bluuebunny/crossref_metadata_2025 huggingface dataset:
Atypical ovarian carcinoid tumor with widespread skeletal metastases: a case report of multiple endocrine neoplasia type 1 in a young woman
Authors: Lou Lei , Zhou Lixia , Wang Wenyan , Li Huina , Li Yuehong
Published: November 2019

Background

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant inherited condition affecting multiple endocrine organs, resulting in significant morbidity and decreased life expectancy. Early tumor identification allows for timely patient management, reduces morbidity, and improves disease outcomes. Patients with MEN1 typically present with primary hyperparathyroidism caused by multiple parathyroid tumors, however, thymic and bronchial carcinoid tumors are also less common manifestations. MEN1-related neuroendocrine tumors often show hematogenous metastasis, with the liver being the most common metastatic site. Skeletal metastases from neuroendocrine tumors are extremely rare.

As few as 50 case reports were identified in a recently published literature review on skeletal metastases from carcinoid tumors. To our knowledge, studies related to MEN1 have not been previously conducted.

Case presentation

We present a case of MEN1-related atypical ovarian carcinoid presenting as the first disease manifestation in a 30-year old woman. After two years, another atypical carcinoid was incidentally diagnosed in the contralateral ovary during a caesarean section. Syndromic MEN1 was not diagnosed clinically despite her young age and bilateral involvement. The patient remained disease-free for two years without further adjuvant treatment prior to clinic presentation with complaints of chest discomfort and body pain. Radiologic and pathologic investigations identified multifocal simultaneous neuroendocrine tumors involving the parathyroid, thymus, pancreas, and adrenal glands, in addition to multiple other metastatic sites. The findings ultimately resulted in the patient being diagnosed with MEN1.

Conclusions

This extremely rare case emphasizes that ovarian carcinoids, especially when bilateral, could be the initial manifestation of MEN1. The significance of this differential diagnosis was highlighted by the subsequent detection of widespread skeletal metastasis resulting from the carcinoid tumors. A low threshold of suspicion, systemic diagnostic work-up, and regular follow-up are of utmost importance to timely diagnosis of MEN1.
Characterizing MRI features of rectal cancers with different KRAS status
Authors: Xu Yanyan , Xu Qiaoyu , Ma Yanhui , Duan Jianghui , Zhang Haibo , Liu Tongxi , Li Lu , Sun Hongliang , Shi Kaining , Xie Sheng , Wang Wu
Published: November 2019

Background

To investigate whether MRI findings, including texture analysis, can differentiate KRAS mutation status in rectal cancer.

Methods

Totally, 158 patients with pathologically proved rectal cancers and preoperative pelvic MRI examinations were enrolled. Patients were stratified into two groups: KRAS wild-type group (KRASwt group) and KRAS mutation group (KRASmt group) according to genomic DNA extraction analysis. MRI findings of rectal cancers (including texture features) and relevant clinical characteristics were statistically evaluated to identify the differences between the two groups. The independent samples t test or Mann-Whitney U test were used for continuous variables. The differences of the remaining categorical polytomous variables were analyzed using the Chi-square test or Fisher exact test. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminatory power of MRI features. The area under the ROC curve (AUC) and the optimal cut-off values were calculated using histopathology diagnosis as a reference; meanwhile, sensitivity and specificity were determined.

Results

Mean values of six texture parameters (Mean, Variance, Skewness, Entropy, gray-level nonuniformity, run-length nonuniformity) were significantly higher in KRASmt group compared to KRASwt group (p < 0.0001, respectively). The AUC values of texture features ranged from 0.703~0.813. In addition, higher T stage and lower ADC values were observed in the KRASmt group compared to KRASwt group (t = 7.086, p = 0.029; t = − 2.708, p = 0.008).

