Genetic testing decision-making experiences within families of colorectal cancer patients: A qualitative study.

PURPOSE: Genetic testing is the gold standard for the diagnosis of hereditary colorectal cancer syndromes but is currently inadequate and nonideal. The decision-making processes regarding genetic testing are even less well known. The present study aims to explore the decision-making experience of genetic testing for colorectal cancer patients and their family members. METHOD: A descriptive qualitative study was employed. Data were collected using individual semi-structured interviews with 5 colorectal cancer patients and 20 family members from November 2020 to April 2021. Interviews were transcribed and analysed using inductive content analysis. RESULTS: Four categories were identified: 1) the source of information for genetic testing, 2) the differentiated attitudes towards genetic testing, 3) genetic testing decisional needs, and 4) the factors influencing genetic testing decision-making. Colorectal cancer patients and their families engaged in two distinct pathways to genetic testing decisions: direct decision-making and indirect decision-making. Throughout these processes, due to the limited source of information, they had information needs that were met and facilitated genetic testing decision-making. CONCLUSIONS: Colorectal cancer patients and family members need knowledge related to genetic testing, but they have limited access to information, which prevents them from making informed decisions. Providing decision aid interventions and informational support are significant steps towards addressing the support needs of this population.

The Validation and Psychometric Properties of the Gaming Instinctual Motivation Scale.

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.

Maternal melatonin levels and temporal dietary intake: results from MY-CARE cohort study.

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 (ß=-0.32, p = 0.034) and higher AUCG (ß = 0.26, p = 0.042), respectively. Macronutrient intake within 12:00-15:59 h was negatively associated with mean melatonin (Fat: ß=-0.28, p = 0.041) and AUCG (Carbohydrate: ß=-0.37, p = 0.003; Protein: ß=-0.27, p = 0.036; Fat: ß=-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 (ß=-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.

Endoplasmic Reticulum Stress-induced Endothelial Dysfunction Promotes Neointima Formation after Arteriovenous Grafts in Mice on High-fat Diet.

OBJECTIVE: Endothelial dysfunction is one candidate for triggering neointima formation after arteriovenous grafts (AVGs), but the factors mediating this process are unclear. The purpose of this study was to investigate the role of endoplasmic reticulum stress (ERS)-induced endothelial dysfunction in neointima formation following AVGs in high-fat diet (HFD) mice. METHODS: CCAAT-enhancer-binding protein-homologous protein (CHOP) knockout (KO) mice were created. Mice were fed with HFD to produce HFD model. AVGs model were applied in the groups of WT ND, WT HFD, and CHOP KO HFD. Human umbilical vein endothelial cells (HUVECs) were cultured with oxidized low density lipoprotein (ox-LDL) (40 mg/L) for the indicated time lengths (0, 6, 12, 24 h). ERS inhibitor tauroursodeoxycholic acid (TUDCA) was used to block ERS. Immunohistochemical staining was used to observe the changes of ICAM1. Changes of ERS were detected by real-time RT-PCR. Protein expression levels and ERS activation were detected by Western blotting. Endothellial cell function was determined by endothelial permeability assay and transendothelial migration assay. RESULTS: HFD increased neointima formation in AVGs associated with endothelial dysfunction. At the same time, ERS was increased in endothelial cells (ECs) after AVGs in mice consuming the HFD. In vitro, ox-LDL was found to stimulate ERS, increase the permeability of the EC monolayer, and cause endothelial dysfunction. Blocking ERS with TUDCA or CHOP siRNA reversed the EC dysfunction caused by ox-LDL. In vivo, knockout of CHOP (CHOP KO) protected the function of ECs and decreased neointima formation after AVGs in HFD mice. CONCLUSION: Inhibiting ERS in ECs could improve the function of AVGs.

Revision and Validation of the Chinese Version of the McGill Quality of Life Questionnaire for ICU End-of-Life Patients.

