Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Variability in Polish Lowland Sheepdogs Assessed by Pedigree and Genomic Data

Simple Summary Dogs are an important part of society. The Polish Lowland Sheepdog (PON) is one of 353 of the world’s largest cynological organization listed dog breeds. Breeds with small population sizes, like the PONs, are often characterized by high inbreeding rates and thus an increased risk of congenital diseases. To examine the endangerment of the PONs, measures for genetic diversity and inbreeding were calculated for the German PON population. The study showed that the PONs had to be classified as a minimally endangered population according to threshold values specified by the European Association for Animal Production. However, the very recent trend showed a slight improvement. Abstract Genetic variability of Polish Lowland Sheepdog (PON) population was evaluated using both pedigree and genomic data. The analyzed pedigree encompassed 8628 PONs, including 153 individuals genotyped on the Illumina CanineHD BeadChip. Runs of homozygosity (ROH) were defined for homozygous stretches extending over 60 to 4300 kb. The inbreeding coefficients FPed based on pedigree data and FROH50 based on ROHs were at 0.18 and 0.31. The correlation between both was 0.41 but 0.52 when excluding animals with less than seven complete generations. The realized effective population size (Ne¯) was 22.2 with an increasing trend over years. Five PONs explained 79% of the genetic diversity of the reference population. The effective population size derived from linkage disequilibrium measured by r² was 36. PANTHER analysis of genes in ROHs shared by ≥50% of the PONs revealed four highly over- or underrepresented biological processes. One among those is the 7.35 fold enriched “forelimb morphogenesis”. Candidate loci for hip dysplasia and patent ductus arteriosus were discovered in frequently shared ROHs. In conclusion, the inbreeding measures of the PONs were high and the genetic variability small compared to various dog breeds. Regarding Ne¯, PON population was minimally endangered according to the European Association for Animal Production.
Additional outreach effort of providing an opportunity to obtain a kit for fecal immunochemical test during the general health check-up to improve colorectal cancer screening rate in Japan: A longitudinal study

Objectives A sufficient screening rate is indispensable to optimize the positive impact of colorectal cancer (CRC) screening. This study aimed to evaluate the effect of an additional outreach of providing an opportunity to obtain a kit for fecal immunochemical test (FIT) during the general health check-up to increase CRC screening rate. Methods This was a longitudinal study using pre-existing data in Kujukuri Town, Japan. The town provided CRC screening in the fiscal year (FY) 2017 using an existing procedure for all beneficiaries of the National Health Insurance, whereas in FY 2018, an additional outreach effort was made to only those with an even number of age (exposed group), who were offered an opportunity to obtain a kit for FIT at the time of general health check-ups but not to those with an odd number of age (control group). To estimate the effectiveness, generalized estimating equation (GEE) with individuals as clusters was performed. Results In total, 3,530 individuals were included (1,708 in the control group and 1,822 in the exposed group). GEE showed significant interaction between the groups (control and exposed) and FYs (2017 and 2018) (p<0.001), indicating that the change in CRC screening rate from 2017 to 2018 was significantly different between the two groups. Although an achieved actual rate of 17.1% in the exposed group in FY 2018 was low, the additional outreach increased the rate by 5.8 percentage point (95% confidence interval, 3.5–8.1) compared with an existing rate. Conclusions Additional outreach of providing an opportunity to obtain a kit for FIT at the time of the general health check-up improved the CRC screening rate. However, screening rate achieved by this strategy remained low, indicating further efforts is required.
Stickler Syndrome: A Review of Clinical Manifestations and the Genetics Evaluation

Stickler Syndrome (SS) is a multisystem collagenopathy frequently encountered by ophthalmologists due to the high rate of ocular complications. Affected individuals are at significantly increased risk for retinal detachment and blindness, and early detection and diagnosis are critical in improving visual outcomes for these patients. Systemic findings are also common, with craniofacial, skeletal, and auditory systems often involved. SS is genotypically and phenotypically heterogenous, which can make recognizing and correctly diagnosing individuals difficult. Molecular genetic testing should be considered in all individuals with suspected SS, as diagnosis not only assists in treatment and management of the patient but may also help identify other at-risk family members. Here we review common clinical manifestation of SS and genetic tests frequently ordered as part of the SS evaluation.
Identification of new susceptibility loci associated with rheumatoid arthritis

