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Abstract There is limited data regarding the added benefit of adjuvant systemic therapy in the management of small, node-negative, HER2+ breast cancer. In a multi-institutional retrospective analysis using the American Society of Clinical Oncology CancerLinQ database, we compared survival outcomes among T1a-c N0 HER2+ patients diagnosed between 2010 to 2021 who received locoregional therapy alone or in combination with adjuvant trastuzumab (+/− chemotherapy). Primary outcomes were invasive disease-free survival (iDFS) and overall survival (OS). Of the 1,184 patients, 436 received locoregional therapy alone. We found a statistically significant improvement in iDFS (HR 0.73, P = 0.003) and OS (HR 0.63, P = 0.023) on univariate analysis with adjuvant trastuzumab with or without chemotherapy which remained statistically significant on multivariate analysis. Three-arm univariate analysis found that iDFS was significantly improved with trastuzumab monotherapy (P = 0.003) and combination therapy (P = 0.027) compared to observation. Subgroup data suggests that T1b/c tumors derive the greatest benefit.

Key features of virtual reality (VR) that impact the effectiveness of pain reduction remain unknown. We hypothesized that specific features of the VR experience significantly impact VR's effectiveness in reducing pain during pediatric burn dressing care. Our randomized controlled trial included children 6 to 17 years (inclusive) who were treated in the outpatient clinic of an American Burn Association-verified pediatric burn center. Participants were randomly assigned (1:1:1) to active VR (playing the VR), passive VR (immersed in the same VR environment without interactions), or standard-of-care. On a scale from 0 to 100, participants rated overall pain (primary outcome) and features of the VR experience (game realism, fun, and engagement). Path analysis assessed the interrelationships among these VR key features and their impact on self-reported pain scores. From December 2016 to January 2019, a total of 412 patients were screened for eligibility, and 90 were randomly assigned (31 in the active VR group, 30 in the passive VR group, and 29 in the standard-of-care group). The current study only included those in the VR groups. The difference in median scores of VR features was not statistically significant between the active (realism, 77.5 [IQR: 50-100]; fun, 100 [IQR: 81-100]; engagement, 90 [IQR: 70-100]) and passive (realism, 72 [IQR: 29-99]; fun, 93.5 [IQR: 68-100]; engagement, 95 [IQR: 50-100]) VR distraction types. VR engagement had a significant direct (-0.39) and total (-0.44) effect on self-reported pain score (p

Being able to quantify gaming motivation in a valid, systematic way has important implications for game designers and gaming user experience researchers. In the present study, we aimed to develop and validate a 30-item Gaming Instinctual Motivation Scale (GIMS) based on Dillon’s 6–11 Framework on instinctual gaming motivation and Lazzaro’s gaming experience model. To validate the scale, we recruited 194 regular gamers (Mage = 22.70 years old, SD = 4.38) to complete the GIMS based on their general gaming experience and their experience playing role-laying games (RPGs), first-person shooters (FPSs), real-time strategy, puzzle, and action games. We used a cross-validation approach and performed exploratory factor analysis and confirmatory factor analysis to test the structure of the scale and the reliability and validity of the scale, respectively. The final version of the GIMS had a one-dimensional structure with 15 items. It also had good construct validity, χ2 (N = 117, df = 86) = 126.28, p = 0.003, CFI = 0.93, TLI = 0.92, and RMSEA = 0.064 (90% CI [0.04, 0.09]), and reliability (CR = 0.89), and an acceptable convergent validity (AVE = 0.35). The one-dimensional structure was generalizable to RPG and FPS games, demonstrating the applicability of the scale to these two gaming genres. Higher scores on the GIMS were also associated with a greater intention to play games.

