Miracle-dz/UniFAR-FTUs huggingface dataset:
RNase H activities counteract a toxic effect of Polymerase η in cells replicating with depleted dNTP pools

Abstract RNA:DNA hybrids are transient physiological intermediates that arise during several cellular processes such as DNA replication. In pathological situations, they may stably accumulate and pose a threat to genome integrity. Cellular RNase H activities process these structures to restore the correct DNA:DNA sequence. Yeast cells lacking RNase H are negatively affected by depletion of deoxyribonucleotide pools necessary for DNA replication. Here we show that the translesion synthesis DNA polymerase η (Pol η) plays a role in DNA replication under low deoxyribonucleotides condition triggered by hydroxyurea. In particular, the catalytic reaction performed by Pol η is detrimental for RNase H deficient cells, causing DNA damage checkpoint activation and G2/M arrest. Moreover, a Pol η mutant allele with enhanced ribonucleotide incorporation further exacerbates the sensitivity to hydroxyurea of cells lacking RNase H activities. Our data are compatible with a model in which Pol η activity facilitates the formation or stabilization of RNA:DNA hybrids at stalled replication forks. However, in a scenario where RNase H activity fails to restore DNA, these hybrids become highly toxic for cells.
Strain engineering of core–shell silicon carbide nanowires for mechanical and piezoresistive characterizations

This study evaluated the mechanical properties and piezoresistivity of core–shell silicon carbide nanowires (C/S-SiCNWs) synthesized by a vapor–liquid–solid technique, which are a promising material for harsh environmental micro electromechanical systems (MEMS) applications. The C/S-SiCNWs were composed of a crystalline cubic (3C) SiC core wrapped by an amorphous silicon dioxide (SiOx) shell; however, TEM observations of the NWs showed that hexagonal polytypes (2H, 4H , and 6H) were partially induced in the core by a stacking fault owing to a Shockley partial dislocation. The stress–strain relationship of the C/S-SiCNWs and SiC cores without an SiOx shell was examined using MEMS-based nanotensile tests. The tensile strengths of the C/S-SiCNWs and SiC cores were 7.0 GPa and 22.4 GPa on average, respectively. The lower strength of the C/S-SiCNWs could be attributed to the SiOx shell with the surface roughness as the breaking point. The Young’s modulus of the C/S-SiCNWs was 247.2 GPa on average, whereas that of the SiC cores had a large value with scatter data ranging from 450 to 580 GPa. The geometrical model of the SiC core based on the transmission electron microscopy observations rationalized this scatter data by the volume content of the stacking fault in the core. The piezoresistive effects of the C/S-SiCNW and SiC core were also evaluated from the I–V characteristics under uniaxial tensile strain. The gauge factor of –30.7 at 0.008 ε for the C/S-SiCNW was approximately two-times larger than that of –15.8 at 0.01 ε for the SiC core. This could be caused by an increase of the surface state density at the SiOx/SiC interface owing to the positive fixed oxide charge of the SiOx shell.
Integrated analysis of gene expression profiles identifies transcription factors potentially involved in psoriasis pathogenesis

