Single-cell exome sequencing and monoclonal evolution of a JAK2-negative myeloproliferative neoplasm.

Tumor heterogeneity presents a challenge for inferring clonal evolution and driver gene identification. Here, we describe a method for analyzing the cancer genome at a single-cell nucleotide level. To perform our analyses, we first devised and validated a high-throughput whole-genome single-cell sequencing method using two lymphoblastoid cell line single cells. We then carried out whole-exome single-cell sequencing of 90 cells from a JAK2-negative myeloproliferative neoplasm patient. The sequencing data from 58 cells passed our quality control criteria, and these data indicated that this neoplasm represented a monoclonal evolution. We further identified essential thrombocythemia (ET)-related candidate mutations such as SESN2 and NTRK1, which may be involved in neoplasm progression. This pilot study allowed the initial characterization of the disease-related genetic architecture at the single-cell nucleotide level. Further, we established a single-cell sequencing method that opens the way for detailed analyses of a variety of tumor types, including those with high genetic complex between patients.

Hemorheology and Inflammatory Marker Changes in Patients with Acute Ischemic Stroke after Intravenous Thrombolysis with Mechanical Thrombectomy.

Objective: To investigate hemorheology and inflammatory marker changes after treatment for acute ischemic stroke (AIS) using intravenous thrombolysis (IVT) with mechanical thrombectomy (MT). Methods: We retrospectively reviewed clinical records of patients with AIS (n=83) treated in The First Affiliated Hospital of Bengbu Medical College between January 2021 and December 2022 (n=83). The control group consisted of 38 patients who underwent IVT alone and the observation group consisted of 45 patients who underwent IVT with MT. We compared differences in mean variables related to hemorheology, inflammatory markers, and total efficacy between the two groups. Results: We found that hemorheology values (plasma viscosity [PV], whole blood viscosity [WBV], fibrinogen [FIB], and hematocrit [HCT]), and the levels of inflammatory markers (tumor necrosis factor ɑ [TNF-ɑ] and interleukin-6 [IL-6]) were higher in the control group than in the observation group after treatment (P<0.05). In addition, the total efficacy of the observation group (93.3%) was higher than that in the control group (76.3%; P=0.016). Conclusions: The clinical efficacy of combined IVT and MT in the treatment of AIS is superior to IVT alone, improving levels of hemorheology and inflammatory markers in patients with AIS.

The study of bioavailability and endogenous circadian rhythm of menaquinone-7, a form of vitamin K2, in healthy subjects.

Menaquinone-7 (MK-7), a multipotent vitamin K2, possesses a wide range of biological activities, a precise curative effect and excellent safety. A simple and rapid LC-APCI-MS/MS method for the determination of MK-7 in human plasma with single liquid-liquid extraction (LLE) extraction and 4·5-min analysis time has been developed and validated. Four per cent bovine serum albumin (BSA) was used as surrogate matrix for standard curves and endogenous baseline subtraction. This method was reproducible and reliable and was used to analyse of MK-7 in human plasma. The endogenous circadian rhythm and bioavailability of MK-7 were investigated in two randomised single-dose, open, one-way clinical trials (Study I and Study II). A total of five healthy male subjects were enrolled in Study I and 12 healthy male subjects in Study II. Single-dose (1 mg) of MK-7 was given to each subject under fasting condition, and all eligible subjects were given a restricting VK2 diet for 4 d prior to drug administration and during the trial. The experiment results of Study I demonstrated that endogenous MK-7 has no circadian rhythm in individuals. Both studies showed MK-7 are absorbed with peak plasma concentrations at about 6 h after intake and has a very long half-life time.

Relationship between plasma circulating cell-free DNA concentration and treatment outcomes including prognosis in patients with advanced non-small cell lung cancer.

