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Spontaneous Spinal Epidural Hematoma (SSEH) is a rare spinal condition. Early surgical intervention is generally indicated to prevent serious permanent neurological deficits. We encountered a case of spontaneous spinal epidural hematomas associated with motor weakness that was treated successfully by surgical evacuation.

Background & Aim: Traumatic brain injury is one of the main causes of death and disability. The aim of this study is to systematically review the articles which assessed some serum factors of traumatic brain injury patients in relation to their outcomes. Methods & Materials/Patients: Databases were searched for relevant publications from 2005 to 2014. Selection criteria were:Studies which evaluate the factors affecting the outcome after TBI, TBI defined as “acute changes in brain function resulting in a strong external force to the head”.Resultswere measured by Glasgow Outcome Score or a comparable measure.Factors were measured in first month after injury and the prognosis was addressed. All papers were checked and approved by a specialist and expert in that field. A systematic review was performed for prognostic factors. Results: Sixty-three studies were included. Most studies used Glasgow Outcome Score at 6 months post-injury as outcome measure, sometimes in combination with other outcome measures. Strong evidence for predicting outcome was found for serum concentration of S100 protein, NSE, MBP, NF-H, GFAP, UCH-L1, blood glucose levels, serum levels of LDH, sodium level, prothrombin time, partial thromboplastin time, platelet count, D.dimer, HSP 70, serum levels of IL-8, number of circulating EPCs, and DNA levels in serum. Moderate evidence for predicting outcome was found for high serum MMP9. Strong evidence of no association was found for WBC count and serum cortisol levels. Moderate evidence of no association was found for serum total cholesterol for other determinants, inconclusive or no evidence or limited evidence was found. Conclusion: S100 protein, NSE, MBP, NF-H, GFAP, UCH-L1, blood glucose levels, serum levels of LDH, sodium level, prothrombin time, Partial thromboplastin time, platelet count, D.dimer, HSP 70, serum levels of IL-8, number of circulating EPCs, and DNA levels in serum predicted outcome after traumatic brain injury. WBC count, serum cortisol levels, total cholesterol and MMP9 did not have predictive value.

l-Asparaginases catalyze the hydrolysis of l-asparagine to l-aspartic acid and ammonia. These enzymes have potential applications in therapeutics and food industry. Tk1656, a highly active and thermostable l-asparaginase from Thermococcus kodakarensis, has been proved effective in selective killing of acute lymphocytic leukemia cells and in reducing acrylamide formation in baked and fried foods. However, it displayed <5 % activity under physiological conditions compared to the optimal activity at 85 °C and pH 9.5. We have attempted engineering of this valuable enzyme to improve the characteristics required for therapeutic and industrial applications. Based on the literature and crystal structure of Tk1656, nine specific mutant variants were designed, produced in Escherichia coli, and the purified mutant enzymes were compared with the wild-type. One of the mutants, K299L, displayed >20 % increase in activity at 85 °C. H158S substitution resulted in >5 °C increase in the optimal temperature. Similarly, a mesophilic-like mutation L56D, resulted in >5-fold increase in activity at pH 7.0 and 37 °C compared to that of the wild-type enzyme. The substrate specificity of the mutant variants remained unchanged. These results demonstrate that L56D and K299L variants of Tk1656 are the potent enzymes for therapeutics and acrylamide mitigation applications, respectively., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Glutamate-cysteine ligase catalytic subunit (GCLC), previously known as gamma-glutamyl-cysteine synthetase, is an essential rate-limiting step in glutathione synthesis. Glutathione modulates multitudes of critical cellular processes and scavenges free radicals. Its deficiency is reported to cause hemolysis of variable severity and is a rare cause of neurological abnormalities such as spinocerebellar ataxia., Clinical Presentation: We report a 55-year-old female patient with progressive late-onset ataxia, lower limb spasticity, and chronic hemolytic anemia found to have a GCLC pathogenic variant and low glutathione level. Magnetic resonance imaging of the head and cervical spine showed global cerebellar atrophy with widened folia and decreased diameter of the upper cervical spine. Blood workup revealed hemolytic anemia with genetic testing confirmed a homozygous variant, c.514 T>A in exon 4 of the GCLC gene, resulting in Ser172Thr (TCC>ACC). Management encompassed a multidisciplinary approach with a trial of high-dose alpha-lipoic acid, glutathione supplement, and physical therapy., Conclusions: GCLC deficiency manifesting with hemolysis has been reported in 12 cases worldwide from 6 independent families, with only 4 cases having additional neurological manifestations. To date, no specific GCLC gene mutation has been attributed to the reported neurological constellation of symptoms. To the best of our knowledge, this is the first case report of late-onset spinocerebellar degeneration as a manifestation of c.514T>A (p. S172T) GCLC pathological variant genetic mutation., Competing Interests: The authors have no conflict of interest to disclose., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, a 3-year prospective study, we evaluated a novel diagnostic concept based on multidisciplinary expertise in Germany. Here we present the systematic investigation of the phenotypic and molecular genetic data of 1,577 patients who had undergone exome sequencing and were partially analyzed with next-generation phenotyping approaches. Molecular genetic diagnoses were established in 32% of the patients totaling 370 distinct molecular genetic causes, most with prevalence below 1:50,000. During the diagnostic process, 34 novel and 23 candidate genotype-phenotype associations were identified, mainly in individuals with neurodevelopmental disorders. Sequencing data of the subcohort that consented to computer-assisted analysis of their facial images with GestaltMatcher could be prioritized more efficiently compared with approaches based solely on clinical features and molecular scores. Our study demonstrates the synergy of using next-generation sequencing and phenotyping for diagnosing ultrarare diseases in routine healthcare and discovering novel etiologies by multidisciplinary teams., (© 2024. The Author(s).)

