Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Roles of the Two Raphe Nuclei in Amiable Social Behavior and Aggression – An Optogenetic Study

Serotonergic mechanisms hosted by raphe nuclei have important roles in affiliative and agonistic behaviors but the separate roles of the two nuclei are poorly understood. Here we studied the roles of the dorsal (DR) and median raphe region (MRR) in aggression by optogenetically stimulating the two nuclei. Mice received three 3 min-long stimulations, which were separated by non-stimulation periods of 3 min. The stimulation of the MRR decreased aggression in a phasic-like manner. Effects were rapidly expressed during stimulations, and vanished similarly fast when stimulations were halted. No carryover effects were observed in the subsequent three trials performed at 2-day intervals. No effects on social behaviors were observed. By contrast, DR stimulation rapidly and tonically promoted social behaviors: effects were present during both the stimulation and non-stimulation periods of intermittent stimulations. Aggressive behaviors were marginally diminished by acute DR stimulations, but repeated stimulations administered over 8 days considerably decreased aggression even in the absence of concurrent stimulations, indicating the emergence of carryover effects. No such effects were observed in the case of social behaviors. We also investigated stimulation-induced neurotransmitter release in the prefrontal cortex, a major site of aggression control. MRR stimulation rapidly but transiently increased serotonin release, and induced a lasting increase in glutamate levels. DR stimulation had no effect on glutamate, but elicited a lasting increase of serotonin release. Prefrontal serotonin levels remained elevated for at least 2 h subsequent to DR stimulations. The stimulation of both nuclei increased GABA release rapidly and transiently. Thus, differential behavioral effects of the two raphe nuclei were associated with differences in their neurotransmission profiles. These findings reveal a surprisingly strong behavioral task division between the two raphe nuclei, which was associated with a nucleus-specific neurotransmitter release in the prefrontal cortex.
The Shiraz Pediatric Eye Study; a Population Based Survey of School Age Children: Rationale, Design and Baseline Characteristics

Purpose: To describe the rationale, study design, methodology, and baseline characteristics of the Shiraz Pediatric Eye Study, a population-based survey of schoolchildren in Shiraz, Iran. Methods: This population-based study included schoolchildren aged 6–12 years from all four educational districts of Shiraz who were recruited in years 2015–2016. Stratified random sampling was used to select 2400 participants from all districts. Data were recorded from a detailed interview and ocular evaluation of each eligible student. The eye examination comprised uncorrected and best corrected visual acuity measurement, refraction, external eye examination (including specific strabismus and lid evaluation tests), slit lamp biomicroscopy, intraocular pressure measurement, the Ishihara color vision test, and stereoacuity. Exophthalmometry, optical biometry, and optical coherence tomography were performed for a randomly selected subset of children. General characteristics and socioeconomic variables were also recorded to assess risk factors. Results: From a total of 2400 selected students, 2001 (83.3%) participated in the study. The mean age of the students was 9.1 ± 1.6 years, and 59.7% were girls. Most children had at least one parent with a diploma or less than diploma (63.5%), and 2.2% had illiterate parents. Conclusion: This study is expected to provide accurate estimates of the prevalence of visual impairments and their related determinants in Shiraz. In addition, it will identify children who should be targeted by blindness prevention programs.
Mechanism by which water and protein electrostatic interactions control proton transfer at the active site of channelrhodopsin

Channelrhodopsins are light-sensitive ion channels whose reaction cycles involve conformation-coupled transfer of protons. Understanding how channelrhodopsins work is important for applications in optogenetics, where light activation of these proteins triggers changes in the transmembrane potential across excitable membranes. A fundamental open question is how the protein environment ensures that unproductive proton transfer from the retinal Schiff base to the nearby carboxylate counterion is avoided in the resting state of the channel. To address this question, we performed combined quantum mechanical/molecular mechanical proton transfer calculations with explicit treatment of the surrounding lipid membrane. The free energy profiles computed for proton transfer to the counterion, either via a direct jump or mediated by a water molecule, demonstrate that, when retinal is all-trans, water and protein electrostatic interactions largely favour the protonated retinal Schiff base state. We identified a conserved lysine group as an essential structural element for the proton transfer energetics in channelrhodopsins.
Differential diagnosis of Norrie disease and X-linked familial exudative vitreoretinopathy (XL-FEVR) based on clinical and molecular evaluation.

