bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical nested 22q11.2 duplications between LCR22B and LCR22D are associated with neurodevelopmental phenotypes including autism spectrum disorder with incomplete penetrance
Authors: Woodward Karen J. , Stampalia Julie , Vanyai Hannah , Rijhumal Hashika , Potts Kim , Taylor Fiona , Peverall Joanne , Grumball Tanya , Sivamoorthy Soruba , Alinejad‐Rokny Hamid , Wray John , Whitehouse Andrew , Nagarajan Lakshmi , Scurlock Jacqueline , Afchani Sabine , Edwards Matthew , Murch Ashleigh , Beilby John , Baynam Gareth , Kiraly‐Borri Cathy , McKenzie Fiona , Heng Julian I. T. 
Published: January 2019

AbstractBackgroundChromosome 22q11.2 is susceptible to genomic rearrangements and the most frequently reported involve deletions and duplications between low copy repeats LCR22A to LCR22D. Atypical nested deletions and duplications are rarer and can provide a valuable opportunity to investigate the dosage effects of a smaller subset of genes within the 22q11.2 genomic disorder region.MethodsWe describe thirteen individuals from six families, each with atypical nested duplications within the central 22q11.2 region between LCR22B and LCR22D. We then compared the molecular and clinical data for patients from this study and the few reported atypical duplication cases, to the cases with larger typical duplications between LCR22A and LCR22D. Further, we analyzed genes with the nested region to identify candidates highly enriched in human brain tissues.ResultsWe observed that atypical nested duplications are heterogeneous in size, often familial, and associated with incomplete penetrance and highly variable clinical expressivity. We found that the nested atypical duplications are a possible risk factor for neurodevelopmental phenotypes, particularly for autism spectrum disorder (ASD), speech and language delay, and behavioral abnormalities. In addition, we analyzed genes within the nested region between LCR22B and LCR22D to identify nine genes (ZNF74, KLHL22, MED15, PI4KA, SERPIND1, CRKL, AIFM3, SLC7A4, and BCRP2) with enriched expression in the nervous system, each with unique spatiotemporal patterns in fetal and adult brain tissues. Interestingly, PI4KA is prominently expressed in the brain, and this gene is included either partially or completely in all of our subjects.ConclusionOur findings confirm variable expressivity and incomplete penetrance for atypical nested 22q11.2 duplications and identify genes such as PI4KA to be directly relevant to brain development and disorder. We conclude that further work is needed to elucidate the basis of variable neurodevelopmental phenotypes and to exclude the presence of a second disorder. Our findings contribute to the genotype–phenotype data for atypical nested 22q11.2 duplications, with implications for genetic counseling.
Assessment of circulating tumor DNA in pediatric solid tumors: The promise of liquid biopsies
Authors: Abbou Samuel D. , Shulman David S. , DuBois Steven G. , Crompton Brian D. 
Published: January 2019

AbstractCirculating tumor DNA can be detected in the blood and body fluids of patients using ultrasensitive technologies, which have the potential to improve cancer diagnosis, risk stratification, noninvasive tumor profiling, and tracking of treatment response and disease recurrence. As we begin to apply “liquid biopsy” strategies in children with cancer, it is important to tailor our efforts to the unique genomic features of these tumors and address the technical and logistical challenges of integrating biomarker testing. This article reviews the literature demonstrating the feasibility of applying liquid biopsy to pediatric solid malignancies and suggests new directions for future studies.
The impact of connectedness on social functioning in youth with brain tumors
Authors: Willard Victoria W. , Russell Kathryn M. , Long Alanna , Phipps Sean 
Published: January 2019