Conclusion

The MRI findings of rectal cancer, especially texture features, showed an encouraging value for identifying KRAS status.
Correction to: Cinnamon extract induces tumor cell death through inhibition of NFκB and AP1
Authors: Kwon Ho-Keun , Hwang Ji-Sun , So Jae-Seon , Lee Choong-Gu , Sahoo Anupama , Ryu Jae-Ha , Jeon Won Kyung , Ko Byoung Seob , Lee Sung Haeng , Park Zee Yong , Im Sin-Hyeog
Published: November 2019

Following publication of the original article [1], the authors have re-evaluated the authorship for this article. The updated author group is:
Serum erythropoietin concentration and its correlation with stage of diabetic retinopathy
Authors: Davidović Sofija , Babić Nikola , Jovanović Sandra , Barišić Sava , Grković Desanka , Miljković Aleksandar
Published: November 2019

Background

Erythropoietin (EPO) is one of the systemic angiogenic factors, and its role in ocular angiogenesis and in diabetic retinopathy (DR) is not yet fully understood. The latest research data reveal a possible correlation of higher erythropoietin concentrations in the blood and in the eye with the development of more advanced stages of DR.

The main aim of this work was to examine the possible influence of serum concentrations of erythropoietin on the development of diabetic retinopathy in patients with diabetes mellitus type 2.

Methods

The research involved 90 patients examined at the University Eye Clinic of the Clinical Center of Vojvodina, Novi Sad, Serbia. The first group comprised 60 patients with diabetes mellitus lasting for 10 years or more, with diabetic retinopathy. The second, control group consisted of 30 healthy individuals. In the first group of 60 patients with diabetes, 30 of them had non-proliferative diabetic retinopathy (NPDR), and 30 had proliferative diabetic retinopathy (PDR). Laboratory EPO serum levels were determined, and they were correlated to the stage of DR. Concentration of EPO was assessed by ELISA method.

Results

The highest average concentration of EPO in serum (9.95 mIU/ml) was determined in the group of people with diabetes with PDR. The lowest average concentration of EPO in the serum (6.90 mIU/ml) was found in the control group. The average concentration of EPO in serum in the group of patients with diabetes with NPDR was 7.00 mIU/ml. The EPO concentration in serum was elevated in the group of PDR, and it was directly proportional to the level of the clinical stadium of PDR, being significantly higher in the moderate and severe subgroup of PDR comparing to the control healthy subjects, NPDR and mild PDR (p = 0.007).

Conclusions

Significantly elevated serum concentration of EPO in the advanced stages of DR, and positive correlation between EPO serum concentration and clinical stages of PDR, suggest that erythropoietin represents an important growth factor from blood, which plays a significant role in retinal ischemia and angiogenesis in diabetic retinopathy, especially in the proliferative stage of this disease.
Occupational social class trajectories in physical functioning among employed women from midlife to retirement
Authors: Lahelma Eero , Pietiläinen Olli , Chandola Tarani , Hyde Martin , Rahkonen Ossi , Lallukka Tea
Published: November 2019

Background

Prior analyses of class differences in health trajectories among employees have often omitted women and transitions to retirement. We examined social class trajectories in physical functioning among Finnish female employees from midlife to retirement age, and whether transitions to retirement modified these trajectories.

Methods

Data were derived from mail surveys at Phases 1–3 (2000–2012) among employees of the City of Helsinki, Finland, aged 40–60 at baseline (n = 8960, 80% women, response rates 69–83%). We included respondents to any of the Phases 1–3 aged 40–72 (n = 6976). We distinguished higher and lower social classes, and employment statuses, i.e. employed, mandatorily retired and disability-retired. Short Form 36 physical component summary was used to measure physical functioning. Mixed-effect growth curve models were used to assess the association of social class and employment status with functioning over age.

Results

For employed women, physical functioning deteriorated faster in the lower than in the higher class, with class trajectories widening in ages 40–65. After mandatory retirement, functioning deteriorated in both classes, whereas after disability retirement, functioning improved. Across employment statuses, functioning converged at older ages, and the disability-retired caught up with the better functioning of the employed and mandatorily retired. Employment status modified the trajectories, as among the continuously employed and mandatorily retired women functioning deteriorated, but among the disability-retired, trajectories improved and reached a similar level with employed and mandatorily retired women. Social class inequalities remained in all employment status groups.