Background: Molecular analysis of the NDP gene to confirm and precise the clinical diagnosis in two patients with X-linked familial exudative vitreoretinopathy (XL-FEVR). Material and methods: We report two patients from unrelated families with NDP gene mutations: a 14-month-old boy (p1) who was found to have severe exudative vitreoretinopathy and a 4-year-old boy with exudative vitreoretinopathy (p2). An extensive clinical examination of the probands, including slit-lamp examination, B-mode ultrasonography and magnetic resonance imaging was conducted, along with genetic analysis of NDP gene. Results: Clinical findings in patient 1 included no light perception, total retinal detachment and hyperplastic primary vitreous in both eyes. The genetic analysis of the NDP gene enabled to identify the novel frameshift mutation c. 222_c223insCG in p1 leading to the premature stop codon and production of aberrant norrin protein. In P2, clinical presentation included high myopia with astigmatism, unilateral fibrous bands and retinal detachment. Genetic testing revealed known point mutation c.362G>A leading to amino-acid alteration and improper protein. Conclusions: Mutation screening of NDP gene identified two different mutations in this region, one of which has not been previously reported.
Myc and ChREBP transcription factors cooperatively regulate normal and neoplastic hepatocyte proliferation in mice

Analogous to the c-Myc (Myc)/Max family of bHLH-ZIP transcription factors, there exists a parallel regulatory network of structurally and functionally related proteins with Myc-like functions. Two related Myc-like paralogs, termed MondoA and MondoB/carbohydrate response element–binding protein (ChREBP), up-regulate gene expression in heterodimeric association with the bHLH-ZIP Max-like factor Mlx. Myc is necessary to support liver cancer growth, but not for normal hepatocyte proliferation. Here, we investigated ChREBP's role in these processes and its relationship to Myc. Unlike Myc loss, ChREBP loss conferred a proliferative disadvantage to normal murine hepatocytes, as did the combined loss of ChREBP and Myc. Moreover, hepatoblastomas (HBs) originating in myc−/−, chrebp−/−, or myc−/−/chrebp−/− backgrounds grew significantly more slowly. Metabolic studies on livers and HBs in all three genetic backgrounds revealed marked differences in oxidative phosphorylation, fatty acid β-oxidation (FAO), and pyruvate dehydrogenase activity. RNA-Seq of livers and HBs suggested seven distinct mechanisms of Myc–ChREBP target gene regulation. Gene ontology analysis indicated that many transcripts deregulated in the chrebp−/− background encode enzymes functioning in glycolysis, the TCA cycle, and β- and ω-FAO, whereas those dysregulated in the myc−/− background encode enzymes functioning in glycolysis, glutaminolysis, and sterol biosynthesis. In the myc−/−/chrebp−/− background, additional deregulated transcripts included those involved in peroxisomal β- and α-FAO. Finally, we observed that Myc and ChREBP cooperatively up-regulated virtually all ribosomal protein genes. Our findings define the individual and cooperative proliferative, metabolic, and transcriptional roles for the “Extended Myc Network” under both normal and neoplastic conditions.
A Historical Perspective on Treatment of Fuchs’ Endothelial Dystrophy: We have Come a Long Way

Fuchs' endothelial corneal dystrophy is a hereditary and progressive vision-threatening disease with a high prevalence in our adult population. In the past two decades, endothelial transplantation has dramatically changed the way we treat these patients. Back then, our limited surgical techniques often resulted in less than ideal outcomes. It was unimaginable for our patients to achieve near perfect visual acuity in such a short span of time. Over the years, we have tenaciously refined our surgical techniques to vastly improve patient outcomes, and with the recent advent of Rho-kinase inhibitors, we may even consider delivering a simple injection to our patients in the future. Our purpose is to take a historical perspective on how far we have come in treating this disorder and how rapidly this field will continue to evolve.
Convolutional Recurrent Neural Networks for Glucose Prediction