Objectives The present study aimed to discover novel susceptibility loci associated with risk of rheumatoid arthritis (RA). Methods We performed a new genome-wide association study (GWAS) in Chinese subjects (1027 RA cases and 2879 controls) and further conducted an expanded meta-analysis with previous GWAS summary data and replication studies. The functional roles of the associated loci were interrogated using publicly available databases. Dual-luciferase reporter and cytokine assay were also used for exploring variant function. Results We identified five new susceptibility loci (IL12RB2, BOLL-PLCL1, CCR2, TCF7 and IQGAP1; pmeta <5.00E−08) with same effect direction in each study cohort. The sensitivity analyses showed that the genetic association of at least three loci was reliable and robust. All these lead variants are expression quantitative trait loci and overlapped with epigenetic marks in immune cells. Furthermore, genes within the five loci are genetically associated with risk of other autoimmune diseases, and genes within four loci are known functional players in autoimmunity, which supports the validity of our findings. The reporter assay showed that the risk allele of rs8030390 in IQGAP1 have significantly increased reporter activity in HEK293T cells. In addition, the cytokine assay found that the risk allele of rs244672 in TCF7 was most significantly associated with increased plasma IL-17A levels in healthy controls. Finally, identified likely causal genes in these loci significantly interacted with RA drug targets. Conclusion This study identified novel RA risk loci and highlighted that comprehensive genetic study can provide important information for RA pathogenesis and drug therapy.
EVEN‐PLUS syndrome: A case report with novel variants in HSPA9 and evidence of HSPA9 gene dysfunction

EVEN‐PLUS syndrome is a rare condition characterized by its involvement of the Epiphyses, Vertebrae, Ears, and Nose, PLUS other associated findings. We report here the fifth case of EVEN‐PLUS syndrome with novel variants c.818 T > G (p.L273X) and c.955C > T (p.L319F) in the HSPA9 gene identified through whole‐exome sequencing. The patient is the first male known to be affected and presented with additional features not previously described with EVEN‐PLUS syndrome. These features include agenesis of the septum pellucidum, a short chest and sternum, 13 pairs of ribs, a single hemivertebra, laterally displaced nipples, hydronephrosis, unilateral cryptorchidism, unilateral single palmar crease, bilateral clubfoot, and hypotonia. qPCR analysis provides supporting evidence for a nonsense‐mediated decay mechanism for the HSPA9 truncating variant. In silico 3D modeling supports the pathogenicity of the c.955C > T (p.L319F) missense variant. The study presented here further describes the syndrome and broadens its mutational and phenotypic spectrum. Our study also lends support to HSPA9 variants as the underlying etiology of EVEN‐PLUS syndrome and ultimately provides a better understanding of the molecular basis of the condition.
Deep-belief network for predicting potential miRNA-disease associations

MicroRNA (miRNA) plays an important role in the occurrence, development, diagnosis and treatment of diseases. More and more researchers begin to pay attention to the relationship between miRNA and disease. Compared with traditional biological experiments, computational method of integrating heterogeneous biological data to predict potential associations can effectively save time and cost. Considering the limitations of the previous computational models, we developed the model of deep-belief network for miRNA-disease association prediction (DBNMDA). We constructed feature vectors to pre-train restricted Boltzmann machines for all miRNA-disease pairs and applied positive samples and the same number of selected negative samples to fine-tune DBN to obtain the final predicted scores. Compared with the previous supervised models that only use pairs with known label for training, DBNMDA innovatively utilizes the information of all miRNA-disease pairs during the pre-training process. This step could reduce the impact of too few known associations on prediction accuracy to some extent. DBNMDA achieves the AUC of 0.9104 based on global leave-one-out cross validation (LOOCV), the AUC of 0.8232 based on local LOOCV and the average AUC of 0.9048 ± 0.0026 based on 5-fold cross validation. These AUCs are better than other previous models. In addition, three different types of case studies for three diseases were implemented to demonstrate the accuracy of DBNMDA. As a result, 84% (breast neoplasms), 100% (lung neoplasms) and 88% (esophageal neoplasms) of the top 50 predicted miRNAs were verified by recent literature. Therefore, we could conclude that DBNMDA is an effective method to predict potential miRNA-disease associations.
GENETIC VARIATION OF SINIPERCA SCHERZERI STEINDACHNER FROM DIFFERENT GEOGRAPHICAL POPULATIONS BY AFLP ANALYSIS