BACKGROUND: Some research found that elevated plasma cell-free DNA (cfDNA) concentrations and poor prognosis are associated in non-small cell lung cancer (NSCLC). However, more studies need to be carried out to verify this conclusion. Therefore, this study investigated the relationship between cfDNA concentration and treatment outcomes including prognosis in patients with advanced NSCLC. METHODS: We retrospectively collected medical records and cfDNA data from 160 patients with advanced NSCLC. Progression-free survival (PFS) were calculated using the Kaplan-Meier method and were compared between groups using the log rank test. Cox regression analysis was used for estimating the independent predictors of PFS. And we used logistic regression to evaluate the relationship between baseline biomarkers and efficacy. In our study, BT1 cfDNA, BT2 cfDNA, and BT3 cfDNA were defined as cfDNA concentration before the first treatment (baseline cfDNA concentration), cfDNA concentration before the second treatment, and cfDNA concentration before the third treatment, respectively. RESULTS: Patients with low cfDNA (BT1 cfDNA < 15 (ng/mL)) were reported a significantly prolonged median progression-free survival (mPFS) compared with patients with patients with high cfDNA (BT1 cfDNA ≥ 15(ng/mL)) (mPFS: 14.6 vs. 8.3 months, P = 0.002), as well as patients with neutrophil/lymphocyte ratio (NLR)<2.98 (mPFS: 13.1 vs. 7.9 months, P = 0.023). In addition, Cox proportional hazards regression analysis identified independent indicators associated with PFS including BT1 cfDNA ≥ 15 (ng/mL), NLR ≥ 2.98 and extrapulmonary metastasis. The best cut-off value for BT3 cfDNA for predicting disease progression is 41.46 (ng/mL) (Area Under the Curve (AUC): 0.652, 95%CI: 0.516-0.788), achieving 90.7% sensitivity and 37.5% specificity for the prediction of disease progression. BT3 cfDNA (OR = 6.08, 95% CI: 1.94-19.57, P = 0.002) was an independent factor for disease progression in patients with advanced NSCLC. CONCLUSIONS: BT1 cfDNA may be a biomarker to assess the prognosis of advanced NSCLC. Patients with advanced NSCLC with lower cfDNA and NLR before treatment had a better prognosis. Increased BT3 cfDNA concentration was an independent factor of disease progression in advanced NSCLC patients. These findings may assist in identifying high-risk patients and guiding treatment strategies.

Association Between Online Health Information-Seeking Behaviors by Caregivers and Delays in Pediatric Cancer: Mixed Methods Study in China.

BACKGROUND: Pediatric cancer patients in China often present at an advanced stage of disease resulting in lower survival and poorer health outcomes. One factor hypothesized to contribute to delays in pediatric cancer has been the online health information-seeking (OHIS) behaviors by caregivers. OBJECTIVE: This study aims to examine the association between OHIS behaviors by caregivers and delays for Chinese pediatric cancer patients using a mixed methods approach. METHODS: This study used a mixed methods approach, specifically a sequential explanatory design. OHIS behavior by the caregiver was defined as the way caregivers access information relevant to their children's health via the Internet. Delays in pediatric cancer were defined as any one of the following 3 types of delay: patient delay, diagnosis delay, or treatment delay. The quantitative analysis methods included descriptive analyses, Student t tests, Pearson chi-square test, and binary logistic regression analysis, all performed using Stata. The qualitative analysis methods included conceptual content analysis and the Colaizzi method. RESULTS: A total of 303 pediatric cancer patient-caregiver dyads was included in the quantitative survey, and 29 caregivers completed the qualitative interview. Quantitative analysis results revealed that nearly one-half (151/303, 49.8%) of patients experienced delays in pediatric cancer, and the primary type of delay was diagnosis delay (113/303, 37.3%), followed by patient delay (50/303, 16.5%) and treatment delay (24/303, 7.9%). In this study, 232 of the 303 (76.6%) caregiver participants demonstrated OHIS behaviors. When those engaged in OHIS behaviors were compared with their counterparts, the likelihood of patient delay more than doubled (odds ratio=2.21; 95% CI 1.03-4.75). Qualitative analysis results showed that caregivers' OHIS behaviors impacted the cancer care pathway by influencing caregivers' symptom appraisal before the first medical contact and caregivers' acceptance of health care providers' diagnostic and treatment decisions. CONCLUSIONS: Our findings suggest that OHIS among Chinese pediatric caregivers may be a risk factor for increasing the likelihood of patient delay. Our government and society should make a concerted effort to regulate online health information and improve its quality. Specialized freemium consultations provided by health care providers via online health informatic platforms are needed to shorten the time for caregivers' cancer symptom appraisal before the first medical contact.

