Miracle-dz/UniFAR-FTUs huggingface dataset:
Behavioral Phenotyping of an Improved Mouse Model of Phelan–McDermid Syndrome with a Complete Deletion of the Shank3 Gene

Abstract Phelan–McDermid syndrome (PMS) is a rare genetic disorder in which one copy of the SHANK3 gene is missing or mutated, leading to a global developmental delay, intellectual disability (ID), and autism. Multiple intragenic promoters and alternatively spliced exons are responsible for the formation of numerous isoforms. Many genetically-modified mouse models of PMS have been generated but most disrupt only some of the isoforms. In contrast, the vast majority of known SHANK3 mutations found in patients involve deletions that disrupt all isoforms. Here, we report the production and thorough behavioral characterization of a new mouse model in which all Shank3 isoforms are disrupted. Domains and tasks examined in adults included measures of general health, neurological reflexes, motor abilities, sensory reactivity, social behavior, repetitive behaviors, cognition and behavioral inflexibility, and anxiety. Our mice are more severely affected than previously published models. While the deficits were typically more pronounced in homozygotes, an intermediate phenotype was observed for heterozygotes in many paradigms. As in other Shank3 mouse models, stereotypies, including increased grooming, were observed. Additionally, sensory alterations were detected in both neonatal and adult mice, and motor behavior was strongly altered, especially in the open field and rotarod locomotor tests. While social behaviors measured with the three-chambered social approach and male-female interaction tests were not strongly impacted, Shank3-deficient mice displayed a strong escape behavior and avoidance of inanimate objects in novel object recognition, repetitive novel object contact, marble burying, and nest building tasks, indicating increased novelty-induced anxiety. Similarly, increased freezing was observed during fear conditioning training and amygdala-dependent cued retrieval. Finally, deficits were observed in both initial training and reversal in the Barnes maze and in contextual fear testing, which are memory tasks involving hippocampal-prefrontal circuits. In contrast, working memory in the Y-maze spontaneous alternation test was not altered. This new mouse model of PMS, engineered to most closely represent human mutations, recapitulates core symptoms of PMS providing improvements for both construct and face validity, compared to previous models.
Knowledge, attitude and practices about complementary feeding among mothers of children aged 6 to 24 months in tertiary care centre of Kumaun region, India

Background: Well-being of child is directly related to the nutritional status of the baby. Malnutrition rate increases between 6 and 18 months- the period of complementary feeding. Complementary feeding is the introduction of semisolid or solid food in infant who is on breast feeding, when mother’s milk is no longer enough to meet the nutritional needs. Understanding the social beliefs, knowledge, attitude and practices about complementary feeding among mothers is an important step prior to designing an intervention strategy to prevent malnutrition in children. Aim of the study was to assess the knowledge, attitude and practices regarding complementary feeding among mothers.Methods: Prospective study including 200 mothers with children between 6 to 24 months of age in GMC Haldwani, from December 2017 to May 2018.Results: Present study shows 60.5% mothers initiate their breast milk soon after delivery. The initiation of complementary food at the age of 8 months, 6 month and 4-5 months were 64 (32%), 104(52%) and 32 (16%) respectively. 68% mothers did not properly clean their children hands and utensils before feeding Use of janam ghutti 64% and dilution of cow milk 79% was the major part of complementary feeding.Conclusions: Mother’s knowledge regarding timing of complementary feeding is inadequate and practices are inappropriate. Majority of them are not aware of the current recommendations. It is essential to give accurate information and education about complementary feeding to prevent malnutrition and improve the health status of children.
Exploring biogeographic patterns of bacterioplankton communities across global estuaries

