers in the PDMS coating until 1 wt % achieved the highest water contact angle (158° ± 2°), the lowest SFE (12.06 mN/m), micro-/nano-roughness, and improved bulk mechanical and anticorrosion properties. The well-distributed PDMS/GO-Fe3O4 (1 wt % nanofillers) bioinspired nanocoating showed the least biodegradability against all the tested microorganisms [Kocuria rhizophila (2.047%), Pseudomonas aeruginosa (1.961%), and Candida albicans (1.924%)]. We successfully developed non-toxic, low-cost, and economical nanostructured superhydrophobic FR composite coatings for long-term ship hull coatings. This study may expand the applications of bio-inspired functional materials because for multiple AF, durability and hydrophobicity are both important features in several industrial applications.

Effect of medication therapy management services on medication-burden quality of life in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) patients commonly receive polypharmacy leading to increased likelihood of drug related problems (DRPs) and poor quality of life. Medication Therapy Management (MTM) services discover and resolve DRPs and may specifically improve Medication-burden Quality of life (MBQoL) in HD patients. We aimed to assess the effect of MTM services on DRPs and MBQoL among HD patients. METHODS: A prospective pre-post study was conducted on 104 patients in an HD unit in Alexandria, Egypt. MBQoL was assessed at baseline and after three months of MTM sessions, using the Arabic, validated version of the Patient Reported Outcomes Measure of Pharmaceutical Therapy (PROMPT) questionnaire. Cohen's d test and multiple linear regression were used to assess the effect size of MTM and the factors affecting MBQoL, respectively. DRPs, adverse events and adherence were also monitored. RESULTS: MBQoL improved significantly after the implementation of MTM (Cohen's d=0.88, p < 0.01) with the largest effect size in the "medicine information and relation with healthcare providers" domain. DRPs decreased significantly after MTM implementation (11.97 ± 4.65 versus 7.63 ± 3.85 per patient, p<0.001). The mean adverse events per patient were also reduced (9.69 ± 4.12 versus 6.56 ± 3.77, p < 0.001). CONCLUSION: Applying MTM services presents an opportunity to improve care for HD patients by improving MBQoL, decreasing DRPs and adverse events.

Europe PMC in 2020.

Europe PMC (https://europepmc.org) is a database of research articles, including peer reviewed full text articles and abstracts, and preprints - all freely available for use via website, APIs and bulk download. This article outlines new developments since 2017 where work has focussed on three key areas: (i) Europe PMC has added to its core content to include life science preprint abstracts and a special collection of full text of COVID-19-related preprints. Europe PMC is unique as an aggregator of biomedical preprints alongside peer-reviewed articles, with over 180 000 preprints available to search. (ii) Europe PMC has significantly expanded its links to content related to the publications, such as links to Unpaywall, providing wider access to full text, preprint peer-review platforms, all major curated data resources in the life sciences, and experimental protocols. The redesigned Europe PMC website features the PubMed abstract and corresponding PMC full text merged into one article page; there is more evident and user-friendly navigation within articles and to related content, plus a figure browse feature. (iii) The expanded annotations platform offers ∼1.3 billion text mined biological terms and concepts sourced from 10 providers and over 40 global data resources.

Mobility of LoRaWAN Gateways for Efficient Environmental Monitoring in Pristine Sites.

Environmental monitoring of delicate ecosystems or pristine sites is critical to their preservation. The communication infrastructure for such monitoring should have as little impact on the natural ecosystem as possible. Because of their wide range capabilities and independence from heavy infrastructure, low-power wide area network protocols have recently been used in remote monitoring. In this regard, we propose a mobile vehicle-mounted gateway architecture for IoT data collection in communication-network-free areas. The limits of reliable communication are investigated in terms of gateway speed, throughput, and energy consumption. We investigate the performance of various gateway arrival scenarios, focusing on the trade-off between freshness of data, data collection rate, and end-node power consumption. Then we validate our findings using both real-world experiments and simulations. In addition, we present a case study exploiting the proposed architecture to provide coverage for Wadi El-Gemal national park in Egypt. The results show that reliable communication is achieved over all spreading factors (SFs) for gateway speeds up to 150 km/h with negligible performance degradation at SFs=11,12 at speeds more than 100 km/h. The synchronized transmission model ensures the best performance in terms of throughput and power consumption at the expense of the freshness of data. Nonsynchronized transmission allows time-flexible data collection at the expense of increased power consumption. The same throughput as semisynchronized transmission is achieved using four gateways at only five times the energy consumption, while a single gateway requires seventeen times the amount of energy. Furthermore, increasing the number of gateways to ten increases the throughput to the level achieved by the synchronized scenario while consuming eight times the energy.