Prenatal stress self-help mindfulness intervention via social media: a randomized controlled trial.

BACKGROUND: Prenatal stress is a pressing issue. However, there is a lack of robust evidence for psychosocial interventions to manage this problem. AIMS: This study aimed to examine the effectiveness of a mindfulness-based intervention on reducing prenatal stress compared to participation in health education groups. METHODS: A randomized controlled trial was conducted in a prenatal clinic of comprehensive tertiary care from April to October 2017. A total of 108 pregnant women were randomly assigned to an intervention or a control group. Participants completed self-report measures of depression, anxiety, perceived stress, fatigue, positive and negative affect, and mindfulness before, immediately after, and 15 weeks after the 4-week intervention period. Generalized estimating equations were used to analyze the intervention outcomes. RESULTS: The results supported greater improvement in terms of perceived stress (Wald χ2=26.94, p<0.001), fatigue (Wald χ2=17.61, p<0.001), positive affect (Wald χ2=9.03, p = 0.011), negative affect (Wald χ2=11.37, p = 0.003), and mindfulness (Wald χ2=24.97, p<0.001) in the intervention group than in the control group. CONCLUSIONS: The self-help mindfulness intervention decreased prenatal stress and negative affect and improved positive affect and mindfulness.

Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): A multicenter, phase 2 study.

Optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is controversial, especially in the context of potential benefit of combining PD-1 blockade with neoadjuvant therapy. This phase 2 study aimed to assess neoadjuvant camrelizumab plus chemotherapy in this population. Patients (clinical stage II-IVA) received two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab-paclitaxel (260 mg/m2 in total on day 1 and day 8) and cisplatin (75 mg/m2 in total on days 1-3) of each 21-day cycle. Surgery was performed approximately 6 weeks after completion of NIC. Primary endpoint was complete pathologic response (CPR) rate in primary tumor. Secondary endpoints were objective response rate (ORR) per RECIST v1.1, 2-year progression-free survival (PFS) rate after surgery, PFS, overall survival (OS) and safety during NIC and perioperative period. Between 17 January 2020 and 8 December 2020, 56 patients were enrolled, and 51 received esophagectomy. Data cutoff date was 25 August 2021. The CPR rate was 35.3% (95% CI, 21.7%-48.9%). NIC had an ORR of 66.7% (95% CI, 40.0%-70.4%) and treatment-related adverse events (TRAEs) of low severity (grade 1-2, 75.0%; grade 3, 10.7%; grade 4-5, no). No perioperative mortality occurred. Three (5.9%) patients had tumor recurrence and one (2.0%) patient died. The 2-year PFS rate, median PFS and median OS had not been reached yet. Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option. Study is ongoing for long-term survival analyses.

Exploring the intercalation binding of tiamulin with DNA using multispectroscopy and a molecular modelling approach.

The binding of tiamulin with calf thymus DNA was systematically investigated using multispectroscopy and molecular modelling techniques. For DNA, once tiamulin was added, viscosity (η) and melting temperature (Tm ) both exhibited an uptrend. The fluorescence performance of the tiamulin-DNA complex did not change with the ionic strength changes. The binding constant (Ka ) of tiamulin for single-stranded DNA (ssDNA, 1.48 × 104 M-1 ) was obviously higher than that for double-stranded DNA (dsDNA, 9.51 × 103 M-1 ) at 291 K. The helix structure became looser and the base stack force became stronger for DNA due to the presence of tiamulin as seen from circular dichroic (CD) spectra. The intercalation binding mode of tiamulin with DNA was disclosed. Molecular modelling also revealed tiamulin inserting into the base pairs with the lowest binding free energy of -18.73 kJ mol-1 using van der Waals forces as well as hydrogen bonds.