Psoriasis is a common inflammatory skin disease mediated by cells and molecules in both the innate and adaptive immune systems. Recently, gene expression profile analysis revealed a large set of immune‐related differentially expressed genes (DEGs) in psoriasis. However, the associations between these DEGs and their transcriptional regulation mechanisms have not been completely elucidated. In this study, several psoriasis Gene Expression Omnibus data sets were systematically analyzed using bioinformatics tools to uncover important transcription factors (TFs) that regulate the expression of immune‐related DEGs and further enhance our understanding of psoriasis pathogenesis. Common DEGs encoding chemokines, cytokines, antimicrobial peptides, and keratins were identified in psoriasis, and extensive correlations existed among these DEGs. Several common TFs that bind the promoters of the DEGs, including the well‐known signal transducer and activator of transcription 1 (STAT1), STAT3, and nuclear factor κ‐light‐chain‐enhancer of activated B cells (NF‐κB) as well as ETS homologous factor (EHF), Fos‐like antigen 1 (FOSL1), and Forkhead box C1 (FOXC1), which are rarely studied in psoriasis, were also identified. STAT1, EHF, FOSL1, STAT3, and NFKB1 were positively correlated with these DEGs in psoriasis lesions, whereas FOXC1 was negatively correlated with most DEGs. The decreased expression of the DEGs was accompanied by the downregulation of STAT1, EHF, FOSL1, STAT3, and NFKB1 and the upregulation of FOXC1 upon blocking interleukin 17 (IL‐17) or tumor necrosis factor α signaling in psoriasis. Additionally, the downregulation of IL37 in psoriasis was negatively correlated with STAT1 and CXCL10, which are associated with Th1 responses. These results suggest that TFs play an important role in the pathogenesis of psoriasis, and interfering with the activity of key TFs may be a promising therapeutic strategy for psoriasis.
Normal body mass index (BMI) can rule out metabolic syndrome

Abstract The aim of the study was to assess whether body mass index (BMI) can be used as a simple and reliable survey test for metabolic syndrome. The study is an observational cohort study among patients who visited the Rambam Periodic Examinations Institute (RPEI). We analyzed the correlation between obesity indices and presence of metabolic syndrome. We identified the ideal value of BMI for identification of patients at risk for metabolic syndrome. We also described the correlation between different BMI values and its negative predictive value (NPV) for metabolic syndrome. During the study years, 23,993 patients visited the RPEI, and 12.5% of them fulfilled the criteria for metabolic syndrome. Women with metabolic syndrome had higher proportion of obesity, when compared with men (89.9% vs 52.6%; P < .0001). Normal BMI had very high NPV to rule out metabolic syndrome among men and women (98% and 96%, respectively). Using receiver-operating characteristic curve, we found BMI 27 to be the ideal value for identification of metabolic syndrome for the entire cohort (area under the curve [AUC] 0.767, 95% confidence interval [CI] 0.758–0.775, P < .0001), for men (AUC 0.726, 95% CI 0.715–0.738, P < .0001), and for women (AUC 0.843, 95% CI 0.831–0.855, P < .0001). BMI below 30 provided NPV of 91.1% to rule out metabolic syndrome. The BMI as single survey measurement of obesity offers high NPV for metabolic syndrome and can be used by physician and patients for this purpose.
Facilitators and Barriers to Movement Integration in Elementary Classrooms: A Systematic Review

ABSTRACT Purpose: A systematic review was conducted to identify facilitators and barriers to movement integration (MI) in elementary school classrooms. Method: Online databases (Educational Resources Information Center, Google Scholar, PsycINFO, and PubMed) served as data sources for the study. Following the PRISMA guidelines, relevant published research on MI was identified and screened for inclusion in a qualitative synthesis. Content analysis of the included articles (N = 28) was used to identify themes of MI facilitators and barriers. Facilitators and barriers were then categorized using a social-ecological framework. Results: A total of 12 themes of MI facilitators and barriers were identified and categorized into two social-ecological levels: institutional factors (e.g., administrative support, resources) and intrapersonal factors (e.g., teacher confidence, ease of implementation). Conclusion: This review can inform research and practice aimed at supporting the implementation of MI in elementary classrooms.
Emotion regulation self-efficacy mediates the relation between happiness emotion goals and depressive symptoms: A cross-lagged panel design.

