Miracle-dz/UniFAR-FTUs huggingface dataset:
Genotypic and phenotypic variation in six patients with solitary median maxillary central incisor syndrome

Solitary Median Maxillary Central Incisor occurs in 1 of 50,000 live births. It is the mildest manifestation of the holoprosencephaly spectrum and is genetically heterogeneous. Here we report six patients with solitary median maxillary central incisor, and a range of other phenotypic anomalies with different degrees of severity, varying from mild signs of holoprosencephaly to associated intellectual disability, and with different genetic background. Using array comparative genomic hybridization, pathogenic copy number variants were found in three of the six patients. Two patients had a deletion at the 18p11 chromosomal region that includes TGIF1 while the other patient had a deletion at 7q36, including the SHH gene. In one patient, a mutation in SIX3 was detected with exome sequencing, while in the two remaining patients all known holoprosencephaly genes were excluded using multiplex ligation‐dependent probe amplification and sequencing, and remain unsolved. One of the two latter patients had isolated solitary median maxillary central incisor without other visible dentofacial anomalies, while the other had clinical features not part of the known holoprosencephaly spectrum. © 2015 Wiley Periodicals, Inc.
Contrast-induced nephropathy: prevention strategies

Contrast-induced nephropathy is defined as worsening in renal function after administration of intravenous contrast and ex-clusion of other causes. Contrast-induced nephropathy is usually manifested as an acute non-oliguric renal failure. Cases of con-trast-induced nephropathy are usually defined by a fixed (0.5 mg/dl) or proportionate (25-50%) rise in serum creatinine levels 24-48 hours after exposure to the contrast medium, in the absence of other causes of renal function impairment. Prevention strategies are based on the correction of factors leading to the development of contrast-induced nephropathy and are divided into choice of less nephrotoxic contrast (non-ionic); improvement in the patient’s clinical status through hydration; use of drugs that reduce renal vaso-constriction and oxidative stress; and temporary suspension of drugs with nephrotoxic potential or that are harmful in case of re-duced glomerular filtration. The development of a protocol with preventive strategies for risk patients, especially in diabetics submit-ted to potentially nephrotoxic contrast can reduce morbidity and associated costs to its development. This review aims at describing the definition and pathogenesis of contrast-induced nephropathy, focusing on the main management recommendations to prevent its occurrence.
Complementary and Alternative Medicine (CAM) use among Children with Asthma in the Egyptian Context

Background: The popularity of complementary and alternative medicine (CAM) is growing globally among adult and pediatric populations, but little is known about its use in children with Asthma in Egypt. Aim: The aim of this study was to explore CAM use among children with asthma in Egypt. Sample: The convenient sample of 550 mothers of children with asthma. Design: A descriptive correlational cross-sectional design was used to conduct the study. Sitting: The study was conducted in Cairo University Specialized Pediatric Hospital at out-patient clinic Tools: Data were collected using a questionnaire sheet designed by the researchers. Included demographic profile, mothers were asked about CAM use including dietary supplement (DS) and non-DS remedies. Results: The majority of women were young with a mean age of twenty six, live in Cairo, unemployed; secondary schools educated, and were multi-gravida. The mean age of the children was three and more than half of them were male . The majority of mothers used some type of CAM remedy for their kids. The most common types used as DS including: Anise seeds& herbal cough. Only few mothers were used Non –DS remedies. The most commonly used ND remedies were massaging the child chest with olive oil and spiritual healing. Relatives, friends and neighbors were the main source of information about CAM for the majority of the mothers. Decrease the respiratory secretions, improve breathing patterns, no side effect were the most important reasons of using CAM as mentioned by the mothers . Eighty-sex percent of mothers were willing to discuss the use of CAM with their doctors or nurses but were not asked. There was a significant positive correlation between’s mother usage of CAM for themselves and their usage for their kids. Conclusion: The prevalence of reported CAM use among Egyptian children with asthma was high with dietary remedies being the most popular modalities. CAM use was associated with older child’s age and perceived poor asthma control. Key words :( Complementary and Alternative Medicine- Dietary Supplement - Non Dietary Supplement remedies - children with asthma)
Macrophage Proliferation Is Regulated through CSF-1 Receptor Tyrosines 544, 559, and 807*