The efficacy and mechanisms of a guided self-help intervention based on mindfulness in patients with breast cancer: A randomized controlled trial.

BACKGROUND: Mindfulness-based interventions (MBIs) can alleviate psychological distress in patients with cancer. However, face-to-face MBIs may be inconvenient for patients. Therefore, guided self-help interventions may be more accessible. The authors investigated the effects of a guided self-help MBI for depression, anxiety, and sleep disorder symptoms in patients with breast cancer and explored the potential underlying mechanisms. METHODS: One hundred forty-four postoperative patients with breast cancer were randomly assigned to an intervention group (6-week guided self-help MBI; n = 72) or a wait-list control group (routine treatment; n = 72). Self-reported depression, anxiety, sleep disorder symptoms, and rumination and worry as potential mediators were assessed at baseline and postintervention. Outcomes were then assessed at 1-month and 3-month follow-up. The intervention's effects over time and the potential mediating effect were analyzed using generalized estimating equations. The trial was registered at the Chinese Clinical Registry (ChiCTR-IOR-16008073). RESULTS: Significant improvements in depression and sleep disorder symptoms occurred in the intervention group compared with wait-list controls, and the improvements were maintained at 1-month and 3-month follow-up. Changes in rumination and worry mediated the intervention's effects on changes in depression and sleep disorder symptoms. CONCLUSIONS: A guided self-help MBI reduced depressive and sleep disorder symptoms by mitigating rumination and worry in patients with breast cancer. These findings support benefits of this accessible psychological intervention in oncology and provide insight into possible mechanisms of action. The current research contributes to discovering effective and widely accessible means for people with physical health conditions and may remove barriers that otherwise would have precluded participation in face-to-face psychological interventions.

Assessment on the binding characteristics of residual marbofloxacin in animal-derived food to bovine/human serum albumin by spectroscopy and molecular modelling.

To assess the toxicity of residual marbofloxacin from animal-derived food, the interaction characteristics of marbofloxacin to bovine/human serum albumins (BSA/HSA) were explored using spectroscopic methods combined with molecular modelling. According to fluorescence spectra and time-resolved fluorescence spectra measurements, quenching of BSA/HSA fluorescence induced by marbofloxacin was characterized as static quenching. A 1:1 ground-state complex of marbofloxacin to BSA/HSA was formed with binding constant (Ka ) 1.66 × 104 /9.74 × 103 M-1 at 291 K. The location of marbofloxacin binding at site I within BSA/HSA was clarified by site marker competitive experiments. Molecular modelling demonstrated that the binding region for marbofloxacin to BSA and HSA were at site I with the lowest binding free energies of -22.86 and -21.60 kJ mol-1 , respectively. Hydrogen bonds and van der Waals forces were dominantly involved in the spontaneous binding. Nonradiation energy transferred from BSA and HSA to marbofloxacin, due to the close distance (r0 ) between marbofloxacin and Trp residues of BSA (4.28 nm) and HSA (3.34 nm). As explained by circular dichroism (CD) spectra, an increased BSA/HSA α-helix structure was observed after binding to marbofloxacin. Ultraviolet-visible (UV-vis) and Fourier transform infrared (FT-IR) spectra suggested that conformation of the two proteins was altered by marbofloxacin.

RDb2C2: an improved method to identify the residue-residue pairing in ß strands.