Estuaries provide an ideal niche to study structure and function of bacterioplankton communities owing to the presence of a multitude of environmental stressors. Bacterioplankton community structures from nine global estuaries were compared to understand their broad‐scale biogeographic patterns. Bacterioplankton community structure from four estuaries of Sundarbans, namely Mooriganga, Thakuran, Matla, and Harinbhanga, was elucidated using Illumina sequencing. Bacterioplankton communities from these estuaries were compared against available bacterioplankton sequence data from Columbia, Delaware, Jiulong, Pearl, and Hangzhou estuaries. All nine estuaries were dominated by Proteobacteria. Other abundant phyla included Bacteroidetes, Firmicutes, Acidobacteria, Actinobacteria, Cyanobacteria, Planctomycetes, and Verrucomicrobia. The abundant bacterial phyla showed a ubiquitous presence across the estuaries. At class level, the overwhelming abundance of Gammaproteobacteria in the estuaries of Sundarbans and Columbia estuary clearly stood out amidst high abundance of Alphaproteobacteria observed in the other estuaries. Abundant bacterial families including Rhodobacteriaceae, Shingomonadaceae, Acidobacteriaceae, Vibrionaceae, and Xanthomondaceae also showed ubiquitous presence in the studied estuaries. However, rare taxa including Chloroflexi, Tenericutes, Nitrospirae, and Deinococcus‐Thermus showed clear site‐specific distribution patterns. Such distribution patterns were also reinstated by nMDS ordination plots. Such clustering patterns could hint toward the potential role of environmental parameters and substrate specificity which could result in distinct bacterioplankton communities at specific sites. The ubiquitous presence of abundant bacterioplankton groups along with their strong correlation with surface water temperature and dissolved nutrient concentrations indicates the role of such environmental parameters in shaping bacterioplankton community structure in estuaries. Overall, studies on biogeographic patters of bacterioplankton communities can provide interesting insights into ecosystem functioning and health of global estuaries.
A Note on Max k-Vertex Cover: Faster FPT-AS, Smaller Approximate Kernel and Improved Approximation

In Maximum $k$-Vertex Cover (Max $k$-VC), the input is an edge-weighted graph $G$ and an integer $k$, and the goal is to find a subset $S$ of $k$ vertices that maximizes the total weight of edges covered by $S$. Here we say that an edge is covered by $S$ iff at least one of its endpoints lies in $S$. We present an FPT approximation scheme (FPT-AS) that runs in $(1/\epsilon)^{O(k)} poly(n)$ time for the problem, which improves upon Gupta et al.'s $(k/\epsilon)^{O(k)} poly(n)$-time FPT-AS [SODA'18, FOCS'18]. Our algorithm is simple: just use brute force to find the best $k$-vertex subset among the $O(k/\epsilon)$ vertices with maximum weighted degrees. Our algorithm naturally yields an efficient approximate kernelization scheme of $O(k/\epsilon)$ vertices; previously, an $O(k^5/\epsilon^2)$-vertex approximate kernel is only known for the unweighted version of Max $k$-VC [Lokshtanov et al., STOC'17]. Interestingly, this has an application outside of parameterized complexity: using our approximate kernelization as a preprocessing step, we can directly apply Raghavendra and Tan's SDP-based algorithm for 2SAT with cardinality constraint [SODA'12] to give an $0.92$-approximation for Max $k$-VC in polynomial time. This improves upon Feige and Langberg's algorithm [J. Algorithms'01] which yields $(0.75 + \delta)$-approximation for some (unspecified) constant $\delta > 0$. We also consider the minimization version (Min $k$-VC), where the goal is to minimize the total weight of edges covered by $S$. We provide an FPT-AS for Min $k$-VC with similar running time of $(1/\epsilon)^{O(k)} poly(n)$, which again improves on a $(k/\epsilon)^{O(k)} poly(n)$-time FPT-AS of Gupta et al. On the other hand, we show that there is unlikely a polynomial size approximate kernelization for Min $k$-VC for any factor less than two.
Use of a Machine Learning Algorithm to Predict Individuals with Suicide Ideation in the General Population