Background: Activation loop Y807F or juxtamembrane domain Y559F mutations compromise CSF-1 receptor-mediated macrophage proliferation. Results: Tyr-559 suppresses constitutive proliferative activity of Tyr-807; ligand-induced Tyr-559 phosphorylation relieves this inhibition and activates pathways. Conclusion: Tyr-807 drives proliferation. Tyr-559 confers ligand dependence. Significance: How individual CSF-1 receptor tyrosines regulate receptor activation and signaling is critical for understanding the function of this disease-relevant receptor. Colony-stimulating factor-1 (CSF-1)-stimulated CSF-1 receptor (CSF-1R) tyrosine phosphorylation initiates survival, proliferation, and differentiation signaling pathways in macrophages. Either activation loop Y807F or juxtamembrane domain (JMD) Y559F mutations severely compromise CSF-1-regulated proliferation and differentiation. YEF, a CSF-1R in which all eight tyrosines phosphorylated in the activated receptor were mutated to phenylalanine, lacks in vitro kinase activity and in vivo CSF-1-regulated tyrosine phosphorylation. The addition of Tyr-807 alone to the YEF backbone (Y807AB) led to CSF-1-independent but receptor kinase-dependent proliferation, without detectable activation loop Tyr-807 phosphorylation. The addition of Tyr-559 alone (Y559AB) supported a low level of CSF-1-independent proliferation that was slightly enhanced by CSF-1, indicating that Tyr-559 has a positive Tyr-807-independent effect. Consistent with the postulated autoinhibitory role of the JMD Tyr-559 and its relief by ligand-induced Tyr-559 phosphorylation, the addition of Tyr-559 to the Y807AB background suppressed proliferation in the absence of CSF-1, but restored most of the CSF-1-stimulated proliferation. Full restoration of kinase activation and proliferation required the additional add back of JMD Tyr-544. Inhibitor experiments indicate that the constitutive proliferation of Y807AB macrophages is mediated by the phosphatidylinositol 3-kinase (PI3K) and ERK1/2 pathways, whereas proliferation of WT and Y559,807AB macrophages is, in addition, contributed to by Src family kinase (SFK)-dependent pathways. Thus Tyr-807 confers sufficient kinase activity for strong CSF-1-independent proliferation, whereas Tyr-559 maintains the receptor in an inactive state. Tyr-559 phosphorylation releases this restraint and may also contribute to the CSF-1-regulated proliferative response by activating Src family kinase.
Indications for Ventricle Assist Devices

Despite widespread use of evidence-based therapies the morbidity and mortality of heart failure has not changed, and it remains the most common hospital discharge diagnosis for patients older than 65 years old of age. Approximately 5 million patients in the United States of America have cardiac failure, and over 550,000 patients are diagnosed with heart failure for the first time each year (Levy et al, 2002; Hunt et al, 2005). The European Society of Cardiology represents countries with a population of more than 900 million, and in their last guidelines they reported that there are at least 15 million patients suffering this disease in those 51 countries (Dickstein et al, 2008). Heart failure is primarily a condition of the elderly (Kannel & Belanger, 1991), and thus the widely recognized “aging of the population” also contributes to the increasing incidence of heart disease. The incidence of cardiac failure approaches 10 per 1,000 population after age 65 years, and approximately about 80% of patients hospitalized with heart failure are older than 65 years old (Masoudi & Havranek, 2002). There are several reasons that may explain why the prevalence of heart failure is increasing: ageing of the population, the success in prolonging survival in coronary patients, and the success in postponing coronary events by effective prevention in those patients at high risk or those patients who have already survived a first event (secondary prevention) (Senni et al, 1999). Advances in medical therapy have resulted in improved survival in patients with moderate and severe heart failure, but the prognosis for end-stage heart failure patients still remains poor. The conclusion of all these aspects is that there is a change in the demographics of heart failure patients in recent years, and an increased survival of older patients with heart disease. At present time, cardiac transplantation remains the gold standard of cardiac replacement therapy. However, the supply of donor hearts is limited and therefore is not an option for many patients because of age and other comorbid conditions. Alternative forms of cardiac replacement therapy are being investigating. This includes cell therapy, xenotransplantation, ventricle assist devices implantation and total artificial heart. Although initially the indications for heart mechanical assistance are similar to those developed in the1960s for the use of intra-aortic balloon pumps the indications have developed into more complex cases which must be considered. Ventricle assist devices are more and more reliable and its size is becoming smaller with the passing of time, improving patient’s outcomes.
Desnervação periférica nas diferentes formas clínicas da doença de Chagas