Abstract Chrononutrition emerges as a novel approach to promote circadian alignment and metabolic health by means of time-of-the-day dietary intake. However, the relationship between maternal circadian rhythm and temporal dietary intake during pregnancy remains understudied. This study aimed to determine the change in melatonin levels in pregnant women across gestation and its association with temporal energy and macronutrient intake. This was a prospective cohort involving 70 healthy primigravidas. During the second and third trimesters, pregnant women provided salivary samples collected at 9:00, 15:00, 21:00, and 3:00 h over a 24 h day for melatonin assay. Data on chrononutrition characteristics were collected using a 3-day food record. Parameters derived from melatonin measurements including mean, amplitude, maximal level, area under the curve with respect to increase (AUCI), and area under the curve with respect to ground (AUCG) were computed. A rhythmic melatonin secretion over the day that remained stable across trimesters was observed among the pregnant women. There was no significant elevation in salivary melatonin levels as pregnancy advanced. In the second trimester, higher energy intake during 12:00–15:59 h and 19:00–06:59 h predicted a steeper melatonin AUCI (β=-0.32, p = 0.034) and higher AUCG (β = 0.26, p = 0.042), respectively. Macronutrient intake within 12:00–15:59 h was negatively associated with mean melatonin (Fat: β=-0.28, p = 0.041) and AUCG (Carbohydrate: β=-0.37, p = 0.003; Protein: β=-0.27, p = 0.036; Fat: β=-0.32, p = 0.014). As pregnant women progressed from the second to the third trimester, a flatter AUCI was associated with a reduced carbohydrate intake during 12:00–15:59 h (β=-0.40, p = 0.026). No significant association was detected during the third trimester. Our findings show that higher energy and macronutrient intakes particularly during 12:00–15:59 h and 19:00–06:59 h are associated with the disparities in maternal melatonin levels. Findings suggest the potential of time-based dietary approaches to entrain circadian rhythm in pregnant women.

Abstract Background Virtual reality (VR) gaming is considered a safe and effective alternative to standard pain alleviation in the hospital. This study addressed the potential effectiveness and feasibility of a VR game that was developed by our research team for repeated at-home burn dressing changes. Methods A randomized clinical trial was conducted among patients recruited from the outpatient burn clinic of a large American Burn Association–verified pediatric burn center between September 2019 and June 2021. We included English-speaking burn patients aged 5–17 years old requiring daily dressing changes for at least 1 week after first outpatient dressing change. One group played an interactive VR game during dressing changes, while the other utilized standard distraction techniques available in the home for up to a week. Both child and caretaker were asked to assess perceived pain on a numerical rating scale (NRS) of 0–10. For the VR group, patients were also asked to rate various aspects of the VR game on a NRS of 0–10 and caregivers were asked questions assessing ease of use. Results A total of 35 children were recruited for this study with 24 fully completing study measures. The majority of participants were male (n=19, 54.3%), White (n=29, 82.9%), and with second degree burns (n=32, 91.4%). Children and caregivers in the VR group reported less pain than the control group at the 4th dressing change. Participants in the VR group showed a clinically meaningful (≥30%) reduction in child-reported overall pain (33.3%) and caregiver-reported worst pain (31.6%) in comparison with subjects in the control group. Children’s satisfaction with the VR remained at a high level across dressing changes over the 1-week period, with reported realism and engagement increasing over time. Over half of the children (54.5%) enjoyed playing the game and did not report any challenges nor any side effects. Conclusions Subjects found the VR to be a useful distraction during home dressing changes and reported no challenges/side effects. VR should be considered as a nonpharmacologic companion for pain management during at-home burn dressing changes. Trial registration ClinicalTrials.gov Identifier: NCT04548635. Registered September 14, 2020—retrospectively registered