Risk Assessment of Pesticide Residues by GC-MSMS and UPLC-MSMS in Edible Vegetables.

In recent years, there has been a significant increase related to pesticide residues in foods, which may increase the risks to the consumer of these foods with the different quality and concentrations of pesticide residues. Pesticides are used for controlling pests that reduce yields. On the other hand, it has become a major public health concern due to its toxic properties. Thus, the objective of the current study employed the application of Quick Easy Cheap Effective Rugged Safe (QuEChERS) method, in combination with gas and liquid chromatography-tandem mass spectrometric detection (GCMSMS, LCMSMS) in order to determine 137 pesticide residues (63 insecticides, 41 acaricides, 40 herbicide, 55 fungicide, nematicide, growth regulator, Chitin synthesis inhibitors, and Juvenile hormone mimics), in 801 vegetables such as 139 tomatoes, 185 peppers, 217 squash, 94 eggplants, and 166 cucumbers from different locations in Hail and Riyadh cities. The results showed that the majority of pesticide residues were detected for each of the following pesticides: acetaimpride, metalaxyl, imidaclopride, bifenthrin, pyridaben, difenoconazole, and azoxystrobien, which were repeated in the samples studied 39, 21, 11, 10, 8, 7, and 5, respectively. In addition, results observed that the tomato was the most contaminated with pesticide residues; it was contaminated with 19 compounds and was followed by pepper, cucumber, and squash, and the last commodity in the contaminated ranking was eggplant. The highest calculated estimated daily intakes (EDIs) were recorded for tomatoes which were estimated between 0.013 to 0.516 mg/kg of body weight per day (bw/day) while the lowest EDIs value was between 0.000002 to 0.0005 mg/kg of bw/day for cucumber. Results indicated that the EDIs values were lower than the acceptable daily intake (ADI) values. Results observed that the most of pesticide residues exposure in food consumption in Saudi Arabia were lower than ADIs. In addition, the highest value for health risk index (HRI) was recorded with Ethion residue in tomato, but in sweet pepper, the highest value for HRI was 127.5 in the form of fipronil residue. On the other hand, results found that the highest values of HRI were 1.54, 1.61, and 0.047 for difenoconazole, bifenthrin, and pyridaben residues in squash, eggplant, and cucumber.

Recovery of health-related quality of life in patients undergoing robot-assisted radical cystectomy with intracorporeal diversion.

