Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical reappraisal of mechanistic links of copy number variants to dimensional constructs of neuropsychiatric disorders in mouse models

Copy number variants are deletions and duplications of a few thousand to million base pairs and are associated with extraordinarily high levels of autism spectrum disorder, schizophrenia, intellectual disability, or attention‐deficit hyperactivity disorder. The unprecedented levels of robust and reproducible penetrance of copy number variants make them one of the most promising and reliable entry points to delve into the mechanistic bases of many mental disorders. However, the precise mechanistic bases of these associations still remain elusive in humans due to the many genes encoded in each copy number variant and the diverse associated phenotypic features. Genetically engineered mice have provided a technical means to ascertain precise genetic mechanisms of association between copy number variants and dimensional aspects of mental illnesses. Molecular, cellular, and neuronal phenotypes can be detected as potential mechanistic substrates for various behavioral constructs of mental illnesses. However, mouse models come with many technical pitfalls. Genetic background is not well controlled in many mouse models, leading to rather obvious interpretative issues. Dose alterations of many copy number variants and single genes within copy number variants result in some molecular, cellular, and neuronal phenotypes without a behavioral phenotype or with a behavioral phenotype opposite to what is seen in humans. In this review, I discuss technical and interpretative pitfalls of mouse models of copy number variants and highlight well‐controlled studies to suggest potential neuronal mechanisms of dimensional aspects of mental illnesses. Mouse models of copy number variants represent toeholds to achieve a better understanding of the mechanistic bases of dimensions of neuropsychiatric disorders and thus for development of mechanism‐based therapeutic options in humans.
A Kinematic Link Between Boxy Bulges, Stellar Bars, and Nuclear Activity in NGC 3079 and NGC 4388

We present direct kinematic evidence for bar streaming motions in two active galaxies with boxy stellar bulges. The Hawaii Imaging Fabry-Perot Interferometer was used on the 3.6 m Canada-France-Hawaii Telescope and the University of Hawaii 2.2 m telescope to derive the two-dimensional velocity field of the line-emitting gas in the disks of the Sc galaxy NGC 3079 and the Sb galaxy NGC 4388. In contrast to previous work based on long-slit data, the detection of the bar potential from the Fabry-Perot data does not rely on the existence of inner Lindblad resonances or strong bar-induced shocks. Simple kinematic models that approximate the intrinsic gas orbits as nonintersecting, inclined elliptical annuli that conserve angular momentum characterize the observed velocity fields. In NGC 3079, bar streaming motions with moderately eccentric orbits (e = b/a ∼ 0.7) aligned along P.A. = 130° intrinsic to the disk (P.A. = 97° on the sky) are detected out to Rb = 3.6 kpc. The orbits become increasingly circular beyond that radius (e = 1 at Rd ≈ 6 kpc). The best model for NGC 4388 includes highly eccentric orbits (e ∼ 0.3) for Rb ≲ 1.5 kpc, which are aligned along P.A. = 135° intrinsic to the disk (P.A. = 100° on the sky). The observed "spiral arms" are produced by having the orbits become increasingly circular from the ends of the bar to the edge of the disk (Rd ≈ 5 kpc) and the intrinsic bar position angle shifting from 135° to 90°. Box-shaped bulges in both NGC 3079 and NGC 4388 are confirmed using new near-infrared images to reduce dust obscuration. Morphological analysis of starlight in these galaxies is combined with the gas kinematics derived from the Fabry-Perot spectra to test evolutionary models of stellar bars that involve transitory, boxy bulges and to quantify the importance of such bars in fueling active nuclei. Our data support the evolutionary bar models but fail to prove convincingly that the stellar bars in NGC 3079 and NGC 4388 directly trigger or sustain the nuclear activity.
Nutritional Supplements for Cancer-Associated Fatigue and Cancer Therapy – A Molecular Basis for Restoring Mitochondrial Function

