Miracle-dz/UniFAR-FTUs huggingface dataset:
Incorporating molecular and functional context into the analysis and prioritization of human variants associated with cancer

BACKGROUND AND OBJECTIVE With recent breakthroughs in high-throughput sequencing, identifying deleterious mutations is one of the key challenges for personalized medicine. At the gene and protein level, it has proven difficult to determine the impact of previously unknown variants. A statistical method has been developed to assess the significance of disease mutation clusters on protein domains by incorporating domain functional annotations to assist in the functional characterization of novel variants. METHODS Disease mutations aggregated from multiple databases were mapped to domains, and were classified as either cancer- or non-cancer-related. The statistical method for identifying significantly disease-associated domain positions was applied to both sets of mutations and to randomly generated mutation sets for comparison. To leverage the known function of protein domain regions, the method optionally distributes significant scores to associated functional feature positions. RESULTS Most disease mutations are localized within protein domains and display a tendency to cluster at individual domain positions. The method identified significant disease mutation hotspots in both the cancer and non-cancer datasets. The domain significance scores (DS-scores) for cancer form a bimodal distribution with hotspots in oncogenes forming a second peak at higher DS-scores than non-cancer, and hotspots in tumor suppressors have scores more similar to non-cancers. In addition, on an independent mutation benchmarking set, the DS-score method identified mutations known to alter protein function with very high precision. CONCLUSION By aggregating mutations with known disease association at the domain level, the method was able to discover domain positions enriched with multiple occurrences of deleterious mutations while incorporating relevant functional annotations. The method can be incorporated into translational bioinformatics tools to characterize rare and novel variants within large-scale sequencing studies.
3D Face Reconstruction via Feature Point Depth Estimation and Shape Deformation

Since a human face can be represented by a few feature points (FPs) with less redundant information, and calculated by a linear combination of a small number of prototypical faces, we propose a two-step 3D face reconstruction approach including FP depth estimation and shape deformation. The proposed approach can reconstruct a realistic 3D face from a 2D frontal face image. In the first step, a coupled dictionary learning method based on sparse representation is employed to explore the underlying mappings between 2D and 3D training FPs, and then the depth of the FPs is estimated. In the second step, a novel shape deformation method is proposed to reconstruct the 3D face by combining a small number of most relevant deformed faces by the estimated FPs. The proposed approach can explore the distributions of 2D and 3D faces and the underlying mappings between them well, because human faces are represented by low-dimensional FPs, and their distributions are described by sparse representations. Moreover, it is much more flexible since we can make any change in any step. Extensive experiments are conducted on BJUT_3D database, and the results validate the effectiveness of the proposed approach.
Delayed puberty: experience of a tertiary care centre in India

Abstract Background: Pubertal delay can be a manifestation of a wide variety of diseases, the proportions of which may vary between developing and industrialised countries. Objective: A retrospective study was undertaken to investigate the aetiology of delayed puberty in northern India. Subjects and Methods: Follow-up records of patients with delayed puberty presenting to the endocrine clinic between 2003 and 2007 were analysed. Results: Forty-two patients (19 boys, 23 girls, age range 14–27 y) of 46 who initially presented had complete evaluation. The main causes of pubertal delay were chronic systemic illnesses (16), e.g. malnutrition, anaemia and chronic infections, hormone deficiencies (11), hypergonadotrophic hypogonadism (7) and constitutional delay (6). While the majority of girls (11/23) were found to have underlying systemic disorders, endocrinopathies (6/19) were the major causes of pubertal delay in boys. Conclusion: Chronic systemic illnesses are the major cause of pubertal delay in developing countries. Social awareness and education leading to early detection and treatment can prevent pubertal delay in a large proportion of cases.
Spatial Face Context with Gender Information for Group Photo Similarity Assessment

Spatial arrangements of people in a photo reflect how people regard themselves in a group. Comparing spatial arrangements of subjects in two group photos can help computer understand similar social semantics and events. In this paper, we incorporate gender information with spatial arrangements of subjects to assess the visual similarity between two group photos. For each group photo, detected faces are represented by a spatial face context. Then, corresponding vertices of spatial face contexts of two group photos are retrieved by graph matching. Gender information and relative face positions are applied to the graph matching results to compute the similarity score. The experimental results show that our method can identify group photos with similar genders of subjects and spatial arrangements compared to the state-of-the-art methods.
Mortality of persons with intellectual disability in residential care in Israel 1991-1997