BACKGROUND: Hospice care for end-of-life patients in the ICU should focus on quality of life. Currently, there are no specific quality-of-life measures for ICU end-of-life patients in China. OBJECTIVE: The aim of this study was to revise and culturally adapt the Taiwanese version of the McGill Quality of Life Questionnaire (MQOL-Taiwan) and to test its reliability and validity to provide an effective instrument for assessing the quality of life of ICU patients at the end of life. METHODS: The revision and cultural adaptation of the MQOL-Taiwan were performed to develop a Chinese version of the McGill Quality of Life Questionnaire for ICU end-of-life patients (MQOL-ICU). A total of 156 ICU doctors, 286 ICU nurses and 120 ICU family members of end-of-life patients were surveyed with the revised scale to evaluate the quality of life of ICU patients at the end of life. The content validity, construct validity, and internal consistency of the scale were measured after the revision. RESULTS: The Chinese version of the MQOL-ICU scale was formed based on the MQOL-Taiwan scale, which includes 8 items. For the Chinese version of the MQOL-ICU, the item-content validity index (I-CVI) ranged from 0.789 to 0.905, and the average scale-level content validity index (S-CVI/Ave) was 0.845. After exploratory factor analysis, the Kaiser-Meyer-Olkin (KMO) value was 0.700, and 3 dominant factors were extracted: physical and psychological symptoms, existential well-being, and support. In addition, 70.385% of the total variance was explained. The internal consistency (Cronbach's α) coefficient of the whole MQOL-ICU was 0.804, and the coefficients for the 3 domains ranged from 0.779 to 0.833. CONCLUSION: The Chinese version of the MQOL-ICU showed good reliability and validity, and it can be used to assess the quality of life of ICU patients at the end of life.

Mindfulness is Associated with Better Sleep Quality in Young Adults by Reducing Boredom and Bedtime Procrastination.

OBJECTIVE: Bedtime procrastination is a relatively new topic of research and has been found to compromise sleep. Researchers have studied the predictors, but only a few studies have focused on the ways to reduce bedtime procrastination. Mindfulness, a novel variable in this research area, may shed some light on how to decrease bedtime procrastination. This study examined a serial mediation model and hypothesized that the relationship between mindfulness and better sleep quality would be serially mediated by lower levels of boredom and bedtime procrastination. METHODS: This study employed a correlational approach and recruited a sample of 220 participants aged between 17 and 30 (M = 20.34 years, SD = 2.86). In the Qualtrics online survey, participants completed a series of questionnaires measuring mindfulness, boredom, bedtime procrastination, and sleep quality. RESULTS: The analyses provided support for our serial mediation model. Mindfulness predicted a lower level of boredom, which in turn predicted a lower level of bedtime procrastination and subsequently better sleep quality. CONCLUSION: Our findings highlighted the role of mindfulness in curbing bedtime procrastination, setting a foundation for future research on the interventions for sleep issues associated with bedtime procrastination. We discussed the theoretical and practical implications of the findings.

Phase I trial of the TNF-α inhibitor certolizumab plus chemotherapy in stage IV lung adenocarcinomas.

We previously identified a chemotherapy-induced paracrine inflammatory loop that paradoxically mitigates the anti-tumor effect of chemotherapy and triggers metastatic propagation in breast and lung cancer models. Therefore, we sought to further validate and translate these findings into patient care by coupling the anti-TNF-α drug certolizumab pegol with standard cisplatin doublet chemotherapy. Here we first validate the anti-metastatic effect of certolizumab in a liver-metastatic Lewis Lung Carcinoma model. We then evaluate the safety, efficacy, and pharmacodynamic effects of certolizumab with cisplatin and pemetrexed in an open label Phase 1 clinical trial (NCT02120807) of eighteen adult patients with stage IV lung adenocarcinomas. The primary outcome is maximum tolerated dose. Secondary outcomes are response rate and progression-free survival (PFS); pharmacodynamic changes in blood and tumor are evaluated as a correlative outcome. There were nine partial responses among 16 patients evaluable (56%, 95% CI 30 to 80%). The median duration of response was 9.0 months (range 5.9 to 42.6 months) and median PFS was 7.1 months (95% CI 6.3 to NR). The standard 400 mg dose of certolizumab, added to cisplatin and pemetrexed, is well-tolerated and, as a correlative endpoint, demonstrates potent pharmacodynamic inhibition of peripheral cytokines associated with the paracrine inflammatory loop.

Humility and Competence: Which Attribute Affects Social Relationships at Work?