In the era of high throughput sequencing, special software is required for the clinical evaluation of genetic variants. We developed REEV (Review, Evaluate and Explain Variants), a user-friendly platform for clinicians and researchers in the field of rare disease genetics. Supporting data was aggregated from public data sources. We compared REEV with seven other tools for clinical variant evaluation. REEV (semi-)automatically fills individual ACMG criteria facilitating variant interpretation. REEV can store disease and phenotype data related to a case to use these for phenotype similarity measures. Users can create public permanent links for individual variants that can be saved as browser bookmarks and shared. REEV may help in the fast diagnostic assessment of genetic variants in a clinical as well as in a research context. REEV (https://reev.bihealth.org/) is free and open to all users and there is no login requirement., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Genome sequence of Geobacillus thermopakistaniensis contains an open reading frame annotated as a type II L-asparaginase (ASNase Gt ). Critical structural analysis disclosed that ASNase Gt might be a type I L-asparaginase. In order to determine whether it is a type I or type II L-asparaginase, we have performed the structural-functional characterization of the recombinant protein as well as analyzed the localization of ASNase Gt in G. thermopakistaniensis. ASNase Gt exhibited optimal activity at 52 °C and pH 9.5. There was a > 3-fold increase in activity in the presence of β-mercaptoethanol. Apparent V max and K m values were 2735 U/mg and 0.35 mM, respectively. ASNase Gt displayed high thermostability with >80 % residual activity even after 6 h of incubation at 55 °C. Recombinant ASNase Gt existed in oligomeric form. Addition of β-mercaptoethanol lowered the degree of oligomerization and displayed that tetrameric form was the most active, with a specific activity of 4300 U/mg. Under physiological conditions, ASNase Gt displayed >50 % of the optimal activity. Localization studies in G. thermopakistaniensis revealed that ASNase Gt is a cytosolic protein. Structural and functional characterization, and localization in G. thermopakistaniensis displayed that ASNase Gt is not a type II but a type I L-asparaginase., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Duplex or vermiform appendix refers to the presence of an appendix beside the naturally occurring one. Although, duplex appendix emerges from the caecum most of the time, yet it is encountered in other parts of the colon. Inflammation of duplex appendix may represent not only a clinical, but also a surgical dilemma, and this would be confusing further among patients who already had prior appendectomy., Case Presentation: We present a case of 29-years old Egyptian male patient with history of appendectomy one and half year before presenting to the emergency department with recurrent acute abdominal pain that was linked to duplex appendicitis abnormally emerged from the mid-ascending colon. The first episode was treated conservatively considering atypical right colon diverticulitis as a potential differential diagnosis. Seven months later the patient was treated by laparoscopic appendectomy and experienced an uneventful pot-operative course., Conclusion: Duplex appendicitis, though rare, should be considered in the differential diagnosis of recurrent acute abdomen even after appendectomy., (© 2024. The Author(s).)

Background: While characteristic facial features provide important clues for finding the correct diagnosis in genetic syndromes, valid assessment can be challenging. The next-generation phenotyping algorithm DeepGestalt analyzes patient images and provides syndrome suggestions. GestaltMatcher matches patient images with similar facial features. The new D-Score provides a score for the degree of facial dysmorphism., Objective: We aimed to test state-of-the-art facial phenotyping tools by benchmarking GestaltMatcher and D-Score and comparing them to DeepGestalt., Methods: Using a retrospective sample of 4796 images of patients with 486 different genetic syndromes (London Medical Database, GestaltMatcher Database, and literature images) and 323 inconspicuous control images, we determined the clinical use of D-Score, GestaltMatcher, and DeepGestalt, evaluating sensitivity; specificity; accuracy; the number of supported diagnoses; and potential biases such as age, sex, and ethnicity., Results: DeepGestalt suggested 340 distinct syndromes and GestaltMatcher suggested 1128 syndromes. The top-30 sensitivity was higher for DeepGestalt (88%, SD 18%) than for GestaltMatcher (76%, SD 26%). DeepGestalt generally assigned lower scores but provided higher scores for patient images than for inconspicuous control images, thus allowing the 2 cohorts to be separated with an area under the receiver operating characteristic curve (AUROC) of 0.73. GestaltMatcher could not separate the 2 classes (AUROC 0.55). Trained for this purpose, D-Score achieved the highest discriminatory power (AUROC 0.86). D-Score's levels increased with the age of the depicted individuals. Male individuals yielded higher D-scores than female individuals. Ethnicity did not appear to influence D-scores., Conclusions: If used with caution, algorithms such as D-score could help clinicians with constrained resources or limited experience in syndromology to decide whether a patient needs further genetic evaluation. Algorithms such as DeepGestalt could support diagnosing rather common genetic syndromes with facial abnormalities, whereas algorithms such as GestaltMatcher could suggest rare diagnoses that are unknown to the clinician in patients with a characteristic, dysmorphic face., (©Alisa Maria Vittoria Reiter, Jean Tori Pantel, Magdalena Danyel, Denise Horn, Claus-Eric Ott, Martin Atta Mensah. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 13.03.2024.)

Machine translation for low-resource languages poses significant challenges, primarily due to the limited availability of data. In recent years, unsupervised learning has emerged as a promising approach to overcome this issue by aiming to learn translations between languages without depending on parallel data. A wide range of methods have been proposed in the literature to address this complex problem. This paper presents an in-depth investigation of semi-supervised neural machine translation specifically focusing on translating Arabic dialects, particularly Egyptian, to Modern Standard Arabic. The study employs two distinct datasets: one parallel dataset containing aligned sentences in both dialects, and a monolingual dataset where the source dialect is not directly connected to the target language in the training data. Three different translation systems are explored in this study. The first is an attention-based sequence-to-sequence model that benefits from the shared vocabulary between the Egyptian dialect and Modern Arabic to learn word embeddings. The second is an unsupervised transformer model that depends solely on monolingual data, without any parallel data. The third system starts with the parallel dataset for an initial supervised learning phase and then incorporates the monolingual data during the training process., (© 2024. The Author(s).)