AbstractPurposeChildren with brain tumors (BT) are at risk for difficulties with social functioning. Research to date has focused on deficits, with no studies identifying areas of strength or resilience. Our objective was to assess the potential influence of connectedness on social functioning in youth with BT as compared with children with other cancers.MethodsChildren with cancer (20 with BT, 33 with other diagnoses) were enrolled on a longitudinal study of psychosocial functioning. The current study included measures from time 2 (+1 year after enrollment; Mage = 13.11 ± 2.31, Mtimesincediagnosis = 4.95 ± 3.74 years) and time 3 (+3 years after enrollment; Mage = 14.98 ± 2.36, Mtimesincediagnosis = 6.82 ± 3.81 years). Youth completed the Hemingway Measure of Adolescent Connectedness (HMAC) at time 2. Two years later, social functioning was assessed by the self‐ and proxy‐report versions of the Social‐Emotional Assets and Resilience Scale (SEARS).ResultsYouth with BT perceived that they were less connected to friends (t(50) = −2.13,P = 0.04), but similarly connected to peers as youth with other cancers. Youth with BT also demonstrated lower social functioning by self‐ and parent report. Connectedness to friends significantly mediated the relationship between diagnostic category and self‐reported social functioning, such that youth with BT who reported being more connected to friends also indicated greater social functioning. Analyses using connectedness to peers and/or parent‐reported social functioning were nonsignificant.ConclusionsPerceiving a connection to a friend may be a protective factor that could mitigate deficits in social functioning in youth with BT. Additional research is needed to further assess the potential benefits of this construct.
Uplifting Runaways
Authors: Bena Iosif , Dudas Emilian , Graña Mariana , Lüst Severin 
Published: January 2019

AbstractWe find a mechanism by which antibranes placed in a warped deformed conifold throat can destroy the stabilization of the size of the sphere at the tip, collapsing it to zero size. This conifold destabilization mechanism can be avoided by turning on a large amount of flux on the sphere, but tadpole cancelation makes this incompatible with a hierarchy of scales in a Type IIB flux compactification. This indicates that antibrane uplift cannot be used to construct stable de Sitter vacua with a small cosmological constant in perturbative String Theory. The values of V and for these KKLT‐like scenarios can be parametrically small, but we find that is still consistent with the de Sitter swampland conjecture. Our results also suggest that there should exist a Klebanov‐Strassler black hole, holographically dual to a deconfined phase with spontaneously broken chiral symmetry.
Combined maternal and post‐weaning high fat diet inhibits male offspring's prostate cancer tumorigenesis in transgenic adenocarcinoma of mouse prostate model
Authors: Liu Yufei , Wu Xiaobo , Jiang Haowen 
Published: January 2019

BackgroundHigh fat diet (HFD) and its responsive change of gut microbiota are associated with numerous diseases in human and animal studies. But how maternal and post‐weaning HFD may influence the tumorigenesis of prostate cancer (PCa) in male offspring has not yet been reported.MethodsWe studied both solitary and combined effects of maternal or/and post‐weaning HFD on the tumorigenesis of prostate in offspring using a transgenic adenocarcinoma of mouse prostate (TRAMP) model. TRAMP male mice (n = 24) were born to and fostered onto control diet or HFD‐fed mothers, the weaned pups were further fed control or fat diet. All mice were sacrificed at the 28th week. The prostate histopathology was performed. The gut microbiota was analyzed by fecal 16S rRNA pyrosequencing, and the serum metabolites were determined by LC‐MS/MS.ResultsOur results indicated that post‐weaning HFD could significantly promote the PCa tumorigenesis in offspring (P = 0.031), and similar results were found in maternal HFD group but with no significant differences (P = 0.056). However, combined maternal and post‐weaning HFD could significantly reduce the PCa tumorigenesis in offspring (P = 0.019). Significant differences in specific microbial populations and serum metabolites were observed across groups. For example, mice with combined maternal and post‐weaning HFD had higher abundance of gut Lachonospiraceae, Roseburia, and Amycolatopsis, increased serum L‐methionine (P = 0.0052), and decreased serum α‐linolenic acid (P < 0.001).ConclusionsThis study highlights the inhibitory effects of combined maternal and post‐weaning HFD on PCa tumorigenesis, and provides new insights into the interactions between diet, gut microbiota, serum metabolites, and PCa.
HOXA10 expression profiling in prostate cancer
Authors: Hatanaka Yuji , de Velasco Marco A. , Oki Takashi , Shimizu Nobutaka , Nozawa Masahiro , Yoshimura Kazuhiro , Yoshikawa Kazuhiro , Nishio Kazuto , Uemura Hirotsugu 
Published: January 2019