Conclusions

Overall, our results suggest evidence for the cumulative disadvantage model, with accumulating work exposures among lower classes potentially contributing to their trajectories of ill health.
Moderating role of job satisfaction on turnover intention and burnout among workers in primary care institutions: a cross-sectional study
Authors: Chen Xuyu , Ran Li , Zhang Yuting , Yang Jinru , Yao Hui , Zhu Sirong , Tan Xiaodong
Published: November 2019

Background

Global countries are suffering from a shortage of health professionals. Turnover intention is closely related to job satisfaction and burnout, making good use of these relationships could alleviate the crisis. Our research aims to examine the mediating role of job satisfaction in the relationship between burnout and turnover intention.

Methods

This research was conducted in Huangpi, China. The convenience sampling method and self-administereded questionnaires were used. 1370 of valid samples were collected with 97.72% effective rate. Descriptive analyses were conducted to describe social demographic factors. The structural equation model (SEM) was performed to adjust model fitting, and the mediation effect test was carried out by using the bootstrap method. Sobel-Z test was used to verify the significance of mediation effect.

Results

The mean age was 36.98 (SD = 9.84). The fitting indices of hypothetical model are not good. After the adjustments,χ2/df = 5.590, GFI = 0.932, AGFI = 0.901, CFI = 0.977, NFI = 0.973, IFI = 0.977, TLI = 0.970, RESEA = 0.058. The revised model fitted well, and the SEM was put up by using the bootstrap method. The mediating effect is partial, and Soble-Z test indicates that the mediation effect is significant. Burnout is negatively correlated with job satisfaction (p < 0.01) and the standardized path coefficient is − 0.41. Job satisfaction is also negatively correlated with turnover intention (p < 0.01) and the standardized path coefficient is − 0.18. Burnout is positively correlated with turnover intention (p < 0.01) and the standardized path coefficient is 0.83.

Conclusions

Job satisfaction is a mediating variable that affects the relationship between burnout and turnover intention. The mediating effect was a partial mediating effect and has a low impact of 7.4%. Improving treatment and giving more promotion opportunities for workers to improve job satisfaction, conducting career planning course and paying attention to employee psychological health to reduce job burnout. The above measures may be helpful to reduce employee turnover rate and alleviating the current situation of a shortage of health personnel in China.
Adiposity and changes in movement-related behaviors in older adult women in the context of the built environment: a protocol for a prospective cohort study
Authors: Cuberek Roman , Pelclová Jana , Gába Aleš , Pechová Jana , Svozilová Zuzana , Přidalová Miroslava , Štefelová Nikola , Hron Karel
Published: November 2019

Background

In older adults, sedentary behaviors increase while physical activity decreases over time following the compositional nature of 24-h behaviors. These changes in movement-related behaviors (MRBs) might be associated with unhealthy weight gain and several health comorbidities. However, information is lacking on how obesity influences longitudinal changes in the composition of MRBs in older adults. Furthermore, the moderating effect of the built environment on prospective associations between obesity and MRBs in older adults is not fully understood. Therefore, using an integrated time-use approach, this study aims to identify prospective associations between obesity and MRBs together with an assessment of the moderating effect of the built environment in elderly women.

Methods

The study was designed as a prospective 7-year follow-up study. It is based on two previous cross-sectional studies that enable the use of participant data (women aged 60+ years,n = 409) as a baseline dataset in the current study. All methods designed for 7-year follow-up are based on previous studies. The data collection comprises device-based measurement of MRBs (ActiGraph GT1M accelerometer), objective assessment of body adiposity (multi-frequency bioelectrical impedance analysis), subjective assessment of the built environment (NEWS-A questionnaire), and other possible confounding factors. Time spent in sedentary behavior, light physical activity, and moderate-to-vigorous physical activity will be used as three components in a composition reflecting individual MRBs. In linear multiple compositional regression analysis assessing the prospective association between obesity and MRBs, the 7-year follow-up composition of the three mentioned components represents the dependent variable. The 7-year changes in the percentage of body fat (body adiposity), baseline composition of MRBs, and parameters of the built environment represent regressors.

