bluuebunny/crossref_metadata_2025_split huggingface dataset:
Notch signaling in mouse blastocyst development and hatching
Authors: Batista Mariana R. , Diniz Patrícia , Torres Ana , Murta Daniel , Lopes-da-Costa Luís , Silva Elisabete 
Published: June 2020

Abstract
Background
Mammalian early embryo development requires a well-orchestrated interplay of cell signaling pathways. Notch is a major regulatory pathway involved in cell-fate determination in embryonic and adult scenarios. However, the role of Notch in embryonic pre-implantation development is controversial. In particular, Notch role on blastocyst development and hatching remains elusive, and a complete picture of the transcription and expression patterns of Notch components during this time-period is not available.

Results
This study provided a comprehensive view on the dynamics of individual embryo gene transcription and protein expression patterns of Notch components (receptors Notch1–4; ligands Dll1 and Dll4, Jagged1–2; and effectors Hes1–2), and their relationship with transcription of gene markers of pluripotency and differentiation (Sox2, Oct4, Klf4, Cdx2) during mouse blastocyst development and hatching. Transcription of Notch1–2, Jagged1–2 and Hes1 was highly prevalent and dynamic along stages of development, whereas transcription of Notch3–4, Dll4 and Hes2 had a low prevalence among embryos. Transcription levels of Notch1, Notch2, Jagged2 and Hes1 correlated with each other and with those of pluripotency and differentiation genes. Gene transcription was associated to protein expression, except for Jagged2, where high transcription levels in all embryos were not translated into protein. Presence of Notch signaling activity was confirmed through nuclear NICD and Hes1 detection, and downregulation of Hes1 transcription following canonical signaling blockade with DAPT. In vitro embryo culture supplementation with Jagged1 had no effect on embryo developmental kinetics. In contrast, supplementation with Jagged2 abolished Jagged1 transcription, downregulated Cdx2 transcription and inhibited blastocyst hatching. Notch signaling blockade by DAPT downregulated transcription of Sox2, and retarded embryo hatching.

Conclusion
Transcription of Notch genes showed a dynamic pattern along blastocyst development and hatching. Data confirmed Notch signaling activity, and lead to the suggestion that Notch canonical signaling may be operating through Notch1, Notch3, Jagged1 and Hes1. Embryo culture supplementation with Jagged1 and Jagged2 unveiled a possible regulatory effect between Jagged1, Cdx2 and blastocyst hatching. Overall, results indicate that a deregulation in Notch signaling, either by its over or under-activation, affects blastocyst development and hatching.
Identification and characterization of male reproduction-related genes in pig (Sus scrofa) using transcriptome analysis
Authors: Yang Wenjing , Zhao Feiyang , Chen Mingyue , Li Ye , Lan Xianyong , Yang Ruolin , Pan Chuanying 
Published: June 2020

Abstract
Background
The systematic interrogation of reproduction-related genes was key to gain a comprehensive understanding of the molecular mechanisms underlying male reproductive traits in mammals. Here, based on the data collected from the NCBI SRA database, this study first revealed the genes involved in porcine male reproduction as well their uncharacterized transcriptional characteristics.

Results
Results showed that the transcription of porcine genome was more widespread in testis than in other organs (the same for other mammals) and that testis had more tissue-specific genes (1210) than other organs. GO and GSEA analyses suggested that the identified test is-specific genes (TSGs) were associated with male reproduction. Subsequently, the transcriptional characteristics of porcine TSGs, which were conserved across different mammals, were uncovered. Data showed that 195 porcine TSGs shared similar expression patterns with other mammals (cattle, sheep, human and mouse), and had relatively higher transcription abundances and tissue specificity than low-conserved TSGs. Additionally, further analysis of the results suggested that alternative splicing, transcription factors binding, and the presence of other functionally similar genes were all involved in the regulation of porcine TSGs transcription.