Siniperca scherzeri Steindachner,a high-valued freshwater fish,is endemic in East Asia.However,its natural resource has declined by the destruction on its ecological environment and excessive capture in fisheries.To investigate and understand its overall genetic background,genetic characteristics and divergences of Siniperca scherzeri Steindachner from Yalujiang River,Haihe River,Yangtze River,Qiantangjiang River,Minjiang River and Xijiang River were analyzed by AFLP methods.Eight primer pairs were selected from 64 EcoRⅠ/MseⅠ primer combinations and used for further practical AFLP analysis.Total 211 bands were scored in 65 individuals with 126 polymorphic bands(59.7%),some population specific bands were also observed.The genetic variation of Yangtze population was the highest(6.7%) among 6 populations,and genetic distances of inter-population were higher than that of intra-population.The analysis of molecular variance(AMOVA) showed that there was significantly genetic differentiation among 6 populations(p0.01). NJ analysis showed that each population formed one group independently,the 6 geographic populations could be obviously grouped into two distinct clades.Yalujiang and Haihe populations are clustered in one clade,Yangtze,Qiantangjiang,Minjiang and Xijiang populations are clustered in another clade.The abundance of genetic variance of S.scherzeri in China maybe resulted from accumulation of a large numbers of mutations under wide distribution ranges in different ecosystems.Genetic divergence among 6 geographical populations are significant,moreover,the genetic relationships are consistent with their geographical distribution.The formation of Qinling Mountains,which lies across the central China from west to east,was invoked to explain the distinct divergence between the northern group and the southern group.
Comparative studies on physiological responses to salt stress in tetraploid Paulownia plants

The different physiological responses were studied by comparing their tolerances to 0, 0.2%, 0.4% and 0.6% NaCl concentrations in diploid Paulownia tomentosa(T2), Paulownia tomentosa × Paulownia fortunei(TF2) and tetraploid Paulownia T4and TF4 plants. The results show that the changing trends of physiological and biochemical indexes of the leaves were consistent on the tetraploids and their dipoids with different salt concentrations; The leaf water and chlorophyll content went down with the increase of salt concentration, and the leaf water and chlorophyll content of the tetraploid Paulownia were higher than those of the diploid Paulownia; The relative conductivity and MDA content increased with the increase of salt concentration, and the tetraploids were less than the diploids; The SOD activity and soluble protein content increased f irst and decreased later; The soluble sugar and praline contents increased with the increase of salt concentrations, and the tetraploids were higher than the diploids; The salt resistance of Paulownia was comprehensively evaluated by subordinate function method based on the relationship between physiological-biochemical indices and salt resistance in the soil with 0.6% NaCl; The salt resistance order as followings: TF4 T4 TF2 T2.
LATCH Score at Discharge: A Predictor of Weight Gain and Exclusive Breastfeeding at 6 Weeks in Term Healthy Babies.

INTRODUCTION World Health Organization recommends exclusive breastfeeding (EBF) for 6 months after birth. However, problems with the baby failing to latch properly are common in the postpartum period contributing to breastfeeding cessation. AIMS AND OBJECTIVES To evaluate the utility of LATCH Score to predict EBF and weight gain at 6 weeks postpartum along with an optimum LATCH Score cutoff. METHODS This prospective cohort study was conducted in India. Ninety-three mother-infant dyads at term gestation were enrolled. Two LATCH score assessments were done by a lactation consultant; first within 24 hours of birth and 2 at discharge. Mothers with low LATCH Scores were counselled before discharge. EBF rate and weight gain velocity were analyzed at 6 weeks. RESULTS LATCH Score ≥ 6 at discharge has the highest sensitivity (92.1%) and specificity (66.7%) for predicting EBF at 6 weeks postpartum (RR = 5.63; 95% CI, 4.32-12.65, P = 0.0003). Receiver operating characteristic (ROC) of LATCH Score at discharge and EBF at 6 weeks had an area under the curve (AUC) of 0.785 with a cutoff ≥ 5.5, showing the highest sensitivity of 93.6% with a false positive rate of 30.1%. LATCH Score > 6 at discharge was significantly associated with higher EBF rate (RR = 0.61; 95% CI, 0.39-0.94) and appropriate weight gain (≥ 20 grams/day) at 6 weeks of age (RR = 0.44; 95% CI, 0.25-0.75). After counselling, the LATCH score significantly improved at discharge in mothers (n = 62) with an initial score < 6 (p< 0.001). CONCLUSIONS LATCH Score is a simple tool to identify mothers who require breastfeeding support and counselling before discharge from the hospital to prevent early breastfeeding cessation.
“Because we all have to grow up”: supporting adolescents in Uganda to develop core competencies to transition towards managing their HIV more independently