Abstract Background Women’s diet and nutritional status during pregnancy are important in influencing birth outcomes. We conducted a systematic scoping review of the best available evidence regarding dietary intake of Malaysian pregnant women, and the associations of maternal diet, anthropometry, and nutrition-related co-morbidities with the infant’s birth weight (IBW). The study objectives were to examine: (1) the adequacy of micronutrient intake among pregnant women; and (2) the association of maternal factors (anthropometry, diet, plasma glucose and blood pressure) during pregnancy with IBW. Methods Eleven search engines such as Proquest, EbscoHost, Scopus, Cochrane Library, Science Direct, Wiley Online Library, PubMed, Google Scholar, MyJournal, BookSC and Inter Library Loan with Medical Library Group were extensively searched to identify the primary articles. Three reviewers independently screened the abstracts and full articles based on the inclusion and exclusion criteria. Extracted data included details about the population characteristics, study methods and key findings related to the review objectives. Seventeen studies published from 1972 to 2021 were included, following the PRISMA-ScR guideline. Results Studies showed that maternal micronutrient intakes including calcium, iron, vitamin D, folic acid, and niacin fell short of the national recommendations. Increased maternal fruit intake was also associated with increased birth weight. Factors associated with fetal macrosomia included high pre-pregnancy body mass index (BMI), excess gestational weight gain (GWG) and high blood glucose levels. Low pre-pregnancy BMI, inadequate GWG, intake of confectioneries and condiments, and high blood pressure were associated with low birth weight. Conclusion This review identified several factors such as the mother’s food habits, comorbidities, BMI and gestational weight gain as the determinants of low birth weight. This implies that emphasis should be given on maternal health and nutrition for the birth outcome.

Chrononutrition has been suggested to have an entrainment effect on circadian rhythm which is crucial for metabolic health. Investigating how chrononutrition affects maternal circadian rhythm can shed light on its role during pregnancy. This study aims to determine chrononutrition characteristics of healthy primigravida during pregnancy and its association with melatonin and cortisol rhythm across gestation. A total of 70 healthy primigravidas were recruited from ten randomly selected government maternal and child clinics in Kuala Lumpur, Malaysia. During the second and third trimesters, chrononutrition characteristics including meal timing, frequency, eating window, breakfast skipping, and late-night eating were determined using a 3-day food record. Pregnant women provided salivary samples at five time-points over a 24 h period for melatonin and cortisol assay. Consistently across the second and third trimesters, both melatonin and cortisol showed a rhythmic change over the day. Melatonin levels displayed an increment toward the night whilst cortisol levels declined over the day. Majority observed a shorter eating window (≤12 h) during the second and third trimesters (66 and 55%, respectively). Results showed 23 and 28% skipped breakfast whereas 45 and 37% ate within 2 h pre-bedtime. During the third trimester, a longer eating window was associated with lower melatonin mean (β = –0.40, p = 0.006), peak (β = –0.42, p = 0.006), and AUCG (β = –0.44, p = 0.003). During both trimesters, a lower awakening cortisol level was observed in pregnant women who skipped breakfast (β = –0.33, p = 0.029; β = –0.29, p = 0.044). Only during the second trimester, breakfast-skipping was significantly associated with a greater cortisol amplitude (β = 0.43, p = 0.003). Findings suggest that certain chrononutrition components, particularly eating window and breakfast skipping have a significant influence on maternal melatonin and cortisol rhythm. Dietary intervention targeting these characteristics may be useful in maintaining maternal circadian rhythm.

