Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of Variants in 15 Genes in 87 Unrelated Chinese Patients with Leber Congenital Amaurosis

Background Leber congenital amaurosis (LCA) is the earliest onset and most severe form of hereditary retinal dystrophy. So far, full spectrum of variations in the 15 genes known to cause LCA has not been systemically evaluated in East Asians. Therefore, we performed comprehensive detection of variants in these 15 genes in 87 unrelated Han Chinese patients with LCA. Methodology/Principal Findings The 51 most frequently mutated exons and introns in the 15 genes were selected for an initial scan using cycle sequencing. All the remaining exons in 11 of the 15 genes were subsequently sequenced. Fifty-three different variants were identified in 44 of the 87 patients (50.6%), involving 78 of the 88 alleles (11 homozygous and 56 heterozygous variants). Of the 53 variants, 35 (66%) were novel pathogenic mutations. In these Chinese patients, variants in GUCY2D are the most common cause of LCA (16.1% cases), followed by CRB1 (11.5%), RPGRIP1 (8%), RPE65 (5.7%), SPATA7 (4.6%), CEP290 (4.6%), CRX (3.4%), LCA5 (2.3%), MERTK (2.3%), AIPL1 (1.1%), and RDH12 (1.1%). This differs from the variation spectrum described in other populations. An initial scan of 55 of 215 PCR amplicons, including 214 exons and 1 intron, detected 83.3% (65/78) of the mutant alleles ultimately found in these 87 patients. In addition, sequencing only 9 exons would detect over 50% of the identified variants and require less than 5% of the labor and cost of comprehensive sequencing for all exons. Conclusions/Significance Our results suggest that specific difference in the variation spectrum found in LCA patients from the Han Chinese and other populations are related by ethnicity. Sequencing exons in order of decreasing risk is a cost-effective way to identify causative mutations responsible for LCA, especially in the context of genetic counseling for individual patients in a clinical setting.
Evaluation of Six Patients with Pulmonary Carcinosarcoma with a Literature Review

Background. Carcinosarcoma of the lung is a rare malignant neoplasm. We evaluated the diagnosis and treatment of six carcinosarcoma cases, including a synchronous tumour and a solitary pulmonary tumour, along with the clinical and histological features and survival times. Methods. From a retrospective analysis of 1076 non-small-cell lung cancer resections performed between January 1996 and January 2011, six patients (0.5%) with pulmonary carcinosarcoma (all males; mean age 58 years; range 53–66) who underwent surgical treatment were studied. Results. The mean tumour pathological T diameter was 7.2 cm (median 6 cm, range 3–14.5 cm). Only one patient was diagnosed with carcinosarcoma preoperatively. The clinical presentation and tumour localisations differed. The operations performed were a lobectomy (n = 4), pneumonectomy (n = 1), and bilobectomy (n = 1). Histologically, the epithelial characteristics of the tumours were consistent with squamous cell carcinoma in most of the patients. A complete resection was performed in all six patients. No mortality occurred in the early postoperative period. The median survival time was 9 (3–25) months. Conclusion. The preoperative diagnosis of carcinosarcoma of the lung is difficult due to the composition of the different histopathological structures. Complete surgical resection is the treatment of choice for pulmonary carcinosarcoma, although further studies are needed.
Pilot Study to Evaluate Hearing Aid Service Delivery Model and Measure Benefit Using Self-Report Outcome Measures Using Community Hearing Workers in a Developing Country

Hearing loss is a major handicap in developing countries with paucity of trained audiologists and limited resources. In this pilot study trained community health workers were used to provide comprehensive hearing aid services in the community. One hundred and eleven patients were fitted with semi-digital hearing aid and were evaluated over a period of six months. They were assessed using self-report outcome measure APHAB. Results show that trained CHWs are effective in detecting disabling hearing loss and in providing HAs. APHAB can identify and pick up significant improvements in communication in daily activities and provides a realistic expectation of the benefits of a hearing aid. The model of using trained CHWs to provide rehabilitative services in audiology along with self-report outcome measures can be replicated in other developing countries.
Effectiveness of caterpillar defenses against three species of invertebrate predators