Objective In this study, we aimed to develop a model predicting individuals with suicide ideation within a general population using a machine learning algorithm. Methods Among 35,116 individuals aged over 19 years from the Korea National Health & Nutrition Examination Survey, we selected 11,628 individuals via random down-sampling. This included 5,814 suicide ideators and the same number of non-suicide ideators. We randomly assigned the subjects to a training set (n=10,466) and a test set (n=1,162). In the training set, a random forest model was trained with 15 features selected with recursive feature elimination via 10-fold cross validation. Subsequently, the fitted model was used to predict suicide ideators in the test set and among the total of 35,116 subjects. All analyses were conducted in R. Results The prediction model achieved a good performance [area under receiver operating characteristic curve (AUC)=0.85] in the test set and predicted suicide ideators among the total samples with an accuracy of 0.821, sensitivity of 0.836, and specificity of 0.807. Conclusion This study shows the possibility that a machine learning approach can enable screening for suicide risk in the general population. Further work is warranted to increase the accuracy of prediction.
MESOPIC AND DARK-ADAPTED TWO-COLOR FUNDUS-CONTROLLED PERIMETRY IN GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE To investigate retinal sensitivity in the junctional zone of geographic atrophy (GA) secondary to age-related macular degeneration using patient-tailored perimetry grids for mesopic and dark-adapted two-color fundus-controlled perimetry. METHODS Twenty-five eyes with GA of 25 patients (prospective, natural-history Directional Spread in Geographic Atrophy study [DSGA; NCT02051998]) and 40 eyes of 40 normal subjects were included. Patient-tailored perimetry grids were generated using annotated fundus autofluorescence data. Customized software positioned test-points along iso-hulls surrounding the GA boundary at distances of 0.43°, 0.86°, 1.29°, 2.15°, and 3.01°. The grids were used for duplicate mesopic and dark-adapted two-color (cyan and red) fundus-controlled perimetry. Age-adjusted reference-data were obtained through regression analysis of normative data followed by spatial interpolation. RESULTS The mean sensitivity loss for mesopic testing decreased with the distance to GA (-10.3 dB [0.43°], -8.2 dB [0.86°], -7.1 dB [1.29°], -6.8 dB [2.15°], and -6.6 dB [3.01°]; P < 0.01). Dark-adapted cyan sensitivity loss exceeded dark-adapted red sensitivity loss for all iso-hulls (-14.8 vs. -11.7 dB, -13.5 vs. -10.1 dB, -12.8 vs. -9.1 dB, -11.6 vs. -8.2 dB, -10.7 vs. -8.0 dB; P < 0.01). CONCLUSION Patient-tailored fundus-controlled perimetry grids allowed for testing of retinal function in the junctional zone of GA with high spatial resolution. A distinct decrease in mesopic sensitivity loss between 0.43° (125 µm) and 1.29° (375 µm) was observed that leveled off at more distant test-points. In proximity to the GA boundary, the results indicate that rod exceeded cone dysfunction.
Development and Validation of a New Tool to Assess Burden of Dietary Sodium Restriction in Patients with Chronic Heart Failure: The BIRD Questionnaire

(1) Background: Burden scales are useful in estimating the impact of interventions from patients’ perspectives. This is overlooked in sodium diet/heart failure (HF). The aim of this study is to develop and validate a specific tool to assess the burden associated with low-sodium diets in HF: the Burden scale In Restricted Diets (BIRD). (2) Methods: Based on the literature and reports from patients, 14 candidate items were identified for the following dietary-related domains: organization, pleasure, leisure, social life, vitality, and self-rated health. The validation study was conducted prospectively. The questionnaire was refined via item reduction according to inter-item correlations and exploratory factor analysis. Internal consistency was determined using Cronbach’s alpha (Cα) and convergent validity by assessing correlations between BIRD and the health-related quality of life (HRQoL) Minnesota Living with HF questionnaire (MLHF). (3) Results: Of the 152 invited patients, 96 (63%) returned the questionnaire. The median score was 6.5 (IQR 2.0–14.0). The results showed good acceptability (non-response rates/item from 2.0% to 12.1%), an excellent internal consistency (Cα = 0.903) and a good convergent validity (rhos = 0.37 (physical), 0.4 (mental), and 0.45 (global); all p < 0.05). (4) Conclusions: BIRD demonstrates good psychometric properties and is useful to quantify the burden associated with sodium restriction. It may help optimize dietary interventions and improve the overall management of patients with HF.
Twenty years of research on attention-deficit/hyperactivity disorder (ADHD): looking back, looking forward