The present study was designed to test the hypothesis that unrealistically high happiness emotion goals lead to decreased emotion regulation self-efficacy, which in turn, leads to depressive symptoms. A cross-lagged panel design with data collection at three time points was used to allow for causal inferences of directionality among study variables. Participants (N = 181) completed a battery of self-report questionnaires at a baseline assessment session (T1). The same measures were completed again at 6- (T2) and 12-month (T3) follow-up sessions. Results of a cross-lagged path analysis indicated that emotion regulation self-efficacy at T2 mediated the relation between happiness emotion goals at T1 and depressive symptoms at T3, thus confirming the primary study hypothesis. To decrease the likelihood that one will experience depressive symptoms, vulnerable individuals may benefit from preemptive efforts that help recalibrate emotion goals in a realistic manner or shift attention toward end-state goals that are not emotion related. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
The subjective world of home care workers in dementia: an “order of worth” analysis

ABSTRACT The perspective of domiciliary workers is needed to recruit a high-quality workforce and meet growing demand. An English ethnographic study yielded extensive insights. To structure analysis of the study data, we apply a method developed by political theorists Boltanski and Thévenot that identifies key variables in different values systems. This “orders of worth” framework is used to map out the distinctive features of the subjective world of home carers. The results can be drawn on to formulate recruitment and retention policies, to design reward strategies or to ensure that training and education opportunities engage effectively with the workforce.
An Overview of the Most Significant Zoonotic Viral Pathogens Transmitted from Animal to Human in Saudi Arabia

Currently, there has been an increasing socioeconomic impact of zoonotic pathogens transmitted from animals to humans worldwide. Recently, in the Arabian Peninsula, including in Saudi Arabia, epidemiological data indicated an actual increase in the number of emerging and/or reemerging cases of several viral zoonotic diseases. Data presented in this review are very relevant because Saudi Arabia is considered the largest country in the Peninsula. We believe that zoonotic pathogens in Saudi Arabia remain an important public health problem; however, more than 10 million Muslim pilgrims from around 184 Islamic countries arrive yearly at Makkah for the Hajj season and/or for the Umrah. Therefore, for health reasons, several countries recommend vaccinations for various zoonotic diseases among preventive protocols that should be complied with before traveling to Saudi Arabia. However, there is a shortage of epidemiological data focusing on the emerging and reemerging of zoonotic pathogens transmitted from animal to humans in different densely populated cities and/or localities in Saudi Arabia. Therefore, further efforts might be needed to control the increasing impacts of zoonotic viral disease. Also, there is a need for a high collaboration to enhance the detection and determination of the prevalence, diagnosis, control, and prevention as well as intervention and reduction in outbreaks of these diseases in Saudi Arabia, particularly those from other countries. Persons in the health field including physicians and veterinarians, pet owners, pet store owners, exporters, border guards, and people involved in businesses related to animal products have adopted various preventive strategies. Some of these measures might pave the way to highly successful prevention and control results on the different transmission routes of these viral zoonotic diseases from or to Saudi Arabia. Moreover, the prevention of these viral pathogens depends on socioeconomic impacts, available data, improved diagnosis, and highly effective therapeutics or prophylaxis.
Chronic lymphocytic leukemia (CLL) treatment: So many choices, such great options

Within a period of just over a decade, managing chronic lymphocytic leukemia (CLL) has become more effective and yet more challenging than ever before. The important improvement in the treatment of CLL can be ascribed to the availability of many new options, mainly with the development of novel targeted therapies, such as ibrutinib, idelalisib, duvelisib and venetoclax. There are now newer tests that reliably define high‐risk patients, and treatment plans can be tailored accordingly. Overall, this indeed is a new era in the treatment of patients with CLL. However, despite this progress, CLL remains an incurable disease and continues to remain challenging. In this brief review, the authors highlight the many great choices available to clinicians who manage patients with CLL and focus on the sequencing of these choices based on the available data.
Parkinson’s disease-linked D620N VPS35 knockin mice manifest tau neuropathology and dopaminergic neurodegeneration