BACKGROUND: Despite the great advance of protein structure prediction, accurate prediction of the structures of mainly ß proteins is still highly challenging, but could be assisted by the knowledge of residue-residue pairing in ß strands. Previously, we proposed a ridge-detection-based algorithm RDb2C that adopted a multi-stage random forest framework to predict the ß-ß pairing given the amino acid sequence of a protein. RESULTS: In this work, we developed a second version of this algorithm, RDb2C2, by employing the residual neural network to further enhance the prediction accuracy. In the benchmark test, this new algorithm improves the F1-score by > 10 percentage points, reaching impressively high values of ~ 72% and ~ 73% in the BetaSheet916 and BetaSheet1452 sets, respectively. CONCLUSION: Our new method promotes the prediction accuracy of ß-ß pairing to a new level and the prediction results could better assist the structure modeling of mainly ß proteins. We prepared an online server of RDb2C2 at http://structpred.life.tsinghua.edu.cn/rdb2c2.html.

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high-risk Chinese individuals.

Identification of deleterious variants in hereditary breast and ovarian cancer (HBOC) susceptibility genes allows for increased clinical surveillance and early detection, and could predict the response to poly (ADP-ribose) polymerase (PARP) inhibitor in patients with advanced ovarian carcinomas. To determine the prevalence and clinical prediction factors for HBOC syndrome, 882 selected individuals underwent multigene panel testing for HBOC risk assessment during the period from January 2015 to March 2018. Overall, 176 deleterious mutations were observed in 19.50% (n = 172) of individuals. Twenty-six of 176 mutations could not be retrieved in related public databases and were considered to be novel. Among patients with ovarian cancer, 115 deleterious mutations were identified in 429 patients (48.6%) with significant enrichment for a family history of breast or ovarian cancer syndrome (P < .05). In the breast cancer subgroup, 31 deleterious mutations were identified in 261 patients. Besides BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%), the most frequently occurring genes, an additional 12 deleterious mutations (38.7%) were found in seven other susceptibility genes. Higher mutation incidence (57.9%) was observed in subjects with histories of breast and ovarian cancer. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of a multigene panel in carrying out risk assessment.

RISE: a database of RNA interactome from sequencing experiments.

We present RISE (http://rise.zhanglab.net), a database of RNA Interactome from Sequencing Experiments. RNA-RNA interactions (RRIs) are essential for RNA regulation and function. RISE provides a comprehensive collection of RRIs that mainly come from recent transcriptome-wide sequencing-based experiments like PARIS, SPLASH, LIGR-seq, and MARIO, as well as targeted studies like RIA-seq, RAP-RNA and CLASH. It also includes interactions aggregated from other primary databases and publications. The RISE database currently contains 328,811 RNA-RNA interactions mainly in human, mouse and yeast. While most existing RNA databases mainly contain interactions of miRNA targeting, notably, more than half of the RRIs in RISE are among mRNA and long non-coding RNAs. We compared different RRI datasets in RISE and found limited overlaps in interactions resolved by different techniques and in different cell lines. It may suggest technology preference and also dynamic natures of RRIs. We also analyzed the basic features of the human and mouse RRI networks and found that they tend to be scale-free, small-world, hierarchical and modular. The analysis may nominate important RNAs or RRIs for further investigation. Finally, RISE provides a Circos plot and several table views for integrative visualization, with extensive molecular and functional annotations to facilitate exploration of biological functions for any RRI of interest.

Factors associated with the utilization of community-based diabetes management care: A cross-sectional study in Shandong Province, China.

