Miracle-dz/UniFAR-FTUs huggingface dataset:
Angelman syndrome in Denmark. Birth incidence, genetic findings, and age at diagnosis

Angelman syndrome (AS) is a neurogenetic disorder caused by loss of expression of the maternal imprinted gene UBE3A on chromosome 15q11.2–q13. Clinical features of AS include severe intellectual disability, a happy disposition, ataxia, mandibular prognatism, and epilepsy. Our objectives were to examine the birth incidence of AS in Denmark and to characterize the size of the 15q11.2–q13 deletions with 1,000K array CGH. In addition, we analyzed genotype differences in regard to age at diagnosis and investigated the occurrence of deletions/duplications outside the 15q11.2–q13 regions. We identified 51 patients with genetically verified AS, which corresponded to a birth incidence of 1:24,580 (95%CI: 1:23,727–1:25,433). Thirty‐six patients showed a deletion; 13 had a Class I deletion and 20 had a Class II deletion. There was bimodal distribution of the BP3 breakpoint. Three patients had larger and atypical deletions, with distal breakpoints telomeric to BP3. Five patients had paternal uniparental disomy (pUPD) of chromosome 15, and four had a verified UBE3A mutation. Additional deletions/duplications outside the 15q11.2–q13 areas were demonstrated in half the participants. Six harbored more than one CNV. Mean age at diagnosis was 21 months (95%CI: 17–23 months) for children with a deletion and 46 months (95%CI: 36–55 months) for children with pUPD or a UBE3A mutation (P < 0.01). The presence of a CNV outside 15q11.2–q13 did not have an impact on age at diagnosis. © 2013 Wiley Periodicals, Inc.
Exercise Assessment for People with End-stage Renal Failure

First paragraph: Progressive loss of kidney function is often described as chronic kidney disease (CKD). Chronic kidney disease may progress to end stage renal failure (ESRF), at which point the kidneys are not able to perform their regulatory and excretory functions. The transition into end-stage renal failure, with the concomitant derangement of normal biochemical, metabolic and endocrine functions, is almost always accompanied by the clinical syndrome of uraemia. Symptoms such as anorexia, generalised lethargy and fatigue, sleep disorder, neurological dysfunction, nausea and vomiting are frequently evident. The appearance of these symptoms is remarkably consistent and appears to coincide with abnormal plasma levels of many substances including urea, creatinine, phosphate, and parathyroid hormone, which have been identified as potential uraemic toxins. Accompanying clinical signs of ESRF include fluid retention (peripheral and pulmonary oedema), raised blood pressure, diminishing haemoglobin levels and abnormal biochemistry (creatinine, serum urea and potassium) (Bommer 1992, Moore 2000).
Intra-operative neurophysiological monitoring

Abstract Intraoperative neurophysiological monitoring has achieved importance due to complexity of cranio-spinal surgical procedures being performed frequently these days. Many studies have proven a decreased neurological complication rate after its introduction. It is broadly of two types: Sensory evoked potentials and motor evoked potentials which are further sub-divided. Its use during surgery requires a controlled anaesthesia technique with no or minimal influence on its recording. Its success depends upon three way communication among the surgeon the neurophysiologist and the anaesthesiologist.
Anti-oncogenic MicroRNA-203 Induces Senescence by Targeting E2F3 Protein in Human Melanoma Cells

Background: MicroRNA-203 is down-regulated, and its exogenous expression inhibits cell growth in human melanoma cells. Results: MicroRNA-203 induced senescence by cell cycle arrest through targeting E2F3. Conclusion: MicroRNA-203 is a novel senescence-associated microRNA in melanoma cells. Significance: This study has revealed the relationship between senescence and carcinogenesis in melanoma cells with respect to dysregulation of anti-oncogenic microRNA-203. MicroRNAs regulate gene expression by repressing translation or directing sequence-specific degradation of their complementary mRNA. We recently reported that miR-203 is down-regulated, and its exogenous expression inhibits cell growth in canine oral malignant melanoma tissue specimens as well as in canine and human malignant melanoma cells. A microRNA target database predicted E2F3 and ZBP-89 as putative targets of microRNA-203 (miR-203). The expression levels of E2F3a, E2F3b, and ZBP-89 were markedly up-regulated in human malignant melanoma Mewo cells compared with those in human epidermal melanocytes. miR-203 significantly suppressed the luciferase activity of reporter plasmids containing the 3′-UTR sequence of either E2F3 or ZBP-89 complementary to miR-203. The ectopic expression of miR-203 in melanoma cells reduced the levels of E2F3a, E2F3b, and ZBP-89 protein expression. At the same time, miR-203 induced cell cycle arrest and senescence phenotypes, such as elevated expression of hypophosphorylated retinoblastoma and other markers for senescence. Silencing of E2F3, but not of ZBP-89, inhibited cell growth and induced cell cycle arrest and senescence. These results demonstrate a novel role for miR-203 as a tumor suppressor acting by inducing senescence in melanoma cells.
Impacto de la prohibición de fumar en espacios cerrados sobre los ingresos por infarto agudo de miocardio en Uruguay

