Miracle-dz/UniFAR-FTUs huggingface dataset:
Mosaic structural variation in children with developmental disorders

Delineating the genetic causes of developmental disorders is an area of active investigation. Mosaic structural abnormalities, defined as copy number or loss of heterozygosity events that are large and present in only a subset of cells, have been detected in 0.2–1.0% of children ascertained for clinical genetic testing. However, the frequency among healthy children in the community is not well characterized, which, if known, could inform better interpretation of the pathogenic burden of this mutational category in children with developmental disorders. In a case–control analysis, we compared the rate of large-scale mosaicism between 1303 children with developmental disorders and 5094 children lacking developmental disorders, using an analytical pipeline we developed, and identified a substantial enrichment in cases (odds ratio = 39.4, P-value 1.073e − 6). A meta-analysis that included frequency estimates among an additional 7000 children with congenital diseases yielded an even stronger statistical enrichment (P-value 1.784e − 11). In addition, to maximize the detection of low-clonality events in probands, we applied a trio-based mosaic detection algorithm, which detected two additional events in probands, including an individual with genome-wide suspected chimerism. In total, we detected 12 structural mosaic abnormalities among 1303 children (0.9%). Given the burden of mosaicism detected in cases, we suspected that many of the events detected in probands were pathogenic. Scrutiny of the genotypic–phenotypic relationship of each detected variant assessed that the majority of events are very likely pathogenic. This work quantifies the burden of structural mosaicism as a cause of developmental disorders.
The Optical Design of the Human Eye: a Critical Review

Cornea, lens and eye models are analyzed and compared to experimental findings to assess properties and eventually unveil optical design principles involved in the structure and function of the optical system of the eye. Models and data often show good match but also some paradoxes. The optical design seems to correspond to a wide angle lens. Compared to conventional optical systems, the eye presents a poor optical quality on axis, but a relatively good quality off-axis, thus yielding higher homogeneity for a wide visual field. This seems the result of an intriguing combination of the symmetry design principle with a total lack of rotational symmetry, decentrations and misalignments of the optical surfaces.
Relationship between ABO Blood Group and Hemorrhage: A Systematic Literature Review and Meta-Analysis

Abstract Several studies have suggested that patients with non–O blood group have an increased risk of both venous and arterial thromboembolic events. On the contrary, the role of ABO blood group on the risk of bleeding complications remains unclear. Thus, we performed a meta-analysis of the literature with the aim of assessing this potential association. MEDLINE and Embase databases were searched from 1946 to March 2012. Studies comparing the prevalence of different ABO blood groups in bleeding patients as well as in controls without bleeding complications were potentially includible. Two reviewers independently selected studies and extracted study characteristics, quality, and outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each trial and pooled using a random-effects model. Twenty-two studies totalling 9,468 bleeding patients and more than 450,000 controls were included. The prevalence of O blood group was significantly higher in bleeding patients than in controls, with a resulting pooled OR of 1.33 (95% CI = 1.25 to 1.42; p < 0.001). The result of this meta-analysis of a very large sample of bleeding patients and controls suggests that O blood group is a potentially important genetic risk factor for bleeding. High-quality prospective studies are warranted to confirm these preliminary findings.
Dry sliding wear characteristics of 0.13 wt. % carbon steel

Wear characteristics of 0.13 wt. % plain carbon steel, heat treated under various conditions, were monitored on a standard pin-on-disk wear testing machine under the normal loads of 2.5, 4.5 and 5.5 kg and at a constant sliding velocity of 1 m/s. Weight loss of the specimen was measured at various time intervals to obtain wear rate. The variation in volume loss with sliding distance indicated the presence of run-in wear followed by steady state wear. The wear mechanism was found to be primarily oxidative in nature, which was confirmed by the analysis of worn surfaces and wear debris generated during sliding. Wear resistance was found to be dependent on the microstructure and morphology of the phases. The wear coefficients calculated for various heat-treated specimens revealed that the ferrite-coarse pearlite, ferrite-fine pearlite, ferrite-tempered martensite and ferrite martensite structures show the wear resistance in decreasing order.
Preventing cerebral palsy in preterm labour: a multiorganisational quality improvement approach to the adoption and spread of magnesium sulphate for neuroprotection