The genome sequence of hyperthermophilic archaeon Pyrobaculum calidifontis contains an open reading frame, Pcal&#95;0039, which encodes a putative DNA ligase. Structural analysis disclosed the presence of signature sequences of ATP-dependent DNA ligases. We have heterologously expressed Pcal&#95;0039 gene in Escherichia coli. The recombinant protein, majorly produced in soluble form, was purified and functionally characterized. Recombinant Pcal&#95;0039 displayed nick-joining activity between 40 and 85 °C. Optimal activity was observed at 70 °C and pH 5.5. Nick-joining activity was retained even after heating for 1 h at 90 °C, indicating highly thermostable nature of Pcal&#95;0039. The nick-joining activity, displayed by Pcal&#95;0039, was metal ion dependent and Mg 2+ was the most preferred. NaCl and KCl inhibited the nick-joining activity at or above 200 mmol/L. The activity catalyzed by recombinant Pcal&#95;0039 was independent of addition of ATP or NAD + or any other nucleotide cofactor. A mismatch adjacent to the nick, either at 3'- or 5'-end, abolished the nick-joining activity. These characteristics make Pcal&#95;0039 a potential candidate for applications in DNA diagnostics. To the best of our knowledge, Pcal&#95;0039 is the only DNA ligase, characterized from genus Pyrobaculum, which exhibits optimum nick-joining activity at pH below 6.0 and independent of any nucleotide cofactor., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Genome analysis of Pyrobaculum calidifontis revealed the presence of α-glucosidase (Pcal&#95;0917) gene. Structural analysis affirmed the presence of signature sequences of Type II α-glucosidases in Pcal&#95;0917. We have heterologously expressed the gene and produced recombinant Pcal&#95;0917 in Escherichia coli. Biochemical characteristics of the recombinant enzyme resembled to that of Type I α-glucosidases, instead of Type II. Recombinant Pcal&#95;0917 existed in a tetrameric form in solution and displayed highest activity at 95 °C and pH 6.0, independent of any metal ions. A short heat-treatment at 90 °C resulted in a 35 % increase in enzyme activity. A slight structural shift was observed by CD spectrometry at this temperature. Half-life of the enzyme was >7 h at 90 °C. Pcal&#95;0917 exhibited apparent V max values of 1190 ± 5 and 3.9 ± 0.1 U/mg against p-nitrophenyl α-D-glucopyranoside and maltose, respectively. To the best of our knowledge, Pcal&#95;0917 displayed the highest ever reported p-nitrophenyl α-D-glucopyranosidase activity among the characterized counterparts. Moreover, Pcal&#95;0917 displayed transglycosylation activity in addition to α-glucosidase activity. Furthermore, in combination with α-amylase, Pcal&#95;0917 was capable of producing glucose syrup from starch with >40 % glucose content. These properties make Pcal&#95;0917 a potential candidate for starch hydrolyzing industry., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Nickel-supported hierarchical zeolite catalysts were prepared through a desilication reassembly process under optimized conditions and applied in one-pot menthol synthesis. In this work, the hierarchical zeolite-supported metal bifunctional catalysts were prepared with the help of desilication re-assembly and wetness impregnation techniques and applied in menthol synthesis via citral hydrogenation. The prepared catalysts were characterized using PXRD, BET, FE-TEM, NH 3 -TPD, H 2 -TPR, pyridine adsorption, and ICP-OES techniques. As a result, the physicochemical and acidic properties, such as mesopore surface area, metal dispersion, acidity, catalytic activity, and strong Lewis acid sites of pure microporous ZSM-5/USY zeolites, were significantly improved. Consequently, with the occurrence of superior physicochemical and acidic properties, the Ni/HZ-0.5 M catalyst exhibited outstanding catalytic activity (100% conversion, TOF 7.12 h -1 ) and menthol selectivity (83%, 4 h) with uniform stability at 100 °C, 1.0 MPa hydrogen. Similarly, the cracking rate decreased with the decrease in Bronsted acid sites.

Many monogenic disorders cause a characteristic facial morphology. Artificial intelligence can support physicians in recognizing these patterns by associating facial phenotypes with the underlying syndrome through training on thousands of patient photographs. However, this 'supervised' approach means that diagnoses are only possible if the disorder was part of the training set. To improve recognition of ultra-rare disorders, we developed GestaltMatcher, an encoder for portraits that is based on a deep convolutional neural network. Photographs of 17,560 patients with 1,115 rare disorders were used to define a Clinical Face Phenotype Space, in which distances between cases define syndromic similarity. Here we show that patients can be matched to others with the same molecular diagnosis even when the disorder was not included in the training set. Together with mutation data, GestaltMatcher could not only accelerate the clinical diagnosis of patients with ultra-rare disorders and facial dysmorphism but also enable the delineation of new phenotypes., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Loss of function variants of GLI3 are associated with a variety of forms of polysyndactyly: Pallister-Hall syndrome (PHS), Greig-Cephalopolysyndactyly syndrome (GCPS), and isolated polysyndactyly (IPD). Variants affecting the N-terminal and C-terminal thirds of the GLI3 protein have been associated with GCPS, those within the central third with PHS. Cases of IPD have been attributed to variants affecting the C-terminal third of the GLI3 protein. In this study, we further investigate these genotype-phenotype correlations. Sequencing of GLI3 was performed in patients with clinical findings suggestive of a GLI3-associated syndrome. Additionally, we searched the literature for reported cases of either manifestation with mutations in the GLI3 gene. Here, we report 48 novel cases from 16 families with polysyndactyly in whom we found causative variants in GLI3 and a review on 314 previously reported GLI3 variants. No differences in location of variants causing either GCPS or IPD were found. Review of published data confirmed the association of PHS and variants affecting the GLI3 protein's central third. We conclude that the observed manifestations of GLI3 variants as GCPS or IPD display different phenotypic severities of the same disorder and propose a binary division of GLI3-associated disorders in either PHS or GCPS/polysyndactyly., (© 2021 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

To the Editor, Radical cystectomy (RC) for bladder cancer is a life-changing surgery, associated with high morbidity and mortality rate. Ileal neobladder seems as an attractive way for urine management post cystectomy but would carry the risk of retaining urine in the ileal pouch for a long time, resulting in serum electrolyte changes, that may add to the patients' morbidity. EAU guidelines recommend against ileal neobladder for patients with liver and renal disorders, as well as for patients > 80 years old [...].