Abstract Background The oral microbiota is acquired very early, but the factors shaping its acquisition are not well understood. Previous studies comparing monozygotic (MZ) and dizygotic (DZ) twins have suggested that host genetics plays a role. However, all twins share an equal portion of their parent’s genome, so this model is not informative for studying parent-to-child transmission. We used a novel study design that allowed us to directly examine the genetics of transmission by comparing the oral microbiota of biological versus adoptive mother-child dyads. Results No difference was observed in how closely oral bacterial community profiles matched for adoptive versus biological mother-child pairs, indicating little if any effect of host genetics on the fidelity of transmission. Both adopted and biologic children more closely resembled their own mother as compared to unrelated women, supporting the role of contact and environment. Mother-child strain similarity increased with the age of the child, ruling out early effects of host genetic influence that are lost over time. No effect on the fidelity of mother-child strain sharing from vaginal birth or breast feeding was seen. Analysis of extended families showed that fathers and mothers were equally similar to their children, and that cohabitating couples showed even greater strain similarity than mother-child pairs. These findings support the role of contact and shared environment, and age, but not genetics, as determinants of microbial transmission, and were consistent at both species and strain level resolutions, and across multiple oral habitats. In addition, analysis of individual species all showed similar results. Conclusions The host is clearly active in shaping the composition of the oral microbiome, since only a few of the many bacterial species in the larger environment are capable of colonizing the human oral cavity. Our findings suggest that these host mechanisms are universally shared among humans, since no effect of genetic relatedness on fidelity of microbial transmission could be detected. Instead our findings point towards contact and shared environment being the driving factors of microbial transmission, with a unique combination of these factors ultimately shaping the highly personalized human oral microbiome. Video abstract

Abstract Background Circadian rhythm plays an important role as our internal body’s clock that synchronizes behavior and physiology according to the external 24-h light-dark cycle. Past studies have associated disrupted circadian rhythm with higher risk of miscarriages, preterm birth and low birth weights. This paper described the protocol of a prospective cohort study which aims to determine the circadian rhythm in pregnant women, identify its association with maternal factors during pregnancy, gestational weight gain, birth and infant outcomes. Methods Ten government maternal and child health clinics in Kuala Lumpur, Malaysia will be randomly selected. Sample size of 438 first-trimester pregnant women will be followed-up until the birth of their infant. Salivary melatonin and cortisol concentration among subsample will be determined using enzyme-linked immunosorbent assay. Data on sleep quality, psychological distress and morningness/eveningness chronotype of pregnant women will be collected using validated questionnaires. Pedometer will be used to measure 5-day physical activity data. Total gestational weight gain will be determined at the end of pregnancy. Utilization of 3-day food record is to capture meal timing and nutrient intake. All measurements will be done in 2nd and 3rd trimester. Birth outcomes will be collected through clinic records and Centers for Disease Control and Prevention (CDC) Neonatal questionnaire. Infants will be followed-up at 6 and 12 months old to obtain anthropometric measurements. Discussion There is a growing recognition of the role of maternal circadian rhythm, which entrains fetal circadian rhythms that may subsequently have long-term health consequences. The present study will identify the effect of circadian rhythm on pregnancy outcomes and infant growth in the first year of life.

Purpose: With the emergence of COVID-19, and the potential inclusion of dental benefits in Medicare, it is critical that dentists are able to engage in legislative advocacy to support public oral health. Dental education has an opportunity to teach advocacy skills to future dentists, although advocacy training in predoctoral dental education has been largely ignored. The purpose of this study was to evaluate fourth-year dental student's attitudes toward advocacy, identify the type and extent of advocacy experiences during dental school, and assess their future intentions to engage in advocacy.Methods: An electronic questionnaire was administered to fourth-year dental students enrolled in their final semester at Ohio State University.Results: Forty-seven students completed the survey (43% response rate). Most (84%) respondents agreed that advocacy training should be a required experience in accreditation standards for predoctoral dental education. Over half (58%) reported seldom or no exposure to legislative and regulatory processes in oral health policy development in the curriculum. Students who participated in grassroots advocacy efforts while in dental school were more likely to contact legislators regarding dental issues (p = 0.005) or public insurance (p = 0.037), and participate in future lobbying efforts (p = 0.019). Students who contributed to PAC while in dental school were more likely to express intentions to contribute in future (p = 0.005).Conclusions: There is limited exposure to legislative advocacy in predoctoral dental education. Dental students with advocacy experience are more likely to report intentions to participate in advocacy as dentists. Dental education has a critical role in preparing future dentist-advocates.