Magnesium sulphate has been demonstrated to be an effective neuroprotectant for babies delivered prematurely (under 37 weeks’ gestational age). Antenatal administration reduces infant mortality and cerebral palsy (CP); however, uptake in the UK has been significantly lower than other countries. A quality improvement (QI) project (PReventing Cerebral palsy in Pre Term labour (PReCePT)) was carried out in the West of England, UK, to raise awareness of evidence and to improve the uptake of magnesium sulphate as neuroprotectant in preterm deliveries. Five National Health Service (NHS) Trusts and the West of England Academic Health Science Network participated in the QI project. The project was underpinned by a multifaceted QI approach that included: patient and clinical coproduction of resources; recruitment of clinical champions to support the local microsystems and create a stimulating/supporting environment for change; Plan, Do, Study, Act cycles; training for over 600 NHS staff and awareness raising and strategic influencing of key leaders. A baseline audit and regular measurement of the number of eligible women receiving magnesium sulphate was undertaken at each hospital site, and the overall programme was evaluated using data from an international benchmarking organisation for neonatal care outcomes—the Vermont Oxford Network. During the project 664 staff received magnesium sulphate training. The use of magnesium sulphate increased across the West of England from an average baseline of 21% over the 2 years preceding the project to 88% by the conclusion of the project. The project was also able to influence the development of a national data collection process for benchmarking the use of magnesium sulphate for neuroprotection in preterm deliveries in the U.K. PReCePT appears to have had a favourable effect on the uptake of magnesium sulphate across the West of England. The project has also provided learning about how to stimulate adoption and spread of evidence using a QI approach across a network.
Novel Zinc-Attenuating Compounds as Potent Broad-Spectrum Antifungal Agents with In Vitro and In Vivo Efficacy

ABSTRACT An increase in the incidence of rare but hard-to-treat invasive fungal pathogens as well as resistance to the currently available antifungal drugs calls for new broad-spectrum antifungals with a novel mechanism of action. Here we report the identification and characterization of two novel zinc-attenuating compounds, ZAC307 and ZAC989, which exhibit broad-spectrum in vitro antifungal activity and in vivo efficacy in a fungal kidney burden candidiasis model. The compounds were identified serendipitously as part of a drug discovery process aimed at finding novel inhibitors of the fungal plasma membrane proton ATPase Pma1. Based on their structure, we hypothesized that they might act as zinc chelators. Indeed, both fluorescence-based affinity determination and potentiometric assays revealed these compounds, subsequently termed zinc-attenuating compounds (ZACs), to have strong affinity for zinc, and their growth inhibitory effects on Candida albicans and Aspergillus fumigatus could be inactivated by the addition of exogenous zinc to fungal growth media. We determined the ZACs to be fungistatic, with a low propensity for resistance development. Gene expression analysis suggested that the ZACs interfere negatively with the expression of genes encoding the major components of the A. fumigatus zinc uptake system, thus supporting perturbance of zinc homeostasis as the likely mode of action. With demonstrated in vitro and in vivo antifungal activity, low propensity for resistance development, and a novel mode of action, the ZACs represent a promising new class of antifungal compounds, and their advancement in a drug development program is therefore warranted.
Legal and Regulatory Considerations Associated with Use of Patient-Generated Health Data from Social Media and Mobile Health (mHealth) Devices

Summary Patient-generated health data are coming into broader use across the health care spectrum and hold great promise as a means to improve care and health outcomes. At the same time, rapid evolution in the social media and mobile health (mHealth) market has promoted an environment in which creation and transmission of personal health information is easy, quick, and appealing to patients. However, adoption of social media and mHealth by providers is hampered by legal and regulatory concerns with regard to data ownership and data use. This article defines common forms of patient-generated health data (PGHD) and describes how PGHD is used in clinical settings. It explores issues related to protection of personal health information, including that of children and adolescents, data security, and other potential barriers such as physician licensure. It also discusses regulatory and legal considerations providers and patients should consider before using social media and mobile health apps. Citation: Petersen C, DeMuro P. Legal and regulatory considerations associated with use of patient-generated health data from social media and mobile health (mHealth) devices. Appl Clin Inf 2015; 6: 16–26 http://dx.doi. org/10.4338/ACI-2014-09-R-0082
Influence of reinforcement structure on the flexural properties of sandwich composite panels