Between likability and competence, people value likable colleagues (regardless of their competence level) more than competent colleagues. If humility replaces competence, the preference might be different since humility is not always associated with positive outcomes. Humility and competence form four archetypes: humble star, humble fool, competent jerk, and incompetent jerk. This study examined the personal and professional preferences for these archetypes in the workplace and how the preference is moderated by colleagues' seniority. There were 475 working adults aged between 21 and 77 (M = 40.34, SD = 11.32) recruited to complete an online survey. While humble fools were more likable than competent jerks in personal interactions, competent jerks received more cooperation than humble fools in professional interactions. Seniority did not affect these findings. Our findings shed light on whether, and when, humility should be highly valued in organizational settings. Promoting humility in the workplace setting might require more caution.

Maternal diet, nutritional status and infant birth weight in Malaysia: a scoping review.

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.

Dinaciclib inhibits the stemness of two subtypes of human breast cancer cells by targeting the FoxM1 and Hedgehog signaling pathway.

Cyclin­dependent kinase (CDK)4/6 inhibitors in combination with endocrine therapy are the current standard of care used in the first­line treatment of hormone receptor­positive/HER2­negative metastatic breast cancer (BC). Although CDK4/6 inhibitors mainly target the cell cycle, emerging evidence has indicated further potential roles of CDKs other than regulating cell cycle progression. The G1 and G2/M transition regulators, including cyclins D and E, as well as their catalytic partners, CDK2, CDK4 and CDK6, have been reported to play crucial roles in pluripotency maintenance and cell fate decisions of human pluripotent stem cells by controlling transcription factors, signaling pathways and epigenetic regulators. Dinaciclib, a CDK1/2/5/9 inhibitor, is currently being evaluated in clinical trials against various cancer types, including BC. However, the underlying molecular mechanisms of CDK1/2/5/9 inhibitors in regulating BC stemness remain poorly understood. The present study aimed to examine the stemness­inhibitory effects of dinaciclib in MCF­7 (luminal) and HCC­1806 (triple­negative) BC cells. We found that this drug not only effectively reduced the self­renewal abilities and other malignant properties, but also dose­dependently decreased the protein expression levels of three BC stem cell markers, CD44, aldehyde dehydrogenase 1 family member A1 (ALDH1A1) and BMI1 proto­oncogene, polycomb ring finger (Bmi1), as well as three embryonic stem cell markers, Oct4, Nanog and Sox2. Moreover, the dinaciclib­induced decrease of Oct4 and Nanog protein expression was able to be restored by co­treatment with MG­132, a proteasome inhibitor. Forkhead box M1 (FoxM1), both a stemness­stimulating transcription factor and a cell cycle regulator, along with the Hedgehog signaling pathway, were identified as the therapeutic targets of dinaciclib. Collectively, the present results demonstrated a novel role of dinaciclib in suppressing BC stemness and indicated its potential use for future cancer treatments.

Chrononutrition is associated with melatonin and cortisol rhythm during pregnancy: Findings from MY-CARE cohort study.

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 (ß = -0.40, p = 0.006), peak (ß = -0.42, p = 0.006), and AUCG (ß = -0.44, p = 0.003). During both trimesters, a lower awakening cortisol level was observed in pregnant women who skipped breakfast (ß = -0.33, p = 0.029; ß = -0.29, p = 0.044). Only during the second trimester, breakfast-skipping was significantly associated with a greater cortisol amplitude (ß = 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.

Psychological state during pregnancy is associated with sleep quality: preliminary findings from MY-CARE cohort study.

Psychological distress during pregnancy may increase the risk of adverse maternal and infant outcomes. Past studies have demonstrated the association between circadian disturbances with psychological health. However, the roles of chronotype and social jetlag on psychological state during pregnancy are yet to be identified. We aimed to examine the psychological state in pregnant women and its relations to chronotype, social jetlag (SJL), sleep quality and cortisol rhythm. The current study included a subsample of participants from an ongoing cohort study. A total of 179 primigravidas (mean age 28.4 ± 4.0 years) were recruited. Chronotype and sleep quality during the second trimester were assessed using the Morning-Eveningness Questionnaire (MEQ) and Pittsburgh Sleep Quality Index (PSQI), respectively. SJL was calculated based on the difference between mid-sleep on workdays and free days. Psychological state of participants was evaluated using the Depression, Anxiety, and Stress Scale-21 (DASS-21). Subsamples (n = 70) provided salivary samples at 5 time points over a 24 h period during the second trimester for cortisol assay. A higher proportion of pregnant women experienced moderate to severe anxiety symptoms (n = 77, 43.0%), followed by depressive (n = 17, 9.5%) and stress (n = 14, 7.8%) symptoms. No association was observed between chronotype and psychological distress during pregnancy. There was no significant difference in cortisol rhythms in relation to psychological distress. SJL and sleep quality were significantly associated with stress symptoms among pregnant women in the second trimester. Poor sleep quality, particularly daytime dysfunction (ß = 0.37, p = .006) and sleep disturbances (ß = 0.23, p = .047), were significantly associated with psychological distress (depressive, anxiety and stress symptoms) during the second trimester. The findings suggest that sleep is a potential modifiable lifestyle factor that can be targeted to improve psychological health among pregnant women.

