Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of machine learning algorithms as integrative tools for validation of next generation sequencing data.

OBJECTIVE While next generation sequencing (NGS) has become the technology of choice for clinical diagnostics, most genetic laboratories still use Sanger sequencing for orthogonal confirmation of NGS results. Previous studies have shown that when the quality of NGS data is high, most calls are indicated by Sanger sequencing, making confirmation redundant. We aimed at establishing a set of criteria that make it possible to distinguish NGS calls that need orthogonal confirmation from those that do not would significantly decrease the amount of work necessary to reach a diagnosis. MATERIALS AND METHODS A data set of 7976 NGS calls confirmed as true or false positive by Sanger sequencing was used to train and test different machine learning (ML) approaches. By varying the size and class balance of the training dataset, we measured the performance of the different algorithms to determine the conditions under which ML is a valid approach for confirming NGS calls in a diagnostic environment. RESULTS Our results indicate that machine learning is a valid approach to find variant calls that need more investigation, but in order to reach the high accuracy required in a clinical environment, the training data set must include enough observations and these observations must be well-balanced between true/false positive NGS calls. CONCLUSIONS Our results show that it is possible to integrate the diagnostic NGS validation workflow with a machine learning approach to reduce the number of Sanger confirmations of high- quality NGS calls, reducing the time and costs of diagnosis.
A brief diet intervention can reduce symptoms of depression in young adults – A randomised controlled trial

There is strong epidemiological evidence that poor diet is associated with depression. The reverse has also been shown, namely that eating a healthy diet rich in fruit, vegetables, fish and lean meat, is associated with reduced risk of depression. To date, only one randomised controlled trial (RCT) has been conducted with elevated depression symptoms being an inclusion criterion, with results showing that a diet intervention can reduce clinical levels of depression. No such RCTs have been performed in young adults. Young adults with elevated levels of depression symptoms and who habitually consume a poor diet were randomly allocated to a brief 3-week diet intervention (Diet Group) or a habitual diet control group (Control Group). The primary and secondary outcome measures assessed at baseline and after the intervention included symptoms of depression (Centre for Epidemiological Studies Depression Scale; CESD-R; and Depression Anxiety and Stress Scale– 21 depression subscale; DASS-21-D), current mood (Profile of Mood States), self-efficacy (New General Self-Efficacy Scale) and memory (Hopkins Verbal Learning Test). Diet compliance was measured via self-report questionnaires and spectrophotometry. One-hundred-and-one individuals were enrolled in the study and randomly assigned to the Diet Group or the Control Group. Upon completion of the study, there was complete data for 38 individuals in each group. There was good compliance with the diet intervention recommendations assessed using self-report and spectrophotometry. The Diet group had significantly lower self-reported depression symptoms than the Control Group on the CESD-R (p = 0.007, Cohen’s d = 0.65) and DASS-21 depression subscale (p = 0.002, Cohen’s d = 0.75) controlling for baseline scores on these scales. Reduced DASS-21 depression subscale scores were maintained on follow up phone call 3 months later (p = .009). These results are the first to show that young adults with elevated depression symptoms can engage in and adhere to a diet intervention, and that this can reduce symptoms of depression. The findings provide justification for future research into the duration of these benefits, the impacts of varying diet composition, and their biological basis.
FPGA implementation of a low-power and area-efficient state-table-based compression algorithm for DSLR cameras

Small image acquisition devices like digital single lens reflex (DSLR) cameras most commonly use Joint Photographic Expects Group (JPEG) coding standard for lossy compression. Although JPEG is a simple coding standard, its compression efficiency is very low as compared to any typical state-of-the-art image coding standards like set partitioning in hierarchical trees (SPIHT). In this paper, a novel state-table-based SPIHT (STS) algorithm and its field programmable gate array (FPGA) implementation is proposed. The STS uses two small state-tables and two extremely small lists. The STS not only provides better compression efficiency than the state-of-the-art JPEG 2000 at high bit rates but also requires very small memory to hold the state-tables and lists in comparison to SPIHT. On average STS requires 0.86\% of the memory needed by SPIHT when evaluated for image sizes ranging from 4 Mpixels to 40 Mpixels. The implementation results show that STS consumes very less FPGA area in comparison to SPIHT-based architectures. The dynamic power dissipation of STS is also less than that of JPEG-like compression standards. This makes our proposed algorithm a better candidate for compression in low-power, low-memory digital image acquisition devices.
Quantifying OHIP in the Context with Oral Health Literacy in Rural and Urban Population.