BACKGROUND: Community-based diabetes management is known to be an important strategy for global diabetes control. In China, community-based diabetes management care, including regular blood glucose tests and guidance on medicine use, dietary control, and physical exercise provided by primary health institutions (PHIs), as one of the key contents of the national essential public health services (EPHS), was implemented since 2009 when the new round of health system reform was initiated. This study aimed to investigate the utilization of community-based diabetes management care services, and explore the factors influencing utilization from both patients' and providers' points of view. METHODS: In total, 2520 type-2 diabetes mellitus (DM) patients registered for EPHS were selected from 63 PHIs in eight counties of Shandong province, China, using multi-stage stratified sampling. Of those, 2166 patients (response rate: 85.4%) completed face-to-face structured questionnaires on their utilization of community-based diabetes management care services. Further, 63 PHIs were surveyed on diabetes care delivery, and 444 primary healthcare providers were purposively sampled from those PHIs to measure their knowledge of diabetes management care delivery, using a self-developed questionnaire. Descriptive statistics were used to analyze the delivery and utilization of diabetes management care services. Multilevel logistic regression models were used to analyze the factors associated with patients' utilization of diabetes management services. RESULTS: All 63 PHIs reported that all the required four diabetes management services were provided through EPHS. However, only 49.6% of the patients reported they fully used these services, with no statistically significant difference between urban and rural patients. Patients who had higher knowledge of diabetes and better self-efficacy in controlling the condition, were more likely to fully utilize diabetes management care. A larger number of PHI health staff per 1000 population was associated with better utilization of care. CONCLUSION: Although community-based diabetes management services are well available to Chinese DM patients under the framework of EPHS, the actual utilization of diabetes management services among the patients was poor. The size of the PHI workforce, patients' knowledge and self-efficacy in controlling diabetes, were important predictors of utilization, and could be enhanced to improve control of diabetes.

Depicting the binding of furazolidone/furacilin with DNA by multiple spectroscopies, voltammetric as well as molecular docking.

The interaction between DNA and furazolidone/furacillin was investigated using various analytical techniques including spectroscopy and electroanalysis and molecular modelling. With the aid of acridine orange (AO), the fluorescence lifetimes of DNA-AO, DNA-furazolidone/furacillin-AO remained almost the same, which proved that the ground state complex was formed due to furazolidone/furacillin binding with DNA. Circular dichroism spectra and Fourier transform infrared spectroscopy showed that the second structure of DNA changed. Viscosity experiments presented that relative viscosity of DNA was increased with the increasing concentrations of furazolidone and almost unchanged for furacilin. In addition, the results of melting temperature (Tm ), ionic strength, site competition experiments, cyclic voltammetry, and molecular docking all proved the intercalation binding mode for furazolidone and groove binding mode for furacilin. The binding constants (Ka ) obtained from Wolfe-Shimmer equation were calculated as 3.66 × 104 L mol-1 and 3.95 × 104 L mol-1 for furazolidone-DNA and furacilin-DNA, respectively.

Effectiveness of two guided self-administered interventions for psychological distress among women with infertility: a three-armed, randomized controlled trial.