OBJECTIVE: To report the health-related quality of life (HRQoL) after robot-assisted radical cystectomy and intracorporeal urinary diversion (iRARC), and to identify factors impacting on return to baseline. PATIENTS AND METHODS: Consecutive patients undergoing iRARC between January 2016 and December 2017 completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core (EORTC-QLQ-C30) and EORTC-QLQ-Muscle-Invasive Bladder Cancer Module (EORTC-QLQ-BLM30) questionnaires before surgery and had a minimum of 12 months follow-up postoperatively. RESULTS: A total of 76 patients met the inclusion criteria at 12 months. Neobladder (NB) cases (n = 24) were younger (57.0 vs 71.0 years, P < 0.001) and fitter than ileal conduit (IC) cases (n = 52), and had higher physical (100.0 vs 93.3, P = 0.039) and sexual functioning (66.7 vs 50.0, P = 0.013) scores at baseline. Longitudinal analysis of the EORTC-QLQ-C30 showed that physical (NB: 93.3 vs 100.0, P = 0.020; IC: 80.0 vs 93.3, P < 0.001) and role functioning scores (NB: 83.3 vs 100.0, P = 0.010; IC: 83.3 vs 100.0, P = 0.017) decreased and fatigue score (NB: 22.2 vs 11.1, P = 0.026; IC: 33.3 vs 22.2, P = 0.008) increased at 3 months in both diversion groups. Scores returned to baseline at 6 months except physical functioning score in IC patients that remained below baseline until 12 months (86.7 vs 93.3, P = 0.012). The global HRQoL score did not show significant change postoperatively in both groups. A major 90-day Clavien-Dindo complication was a significant predictor (odds ratio [OR] 0.11, 95% confidence interval [CI] 0.02-0.62; P = 0.012) of deteriorated global HRQoL score at 3 months, while occurrence of a late complication (OR 0.14, 95% CI 0.03-0.65; P = 0.013) was a predictor of deteriorated global HRQoL score at 12 months. Longitudinal analysis of the EORTC-QLQ-BLM30 showed that urinary problems (NB: 14.3 vs 38.3, P < 0.001; IC: 5.6 vs 19.1, P < 0.001) and future perspective (NB: 33.3 vs 44.4, P = 0.004; IC: 22.2 vs 44.4, P < 0.001) scores were better than baseline at 3 months. Sexual function deteriorated significantly at 3 months (NB: 8.3 vs 66.7, P < 0.001; IC: 4.2 vs 50.0, P < 0.001) and then showed improvement at 12 months but was still below baseline (NB: 33.3 vs 66.7, P = 0.001; IC: 25.0 vs 50.0, P < 0.001). Involvement in penile rehabilitation was shown to be a significant predictor (ß 18.62, 95% CI 6.06-30.45; P = 0.005) of higher sexual function score at 12 months. CONCLUSION: While most functional domains and symptoms scales recover to or exceed baseline within 6 months of iRARC, physical function remains below baseline in IC patients up to 12 months. Global HRQoL is preserved for both types of urinary diversion; however, postoperative complications seem to be the main driving factor for global HRQoL. Sexual function is adversely affected after iRARC suggesting that structured rehabilitation of sexual function should be an integral part of the RC pathway.

Predictive urinary RNA biomarkers of kidney injury after extracorporeal shock wave lithotripsy.

BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) is considered one of the best choices for the treatment of various kinds of urinary tract calculi, although it might cause acute kidney injury. OBJECTIVE: To measure the urinary long non-coding RNA-messenger RNA (LncRNA-mRNA) panel before and after ESWL to evaluate post-ESWL renal injury in a reliable and non-invasive method. PATIENTS AND METHODS: The study included 60 patients with renal stones treated with ESWL and 30 healthy volunteers. Voided urine samples were obtained before, 2 h, and 1 day after ESWL. We measured the urinary level of LncRNA (SBF2-AS1, FENDRR-19) and mRNA (GBP1, NLRP3) by real-time qPCR and compared the results with serum creatinine and eGFR. RESULTS: LncRNA (SBF2-AS1, FENDRR-19) and mRNA (GBP1, NLRP3) levels were higher in patients with renal stones when compared with healthy volunteers. They showed a statistically significant increase in the level of LncRNA-mRNA panel in baseline and after ESWL treatment. CONCLUSION: LncRNA (SBF2-AS1, FENDRR-19) and mRNA (GBP1, NLRP3) levels were significantly elevated following ESWL treatment, highlighting the usefulness of urinary biomarkers in identifying patients at higher risk of developing renal injury after ESWL treatment.

Cytotoxic T Cell Expression of Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) in Viral Hepatitis C-Mediated Hepatocellular Carcinoma.

Virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, despite successful treatment, hepatitis C virus (HCV) may progress to HCC from initiated liver cirrhosis. Cytotoxic T cells (Tcs) are known to be involved in HCV-related cirrhotic complications and HCC pathogenesis. The inhibitory checkpoint leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on Tcs. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression and to evaluate LAIR-1 expression as a noninvasive biomarker for HCC progression in the context of liver cirrhosis related to HCV genotype 4 (G4) in Egyptian patients' peripheral venous blood liquid biopsy. A total of 64 patients with HCC and 37 patients with liver cirrhosis were enrolled in this case-controlled study, and their LAIR-1 expression on Tc related to the progression of liver cirrhosis was examined and compared to that of the apparently healthy control group (n = 20). LAIR-1 expression was analyzed using flow cytometry. Results: The HCC group had significantly higher LAIR-1 expression on Tc and percentage of Tc positive for LAIR-1 (LAIR-1+Tc%) than the HCV G4-related liver cirrhosis group. LAIR-1+Tc% was correlated with the HCC surrogate tumor marker AFP (r = 0.367, p = 0.001) and insulin resistance and inflammation prognostic ratios/indices. A receiver operating characteristic (ROC) curve revealed that adding LAIR-1+Tc% to AFP can distinguish HCC transformation in the Egyptian patients' cohort. Upregulated LAIR-1 expression on Tc could be a potential screening noninvasive molecular marker for chronic inflammatory HCV G4 related liver cirrhosis. Moreover, LAIR-1 expression on Tc may be one of the players involved in the progression of liver cirrhosis to HCC.