AIM The present study was undertaken to assess the knowledge and awareness of oral health literacy among rural and urban people and to correlate it with the oral health-related quality of life (OHRQoL). MATERIALS AND METHODS The present study was conducted among the rural and urban population visiting the outpatient department. The study questionnaire was used to assess oral health literacy and these questions were framed based on the various aspects like general demographics, dental visit, and dentition status. A validated questionnaire to record the oral health impact profile (OHIP) was used to assess the quality of life. Further, the rapid estimate of adult literacy in dentistry-30 (REALD-30), the word recognition test, was used to assess oral health literacy. RESULTS Out of 1,000 participants, 500 were from the urban population and 500 from a rural area. The mean age of participants in the rural and urban population was 32.22 ± 10.66 and 30.43 ± 10.3, respectively. The mean score of OHIP in rural and urban participants was found to be 6.46 ± 6.815 and 6.34 ± 8.492, respectively. The mean score of REALD-30 in rural and urban participants was found to be 12.88 ± 7.214 and 20.9 ± 7.334, respectively. CONCLUSION Results suggest that dental health literacy have an independent effect on dental health outcomes.
Eruptive squamous cell carcinoma in a patient treated with concomitant pembrolizumab and imiquimod

Pembrolizumab, a humanized monoclonal antibody against programmed cell death 1, is used for various malignant neoplasms. Toll‐like receptor (TLR) agonists, specifically targeting the TLR9 subfamily (TLR7–9), are treatment options for solid tumors and hematological malignancies. We experienced a case of eruptive squamous cell carcinoma (SCC) in a patient treated concomitantly with pembrolizumab and imiquimod, a TLR7 agonist. A 75‐year‐old woman who was given a diagnosis of bladder cancer with lung metastasis received pembrolizumab for 3 months when she was referred to our department for the evaluation of skin rashes on her hands. Her skin lesions were diagnosed as well‐differentiated SCC and treated with topical imiquimod. Two months after the start of imiquimod, more than 10 reddish papules appeared on her hands. The histological diagnosis of a new plaque was the same as an earlier biopsy. We herein describe this case in detail and provide a published work review.
Sorption of Heavy Metal Cations on Mesoporous ZSM-5 and Mordenite Zeolites

Desilication and dealumination techniques were used to obtain mesoporous ZSM-5 and mordenite zeolites. The study provides insight into specific structural, textural, and sorption properties of obtained materials with different Si/Al ratios. Subsequent dealumination and desilication procedures were found to be efficient methods of generating a secondary system of mesopores in mordenite and ZSM-5 crystals while preserving their microporous character. The investigated materials were evaluated in terms of their sorption properties of selected heavy metal cations (Cd2+, Cr3+, and Pb2+). Particular emphasis was placed on the structural examination of the materials via infrared spectroscopy (FT-IR). Other research methods included X-ray diffraction (XRD), X-ray fluorescence (XRF), nuclear magnetic resonance (NMR) and atomic absorption spectrometry (AAS).
Using ESDM 12 hours per week in children with autism spectrum disorder: feasibility and results of an observational study.