EMG examination was performed in 41 patients with Chagas' disease, belonging to the several clinical forms of the disease. Constant and direct relationship between the amount of muscle skeletal denervation and the clinical forms has been shown. In addition light peripheral axonal neuropathy was seen. Both muscular and sensory denervation was intense in the group with cardio-digestive form, moderate in the groups with either cardiac or digestive form and light in the group with the indeterminate form. The severity of the clinical symptoms was not related with the amount of peripheral denervation.
Cellular innate immune responses to lung resection via video- assisted thoracoscopic surgery (VATS) and thoracotomy : predictors of post-operative pneumonia

presented at The Society for Cardiothoracic Surgeons of Great Britain and Ireland, Annual Meeting, Brighton, March 2013. Awarded the Society Thoracic Medal. Jones RO, Brittan M, Anderson NH, Conway Morris A, Murchison JT, Simpson AJ, Walker WS. Cellular Innate Immune Responses to Lung Resection Predict Post- Operative Pneumonia. OBJECTIVE: Post-operative pneumonia is an important cause of morbidity and mortality following lung cancer resection. We hypothesise that early changes in innate immune parameters may help identify patients at greatest post-operative risk and potentially identify future therapeutic strategies. METHODS: Patients undergoing lung resection for suspected bronchogenic carcinoma were recruited. Blood was sampled pre-operatively and at 6, 24 and 48 hours post- operatively. Neutrophil phagocytic capacity, monocyte subset changes and cytokine release from lipopolysaccharide (LPS)-stimulated monocytes were quantified in all patients at all time points. Bronchoalveolar lavage (BAL) was performed in the contralateral lung preand post-operatively. Screening for pneumonia was performed 72-hours post-operatively. RESULTS: 40 patients were studied of which 14 (35%) developed post-operative pneumonia. Pre-operatively, a blood neutrophil count above 5.04x10/L had a relative risk (RR) for pneumonia of 3.3 (95% confidence interval (CI95) 1.1-10.1), and a BAL cell count of greater than 1.04x10/ml had a RR of 3.4 (CI95 1.3-9.0), whilst LPS- stimulated monocyte secretion of IL-12 of less than 0.15 pg/ml/μg protein had a RR of 3.0 (CI95 1.2-7.3). At 24 hours post-operatively, LPS-stimulated release from
Exome sequencing reveals a novel CWF19L1 mutation associated with intellectual disability and cerebellar atrophy

Intellectual disability (ID) with cerebellar ataxia comprises a genetically heterogeneous group of neurodevelopmental disorders. We identified a homozygous frameshift mutation in CWF19L1 (c.467delC; p.(P156Hfs*33)) by a combination of linkage analysis and Whole Exome Sequencing in a consanguineous Turkish family with a 9‐year‐old boy affected by early onset cerebellar ataxia and mild ID. Serial MRI showed mildly progressive cerebellar atrophy. Absent C19L1 protein expression in lymphoblastoid cell lines strongly suggested that c.467delC is a disease‐causing alteration. One further pregnancy of the mother had been terminated at 22 weeks of gestation because of a small cerebellum and agenesis of corpus callosum. The homozygous CWF19L1 variant was also present in the fetus. Postmortem examination of the fetus in addition showed unilateral hexadactyly and vertebral malformations. These features have not been reported and may represent an expansion of the CWF19L1‐related phenotypic spectrum, but could also be due to another, possibly autosomal recessive disorder. The exact function of the evolutionarily highly conserved C19L1 protein is unknown. So far, homozygous or compound heterozygous mutations in CWF19L1 have been identified in two Turkish siblings and a Dutch girl, respectively, affected by cerebellar ataxia and ID. A zebrafish model showed that CWF19L1 loss‐of‐function mutations result in abnormal cerebellar morphology and movement disorders. Our report corroborates that loss‐of‐function mutations in CWF19Ll lead to early onset cerebellar ataxia and (progressive) cerebellar atrophy. © 2016 Wiley Periodicals, Inc.
Salience in a social landscape: electrophysiological effects of task-irrelevant and infrequent vocal change.