In Israel, the Division for Mental Retardation provides service to 6022 persons (all ages) in 53 residential centres, 1280 persons in community-related residential facilities, and about 13,000 persons who participate in day care facilities. This accounts for about 20,000 persons out of the Israeli population of approximately six million. Every case of death in a residential facility is reported immediately to the Office of the Medical Director, who reviews and decides upon any further investigation. In case of suspected malpractice, a review committee is appointed. Each case of death in an institution is also investigated immediately by the local police, who decide upon the need for an autopsy. The present study reports on the number of deaths for the period 1991-1997 in Israeli residential centres. Some 450 deaths were reported, corresponding to a mortality rate of 10.25 deaths per 1000 population per year. The number of deaths compared with those in the general population. Information on the age and sex distribution, level of intellectual disability, ethnic background and cause of death is presented.
Prevention of vitamin D deficiency in mothers and infants worldwide — a paradigm shift

Abstract Vitamin D deficiency in mothers and infants is a global health disorder despite recognition that it is preventable. Recent data support the theory that vitamin D deficiency in adults and children may increase the risk of infections and auto-immune diseases. In most cases, vitamin D deficiency is caused by sunlight deprivation and inadequate corrective vitamin D intake. There is a strong mother/infant vitamin D relationship that affects vitamin D status both in utero and in infancy. Recognition that vitamin D deficiency is a worldwide mother/infant health problem is a basis on which to modify public health strategies to reduce the burden of disease and improve maternal and child vitamin D nutrition. This review provides an update on vitamin D function and the global scope and implications of vitamin D deficiency as it relates to pregnancy and infancy. It also addresses a combined strategy to prevent vitamin D deficiency during pregnancy, lactation and infancy.
The management of cochlear nerve deficiency

Abstract The assessment process is critical in deciding whether a profoundly deaf child with cochlear nerve deficiency (CND) will be suitable for a cochlear or auditory brainstem implant (ABI). Magnetic resonance imaging (MRI) using submillimetric T2 weighted gradient echo or turbo spin echo sequences is mandatory for all profoundly deaf children to diagnose CND. Evidence of audition on behavioural or electrophysiological tests following both auditory and electrical stimulation sometimes allows identification of significant auditory tissue not visible on MRI. In particular electric auditory brainstem response (EABR) testing may allow some quantification of auditory tissue and help decide whether a cochlear implant will be beneficial. Age and cognitive development are the most critical factors in determining ABI benefit. Hearing outcomes from both cochlear implants and ABIs are variable and likely to be limited in children with CND. A proportion of children will get no benefit. Usually the implants would be expected to provide recognition of environmental sounds and understanding of simple phonetics. Most children will not develop normal speech and they will often need to learn to communicate with sign language. The ABI involves a major neurosurgical procedure and at present the long term outcomes are unknown. It is therefore essential that parents who are considering this intervention have plenty of time to consider all aspects and the opportunity for in depth discussion.
CI outcomes in children: Are the NICE guidelines appropriate for adults?

Introduction Currently the NICE guidelines allow adults to be offered NHS funding for unilateral cochlear implantation if they meet the audiological criteria of thresholds of 90 dBHL or worse at 2 and 4 kHz bilaterally, and obtain insufficient benefit from hearing aids, defined as scoring lower than 50% on BamfordKowal-Bence (BKB) sentence testing in quiet conditions (NICE Technical Appraisal Guidance (TAG166), 2009). There is evidence to indicate this criteria is too restrictive and as a result, adults who are predicted to have a successful outcome from implantation are being turned away (Lamb and Archbold, 2013). For children under the age of 19 years, the NICE definition of inadequate benefit from hearing aids is judged according to whether the multi-disciplinary team consider that their speech, language, and listening skills are delayed due to their hearing loss. As such we are able to offer implant(s) to these young people who score higher than 50% on BKB testing. The RNTNE Cochlear Implant Department and St Thomas’Hearing Implant Centre have collaborated to present the outcomes in 16 older children who did not meet adult BKB speech perception criteria, but who went on to have cochlear implantation based on the paediatric criteria. We will discuss whether the outcomes from these children can be used as supporting evidence towards relaxation of the adult criteria.
The role of the Utah Artificial Ear project in the development of the modern cochlear implant

Abstract The cochlear implant has provided the first substantial restoration of a human sense by a medical intervention. This accomplishment was brought about by the efforts, over a 50+ year period, of many individuals in laboratories around the world. In this paper, we recount the history of one of the early projects – the Utah Artificial Ear project. In 1970 researchers at the University of Utah began work on an auditory prosthesis. A critical early decision was to create a ‘transparent’ link between external signal processing and the electrodes implanted in the cochlea, i.e., a percutaneous pedestal. The pedestal allowed D. Eddington, then a graduate student, to conduct, in 1975–1978, the first thorough, parametric, psychophysical studies of electrical stimulation of the cochlea in multiple human volunteers. The early work by Eddington and colleagues evolved in 1983 into the 4-channel, Ineraid cochlear implant. Many years later, highly effective, modern signal processing algorithms, e.g., continuous interleaved sampling (CIS), fine structure processing (FSP), and virtual channel processing, were first tested and developed with the aid of Ineraid patients fit with pedestals of the Utah design. Because for many years the Ineraid provided as high a level of speech understanding as that provided by other devices and because the percutaneous pedestal allowed the first testing of many modern signal processing algorithms, the Utah Artificial Ear project may be viewed as one of the most valuable research projects in the history of cochlear implants.
Comparison of outcomes in children with hearing aids and cochlear implants