Abstract New types of sandwich panels were built by filling foam in woven spacer fabric and combining the epoxy resin on the surface. To investigate the effect of the fabric structure on the flexural property of panels, different types of spacer fabrics were woven with reinforcing material, technical polyester filaments. Then the new types of composite panels were built, and the flexural property of each type of sandwich composite panels was tested. The analysis indicated that the flexural strength first increased and then decreased with increase of the bonding yarn density showing parabola tendency. It was proved that the flexural strength reached the maximum when the binding yarn density rose to 1·99 ends cm−2 by regression analysis. The flexural load of the panels increased with the increase of the bonding yarn height. Different failure behaviours were found for different type of composite panels.
PACSIN2 accelerates nephrin trafficking and is up-regulated in diabetic kidney disease

Nephrin is a core component of podocyte (glomerular epithelial cell) slit diaphragm and is required for kidney ultrafiltration. Down‐regulation or mislocalization of nephrin has been observed in diabetic kidney disease (DKD), characterized by albuminuria. Here, we investigate the role of protein kinase C and casein kinase 2 substrate in neurons 2 (PACSIN2), a regulator of endocytosis and recycling, in the trafficking of nephrin and development of DKD. We observe that PACSIN2 is up‐regulated and nephrin mislocalized in podocytes of obese Zucker diabetic fatty (ZDF) rats that have altered renal function. In cultured podocytes, PACSIN2 and nephrin colocalize and interact. We show that nephrin is endocytosed in PACSIN2‐positive membrane regions and that PACSIN2 overexpression increases both nephrin endocytosis and recycling. We identify rabenosyn‐5, which is involved in early endosome maturation and endosomal sorting, as a novel interaction partner of PACSIN2. Interestingly, rabenosyn‐5 expression is increased in podocytes in obese ZDF rats, and, in vitro, its overexpression enhances the association of PACSIN2 and nephrin. We also show that palmitate, which is elevated in diabetes, enhances this association. Collectively, PACSIN2 is up‐regulated and nephrin is abnormally localized in podocytes of diabetic ZDF rats. In vitro, PACSIN2 enhances nephrin turnover apparently via a mechanism involving rabenosyn‐5. The data suggest that elevated PACSIN2 expression accelerates nephrin trafficking and associates with albuminuria. —Dumont, V. , Tolvanen, T. A. , Kuusela, S. , Wang, H. , Nyman, T. A. , Lindfors, S. , Tienari, J., Nisen, H. , Suetsugu, S. , Plomann, M. , Kawachi, H. , Lehtonen, S. PACSIN2 accelerates nephrin trafficking and is up‐regulated in diabetic kidney disease. FASEB J. 31, 3978–3990 (2017). www.fasebj. org—Dumont, Vincent, Tolvanen, Tuomas A. , Kuusela, Sara, Wang, Hong, Nyman, Tuula A. , Lindfors, Sonja, Tienari, Jukka, Nisen, Harry, Suetsugu, Shiro, Plomann, Markus, Kawachi, Hiroshi, Lehtonen, Sanna PACSIN2 accelerates nephrin trafficking and is up‐regulated in diabetic kidney disease. FASEB J. 31, 3978–3990 (2017)
Hydrostatic Parameters and Domain Effects in Novel 2-2 Composites Based on PZN-0.12PT Single Crystals

