bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D receptor methylation attenuates the association between physical activity and type 2 diabetes mellitus: A case‐control study
Authors: Yu Songcheng , Feng Yinhua , Qu Chenling , Yu Fei , Mao Zhenxing , Wang Chongjian , Li Wenjie , Li Xing 
Published: November 2021

AbstractBackgroundPhysical activity and vitamin D receptor (VDR) have been associated with type 2 diabetes mellitus (T2DM). However, the associations of VDR methylation with T2DM and physical activity remained unknown. We aimed to investigate whether VDR methylation was a link between physical activity and T2DM.MethodsA 1:1 matching case‐control study was designed based on the Henan Rural Cohort Study, including 272 pairs of T2DM patients and nonpatients. Physical activity level was assessed using the International Physical Activity Questionnaire. The high‐resolution melt method was applied to determine the methylation level of the promoter region of VDR. The association between physical activity and T2DM was analyzed with a conditional logistic regression model. The effect modification of VDR methylation levels on the association between physical activity and T2DM was conducted. A multivariate correlation analysis model was applied to investigate correlations of VDR methylation with insulin sensitivity.ResultsPhysical activity level was associated with T2DM risk (crude model: odds ratio [OR] 0.611; 95% CI, 0.416‐0.897; adjusted model: OR 0.619; 95% CI, 0.418‐0.917). In effect modification analysis, the effects of physical activity on T2DM were stronger for low VDR methylation levels than for high (P = .025). Moreover, VDR methylation levels were associated with insulin (r = −0.089, P = .039) as well as homeostatic model assessment of insulin resistance (r = −0.098, P = .022).ConclusionsThe methylation status of the VDR promoter is associated with the secretion and sensitivity of insulin. VDR methylation attenuates the association between physical activity and T2DM, indicating that proactively physical activity may reduce the risk of T2DM, especially in people with low VDR methylation level.
A comparative study of IL‐6, CRP and NT‐proBNP levels in post‐COVID multisystem inflammatory syndrome in children (MISC) and Kawasaki disease patients
Authors: Ganguly Mimi , Nandi Alolika , Banerjee Paramita , Gupta Purbasha , Sarkar Subhajit Dey , Basu Surupa , Pal Priyankar 
Published: November 2021

AbstractBackgroundPost‐COVID multisystem hyperinflammatory syndrome in children (MISC) has clinical and laboratory similarities with Kawasaki disease (KD). Inflammatory markers like C‐reactive protein (CRP), interleukin 6 (IL6) as well as N‐terminal probrain natriuretic peptide (NT‐proBNP) are elevated in both. This study attempts a comparative analysis of the 3 markers in an attempt at early differentiation for planning appropriate management.MethodologyThis analytical study conducted at the Institute of Child Health, Kolkata, India compared the levels of the above 3 markers at admission between 72 patients with KD, 30% of whom had coronary artery lesions (CALs) collected over a period of 18 months (Jan 2017‐June 2018), with 71 MISC patients over a period of 6 months (July 2020‐December 2020). The non‐parametric Mann‐Whitney U test was used to test for similarity in distributions of the samples of CRP, NT‐proBNP and IL6 in KD and MISC patients using correction factor for similar ranks. The 3 parameters were compared using receiver operating characteristic (ROC) curve analysis.ResultsMean IL6 value in KD was 83.22 pg/mL and in MISC 199.91 pg/mL, which was not found to be statistically significant (P = .322 > .05).However mean NT‐proBNP (914.91 pg/mL) with CRP level (96.32 mg/L) in KD was significantly lower (P < .05 for both cases) than that in MISC (9141.16 pg/mL and 145.66 mg/L respectively). ROC analysis showed NT‐proBNP has the best sensitivity and specificity in predicting MISC.ConclusionNT‐proBNP and CRP are significantly higher among MISC patients; ROC analysis shows levels >935.7 pg/mL and >99.55 mg/L respectively might act as a guide to differentiate between them.
Efficacy of dacomitinib in patients with EGFR‐mutated NSCLC and brain metastases
Authors: Zhang Jinyao , Wang Yan , Liu Ziling , Wang Lin , Yao Yu , Liu Yutao , Hao Xue Zhi , Wang Jianyang , Xing Puyuan , Li Junling 
Published: November 2021