is now the leading cause of death in the world. In the U.S., one in two men and one in three women will be diagnosed with a non-skin cancer in their lifetime. Cancer patients are living longer than ever before. For instance, when detected early, the five-year survival for breast cancer is 98%, and it is about 84% in patients with regional disease. However, the diagnosis and treatment of cancer is very distressing. Cancer patients frequently suffer from pain, disfigurement, depression, fatigue, physical dysfunctions, frequent visits to doctors and hospitals, multiple tests and procedures with the possibility of treatment complications, and the financial impact of the diagnosis on their life. This book presents a number of ways that can help cancer patients to look, feel and become healthier, take care of specific symptoms such as hair loss, arm swelling, and shortness of breath, and improve their intimacy, sexuality, and fertility.
Efficient Segmentation of a Breast in B-Mode Ultrasound Tomography Using Three-Dimensional GrabCut (GC3D)

As an emerging modality for whole breast imaging, ultrasound tomography (UST), has been adopted for diagnostic purposes. Efficient segmentation of an entire breast in UST images plays an important role in quantitative tissue analysis and cancer diagnosis, while major existing methods suffer from considerable time consumption and intensive user interaction. This paper explores three-dimensional GrabCut (GC3D) for breast isolation in thirty reflection (B-mode) UST volumetric images. The algorithm can be conveniently initialized by localizing points to form a polygon, which covers the potential breast region. Moreover, two other variations of GrabCut and an active contour method were compared. Algorithm performance was evaluated from volume overlap ratios (TO, target overlap; MO, mean overlap; FP, false positive; FN, false negative) and time consumption. Experimental results indicate that GC3D considerably reduced the work load and achieved good performance (TO = 0.84; MO = 0.91; FP = 0.006; FN = 0.16) within an average of 1.2 min per volume. Furthermore, GC3D is not only user friendly, but also robust to various inputs, suggesting its great potential to facilitate clinical applications during whole-breast UST imaging. In the near future, the implemented GC3D can be easily automated to tackle B-mode UST volumetric images acquired from the updated imaging system.
Spatial organization of chromatin domains and compartments in single chromosomes

Spatial organization inside the nucleus In eukaryotic cells, DNA is packaged into a complex macromolecular structure called chromatin. Wang et al. have developed an imaging method to map the position of multiple regions on individual chromosomes, and the results confirm that chromatin is organized into large contact domains called TADS (topologically associating domains). Unexpectedly, though, folding deviates from the classical fractal-globule model at large length scales. Science, this issue p. 598 Imaging that maps chromatin domains reveals polarized arrangements of chromatin compartments and nonfractal chromosome folding. The spatial organization of chromatin critically affects genome function. Recent chromosome-conformation-capture studies have revealed topologically associating domains (TADs) as a conserved feature of chromatin organization, but how TADs are spatially organized in individual chromosomes remains unknown. Here, we developed an imaging method for mapping the spatial positions of numerous genomic regions along individual chromosomes and traced the positions of TADs in human interphase autosomes and X chromosomes. We observed that chromosome folding deviates from the ideal fractal-globule model at large length scales and that TADs are largely organized into two compartments spatially arranged in a polarized manner in individual chromosomes. Active and inactive X chromosomes adopt different folding and compartmentalization configurations. These results suggest that the spatial organization of chromatin domains can change in response to regulation.
Prediction of 6-month survival of nursing home residents with advanced dementia using ADEPT vs hospice eligibility guidelines.