Introduccion:la exposicion al humo de tabaco ambiental aumenta 31% el riesgo de infarto entre no fumadores. En paises desarrollados se observo reduccion de los ingresos por infarto agudo de miocardio al prohibirse fumar en espacios cerrados. El presente estudio evaluo el impacto de la prohibicion de fumar sobre el infarto agudo de miocardio en Uruguay, el primer pais libre de humo de tabaco en las Americas.Material y metodo: se realizo un estudio ecologico comparando los ingresos por infarto en los 24 meses anteriores y posteriores a marzo de 2006 (fecha de la aprobacion de la normativa que establecio la prohibicion de fumar en espacios cerrados de uso publico). Se analizaron retrospectivamente las historias clinicas de los pacientes residentes en el pais que tuvieran infarto de miocardio como diagnostico principal de ingreso. El analisis estadistico se realizo mediante el test de chi cuadrado.Resultados: en las 37 instituciones participantes ingresaron 7.949 pacientes (66,4 ± 12,6 anos, 35,1% mujeres), 4.346 en los dos anos previos a las medidas y 3.603 en los dos anos siguientes, lo que implico una reduccion de 17,1%. Hubo mayor reduccion a menor edad de los pacientes: 65 anos: 16,9%, p < 0,05. Los viernes y sabados los ingresos descendieron 24,2%, de domingos a jueves 14,3% (p < 0,05). En los centros privados hubo 22,0% de reduccion, en los publicos 6,3%, p < 0,05.Conclusiones: la prohibicion de fumar en espacios cerrados se asocio a una disminucion en los ingresos por infarto agudo de miocardio en nuestro pais, siendo este efecto particularmente importante entre los mas jovenes. El beneficio predomino viernes y sabado y fue menor entre quienes se asisten en el sector publico.
Biological and Structural Characterization of Trypanosoma cruzi Phosphodiesterase C and Implications for Design of Parasite Selective Inhibitors*

Background: Cyclic nucleotide specific phosphodiesterases (PDEs) are essential enzymes in many parasitic protozoa and represent important new drug targets. Results: The crystallographic structure and enzymatic properties of Trypanosoma cruzi phosphodiesterase C (TcrPDEC) have been determined. Conclusion: A parasite-specific pocket next to the TcrPDEC active site might allow designing parasite-specific inhibitors. Significance: The findings highlight the potential of PDEs as anti-parasite drug targets. Trypanosoma cruzi phosphodiesterase C (TcrPDEC) is a potential new drug target for the treatment of Chagas disease but has not been well studied. This study reports the enzymatic properties of various kinetoplastid PDECs and the crystal structures of the unliganded TcrPDEC1 catalytic domain and its complex with an inhibitor. Mutations of PDEC during the course of evolution led to inactivation of PDEC in Trypanosoma brucei/Trypanosoma evansi/Trypanosoma congolense, whereas the enzyme is active in all other kinetoplastids. The TcrPDEC1 catalytic domain hydrolyzes both cAMP and cGMP with a Km of 23.8 μm and a kcat of 31 s−1 for cAMP and a Km of 99.1 μm and a kcat of 17 s−1 for cGMP, thus confirming its dual specificity. The crystal structures show that the N-terminal fragment wraps around the TcrPDEC catalytic domain and may thus regulate its enzymatic activity via direct interactions with the active site residues. A PDE5 selective inhibitor that has an IC50 of 230 nm for TcrPDEC1 binds to TcrPDEC1 in an orientation opposite to that of sildenafil. This observation, together with the screen of the inhibitory potency of human PDE inhibitors against TcrPDEC, implies that the scaffold of some human PDE inhibitors might be used as the starting model for design of parasite PDE inhibitors. The structural study also identified a unique parasite pocket that neighbors the active site and may thus be valuable for the design of parasite-specific inhibitors.
Drug repositioning for SARS-CoV-2 by Gaussian kernel similarity bilinear matrix factorization

Coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently spreading rapidly around the world. Since SARS-CoV-2 seriously threatens human life and health as well as the development of the world economy, it is very urgent to identify effective drugs against this virus. However, traditional methods to develop new drugs are costly and time-consuming, which makes drug repositioning a promising exploration direction for this purpose. In this study, we collected known antiviral drugs to form five virus-drug association datasets, and then explored drug repositioning for SARS-CoV-2 by Gaussian kernel similarity bilinear matrix factorization (VDA-GKSBMF). By the 5-fold cross-validation, we found that VDA-GKSBMF has an area under curve (AUC) value of 0.8851, 0.8594, 0.8807, 0.8824, and 0.8804, respectively, on the five datasets, which are higher than those of other state-of-art algorithms in four datasets. Based on known virus-drug association data, we used VDA-GKSBMF to prioritize the top-k candidate antiviral drugs that are most likely to be effective against SARS-CoV-2. We confirmed that the top-10 drugs can be molecularly docked with virus spikes protein/human ACE2 by AutoDock on five datasets. Among them, four antiviral drugs ribavirin, remdesivir, oseltamivir, and zidovudine have been under clinical trials or supported in recent literatures. The results suggest that VDA-GKSBMF is an effective algorithm for identifying potential antiviral drugs against SARS-CoV-2.
Maternal Knowledge and Child Health

Abstract The first three years of life are of prime importance from the development point of view, so care during this stage has crucial influence on child’s growth and development. The present longitudinal study was conducted on 120 rural children from birth to eighteen months of age from Hisar district of Haryana. Mothers of these children were interviewed for prevalent child care practices followed by them. Solomon’s Experimental-control group was used for assessing the impact of intervention. The experimental group was imparted intervention related to feeding practices, immunization and morbidity through visual packages, video cassette, slides and folders. Individual and group sessions were conducted as per requirement. Results indicated that impact of intervention on the mother’s knowledge was found increasing in experimental group than their counterparts. Feeding practices adopted by the family were also found to be better and improvement in immunization status was also noted in experimental group. Positive impact of intervention was found on morbidity status of children in both the post testings.
EFEK DAUN SIRIH ( PIPER BETLE L.) TERHADAP PENYEMBUHANLUKA INSISI KULIT KELINCI(Oryctolagus cuniculus)

Abstract: Kind of research on betel leaf was done as response to growing empirical reality in society, the exploit of betel leaf for treatment and cure disease. As with antibiotics, betel leaf also has antiseptic power, because of a variety of substances contained in them. Saponins and tannins are as an antiseptic on the injury surface, working as a bacteriostatic normally used for infections of the skin, mucosa and against infection Injury. This research aimed to determine the effects of betel leaf on injury healing of rabbit skin incision. This research uses experimental methods, by using 4 rabbits as test animals. Right and left of back rabbit incision along the 5 cm and a depth of 2 mm. Injuries on the right backare given betel leafs while on the left back are not given betel leafs. Giving betel leafs and length measurements injury must done every day for 2 weeks. From the experimental results, rabbit skinincisionweregivenbetelleafdry fasterandthe incisionhealedcompared withthose not givenbetel leaf.The conclusionthatthe provision ofbetelleafhas the effect ofaccelerating injury healing ofrabbit skinincision. Keyword : betel leaf, incision wound Abstrak: Berbagai penelitian terhadap daun sirih dilakukan sebagai reaksi atas kenyataan empiris yang terus berkembang di masyarakat, yaitu memanfaatkan daun sirih untuk pengobatan dan penyembuhan penyakit. Seperti halnya dengan antibiotika, daun sirih juga mempunyai daya antiseptik. Saponin dan tannin bersifat sebagai antiseptik pada luka permukaan, bekerja sebagai bakteriostatik yang biasanya digunakan untuk infeksi pada kulit, mukosa dan melawan infeksi pada luka. Penelitian ini bertujuan untuk mengetahui efek pemberian daun sirih terhadap penyembuhan luka insisi kulit kelinci. Penelitian ini menggunakan metode eksperimental, dengan menggunakan 4 ekor kelinci sebagai hewan uji. Punggung kanan dan kiri kelinci diinsisi sepanjang 5 cm dan kedalamam 2 mm. Luka pada punggung kanan diberi daun sirih sedangkan luka pada punggung kiri tidak diberi daun sirih. Pemberian daun sirih dan pengukuran panjang luka dilakukan setiap hari selama 2 minggu. Dari hasil percobaan luka insisi kulit kelinci yang diberi daun sirih lebih cepat kering dan sembuh dibandingkan dengan luka insisi yang tidak diberi daun sirih. Kesimpulan yang didapat yaitu pemberian daun sirih memiliki efek untuk mempercepat penyembuhan luka insisi kulit kelinci. Keyword : daun sirih, luka insisi
Orodental manifestations in ectodermal dysplasia—A review