STUDY QUESTION: What is the effect of two guided self-administered interventions on psychological distress in women undergoing IVF or ICSI? SUMMARY ANSWER: A brief mindfulness intervention significantly reduced depression and improved sleep quality, while the gratitude journal intervention showed no significant effect on any outcome variables. WHAT IS KNOWN ALREADY: Mindfulness and gratitude journal interventions have been found to be beneficial in reducing negative affect and improving well-being. However, there are very few mental health professionals who implement such interventions in low- and middle-income countries. Therefore, two guided self-administered interventions for women with infertility were designed to help them cope with their psychological distress. STUDY DESIGN, SIZE, DURATION: A three-armed, randomized controlled trial was designed to evaluate the mindfulness and gratitude journal interventions for women undergoing IVF/ICSI. Between May 2016 and November 2017, at the reproductive center in a public hospital, 234 women were randomly assigned to the brief mindfulness group (BMG, n = 78), gratitude journal group (GJG, n = 78) or control group (CG, n = 78). The inclusion criteria were being a woman undergoing her first cycle of IVF, having at least junior middle school education and having no biological or adopted children. PARTICIPANTS/MATERIALS, SETTING, METHODS: Female infertility patients (n = 346) were approached, and 112 did not meet the inclusion criteria. All three randomized groups completed questionnaires on the day of down-regulation (T1), the day before embryo(s) transfer (T2), and 3 days before the pregnancy test (T3). The BMG completed four sessions and listened to a 20-minute audio daily, including guided mindfulness breathing and body scan. The GJG completed four sessions and wrote three gratitude journals daily. The CG received routine care. A generalized estimating equation was used in an intention-to-treat analysis. The primary outcome was depression. Secondary outcomes were anxiety, sleep quality, infertility-related stress, mindfulness and gratitude. MAIN RESULTS AND THE ROLE OF CHANCE: Participants of the BMG showed decreased depression (mean difference (MD) = -1.69, [-3.01, -0.37], d = 0.44) and improved sleep quality (MD = -1.24, [-1.95, -0.39], d = 0.43) compared to the CG, but the effect was not significant for anxiety, Fertility Problem Inventory totals, mindfulness, gratitude scores or pregnancy rates. The BMG showed a significant reduction in depression and improvement in sleep quality between T1 and T2, a continuous significant reduction between T1 and T3 and no reduction between T2 and T3. There were no significant effects on any of the variables for the GJG. LIMITATIONS, REASONS FOR CAUTION: The inclusion criteria may result in bias because some participants with low education were excluded and only women with infertility were included. A low compliance rate occurred in the gratitude journals group. Moreover, men were not included in this study. Further research should consider including spouses of the target population. WIDER IMPLICATIONS OF THE FINDINGS: The brief mindfulness intervention was beneficial in decreasing depression and improving sleep quality. Implementation of guided self-administered mindfulness could make the psychological counseling service more accessible for patients with infertility in resource-poor settings. The efficiency and feasibility of the gratitude journal intervention needs to be investigated further. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Social Science Foundation (17BSH054). The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16008452. TRIAL REGISTRATION DATE: 9 May 2016. DATE OF FIRST PATIENT'S ENROLMENT: 15 May 2016.

Self-management and psychological resilience moderate the relationships between symptoms and health-related quality of life among patients with hypertension in China.

PURPOSE: To examine whether and how self-management and psychological resilience could moderate the relationships between symptoms and health-related quality of life (HRQoL) among hypertensive patients in China. METHODS: This was a cross-sectional study of 220 participants recruited from January to May, 2018. Demographic and clinical information were obtained from medical records and by patient interview. The Chinese version of 17-item Hypertension-specific Symptom Scale, 21-item Self-Management Scale, and 10-item Connor-Davidson Resilience Scale (CD-RISC-10) as well as Short Form 12 Health Survey (SF-12) were used to collect information in this research. The moderation effects of self-management and psychological resilience were explored using the PROCESS macro for SPSS. RESULTS: Among all patients, 128 (58.2%) were female, 106 (48.2%) had a bachelor degree or higher, and 133 (60.5%) had moderate to severe Charlson Comorbidity Index. Both self-management and psychological resilience were negatively correlated to symptoms (r = - 0.259, p < 0.001; r = - 0.282, p < 0.001) but positively correlated to physical (r = 0.316, p < 0.001; r = 0.344, p < 0.001) and mental (r = 0.273, p < 0.001; r = 0.309, p < 0.001) HRQoL. After controlling for potential covariates, self-management could moderate the associations between symptoms and physical HRQoL (p = 0.041, ΔR2 = 0.010), while psychological resilience could moderate the relationships between symptoms and mental HRQoL (p = 0.02, ΔR2 = 0.010). CONCLUSIONS: For hypertension patients, HRQoL is dependent on the severity of symptoms, engagement of self-management behaviors, and psychological resilience, which should be carefully considered when to improve patients' HRQoL by health care providers.

Variability of ecological executive function in children and adolescents genetically at high risk for schizophrenia: a latent class analysis.