AbstractBackgroundDacomitinib is a second‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which is superior to first‐generation EGFR TKI in ARCHER 1050. However, the activity of dacomitinib in the central nervous system (CNS) is not known as ARCHER 1050 did not include patients with baseline brain metastases. This study aimed to describe dacomitinib's activity in the CNS in a real‐world setting.Patients and MethodsThirty‐two patients who were receiving dacomitinib for advanced non‐small‐cell lung cancer (NSCLC) with EGFR mutations and brain metastasis were included in this study. Patients who received prior EGFR TKIs were excluded from this trial. Case report forms were collected to determine treatment outcomes.ResultsAmong 32 patients with EGFR‐mutated NSCLC and brain disease, eight were included in the CNS evaluable for response group. The intracranial objective response rate (iORR) was 87.5% (95% confidence interval [CI] 47.3–99.7%) and the intracranial disease control rate (iDCR) was 100% (95% CI 63.1–100%). In 30 evaluable patients with measurable or nonmeasurable brain lesions, the iORR was 66.7% (95% CI 47.2–82.7%) and the iDCR was 100% (95% CI 88.4–100%). Median intracranial duration of response (iDoR) and intracranial progression‐free survival (iPFS) were not reached, with a one‐year iDoR rate of 72.2% (95% CI 48.7–95.7%) and a 1‐year iPFS rate of 71.2% (95% CI 51.0–91.4%), respectively. The majority of patients experienced low‐grade (G1/2) toxicities, which are reversible.ConclusionThis study suggests that dacomitinib demonstrated CNS efficacy in patients with EGFR TKI‐naïve EGFR‐mutated NSCLC in the real‐world setting. The safety profile was tolerable and manageable.
Genes identified in rodent studies of alcohol intake are enriched for heritability of human substance use
Authors: Huggett Spencer B. , Johnson Emma C. , Hatoum Alexander S. , Lai Dongbing , Srijeyanthan Jenani , Bubier Jason A. , Chesler Elissa J. , Agrawal Arpana , Palmer Abraham A. , Edenberg Howard J. , Palmer Rohan H. C. 
Published: November 2021

AbstractBackgroundRodent paradigms and human genome‐wide association studies (GWAS) on drug use have the potential to provide biological insight into the pathophysiology of addiction.MethodsUsing GeneWeaver, we created rodent alcohol and nicotine gene‐sets derived from 19 gene expression studies on alcohol and nicotine outcomes. We partitioned the SNP heritability of these gene‐sets using four large human GWAS: (1) alcoholic drinks per week, (2) problematic alcohol use, (3) cigarettes per day, and (4) smoking cessation. We benchmarked our findings with curated human alcohol and nicotine addiction gene‐sets and performed specificity analyses using other rodent gene‐sets (e.g., locomotor behavior) and other human GWAS (e.g., height).ResultsThe rodent alcohol gene‐set was enriched for heritability of drinks per week, cigarettes per day, and smoking cessation, but not problematic alcohol use. However, the rodent nicotine gene‐set was not significantly associated with any of these traits. Both rodent gene‐sets showed enrichment for several non‐substance‐use GWAS, and the extent of this relationship tended to increase as a function of trait heritability. In general, larger gene‐sets demonstrated more significant enrichment. Finally, when evaluating human traits with similar heritabilities, both rodent gene‐sets showed greater enrichment for substance use traits.ConclusionOur results suggest that rodent gene expression studies can help to identify genes that contribute to the heritability of some substance use traits in humans, yet there was less specificity than expected. We outline various limitations, interpretations, and considerations for future research.
How hedonic and perceived community benefits from employee CSR involvement drive CSR advocacy behavior to co‐workers
Authors: Chomvilailuk Rojanasak , Butcher Ken 
Published: November 2021

