Miracle-dz/UniFAR-FTUs huggingface dataset:
Early embryonic exposure of ionizing radiations disrupts zebrafish pigmentation

Studies have demonstrated that zebrafish are powerful tools for monitoring environmental toxicity, including radiation hazard. Here we investigated the developmental toxicity of ionizing radiation (IR) in an in vivo embryonic zebrafish model. The effects of heavy ion (12C6+), proton, and X‐ray radiation on early zebrafish embryos were determined. A similar dose‐dependent decrease in the hatch and survival rate of zebrafish embryos was observed after exposure to these irradiations. Exposure of zebrafish embryos to 1–4 Gy IR caused significant loss of pigmentation. Quantitative real‐time reverse transcription polymerase chain reaction, western blot analysis, and in situ hybridization (ISH) experiment revealed that atp5α1 was markedly upregulated in irradiated zebrafish embryos. In addition, IR resulted in a rapid decrease in total adenosine triphosphate (ATP) generation. With dual functions of synthesizing or hydrolyzing ATP, ATP synthase regulated H+ transport crossing the mitochondrial inner. Administration of the mitochondrial ATP synthase inhibitor, oligomycin, partially restored pigmentation in irradiated zebrafish embryos, but the ATPase inhibitor, BTB06584, had no effect. Taken together, these results showed that IR exposure downregulated zebrafish pigmentation through regulation of H+ ion transport in mitochondria.
Comparison between endoscopic sphincterotomy vs endoscopic sphincterotomy associated with balloon dilation for removal of bile duct stones: A systematic review and meta-analysis based on randomized controlled trials

AIM To compare gallstones removal rate and incidence of bleeding, pancreatitis, use of mechanical lithotripsy, cholangitis and perforation between isolated sphincterotomy vs sphincterotomy associated with balloon dilation of papilla in choledocholithiasis through the meta-analysis of randomized clinical trials. METHODS We conducted a systematic review according to the PRISMA guidelines. Literature search was restricted to randomized controlled trials (RCTs) on MedLine, Cochrane Library, LILACS, and EMBASE database platforms in July 2017. The manual search included references of retrieved articles. We extracted data focusing on outcomes: The primary endpoint was the stones removal rate; Secondary endpoints were rates of pancreatitis, bleeding, use of mechanical lithotripsy (ML), perforation and cholangitis. RESULTS Eleven RCTs with 1824 patients were included. EST was associated with more post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding [FE RD-0.02, CI (-0.03, -0.00), I2 = 33%, P = 0.05] and more need of mechanical lithotripsy in general [RE RD-0.16, CI (-0.25, -0.06), I2 = 90%, P = 0.002] and in subgroup analysis of stones greater than 15 mm [RE RD-0.20, CI (-0.38, -0.02), I2 = 82%, P = 0.003]. Incidence of pancreatitis [FE RD-0.01, CI (-0.03, 0.01), I2 = 0, P = 0.36], cholangitis [FE RD-0.00, CI (-0.01, 0.01), I2 =0, P = 0.97] and perforation [FE RD-0.01, CI (-0.01, 0.00), I2 = 0, P = 0.23] was similar between the groups as well as similar stone removal rates in general [FE RD-0.01, CI (-0.01, 0.04), I2 = 0, P = 0.23] and pooled analysis of stones greater than 15 mm [FE RD-0.02, CI (-0.02, 0.07), I2 = 11%, P = 0.31]. CONCLUSION Through meta-analysis of randomized clinical trials we found that isolated sphincterotomy was associated with more post-ERCP bleeding and more need for mechanical lithotripsy. However, there was no statistical difference in the stone removal rate between isolated sphincterotomy and sphincterotomy associated with balloon dilation in the approach to remove gallstones.
Extending Populus seed longevity by controlling seed moisture content and temperature