During human organogenesis, lung development is a timely and tightly regulated developmental process under the control of a large number of signaling molecules. Understanding how genetic variants can disturb normal lung development causing different lung malformations is a major goal for dissecting molecular mechanisms during embryogenesis. Here, through exome sequencing (ES), array CGH, genome sequencing (GS) and Hi-C, we aimed at elucidating the molecular basis of bilateral isolated lung agenesis in three fetuses born to a non-consanguineous family. We detected a complex genomic rearrangement containing duplicated, triplicated and deleted fragments involving the SHH locus in fetuses presenting complete agenesis of both lungs and near-complete agenesis of the trachea, diagnosed by ultrasound screening and confirmed at autopsy following termination. The rearrangement did not include SHH itself, but several regulatory elements for lung development, such as MACS1, a major SHH lung enhancer, and the neighboring genes MNX1 and NOM1. The rearrangement incorporated parts of two topologically associating domains (TADs) including their boundaries. Hi-C of cells from one of the affected fetuses showed the formation of two novel TADs each containing SHH enhancers and the MNX1 and NOM1 genes. Hi-C together with GS indicate that the new 3D conformation is likely causative for this condition by an inappropriate activation of MNX1 included in the neo-TADs by MACS1 enhancer, further highlighting the importance of the 3D chromatin conformation in human disease., (© 2021. The Author(s).)

Aims: Depression and anxiety are the most common and prevalent mental health issues among undergraduate students. This study aimed to investigate the prevalence of anxiety and depression, their associated predictors, and to assess knowledge and use of antidepressant medications among university students in Jordan., Methods: A cross-sectional survey-based study was conducted in Jordan among undergraduate students from all levels of study. Istilli et al's questionnaire, the PHQ-9 and generalised anxiety disorder (GAD) scales were used in this study to explore the study objectives. Logistic regression analysis was used to identify predictors of anxiety and depression., Results: A total of 1582 undergraduate students participated in the study. Prevalence of depression was 22.3% (n = 330), with proportions of minimal, mild, moderate, moderately severe and severe depression to be 15.9%, 32.4%, 29.5%, 14.7% and 7.6%, respectively. Prevalence of anxiety was 15.8% (n = 173), with proportions of mild, moderate and severe anxiety to be 46.4%, 37.8% and 15.8%, respectively. Female students and those with low income (<500 JD) had higher depression mean scores compared with others. Females, arts and engineering students, divorced and those who have four or more children had higher anxiety mean scores compared with others., Conclusion: Findings of this study addressed the importance of taking serious measures and interventions to prevent the development of severe mental illness among university students., (© 2021 John Wiley & Sons Ltd.)

End-stage liver disease and its related complications exert a huge disease burden and reduce the survival rates of many patients. Albumin administration for patients with decompensated liver cirrhosis has been a controversial topic of discussion. The aim of this study is to investigate whether albumin reduces the mortality and complications of liver cirrhosis compared to standard medical therapy (SMT) alone. Clinical trials in which albumin administration was compared to SMT in patients with liver cirrhosis were included in this meta-analysis. The primary outcome of this study was to evaluate the effect on reducing all-cause mortality. Ascites control, renal failure and hepatic encephalopathy were evaluated as secondary outcomes. Nine clinical trials with 1231 patients were recruited and analyzed using the quality effect model. Mortality rate was significantly reduced in the albumin group [relative risk (RR) 0.73, 95% confidence interval (CI) 0.56-0.96]. Heterogeneity was mild across all studies (I2 23.3%). Studies reporting long-term albumin (LTA) administration were found to have a significant decrease in mortality (RR 0.57, 95% CI 0.44-0.73). However, studies reporting short-term albumin administration were found to have no effect on mortality (RR 0.90, 95% CI 0.56-1.45). Furthermore, there was a significant decrease in the incidence of all secondary outcomes. This meta-analysis provides evidence that LTA administration is significantly effective in reducing the mortality of liver cirrhosis compared to SMT. Albumin administration was also shown to reduce the occurrence of ascites, renal failure and hepatic encephalopathy as complications of liver cirrhosis., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Benign prostatic hyperplasia (BPH) is a common male disorder. Febuxostat is a non-purine, selective inhibitor of xanthine oxidase (XO), which has a strong antioxidant capacity and pleiotropic pharmacological properties. This study's objective was to explore the potential ameliorative effects of febuxostat against testosterone-induced BPH in rats. Febuxostat (10 mg/kg/day, per os [p.o.]) prevented increased prostate index levels, serum levels of prostate-specific antigen (PSA), and testosterone levels compared to animals treated with testosterone alone, when administered for 28 days. Histological examination indicated that febuxostat dramatically ameliorated pathological changes in the prostate architecture compared to the testosterone group. Similarly, febuxostat markedly improved testosterone-induced oxidative stress by inhibiting the increase in lipid peroxide and nitrite content, and by reducing the level of depletion of reduced glutathione (GSH) and superoxide dismutase (SOD) activity, which significantly reduced the prostate content of pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6). Furthermore, febuxostat significantly reduced the prostatic content, both in terms of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) messenger ribonucleic acid (mRNA) levels, and of protein levels. Moreover, compared to the testosterone group, febuxostat's beneficial effects prevented the increase in growth factors, comprising vascular endothelial cell growth factor A (VEGF-A) and transforming growth factor beta (TGF-β) protein levels. Its ameliorating effects were equal to those of finasteride, which is the most widely used remedy for BPH. In conclusion, this study provides novel evidence that febuxostat experimentally attenuates testosterone-induced BPH in rats, at least in part by inhibiting iNOS/COX-2 and VEGF/TGF-β pathways., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The phase stability and microstructure of ZrO 2 -5CaO and ZrO 2 -24MgO mixed coating (wt%) by air plasma spraying on 304 stainless steel substrates were investigated. A Ni-5Al (wt%) metallic bond coating was firstly sprayed between the substrate and the ceramic top layer. The results were compared with the individual coatings of ZrO 2 -5CaO and ZrO 2 -24MgO for a better understanding of the correlation between their microstructures and mechanical properties. Mixed zirconia coating was found to have a mixture of cubic and tetragonal phases that stabilized under different plasma spray conditions. Microscopic observations and elemental composition analysis of as-sprayed mixed coating showed that modified ceramic-matrix grains had been formed. Microsized ZrO 2 -5CaO particles were embedded in the matrix grain creating an intragranular microstructure. Results indicated that ceramic-matrix grains provided a diffusion barrier for the growth of oxides induced stress near and onto the bond layer that reduced cracks, thereby overcoming the top delamination of the ceramic coating. Moreover, disparity in wear resistance and microhardness behavior of the coatings was influenced by initial feedstock powder and matrix microstructures. Improvement in the wear resistance of the mixed zirconia coating was attributed to a decrease in oxide content, which resulted in an increase in intersplat cohesive strength.