Can pregnancy aggravate the criticality of COVID-19 infection in obese asthmatic peripartum woman? A peripartum COVID-19 mortality case report.

As coronavirus disease 2019 (COVID-19) sweeps all over the world, Information about COVID-19 is evolving rapidly and interim guidance by multiple organisations is constantly being updated and expanded. Early with discovery of COVID 19, it was reported that pregnancy did affect the progress of the disease severity. Recently, Centres for Disease Control and Prevention (CDC) reported that pregnancy is a risk factors for COVID-19 severity. The current case report is presenting a peripartum COVID-19 positive mortality case.

Point of Care Exome Sequencing Reveals Allelic and Phenotypic Heterogeneity Underlying Mendelian disease in Qatar.

The effectiveness of next generation sequencing at solving genetic disease has motivated the rapid adoption of this technology into clinical practice around the world. In this study, we use whole exome sequencing (WES) to assess 48 patients with Mendelian disease from 30 serial families as part of the "Qatar Mendelian Disease pilot program" - a coordinated multi-center effort to build capacity and clinical expertise in genetic medicine in Qatar. By enrolling whole families (parents plus available siblings), we demonstrate significantly improved discriminatory power for candidate variant identification over trios for both de novo and recessive inheritance patterns. For the same index cases, we further demonstrate that even in the absence of families, variant prioritization is improved up to 8-fold when a modest set of population-matched controls is used vs large public databases, stressing the poor representation of Middle Eastern alleles in presently available databases. Our in-house pipeline identified candidate disease variants in 27 of 30 families (90%), 23 of which (85%) harbor novel pathogenic variants in known disease genes, pointing to significant allelic heterogeneity and founder mutations underlying Mendelian disease in the Middle East. For 6 of these families, the clinical presentation was only partially explained by the candidate gene, suggesting phenotypic expansion of known syndromes. Our pilot study demonstrates the utility of WES for Middle Eastern populations, the dramatic improvement in variant prioritization conferred by enrolling population-matched controls and/or enrolling additional unaffected siblings at the point-of-care, and 25 novel disease-causing alleles, relevant to newborn and premarital screening panels in regional populations.

Nuclear Magnetic Resonance Metabolomics Approach for the Analysis of Major Legume Sprouts Coupled to Chemometrics.

Legume sprouts are a fresh nutritive source of phytochemicals of increasing attention worldwide owing to their many health benefits. Nuclear magnetic resonance (NMR) was utilized for the metabolite fingerprinting of 4 major legume sprouts, belonging to family Fabaceae, to be exploited for quality control purposes. Thirty-two metabolites were identified belonging to different classes, i.e., fatty acids, sugars, amino acids, nucleobases, organic acids, sterols, alkaloids, and isoflavonoids. Quantitative NMR was employed for assessing the major identified metabolite levels and multivariate data analysis was utilized to assess metabolome heterogeneity among sprout samples. Isoflavones were detected exclusively in Cicer sprouts, whereas Trigonella was characterized by 4-hydroxyisoleucine. Vicia sprouts were distinguished from other legume sprouts by the presence of L-Dopa versus acetate abundance in Lens. A common alkaloid in all sprouts was trigonelline, detected at 8-25 µg/mg, suggesting its potential role in legume seeds' germination. Trigonelline was found at highest levels in Trigonella sprouts. The aromatic NMR region data (δ 11.0-5.0 ppm) provided a better classification power than the full range (δ 11.0-0.0 ppm) as sprout variations mostly originated from secondary metabolites, which can serve as chemotaxonomic markers.

Bioassay-Guided Isolation, Metabolic Profiling, and Docking Studies of Hyaluronidase Inhibitors from Ravenala madagascariensis.