AbstractThis study seeks to determine how organizational citizenship behavior (OCB) can be influenced by employee perception of the benefits arising from their involvement with corporate social responsibility (CSR) activities. The work is significant because of growing investment in CSR activities involving employees and increased firm expectations of employee dissemination of CSR information. A unique model examined how two types of perceived benefits, accruing to US‐based employees from their CSR engagement, impacted OCB. The variable of co‐worker‐directed CSR advocacy was used as a unique measure of OCB. An integrative theoretical framework combined social exchange theory with organizational citizenship behavior to provide a more comprehensive understanding of relationships. The first employee benefit tested was hedonic value, while the second was perceived community value. CSR reputation was modeled as a mediating variable. Data were collected via two scenario‐based experiments based at each respondents’ workplace. Analytical techniques included analysis of co‐variance and structural equation modeling using partial least squares. While both types of benefit had a significant effect on co‐worker‐directed CSR advocacy, the pathways differed. Perceived community value had a stronger effect on the mediating variable of CSR reputation, and consequently a significant indirect effect on the dependent variable. In contrast, hedonic value directly affected co‐worker‐directed CSR advocacy with CSR reputation playing no mediating role. This study contributes to the CSR literature through better understanding of the processes leading to the organizational citizenship behavior variable of co‐worker‐directed CSR advocacy. This dependent variable extends previous conceptualizations of OCB.
Circulating naïve and effector memory T cells correlate with prognosis in head and neck squamous cell carcinoma
Authors: Takahashi Hideyuki , Sakakura Koichi , Ida Shota , Kawabata‐Iwakawa Reika , Matsuyama Toshiyuki , Tada Hiroe , Mito Ikko , Chikamatsu Kazuaki 
Published: November 2021

AbstractT‐cell memory is an important mechanism for long‐term protection against diverse pathogens. Generation and persistence of memory T cells are vital components of anti‐tumor immunity, given their ability to persist for prolonged durations, as well as activate and migrate rapidly. In the present study, we investigated the clinical and prognostic significance of T‐cell subsets in the peripheral circulation of patients with head and neck squamous cell carcinoma (HNSCC). Moreover, we calculated the enrichment scores of T‐cell subsets in primary tumor tissues and compared their clinical characteristics using a public database. Multivariate survival analyses of circulating T‐cell parameters revealed that clinical parameters, except M factor, were not independent prognostic factors, whereas proportions of CD8+ T cells, naïve T cells (TNs), effector memory T cells (TEMs), and CD38+CD8+ T cells were independent prognostic factors, suggesting the importance of these peripheral T‐cell parameters as independent prognostic biomarkers. Consistent with these results, the T‐cell enrichment analysis indicated that enrichment of CD8+ TNs in the tumor microenvironment was an independent prognostic factor. Moreover, an ex vivo experiment demonstrated significantly less cytotoxic activity in CD38+ T cells than in CD38− T cells. These findings suggest that T‐cell memory‐related parameters in both systemic immunity and the tumor microenvironment could be used as prognostic biomarkers regardless of clinical characteristics. Further characterization of circulating T cells would lead to the development of novel biomarkers for patients with HNSCC.
Malignant acanthosis nigricans and diseases with extensive oral papillary hyperplasia
Authors: Liu Y. , Xu X. , Yang Y. , Hu H. , Jiang X. , Xiong X. , Meng W. 
Published: November 2021

Summary
Oral papillary lesions represent a variety of developmental and neoplastic conditions. Early diagnoses of different papillary lesions are challenging for oral medicine specialists. Malignant acanthosis nigricans (MAN) is a rare cutaneous disorder and a potential marker of underlying hidden tumours. It is characterized by papillary lesions that always involve the oral mucosa. In oral medicine specialities, MAN is not well understood. When the early signs of MAN are extensive oral lesions and slight cutaneous pigmentation without obvious florid cutaneous papillomatosis, the diagnosis can be incorrect or delayed. Oral medicine specialists should ask affected patients to provide details of their medical history and conduct a timely systemic examination.
Childhood obesity: A review of current and future management options
Authors: Apperley Louise J. , Blackburn James , Erlandson‐Parry Karen , Gait Lucy , Laing Peter , Senniappan Senthil 
Published: November 2021