In a dynamically changing social environment, humans have to face the challenge of prioritizing stimuli that compete for attention. In the context of social communication, the voice is the most important sound category. However, the existing studies do not directly address whether and how the salience of an unexpected vocal change in an auditory sequence influences the orientation of attention. In this study, frequent tones were interspersed with task-relevant infrequent tones and task-irrelevant infrequent vocal sounds (neutral, happy and angry vocalizations). Eighteen healthy college students were asked to count infrequent tones. A combined event-related potential (ERP) and EEG time-frequency approach was used, with the focus on the P3 component and on the early auditory evoked gamma band response, respectively. A spatial-temporal principal component analysis was used to disentangle potentially overlapping ERP components. Although no condition differences were observed in the 210-310 ms window, larger positive responses were observed for emotional than neutral vocalizations in the 310-410 ms window. Furthermore, the phase synchronization of the early auditory evoked gamma oscillation was enhanced for happy vocalizations. These findings support the idea that the brain prioritizes the processing of emotional stimuli, by devoting more attentional resources to salient social signals even when they are not task-relevant.
14q13 distal microdeletion encompassing NKX2‐1 and PAX9: Patient report and refinement of the associated phenotype

Chromosome 14q11‐q22 deletion syndrome (OMIM 613457) is a rare genomic disorder whose associated phenotype is heterogeneous, depending on the size, and, mostly, on the deleted region. We report the clinical and molecular characterization of a female newborn, whose phenotype was characterized by poor growth, dysmorphic facial features, subclinical hypothyroidism, and mild reduction of CD3CD8 Lymphocytes with increased CD4/CD8 ratio. By array‐CGH, we identified a 4.08 de novo interstitial deletion of the 14q13.2q21. 1 region, which includes 16 OMIM genes.Our patient phenotype is compared with other published cases, for a better classification of the 14q11‐q22 deletion syndrome. We demonstrated that the 14q13.2q21. 1 deletion, which encompasses NKX2‐1, but not FOXG1 gene and HPE8 region, identifies a well defined, more benign, microdeletion syndrome. This report confirms that an early identification with accurate characterization of the genomic disorders is of great relevance, enabling proper genetic counseling of the reproductive risk, as well as disease prognosis, and patient management. © 2016 Wiley Periodicals, Inc.
Le virus de la varicelle et du zona : un alphaherpesvirus pas vraiment comme les autres…

Le virus de la varicelle et du zona (VZV) est un alphaherpesvirus qui nous est familier en raison des deux pathologies dont il est responsable : la varicelle et le zona resultant de la reactivation du virus reste latent dans les ganglions sensoriels. Parmi les quelque 120 herpesvirus connus, seuls huit, dont le VZV et le virus de l’herpes simplex de type 1 ou 2 (HSV1, 2) infectent l’homme. Alors qu’il a ete longtemps admis que les donnees concernant le HSV pouvaient etre extrapolees au VZV, il apparait a present que ces deux virus different a plus d’un point, en particulier dans les mecanismes moleculaires qui regissent la latence. Leurs differences apparaissent egalement au niveau clinique. Dans nos contrees temperees, le VZV est responsable d’une infection primaire tres tot dans l’enfance et sa reactivation symptomatique, tres souvent unique, est plus frequemment observee chez les individus âges. Le HSV1, par contre, est responsable d’une primo-infection qui survient a un âge plus avance et les episodes de reactivation dont il est responsable sont recurrents et diminuent avec l’âge. Une meilleure connaissance de la biologie du VZV a permis de developper des antiviraux efficaces et de developper un vaccin pediatrique dont l’efficacite a ete demontree aux Etats-Unis apres dix ans de vaccination massive.
Antifungal activity of thyme oil against Geotrichum citri‐aurantii in vitro and in vivo