Validation of the Chinese Version of the Quality of Dying and Death Questionnaire for Family Members of ICU Patients.

CONTEXT: The quality of end-of-life care services directly affects the end-of-life quality of life of patients and their families. At present, there are no standard tools in China for assessing the quality of dying and death (QODD) of critical intensive care unit (ICU) patients. OBJECTIVES: This study aimed to introduce the Chinese version of the QODD questionnaire for family members of ICU patients, after transcultural adaptation and validation, to provide an effective instrument for assessing the quality of end-of-life care of ICU patients in China, fill the gap in the evaluation of the quality of end-of-life care of critical ICU patients in China, and offer a theoretical basis and practical guidance during purposeful intervention. METHODS: This study involved the main adult caregivers or principal family members of 149 dying critically ill patients. The original QODD scale was translated using the double forward and backward method. Nine cultural adaptation experts adapted the Chinese version of the QODD scale for completion by family members of ICU patients. Then, we carried out content validity, structural validity, internal consistency, confirmatory factors, and item correlation analysis of the modified scale. RESULTS: The Chinese version of the QODD for family members of ICU patients was developed after some items were deleted or modified. The content validity index was 0.93, indicating that all items were correlated with the measurement of death quality. The Kaiser-Meyer-Olkin value was 0.797, suggesting that the correlations between items were high. The Cronbach's α was 0.865, indicating good internal consistency. In confirmatory factor analysis, the fit indices were χ2 = 207.327, non-normed fit index = 0.916, root mean square error of approximation = 0.033, and comparative fit index = 0.93, indicating a good fit of the five-factor model of the Chinese version of the QODD questionnaire for family members of ICU patients. CONCLUSION: The Chinese version of the QODD questionnaire for family members of ICU patients is a reliable and effective instrument for evaluating the quality of death among patients who die in the ICU and can be applied to clinical practice and research.

A Clinical Genomics-Guided Prioritizing Strategy Enables Selecting Proper Cancer Cell Lines for Biomedical Research.

Selecting appropriate cell lines to represent a disease is crucial for the success of biomedical research, because the usage of less relevant cell lines could deliver misleading results. However, systematic guidance on cell line selection is unavailable. Here we developed a clinical Genomics-guided Prioritizing Strategy for Cancer Cell Lines (CCL-cGPS) and help to guide this process. Statistical analyses revealed CCL-cGPS selected cell lines were among the most appropriate models. Moreover, we observed a linear correlation between the drug response and CCL-cGPS score of cell lines for breast and thyroid cancers. Using RT4 cells selected by CCL-GPS, we identified mebendazole and digitoxin as candidate drugs against bladder cancer and validate their promising anticancer effect through in vitro and in vivo experiments. Additionally, a web tool was developed. In conclusion, CCL-cGPS bridges the gap between tumors and cell lines, presenting a helpful guide to select the most suitable cell line models.

Novel Double Endobutton Technique Combined with Three-Dimensional Printing: A Biomechanical Study of Reconstruction in Acromioclavicular Joint Dislocation.