The present study aimed to investigate the psychosocial impacts of large-scale solar (LSS) power projects. There were 225 participants (n = 109 women, n = 3 did not indicate gender) participated in our study by completing a series of questionnaires. We found that participants who lived farther from the LSS power project location and those who viewed the project as being impactful were optimistic about the benefits LSS power projects could bring. Our participants also demonstrated support for renewable energy development in Malaysia. These findings may provide important implications for the implementation and execution of LSS power projects and policies.

The thymus is a critical organ for the development of the adaptive immune system and thymic epithelial tumors (TETs; thymomas and thymic carcinomas) are often associated with auto-immune paraneoplastic conditions. However, the immunobiology of TETs is not well described. An evaluation of the tumor microenvironment, with particular focus on expression of immunotherapeutic targets, may facilitate and prioritize development of immunotherapy strategies for patients with TETs.Tumor tissues from 23 patients with WHO Type B2/B3 thymoma (n = 12) and thymic carcinoma (n = 11) were identified and clinical outcomes were annotated. The expression of membranous PD-L1 on tumor cells, CD3+ and CD8+ tumor infiltrating lymphocytes (TILs), co-stimulatory (CD137, GITR, ICOS), and co-inhibitory immune checkpoint molecules (PD-1, CTLA-4, TIM-3) were assessed semi-quantitatively using immunohistochemistry.PD-L1 positivity (≥ 25% of tumor membrane expression) was frequent in TETs (15/23, 65%), more common in thymomas compared to thymic carcinomas (p

In 1993, the first few cases of teacher bullying, when teachers used their power to punish, manipulate or disparage a student beyond what would be a reasonable disciplinary procedure, began to catch the mainstream media's attention. Since then, few studies have focused on teacher bullying globally and even lesser in Asia, where such a phenomenon carries a stigma attached to it. Considering the stark differences between Western and Asian cultures, especially in terms of the power distances between students and teachers, there emerges a need to address this gap in the teacher bullying literature. The study aims to investigate how teacher bullying occurs in an Asian context, with Singapore as the chosen sample of interest. Using semi-structured interviews, the experiences of the non-probability sample of affected students (four men, one woman), were examined through an Interpretative Phenomenological perspective. Findings indicated that teacher bullying existed, involving public humiliation of students, such as shaming, as well as other forms of abusive power towards students. Key findings included a two-stage process of teacher bullying in the form of disparagement amongst other significant findings. It is recommended that policies address acceptable and appropriate behaviour within the teaching context.

As COVID-19 drastically affects cross-border mobility, virtual mobility emerges as a viable alternative to cope with the crisis. This article reports on the integrated findings of an exploratory sequential mixed methods design to understand benefits and challenges of virtual mobility at a Chinese university and future projection of outbound student mobility. The mixed methods design used in this study is characterized by an initial quantitative phase of data collection and analysis, followed by a phase of qualitative data collection and analysis, with a final phase of integration or linking of data from the two separate strands of data. The study suggests Chinese students appreciate the flexibility and economic advantages of virtual mobility but also express concerns on several limitations. Online mobility may be viewed as a complement or alternative for Chinese institutions when the COVID-19 crisis is over. As Chinese universities are promoting internationalization at home, the number of virtual programmes available to Chinese students will surge. In this context, coupled with the stress of geopolitical instability, the growth in Chinese student mobility may be entering a period of contraction, which may exert profound impacts on a global scale.