Significance The neuropathological spectrum of Parkinson’s disease (PD) brains harboring VPS35 mutations is not yet clear since only a single mutation carrier has been evaluated at autopsy. D620N VPS35 knockin mice developed here represent one of the first models of inherited PD that develop the robust and progressive degeneration of nigral dopaminergic neurons. Furthermore, these mice develop robust and widespread tau-positive pathology and axonal damage but lack signs of Lewy pathology positive for α-synuclein. VPS35 knockin mice indicate that the D620N mutation is sufficient for the development of tau abnormalities but not α-synuclein. The D620N VPS35 knockin mice provide an important new tool for distinguishing the neuropathological consequences and mechanisms of familial VPS35 mutations, including the intersection with other PD genetic risk factors. Mutations in the vacuolar protein sorting 35 ortholog (VPS35) gene represent a cause of late-onset, autosomal dominant familial Parkinson’s disease (PD). A single missense mutation, D620N, is considered pathogenic based upon its segregation with disease in multiple families with PD. At present, the mechanism(s) by which familial VPS35 mutations precipitate neurodegeneration in PD are poorly understood. Here, we employ a germline D620N VPS35 knockin (KI) mouse model of PD to formally establish the age-related pathogenic effects of the D620N mutation at physiological expression levels. Our data demonstrate that a heterozygous or homozygous D620N mutation is sufficient to reproduce key neuropathological hallmarks of PD as indicated by the progressive degeneration of nigrostriatal pathway dopaminergic neurons and widespread axonal pathology. Unexpectedly, endogenous D620N VPS35 expression induces robust tau-positive somatodendritic pathology throughout the brain as indicated by abnormal hyperphosphorylated and conformation-specific tau, which may represent an important and early feature of mutant VPS35-induced neurodegeneration in PD. In contrast, we find no evidence for α-synuclein–positive neuropathology in aged VPS35 KI mice, a hallmark of Lewy body pathology in PD. D620N VPS35 expression also fails to modify the lethal neurodegenerative phenotype of human A53T-α-synuclein transgenic mice. Finally, by crossing VPS35 KI and null mice, our data demonstrate that a single D620N VPS35 allele is sufficient for survival and early maintenance of dopaminergic neurons, indicating that the D620N VPS35 protein is fully functional. Our data raise the tantalizing possibility of a pathogenic interplay between mutant VPS35 and tau for inducing neurodegeneration in PD.
Socio‐economic inequality in oral health in childhood to young adulthood, despite full dental coverage

The aim of this cross‐sectional study was to assess differences in caries experience according to socio‐economic status (SES) in a health‐care system with full coverage of dental costs for children up to the age of 18 yr. In 2011 and 2014, by performing hurdle negative binomial models, we obtained data on 3,022 children and young adults aged 5, 8, 11, 14, 17, 20, and 23 yr, living in four cities in the Netherlands. At all ages between 5 and 23 yr, the percentages of children with caries‐free dentitions were lower and mean caries experience were higher in low‐SES than in high‐SES participants. In 5‐yr‐old children with dmft > 0, mean caries experience was 3.6 in those with low SES and 2.3 in those with high SES. In 23‐yr‐old participants, these estimates were 6.8 and 4.4, respectively (P < 0.05). Low‐SES children have a greater risk of more caries experience than high‐SES children. Thus, in a system with full free paediatric dental coverage, socio‐economic inequality in caries experience still exists. Dental health professionals, well‐child care doctors and nurses, general practitioners, and elementary school teachers should collaborate to promote oral health at the community level, with specific targeting of low‐SES families. We further need policy measures to curtail, at community level, the increasing availability and consumption of highly processed, carbohydrate‐rich foods, with particular attention for low‐SES families.
Functional outcome after the nonsurgical treatment for adolescent spasmodic valgus foot