Oral signs and symptoms are present in most ectodermal dysplasias (EDs). The aim of this article is to summarize some of the literature on current knowledge of oral manifestations and orofacial function in EDs. The review will focus on the most common forms where dental manifestations can be crucial for a differential diagnosis of ED among individuals with hypodontia and oligodontia, and preferably where the investigations included persons who had a genetically verified diagnosis. Disturbances in tooth development are common and can appear as tooth agenesis, variations in size and shape of teeth, defects in the mineralized tissues, and problems in tooth eruption. Abnormalities in number, size, and shape of teeth, and reduced salivary secretion, present in isolated oligodontia as well as in hypohidrotic ED and incontinentia pigmenti. In some more rare EDs these symptoms appear in combination with clefts of lip and/or palate in some affected individuals. Leukokeratosis in the oral mucosa presents in 70% of genetically confirmed cases of pachyonychia congenita. Also, orofacial function is often affected in ED, due to malformations, an incomplete dentition, and low salivary secretion which can compromise chewing, swallowing, and speech. In conclusion, there is a clinical overlap in oral signs and symptoms between isolated oligodontia and the most common EDs. Studies with genetically confirmed diagnoses and larger cohorts, as well as multicenter collaboration and the establishing of international registries, would create a basis for refined diagnostics, where oral examinations should be an integrated part of clinical assessment. © 2014 Wiley Periodicals, Inc.
Sialic Acid Associated with αvβ3 Integrin Mediates HIV-1 Tat Protein Interaction and Endothelial Cell Proangiogenic Activation*

Background: HIV-1 Tat engages αvβ3, leading to endothelial cell (EC) proangiogenic activation. Results: Sialic acid (NeuAc)-binding lectins and neuraminidase partially inhibit Tat/αvβ3 interaction and consequent EC proangiogenic activation. Conclusion: Endothelial αvβ3-associated NeuAc is involved in Tat interaction and consequent EC proangiogenic activation. Significance: Integrin-associated NeuAc can be considered a target for the development of new treatments for angiogenesis/AIDS-associated pathologies. Sialic acid (NeuAc) is a major anion on endothelial cells (ECs) that regulates different biological processes including angiogenesis. NeuAc is present in the oligosaccharidic portion of integrins, receptors that interact with extracellular matrix components and growth factors regulating cell adhesion, migration, and proliferation. Tat is a cationic polypeptide that, once released by HIV-1+ cells, accumulates in the extracellular matrix, promoting EC adhesion and proangiogenic activation by engaging αvβ3. By using two complementary approaches (NeuAc removal by neuraminidase or its masking by NeuAc-binding lectin from Maackia amurensis, MAA), we investigated the presence of NeuAc on endothelial αvβ3 and its role in Tat interaction, EC adhesion, and proangiogenic activation. αvβ3 immunoprecipitation with biotinylated MAA or Western blot analysis of neuraminidase-treated ECs demonstrated that NeuAc is associated with both the αv and the β3 subunits. Surface plasmon resonance analysis demonstrated that the masking of αvβ3-associated NeuAc by MAA prevents Tat/αvβ3 interaction. MAA and neuraminidase prevent αvβ3-dependent EC adhesion to Tat, the consequent FAK and ERK1/2 phosphorylation, and EC proliferation, migration, and regeneration in a wound-healing assay. Finally, MAA inhibits Tat-induced neovascularization in the ex vivo human artery ring sprouting assay. The inhibitions are specific because the NeuAc-unrelated lectin from Ulex europaeus is ineffective on Tat. Also, MAA and neuraminidase affect only weakly integrin-dependent EC adhesion and proangiogenic activation by fibronectin. In conclusion, NeuAc is associated with endothelial αvβ3 and mediates Tat-dependent EC adhesion and proangiogenic activation. These data point to the possibility to target integrin glycosylation for the treatment of angiogenesis/AIDS-associated pathologies.
PDZ Domain-containing 1 (PDZK1) Protein Regulates Phospholipase C-β3 (PLC-β3)-specific Activation of Somatostatin by Forming a Ternary Complex with PLC-β3 and Somatostatin Receptors*