A novel 0.88Pb(Zn1/3Nb2/3)O3-0.12PbTiO3 crystal/polymer composite with 2-2 connectivity is studied at variable orientations of spontaneous polarisation vector of the crystal component. Orientation and volume-fraction dependences of the hydrostatic piezoelectric coefficients dh*, eh*, and gh* and hydrostatic electromechanical coupling factor kh* are related to the important role of the piezoelectric and elastic anisotropy of single-domain layers of the 2-2 composite. The record value of |eh∗|≈77 C/m2 near the absolute-minimum point and the correlation between the hydrostatic (eh*) and piezoelectric (e3j*) coefficients and between the hydrostatic (gh*) and piezoelectric (g3j*) coefficients are first established. This discovery is of value for hydrostatic and piezotechnical applications. The hydrostatic performance of the composite based on the single-domain 0.88Pb(Zn1/3Nb2/3)O3-0.12PbTiO3 crystal is compared to the performance of the 2–2 composites based on either the same polydomain crystal or the related single-domain crystal.
Clostridium butyricum regulates visceral hypersensitivity of irritable bowel syndrome by inhibiting colonic mucous low grade inflammation through its action on NLRP6

Visceral hypersensitivity induced by stress is quite common in irritable bowel syndrome (IBS) patients. Probiotics play an important role in reducing visceral hypersensitivity in IBS patients. However, the mechanism has not been clearly elucidated. In this study, we investigated the role of nod-like receptor pyrin domain-containing protein 6 (NLRP6) in Clostridium butyricum-regulated IBS induced by stress. Our results showed that NLRP6 was down-regulated in IBS group colon tissues. In addition, IL-18, IL-1β, myeloperoxidase (MPO), d-lactic acid (D-LA), and CD172a were up-regulated in the IBS group of colonic mucous. IL-18 and IL-1β were also increased after the NLRP6 gene was silenced. Pathological score suggested low inflammation of colonic mucous rather than terminal ileum. Water-avoidance stress (WAS) showed visceral hypersensitivity to colonic distension. However, treatment with Clostridium butyricum reversed these results, exerting a beneficial effect. In conclusion, Clostridium butyricum may exert a beneficial action on visceral hypersensitivity of IBS by inhibiting low grade inflammation of colonic mucous through its action on NLRP6.
Targeted Haplotype Comparisons between South African Wheat Cultivars Appear Predictive of Pre-harvest Sprouting Tolerance

Pre-harvest sprouting (PHS) has been a serious production constraint for over two decades, especially in the summer rainfall wheat production regions of South Africa. It is a complex genetic trait controlled by multiple genes, which are significantly influenced by environmental conditions. This complicates the accurate prediction of a cultivar's stability in terms of PHS tolerance. A number of reports have documented the presence of major QTL on chromosomes 3A and 4A of modern bread wheat cultivars, which confer PHS tolerance. In this study, the SSR marker haplotype combination of chromosomes 3A and 4A of former and current South African cultivars were compared with the aim to select for improved PHS tolerance levels in future cultivars. A total of 101 wheat cultivars, including a susceptible cultivar and five international tolerant sources, were used in this study. These cultivars and donors were evaluated for their PHS tolerance by making use of a rain simulator. In addition, five seeds of each entry were planted out into seedling trays and leaf material harvested for DNA isolation. A modified CTAB extraction method was used before progressing to downstream PCR applications. Eight SSR markers targeted from the well-characterized 3A and 4A QTL regions associated with PHS tolerance, were used to conduct targeted haplotype analysis. Additionally, recently published KASP SNP markers, which identify the casual SNP mutations within the TaPHS1 gene, were used to genotype the germplasm. The haplotype marker data and phenotypic PHS data were compared across all cultivars and different production regions. A relative change in observed phenotypic variation percentage was obtained per marker allele and across marker haplotype combinations when compared to the PHS susceptible cultivar, Tugela-DN. Clear favorable haplotypes, contributing 40–60% of the variation for PHS tolerance, were identified for QTL 3A and 4A. Initial analyses show haplotype data appear to be predictive of PHS tolerance status and germplasm can now be selected to improve PHS tolerance. These haplotype data are the first of its kind for PHS genotyping in South Africa. In future, this can be used as a tool to predict the possible PHS tolerance range of a new cultivar.
Sampling efficiency in digital camera performance standards