Conclusions
Overall, this analysis revealed an extensive gene set involved in the regulation of porcine male reproduction and their dynamic transcription patterns. Data reported here provide valuable insights for a further improvement of the economic benefits of pigs as well as future treatments for male infertility.
Association of circulating SLAMF7+Tfh1 cells with IgG4 levels in patients with IgG4-related disease
Authors: Higashioka Kazuhiko , Ota Yuri , Maehara Takashi , Moriyama Masafumi , Ayano Masahiro , Mitoma Hiroki , Akahoshi Mitsuteru , Arinobu Yojiro , Horiuchi Takahiko , Nakamura Seiji , Akashi Koichi , Niiro Hiroaki 
Published: June 2020

AbstractBackgroundFollicular helper CD4+T (Tfh) cells have a critical role in IgG4 production by B cells in IgG4-related disease (IgG4-RD). Recent studies including ours showed that SLAMF7+CD4+T cells are an important pathological driver of IgG4-RD. In this study, we have sought to elucidate a relationship between helper CD4+T (Th), particularly Tfh, cells and SLAMF7+CD4+T cells in IgG4-RD.ResultsThe patients with IgG4-RD enrolled in this study were aged 66 ± 12 years and their titers of serum IgG4 were 372 ± 336 mg/dl. Th1 cells, activated circulating Tfh1 (cTfh1), and activated cTfh2 cells increased in IgG4-RD. SLAMF7 was mainly expressed on Th1 and cTfh1, but not cTfh2, cells in the patients. SLAMF7+cTfh1 cells were PD-1/CD28 double-positive, whereas SLAMF7+Th1 cells were CD28 negative. Positive correlations were noted between serum IgG4 levels and the number of activated cTfh2 cells and SLAMF7+cTfh1 cells, but not SLAMF7+Th1 cells. Intriguingly, among cTfh1 cells, activated SLAMF7+cTfh1 cells were high producers of IL-10 along with IL-21. Blimp-1, but not Bcl-6, mRNA was expressed at high levels in activated SLAMF7+cTfh1 cells. In addition to CD4+T cells, the frequency of SLAMF7+fraction was higher in memory B cells than naïve B cells in patients with IgG4RD. Finally, upon stimulation via B-cell receptor and CD40, Tfh1-associated cytokines, IL-21 and IFN-γ, most significantly induced SLAMF7 expression in memory B cells.ConclusionsTogether, these results suggest that circulating SLAMF7+Tfh1 cells, along with Tfh2 cells, play a pathologic role in IgG4 production in IgG4-RD.
Frailty transitions predict healthcare use and Medicare payments in older Mexican Americans: a longitudinal cohort study
Authors: Li Chih-Ying , Al Snih Soham , Chou Lin-Na , Karmarkar Amol , Kuo Yong-Fang , Markides Kyriakos S. , Ottenbacher Kenneth J. 
Published: June 2020

Abstract
Background
Little is known regarding the impact of transitions in frailty on healthcare use and payment in older Mexican Americans. We address this gap in knowledge by investigating the effect of early transitions in physical frailty on the use of healthcare services and Medicare payments involving older Mexican Americans.

Methods
Longitudinal analyses were conducted using the Hispanic Established Populations for the Epidemiological Study of the Elderly (Hispanic-EPESE) survey data from five Southwest states linked to the Medicare claims files from the Centers for Medicare and Medicaid Services. Seven hundred and eighty-eight community-dwelling Mexican Americans 72 years and older in 2000/01 were studied. We used a modified Frailty Phenotype (unintentional weight loss, weakness, self-reported exhaustion and slow walking speed) to classify frailty status (non-frail, pre-frail or frail). Each participant was placed into one of 5 frailty transition groups: 1) remain non-frail, 2) remain pre-frail, 3) remain frail, 4) improve (pre-frail to non-frail, frail to non-frail, frail to pre-frail) and 5) worse (non-frail to pre-frail, non-frail to frail, pre-frail to frail). The outcomes for the one-year follow-up period (2000–2001) were: (a) healthcare use (hospitalization, emergency room [ER] admission and physician visit); and (b) Medicare payments (total payment and outpatient payment).

Results
Mean age was 78.8 (SD = 5.1) years and 60.3% were female in 1998/99. Males who remained pre-frail (Odds Ratio [OR] = 3.49, 1.13–10.8, remained frail OR = 6.92, 1.61–29.7) and transitioned to worse frail status (OR = 4.49, 1.74–11.6) had significantly higher hospitalization risk compared to individuals who remained non-frail. Males in the ‘worsened’ groups, and females in the ‘improved’ groups, had significantly higher Medicare payments than individuals who remained non-frail (Cost Ratio [CR] = 2.00, 1.30–3.09; CR = 1.53, 1.12–2.09, respectively].