Control of blood glucose is essential for diabetes management. Current digital therapeutic approaches for subjects with type 1 diabetes mellitus such as the artificial pancreas and insulin bolus calculators leverage machine learning techniques for predicting subcutaneous glucose for improved control. Deep learning has recently been applied in healthcare and medical research to achieve state-of-the-art results in a range of tasks including disease diagnosis, and patient state prediction among others. In this paper, we present a deep learning model that is capable of forecasting glucose levels with leading accuracy for simulated patient cases (root-mean-square error (RMSE) = 9.38 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 0.71 [mg/dL] over a 30-min horizon, RMSE = 18.87 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 2.25 [mg/dL] over a 60-min horizon) and real patient cases (RMSE = 21.07 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 2.35 [mg/dL] for 30 min, RMSE = 33.27 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 4.79% for 60 min). In addition, the model provides competitive performance in providing effective prediction horizon (<inline-formula><tex-math notation="LaTeX">$\text{PH}_{\text{eff}}$</tex-math></inline-formula>) with minimal time lag both in a simulated patient dataset (<inline-formula><tex-math notation="LaTeX">$\text{PH}_{\text{eff}}$</tex-math></inline-formula> = 29.0 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 0.7 for 30 min and <inline-formula><tex-math notation="LaTeX">$\text{PH}_{\text{eff}}$</tex-math></inline-formula> = 49.8 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 2.9 for 60 min) and in a real patient dataset (<inline-formula><tex-math notation="LaTeX">$\text{PH}_{\text{eff}}$</tex-math></inline-formula> = 19.3 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 3.1 for 30 min and <inline-formula><tex-math notation="LaTeX">$\text{PH}_{\text{eff}}$</tex-math></inline-formula> = 29.3 <inline-formula><tex-math notation="LaTeX">$\pm$</tex-math></inline-formula> 9.4 for 60 min). This approach is evaluated on a dataset of ten simulated cases generated from the UVA/Padova simulator and a clinical dataset of ten real cases each containing glucose readings, insulin bolus, and meal (carbohydrate) data. Performance of the recurrent convolutional neural network is benchmarked against four algorithms. The proposed algorithm is implemented on an Android mobile phone, with an execution time of 6 ms on a phone compared to an execution time of 780 ms on a laptop.
Machine Learning Based Classification of Deep Brain Stimulation Outcomes in a Rat Model of Binge Eating Using Ventral Striatal Oscillations

Neuromodulation-based interventions continue to be evaluated across an array of appetitive disorders but broader implementation of these approaches remains limited due to variable treatment outcomes. We hypothesize that individual variation in treatment outcomes may be linked to differences in the networks underlying these disorders. Here, Sprague-Dawley rats received deep brain stimulation separately within each nucleus accumbens (NAc) sub-region (core and shell) using a within-animal crossover design in a rat model of binge eating. Significant reductions in binge size were observed with stimulation of either target but with significant variation in effectiveness across individuals. When features of local field potentials (LFPs) recorded from the NAc were used as predictors of the pre-defined stimulation outcomes (response or non-response) from each rat using a machine-learning approach (lasso), stimulation outcomes could be predicted with greater accuracy than expected by chance (effect sizes: core = 1.13, shell = 1.05). Further, these LFP features could be used to identify the best stimulation target for each animal (core vs. shell) with an effect size = 0.96. These data suggest that individual differences in underlying network activity may contribute to the variable outcomes of circuit based interventions and that measures of network activity have the potential to individually guide the selection of an optimal stimulation target and improve overall treatment response rates.
Impact of a Multidisciplinary Infection Prevention Initiative on Central Line and Urinary Catheter Utilization in a Long-term Acute Care Hospital