Background: Collectively, an estimated 5% of the population have a genetic disease. Many of them feature characteristics that can be detected by facial phenotyping. Face2Gene CLINIC is an online app for facial phenotyping of patients with genetic syndromes. DeepGestalt, the neural network driving Face2Gene, automatically prioritizes syndrome suggestions based on ordinary patient photographs, potentially improving the diagnostic process. Hitherto, studies on DeepGestalt's quality highlighted its sensitivity in syndromic patients. However, determining the accuracy of a diagnostic methodology also requires testing of negative controls., Objective: The aim of this study was to evaluate DeepGestalt's accuracy with photos of individuals with and without a genetic syndrome. Moreover, we aimed to propose a machine learning-based framework for the automated differentiation of DeepGestalt's output on such images., Methods: Frontal facial images of individuals with a diagnosis of a genetic syndrome (established clinically or molecularly) from a convenience sample were reanalyzed. Each photo was matched by age, sex, and ethnicity to a picture featuring an individual without a genetic syndrome. Absence of a facial gestalt suggestive of a genetic syndrome was determined by physicians working in medical genetics. Photos were selected from online reports or were taken by us for the purpose of this study. Facial phenotype was analyzed by DeepGestalt version 19.1.7, accessed via Face2Gene CLINIC. Furthermore, we designed linear support vector machines (SVMs) using Python 3.7 to automatically differentiate between the 2 classes of photographs based on DeepGestalt's result lists., Results: We included photos of 323 patients diagnosed with 17 different genetic syndromes and matched those with an equal number of facial images without a genetic syndrome, analyzing a total of 646 pictures. We confirm DeepGestalt's high sensitivity (top 10 sensitivity: 295/323, 91%). DeepGestalt's syndrome suggestions in individuals without a craniofacially dysmorphic syndrome followed a nonrandom distribution. A total of 17 syndromes appeared in the top 30 suggestions of more than 50% of nondysmorphic images. DeepGestalt's top scores differed between the syndromic and control images (area under the receiver operating characteristic [AUROC] curve 0.72, 95% CI 0.68-0.76; P<.001). A linear SVM running on DeepGestalt's result vectors showed stronger differences (AUROC 0.89, 95% CI 0.87-0.92; P<.001)., Conclusions: DeepGestalt fairly separates images of individuals with and without a genetic syndrome. This separation can be significantly improved by SVMs running on top of DeepGestalt, thus supporting the diagnostic process of patients with a genetic syndrome. Our findings facilitate the critical interpretation of DeepGestalt's results and may help enhance it and similar computer-aided facial phenotyping tools., (©Jean Tori Pantel, Nurulhuda Hajjir, Magdalena Danyel, Jonas Elsner, Angela Teresa Abad-Perez, Peter Hansen, Stefan Mundlos, Malte Spielmann, Denise Horn, Claus-Eric Ott, Martin Atta Mensah. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 22.10.2020.)

Hand hyperphalangism leading to shortened index fingers with ulnar deviation, hallux valgus, mild facial dysmorphism and respiratory compromise requiring assisted ventilation are the key features of Chitayat syndrome. This condition results from the recurrent heterozygous missense variant NM&#95;006494.2:c.266A>G; p.(Tyr89Cys) in ERF on chromosome 19q13.2, encoding the ETS2 repressor factor (ERF) protein. The pathomechanism of Chitayat syndrome is unknown. To date, seven individuals with Chitayat syndrome and the recurrent pathogenic ERF variant have been reported in the literature. Here, we describe six additional individuals, among them only one presenting with a history of assisted ventilation, and the remaining presenting with variable pulmonary phenotypes, including one individual without any obvious pulmonary manifestations. Our findings widen the phenotype spectrum caused by the recurrent pathogenic variant in ERF, underline Chitayat syndrome as a cause of isolated skeletal malformations and therefore contribute to the improvement of diagnostic strategies in individuals with hand hyperphalangism., (© 2020 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Genome-wide analysis methods, such as array comparative genomic hybridization (CGH) and whole-genome sequencing (WGS), have greatly advanced the identification of structural variants (SVs) in the human genome. However, even with standard high-throughput sequencing techniques, complex rearrangements with multiple breakpoints are often difficult to resolve, and predicting their effects on gene expression and phenotype remains a challenge. Here, we address these problems by using high-throughput chromosome conformation capture (Hi-C) generated from cultured cells of nine individuals with developmental disorders (DDs). Three individuals had previously been identified as harboring duplications at the SOX9 locus and six had been identified with translocations. Hi-C resolved the positions of the duplications and was instructive in interpreting their distinct pathogenic effects, including the formation of new topologically associating domains (neo-TADs). Hi-C was very sensitive in detecting translocations, and it revealed previously unrecognized complex rearrangements at the breakpoints. In several cases, we observed the formation of fused-TADs promoting ectopic enhancer-promoter interactions that were likely to be involved in the disease pathology. In summary, we show that Hi-C is a sensible method for the detection of complex SVs in a clinical setting. The results help interpret the possible pathogenic effects of the SVs in individuals with DDs., (Copyright © 2020 American Society of Human Genetics. All rights reserved.)