Conclusions
Healthcare use and Medicare payments differed by frailty transition status. The differences varied by sex. Research is necessary to elucidate the relationship between frailty transitions and outcomes, sex difference and Medicare payment for older Mexican Americans living in the community.
What lies beneath: a retrospective, population-based cohort study investigating clinical and resource-use characteristics of institutionalized older people in Catalonia
Authors: Amblàs-Novellas Jordi , Santaeugènia Sebastià J. , Vela Emili , Clèries Montse , Contel Joan C. 
Published: June 2020

Abstract
Background
Planning population care in a specific health care setting requires deep knowledge of the clinical characteristics of the target care recipients, which tend to be country specific. Our area virtually lacks any descriptive, far-reaching publications about institutionalized older people (IOP). We aimed to investigate the demographic and clinical characteristics of institutionalized older people (IOP) ≥65 years old and compare them with those of the rest of the population of the same age.

Methods
Retrospective analysis (total cohort approach) of clinical and resource-use characteristics of IOP and non-IOP older than 65 years in Catalonia (North-East Spain). Variables analysed included age and sex, diagnoses, morbidity burden—using Adjusted Morbidity Groups (GMA, Grupos de Morbilidad Ajustada)—, mortality, use of resources, and medications taken. All data were obtained from the administrative database of the local healthcare system.

Results
This study included 93,038, 78,458, 68,545 and 67,456 IOP from 2011, 2013, 2015 and 2017, respectively. In this interval, an increase in median age (83 vs. 87 years), in women (68.64% vs. 72.11%) and in annual mortality (11.74% vs. 20.46%) was observed. Compared with non-IOP (p < 0.001 in all comparisons), IOP showed a higher annual mortality (20.46% vs. 3.13%), a larger number of chronic diseases (specially dementia: 46.47% vs. 4.58%), higher multimorbidity (15.2% vs. 4.2% with GMA of maximum complexity), and annual admissions to acute care (47.6% vs. 27.7%) and skilled nursing facilities (27.8% vs. 7.4%), mean length of hospital stay (10.0 vs. 7.2 days) and mean of medications taken (11.7 vs. 8.0).

Conclusions
There is a growing gap between the clinical and demographic characteristics of age-matched IOP and non-IOP, which overlaps with a higher mortality rate of IOP. The profile of resources utilization of IOP compared with non-IOP strongly suggests a deficiency of preventive actions and stresses the need to rethink the care model for IOP from a social and health care perspective.
The effect of a dementia awareness class on changing dementia attitudes in adolescents
Authors: Farina Nicolas , Hughes Laura J. , Jones Ellen , Parveen Sahdia , Griffiths Alys W. , Galvin Kathleen , Banerjee Sube 
Published: June 2020

Abstract
Background
Current evidence suggests that negative and stigmatising attitudes towards dementia may develop at a young age. There are a number of dementia education and awareness initiatives aimed at reducing stigma, though they have not been robustly evaluated to establish the impact on dementia attitudes or suitability in adolescent populations. This study explored the efficacy and satisfaction of one such initiative (Dementia Friends) in a British adolescent sample.

Methods
301 adolescents (M = 12.6 years old, SD = 0.73) were assigned to either receive Dementia Friends (a 60-min interactive class that teaches about dementia and its effects on people’s lives) or education as usual. All participants completed a series of validated questionnaires pre- and post-intervention, related to dementia attitudes (Brief A-ADS and KIDS).

Results
Adolescents in the dementia awareness group showed little to no improvements between time-points. The change scores in the dementia awareness group did not significantly differ to the control group based on both KIDS (d = − 0.003, p = 0.98) and Brief A-ADS (d = 0.14, p = 0.13) measures. There was no Group x Time effect after controlling for confounding variables.