The efficacies of larval defenses against invertebrate predators representing different (but overlapping) foraging guilds were compared by offering 34 species (287 individuals) of lepidopteran larvae to Paraponera clavata ants, Apiomerus pictipes bugs, and Polistes instabilis wasps. Overall, the ants were the most likely to eat caterpillar prey, and the wasps were the most cautious. Larval chemistry and diet breadth were significant predic- tors of rejection by the group of predators; chemically defended specialist herbivores were better protected than generalist herbivores without known chemical defenses. These results provide evidence for the poten- tial importance of predators in maintaining diet breadth of phytophagous insects, and they suggest that plant chemistry is part of a mechanism for restricting diet breadth. Other important larval defenses included size, morphology, and coloration. Large prey (heavier than 1 g) were less acceptable than smaller prey (lighter than 200 mg) for the wasps and bugs but not for the ants; hairs deterred predation by the ants and bugs but not by the wasps; and brightly colored caterpillars were frequently rejected by the wasps but not by the ants and bugs.
Quality of life and baseline characteristics associated with depressive symptoms among patients with heart disease

We sought to examine factors associated with depressive symptoms among patients with heart disease. Data from 197 patients admitted for coronary artery disease were examined using multivariate predictive models. Women and unmarried patients were more likely to report depressive symptoms. In multivariate models, we observed that depressive symptoms were associated with the level of tangible social (but not emotional) support, bodily pain, and vitality, but not the number of comorbidities, gender, or marital status.
Epididymal Region-Specific miRNA Expression and DNA Methylation and Their Roles in Controlling Gene Expression in Rats

Region-specific gene expression is an intriguing feature of the mammalian epididymis. This unique property is essential for sperm maturation and storage, and it also implicates stringent and multi-level regulations of gene expression. Over the past decade, the androgen-driven activation of epididymal gene transcription has been extensively studied. However, it still remains largely unexplored whether and how other regulatory mechanisms, such as miRNAs and DNA methylation, are involved in controlling regional gene expression in the epididymis. Using microarray-based approaches, we studied the regional miRNA expression and DNA methylation profiles in 4 distinct epididymal regions (initial segment, caput, corpus and cauda) of rats. We found that the miR-200 family members were more expressed in caput, compared with cauda. By GSEA analysis, the differential expression of miR-200 family between caput and cauda was shown to be negatively correlated with their predicted target genes, among which 4 bona fide targets were verified by luciferase reporter assay. Predicted target genes of miR-200 family have enriched functions in anti-apoptosis, cell transportation and development, implying the regional diversity in epididymal functions. On the other hand, we revealed epididymal DNA methylation of 2002 CpG islands and 2771 gene promoters (-3.88-0.97kb), among which 1350 (67.43%) CpG islands and 2095 (75.60%) promoters contained region-specific DNA methylation. We observed significant and distinct functional enrichment in genes with specifically methylated promoters in each epididymal regions, but these DNA methylations did not show significant correlation with repressed gene transcription in the mature epididymis. Conclusively, we investigated the regional miRNA expression and DNA methylation in the rat epididymis and revealed a potential role of miR-200 family in gene expression regulation between caput and cauda. This may contribute to the distinct physiological function in sperm maturation / storage of caput / cauda epididymis.
Evolutionary Conditions in Dissipative MHD Systems Revisited

The evolutionary conditions of dissipative continuous magnetohydrodynamic (MHD) shocks are studied. We modify Hada’s approach to the stability analysis of the MHD shock waves. The matching conditions between perturbed shock structure and asymptotic wave modes show that all types of the MHD shocks, including intermediate shocks, are evolutionary and perturbed solutions are uniquely defined. We also adapt our formalism to MHD shocks in systems with resistivity but no viscosity, which is often used in numerical simulations, and we show that all types of shocks found in such systems satisfy the evolutionary conditions and perturbed solutions are uniquely defined. These results suggest that intermediate shocks may appear in physical systems.
TSI ultrasound elastography for the diagnosis of chronic allograft nephropathy in kidney transplanted patients

Purpose To answer the question whether the TSI (tissue strain imaging) sonoelastography technique can contribute to the diagnosis of chronic renal allograft damage. Material and methods A prospective study of 112 patients between June 2010 and April 2011 was conducted to compare elastography data with biopsy results and laboratory parameters in order to determine whether any correlations exist. Elastography parameters were acquired with a high-end ultrasound system and analyzed using the semiquantitative strain ratio. For comparison, patients were divided into three groups based on biopsy findings (Banff classification): group A: biopsy not necessary; group B: Banff grade I; group C: Banff grades II and III. Correlations were assessed by means of correlation (Pearson) and regression analysis. Differences between ordinal groups were tested for statistical significance by the Mann-Whitney U test. Results Mean patient age was 54.2 ± 15.01 years. Fifty-nine percent of the patients were male. The calculated TSI strain ratio of groups A and C differed significantly (p = 0.024). Groups B and C (p = 0.056) and groups A and B (p = 0.88) showed no significant difference. The TSI strain ratio did not correlate with glomerular filtration rate (r = 0.105) or creatinine (r = 0.092). Conclusion The TSI sonoelastography technique can contribute to the differentiation of different stages of renal graft damage (according to Banff classification). However, significant results were not observed for all investigated features. The TSI technique should be further evaluated in future studies including larger numbers of patients.
Morphologic Variability of the Shoulder between the Populations of North American and East Asian