Background: Peptic ulcer disease causes significant mortality and morbidity. Plant kingdom provides a useful source for the development of new antiulcer agents. Croton macrostachyus is traditionally used to treat peptic ulcer in Ethiopia. This study aimed to evaluate the antiulcer activity of C. macrostachyus root extracts in rodents using different models., Methods: The crude extract was obtained by cold maceration in 80% methanol and fractionated with chloroform, ethyl acetate, and distilled water. The antiulcer activity was evaluated using pylorus ligation-induced ulcer model in Sprague Dawley rats and acidified ethanol-induced ulcer model in Swiss albino mice. The test groups received three doses (100, 200, and 400 mg/kg) of the crude extract and fractions for 7 days before induction of ulcer. Positive controls received omeprazole 30 mg/kg for the pylorus ligation-induced ulcer model and sucralfate 100 mg/kg for the acidified ethanol-induced ulcer model. Negative controls received vehicle (2% tween 80)., Results: The crude hydromethanolic extract of C. macrostachyus showed significant ( p < 0.05) antiulcer activity on both pyloric ligation and HCl/ethanol-induced ulcer in rats and mice. It has antisecretary effect ( p < 0.001) as well. All three administered doses of chloroform fraction ( p < 0.05) and only higher doses of ethyl acetate fraction ( p < 0.05) possessed significant antiulcer activity. In contrast, the aqueous fraction did not have significant antiulcer effect at all tested doses., Conclusion: The present study demonstrated that the crude extract, chloroform, and ethyl acetate fractions possessed significant dose-dependent antiulcer activity., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Alefe Norahun Mekonnen et al.)

The aim was to explore the impact of periconceptional folic acid or flaxseed oil (FXO) supplementation on fertility, progesterone profile, and blood chemistry in pregnant ewes during the breeding season. In total, 54 Ossimi ewes were divided into three groups (18 animals each). The control treatment (CON) fed a basal diet only, while the others fed the basal diet and supplemented every other day with a single bolus of folic acid (FO 500 μg/head) or flaxseed oil (FX 50 ml/head). During the early stage of pregnancy, the FO and FX groups showed significantly higher serum antioxidant activity (glutathione and superoxide dismutase) as compared with the control CON group (P = 0.012 and 0.007, respectively). Although no significant variations were detected in the serum nitric oxide levels during the early stage and mid-stage of pregnancy, the FO and FX groups showed significantly lower serum nitric oxide concentration in the late stage of pregnancy (P = 0.001). The FO and FX groups showed significantly higher serum progesterone concentrations during the early stage (10.9 and 11.4 ng/ml, respectively) and mid-stage (22.2 and 23.4 ng/ml, respectively) of pregnancy as compared with the CON group (7.72 and 13.9 ng/ml, respectively). The FX group exhibited a significantly higher lambing rate (P = 0.034), as well as the proportion of female lambs (P = 0.029) as compared with the CON group. In conclusion, supplementing Ossimi ewes with folic acid or FXO significantly improved the progesterone profile during pregnancy. Moreover, the FXO supplementation significantly increased the lambing rate and the female lamb rate as compared with the control group.

Objective : To compare bilateral orchidectomy, as the classical 'gold standard' androgen-deprivation therapy (ADT), and ADT using a luteinising hormone-releasing hormone (LHRH) antagonist (degarelix) for the treatment of metastatic prostate cancer regarding their short-term biochemical efficacy, testosterone castrate level, tolerability, and effect on health-related quality of life (HRQoL). Patients and methods : A total of 60 patients with newly diagnosed metastatic prostate cancer were managed by either bilateral orchidectomy or degarelix injection as ADT. Both groups were compared according to their prostate-specific antigen (PSA) nadir and testosterone level at the 6-month follow-up. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) after 12 months. Results : Bilateral orchidectomy and degarelix showed comparable results for PSA reduction, but there was a statistically significantly lower castrate level of testosterone in the bilateral orchidectomy group. Using the EROTC QLQC-30, bilateral orchidectomy was associated with better HRQoL, better global health status, and better functional status. Conclusion : Bilateral orchidectomy resulted in lower castrate levels of testosterone, which may be associated with better disease control, together with better HRQoL and general health status compared to LHRH antagonist (degarelix). These results indicate that we should consider revisiting bilateral orchidectomy as a valuable and effective treatment option for ADT. Abbreviations : ADT: androgen-deprivation therapy; EORTC (QLQ-C30): European Organisation for Research and Treatment of Cancer (Quality of Life Questionnaire-Core 30); HRQoL: health-related quality of life., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

This work demonstrates a record 160 m long visible light communication (VLC) link using LED transmitters and an image sensor-based receiver, for distance-critical applications. This marks the longest VLC distance achieved to date, using a combination of novel modulation technique at the transmitter and an undersampling-based receiver incorporating adaptive threshold decisioning. Experimental results demonstrate low bit error rate (BER) performance at the achieved communication distance.

Pullulan-hydrolysing enzymes, more commonly known as debranching enzymes for starch and other polysaccharides, are of great interest and have been widely used in the starch-saccharification industry. Type III pullulan hydrolase from Thermococcus kodakarensis (TK-PUL) possesses both pullulanase and α-amylase activities. Until now, only two enzymes in this class, which are capable of hydrolysing both α-1,4- and α-1,6-glycosidic bonds in pullulan to produce a mixture of maltose, panose and maltotriose, have been described. TK-PUL shows highest activity in the temperature range 95-100°C and has a pH optimum in the range 3.5-4.2. Its unique ability to hydrolyse maltotriose into maltose and glucose has not been reported for other homologous enzymes. The crystal structure of TK-PUL has been determined at a resolution of 2.8 Å and represents the first analysis of a type III pullulan hydrolyse. The structure reveals that the last part of the N-terminal domain and the C-terminal domain are significantly different from homologous structures. In addition, the loop regions at the active-site end of the central catalytic domain are quite different. The enzyme has a well defined calcium-binding site and possesses a rare vicinal disulfide bridge. The thermostability of TK-PUL and its homologues may be attributable to several factors, including the increased content of salt bridges, helical segments, Pro, Arg and Tyr residues and the decreased content of serine.