Discussion

This study will use an integrated time-use approach to explore causality from obesity to device-measured behaviors in older women. The design and respective analysis consider the compositional nature of MRBs data and the potential moderating effects of various factors. A comprehensive assessment of causality may help to develop multilevel interventional models that enhance physical activity in older adults.
The effects of deep neck muscle-specific training versus general exercises on deep neck muscle thickness, pain and disability in patients with chronic non-specific neck pain: protocol for a randomized clinical trial (RCT)
Authors: Kashfi Pegah , Karimi Noureddin , Peolsson Anneli , Rahnama Leila
Published: November 2019

Background

Altered thickness, cross-sectional area and activity of deep neck muscles have frequently been reported in patients with chronic non-specific neck pain (CNNP). It is claimed that these muscles do not recover spontaneously. These muscles provide a considerable amount of cervical stability. Therefore, various therapeutic exercises have been recommended to recover from resulting complications. However, most exercise protocols do not target deep neck muscles directly. Thus, this might be a reason for long-lasting complications. Accordingly, the purpose of the present study is to discuss a randomized controlled trial (RCT) protocol in which we aim to investigate and compare the effects of neck-specific exercise programmes versus general exercise programmes in patients with CNNP.

Methods

A 2*2 factorial RCT with before-after design. Sixty-four participants with CNNP will be recruited into the study. They will be randomly divided into two groups, including specific neck exercise and general exercise. Each exercise programme will be carried out three times a week and will last for 8 weeks. Primarily, dorsal and ventral neck muscle thickness, pain and disability and secondarily, muscle strength, quality of life, sleep quality, fear avoidance and neck range of motion will be assessed at the baseline and immediately at the end of the exercise protocol.

Discussion

The results of this study will inform clinicians on which type of exercise is more beneficial for patients with CNNP.

Trial registration

IRCT2017091620787N2, Sep 16 2017.
Wrist pain: a systematic review of prevalence and risk factors– what is the role of occupation and activity?
Authors: Ferguson R. , Riley N. D. , Wijendra A. , Thurley N. , Carr A. J. , BJF Dean
Published: November 2019

Objective

To evaluate the prevalence and risk factors of wrist pain.

Methods

Systematic review. Data sources: The MEDLINE and EMBASE via OVID, CINAHL and SPORTDiscus via EBSCO databases were searched from database inception to 9th March 2018. Specific criteria were used to define inclusion and exclusion. Data was extracted independently by a pair of reviewers.

Results

In total 32 cross sectional studies were identified for inclusion (1 with a longitudinal component). The median prevalence of wrist pain in the general population and non-manual workers within the short term (within last week) was 6 and 4.2% within the medium term (> 1 week and within a year). The median prevalence of wrist pain in physically demanding occupations and sports people was 10% within the short term and 24% within the medium term. Non-modifiable factors associated with wrist pain included increased age (1 study in adults and 3 studies in children/adolescents) and female sex (2 studies). Modifiable risk factors included high job physical strain (2 studies), high job psychological strain (1 study), abnormal physeal morphology in children/adolescents (2 studies), high frequency impact tool use (1 study) and effort reward imbalance (1 study).

Conclusions

Wrist pain is highly prevalent in groups who partake in physically demanding activities from day to day such as manual labourers and sportspeople. It is less prevalent in the general population and non-manual workers, although there is a relative lack of research in the general population.

Trial registration

The review protocol was registered with PROSPERO under the registration numberCRD42018090834.

Level of Evidence

1 (Prognostic study).
Effectiveness of flipped classroom combined with team-, case-, lecture- and evidence-based learning on ophthalmology teaching for eight-year program students
Authors: Ding Chun , Li Shengguo , Chen Baihua
Published: November 2019

Background

This study aimed to investigate the benefits and challenges of the flipped classroom combined with team-, case-, lecture- and evidence-based learning (FC-TCLEBL) for ophthalmology teaching for eight-year program students.