The poplar species Populus davidiana and P. koreana are widely grown in plantations and as biofuel resources, but little is known about ex-situ seed conservation in poplar. To identify the optimal long-term seed storage conditions for these species, we evaluated the viability of seeds with different seed water contents (SWCs) at various storage temperatures and time periods. P. davidiana seeds with <6% SWC could be stored at room temperature (RT) for 4 weeks, while P. koreana seeds showed no storability at RT. P. davidiana seeds with 3% SWC showed 74% viability after 36 months of storage at 4°C, while those with 9–18% SWC showed >89% viability after 48 months of storage at -18°C. Long-term storage at -80°C was best for P. davidiana seeds with a wide range of SWCs (3–24%), with 91–98% of normal germination after 48 months of storage. However, the normal germination of P. koreana seeds with 3–24% SWC declined to <20% after 36 months of storage, even at -18°C and -80°C. No significant difference was observed between seeds immersed vs. not immersed in liquid nitrogen for both species. Our findings increase the possibility for long-term seed conservation for both Populus species.
HMDB 4.0: the human metabolome database for 2018

Abstract The Human Metabolome Database or HMDB (www.hmdb.ca) is a web-enabled metabolomic database containing comprehensive information about human metabolites along with their biological roles, physiological concentrations, disease associations, chemical reactions, metabolic pathways, and reference spectra. First described in 2007, the HMDB is now considered the standard metabolomic resource for human metabolic studies. Over the past decade the HMDB has continued to grow and evolve in response to emerging needs for metabolomics researchers and continuing changes in web standards. This year's update, HMDB 4.0, represents the most significant upgrade to the database in its history. For instance, the number of fully annotated metabolites has increased by nearly threefold, the number of experimental spectra has grown by almost fourfold and the number of illustrated metabolic pathways has grown by a factor of almost 60. Significant improvements have also been made to the HMDB’s chemical taxonomy, chemical ontology, spectral viewing, and spectral/text searching tools. A great deal of brand new data has also been added to HMDB 4.0. This includes large quantities of predicted MS/MS and GC–MS reference spectral data as well as predicted (physiologically feasible) metabolite structures to facilitate novel metabolite identification. Additional information on metabolite-SNP interactions and the influence of drugs on metabolite levels (pharmacometabolomics) has also been added. Many other important improvements in the content, the interface, and the performance of the HMDB website have been made and these should greatly enhance its ease of use and its potential applications in nutrition, biochemistry, clinical chemistry, clinical genetics, medicine, and metabolomics science.
Anterolateral Motor Cortex Connects with a Medial Subdivision of Ventromedial Thalamus through Cell Type-Specific Circuits, Forming an Excitatory Thalamo-Cortico-Thalamic Loop via Layer 1 Apical Tuft Dendrites of Layer 5B Pyramidal Tract Type Neurons

The anterolateral motor cortex (ALM) and ventral medial (VM) thalamus are functionally linked to support persistent activity during motor planning. We analyzed the underlying synaptic interconnections using optogenetics and electrophysiology in mice (female/male). In cortex, thalamocortical (TC) axons from VM thalamus excited VM-projecting pyramidal tract (PT) neurons in layer 5B of ALM. These axons also strongly excited layer 2/3 neurons (which strongly excite PT neurons, as previously shown) but not VM-projecting corticothalamic (CT) neurons in layer 6. The strongest connections in the VM → PT circuit were localized to apical tuft dendrites of PT neurons, in layer 1. These tuft inputs were selectively augmented after blocking hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. In thalamus, axons from ALM PT neurons excited ALM-projecting VM neurons, located medially in VM. These axons provided weak input to neurons in mediodorsal nucleus, and little or no input either to neurons in the GABAergic reticular thalamic nucleus or to neurons in VM projecting to primary motor cortex (M1). Conversely, M1 PT axons excited M1- but not ALM-projecting VM neurons. Our findings indicate, first, a set of cell type-specific connections forming an excitatory thalamo-cortico-thalamic loop for ALM ↔ VM communication and a circuit-level substrate for supporting reverberant activity in this system. Second, a key feature of this loop is the prominent involvement of layer 1 synapses onto apical dendrites, a subcellular compartment with distinct signaling properties, including HCN-mediated gain control. Third, the segregation of the ALM ↔ VM loop from M1-related circuits of VM adds cellular-level support for the concept of parallel pathway organization in the motor system. SIGNIFICANCE STATEMENT Anterolateral motor cortex (ALM), a higher-order motor area in the mouse, and ventromedial (VM) thalamus are anatomically and functionally linked, but their synaptic interconnections at the cellular level are unknown. Our results show that ALM pyramidal tract neurons monosynaptically excite ALM-projecting thalamocortical neurons in a medial subdivision of VM thalamus, and vice versa. The thalamo-cortico-thalamic loop formed by these recurrent connections constitutes a circuit-level substrate for supporting reverberant activity in this system.
Implementation of Dialectical Behavior Therapy with Suicidal and Self-Harming Adolescents in a Community Clinic