Conclusions
Dementia Friends is successful in terms of reach and impact, though this study suggests that it may fall short of achieving its goal of improving attitudes towards dementia. Importantly, Dementia Friends did not have a negative effect on attitudes, and the majority of adolescents enjoyed the sessions. It is important that these findings are replicated in a larger randomised-controlled study.
Noninvasive KRAS mutation estimation in colorectal cancer using a deep learning method based on CT imaging
Authors: He Kan , Liu Xiaoming , Li Mingyang , Li Xueyan , Yang Hualin , Zhang Huimao 
Published: June 2020

Abstract
Background
The detection of Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer (CRC) is key to the optimal design of individualized therapeutic strategies. The noninvasive prediction of the KRAS status in CRC is challenging. Deep learning (DL) in medical imaging has shown its high performance in diagnosis, classification, and prediction in recent years. In this paper, we investigated predictive performance by using a DL method with a residual neural network (ResNet) to estimate the KRAS mutation status in CRC patients based on pre-treatment contrast-enhanced CT imaging.

Methods
We have collected a dataset consisting of 157 patients with pathology-confirmed CRC who were divided into a training cohort (n = 117) and a testing cohort (n = 40). We developed an ResNet model that used portal venous phase CT images to estimate KRAS mutations in the axial, coronal, and sagittal directions of the training cohort and evaluated the model in the testing cohort. Several groups of expended region of interest (ROI) patches were generated for the ResNet model, to explore whether tissues around the tumor can contribute to cancer assessment. We also explored a radiomics model with the random forest classifier (RFC) to predict KRAS mutations and compared it with the DL model.

Results
The ResNet model in the axial direction achieved the higher area under the curve (AUC) value (0.90) in the testing cohort and peaked at 0.93 with an input of ’ROI and 20-pixel’ surrounding area. AUC of radiomics model in testing cohorts were 0.818. In comparison, the ResNet model showed better predictive ability.

Conclusions
Our experiments reveal that the computerized assessment of the pre-treatment CT images of CRC patients using a DL model has the potential to precisely predict KRAS mutations. This new model has the potential to assist in noninvasive KRAS mutation estimation.
A convenient clinical nomogram for predicting the cancer-specific survival of individual patients with small-intestine adenocarcinoma
Authors: Wang Na , Yang Jin , Lyu Jun , Liu Qingqing , He Hairong , Liu Jie , Li Li , Ren Xuequn , Li Zhendong 
Published: June 2020

Abstract
Background
The objective of this study was to develop a practical nomogram for predicting the cancer-specific survival (CSS) of patients with small-intestine adenocarcinoma.

Methods
Patients diagnosed with small-intestine adenocarcinoma between 2010 and 2015 were selected for inclusion in this study from the Surveillance, Epidemiology, and End Results (SEER) database. The selected patients were randomly divided into the training and validation cohorts at a ratio of 7:3. The predictors of CSS were identified by applying both forward and backward stepwise selection methods in a Cox regression model. The performance of the nomogram was measured by the concordance index (C-index), the area under receiver operating characteristic curve (AUC), calibration plots, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and decision-curve analysis (DCA).

Results
Multivariate Cox regression indicated that factors including age at diagnosis, sex, marital status, insurance status, histology grade, SEER stage, surgery status, T stage, and N stage were independent covariates associated with CSS. These factors were used to construct a predictive model, which was built and virtualized by a nomogram. The C-index of the constructed nomogram was 0.850. The AUC values indicated that the established nomogram displayed better discrimination performance than did the seventh edition of the American Joint Committee on Cancer TNM staging system in predicting CSS. The IDI and NRI also showed that the nomogram exhibited superior performance in both the training and validation cohorts. Furthermore, the calibrated nomogram predicted survival rates that closely corresponded to actual survival rates, while the DCA demonstrated the considerable clinical usefulness of the nomogram.

Conclusion
We have constructed a nomogram for predicting the CSS of small-intestine adenocarcinoma patients. This prognostic model may improve the ability of clinicians to predict survival in individual patients and provide them with treatment recommendations.
Association between Epstein-Barr virus infection and gastric cancer: a systematic review and meta-analysis
Authors: Tavakoli Ahmad , Monavari Seyed Hamidreza , Solaymani Mohammadi Farid , Kiani Seyed Jalal , Armat Saber , Farahmand Mohammad 
Published: June 2020

Abstract
Background
Numerous studies conducted over the past 30 years have pointed to the presence of Epstein–Barr virus (EBV) in gastric cancer samples. This study was aimed to provide a meta-analytic review of the prevalence of EBV in gastric cancer patients, and to clarify the relationship between EBV infection and gastric cancer.