Methods

FC-TCLEBL and the traditional lecture-based classroom (LBC) were compared based on student and teacher feedback questionnaires, student learning burden, and scores on standardized tests as well as their effects on the abilities of clinical thinking, scientific research, active-learning, practical application, humanistic care and communication with patients.

Results

Both the students and teachers were more satisfied with the FC-TCLEBL model. More students in the FC-TCLEBL group agreed that the course helped them to develop skills in creative thinking, problem solving, and teamwork. Students in the FC-TCLEBL group spent significantly more time preparing for class than those in the LBC group, but the time spent on review was significantly lower in the FC-TCLEBL group. The students from the FC-TCLEBL group performed better in a post-test on diabetic retinopathy (DR) as compared to the LBC group.

Conclusions

FC-TCLEBL teaching model is effective and suitable for ophthalmology teaching.
Evaluation of safety attitudes of hospitals and the effects of demographic factors on safety attitudes: a psychometric validation of the safety attitudes and safety climate questionnaire
Authors: Zhao Chuang , Chang Qing , Zhang Xi , Wu Qijun , Wu Nan , He Jiao , Zhao Yuhong
Published: November 2019

Background

The objectives of this study are to test the psychometric properties of the safety attitudes and safety climate questionnaire Chinese simplified version (SAQ-CS), to test the safety attitudes of health professionals in tertiary hospitals in the Liaoning province and to explore the effects of demographic factors on safety attitudes.

Methods

The SAQ-CS was used to conduct a cross-sectional survey in nine tertiary hospitals in Liaoning province.

Results

Cronbach’s alpha of each subscale of SAQ-CS were > 0.7, the values of GFI, TLI, and CFI were > 0.8, and RMSEA values ranged from 0.048–0.199. The mean of the safety attitudes of 2157 health professionals was 4.00, indicating a good safety attitude, with a positive response rate (% of items that scored ≥4) of 51.1%. The stress recognition subscale had the lowest score, with a mean of 2.73 and a positive response rate of 17.8%. A multiple linear regression equation revealed that demographic factors like gender, age, and training participation significantly affected the scores (βgender > 0.06, βage < − 0.08, βtraining < − 0.07, p < 0.05).

Conclusions

The psychometric properties of SAQ-CS are good and stable. Health professionals rate teamwork climate, safety climate, perception of management, and work conditions in Liaoning province are perceived as good; however, the stress of the health professionals is poor. To improve safety attitudes, it is necessary to not only reduce the stress of health professionals, but also to pay more attention to men, older health professionals, and health professionals who have not participated in safety training.
Make it complicated: a qualitative study utilizing a complexity framework to explain improvement in health care
Authors: Storkholm Marie Höjriis , Mazzocato Pamela , Savage Carl
Published: November 2019

Background

Successful application of Quality Improvement (QI) methods is challenging, and awareness of the role context plays has increased. Complexity science has been advocated as a way to inform change efforts. However, empirical support is scarce, and it is still difficult to grasp the practical implications for QI interventions. The aim of this study was to use a complexity-based leadership framework to explain how managers in a clinical department addressed external requirements to cut costs without compromising patient outcomes and experience.

Methods

Explanatory case study design of a Danish OB/GYN department tasked to improve efficiency. Data came from documents, 30 interviews, and 250 h of observations over 3 years. A Complexity Analysis Framework that combined two complexity-based leadership frameworks was developed to analyze all changes implemented to reduce cost, while maintaining clinical quality.