The object of this research was to examine the feasibility and effectiveness of Dialectical Behavior Therapy (DBT) with suicidal and self-harming adolescents treated in a community clinic. A group of 24 adolescents at high risk for suicide were enrolled in 6 months of comprehensive DBT, provided by therapists and trainees at a county-run outpatient mental health clinic serving disadvantaged, ethnic minority clients. Results showed significant pre/post-treatment decreases in suicide attempts, non-suicidal self-injury behaviors (NSSI), and suicidal ideation. Results also showed significant decreases in other suicide risk factors, including emotion dysregulation, depression, impulsivity, BPD symptoms, psychopathology, PTSD symptoms, and substance use, as well as increases in family expressiveness and reasons for living. Treatment retention and satisfaction rates were high. As many youth at risk for suicide will be treated in community settings, findings showing that receiving DBT in a community clinic resulted in significant improvements across a range of suicide risk factors are an important contribution to the adolescent suicide prevention literature.
Using Visual Thinking Strategies to Improve Mathematics Instruction.

The purpose of the study was to explore the use of Visual Thinking Strategies as it applied to mathematics instruction for teachers in a small, urban elementary school containing grades 1-6 in a large Midwestern metropolis. This study was implemented to address the problem of low math scores in urban schools that have students with low socioeconomic status compounded by the way math concepts are generally taught. This study was qualitative and followed the heuristic tradition of research. The unit of analysis was the experiences of teachers with VTS, as we explored their implementation of the visual thinking strategies in the classroom gathered from open-ended surveys, observations, informal reflective conversations, in-depth interviews, and reflective journals analyzed during the illumination step of the heuristic process in a focus group discussion. The central question that guided the study was, how can Visual Thinking Strategies (VTS) improve mathematics instruction? There were three contributing parts explored, teacher “moves,” restatements of evidence regarding explicit teaching of mathematical concepts, and academic vocabulary. Five teachers in the building became co-researchers
Further evidence for a differential interaction of brivaracetam and levetiracetam with the synaptic vesicle 2A protein

Brivaracetam (BRV) and levetiracetam (LEV) are effective antiepileptic drugs that bind selectively to the synaptic vesicle 2A (SV2A) protein. BRV differs from LEV in preclinical studies in that it exhibits a more potent and complete seizure protection across animal models. We reported previously that an allosteric modulator of the SV2A protein had differential effects on BRV compared with LEV, suggesting that they act at different sites or with different conformations of the SV2A protein. If this is the case, then we hypothesized that mutations of specific amino acids in the SV2A protein may have differential effects on BRV and LEV binding by the modulator. Mutation of some amino acids identified previously in the binding site of racetams to the SV2A protein had marked effects on binding of both [3H]BRV and [3H]LEV (eg, W300F, F277A, G303A, F658A, Y462A, W666A, I663A, D670A, and V661A). However, 3 amino acids were identified (K694, I273, and S294) in which mutation lost the effect of the modulator on [3H]LEV binding with no effect on the modulation of [3H]BRV binding. These results confirm that BRV and LEV bind to the human synaptic vesicle 2A protein at closely related sites but interact with these sites in a different way.
Association between local-level resources for home care and home deaths: A nationwide spatial analysis in Japan