Background The aim of this study was to determine if there were significant differences in glenohumeral joint morphology between North American and East Asian populations that may influence sizing and selection of shoulder arthroplasty systems. Methods Computed tomography reconstructions of 92 North American and 58 East Asian patients were used to perform 3-dimensional measurements. The proximal humeral position was normalized in all patients by aligning it with the scapular plane utilizing anatomic landmarks. Measurements were performed on the humerus and scapula and included coronal and axial humeral head radius, humeral neck shaft and articular arc angles, glenoid height and width, and critical shoulder angle. Glenohumeral relationships were also measured and included lateral distance to the greater tuberosity and acromion, abduction lever arm, and acromial index. Parametric and nonparametric statistical analyses were used to compare population metrics. Results East Asian glenohumeral measurements were significantly smaller for all linear metrics (p < 0.05), with the exception of acromial length, which was greater than in the North American cohort (p < 0.001). The increase in acromial length affected all measurements involving the acromion including abduction lever arms. No difference was found between the neck shaft and articular angular measurements. Conclusions The East Asian population exhibited smaller shoulder morphometrics than their North American cohort, with the exception of an extended acromial overhang. The morphologic data can provide some additional factors to consider when choosing an optimal shoulder implant for the East Asian population, in addition to creating future designs that may better accommodate this population.
Phenotypic variation in Acidovorax radicisN35 influences plant growth promotion.

Acidovorax radicis N35, isolated from surface-sterilized wheat roots (Triticum aestivum), showed irreversible phenotypic variation in nutrient broth, resulting in a differing colony morphology. In addition to the wild-type form (rough colony type), a phenotypic variant form (smooth colony type) appeared at a frequency of 3.2 × 10(-3) per cell per generation on NB agar plates. In contrast to the N35 wild type, the variant N35v showed almost no cell aggregation and had lost its flagella and swarming ability. After inoculation, only the wild-type N35 significantly promoted the growth of soil-grown barley plants. After co-inoculation of axenically grown barley seedlings with differentially fluorescently labeled N35 and N35v cells, decreased competitive endophytic root colonization in the phenotypic variant N35v was observed using confocal laser scanning microscopy. In addition, 454 pyrosequencing of both phenotypes revealed almost identical genomic sequences. The only stable difference noted in the sequence of the phenotype variant N35v was a 16-nucleotide deletion identified in a gene encoding the mismatch repair protein MutL. The deletion resulted in a frameshift that revealed a new stop codon resulting in a truncated MutL protein missing a functional MutL C-terminal domain. The mutation was consistent in all investigated phenotype variant cultures and might be responsible for the observed phenotypic variation in A. radicis N35.
Astrocytes from the Contused Spinal Cord Inhibit Oligodendrocyte Differentiation of Adult Oligodendrocyte Precursor Cells by Increasing the Expression of Bone Morphogenetic Proteins

Promotion of remyelination is an important therapeutic strategy to facilitate functional recovery after traumatic spinal cord injury (SCI). Transplantation of neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) has been used to enhance remyelination after SCI. However, the microenvironment in the injured spinal cord is inhibitory for oligodendrocyte (OL) differentiation of NSCs or OPCs. Identifying the signaling pathways that inhibit OL differentiation in the injured spinal cord could lead to new therapeutic strategies to enhance remyelination and functional recovery after SCI. In the present study, we show that reactive astrocytes from the injured rat spinal cord or their conditioned media inhibit OL differentiation of adult OPCs with concurrent promotion of astrocyte differentiation. The expression of bone morphogenetic proteins (BMP) is dramatically increased in the reactive astrocytes and their conditioned media. Importantly, blocking BMP activity by BMP receptor antagonist, noggin, reverse the effects of active astrocytes on OPC differentiation by increasing the differentiation of OL from OPCs while decreasing the generation of astrocytes. These data indicate that the upregulated bone morphogenetic proteins in the reactive astrocytes are major factors to inhibit OL differentiation of OPCs and to promote its astrocyte differentiation. These data suggest that manipulation of BMP signaling in the endogenous or grafted NSCs or OPCs may be a useful therapeutic strategy to increase their OL differentiation and remyelination and enhance functional recovery after SCI.
Accurate Document Categorization of OCR-Generated Text