Results

Managers reframed the efficiency requirement as an opportunity for quality improvement. Multiple simple, complicated, and complex situations were addressed with an adaptive approach to quality improvement. Changes were made to clinical pathways for individual conditions (n = 37), multiple conditions (n = 7), and at the organizational level (n = 9). At the organizational level, changes addressed referral practice, physical space in the department, flow and capacity, discharge speed, and managerial support. Managers shared responsibility with staff; together they took a “professional path” and systematically analyzed each clinical pathway through process mapping, attentive to patterns that emerged, before deciding on the next steps, such as a engaging in a complex process of probing – the iterative development and testing of new responses.

Conclusions

Quality improvement efforts could benefit from an understanding of the importance of learning and sharing responsibility to deal with the co-existing degrees of contextual complexity in modern health care. By “making things complicated” through a systematic analysis that engages staff in an open and reflective dialog, clinical praxis and established organizational structures can be questioned and improved. The Complexity Analysis Framework could then help managers to identify improvement opportunities, know when to implement technical solutions, and when to keep abreast of emerging patterns and allow appropriate responses to complex challenges to evolve.
The association of cognitive functioning as measured by the DemTect with functional and clinical characteristics of COPD: results from the COSYCONET cohort
Authors:   the COSYCONET study group, von Siemens Sarah Marietta , Perneczky Robert , Vogelmeier Claus F. , Behr Jürgen , Kauffmann-Guerrero Diego , Alter Peter , Trudzinski Franziska C. , Bals Robert , Grohé Christian , Söhler Sandra , Waschki Benjamin , Lutter Johanna I. , Welte Tobias , Jörres Rudolf A. , Kahnert Kathrin
Published: November 2019

Alterations of cognitive functions have been described in COPD. Our study aimed to disentangle the relationship between the degree of cognitive function and COPD characteristics including quality of life (QoL).

Data from 1969 COPD patients of the COSYCONET cohort (GOLD grades 1–4; 1216 male/ 753 female; mean (SD) age 64.9 ± 8.4 years) were analysed using regression and path analysis. The DemTect screening tool was used to measure cognitive function, and the St. George‘s respiratory questionnaire (SGRQ) to assess disease-specific QoL.

DemTect scores were < 9 points in 1.6% of patients and < 13 points in 12% when using the original evaluation algorithm distinguishing between < 60 or > =60 years of age. For statistical reasons, we used the average of both algorithms independent of age in all subsequent analyses. The DemTect scores were associated with oxygen content, 6-min-walking distance (6-MWD), C-reactive protein (CRP), modified Medical Research Council dyspnoea scale (mMRC) and the SGRQ impact score. Conversely, the SGRQ impact score was independently associated with 6-MWD, FVC, mMRC and DemTect. These results were combined into a path analysis model to account for direct and indirect effects. The DemTect score had a small, but independent impact on QoL, irrespective of the inclusion of COPD-specific influencing factors or a diagnosis of cognitive impairment.

We conclude that in patients with stable COPD lower oxygen content of blood as a measure of peripheral oxygen supply, lower exercise capacity in terms of 6-MWD, and higher CRP levels were associated with reduced cognitive capacity. Furthermore, a reduction in cognitive capacity was associated with reduced disease-specific quality of life. As a potential clinical implication of this work, we suggest to screen especially patients with low oxygen content and low 6-MWD for cognitive impairment.
Restructured Lactococcus lactis strains with emergent properties constructed by a novel highly efficient screening system
Authors: Liu Fulu , Zhang Yating , Qiao Wanjin , Zhu Duolong , Xu Haijin , Saris Per Erik Joakim , Qiao Mingqiang
Published: November 2019

Background

After 2.83% genome reduction in Lactococcus lactis NZ9000, a good candidate host for proteins production was obtained in our previous work. However, the gene deletion process was time consuming and laborious. Here, we proposed a convenient gene deletion method suitable for large-scale genome reduction in L. lactis NZ9000.

Results

Plasmid pNZ5417 containing a visually selectable marker PnisZ-lacZ was constructed, which allowed more efficient and convenient screening of gene deletion mutants. Using this plasmid, two large nonessential DNA regions, L-4A and L-5A, accounting for 1.25% of the chromosome were deleted stepwise in L. lactis 9k-3. When compared with the parent strain, the mutant L. lactis 9k-5A showed better growth characteristics, transformability, carbon metabolic capacity, and amino acids biosynthesis.