Background: Adolescent spasmodic valgus foot is usually associated with resistant pain and deformity. It shows controversy regarding its incidence, etiology, and treatment. Our study aimed to evaluate the functional outcome after the nonsurgical treatment for such condition. Methods: This study included 50 planovalgus feet secondary to peroneal or peroneo-extensor spasm in 33 adolescents with a mean age of 14 ± 2.8 years. The procedure included foot manipulation under general anesthesia, sinus tarsi injection with corticosteroids, and a walking cast in the neutral position. Patients were evaluated functionally (using the American Orthopedic Foot and Ankle Society (AOFAS)) and radiologically before the procedure, after cast removal, and 3, 9, and 18 months later with special attention given for recurrence during the follow-up period with a mean duration of 22.5 ± 3.5 months. Results: Once general anesthesia had been conducted, the deformity was corrected without any manipulation, and full passive inversion could be easily obtained in 26 feet, the deformity was corrected only after manipulation, and full passive inversion had been obtained in 14 feet, while 10 feet remained stiff even after manipulation. The mean AOFAS score was significantly improved (p < 0.001) from 40.9 ± 3.5 at presentation to 73.56 ± 5.2 at the last follow-up in which 12 feet was painless and freely mobile and 24 feet had partial relapse, while 14 feet had complete relapse. Conclusion: The nonsurgical treatment for adolescent spasmodic valgus foot could be a simple and effective treatment. Apart from limited complete recurrence, the overall functional outcome was satisfactory. Level of evidence: type IV case series.
The Million Person Study relevance to space exploration and Mars

Abstract Understanding the health consequences of exposure to radiation received gradually over time is critically needed. The National Aeronautics and Space Administration (NASA) bases its safety standards on the acute exposures received by Japanese atomic bomb survivors. Such a brief exposure differs appreciably from the chronic radiation received during a two to three year mission to Mars. NASA also applies an individual risk-based system for radiation protection that accounts for age, sex, smoking history, and individual life styles. Because the Japanese life span study (LSS) reports women to be at 2 to 3 times greater lifetime risk of developing cancer than men, female astronauts are allowed less time in space. Another concern is the potential behavioral and cognitive impairments from galactic cosmic radiation (GCR) impinging on the nervous system that might jeopardize the mission, and, possibly, lead to dementia later in life. GCR are high-velocity heavy ions traveling through space. There are no human circumstances/analogs similar to GCR that can provide direct information on the possible effects of such high-LET exposure to brain tissue. The MPS provides a more representative group (healthy men and women) for risk estimates than the 1945 Japanese population exposed briefly to the atomic bombs. The permissible career exposure limit set by NASA for each astronaut is a 3% risk of exposure-induced death (REID) from cancer at a 95% confidence level to account for uncertainties in risk projections. Because the MPS is 10 times larger than the LSS, the 95% confidence levels will be narrower and thus allow more time in space, all things being equal. Sex-specific differences in radiation risk can be examined more fully in the MPS with over 250,000 women compared with about 32,000 women in the LSS. Non-cancer outcomes such as neurological disorders also can be evaluated following low-dose rate exposures to high-LET alpha particles. Workers at several nuclear facilities had intakes of radionuclides, such as plutonium, that exposed brain tissue to alpha particles (Helium nuclei) for life. Such workers are being evaluated for mortality from dementia and other motor neuron diseases; can be evaluated for clinically diagnosed incidences of these conditions; and, though challenging, could be interviewed and ask to take cognition tests. Ischemic heart disease is also under study. The MPS, thus, provides another line of human inquiry to assist in decision-making and policy guidance for space missions beyond earth orbit.
Mechanisms That Underlie Coordination in Children With Developmental Coordination Disorder

The authors examined potential mechanisms underlying motor coordination in children with developmental coordination disorder (DCD). Because children with DCD experience difficulty processing visual, auditory, and vibrotactile information, the authors explored patterns of choice reaction time (RT) in young (6-7 years) and older (9-10 years) children with and without DCD by using a compatibility-incompatibility paradigm and different sensory modalities. Young children responded more slowly than older children to visual, auditory, and vibrotactile stimuli. Children with DCD took longer than typical children to process visual and vibrotactile stimuli under more complex stimulus-response mappings. Young children with DCD responded more slowly than typical children to visual and vibrotactile information under incompatible conditions. Children with DCD responded faster than unaffected children to auditory stimuli. The results suggest that there is a developmental nature in the processing of visual and auditory input and imply that the vibrotactile sensory modality may be key to the motor coordination difficulties of children with DCD.