BackgroundHOX genes encode transcription factors that play key roles in modulating normal tissue morphogenesis, differentiation and homeostasis. Disruption of normal HOX gene expression occurs frequently in human cancers and is associated with both tumor promoting and suppressing activities. Among these is, HOXA10, a pleiotropic gene that is critical for normal prostate development. In this study we characterized HOXA10 expression in human and mouse PCa to gain insights into its clinical significance.MethodsA meta‐analysis of HOXA10 mRNA expression was carried out across several publicly available data sets. Expression of HOXA10 protein expression was assessed by immunohistochemistry (IHC) using human radical prostatectomy (RP) cases. We correlated HOXA10 expression to clinicopathological features and investigated its relationship to biochemical recurrence (BCR) after RP by the Kaplan‐Meier method. HOXA10 mRNA and IHC protein expression was also examined in a mouse model of Pten‐null PCa.ResultsA meta‐analysis of HOXA10 gene expression indicated dysregulated expression of HOXA10 in human PCa. IHC profiling of HOXA10 revealed inverse correlations between HOXA10 expression and Gleason pattern, Gleason score, and pathological stage (P < 0.01). Patients with low expression profiles of HOXA10 were associated with a higher risk of BCR, (OR, 3.54; 95%CI, 1.21‐16.14; P = 0.049) whereas patients with high HOXA10 expression experienced longer times to BCR (P = 0.045). However, HOXA10 was not an independent predictor of BCR (OR, 1.52; 95%CI, 0.42‐5.54; P = 0.52). Evaluation of expression patterns of HOXA10 in mouse prostate tumors mimicked that of humans.ConclusionsOur findings show that HOXA10 expression is inversely associated with tumor differentiation and high HOXA10 expression is associated with improved BCR‐free survival. This study provides human and mouse evidence to suggest tumor suppressive roles for HOXA10 in the context of prostate cancer.
Evaluating the performance of sample preparation methods for ultra‐performance liquid chromatography/mass spectrometry based serum metabonomics
Authors: Chan Wan , Zhao Yao , Zhang Jiayin 
Published: January 2019

RationaleMetabonomics investigating perturbation to endogenous metabolism in response to external stimuli is emerging as a powerful tool for clinical diagnosis as well as in many other areas. The ability to retrieve reliable and reproducible information from complex biological fluids such as serum is crucial for its further applications.MethodsIn this study, the performance of the commonly used sample preparation methods for ultra‐performance liquid chromatography/mass spectrometry (UPLC/MS)‐based metabonomics was investigated. Specifically, we compared the extraction efficiencies, the method reproducibility, and the ability to identify potential biomarkers using solvent‐based protein precipitation and solid‐phase extraction (SPE) for serum metabonomic studies. Differences between extraction methods were explored using principal component analysis (PCA) and orthogonal partial least squares‐discrimination analysis (OPLS‐DA).ResultsAmong the sample preparation methods tested, solvent‐based protein precipitation using methanol has demonstrated the best analytical precision and extraction efficiency. Furthermore, this study revealed, for the first time, gender‐specific differences in levels of two lysophosphatidylcholines (lysoPC 18:0 and lysoPC 18:1) in rat serum samples.ConclusionsThe performance of sample preparation methods for UPLC/MS‐based serum metabonomics was evaluated systematically. Results showed sample preparation by solvent precipitation using methanol provided the best analytical precision and extraction efficiency for UPLC/MS‐based serum metabonomics.
Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis
Authors: Sghaier Ikram , Brochot Etienne , Loueslati Besma Y. , Almawi Wassim Y. 
Published: January 2019

SummaryHCV has been associated with a pro‐inflammatory state, which predisposes to hepatocellular carcinoma (HCC). However, the different molecular mechanisms underlying the effect of HCV infection on HCC progression remain unclear. Although HCV infection illustrates the potential role of host genetics in the outcome of infectious diseases, there is no clear overview of some single nucleotide polymorphisms (SNPs) influencing spontaneous or treatment‐induced HCV eradication. We studied the possible role of HCV infection in the processes of HCC initiation and performed a systematic analysis using data mining approaches to identify host polymorphisms associated with treatment response and HCC development using topological analysis of protein‐proteins interactions (PPI) networks. On the basis of our analysis performed, we identified key hub proteins related to HCV‐treatment response infection and to HCC development. Host genetic polymorphisms, such as inosine triphosphatase (ITPA), interferon, lambda 3 (IFNL3), Q5 interferon, lambda 4 (IFNL4), toll‐like receptors (TLRs) and interferon‐stimulated gene 15 (ISG‐15), were identified as key genes for treatment prediction and HCC evolution. By comparing unique genes for HCV‐treatment response and genes particular to HCV‐HCC development, we found a common PPI network that may participate in more extensive signalling processes during anti‐HCV treatment, which can play important roles in modulating the immune response to the occurrence of HCC. Data mining is an effective tool for identifying potential regulatory pathways involved in treatment response and HCC development. Our study may contribute to a better understanding of HCV immunopathogenesis and highlights the complex role of host genetics in HCV clearance.
Changes in emotional intelligence of university students participating in psychological workshops and their predictors
Authors: Kuk Anna , Guszkowska Monika , Gala-Kwiatkowska Anna 
Published: January 2019