The genome of the hyperthermophilic archaeon Pyrobaculum calidifontis contains an open reading frame, Pcal&#95;1032, annotated as glucokinase. Amino acid sequence analysis showed that Pcal&#95;1032 belonged to ROK (repressor, open reading frame, and kinase) family of sugar kinases. To examine the properties of Pcal&#95;1032, the coding gene was cloned and expressed in Escherichia coli. However, expression of the gene was low resulting in a poor yield of the recombinant protein. A single site directed mutation in Pcal&#95;1032 gene, without altering the amino acid sequence, resulted in approximately tenfold higher expression. Purified recombinant Pcal&#95;1032 efficiently phosphorylated various hexoses with a marked preference for glucose. ATP was the most preferred phosphoryl group donor. Optimum temperature and pH for the glucokinase activity of Pcal&#95;1032 were 95 °C and 8.5, respectively. Catalytic efficiency (k cat /K m ) towards glucose was 437 mM -1  s -1 . The recombinant enzyme was highly stable against temperature with a half-life of 25 min at 100 °C. In addition, Pcal&#95;1032 was highly stable in the presence of denaturants. There was no significant change in the CD spectra and enzyme activity of Pcal&#95;1032 even after overnight incubation in the presence of 8 M urea. To the best of our knowledge, Pcal&#95;1032 is the most active and highly stable glucokinase characterized to date from archaea, and this is the first description of the characterization of a glucokinase from genus Pyrobaculum.

Forty female goats in the third parity were randomly divided into four similar groups. The experiment was started 20 days before mating and lasted until the end of the suckling period for 60 days and weaning their kids. The first group were fed diet without supplementation and kept as control while in the second, third and fourth groups, each doe was fed diets with rumen protected choline (RPC) at the rate of 10, 20 and 40 g/day, respectively. Results showed that number of doe kidding twins and triplets and litter weight of kids born per group increased with increasing the level of RPC in the diet of goats and viability rate of born kids during the suckling period improved due to RPC supplementation in the diets of their mothers. Duration of estrous, days from weaning to estrous, days from kidding to estrous and kidding interval decreased significantly, while conception rate increased due to adding RPC. Milk choline concentrations and total choline secretion though milk were progressively increased significantly with increasing the level of RPC supplementation. Live body weight and daily body gain of their suckling male and female kids at weaning increased significantly with increasing RPC levels in the diets of their mothers., (© 2017 Japanese Society of Animal Science.)

The chaperonin genes encoding GroEL Gt (ESU72018) and GroES Gt (ESU72017), homologues of bacterial GroEL and GroES, from Geobacillus thermopakistaniensis were cloned and expressed in Escherichia coli. The purified gene products possessed the ATPase activity similar to other bacterial and eukaryal counterparts. Recombinant GroEL Gt and GroES Gt were able to refold the denatured insoluble aggregates of α-amylase from Bacillus licheniformis into soluble and active form. Furthermore, GroEL Gt and GroES Gt successfully enhanced the thermostability of porcine heart malate dehydrogenase. Expression of GroEL Gt gene in E. coli cells enhanced the thermotolerance of the host. Furthermore, soluble production of recombinant alcohol dehydrogenase from Bacillus subtilis strain R5 in E. coli, initially produced as insoluble aggregates, was achieved by co-expressing the gene with GroEL Gt . Our results implied that GroEL Gt could assist folding of nascent protein in E. coli with the help of host co-chaperonin without requiring additional ATP. This system can be used for soluble production of recombinant proteins which otherwise are produced in insoluble form in E. coli. To the best of our knowledge this is the first report on functional characterization and applications of chaperonins from genus Geobacillus., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Tk1884, an open reading frame encoding α-amylase in Thermococcus kodakarensis, was cloned with the native signal sequence and expressed in Escherichia coli. Heterologous gene expression resulted in secretion of the recombinant protein to the extracellular culture medium. Extracellular α-amylase activity gradually increased after induction. Tk1884 was purified from the extracellular medium, and its molecular mass determined by electrospray ionization mass spectrometry indicated the cleavage of a few amino acids. The N-terminal amino acid sequence of the purified Tk1884 was determined, which revealed that the signal peptide was cleaved between Ala26 and Ala27 by E. coli signal peptidase. To the best of our knowledge, this is the first report describing an archaeal signal sequence recognized and cleaved by E. coli signal peptidase.

The objective of this study was to evaluate the impact of thermal stress on milk production and physiological traits of Baladi goats under subtropical Egyptian conditions. Sixty dairy Baladi goats were exposed to three different levels of temperature-humidity index (THI), including low (less than 70), moderate (over 70 and up to 80), and high levels (over 80). The influence of THI on the milk composition and physiological, hematological, and biochemical traits was investigated. Rectal temperature and respiration rate were significantly greater at the higher THI than at low and moderate THI (p = 0.016 and 0.002, respectively). Baladi goats had decreased daily milk yield in a rate of 27.3 and 19.3 % at high THI level, compared with low and moderate THI, respectively (p = 0.031). On the contrary, no significant differences have been reported in protein, fat, and total solids percentages at different THI levels. Total leucocyte count, serum glucose, and total protein were significantly reduced at high THI in comparison with low and moderate THI levels (p = 0.043, 0.001, and 0.001, respectively). However, dairy goats maintained relatively stable estimates for erythrocytes count, hemoglobin, serum triglycerides, cholesterol, catalase, total antioxidant capacity, and triiodothyronine at different THI levels. Our results indicate that dairy Baladi goats can tolerate THI levels up to 80; however, variable reduction in milk yield and few biochemical (serum total protein and glucose) and hematological (leucocytes count) parameters have been reported at a THI level higher than 80.