OBJECTIVE: To reconstruct the acromioclavicular (AC) joint using an adjusted closed-loop double Endobutton technique via a guiding locator that was applied using three-dimensional (3D) printing technology. At the same time, the reliability and safety of the novel double Endobutton (NDE) were tested by comparing the biomechanics of this technique with the TightRope (TR) approach. METHODS: This retrospective study was conducted between January 2017 and January 2019. The Department of Anatomy at Southern Medical University obtained 18 fresh-frozen specimens (8 left and 10 right; 12 men and 6 women). First, the guiding locators were applied using 3D printing technology. After preparation of materials, specimens were divided into an NDE group, a TR group, and a normal group. In the NDE and TR groups, the navigation module was used to locate and establish the bone tunnels; after that, the NDE or TR was implanted. However, the Endobuttons were fixed while pressing the distal clavicle downwards and the length of the loop could be adjusted by changing the upper Endobutton in the NDE group while the suture button construct was tensioned and knotted after pressing down the distal clavicle in the TR. Finally, load testing in anterior-posterior (AP), superior-inferior (SI), and medial-lateral (ML) directions as well as load-to-failure testing in the SI direction were undertaken to verify whether the NDE or TR had better biomechanics. RESULTS: In the load testing, the displacements of the NDE and TR groups in the AP, SI, and ML direction were significantly shorter than those of the normal group (P < 0.05). In the load-to-failure testing, the ultimate load of the NDE and TR groups had significantly higher increases than the normal group (722.16 ± 92.04 vs 564.63 ± 63.05, P < 0.05; 680.20 ± 110.29 vs 564.63 ± 63.05, P < 0.05). However, there was no statistically significant difference between the two techniques for these two tests (P > 0.05). In the NDE group, four of six failures were a result of tunnel fractures of the coracoid, while two of six were due to suture breakage. In the TR, three failures were due to coracoid tunnel fractures, one was a result of a clavicle tunnel fracture, and the rest were due to suture breakage. In the normal group, half of the failures were a result of avulsion fractures of the conical ligament at the point of the coracoid process, and the other three were due to rupture of the conical ligament, fracture of the distal clavicle, and fracture of the scapular body. CONCLUSION: As for the TR technique, the stability and strength of the AC joint were better in patients who underwent reconstruction using the NDE technique than in the intact state.

Circadian rhythm and its association with birth and infant outcomes: research protocol of a prospective cohort study.

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.

scCATCH: Automatic Annotation on Cell Types of Clusters from Single-Cell RNA Sequencing Data.

Recent advancements in single-cell RNA sequencing (scRNA-seq) have facilitated the classification of thousands of cells through transcriptome profiling, wherein accurate cell type identification is critical for mechanistic studies. In most current analysis protocols, cell type-based cluster annotation is manually performed and heavily relies on prior knowledge, resulting in poor replicability of cell type annotation. This study aimed to introduce a single-cell Cluster-based Automatic Annotation Toolkit for Cellular Heterogeneity (scCATCH, https://github.com/ZJUFanLab/scCATCH). Using three benchmark datasets, the feasibility of evidence-based scoring and tissue-specific cellular annotation strategies were demonstrated by high concordance among cell types, and scCATCH outperformed Seurat, a popular method for marker genes identification, and cell-based annotation methods. Furthermore, scCATCH accurately annotated 67%-100% (average, 83%) clusters in six published scRNA-seq datasets originating from various tissues. The present results show that scCATCH accurately revealed cell identities with high reproducibility, thus potentially providing insights into mechanisms underlying disease pathogenesis and progression.

SMARCA4-Deficient Thoracic Sarcomatoid Tumors Represent Primarily Smoking-Related Undifferentiated Carcinomas Rather Than Primary Thoracic Sarcomas.