Methods
A literature search was performed electronically using online databases for English language publications until July 1, 2019. The pooled EBV prevalence and 95% confidence intervals (CIs) were estimated using a random-effects model. To determine the association between EBV and gastric cancer, pooled odds ratio (OR) and its 95% CI were computed for case-control studies. Two separate analyses were performed on data from case-control studies with matched and non-match pairs designs to calculate the pooled estimates of ORs.

Results
The pooled prevalence of EBV in 20,361 gastric cancer patients was 8.77% (95% CI: 7.73–9.92%; I2 = 83.2%). There were 20 studies with matched pairs design, including tumor and tumor-adjacent normal tissue pairs from 4116 gastric cancer patients. The pooled ORs were 18.56 (95% CI: 15.68–21.97; I2 = 55.4%) for studies with matched pairs design and 3.31 (95% CI: 0.95–11.54; I2 = 55.0%) for studies with non-matched pairs design. The proportion of EBV-associated gastric cancer among male cases was significantly higher than among female cases (10.83%, vs. 5.72%) (P < 0.0001). However, the pooled OR estimate for EBV-associated gastric cancer was significantly higher among females (21.47; 95% CI: 15.55–29.63; I2 = 0%) than in males (14.07; 95% CI: 10.46–18.93; I2 = 49.0%) (P = 0.06). EBV was more prevalent in the cardia (12.47%) and the body (11.68%) compared to the antrum (6.29%) (P = 0.0002).

Conclusions
EBV infection is associated with more than 18 times increase the risk of gastric cancer. Although the prevalence of EBV was higher in male patients than in female patients with gastric cancer, women are more likely than men to develop EBV-associated gastric cancer. Our findings showed that using tumor-adjacent normal tissues as the control group provides more robust and accurate results regarding the relationship between EBV infection and gastric cancer.
The ACCEPT-study: design of an RCT with an active treatment control condition to study the effectiveness of the Dutch version of PEERS® for adolescents with autism spectrum disorder
Authors: van Pelt B. J. , Idris S. , Jagersma G. , Duvekot J. , Maras A. , van der Ende J. , van Haren N. E. M. , Greaves-Lord K. 
Published: June 2020

Abstract
Background
Social skills interventions are commonly deployed for adolescents with autism spectrum disorder (ASD). Because effective and appropriate social skills are determined by cultural factors that differ throughout the world, the effectiveness of these interventions relies on a good cultural fit.
Therefore, the ACCEPT study examines the effectiveness of the Dutch Program for the Education and Enrichment of Relational Skills (PEERS®) social skills intervention.

Methods/design
This study is a two-arm parallel group randomized controlled trial (RCT) in which adolescents are randomly assigned (after baseline assessment) to one of two group interventions (PEERS® vs. active control condition). In total, 150 adolescents are to be included, with multi-informant involvement of their parents and teachers. The ACCEPT study uses an active control condition (puberty psychoeducation group training, focussing on social-emotional development) and explores possible moderators and mediators in improving social skills. The primary outcome measure is the Contextual Assessment of Social Skills (CASS). The CASS assesses social skills performance in a face to face social interaction with an unfamiliar, typically developing peer, making this a valuable instrument to assess the social conversational skills targeted in PEERS®. In addition, to obtain a complete picture of social skills, self-, parent- and teacher-reported social skills are assessed using the Social Skills improvement System (SSiS-RS) and Social Responsiveness Scale (SRS-2). Secondary outcome measures (i.e. explorative mediators) include social knowledge, social cognition, social anxiety, social contacts and feelings of parenting competency of caregivers. Moreover, demographic and diagnostic measures are assessed as potential moderators of treatment effectiveness. Assessments of adolescents, parents, and teachers take place at baseline (week 0), intermediate (week 7), post intervention (week 14), and at follow-up (week 28).

Conclusion
This is the first RCT on the effectiveness of the PEERS® parent-assisted curriculum which includes an active control condition. The outcome of social skills is assessed using observational assessments and multi-informant questionnaires. Additionally, factors related to social learning are assessed at several time points, which will enable us to explore potential mediators and moderators of treatment effect.

Trail registration
Dutch trail register NTR6255 (NL6117). Registered February 8th, 2017 - retrospectively registered.