In this clinical review we summarise what in our view have been some the most important advances in the past two decades, in terms of diagnostic definition, epidemiology, genetics and environmental causes, neuroimaging/cognition and treatment of attention-deficit/hyperactivity disorder (ADHD), including: (1) the most recent changes to the diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases; (2) meta-analytic evidence showing that, after accounting for diagnostic methods, the rates of ADHD are fairly consistent across Western countries; (3) the recent finding of the first genome-wide significant risk loci for ADHD; (4) the paradigm shift in the pathophysiological conceptualisation of ADHD from alterations in individual brain regions to a complex dysfunction in brain networks; (5) evidence supporting the short-term efficacy of ADHD pharmacological treatments, with a different profile of efficacy and tolerability in children/adolescents versus adults; (6) a series of meta-analyses showing that, while non-pharmacological treatment may not be effective to target ADHD core symptoms, some of them effectively address ADHD-related impairments (such as oppositional behaviours for parent training and working memory deficits for cognitive training). We also discuss key priorities for future research in each of these areas of investigation. Overall, while many research questions have been answered, many others need to be addressed. Strengthening multidisciplinary collaborations, relying on large data sets in the spirit of Open Science and supporting research in less advantaged countries will be key to face the challenges ahead.
Mucosal Changes in the Small Intestines in Portal Hypertension: First Study Using the Pillcam SB3 Capsule Endoscopy System

Background/Aims To evaluate patients with portal hypertension (PH) of varied etiologies for portal hypertensive enteropathy (PHE) using the PillCam SB3 capsule endoscopy (CE) system. Methods Consecutive patients with PH presenting with unexplained anemia and/or occult gastrointestinal bleeding were evaluated using the PillCam SB3 CE system. Abnormal findings were categorized as vascular or non-vascular. The patients with ongoing bleeding caused by PHE were treated. The correlation of the CE scores of PHE with the clinical, laboratory, and endoscopic features was determined. Results Of the 43 patients included in the study, 41 (95.3%) showed PHE findings. These included varices (67.4%), red spots (60.5%), erythema (44.2%), villous edema (46.5%), telangiectasia (16.3%), and polyps (16.3%). The CE scores varied from 0 to 8 (mean±standard deviation, 4.09±1.8). Five patients (11.6%) showed evidence of ongoing or recent bleeding due to PHE. Three of these five patients underwent endotherapy, and one patient underwent radiological coil placement. Conclusions The PillCam SB3 CE system revealed a high prevalence of PHE in the patients with PH. Using this system, evidence of bleeding due to PHE was found in a small but definite proportion of the patients.
A Multicomponent Neuronal Response Encodes the Larval Decision to Pupariate upon Amino Acid Starvation

Organisms need to coordinate growth with development, particularly in the context of nutrient availability. Thus, multiple ways have evolved to survive extrinsic nutrient deprivation during development. In Drosophila, growth occurs during larval development. Larvae are thus critically dependent on nutritional inputs; but after critical weight, they pupariate even when starved. How nutrient availability is coupled to the internal metabolic state for the decision to pupariate needs better understanding. We had earlier identified glutamatergic interneurons in the ventral ganglion that regulate pupariation on a protein-deficient diet. Here we report that Drosophila third instar larvae (either sex) sense arginine to evaluate their nutrient environment using an amino acid transporter Slimfast. The glutamatergic interneurons integrate external protein availability with internal metabolic state through neuropeptide signals. IP3-mediated calcium release and store-operated calcium entry are essential in these glutamatergic neurons for such integration and alter neuronal function by reducing the expression of multiple ion channels. SIGNIFICANCE STATEMENT Coordinating growth with development, in the context of nutrient availability is a challenge for all organisms in nature. After attainment of “critical weight,” insect larvae can pupariate, even in the absence of nutrition. Mechanism(s) that stimulate appropriate cellular responses and allow normal development on a nutritionally deficient diet remain to be understood. Here, we demonstrate that nutritional deprivation, in postcritical weight larvae, is sensed by special sensory neurons through an amino acid transporter that detects loss of environmental arginine. This information is integrated by glutamatergic interneurons with the internal metabolic state through neuropeptide signals. These glutamatergic interneurons require calcium-signaling-regulated expression of a host of neuronal channels to generate complex calcium signals essential for pupariation on a protein-deficient diet.
The Volume of Hippocampal Subfields in Relation to Decline of Memory Recall Across the Adult Lifespan