INTRODUCTION: Highly aggressive thoracic neoplasms characterized by SMARCA4 (BRG1) deficiency and undifferentiated round cell or rhabdoid morphology have been recently described and proposed to represent thoracic sarcomas. However, it remains unclear whether such tumors may instead represent sarcomatoid carcinomas, and how their clinicopathologic characteristics compare with those of nonsarcomatoid SMARCA4-deficient non-small cell lung carcinomas (SD-NSCC). METHODS: We identified 22 SMARCA4-deficient thoracic sarcomatoid tumors (SD-TSTs) with round cell and/or rhabdoid morphology and 45 SD-NSCCs, and comprehensively analyzed their clinicopathologic, immunohistochemical, and genomic characteristics using 341-468 gene next-generation sequencing and other molecular platforms. RESULTS: The relationship of SD-TSTs with NSCC was supported by (1) the presence of NSCC components juxtaposed with sarcomatoid areas in five cases, (2) focal expression of NSCC lineage markers TTF1 or p40 in four additional cases, (3) smoking history in all except one patient (mean = 51 pack-years), accompanied by genomic smoking signature, and (4) high tumor mutation burden (mean = 14.2 mutations per megabase) and mutations characteristic of NSCC in a subset. Compared with SD-NSCCs, SD-TSTs exhibited considerably larger primary tumor size (p < 0.0001), worse survival (p = 0.004), and more frequent presentation at younger age (30-50 years) despite heavier smoking history. Distinctive pathologic features of SD-TSTs included consistent lack of adhesion molecule claudin-4, SMARCA2 (BRM) codeficiency, and frequent expression of stem cell markers. CONCLUSIONS: SD-TSTs represent primarily smoking-associated undifferentiated/de-differentiated carcinomas rather than primary thoracic sarcomas. Despite their histogenetic relationship with NSCC, these tumors have unique clinicopathologic characteristics, supporting their recognition as a distinct entity. Further studies are warranted to determine therapeutic approaches to this novel class of exceptionally aggressive thoracic tumors.

Prediction of Adverse Drug Reactions by Combining Biomedical Tripartite Network and Graph Representation Model.

As one of the primary contributors to high clinical attrition rates of drugs, toxicity evaluation is of critical significance to new drug discovery. Unsurprisingly, a vast number of computational methods have been developed at various stages of development pipeline to evaluate potential adverse drug reactions (ADRs). Despite previous success of these methods on individual ADR or certain drug family, there are great challenges to toxicity evaluation. In this study, a novel strategy was developed to predict the drug-ADR associations by combining deep learning and the biomedical tripartite network. This heterogeneous network contains biomedical linked data of three entities, for example, drugs, targets, and ADRs. For the first time, GraRep, a deep learning method for distributed representations, is introduced to learn graph representations and identify hidden features from the tripartite network which are further used for ADR prediction. Through this approach, drug-ADR associations could possibly be discovered from a systemic perspective. The accuracy of our method is 0.95 based on internal resource validation and 0.88 based on external resource validation. Moreover, our results show the prediction accuracy using the tripartite network is better than the one with bipartite network, suggesting the model performance can be improved with further enrichment on information. According to the result of 10-fold cross validation, the deep learning model outperforms two traditional methods (topology-based measures and chemical structure-based measures). Additionally, predictive models are also constructed using other deep learning methods, and comparable results are achieved. In summary, the biomedical tripartite network-based deep learning model proposed here proves to offer a promising solution for prediction of ADRs.

Mechanism of Shaoyao Decoction in treatment of ulcerative colitis based on network pharmacology and molecular docking technology / 中草药

Objective: Network pharmacology and molecular docking technology were used to study the material basis and possible mechanism of Shaoyao Decoction in treatment of ulcerative colitis (UC). Methods: TCMSP and TCMID were used to obtain the potential active components and drug targets of Shaoyao Decoction. GeneCard and OMIM were used to search disease targets. The common targets obtained by matching drug targets and disease targets were imported into String to construct a PPI network, and Cyto NCA plug-in was used to screen key targets. The network diagram was drawn by connecting the key targets with the corresponding components, so as to screen the key components. GO and KEGG enrichment analyses were performed on key targets. SYBYL-X2.0 software was used to dock the molecules of the key components with the key targets. The rat UC model was replicated in vivo. After the intervention of Shaoyao Decoction, the disease activity index was observed, the colonic pathological damage was evaluated, and the levels of TNF-α, IL-4 and CXCR4 were detected by ELISA. Results: A total of 424 potential active components were found in Shaoyao Decoction. The key components included quercetin, palmitic acid, catechin, and procyanidins, etc. Its 41 key targets for UC were mainly related to the positive regulation of transcription, the negative regulation of apoptosis process, the signal transduction, and other biological processes. The key targets played a role in treating UC through signaling pathways such as TNF, HIF-1, cancer pathway, TLR, PI3K-Akt, et al. Molecular docking results showed that key components had good binding activity with corresponding targets. Shaoyao Decoction improved colon pathological damage, down-regulated the level of TNF-α and CXCR4, and up-regulated the level of IL-4 in vivo. Conclusion: Shaoyao Decoction has the characteristics of "multi-components, multi-targets, multi-pathways" in treatment of UC, which lays a foundation for further study of its mechanism.