Aims: To investigate antifungal effect of thyme oil on Geotrichum citri‐aurantii arthroconidia germination and germ tube elongation, to reveal effects of thyme oil on morphological structures on fungal hyphae and arthroconidia and to assess potential bio‐control capacities of thyme oil against disease suppression in vivo conditions.
Siderophores mediate reduced and increased uptake of cadmium by Streptomyces tendae F4 and sunflower (Helianthus annuus), respectively

Aims: As a toxic metal, cadmium (Cd) affects microbial and plant metabolic processes, thereby potentially reducing the efficiency of microbe or plant‐mediated remediation of Cd‐polluted soil. The role of siderophores produced by Streptomyces tendae F4 in the uptake of Cd by bacteria and plant was investigated to gain insight into the influence of siderophores on Cd availability to micro‐organisms and plants.
Neural correlates of deception: lying about past events and personal beliefs

Abstract Although a growing body of literature suggests that cognitive control processes are involved in deception, much about the neural correlates of lying remains unknown. In this study, we tested whether brain activation associated with deception, as measured by functional magnetic resonance imaging (fMRI), can be detected either in preparation for or during the execution of a lie, and whether they depend on the content of the lie. We scanned participants while they lied or told the truth about either their personal experiences (episodic memories) or personal beliefs. Regions in the frontal and parietal cortex showed higher activation when participants lied compared with when they were telling the truth, regardless of whether they were asked about their past experiences or opinions. In contrast, lie-related activation in the right temporal pole, precuneus and the right amygdala differed by the content of the lie. Preparing to lie activated parietal and frontal brain regions that were distinct from those activated while participants executed lies. Our findings concur with previous reports on the involvement of frontal and parietal regions in deception, but specify brain regions involved in the preparation vs execution of deception, and those involved in deceiving about experiences vs opinions.
Conjugation of Glutathione to Oxidized Tyrosine Residues in Peptides and Proteins*

Background: Tyrosyl radicals react with superoxide to form bicyclic hydroperoxides that contains an α-β unsaturated carbonyl. Results: GSH undergoes Michael addition with Tyr hydroperoxides in peptides and myoglobin. Conclusion: Proteins that form hydroperoxides through radical-mediated oxidation should readily form GSH-Tyr adducts. Significance: This is a novel mechanism of protein-glutathione adduct formation, and similar chemistry could result in Cys-Tyr cross-linking of proteins during oxidative stress. Tyrosine residues are sensitive to oxidation and can be converted to hydroperoxides either by superoxide reacting with the Tyr radical or by singlet oxygen. These hydroperoxides rearrange to bicyclic derivatives that are readily reduced to more stable hydroxides. The aromatic character of tyrosine is lost, but the product contains an α-β unsaturated carbonyl group and is, therefore, an electrophile. We have generated hydroxide derivatives of several Tyr-containing peptides and shown using liquid chromatography/mass spectrometry that they undergo Michael addition with GSH. For Tyr-Gly, rate constants of 9.2 and 11.8 m−1min−1 were measured for the two chromatographically distinct isomers. Unusual for GSH addition to an electrophile, the reaction is reversible, with a half-life of many hours for the reverse reaction. These kinetics indicate that with a typical cellular concentration of 5 mm GSH, >95% Tyr-Gly hydroxide would become conjugated with a half-life of ∼15 min. Sperm whale myoglobin forms a hydroperoxide on Tyr-151 in a hydrogen peroxide/superoxide-dependent reaction. We show that its hydroxide derivative reacts with GSH to form a conjugate. Detection of the conjugate required stabilization by reduction; otherwise, the reverse reaction occurred during tryptic digestion and analysis. Our findings represent a novel mechanism for peptide or protein glutathionylation involving a carbon-sulfur cross-link between oxidized Tyr and Cys. As with other electrophiles, the oxidized Tyr should undergo a similar reaction with Cys residues in proteins to give intramolecular or intermolecular protein cross-links. This mechanism could give rise to protein cross-linking in conditions of oxidative stress.