AbstractObesity is becoming increasingly prevalent in paediatric populations worldwide. In addition to increasing prevalence, the severity of obesity is also continuing to rise. Taken together, these findings demonstrate a worrying trend and highlight one of the most significant challenges to public health. Childhood obesity affects multiple organs in the body and is associated with both significant morbidity and ultimately premature mortality. The prevalence of complications associated with obesity, including dyslipidaemia, hypertension, fatty liver disease and psychosocial complications are becoming increasingly prevalent within the paediatric populations. Treatment guidelines currently focus on intervention with lifestyle and behavioural modifications, with pharmacotherapy and surgery reserved for patients who are refractory to such treatment. Research into adult obesity has established pharmacological novel therapies, which have been approved and established in clinical practice; however, the research and implementation of such therapies in paediatric populations have been lagging behind. Despite the relative lack of widespread research in comparison to the adult population, newer therapies are being trialled, which should allow a greater availability of treatment options for childhood obesity in the future. This review summarizes the current evidence for the management of obesity in terms of medical and surgical options. Both future therapeutic agents and those which cause weight loss but have an alternative indication are also included and discussed as part of the review. The review summarizes the most recent research for each intervention and demonstrates the potential efficacy and limitations of each treatment option.
Expanding the spectrum of syndromic PPP2R3C‐related XY gonadal dysgenesis to XX gonadal dysgenesis
Authors: Altunoglu Umut , Börklü Esra , Shukla Anju , Escande‐Beillard Nathalie , Ledig Susanne , Azaklı Hülya , Nayak Shalini S. , Eraslan Serpil , Girisha Katta Mohan , Kennerknecht Ingo , Kayserili Hülya 
Published: November 2021

AbstractHomozygous variants in PPP2R3C have been reported to cause a syndromic 46,XY complete gonadal dysgenesis phenotype with extragonadal manifestations (GDRM, MIM# 618419) in patients from four unrelated families, whereas heterozygous variants have been linked to reduced fertility with teratozoospermia (SPGF36, MIM# 618420) in male carriers. We present eight patients from four unrelated families of Turkish and Indian descent with three different germline homozygous PPP2R3C variants including a novel in‐frame duplication (c.639_647dupTTTCTACTC, p.Ser216_Tyr218dup). All patients exhibit recognizable facial dysmorphisms allowing gestalt diagnosis. In two 46,XX patients with hypergonadotropic hypogonadism and nonvisualized gonads, primary amenorrhea along with absence of secondary sexual characteristics and/or unique facial gestalt led to the diagnosis. 46,XY affected individuals displayed a spectrum of external genital phenotypes from ambiguous genitalia to complete female. We expand the spectrum of syndromic PPP2R3C‐related XY gonadal dysgenesis to both XY and XX gonadal dysgenesis. Our findings supported neither ocular nor muscular involvement as major criteria of the syndrome. We also did not encounter infertility problems in the carriers. Since both XX and XY individuals were affected, we hypothesize that PPP2R3C is essential in the early signaling cascades controlling sex determination in humans.
Indigenous Australian drinking risk: Comparing risk categorisations based on recall of recent drinking occasions to AUDIT‐C screening in a representative sample
Authors: Conigrave James H. , Conigrave Katherine M. , Wilson Scott , Lee K. S. Kylie 
Published: November 2021

AbstractIntroductionAboriginal and Torres Strait Islander (Indigenous) Australians have identified alcohol consumption as an area of concern. Accurate screening tools are required to help detect and assist at‐risk drinkers, and to provide accurate data to policy makers. The Finnish method (determining drinking patterns based on the last two to four drinking occasions), has been proposed as a culturally appropriate and effective screening tool for detecting Indigenous Australians at risk from alcohol consumption. While it has been found to be valid and acceptable for use with Indigenous Australians, the Finnish method has not been compared to the three‐item Alcohol Use Disorders Identification Test—Consumption (AUDIT‐C) which is currently recommended by the Australian government for use in Aboriginal community‐controlled health services.MethodsWe compared the performance of the AUDIT‐C and Finnish method as screening tools for detecting harms experienced from alcohol in a representative, cross‐sectional, sample of Indigenous Australians.ResultsAUDIT‐C was substantially faster for participants to complete than the Finnish method. Metrics derived from both the AUDIT‐C and Finnish method were similarly linked to the frequency of self‐reported International Classification of Diseases, 11th revision dependence symptoms and harms.Discussion and ConclusionsThe AUDIT‐C is likely most appropriate for use in clinical settings due to its speed and ease of use. The Finnish method provides relatively detailed information about drinking and is better suited to population surveys.
Competitive location‐based and trajectory‐based mobile targeting
Authors: Cezar Asunur , Raghunathan Srinivasan 
Published: November 2021