Sustaining optimal adherence is the major challenge facing adolescents living with HIV (ALHIV), particularly in low‐resource settings, where “second‐line” is often the last accessible treatment option. We explored the knowledge and skills adolescents need in order to maintain improved adherence behaviours, and the specific ways clinicians and caregivers may support young people to do so more independently.
Improved Extraction Efficiency of Antioxidant Bioactive Compounds from Tetraselmis chuii and Phaedoactylum tricornutum Using Pulsed Electric Fields

Pulsed electric fields (PEF) is a promising technology that allows the selective extraction of high-added value compounds by electroporation. Thus, PEF provides numerous opportunities for the energy efficient isolation of valuable microalgal bioactive substances (i.e., pigments and polyphenols). The efficiency of PEF-assisted extraction combined with aqueous or dimethyl sulfoxide (DMSO) solvents in recovering pigments and polyphenols from microalgae Tetraselmis chuii (T. chuii) and Phaeodactylum tricornutum (P. tricornutum) was evaluated. Two PEF treatments were applied: (1 kV/cm/400 pulses, 3 kV/cm/45 pulses), with a specific energy input of 100 kJ/kg. The total antioxidant capacity (TAC) was positively influenced by the use of DMSO. The highest TAC in the T. chuii culture was achieved at a lower extraction time and electric field than for P. tricornutum. The use of DMSO only improved the polyphenols′ extraction for P. tricornutum, whereas the PEF and extraction time were more important for T. chuii. Carotenoids and chlorophyll a were more efficiently extracted using DMSO, while chlorophyll b levels were higher following aqueous extraction for both microalgae. In P. tricornutum, the TAC and pigment extraction efficiency were in general higher at lower extraction times. It can be concluded that PEF may be a promising alternative for the enhancement of the selective extraction of antioxidant bioactive compounds from microalgae.
Sleep characteristics and HbA1c in patients with type 2 diabetes on glucose-lowering medication

Introduction To examine the association of sleep duration, insomnia, and obstructive sleep apnea (OSA) with hemoglobin A1c (HbA1c) in a cohort of patients with type 2 diabetes (T2D) on glucose-lowering medications. Research design and methods 13 346 patients with T2D were included in the present analysis (mean age: 60.2 years; 56.6% were on antidiabetic drug monotherapy; 43.4% received at least two glucose-lowering medications). Sleep duration (short: ≤6 hours/day; normal: 7–8 hours/day; long: ≥9 hours/day) and frequency of insomnia symptoms were self-reported. The risk of OSA was considered high if at least two of the following conditions were fulfilled: regular snoring, frequent daytime sleepiness, and either obesity (≥30 kg/m2) or hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg). Associations between sleep variables and HbA1c were investigated by analysis of covariance or linear regression (adjusted for, eg, participants’ age, sex, ethnic background, and systolic blood pressure). Results Long sleep duration and a high risk for OSA were independently associated with higher HbA1c values (long vs normal sleep duration: +0.10% (95% CI 0.03 to 0.18); high vs low risk for OSA: +0.07% (95% CI 0.02 to 0.11), both p=0.004). No robust association was found of short sleep duration and frequent insomnia symptoms with HbA1c. Finally, a positive dose–response association between the number of sleep problems per subject (range: 0–3) and HbA1c was observed (β=0.04% (0.02 to 0.06), p=0.002). However, all significant associations were small. Conclusion Screening for and treatment of sleep problems may help lower HbA1c levels in patients with T2D on glucose-lowering medications.
High frequency regeneration and transformation of indica rice variety Pusa Sugandh2