Objective: To report our experience for the initial management of patients with newly diagnosed bladder tumours using our team approach for each case and using an aggressive extended transurethral resection of bladder tumour (TURBT) in order to investigate the real need for a routine 'second-look' cystoscopy in the current era., Patients and Methods: The study included 50 consecutive patients admitted to the urology department, of our tertiary care centre, for management of newly diagnosed bladder cancer. Exclusion criteria included past history of bladder tumour, palpable mass on bimanual examination under anaesthesia, presence of residual tumour at the end of resection, and patients with tumours of the bladder dome as thorough resection is difficult to achieve in this area without an attendant risk. Patients that had pathologically confirmed carcinoma in situ were also excluded. White-light cystoscopy was used in all of the cases. Extended TURBT was defined as resection of the whole tumour, resection of the tumour base and 1 cm of apparently normal bladder wall around the circumference of the tumour., Results: The median (range) age of the patients was 52 (39-60) years. After initial TURBT, 10 patients (20%) were identified as having muscle-invasive bladder cancer. Of the remaining 40 patients, three had low-grade Ta disease, and so second biopsies were not taken. The remaining 37 patients had T1, grade 2-3 disease and none of them had evident residual disease at the site of tumour resection., Conclusion: Re-staging TURBT could be safely omitted for select groups of patients. An experienced surgeon and teamwork, together with an extended TURBT can accurately achieve complete tumour resection, with accurate tumour staging, on initial resection.

Objectives: To present a novel ureteric re-implantation technique for primary obstructed megaureter (POM) that ensures success in the short- and long-term, as conventional techniques are not ideal for megaureters especially in children, with ureteric stenosis and reflux being common complications after re-implantation., Patients and Methods: Between 2009 and 2012, 22 paediatric patients with POM were enrolled. We performed a new technique for re-implantation of these ureters to ensure minimal incidence of ureteric strictures and easy subsequent endoscopic access. We performed follow-up voiding cystourethrography (VCUG) at 6 months postoperatively., Results: The cohort comprised 14 boys and eight girls, with a median age of 22 months. Six patients underwent bilateral re-implantation. The mean (range) duration of indwelling ureteric catheterisation was 7.8 (4-14) days. There were no complications in the perioperative and postoperative periods. There was no reflux on follow-up VCUG in any of the patients. One patient developed Grade I reflux after 1 year and presented with a urinary tract infection. Diagnostic cystoscopy was performed in 13 patients showing that the nipple was directed similarly to the native ureteric orifice., Conclusion: The embedded-nipple technique for re-implantation of POM guarantees successful results and permits easy subsequent ureteroscopic access when needed.

Objectives: To assess whether the detubularised isolated ureterosigmoidostomy (DIUS) technique is safe for urinary diversion after radical cystectomy., Patients and Methods: The study included 10 patients (mean age 61.8 years) with invasive bladder tumour, operated at the Alexandria University, Egypt. The diversion in all patients was through a DIUS, with ureteric reimplantation by an antirefluxing procedure, using an embedded-nipple technique. The patients were evaluated before and after surgery using radiological and manometric studies, and the results analysed statistically using Student's t-test., Results: Nine of the 10 patients could differentiate between urinary and stool sensation, and evacuate them separately. The mean (range) daytime frequency was 4.1 (3-5) and the mean night-time frequency was 0.5 (0-1). Before and after surgery, the respective mean resting anal pressure was 71 and 74 cm H2O (P = 0.004), the volume at first desire to defecate was 54 and 72 mL (P = 0.004) and the maximum tolerable volume was 140 and 160 mL (P < 0.001). The anorectal inhibitory reflex was lost in all patients after surgery. The mean (SD, range) basal pouch pressure was 5 (3.33, 0-10) cmH2O, and the end pressure was 13.2 (4.42, 9-20) cmH2O., Conclusion: Although the Mainz II pouch has a documented efficacy for urinary diversion after radical cystectomy, the modifications we applied to the DIUS improved that method of diversion, by separating urine and stool evacuation, maintaining continence, and with a low frequency and better protection of the upper urinary tracts, resulting in an improvement in the patients' quality of life.

Objectives: To assess the emptying pattern and patient satisfaction after constructing a detubularised isolated ureterosigmoidostomy (DIUS) following a cystectomy, introduced to overcome the poor outcome of conventional ureterosigmoidostomy, to improve the emptying pattern and accordingly patients' quality of life., Patients and Methods: The study included 122 patients who were treated with a DIUS diversion after cystectomy. The minimum follow-up of the patients was 6 months. The frequency of emptying and continence during the day and night were recorded. The ability of the patients to discriminate between urine and stool was assessed. The patients' overall satisfaction with the outcome was categorised as fully satisfied, moderately satisfied or not satisfied., Results: In all, 95 patients were available for this evaluation; all patients were completely continent during the day and night. The mean emptying frequency was 3.9 during the day and 1.7 during the night. All patients were able to feel the desire to empty and the mean holding time was 35 min. Fifty-two patients (55%) could pass solid stools once per day, with minimal urine at the end of voiding, and the remaining evacuations were of clear urine only. Thirty-two patients (34%) were able to differentiate between urine and stool sensation before emptying. For satisfaction, 82 patients reported full satisfaction, 13 were moderately satisfied, and none regretted the diversion., Conclusions: The DIUS diversion provides continence during the day and night, with a satisfactory emptying habit. Patients with a DIUS diversion can tolerate a full pouch comfortably, with no leakage, and they can discriminate between urine and stool evacuations.

Percutaneous nephrostomy (PCN) has been widely used to drain an infected, obstructed kidney. Few major complications have been associated with it. Few publications have reported the misplacement of nephrostomy tube into the inferior vena cava (IVC), following percutaneous nephrolithotomy. We report a case of a misplaced silicon catheter, through the left renal vein, extending into the IVC, following nephrostomy tube exchange. Our case was safely managed, and we concluded that although PCN and nephrostomy tube exchange are relatively simple procedures, they should be done cautiously, by a well-trained urologist, and preferably under ultrasound or fluoroscopic guidance.