Background: The hippocampus is an important limbic structure closely related to memory function. However, few studies have focused on the association between hippocampal subfields and age-related memory decline. We investigated the volume alterations of hippocampal subfields at different ages and assessed the correlations with Immediate and Delayed recall abilities. Materials and Methods: A total of 275 participants aged 20–89 years were classified into 4 groups: Young, 20–35 years; Middle-early, 36–50 years; Middle-late, 51–65 years; Old, 66–89 years. All data were acquired from the Dallas Lifespan Brain Study (DLBS). The volumes of hippocampal subfields were obtained using Freesurfer software. Analysis of covariance (ANCOVA) was performed to analyze alterations of subfield volumes among the 4 groups, and multiple comparisons between groups were performed using the Bonferroni method. Spearman correlation with false discovery rate correction was used to investigate the relationship between memory recall scores and hippocampal subfield volumes. Results: Apart from no significant difference in the left parasubiculum (P = 0.269) and a slight difference in the right parasubiculum (P = 0.022), the volumes of other hippocampal subfields were significantly different across the adult lifespan (P < 0.001). The hippocampal fissure volume was increased in the Old group, while volumes for other subfields decreased. In addition, Immediate recall scores were associated with volumes of the bilateral molecular layer, granule cell layer of the dentate gyrus (GC-DG), cornus ammonis (CA) 1, CA2/3, CA4, left fimbria and hippocampal amygdala transition area (HATA), and right fissure (P < 0.05). Delayed recall scores were associated with the bilateral molecular layer, GC-DG, CA2/3 and CA4; left tail, presubiculum, CA1, subiculum, fimbria and HATA (P < 0.05). Conclusion: The parasubiculum volume was not significantly different across the adult lifespan, while atrophy in dementia patients in some studies. Based on these findings, we speculate that volume changes in this region might be considered as a biomarker for dementia disorders. Additionally, several hippocampal subfield volumes were significantly associated with memory scores, further highlighting the key role of the hippocampus in age-related memory decline. These regions could be used to assess the risk of memory decline across the adult lifespan.
Global genetic insight contributed by consanguineous Pakistani families segregating hearing loss

Consanguineous Pakistani pedigrees segregating deafness have contributed decisively to the discovery of 31 of the 68 genes associated with nonsyndromic autosomal recessive hearing loss (HL) worldwide. In this study, we utilized genome‐wide genotyping, Sanger and exome sequencing to identify 163 DNA variants in 41 previously reported HL genes segregating in 321 Pakistani families. Of these, 70 (42.9%) variants identified in 29 genes are novel. As expected from genetic studies of disorders segregating in consanguineous families, the majority of affected individuals (94.4%) are homozygous for HL‐associated variants, with the other variants being compound heterozygotes. The five most common HL genes in the Pakistani population are SLC26A4, MYO7A, GJB2, CIB2 and HGF, respectively. Our study provides a profile of the genetic etiology of HL in Pakistani families, which will allow for the development of more efficient genetic diagnostic tools, aid in accurate genetic counseling, and guide application of future gene‐based therapies. These findings are also valuable in interpreting pathogenicity of variants that are potentially associated with HL in individuals of all ancestries. The Pakistani population, and its infrastructure for studying human genetics, will continue to be valuable to gene discovery for HL and other inherited disorders.