AbstractThe aim of this study was to determine changes in the emotional intelligence of university students who participated in psychological workshops and their predictors. The examinations were organized within a quasi-experimental design that evaluated pretest-posttest values of emotional intelligence. The intervention, which adopted the form of psychological workshops, was aimed to improve the ability to control emotional states, modify cognitive patterns and expand the array of communicational behaviours. The study examined 30 university students of a physical education course aged 19 to 24 years. The study used the Popular Questionnaire of Emotional Intelligence, the Social Competence Questionnaire, the General Health Questionnaire and the Courtauld Emotional Scale. Significant increases in emotional intelligence were observed in students participating in the psychological workshops, although varied depending on its dimensions. The highest differentiation between the measurements was found for understanding of emotions, whereas the lowest - for empathy. Greater increases in emotional intelligence can be expected in young students, who are more willing to suppress depression and reveal lower social competencies and greater intensification of depression symptoms. Psychological workshops can be an effective method to improve emotional intelligence of university students who prepare to the profession of a physical education teacher or a coach.
Impact of Sleep Deprivation on the Hypothalamic–Pituitary–Gonadal Axis and Erectile Tissue
Authors: Lee D. S. , Choi J. B. , Sohn D. W. 
Published: January 2019

Abstract

Introduction
It is unclear how sleep deprivation (SD) exerts a negative effect on men’s health in terms of hypogonadism.

Aim
To evaluate the hypothalamic–pituitary–gonadal (HPG) axis in subjects with SD and ultimately to evaluate the erectile tissue in response to the hormonal changes.

Methods
56 male Wistar rats were used. First, 16 rats (16 weeks old) were subjected to 72 hours of SD, and the following were compared with 16 control rats: (i) levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and cortisol; (ii) the expression of the kisspeptin mRNA in the brain; and (iii) assessment of immunohistochemistry (IHC) of brain and testis. To further investigate whether testosterone reduction due to SD could affect erectile tissue, an additional 24 rats were divided into 3 groups (control, SD, and SD with T supplementation [SDT]) and compared: (i) T and cortisol levels were quantified, and (ii) endothelial nitric oxide synthase (eNOS)/ neuronal nitric oxide synthase (nNOS)/NOX-2 expression in cavernosal tissue was assessed by measuring mRNA levels and performing Western blotting and IHC.

Main Outcome Measure
Compared with the levels in the control group, the LH level was markedly decreased, and T levels were subsequently decreased in the SD group, whereas the level of the kisspeptin mRNA and IHC for kisspeptin, GnRH, and FSH were not different.

Results
In cavernosal tissues, levels of the eNOS/nNOS mRNAs and proteins tended to be lower, and NOX-2 levels (mRNA and protein) tended to be higher in the SD group than those in the control group and SDT group. IHC for eNOS/nNOS revealed lower-intensity staining in the SD group than in the control and SDT groups, whereas the NOX-2 intensity was higher in the SD group than in the other groups. A lower cortisol level was observed in the control group than in the SD and SDT groups, whereas the level was similar between the SD and SDT groups. The intracavernosal pressure/mean arterial blood pressure (%) values were also decreased in the SD group but not on testosterone injection.

Clinical Implications
Even short-term SD can produce secondary hypogonadism, which impairs men’s health.

Strength & Limitations
To the best of our knowledge, this study is the first to show the effects of SD on the whole HPG axis. The weakness is that this study only investigated acute SD.