The purpose of this research was to examine the application of the Latent Semantic Indexing (LSI) algorithm to the categorization of Optical Character Recognition (OCR)-generated documents (or text). LSI is a robust dimensionality reduction technique for the processing of textual data. The technique can be applied to collections of documents independent of subject matter or language. Given a collection of documents, LSI indexing can be employed to create a vector space in which both the documents and their constituent terms can be represented. In practice, vector spaces of several hundred dimensions are typically employed. The resulting vector space possesses some unique properties that make it well suited to a range of information-processing problems. Of particular interest to the document conversion community is the fact that the technique is highly resistant to noise in text that is generated by the OCR conversion process. Noise in OCR-generated documents nominally takes the form of missing characters or improperly interpreted characters that result in word misspellings. Normally, human operators are employed to perform corrective post processing of noisy OCR-generated text prior to categorization or other document workflow processes that require highly accurate text (e.g., Boolean searches). A technology such as LSI that could eliminate human review and editing of OCR-generated text, while maintaining highly accurate categorization or information retrieval rates, would result in a dramatic increase in workflow throughput with substantial labor savings.
How does the choice of A-level subjects vary with students' socio-economic status in English state schools?

The reasons why students from lower socio-economic groups are under-represented at high status universities are not yet entirely understood, but evidence suggests that part of the gap may be a consequence of differential choice of A-levels by social background. The Russell Group of universities has since 2011 published guidance on A-level subject choices, describing some A-levels as ‘facilitating’ in that choosing these helps keep the largest number of Russell Group degree courses open. The numbers of students gaining AAB in facilitating subjects has subsequently been developed as a performance measure for individual schools and sixth form colleges, and, in aggregate, as a government Social Mobility Indicator. While it is clear that there is a gap between the proportions of students in maintained and private schools achieving this measure, there is little other work to date on how social background is related to the take-up of facilitating subjects, or to a more fine-grained categorization of all the large number of ‘non-facilitating’ subjects. I develop a taxonomy of all 96 A-levels certified for English students in 2014/15 beyond the facilitating/non-facilitating dichotomy according to Russell Group members’ expressed preferences, and use it to analyse the A-level subject choices of three A-level cohorts (2010–2012), using National Pupil Database data. I find that large differentials in A-level subject choice exist by social background, particularly for facilitating subjects. These differentials substantially disappear when GCSE attainment and subject choices are taken into account. Closing this choice gap at A-level is likely therefore to depend on reducing differentials in attainment and subject choice by social background at GCSE. The introduction of the EBacc may help with the GCSE subject choice element.
A Model of Competitive Stock Trading Volume

A model of competitive stock trading is developed in which investors are heterogeneous in their information and private investment opportunities and rationally trade for both informational and noninformational motives. I examine the link between the nature of heterogeneity among investors and the behavior of trading volume and its relation to price dynamics. It is found that volume is positively correlated with absolute changes in prices and dividends. I show that informational trading and noninformational trading lead to different dynamic relations between trading volume and stock returns.
Molecular basis for memory storage and addiction

This thesis is mainly divided into two parts. In the first part, a mathematical model of the bistable switch is developed with the help of which a zone is defined where the CaMKII − PP1 switch remains bistable. For each pair of CaMKII and PP1, the critical stimulus concentration and the active CaMKII concentration is calculated which leads to autophosphorylation of CaMKII. The change in the critical stimulus and active CaMKII with respect to CaMKII and PP1 is also plotted. The critical stimulus concentration increases in a linear manner with change in CaMKII and PP1 for the upper limit while it changes randomly for the lower limits. For active CaMKII, the change is of sigmoidal nature in case of both upper and lower limits for CaMKII and PP1. A novel correlation is developed for measuring the critical stimulus intensity required for CaMKII to undergo direct autophosphorylation which leads to long term memory formation with a goodness of fit 99.74 %. In the second part of the thesis, a mechanism is proposed for the inhibition of morphine on long-term potentiation of GABA-A mediated synaptic transmission (LTP-GABA). Morphine binding on µ − opioid receptors on the presynaptic GABAergic cells results in inhibition of activation of sGC by blocking the NO binding site. Retrogradely travelling NO is not able to bind sGC and activates it in the presence of morphine which results in the inhibition of activation of cGMP and PKG. As a result, LTP-GABA is not produced which increases the chances of addiction. A mathematical model is presented for morphine inhibition on LTP-GABA and its implication in addiction. A two step model of sGC activation is used, where morphine inhibits the NO during the first step and consequently blocks sGC activation. The dependence of morphine inhibition on various parameters such as morphine dissociation, morphine concentration, NO removal and rate of inhibition is also studied.