Abstract Background Prolonged central line (CL) and urinary catheter (UC) use can increase risk of central line–associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI). Methods This interventional study conducted in a 76-bed long-term acute care hospital (LTACH) in Southeast Michigan was divided into 3 periods: pre-intervention (January 2015–June 2015), intervention (July–November 2015), and postintervention (December 2015–March 2017). During the intervention period, a multidisciplinary infection prevention team (MIPT) made weekly recommendations to remove unnecessary CL/UC or switch to alternate urinary/intravenous access. Device utilization ratios (DURs) and infection rates were compared between the study periods. Interrupted time series (ITS) and 0-inflated poisson (ZIP) regression were used to analyze DUR and CLABSI/CAUTI data, respectively. Results UC-DUR was 31% in the pre- and postintervention periods and 21% in the intervention period. CL-DUR decreased from 46% (pre-intervention) to 39% (intervention) to 37% (postintervention). The results of ITS analysis indicated nonsignificant decrease and increase in level/trend in DURs coinciding with our intervention. The CAUTI rate per catheter-days did not decrease during intervention (4.36) compared with pre- (2.49) and postintervention (1.93). The CLABSI rate per catheter-days decreased by 73% during intervention (0.39) compared with pre-intervention (1.45). Rates again quadrupled postintervention (1.58). ZIP analysis indicated a beneficial effect of intervention on infection rates without reaching statistical significance. Conclusions We demonstrated that a workable MIPT initiative focusing on removal of unnecessary CL and UC can be easily implemented in an LTACH requiring minimal time and resources. A rebound increase in UC-DURs to pre-intervention levels after intervention end indicates that continued vigilance is required to maintain performance.
Novel Biological and Technological Platforms for Dental Clinical Use

Human teeth have a limited capacity to regenerate and thus biological reconstruction of damaged or lost dental tissues remains a significant challange in modern dentistry. Recent efforts focus on alternative therapeutic approaches for partial or whole tooth regeneration that complement traditional dental treatments using sophisticated materials and dental implants. These multidisciplinary approaches are based on the combination of stem cells with advanced tissue engineer products and computing technology, and they hold great promise for future applications in dentistry. The administration to patients of dynamic biological agents composed by stem cells and scaffolds will certainly increase the regenerative capacity of dental pathological tissues. The design of innovative materials for tissue restoration, diagnostics, imaging, and targeted pharmaceutical treatment will significantly improve the quality of dental care and will have a major societal impact. This review depicts the current challenges in dentistry and describes the possibilities for novel and succesful therapeutic applications in the near future.
Need A Boost? A Comparison of Traditional Commuting Models with the XGBoost Model for Predicting Commuting Flows (Short Paper)

Commuting models estimate the number of commuting trips from home to work locations in a given area. Since their infancy, they have been increasingly used in a variety of fields to reduce traffic and pollution, drive infrastructure choices, and solve a variety of other problems. Traditional commuting models, such as gravity and radiation models, typically have a strict structural form and limited number of input variables, which may limit their ability to predict commuting flows as well as machine learning models that might better capture the complex dynamics of the commuting process. To determine whether machine learning models might add value to the field of commuter flow prediction, we compare and discuss the performance of two standard traditional models with the XGBoost machine learning algorithm for predicting home to work commuter flows from a well-known United States commuting dataset. We find that the XGBoost model outperforms the traditional models on three commonly used metrics, indicating that machine learning models may add value to the field of commuter flow prediction. 2012 ACM Subject Classification Applied computing → Law, social and behavioral sciences
Association of the WNT3 Variations and the Risk of Non-Syndromic Cleft Lip and Palate in a Population of Iranian Infants

Background: Nonsyndromic cleft lip and/or palate (NSCL/P) is the most common orofacial birth defect, often attributed to ethnic and environmental differences. Up to now, linkage analyses and genome-wide association studies have identified several genomic susceptibility regions for NSCL/P. The WNT genes including WNT3 are strong candidates for NSCL/P, since they are involved in regulating mid-face development and upper lip fusion. This study tested association of the WNT3 polymorphisms, rs-3809857 G/T and rs9890413 G/A, with the risk of NSCL/P in a population of Iranian infants. Methods: The allelic and genotypic frequencies for each participant were determined in 113 unrelated Iranian subjects with NSCL/P and 220 control subjects using PCR and restriction fragment length polymorphism (RFLP) methods. A p-value of ≤0.05 was considered statistically significant. Results: The WNT3 rs3809857 GT genotype was significantly lower (p=0.039, OR=0.55, 95% CI=0.30–0.97) in the NSCL/P (21.2%) than the control group (30.42%). For the WNT3 rs9890413 G/A polymorphism, neither genotype nor allele frequencies were significantly different between the case and control groups. Conclusion: Our results indicated that the WNT3 rs3809857 GT genotype may have a protective effect against NSCL/P in Iranian population.
Processivity of dimeric kinesin‐1 molecular motors