Conclusion
Based on the findings from this study, acute SD causes pituitary hypogonadism, and reduced T levels decrease erectile function by inducing superoxide accumulation in the cavernosal tissue and inhibiting nitric oxide synthase activity.
Assessment of Body Image, Sexual Function, and Attractiveness in Women With Genital Prolapse: A Cross-Sectional Study With Validation of the Body Image in the Pelvic Organ Prolapse (BIPOP) Questionnaire
Authors: Moroni R. M. , Alves da Silva Lara L. , Ferreira C. H. J. , de Mello Constantino M. , Oliveira Brito L. G. 
Published: January 2019

Abstract

Introduction
Women’s sense of attractiveness and body image, and the impact of pelvic organ prolapse (POP) over these constructs, are likely influenced by social and cultural background.

Aim
To evaluate sexual function and body image in women with POP, to compare the sense of attractiveness between women with and without POP, and to translate the Body Image in the Pelvic Organ Prolapse (BIPOP) questionnaire into Brazilian Portuguese and validate it in this population.

Methods
In this cross-sectional study of 105 Brazilian women with POP, we administered the BIPOP (scored from 1 to 5, with higher scores indicating worse body image), the Female Sexual Function Inventory (FSFI) (scored from 2 to 36, with higher scores indicating lower risk for sexual dysfunction), and the Attractiveness subscale of the Body Attitudes Scale questionnaire (BAQ) (scored from 5 to 35, with higher score indicating better body image). We also included 100 control women who completed the BAQ Attractiveness subscale questionnaire.

Main Outcome Measure
The main outcome measure included BIPOP, FSFI, and BAQ Attractiveness scores.

Results
Mean BIPOP scores were 3.09 ± 1.08 in women with any POP, 3.05 ± 1.00 in those with lesser-stage POP (1 or 2), and 3.13 ± 1.15 in those with advanced-stage POP (3 or 4). There were no significant differences in score according to prolapse staging (P = .71). FSFI scores were independently associated with BIPOP scores (β = –0.052; P = .02). The mean scores for the BAQ Attractiveness subscale was 17.01 ± 4.07 in women with POP and 16.97 ± 4.60 in those without POP (P = .93). Older age was the sole characteristic associated with being sexually inactive in women with POP; regarding sexual function, a better body image and higher attractiveness scores were independently associated with a higher FSFI score. As for the Portuguese validation of the BIPOP instrument, the adapted version maintained good internal consistency (α = 0.908), good reliability (intraclass correlation coefficient, 0.94), and adequate construct validity.

Clinical Implications
Women with POP may not relate sexual function or attractiveness to POP extension. An impaired body image is associated with worse perception of attractiveness and increased risk for sexual dysfunction.

Strength & Limitations
As strengths, we used a specific genital body image scale, and this is first study of its kind among Brazilian women. As for weaknesses, we encountered low educational levels in the women with POP.

Conclusion
Among women with POP, the anatomic features of the prolapse do not seem to interfere with genital body image or with sexual function. In addition, the presence of POP was not associated with being sexually active or inactive.
Healthcare Experiences and Needs of Consensually Non-Monogamous People: Results From a Focus Group Study
Authors: Vaughan M. D. , Jones P. , Taylor B. A. , Roush J. 
Published: January 2019

Abstract

Background
Individuals engaged in consensual non-monogamy (CNM) face broad and potentially harmful experiences of sexual stigma in society, yet no published empirical literature has examined the experiences of this population within the healthcare system.

Aim
The present investigation sought to explore positive and negative experiences of CNM individuals within the healthcare system, as well as specific needs of these patients regarding inclusive healthcare practices.

Methods
20 CNM-identified adults from a non-profit organization serving CNM individuals completed a brief survey and participated in 1 of 3 focus groups of 70 minutes duration centered on their healthcare needs and experiences.

Outcomes
CNM patients report challenges in addressing their healthcare needs related to lack of provider knowledge, inadequate preventative screenings, and stigmatizing behaviors that impact their health and trust in the healthcare system.

Clinical Implications
Healthcare providers must monitor and work to avoid assumptions and pathologization of individuals who engage in CNM, creating an open, accepting environment to work collaboratively with CNM individuals to meet their unique sexual health needs.

Strength & Limitations
Although the present sample is diverse with respect to sexual and gender identity and socioeconomic status, it may not represent the experiences of CNM individuals outside of the midwestern United States and those who do not identify as polyamorous.

Conclusion
CNM individuals frequently experience sexual stigma in interactions with the healthcare system that interferes with receipt of sensitive, medically accurate care relevant to their unique needs and experiences.