Aim Little is known about whether and how local-level resources regarding home care are associated with the prevalence of home deaths. We aimed to investigate whether geographic patterns of the resources for home care were associated with the prevalence of home deaths, taking spatial variation into consideration. Methods We conducted an ecological cross-sectional study in Japan using nationwide data in 2014. The areal unit was the municipality, the smallest administrative unit in Japan. We investigated the association between the percentage of home deaths and the resources of home care support clinics with available 24-hour-a-day functions, considering the geographic effect of neighboring municipalities by applying a geographically weighted regression model. Results The mean and standard deviation of the percentages of home deaths were 11.4% (5.0%), and those of the number of home care support clinics per 10,000 elderly population were 3.4 (3.7). The percentages of home deaths in neighboring municipalities tended to be significantly correlated (Moran’s I 0.34, p<0.001). Adjusting for the number of hospital beds, total population, and the socio-economic status of municipality, the results of an ordinary least squares regression model showed a positive correlation between the percentage of home deaths and the local resources for home care support clinics per 10,000 elderly population (regression coefficient 0.15, 95% confidence interval 0.07, 0.22), while the existence of spatial autocorrelation of the residual was suggested (Moran’s I of the residual 0.227, p<0.001). The geographically weighted regression model showed local regression coefficients varying across municipalities with a better model fit over the analogous ordinary least squares model (adjusted R2 0.414 vs. 0.131). Conclusion Home deaths were more prevalent in municipalities with greater home care resources. This association was geographically varied and further strengthened in some areas.
Individual Differences in Children’s Suggestibility: An Updated Review

ABSTRACT The present review is intended as an overview of our current understanding of how children’s individual characteristics, in terms of demographic, cognitive, and psycho-social variables, may influence their susceptibility to suggestion. The goals are to revisit conceptual models of the mechanisms of suggestibility, to provide an updated practical guide for practitioners, and to make recommendations for future research. Results suggest that children with intellectual impairment and those with nascent language skills may be particularly vulnerable to suggestion. Further, memory for separate events, theory of mind, executive function, temperament, and social competence may not be related to suggestibility, whereas additional work is needed to clarify the potential contributions of knowledge, stress, mental health, parental elaborative style, and adverse experiences/maltreatment to children’s suggestibility.
PPAR-Induced Fatty Acid Oxidation in T Cells Increases the Number of Tumor-Reactive CD8+ T Cells and Facilitates Anti–PD-1 Therapy

PPAR signal activation enhanced the efficacy of PD-1 blockade cancer immunotherapy. The PPAR signal boosts fatty acid oxidation to rescue T cells from apoptosis by upregulating anti-apoptotic genes including bcl2, thus increasing the number of killer T cells. Although PD-1 blockade cancer immunotherapy has shown potential for a wide range of patients with cancer, its efficacy is limited, in part, due to the loss of effector cytotoxic T lymphocytes (CTLs) via terminal differentiation–induced apoptosis. We previously demonstrated that mitochondrial activation, by the agonists of peroxisome proliferator–activated receptor γ (PPARγ) coactivator 1-α (PGC-1α)/transcription factor complexes, had synergistic effects with a PD-1–blocking monoclonal antibody in a mouse tumor model. In the current study, we examined the molecular mechanism of the synergistic effects of bezafibrate, an agonist of PGC-1α/ PPAR complexes, which enhanced the tumoricidal effects of PD-1 blockade. Bezafibrate activated CTL mitochondria and upregulated oxidative phosphorylation as well as glycolysis, resulting in more proliferation of naïve T cells and improved effector function in CTLs. Bezafibrate also increased fatty acid oxidation (FAO) and mitochondrial respiratory capacity, which supports the extra energy demands of cells in emergencies, allowing cell survival. Carnitine palmitoyl transferase 1 (Cpt1), which is needed for FAO, and Bcl2 were both upregulated. Cpt1 and Bcl2 can form a complex to prevent apoptosis of CTLs. Together, these results indicate that bezafibrate increases or maintains the number of functional CTLs by activating mitochondrial and cellular metabolism, leading in turn to enhanced antitumor immunity during PD-1 blockade. Cancer Immunol Res; 6(11); 1375–87. ©2018 AACR.
FEM Investigation of the Stress Distribution over Mandibular Bone Due to Screwed Overdenture Positioned on Dental Implants