CONTEXT Estimating life expectancy is challenging in advanced dementia, potentially limiting the use of hospice care in these patients. OBJECTIVE To prospectively validate and compare the performance of the Advanced Dementia Prognostic Tool (ADEPT) and hospice eligibility guidelines to estimate 6-month survival in nursing home residents with advanced dementia. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study conducted in 21 nursing homes in Boston, Massachusetts, of 606 residents with advanced dementia who were recruited between November 1, 2007, and July 30, 2009. Data were ascertained at baseline to determine the residents' ADEPT score (range, 1.0-32.5; higher scores indicate worse prognosis) and whether they met Medicare hospice eligibility guidelines. Survival was followed up to 6 months. MAIN OUTCOME MEASURES Assessment and comparison of the performance of the ADEPT score and hospice guidelines to predict 6-month survival using sensitivity, specificity, and the area under the receiver operating characteristic (AUROC) curve. RESULTS At baseline, the residents' mean (SD) ADEPT score was 10.1 (3.1) points and 65 residents (10.7%) met hospice eligibility guidelines. Over 6 months, 111 residents (18.3%) died. The AUROC for the ADEPT score's prediction of 6-month mortality as a continuous variable was 0.67 (95% confidence interval [CI], 0.62-0.72). The AUROC for Medicare hospice eligibility guidelines was 0.55 (95% CI, 0.51-0.59), the specificity was 0.89 (95% CI, 0.86-0.92), and the sensitivity was 0.20 (95% CI, 0.13-0.28). Using a cutoff of 13.5 on the ADEPT score, which also had specificity of 0.89, the AUROC was 0.58 (95% CI, 0.54-0.63) and the sensitivity was 0.27 (95% CI, 0.19-0.36). CONCLUSIONS When prospectively validated at the bedside and used as a continuous measure, the ability of the ADEPT score to identify nursing home residents with advanced dementia at high risk of death within 6 months was modest, albeit better than hospice eligibility guidelines. Care provided to these residents should be guided by their goals of care rather than estimated life expectancy.
Anti-Epstein–Barr virus antibodies in Beijing during 2013–2017: What we have found in the different patients

Background Epstein–Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC) which is prevalent in South China, and its association with systemic lupus erythematosus (SLE) or other autoimmune diseases has not been studied in the mainland of China. The EBV serological tests have been performed on patients with various diseases or manifestations for years at our institution and their values need to be evaluated. Methods For routine medical purposes, anti-EB viral capsid antigen (VCA) IgG, IgA and IgM antibodies, anti-EBV diffuse early antigen (EA-D) IgA antibodies, and anti-EBV nuclear antigen-1(EBNA-1) IgG antibodies were tested with commercial enzyme-linked immunosorbent assay (ELISA) in patients visiting Peking Union Medical College Hospital between 2013 and 2017. The test results were analyzed in this retrospective study. Results There were a total of 11122 serum samples available to be tested in the study. As indicators of past EBV infection, the prevalence of VCA-IgG/EBNA1-IgG were 66.6%/58.5%, 84.3%/78.8%, 92.9%/87.0% and 98.5%/95.4% in patients aged under 5 years, 6–10 years, 11–20 years and 21–30 years old, respectively, and these values maintained at this highest rate as age increased further. The prevalence of VCA-IgM, as a parameter of acute EBV infection, was 14.6%, 10.2%, 10.4%, 6.3% and 3.1% in patients aged under 5 years, 6–10 years,11–20 years, 21–30 years, 31–40 years old, respectively, and decreased to 2%~3% in older patients. Patients with elevated serum liver enzymes were more likely to have a higher prevalence of EA/D IgA antibody (P < 0.01) and young patients (≤30 years) with lymphadenopathy were more likely to have higher prevalence of VCA-IgM antibody (P < 0.01). The prevalence of VCA-IgA and EAD-IgA were 87.0% and 59.2% in NPC patients, respectively, and both were significantly higher (P < 0.001) than that in non-NPC patients. The prevalence of VCA-IgA was 45.4% and 25.6% in SLE patients and patients with other autoimmune diseases, respectively, which were significantly (P < 0.001) and mildly (P = 0.039) higher than their controls. In pediatric SLE patients between 6 and10 years old, the prevalence of VCA-IgG, VCA-IgA and EBNA1-IgG was 100%, 59.5% and 100%, respectively, all being significantly higher than the age (6-10y) related controls (P< 0.01). In the 705 cerebral spinal fluid (CSF) specimens, VCA-IgG, VCA-IgM, VCA-IgA and EAD-IgA were found to be positive in 12.1%, 0.15%, 0.25% and 0.25%, respectively. There were 157 paired specimens (CSF and serum were collected simultaneously) and VCA-IgG was identified as positive in 12.7% of the CSF and 100% of the serum specimens. Conclusions Around 98% of Chinese patients were infected with EBV before 30 years of age and the highest rate of acute EBV infection were observed in patients under 5 years old. EBV infection was found to be associated with elevated serum liver enzymes, NPC and SLE. Acute anti-EBV antibody was valued for young patients with lymphadenopathy but limited value for CNS neuropathy.
Journal of Systems and Information Technology