A study was undertaken to examine the interactive effects of rice genotypes, media composition and desiccation treatment on regeneration frequency (RF) and total number of regenerated plantlets (green shoot induction, GSI). Out of four tested genotypes, the aromatic indica rice variety Pusa Sugandh2 (PS2) showed similar regeneration frequency (94±12.81) and green shoot induction (387.33±2.91) on RM-1 medium as that of japonica genotype Taipei 309 (TP309), which was significantly higher than those in Pusa Basmati1 (PB1) and IR64. The better performing genotype (PS2) was subjected to genetic transformation using AtDREB1A by biolistic method. The regeneration frequency of transformed embryogenic calli of PS2 was found to be 87.02% which was not significantly different from non-transformed embryogenic calli of PS2, where as 50% lower frequency was observed in case of GSI (178.66±0.28). Successful transformants were analysed by PCR using hptII and DREB specific primers. High frequency regeneration coupled with genetic transformation makes PS2 a preferred genotype for large scale functional validation of candidate genes in transgenics.
Altered awareness of cognitive and neuropsychiatric symptoms in Parkinson's disease and Dementia with Lewy Bodies: A systematic review

Altered awareness of cognitive and neuropsychiatric symptoms is a common feature of neurodegeneration, which can significantly impact on quality of life, medication concordance and personal safety. Elucidating how awareness is affected by common alpha‐synucleinopathies therefore has significant clinical relevance. We performed a systematic review of the literature on awareness of cognitive and neuropsychiatric symptoms in Parkinson's disease and Dementia with Lewy Bodies.
Control of translation by eukaryotic mRNA transcript leaders—Insights from high‐throughput assays and computational modeling

Eukaryotic gene expression is tightly regulated during translation of mRNA to protein. Mis‐regulation of translation can lead to aberrant proteins which accumulate in cancers and cause neurodegenerative diseases. Foundational studies on model genes established fundamental roles for mRNA 5′ transcript leader (TL) sequences in controlling ribosome recruitment, scanning, and initiation. TL cis‐regulatory elements and their corresponding trans‐acting factors control cap‐dependent initiation under unstressed conditions. Under stress, cap‐dependent initiation is suppressed, and specific mRNA structures and sequences promote translation of stress‐responsive transcripts to remodel the proteome. In this review, we summarize current knowledge of TL functions in translation initiation. We focus on insights from high‐throughput analyses of ribosome occupancy, mRNA structure, RNA Binding Protein occupancy, and massively parallel reporter assays. These data‐driven approaches, coupled with computational analyses and modeling, have paved the way for a comprehensive understanding of TL functions. Finally, we will discuss areas of future research on the roles of mRNA sequences and structures in translation.
Virtual Reality exposure therapy for public speaking anxiety in routine care: a single-subject effectiveness trial

ABSTRACT Virtual Reality (VR) can be used as a therapeutic tool to conduct efficacious in-session exposure therapy by presenting virtual equivalents of phobic stimuli, yet past hardware restrictions hindered implementation in routine care and effectiveness studies. The current study examines the effectiveness of a VR-assisted treatment protocol for public speaking anxiety with demonstrated efficacy, this time in routine care, using affordable VR hardware. Participants (n = 23) were recruited via a private clinic and treated by one of four psychologists with only minimal VR-training. Using a single-subject design and dual-slope modeling (adjusting the treatment-onset slope for treatment effects), we found a significant, large decrease in self-rated public speaking anxiety following the primary three-hour session, similar in magnitude to the previous efficacy trial. Multilevel modeling of in-session process measures suggests that the protocol works as intended, by decreasing catastrophic belief expectancy and distress, and increasing perceived performance quality. Adherence to the online transition program that followed—encouraging in-vivo exposure—was relatively poor, yet symptoms decrease continued. No change was observed over the three-month follow-up period. We conclude that VR exposure therapy can be effective under routine care conditions and is an attractive approach for future, large-scale implementation and effectiveness trials.