One of the first ISO digital camera standards to address image microstructure was ISO 12233, which introduced the SFR, spatial frequency response, based on the analysis of edge features in digital images. The SFR, whether derived from edges or periodic signals, describes the capture of image detail as a function of spatial frequency. Often during camera testing, however, there is an interest in distilling SFR results down to a single value that can be compared with acceptable tolerances. As a measure of limiting resolution, it has been suggested that the frequency at which the SFR falls to, e.g., 10%, can be used. We use this limiting resolution to introduce a sampling efficiency measure, being considered under the current ISO 12233 standard revision effort. The measure is the ratio of limiting resolution frequency to that implied by the image (sensor) sampling alone. The rationale and details of this measure are described, as are example measurements. One-dimensional sampling efficiency calculations for multiple directions are included in a two-dimensional analysis.
Use of Sealants in Pancreatic Surgery: Critical Appraisal of the Literature

Background/Aims: Fibrin sealants containing both fibrin and thrombin have been used to control bleeding, reinforce suture lines and enhance tissue healing. However, the literature provides contradictory results. Methods: A systematic literature search was performed to determine the use of fibrin sealants in pancreatic surgery. These articles were then critically appraised according to their methodologies, outcomes and conclusions. Results: Twenty-four studies were found, including 6 controlled randomized trials. Of these, 16 studies were analyzed. Many methodological flaws and lack of consistency in definitions were found, making comparisons between studies difficult if not impossible. Conclusion: Because of the heterogeneity and lack of high-level evidence, the current literature does not allow us any conclusion: neither is there proof that fibrin sealants are of any real utility in pancreatic surgery, nor that they do not work. Further large-scale controlled trials are necessary before concluding that they do or do not provide any advantages in pancreatic surgery.
Digital Control Techniques Based on Voltage Source Inverters in Renewable Energy Applications: A Review

In the modern era, distributed generation is considered as an alternative source for power generation. Especially, need of the time is to provide the three-phase loads with smooth sinusoidal voltages having fixed frequency and amplitude. A common solution is the integration of power electronics converters in the systems for connecting distributed generation systems to the stand-alone loads. Thus, the presence of suitable control techniques, in the power electronic converters, for robust stability, abrupt response, optimal tracking ability and error eradication are inevitable. A comprehensive review based on design, analysis, validation of the most suitable digital control techniques and the options available for the researchers for improving the power quality is presented in this paper with their pros and cons. Comparisons based on the cost, schemes, performance, modulation techniques and coordinates system are also presented. Finally, the paper describes the performance evaluation of the control schemes on a voltage source inverter (VSI) and proposes the different aspects to be considered for selecting a power electronics inverter topology, reference frames, filters, as well as control strategy.
A Critical Review of Adolescent Substance Abuse Group Treatments

Objective: Evidence-based social work requires the use of interventions that are supported by good research evidence. This article reviews the empirical research on adolescent alcohol and other drug (AOD) abuse group treatments. Despite the popularity of group work, searches of the academic literature yielded only 13 adolescent group treatments for which AOD use outcomes have been reported. These treatments and the studies that evaluated them are systematically reviewed. Method: Methodological, efficacy rating, and treatment factor criteria are applied to these studies. Results: Statistically significant reductions in pre-, post-, and/or follow-up use rates of one or more substances were reported for 10 of the 13 reviewed treatments, but only two met Chambless and Hollon's (1998) criteria for “possible efficacy. ” Similarities between the two possibly efficacious treatments, as well as among the three treatments with no indication of positive outcomes are described. A major limitation of the studies overall was the lack of group treatment factor descriptions and analyses. Conclusion: If the state of the science is to advance, adolescent AOD group treatment researchers must improve study designs and reporting on group-related treatment factors. Based on the limited information provided, treatment factors and/or active ingredients that may distinguish effective vs. ineffective group work are discussed. Finally, the evidence suggests that group work is a viable modality for treating adolescent AOD abuse despite recent concerns to the contrary. Recommendations for advancing the state of the science are made.