BACKGROUND Early intervention for Autism Spectrum Disorder (ASD) in France is heterogeneous and poorly evaluated to date. Early Start Denver Model (ESDM) is a developmental and behavioral model of intervention for toddlers with ASD which has already shown very interesting outcomes on the development of children with ASD in various studies with different settings. However, it is not possible with the current research to agree on the best setting. Thus, we implemented an ESDM program according to our context where children are often pre-schooling early from 30 months old. This therapy was applied by a multidisciplinary team working in close collaboration with parents and other partners. SUBJECTS AND METHODS A prospective observational study including 19 toddlers with ASD was conducted. We evaluated improvement on the cognitive level of toddlers with ASD receiving therapist-delivered ESDM intervention for 12 hours per week. RESULTS Significant improvements in verbal and nonverbal cognitive skills at the Mullen Scale of Early Learning were obtained after 10 months of intervention in our sample. The largest improvement was in receptive language development quotient with a mean improvement of 19.6 points. We also observed promising outcomes in daily adaptive behavior, with a slight improvement in communication at the Vineland Adaptive Behavioral Scale. These outcomes, when compared to the conclusions of previous studies, are leading us to the need for a therapy duration beyond 10 months. CONCLUSIONS Our outcomes were very encouraging even with low cognitive and nonverbal children. These outcomes may be confirmed in a multicenter randomized controlled trial that is ongoing.
Differential DNA methylation correlates with response to methotrexate in rheumatoid arthritis

Abstract Objectives Identifying blood-based biomarkers that predict treatment response in RA is a clinical priority. We investigated differential DNA methylation as a candidate biomarker of response for the first-line drug used in RA, MTX. Methods DNA methylation was measured in DNA samples from individuals recruited to the Rheumatoid Arthritis Medication Study. Differentially methylated positions were compared between whole blood samples collected at baseline and at 4 weeks from patients who, by 6 months, had a good (n = 34) or poor response (n = 34) to MTX using linear modelling, adjusting for gender, age, cell composition, baseline 28-joint disease activity score (DAS28) and smoking status. Analyses also compared methylation with changes in DAS28 and changes in swollen joint count and tender joint count, and changes in CRP over the initial 6 months after MTX commencement. Differentially methylated positions showing significant differences with any response parameter were tested using pyrosequencing in an independent group of 100 patients from the Rheumatoid Arthritis Medication Study. Results In the discovery group, two CpG sites showed methylation changes at 4 weeks associated with clinical EULAR response by 6 months. Significant changes in methylation for three differentially methylated positions associated with change in tender joint counts, three with change in swollen joint count and a further four with change in CRP. Of the 12 CpGs, four showed replicated association in an independent dataset of samples from the Rheumatoid Arthritis Medication Study. Conclusion These data represent an advance on current practice by contributing to a personalized medicine strategy allowing an escalation or change in therapy as early as 4 weeks.
The Reverse Side of a Coin: “Factor-Free” Ribosomal Protein Synthesis In Vitro is a Consequence of the In Vivo Proofreading Mechanism

This paper elucidates a close connection between two well-known facts that until now have seemed independent: (i) the quality control (“proofreading”) of the emerging amino acid sequence, occurring during the normal, elongation-factor-dependent ribosomal biosynthesis, which is performed by removing those Aa-tRNAs (aminoacyl tRNAs) whose anticodons are not complementary to the exhibited mRNA codons, and (ii) the in vitro discovered existence of the factor-free ribosomal synthesis of polypeptides. It is shown that a biological role of proofreading is played by a process that is exactly opposite to the step of factor-free binding of Aa-tRNA to the ribosome-exposed mRNA: a factor-free removal of that Aa-tRNA whose anticodon is not complementary to the ribosome-exhibited mRNA codon.
Emergence, molecular mechanisms and global spread of carbapenem-resistant Acinetobacter baumannii