Abstract Objectives The purpose of this study was to document the performance of a group of children with moderately severe to severe hearing loss who use hearing aids on a range of speech recognition, speech–language, and literacy measures and to compare these results to children with severe to profound hearing loss, who have learned language through cochlear implants. Methods This study involved 41 children with bilateral sensorineural hearing impairment, aged 6–18 years. Twenty children had moderately severe/severe hearing loss and used hearing aids, and 21 had severe to profound hearing loss and used cochlear implants. Communication and academic skills were assessed using speech recognition tests and standardized measures of speech production, language, phonology, and literacy. Results The two groups did not differ in their open-set speech recognition abilities or speech production skills. However, children with hearing aids obtained higher scores than their peers with cochlear implants in the domains of receptive vocabulary, language, phonological memory, and reading comprehension. The findings also indicate that children with moderately severe or severe hearing loss can develop spoken language skills that are within the range expected for normal hearing children. Conclusions School-aged children with moderately severe and severe hearing loss performed better in several domains than their peers with profound hearing loss who received cochlear implants between age 2 and 5 years. Further research is required to evaluate the benefits of hearing aids and cochlear implants in children with hearing loss who are diagnosed and receive intervention within the first year of life.
Screening for latent tuberculosis infection: performance of tuberculin skin test and interferon-γ release assays under real-life conditions

Objectives To characterise optimal screening strategies for latent tuberculosis infection (LTBI) prior to the initiation of anti-tumour necrosis factor therapy. Methods Patients in 62 German rheumatology centres were evaluated for LTBI. Each patient was screened with a tuberculin skin test (TST) and one form of an interferon-γ release assay (IGRA), either TSPOT.TB (TSPOT) or Quantiferon TB Gold (QFT). Results A total of 1529 patients with rheumatological disease were tested with a TST, 844 with TSPOT and 685 with QFT. TST was positive in 11.3% (n=173). The prevalence of LTBI was 8.0% when defined as a positive TST and no previous Bacille Calmette-Guérin (BCG) vaccination and 7.9% when based on a positive IGRA. Combining both estimates increased the prevalence of LTBI to 11.1%. Clinical risk factors for LTBI were found in 122 patients (34 with a history of prior TB, 81 close contacts and 27 with suggestive chest x-ray lesions). A compound risk factor (CRF) was defined as the presence of at least one of these three risk factors. Statistical analyses were conducted to examine the association between CRF and LTBI test outcomes. In multivariate analysis, TST was influenced by CRF (OR 6.2; CI 4.08 to 9.44, p<0.001) and BCG vaccination status (OR 2.9; CI 2.00 to 4.35, p<0.001). QFT and TSPOT were only influenced by CRF (QFT: OR 2.6; CI 1.15 to 5.98, p=0.021; TSPOT: OR 8.7; CI 4.83 to 15.82, p<0.001). ORs and the agreement of TST and IGRA test results varied by rheumatological disease. Conclusion LTBI test results in an individual patient need to be considered in the context of prior BCG vaccination and clinical risk factors. In patient populations with low rates of TB incidence and BCG vaccination, the use of both TST and IGRA may maximise sensitivity in detecting LTBI but may also reduce specificity.
Clinical and pathological significance of interleukin 6 overexpression in systemic sclerosis

Objective To determine the potential clinical and pathological significance of altered expression of interleukin 6 (IL-6) in systemic sclerosis (SSc). Methods Serum IL-6 and soluble IL-6 receptor levels were measured in patients with SSc (n=68) and healthy controls (n=15). Associations between serum IL-6 level and C reactive protein, platelet count and key clinical outcomes in SSc were explored. Expression of IL-6 in skin biopsies was also examined and western blot and reverse transcription PCRanalysis were performed using cultured dermal fibroblasts. The effect of IL-6 trans-signalling on production of extracellular matrix proteins was assessed and downstream signalling pathways were examined using pharmacological inhibitors. Results Serum IL-6 level was frequently elevated in patients with SSc, particularly in those with diffuse cutaneous SSc (dcSSc) with thrombocytosis and elevated acute phase markers. Prominent expression in the skin was observed in dermal fibroblasts, mononuclear cells and endothelial cells in patients with early dcSSc. In vitro experiments supported a potent profibrotic effect of IL-6 trans-signalling via the JAK2/STAT3 and ERK pathways. High IL-6 expression early in dcSSc appears to be associated with more severe skin involvement at 3 years and worse long-term survival than in those without elevated IL-6 levels. Conclusion Our results confirm the overexpression of IL-6 in dcSSc and support the potential of IL-6 as a surrogate marker for clinical outcome in this disease. The data also provide rationale for clinical studies targeting IL-6 trans-signalling as a potential antifibrotic therapy for SSc.
Sun Protection for Children: A Review