The exact etiopathogenesis of peri-implant diseases remains unclear. While significant information on molecular markers is available, studies on biomarkers related to possible biocorrosion are sparse. This study aimed to evaluate periimplant crevicular fluid (PICF) for possible titanium (Ti) contamination and explore associations between clinical findings, inflammatory mediators, and Ti levels. Materials and Methods: Patients with implant-supported restoration (≥ 1 year in function) were recruited for this cross-sectional study. Demographics, systemic, and periodontal health history were recorded. Clinical evaluations were conducted to reach peri-implant/periodontal diagnoses and grade severity of periimplant soft tissue inflammation. Crevicular fluid (CF) was collected from both implants and adjacent teeth (PICF, gingival crevicular fluid [GCF]) and analyzed for Ti (inductively coupled plasma mass spectrometry) and inflammatory mediators (V-plex assays). Multiple regression analysis with a linear mixed effect model was used to analyze possible associations between clinical diagnosis, PICF/GCF cytokine, and Ti concentrations. Results: Seventy-seven patients (aged 62 ± 2 years; 39 male) with 117 implants (9 ± 1 years in function) were recruited. Diabetes, positive periodontitis history, and current/former smoking were reported by 8%, 39%, and 39% of subjects, respectively. Seventy-nine implant sites (63 patients) were included in CF cytokine analysis, and 45 of these sites (42 patients) were paired with Ti analysis. Statistically significant increases from health to disease were noted in log-transformed PICF concentrations of IL-1β, IL-6, IL-10, and INF-γ (P ≤ .05). Also, statistically significant increases from health to severe clinical inflammation were detected in log-transformed PICF concentrations of IL-8, IL-13, and TNF-α (P ≤ .05). Ti was detected in the majority (82%) of PICF and GCF samples. There was no statistically significant difference in log-transformed Ti concentration based on disease status. However, logtransformed Ti concentration was positively correlated to IL-1β, IL-2, IL-4, IL-8, IL-13, and INF-γ concentrations when data were adjusted for site-specific health (P ≤ .05). Conclusion: Ti was detectable in PICF and adjacent GCF, even in health. Specific inflammatory mediator concentrations were increased in peri-implant disease and significantly associated with Ti concentrations, even when data were adjusted for peri-implant health status. Increased GCF inflammatory mediator concentrations were also associated with increased Ti concentrations. Ti effects on peri-implant as well as periodontal tissues require additional longitudinal investigations. [ABSTRACT FROM AUTHOR]

Abstract Background The farnesoid X receptor (FXR), pregnane X receptor (PXR), and vitamin D receptor (VDR) are three closely related nuclear hormone receptors in the NR1H and 1I subfamilies that share the property of being activated by bile salts. Bile salts vary significantly in structure across vertebrate species, suggesting that receptors binding these molecules may show adaptive evolutionary changes in response. We have previously shown that FXRs from the sea lamprey (Petromyzon marinus) and zebrafish (Danio rerio) are activated by planar bile alcohols found in these two species. In this report, we characterize FXR, PXR, and VDR from the green-spotted pufferfish (Tetraodon nigriviridis), an actinopterygian fish that unlike the zebrafish has a bile salt profile similar to humans. We utilize homology modelling, docking, and pharmacophore studies to understand the structural features of the Tetraodon receptors. Results Tetraodon FXR has a ligand selectivity profile very similar to human FXR, with strong activation by the synthetic ligand GW4064 and by the primary bile acid chenodeoxycholic acid. Homology modelling and docking studies suggest a ligand-binding pocket architecture more similar to human and rat FXRs than to lamprey or zebrafish FXRs. Tetraodon PXR was activated by a variety of bile acids and steroids, although not by the larger synthetic ligands that activate human PXR such as rifampicin. Homology modelling predicts a larger ligand-binding cavity than zebrafish PXR. We also demonstrate that VDRs from the pufferfish and Japanese medaka were activated by small secondary bile acids such as lithocholic acid, whereas the African clawed frog VDR was not. Conclusions Our studies provide further evidence of the relationship between both FXR, PXR, and VDR ligand selectivity and cross-species variation in bile salt profiles. Zebrafish and green-spotted pufferfish provide a clear contrast in having markedly different primary bile salt profiles (planar bile alcohols for zebrafish and sterically bent bile acids for the pufferfish) and receptor selectivity that matches these differences in endogenous ligands. Our observations to date present an integrated picture of the co-evolution of bile salt structure and changes in the binding pockets of three nuclear hormone receptors across the species studied.