Purpose – The purpose of this research is to explore the general and specific gratifications obtained from using microblog and WeChat. Design/methodology/approach – To cast light on the difference of gratifications to use microblog and WeChat, 18 interviews with social media users in China were conducted. Findings – The results reveal that, three types of gratifications were obtained from using both microblog and WeChat: content gratification, social gratification, and hedonic gratification. Also, the strength and components of each gratification for microblog and WeChat were different. Content gratification plays the most salient role in using microblog, while social gratification is the most important for WeChat usage. In addition, content gratification of microblog usage is related to information seeking and information sharing, while social gratification of WeChat usage is constituted by private social networking and convenient communication. Furthermore, content gratification of WeChat usage refers to high-quality information provided and information sharing; and entertainment and passing time develop hedonic gratification of microblog usage, while that of WeChat usage refers to entertainment. Originality/value – Extant research has mainly focused on the gratifications of one social media, lacks of studies comparing the motivations in using different social media. Also, only a little research has identified the components of different gratifications and how they affect the adoption of different social media. The current study attempts to fill these research gaps.
Damage-induced reactive oxygen species regulate vimentin and dynamic collagen-based projections to mediate wound repair

Tissue injury leads to early wound-associated reactive oxygen species (ROS) production that mediate tissue regeneration. To identify mechanisms that function downstream of redox signals that modulate regeneration, a vimentin reporter of mesenchymal cells was generated by driving GFP from the vimentin promoter in zebrafish. Early redox signaling mediated vimentin reporter activity at the wound margin. Moreover, both ROS and vimentin were necessary for collagen production and reorganization into projections at the leading edge of the wound. Second harmonic generation time-lapse imaging revealed that the collagen projections were associated with dynamic epithelial extensions at the wound edge during wound repair. Perturbing collagen organization by burn wound disrupted epithelial projections and subsequent wound healing. Taken together our findings suggest that ROS and vimentin integrate early wound signals to orchestrate the formation of collagen-based projections that guide regenerative growth during efficient wound repair.
The Influence of Psychological Factors on the Michigan Hand Questionnaire

Background: Psychosocial factors help account for the gap between impairment and disability. This study examines the relationship between the Michigan Hand Questionnaire (MHQ) and commonly used psychological measures in patients with upper extremity illness. Methods: A cohort of 135 new or follow-up patients presenting to an urban academic hospital–based hand surgeon were invited to complete a web-based version of the MHQ, Abbreviated Pain Catastrophizing Scale (PCS), and two Patient-Reported Outcomes Measurement Information System (PROMIS)-based questionnaires: Pain Interference and Depression. Bivariate and multivariable analyses measured the correlation of these psychological measures with MHQ. Results: Accounting for potential confounding factors in multivariable regression, upper extremity disability as rated by the MHQ was independently associated with PROMIS Depression, PROMIS Pain Interference, visit type, and working status. The model accounted for 37% of the variability in MHQ scores, with PROMIS Pain Interference having the most influence. Conclusion: Among the non-pathophysiological factors that contribute to patient-to-patient variation in MHQ scores, the measure of less effective coping strategies and symptoms of depression were most influential. Our data add to the evidence of the pivotal role of emotional health in upper extremity symptoms and limitations and the importance of psychosocial considerations in the care of hand illness.
Population bottlenecks and patterns of human polymorphism.