The objective of the present investigation was to evaluate how dental implant positioning can influence the masticatory stress distribution over screwed mandibular prosthodontics restoration and over the surrounding bone tissue. Moreover, the dental implant components and overdenture bar strengths under masticatory cycles have been investigated in order to evaluate possible screw and prosthesis breakage. A “virtual jaw” model and 3D dental implant were reproduced to realise finite element analysis in order to underline the parameters and the mechanical characteristics of the bone and of the dental implants connected to the overdenture bar. The distribution of a nonspecific chewing phase, analysing the overall load on the fixtures of the lower jaw, was performed. The study investigating frontal and horizontal planes and vertical directions of occlusal forces showed how position and perspective of fixtures strongly influenced the stress distribution and the consequent jawbone tissue remodelling. Prostheses elements such as cantilever, passing screws, and dental implants are strictly related to the correct selection of dental implant position. This study suggested a virtual method to guide the surgeon in the choice of implant number, position, diameter, and length, and cantilever length and shape, and to evaluate the prospective stress distribution of chewing strengths for a correct prosthesis rehabilitation.
Relationship of electrophysiological dysfunction and clinical severity in SCN2A‐related epilepsies

Variants in the SCN2A gene cause a broad spectrum of epilepsy syndromes of variable severity including benign neonatal‐infantile epilepsy (BFNIE), developmental and epileptic encephalopathies (DEE), and other neuropsychiatric disorders. Here, we studied three newly identified variants, which caused distinct phenotypes observed in nine affected individuals of three families, including BFNIE, and DEE with intractable neonatal seizures. Whole cell patch‐clamp recordings of transfected tsA201 cells disclosed an increased current density and an increased subthreshold sodium inward current upon an action potential stimulus (p.(Lys908Glu)), a hyperpolarizing shift of the activation curve (p.(Val208Glu) and p.(Thr773Ile)), and an increased persistent current (p.(Thr773Ile)). To evaluate genotype–phenotype correlations, we next developed scoring systems for both the extent of the electrophysiological dysfunction and the severity of the clinical phenotype and applied those to 21 previously and newly functionally characterized SCN2A variants. All inherited variants were associated with a mild clinical phenotype and a lower electrophysiological score compared to those occurring de novo and causing severe phenotypes. Our results thus reveal a nice correlation between the extent of channel dysfunction and the clinical severity.
Correlation between Basal Insulin Glargine Dose Required in Achieving Target Fasting Blood Glucose and Various Clinical and Laboratory Parameters in Hospitalized Noncritical Patients

Aims: The primary objective was to study the interrelationship between the basal insulin glargine dose and baseline clinical and laboratory parameters in noncritically ill hospitalized patients who have achieved the stable fasting blood glucose in the target range of 100–140 mg/dl. Patients and Methods: This was retrospective, cross-sectional, observational study. Consenting, nonpregnant, adult patients on basal-bolus insulin who had fasting capillary blood glucose in the range of 100–140 mg/dl as measured by glucometer for 3 consecutive days were included in this study. Patient receiving any basal insulin other than insulin glargine were excluded from this study. The data collected for these patients included age, sex, glycated hemoglobin (HBA1c) at the time of admission, timing of basal insulin, basal insulin dose (BID), BID/kg, weight, and serum creatinine. BID/kg was correlated with other parameters using regression analysis (Pearson's). Comparison of BID/kg in various subgroups was analyzed using Student's t- test. Parametric data of more than three groups were compared using ANOVA. The P < 0.05 was considered as statistically significant. Results: A total of 180 patients were included in the study. On correlating the BID/kg with various parameters, we found statistically significant correlation between BID/kg and glycated hemoglobin (HbA1c) at the time of admission (P = 0.044). Patients with HbA1c ≥8.0% had higher BID/kg compared to those with HbA1c <8.0% (P = 0.004). The mean BID in patients with renal failure was significantly higher compared to those without renal failure. Conclusion: HbA1c at the time of admission is the most important parameter for determining the appropriate BID in hospitalized patients. Patients with renal failure may require a higher dose of basal insulin than those not having renal failure.