Acinetobacter baumannii is a nosocomial pathogen that has emerged as a global threat because of high levels of resistance to many antibiotics, particularly those considered to be last-resort antibiotics, such as carbapenems. Although alterations in the efflux pump and outer membrane proteins can cause carbapenem resistance, the main mechanism is the acquisition of carbapenem-hydrolyzing oxacillinase-encoding genes. Of these, oxa23 is by far the most widespread in most countries, while oxa24 and oxa58 appear to be dominant in specific regions. Historically, much of the global spread of carbapenem resistance has been due to the dissemination of two major clones, known as global clones 1 and 2, although new lineages are now common in some parts of the world. The analysis of all publicly available genome sequences performed here indicates that ST2, ST1, ST79 and ST25 account for over 71 % of all genomes sequenced to date, with ST2 by far the most dominant type and oxa23 the most widespread carbapenem resistance determinant globally, regardless of clonal type. Whilst this highlights the global spread of ST1 and ST2, and the dominance of oxa23 in both clones, it could also be a result of preferential selection of carbapenem-resistant strains, which mainly belong to the two major clones. Furthermore, ~70 % of the sequenced strains have been isolated from five countries, namely the USA, PR China, Australia, Thailand and Pakistan, with only a limited number from other countries. These genomes are a vital resource, but it is currently difficult to draw an accurate global picture of this important superbug, highlighting the need for more comprehensive genome sequence data and genomic analysis.
Surgical site infection following cesarean section in a general hospital in Kuwait: trends and risk factors

Abstract Surgical site infections (SSI) are a significant cause of post-surgical morbidity and mortality. The objectives of this study were to determine the prevalence of SSI and identify risk factors for infections following cesarean section (CS). A prospective study of SSI after CS was carried out from January 2014 to December 2016 using the methodology of the American National Nosocomial Infection Surveillance System. Suspected SSIs were confirmed clinically by the surgeon, and or, by culture. Seven thousand two hundred thirty five CS were performed with an overall SSI prevalence of 2.1%, increasing from 1.7% in 2014 to 2.95% in 2016 (P = 0.010). Of 152 cases of SSI, the prevalence of infection was 46.7% in women ⩽30 years and 53.3% in women >30 years (P = 0.119). Of 148 culture samples from as many women, 112 (75.7%) yielded growth of microorganisms with 42 (37.5%) of isolates being multi-drug resistant (MDR). Women who did not receive prophylactic antibiotics (35.5%) developed SSI more often than those who did (P < 0.0001). These findings suggest that emergency CS and inappropriate antibiotic prophylaxis are risk factors for developing SSI. In the light of the emergence of MDR bacteria there is a need to implement revised prophylactic antibiotic policy as part of antimicrobial stewardship to decrease SSI rates.
Implementation of advanced Optimum Contribution Selection in small-scale breeding schemes: prospects and challenges in Vorderwald cattle

Vorderwald cattle are a regional cattle breed from the Black Forest in south western Germany. In recent decades, commercial breeds have been introgressed to upgrade the breed in performance traits. On one hand, native genetic diversity of the breed should be conserved. On the other hand, moderate rates of genetic gain are needed to satisfy breeders to keep the breed. These goals are antagonistic, since the native proportion of the gene pool is negatively correlated to performance traits and the carriers of introgressed alleles are less related to the population. Thus, a standard Optimum Contribution Selection (OCS) approach would lead to reinforced selection on migrant contributions (MC). Our objective was the development of strategies for practical implementation of an OCS approach to manage the MC and native genetic diversity of regional breeds. Additionally, we examined the organisational efforts and the financial impacts on the breeding scheme of Vorderwald cattle. We chose the advanced Optimum Contribution Selection (aOCS) to manage the breed in stochastic simulations based on real pedigree data. In addition to standard OCS approaches, aOCS facilitates the management of the MC and the rate of inbreeding at native alleles. We examined two aOCS strategies. Both strategies maximised genetic gain, while strategy (I) conserved the MC in the breeding population and strategy (II) reduced the MC at a predefined annual rate. These two approaches were combined with one of three flows of replacement of sires (FoR strategies). Additionally, we compared breeding costs to clarify about the financial impact of implementing aOCS in a young sire breeding scheme. According to our results, conserving the MC in the population led to significantly (P < 0.01) higher genetic gain (1.16 ± 0.13 points/year) than reducing the MC (0.88 ± 0.10 points/year). In simulation scenarios that conserved the MC, the final value of MC was 57.6% ± 0.004, while being constraint to 58.2%. However, reducing the MC is only partially feasible based on pedigree data. Additionally, this study proves that the classical rate of inbreeding can be managed by constraining only the rate of inbreeding at native alleles within the aOCS approach. The financial comparison of the different breeding schemes proved the feasibility of implementing aOCS in Vorderwald cattle. Implementing the modelled breeding scheme would reduce costs by 1.1% compared with the actual scheme. Reduced costs were underpinned by additional genetic gain in superior simulation scenarios compared to expected genetic gain in reality (+4.85%).
Cryo‐EM map interpretation and protein model‐building using iterative map segmentation