Executive impairments have been observed both in patients with schizophrenia and in their unaffected first-degree relatives. Very few studies have investigated neurocognitive subgroups in unaffected first-degree relatives and in healthy participants using data-driven methods. The study included a high-risk group consisting of 100 unaffected young offspring and siblings of patients with schizophrenia and 198 healthy controls, all aged between 9 and 23 years. Executive function, victimization, and emotional and behavioral problems of participants were assessed by a series of self-report scales. Neurocognitive subgroups were investigated using latent class analysis of executive function measures. Four neurocognitive clusters were identified: a good performance cluster, a good self-control cluster, a low self-control cluster, and a severe impairment cluster. Participants in severe impaired executive function cluster reported a significantly higher level of victimization and had more prominent emotional and behavioral problems than the good performance cluster. Neurocognitive differences between high-risk young people and healthy controls were driven by individuals who have severe and global, rather than selective, executive deficits. Our results may provide clues to an explanation of the mechanisms behind executive impairments in young individuals at genetic risk and help to identify new targets for early interventions.

Development and clinical validation of a circulating tumor DNA test for the identification of clinically actionable mutations in nonsmall cell lung cancer.

Molecular analysis of potentially actionable mutations has become routine practice in oncological pathology. However, testing a wide range of oncogenes and mutations can be technically challenging because of limitations associated with tumor biopsy. Circulating tumor DNA (ctDNA) is a potential tool for the noninvasive profiling of tumors. In this study, we developed a next-generation sequencing (NGS)-based test for the detection of clinically relevant mutations in ctDNA and evaluated the feasibility of using this ctDNA NGS-based assay as an alternative to tissue genotyping. Tissue and matched blood samples were obtained from 72 patients with advanced nonsmall cell lung cancer (NSCLC). NGS-based testing was performed using plasma cell-free DNA (cfDNA) samples of all 72 patients as well as tumor DNA samples of 46 patients. Of the remaining 26 patients, tDNA was tested by amplification refractory mutation system PCR (ARMS-PCR) because of insufficient tissue sample or quality for NGS. Of the 46 patients who had tDNA and cfDNA NGS performed, we found 20 patients were concordant between tDNA and ctDNA alterations and 21 sample pairs were discordant because of additional alterations found in tDNA. Considering all clinically relevant alterations, the concordance rate between tDNA and ctDNA alterations was 54.9% with a sensitivity of 53.2% and a specificity of 75.0%. Our findings demonstrate that targeted NGS using cfDNA is a feasible approach for rapid and accurate identification of actionable mutations in patients with advanced NSCLC, and may provide a safe and robust alternative approach to tissue biopsy.

The divergent impact of catechol-O-methyltransferase (COMT) Val158Met genetic polymorphisms on executive function in adolescents with discrete patterns of childhood adversity.

PURPOSE: Catechol-O-methyltransferase (COMT) Val158Met functional polymorphisms play a crucial role in the development of executive function (EF), but their effect may be moderated by environmental factors such as childhood adversity. The present study aimed at testing the divergent impact of the COMT Val158Met genotype on EF in non-clinical adolescents with discrete patterns of childhood adversity. METHODS: A total of 341 participants completed the Childhood Trauma Questionnaire, the self-reported version of the Behavior Rating Inventory of Executive Function, and self-administered questionnaires on familial function. The participants' COMT Val158Met genotype was determined. Associations among the variables were explored using latent class analysis and general linear models. RESULTS: We found that Val/Val homozygotes showed significantly worse performance on behavioral shift, relative to Met allele carriers (F=5.921, p=0.015, Partial η2=0.018). Moreover, three typical patterns of childhood adversity, namely, low childhood adversity (23.5%), childhood neglect (59.8%), and high childhood adversity (16.7%), were found. Both childhood neglect and high childhood adversity had a negative impact on each aspect of EF and on global EF performance. Importantly, these results provided evidence for significant interaction effects, as adolescents with the Val/Val genotype showed inferior behavioral shift performance than Met carriers (F=6.647, p=0.010, Partial η2=0.020) in the presence of high childhood adversity. Furthermore, there were no differences between the genotypes for childhood neglect and low childhood adversity. CONCLUSIONS: Overall, this is the first study to show that an interaction between the COMT genotype and childhood adversity affects EF in non-clinical adolescents. These results suggest that the COMT genotype may operate as a susceptibility gene vulnerable to an adverse environment.