Chronic ultraviolet exposure results in premature skin aging (photoaging), dyspigmentation, sallow color, textural changes, loss of elasticity, and premalignant actinic keratoses. UVB radiation is mainly responsible for acute damages such as sunburn, and long-term damage including melanoma. Today the sun's ultraviolet radiation (UVR) induced skin cancer is a major issue worldwide. History of sun exposure and sunburns are the most important behavioral risks. Childhood sun exposure is considered as a substantial risk because a child’s skin has a thinner stratum corneum, lower levels of protective melanin, and a higher surface area to body-mass-ratio. Thus, protection against UVR in childhood is essential. Research has shown that people who have had a sunburn in childhood or were in the sun unprotected are more likely to have skin cancer. In this article, we review the literature to address the protection of children against sun and skin cancer.
Constant light induces alterations in melatonin levels, food intake, feed efficiency, visceral adiposity, and circadian rhythms in rats

Abstract Melatonin levels, metabolic parameters, circadian rhythm activity patterns, and behavior were observed in rats subjected to a 12-h/12-h light/dark cycle (LD) compared to animals exposed to continuous dark (DD) or continuous light (LL). LD and DD animals were similar in melatonin levels, food intake, relative food intake, feed efficiency, water intake, circadian activity levels, and behavior. LL animals had lower melatonin levels in the subjective dark compared to LD and DD animals. Food intake, relative food intake, and water intake values were lower and feed efficiency was more positive in LL animals compared to LD and DD animals. In addition, LL animals exhibited greater visceral adiposity than the other two groups. The circadian rhythmicity of activity became free-running in LL animals and there was a decrease in overall activity. Notable behavioral changes in LL animals were an increase in irritability and excitability. Results indicate that a decrease in melatonin levels and concomitant changes in metabolism, circadian rhythms, and behavior are consequences of exposure to constant light.
The preventive efficacy of methylcobalamin on rat peripheral neuropathy influenced by diabetes via neural IGF-1 levels

Abstract We investigated the preventive efficacy of exogenous methylcobalamin on sciatic nerve IGF-1 expression down-regulation and peripheral nerve deficit under different conditions (hyperglycemia and duration) of experimental diabetes in rats. Hyperglycemia was induced with streptozotocin, and stratified by exogenous insulin into mild and severe conditions. Duration of diabetes was ranged from 2–12 weeks. A single dose of methylcobalamin was intramuscularly administrated. Three groups of rats were compared in this study: (i) control group (NC, n = 30); (ii) saline-treated control diabetic group (n = 30); and (iii) methylcobalamin-treated diabetic group (n = 30). The study demonstrated a progressive decrease of sciatic nerve IGF-1 mRNA and peptide contents, and peripheral nerve dysfunction in the saline-treated diabetics over 12 weeks in contrast to the normal control non-diabetics (P < 0.01–0.0025). The IGF-1 reduction was delayed, which was consistent with retardation in nerve velocity conduction and structural impairment, in the methylcobalamin-treated diabetics, especially with mild hyperglycemia and shorter duration as compared with the saline-treated diabetics (P < 0.05–0.01). No effect of methylcobalamin on blood glucose was shown in the treated groups. It is concluded that exogenous methylcobalamin delayed onset of diabetic peripheral neuropathy via up-regulation of neural IGF-1 gene expression, and a better neuroprotective effect could be achieved in the presence of good control of hyperglycemia, especially at early stage of diabetes.
Early malnutrition diffusely affects children contrast sensitivity to sine-wave gratings of different spatial frequencies

Abstract Cognitive, behavioral and neurophysiological deficits, associated with malnutrition, are described in the literature. The aim of this study was to evaluate the visual contrast sensitivity in children with early malnutrition, classified according to the anthropometric parameters of Waterlow. Visual contrast sensitivity of 16 boys from 7–10 years old was measured using the staircase psychophysical method, using vertical sine-wave gratings of 0.25, 1.0, 2.0 and 8.0 cycles per degree (cpd) of visual angle. Malnourished children were approximately 3.3, 10.9 and 6.6 times less sensitive to the frequencies of 0.25, 1.0 and 2.0 cpd, respectively, although they were approximately 1.1 times more sensitive to the frequency of 8.0 cpd. It is likely that early malnutrition adversely affected the magnocellular pathway on the one hand, since early malnourished children needed more contrast to detect low and low-to-medium frequencies; on the other hand, early malnutrition did not affect the parvocellular pathway, since there was an increase of sensitivity to the highest frequency.