Fay and Wu (1999) examine a historical model in which a population quickly shrinks, stays small for some time, and then suddenly recovers its original population size, at which it stays until samples are drawn from it. This is a bottleneck model of the kind traditionally used in population genetics (Nei, Maruyama, and Chakraborty 1975); however, it is not the model that is most commonly considered in the context of genetic evidence of human population size change. That model is one of population size expansion, and it pervades the literature on analysis of mitochondrial DNA (e.g., Rogers and Harpending 1992), as well as the more recent literature on microsatellites (e.g., Kimmel et al. 1998), some of which explicitly confounds ‘‘expansion’’ with ‘‘bottleneck. ’’ Fay and Wu (1999) repeatedly cite Hey (1997), who showed that nuclear genes and mtDNA are not both consistent with simple historical models. However, Hey’s paper explored only models of constant population size and models of expansion. Both of these models are considerably simpler than a bottleneck model, and they were the models that had received most of the attention in the literature. However, Hey’s (1997) paper may have contributed to a confusion over models, for the final sentence did mention ‘‘bottleneck. ’’ Fay and Wu (1999) bring up a valuable point, that the time over which the pattern of polymorphism responds to a change in population size will be greater for larger populations. This means that the polymorphism patterns of genes with inherently different population sizes (e.g., mtDNA and nuclear genes) may be out of phase with one another if the period of population size fluctuation is sufficiently short and the fluctuation has been recent. Fay and Wu’s letter is also timely in light of the increasing amount of nuclear gene data that are emerging. Since Hey’s (1997) paper, which focused mostly on a few small data sets, larger data sets from PDHA1 (Harris and Hey 1999), b-globin (Harding et al. 1997), dystrophin (Zietkiewicz et al. 1998), and lipoprotein lipase (Clark et al. 1998) have been published, and all reveal an abundance of intermediate frequency polymorphism and positive values for Tajima’s D (Tajima 1989b). Also recently, small samples from a series of X-linked loci revealed that five out of six loci had positive values of D (although three were just slightly positive) (Nachman et al. 1998). Thus, the overall im-
Structural determinants of nuclear export signal orientation in binding to exportin CRM1

The Chromosome Region of Maintenance 1 (CRM1) protein mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure. The plasticity of the CRM1-NES interaction is not well understood, as there are many NES sequences that seem incompatible with structures of the NES-bound CRM1 groove. Crystal structures of CRM1 bound to two different NESs with unusual sequences showed the NES peptides binding the CRM1 groove in the opposite orientation (minus) to that of previously studied NESs (plus). Comparison of minus and plus NESs identified structural and sequence determinants for NES orientation. The binding of NESs to CRM1 in both orientations results in a large expansion in NES consensus patterns and therefore a corresponding expansion of potential NESs in the proteome. DOI: http://dx.doi. org/10.7554/eLife.10034. 001
Acute Kidney Injury in Children with Plasmodium falciparum Malaria: Determinants for Mortality

♦ Background: Acute kidney injury (AKI) in P. falciparum malaria infection is an important morbidity in children. The purpose of the present study was done to observe the renal involvement, associated morbidities and outcome. ♦ Methods: Out of 156 patients with severe P. falciparum malaria, diagnosed on the basis of compatible clinical presentations and positive malarial parasites in the peripheral blood smear and/or histidine rich protein 2 antigen, 31 had AKI at presentation and were analyzed. ♦ Results: Of 31 (19.9%) patients with AKI, 4 were classified at risk, 11 injury, and 16 failure stage, as per pRIFLE criteria (pediatric version of RIFLE [R = risk, I = injury, F = failure, L = loss E = end-stage kidney disease]). Mean age of children with AKI was 7.7 ± 3.2 years. A significantly higher proportion of patients with AKI had hypoglycemia (41.9%), pulmonary edema (32.2%), and disseminated intravascular coagulation (DIC) (29.0%) compared to those without AKI (18.4%, 4.8%, and 3.2%, respectively). Twelve patients (38.7%) required peritoneal dialysis (PD), 8 (25.8%) died, and all were in failure stage. The non-survivors had significantly higher blood urea (p = 0.005) and serum creatinine levels (p = 0.042), lower glomerular filtration rate (p < 0.001), longer duration of illness (p = 0.003), and oliguria/anuria (p = 0.001) than survivors at admission. On logistic regression analysis, the disseminated intravascular coagulation (DIC), jaundice and parasite density (≥ 3+) were found to be significant factors contributing to mortality in children with AKI. ♦ Conclusions: Acute kidney injury in falciparum malaria is one of the severe systemic complications. Duration of illness and presence of comorbidities adversely affected the outcome.