A procedure for building protein chains into maps produced by single‐particle electron cryo‐microscopy (cryo‐EM) is described. The procedure is similar to the way an experienced structural biologist might analyze a map, focusing first on secondary structure elements such as helices and sheets, then varying the contour level to identify connections between these elements. Since the high density in a map typically follows the main‐chain of the protein, the main‐chain connection between secondary structure elements can often be identified as the unbranched path between them with the highest minimum value along the path. This chain‐tracing procedure is then combined with finding side‐chain positions based on the presence of density extending away from the main path of the chain, allowing generation of a Cα model. The Cα model is converted to an all‐atom model and is refined against the map. We show that this procedure is as effective as other existing methods for interpretation of cryo‐EM maps and that it is considerably faster and produces models with fewer chain breaks than our previous methods that were based on approaches developed for crystallographic maps.
Developmental differences in temporal schema acquisition impact reasoning decisions

ABSTRACT Schemas capture patterns across multiple experiences, accumulating information about common event structures that guide decision making in new contexts. Schemas are an important principle of leading theories of cognitive development; yet, we know little about how children and adolescents form schemas and use schematic knowledge to guide decisions. Here, we show that the ability to acquire schematic knowledge based on the temporal regularities of events increases during childhood and adolescence. Furthermore, we show that temporally mediated schematic knowledge biases reasoning decisions in an age-dependent manner. Participants with greater temporal schematic knowledge were more likely to infer that temporally related items shared other, non-temporal properties, with adults showing the greatest relationship between schema knowledge and reasoning choices. These data indicate that the mechanisms underlying schema formation and expression are not fully developed until adulthood and may reflect the ongoing maturation of hippocampus and prefrontal cortex through adolescence.
Immunohistochemically Detected Expression of ATRX, TSC2, and PTEN Predicts Clinical Outcomes in Patients With Grade 1 and 2 Pancreatic Neuroendocrine Tumors

Supplemental Digital Content is available in the text Objective: The goal of this retrospective study was to clarify the clinical implications of immunohistochemically detected protein expression for genes that are frequently mutated in pancreatic neuroendocrine tumors (PNETs). Background: The clinical management of PNETs is hindered by their heterogenous biological behavior. Whole-exome sequencing recently showed that 5 genes (DAXX/ATRX, MEN1, TSC2, and PTEN) are frequently mutated in PNETs. However, the clinical implications of the associated alterations in protein expression remain unclear. Methods: We collected Grade 1 and 2 (World Health Organization 2017 Classification) primary PNETs samples from 100 patients who underwent surgical resection. ATRX, DAXX, MEN1, TSC2, and PTEN expression were determined immunohistochemically to clarify their relationships with prognosis and clinicopathological findings. Results: Kaplan–Meier analysis indicated that loss of TSC2 (n = 58) or PTEN (n = 37) was associated with significantly shorter overall survival, and that loss of TSC2 or ATRX (n = 41) was associated with significantly shorter recurrence-free survival. Additionally, loss of ATRX or TSC2 was significantly associated with nodal metastasis. In a multivariate analysis, combined loss of TSC2 and ATRX (n = 31) was an independent prognostic factor for shorter recurrence-free survival (hazard ratio 10.1, 95% confidence interval 2.1–66.9, P = 0.003) in G2 PNETs. Conclusions: Loss of ATRX, TSC2, and PTEN expression might be useful as a method of clarifying the behavior and clinical outcomes of Grade 1 and 2 PNETs in routine clinical practice. Combined loss of TSC2 and ATRX had an especially strong, independent association with shorter recurrence-free survival in patients with G2 PNETs. Loss of pairs in ATRX, TSC2, or PTEN would be useful for selecting the candidate for postoperative adjuvant therapy.