Kinesin‐1 is a homodimeric motor protein that can move along microtubule filaments by hydrolyzing ATP with a high processivity. How the two motor domains are coordinated to achieve such high processivity is not clear. To address this issue, we computationally studied the run length of the dimer with our proposed model. The computational data quantitatively reproduced the puzzling experimental data, including the dramatically asymmetric character of the run length with respect to the direction of external load acting on the coiled‐coil stalk, the enhancement of the run length by addition of phosphate, and the contrary features of the run length for different types of kinesin‐1 with extensions of their neck linkers compared with those without extension of the neck linker. The computational data on other aspects of the movement dynamics such as velocity and durations of one‐head‐bound and two‐head‐bound states in a mechanochemical coupling cycle were also in quantitative agreement with the available experimental data. Moreover, predicted results are provided on dependence of the run length upon external load acting on one head of the dimer, which can be easily tested in the future using single‐molecule optical trapping assays.
Genome-Wide Characterization of Endogenous Retroviruses in Bombyx mori Reveals the Relatives and Activity of env Genes

Endogenous retroviruses (ERVs) are retroviral sequences that remain fixed in the host genome, where they could play an important role. Some ERVs have been identified in insects and proven to have infectious properties. However, no information is available regarding Bombyx mori ERVs (BmERVs) to date. Here, we systematically identified 256 potential BmERVs in the silkworm genome via a whole-genome approach. BmERVs were relatively evenly distributed across each of the chromosomes and accounted for about 25% of the silkworm genome. All BmERVs were classified as young ERVs, with insertion times estimated to be less than 10 million years. Seven BmERVs possessing the env genes were identified. With the exception of the Orf133 Helicoverpa armigera nuclear polyhedrosis virus, the env sequences of BmERVs were distantly related to genes encoding F (Fa and Fb) and GP64 proteins from Group I and Group II NPVs. In addition, only the amino acid sequence of the BmERV-21 envelope protein shared a similar putative furin-like cleavage site and fusion peptide with Group II baculoviruses. All of the env genes in the seven BmERVs were verified to exist in the genome and be expressed in the midgut and fat bodies, which suggest that BmERVs might play an important role in the host biology.
Foveal Avascular Zone and Vessel Density in Healthy Subjects: An Optical Coherence Tomography Angiography Study

Purpose: To report the normal characteristics and correlations of the foveal microvascular networks using optical coherence tomography angiography (OCTA) in a healthy Iranian population. Methods: Enface 3x3 OCTA images were obtained using the RTVue Avanti spectral-domain optical coherence tomography with AngioVue software (Optovue, Fremont, CA, USA). Foveal avascular zone (FAZ) area, central foveal point thickness and inner retinal thickness at the foveal center and the vascular density of the superficial retinal capillary plexus (SCP) and deep retinal capillary plexus (DCP) in the fovea were recorded. Results: Seventy normal eyes of 70 subjects (range, 9 to 71 years) were studied. Mean FAZ area was 0.32 ± 0.11 (range, 0.13-0.67) mm2 in SCP and 0.50 ± 0.13 (range, 0.19-0.94) mm2 in DCP. Mean SCP vessel density was 29.6 ± 4.7 (range, 16.3-40.3) % in the fovea. Mean DCP vessel density was 27.0 ± 5.9 (range, 15.0-45.2) % in the fovea. The FAZ area at SCP level was negatively correlated to the central subfield thickness (P < 0.001). The FAZ area at DCP level correlated negatively to the central subfield thickness and was significantly associated to age (both P < 0.001). The foveal SCP vessel density significantly correlated with foveal thickness and the foveal DCP vessel density correlated significantly with central foveal subfield thickness and was inversely related to age (all P < 0.05). Conclusion: In this study, central foveal subfield thickness was a major determinant of the FAZ size and foveal vessel density. Age was a determinant for FAZ area and whole image vessel density in DCP.