AbstractAdvances in mobile analytics have enabled sellers to target mobile consumers using geolocation and the more granular mobile trajectory information. Using a game‐theoretical model of a context in which two competing sellers choose to target mobile consumers using location or trajectory, we examine the long‐term implications for sellers, consumers, and the social welfare. We show that mobile targeting, either location‐based or trajectory‐based, by both sellers indeed emerges as the equilibrium; however, trajectory‐based targeting need not always emerge as the equilibrium. For instance, location‐based targeting emerges as the equilibrium if the consumers’ disutility from a consumption delay (i.e., time cost) is low relative to their transportation cost. The primary driver of our findings relates to the role of location and travel direction information in exposing (or masking) the degree of consumer heterogeneity and the competitive advantage a seller has over the other in attracting a consumer.
Carabid adaptation to a collembolan diet: hunting efficiency and nutritional value
Authors: Baulechner Dennis , Jauker Frank , Wolters Volkmar 
Published: November 2021

1. Collembola are an important potential food source for carnivorous arthropods living on the soil surface. Nevertheless, due to their effective evasive manoeuvres, Collembola are not an easy prey. Several carabid groups, however, have evolved morphological specialisations to overcome this otherwise effective defence strategy. The adaptive value of this specialisation is still unclear, since some generalist carabids also consume collembolans.2. Feeding experiments with the collembolan specialist Notiophilus biguttatus and four generalist carnivorous carabids revealed that the specialised species are more efficient in hunting Collembola than the generalist species.3. A comparison between specialised and generalist carabid species subjected to a pure collembolan diet further suggests that Collembola are only a dietary supplement for generalists: the generalist carnivore Bembidion lampros decreased in weight and had a higher mortality rate when fed exclusively with collembolans.4. Analogously, a third experiment shows that edaphic mites or other non‐collembolan soil arthropods are just a nutritional supplement for N. biguttatus, since mortality increased when they were fed exclusively with these groups. The adaptation toward Collembola as prey, in contrast, does not constrain N. biguttatus, since they even increased in weight when fed with drosophila.5. The enhanced hunting efficiency of N. biguttatus on Collembola compared to generalist species supports the hypothesis that the convergent evolution of mandibles in all collembolan specialist carabids is highly adaptive. The advantage of specialisation most probably is reinforced by the fact that generalist carabids are not real competitors for specialists, due to their poor efficiency in utilising collembolans.
Long‐term consequences of peri‐adolescent social isolation on social preference, anxiety‐like behaviour, and vasopressin neural circuitry of male and female rats
Authors: Kinley Brianna L. , Kyne Robert F. , Lawton‐Stone Tamijah S. , Walker Deena M. , Paul Matthew J. 
Published: November 2021

AbstractSocial isolation during the juvenile and adolescent stages (peri‐adolescent social isolation) can have long‐term consequences for behavioural and neural development. Most of this research, however, has relied on data from males, and very few studies have included both sexes. The present study investigated the impact of peri‐adolescent social isolation on social preference, anxiety‐like behaviour, and vasopressin neural circuitry of male and female Long Evans rats. Rats were either housed alone for 3 weeks beginning at weaning (Isolated) or in groups (Group‐housed). In adulthood, rats were tested in social preference, open field, marble burying, and light/dark box tests, and brains were processed for vasopressin immunohistochemistry. Isolated males exhibited a lower social preference score and spent more time in the light zone of the light/dark box than their group‐housed counterparts. Isolated and Group‐housed females did not differ in these measures. Peri‐adolescent social isolation did not alter vasopressin fibre density in target areas known to influence social and anxiety‐like behaviours (the lateral septum or lateral habenula), but increased fibre density in an output pathway of the circadian pacemaker (projections to the paraventricular nucleus of the thalamus); an effect detected across both sexes. A previously unreported sex difference was also detected for vasopressin fibre density in the paraventricular nucleus of the thalamus (females > males). These findings demonstrate long‐term consequences of peri‐adolescent social isolation on social preference, anxiety‐like behaviour, and the circadian vasopressin pathway and suggest that socio‐affective development of males is more vulnerable to social stressors during the juvenile and adolescent stages.