Hyaluronidase enzyme (HAase) has a role in the dissolution or disintegration of hyaluronic acid (HA) and in maintaining the heathy state of skin. Bioassay-guided fractionation of Ravenala madagascariensis (Sonn.) organ extracts (leaf, flower, stem, and root) testing for hyaluronidase inhibition was performed followed by metabolic profiling using LC-HRMS. Additionally, a hyaluronidase docking study was achieved using Molecular Operating Environment (MOE). Results showed that the crude hydroalcoholic (70% EtOH) extract of the leaves as well as its n-butanol (n-BuOH) partition showed higher HAase activity with 64.3% inhibition. Metabolic analysis of R. madagascariensis resulted in the identification of 19 phenolic compounds ranging from different chemical classes (flavone glycosides, flavonol glycosides, and flavanol aglycones). Bioassay-guided purification of the leaf n-BuOH partition led to the isolation of seven compounds that were identified as narcissin, rutin, epiafzelechin, epicatechin, isorhamnetin 7-O-glucoside, kaempferol, and isorhamnetin-7-O-rutinoside. The docking study showed that narcissin, rutin, and quercetin 3-O-glucoside all interact with HAase through hydrogen bonding with the Asp111, Gln271, and/or Glu113 residues. Our results highlight Ravenala madagascariensis and its flavonoids as promising hyaluronidase inhibitors in natural cosmetology preparations for skin care.

Outcome of staged buccal mucosal graft for repair of long segment anterior urethral stricture.

BACKGROUND: Long anterior urethral stricture due to variable etiological factors constitutes a challenge for reconstruction. We evaluated our centers experience with cases of long anterior urethral stricture due to different etiologies that were managed by 2-stage substitution urethroplasty using buccal mucosal graft procedure. METHODS: During the period between November 2009 and November 2016. All cases with long anterior urethral stricture that were planned for substitution urethroplasty in our department were enrolled in this study. The first stage was excision of most fibrotic areas of the urethral plate, the remaining of the urethra is laid open and augmented with buccal mucosal graft for second stage closure after 6-9 months. RESULTS: The study included 123 patients who underwent first stage, 105 patients of them underwent second stage urethroplasty. Eighteen cases were missed after first stage. The mean (range) age was 38.4 (17-60 years). The mean (range) stricture length was 8.3 (4-13 cm). The cause of stricture was idiopathic in 47, inflammatory in 15, lichen sclerosus in 26 and post failed hypospadias repair in 35 patients. First stage was complicated by graft contracture in 11 (8.9%) patients that needed re-grafting, 5(4.1%) patient had bleeding from the buccal mucosa site that needed haemostatic sutures, oral numbness was reported in 7 (5.7%) patients. Second stage was complicated by wound dehiscence in 2(1.9%) patients, restricture in 11 (10.5%), fistula in 6 (5.7%) patients, meatal stenosis in 3 (2.9%). The overall success rate was 79.1% (83 cases out of 105) with a mean (range) follow-up of 34.7 (10-58 months). CONCLUSIONS: Staged urethroplasty using buccal mucosal graft procedure is an effective surgical option for patients with long anterior urethral strictures especially for patients with lichen sclerosus and those with failed previous surgical repair.

Relationship between DYNLT1 and Beclin1 expression and the fertilising potential of human spermatozoa.

This study aimed to evaluate dynein light chain type 1 (DYNLT1) mRNA expression in mature spermatozoa and to investigate its association with Beclin1 expression to help in understanding of pathogenesis of male infertility. It included 60 infertile men divided into idiopathic (n = 20), accessory gland inflammation (n = 20), and varicocele (n = 20) groups, and 20 healthy fertile men as a control group. Semen parameters were evaluated according to the 2010 World Health Organization criteria. Mature spermatozoa were isolated by Sil-select gradient. Relative quantification of DYNLT1 and Beclin1 mRNA expression in whole sperm pellet and mature spermatozoa was done using real-time PCR. Beclin1 protein was assessed in whole sperm pellet and mature spermatozoa by ELISA. Beclin1 mRNA and protein were significantly increased in spermatozoa from infertile patients of different aetiologies in comparison to healthy controls (p < .05). However, DYNLT1 mRNA expression was significantly decreased in infertile groups than controls (p < .05). Mature spermatozoa extracted from all studied subjects showed increased DYNLT1 mRNA and decreased Beclin1 mRNA and protein expression compared with the whole sample. It is concluded that decreased Beclin1 and increased DYNLT1 mRNA expression in mature spermatozoa may provide an insight into the biological processes that are activated or suppressed during sperm maturation.