Background: The four PLC-β subtypes (β1–β4) have different roles in GPCR-mediated signaling despite having similar structures and regulatory modes. Results: PDZK1 mediates the physical coupling of PLC-β3 to SSTRs using different PDZ domains. Conclusion: PLC-β3 is specifically involved in SSTR-mediated signaling via its interaction with PDZK1. Significance: The subtype-specific role of PLC-β is mediated by differential interactions with PDZ proteins and GPCRs. Phospholipase C-β (PLC-β) is a key molecule in G protein-coupled receptor (GPCR)-mediated signaling. Many studies have shown that the four PLC-β subtypes have different physiological functions despite their similar structures. Because the PLC-β subtypes possess different PDZ-binding motifs, they have the potential to interact with different PDZ proteins. In this study, we identified PDZ domain-containing 1 (PDZK1) as a PDZ protein that specifically interacts with PLC-β3. To elucidate the functional roles of PDZK1, we next screened for potential interacting proteins of PDZK1 and identified the somatostatin receptors (SSTRs) as another protein that interacts with PDZK1. Through these interactions, PDZK1 assembles as a ternary complex with PLC-β3 and SSTRs. Interestingly, the expression of PDZK1 and PLC-β3, but not PLC-β1, markedly potentiated SST-induced PLC activation. However, disruption of the ternary complex inhibited SST-induced PLC activation, which suggests that PDZK1-mediated complex formation is required for the specific activation of PLC-β3 by SST. Consistent with this observation, the knockdown of PDZK1 or PLC-β3, but not that of PLC-β1, significantly inhibited SST-induced intracellular Ca2+ mobilization, which further attenuated subsequent ERK1/2 phosphorylation. Taken together, our results strongly suggest that the formation of a complex between SSTRs, PDZK1, and PLC-β3 is essential for the specific activation of PLC-β3 and the subsequent physiologic responses by SST.
Life in varying environments: experimental evidence for delayed effects of juvenile environment on adult life history.

1. The effects of environment experienced during early development on phenotype as an adult has started to gain vast amounts of interest in various taxa. Some evidence on long-term effects of juvenile environment is available, but replicated experimental studies in wild animals are still lacking. 2. Here we report the first replicated experiment in wild mammals which examines the long-term effects of juvenile and adult environments on individual fitness (reproduction, survival and health). The early development of bank vole (Myodes glareolus) individuals took place in either food-supplemented or un-supplemented outdoor enclosures. After the summer, adult individuals were reciprocally changed to either a similar or opposite resource environment to overwinter. 3. Adult environment had an overriding effect on reproductive success of females so that females overwintering in food-supplemented enclosures had a higher probability of breeding and advanced the initiation of breeding. However, the characteristics of their litters were determined by juvenile environment: females initially grown in food-supplemented conditions subsequently produced larger litters with bigger pups and a male-biased sex ratio. 4. In males, individuals growing in un-supplemented conditions had the highest survival irrespective of adult environment during winter, whereas in females, neither the juvenile nor adult environments affected their survival significantly. The physiological condition of voles in spring, as determined by haematological parameters, was also differentially affected by juvenile (plasma proteins and male testosterone) and adult (haematocrit) environments. 5. Our results suggest that (i) life-history trajectories of voles are not strictly specialized to a certain environment and (ii) the plastic life-history responses to present conditions can actually be caused by delayed effects of the juvenile environment. More generally, the results are important for understanding the mechanisms of delayed life-history effects as well as recognizing their population dynamic consequences.
Periventricular nodular heterotopia in Smith‐Magenis syndrome

Smith‐Magenis syndrome (SMS) is caused by an interstitial microdeletion of chromosome 17p11.2. A few patients with the typical SMS phenotype have RAI1 gene mutations. The syndrome is characterized by minor craniofacial anomalies, short stature, sleep disturbances, behavioural and neurocognitive abnormalities, as well as variable multisystemic manifestations. Periventricular nodular heterotopia (PNH) is a genetically heterogeneous neuronal migration disorder characterized by subependymal heterotopic nodules, and is variably associated with other brain malformations, epileptic seizures and intellectual disability. Here we report on two patients harboring deletions of the 17p11.2 region in whom the SMS typical phenotype was associated with bilateral PNH. Our observations expand the spectrum of chromosomal rearrangements associated with PNH and indicate that abnormal neuronal migration may contribute to the neurocognitive phenotype of SMS. © 2014 Wiley Periodicals, Inc.