Conclusions

Thus, this study provides a convenient and efficient system for large-scale genome deletion in L. lactis through application of visually selectable marker, which could be helpful for rapid genome streamlining and generation of restructured L. lactis strains that can be used as cell factories.
Circ_ZNF124 promotes non-small cell lung cancer progression by abolishing miR-337-3p mediated downregulation of JAK2/STAT3 signaling pathway
Authors: Li Qianping , Huang Qin , Cheng Shaofei , Wu Song , Sang Hongyang , Hou Junyi
Published: November 2019

Background

Previous genome-wide transcriptome profiling found circ_ZNF124 was highly expressed in lung adenocarcinoma, however, the role of circ_ZNF124 in non-small cell lung cancer (NSCLC) is still unknown. The purpose of this study was to investigate the role and molecular mechanism of circ_ZNF124 in NSCLC development.

Methods

The expression of circ_ZNF124, miR-337-3p and JAK2 (Janus Kinase 2) in lung cancer cell lines and normal epithelial cells were detected by qRT-PCR (quantitative real-time PCR). siRNA was used to knockdown circ_ZNF124 expression in cells. The effects of circ_ZNF124 in NSCLC cells were determined by cell growth, cell migration, cell cycle analysis and colony formation. Bioinformatics analysis, RNA immunoprecipitation, luciferase assay and western blots were used to study the molecular mechanism of circ_ZNF124 in NSCLC.

Results

The results showed that circ_ZNF124 expression was highly upregulated in NSCLC cells than in normal epithelial cells. Knockdown of circ_ZNF124 by using siRNA significantly decreased cell growth, promoted cell cycle arrested in sub-G1 phase, impaired cell migration and colony formation. Bioinformatic analysis discovered that miR-337-3p was a direct target of circ_ZNF124. In contrast to circ_ZNF124, miR-337-3p expression was significantly downregulated in NSCLC cells. Biotin labeled circ_ZNF124 immunoprecipitation and luciferase assay showed that miR-337-3p could directly bind to and affect circ_ZNF124 activity. The regulation of circ_ZNF124 on miR-337-3p was also investigated. Further analysis showed that despite STAT3 (signal transducer and activator of transcription 3), JAK2 was also a target of miR-337-3p, overexpression of miR-337-3p greatly downregulated JAK2, STAT3 and JAK2/STAT3 downstream regulated oncogenes HIF1a (Hypoxia-inducible factor 1-alpha), BCL2 (B cell lymphoma 2) and c-FOS expression, however, the roles of miR-337-3p in JAK2/STAT3 signaling pathway were greatly inhibited in the presence of circ_ZNF124.

Conclusion

In NSCLC, highly expressed circ_ZNF124 promoted the activation of JAK2/STAT3 signaling pathway by acting as a sponge of miR-337-3p, thus promoting the occurrence and development of NSCLC. Circ_ZNF124 could be a potential biomarker or target for the treatment of NSCLC patients in the future.
Clinical-biological characteristics and treatment outcomes of pediatric pro-B ALL patients enrolled in BCH-2003 and CCLG-2008 protocol: a study of 121 Chinese children
Authors: Gao Chao , Liu Shu-Guang , Yue Zhi-Xia , Liu Yi , Liang Jing , Li Jun , Zhang Yuan-Yuan , Yu Jiao-Le , Wu Ying , Lin Wei , Zheng Hu-Yong , Zhang Rui-Dong
Published: November 2019

Background

Although leukemic blast cells of Pro-B cell acute lymphoblastic leukemia (ALL) are arrested at the same stage of B cell differentiation, the immature B cell subtype is still biologically heterogeneous and is associated with diverse outcomes. This study aimed to explore the clinical-biological characteristics of pediatric pro-B ALL and factors associated with outcomes.

Methods

This study enrolled 121 pediatric patients aged 6 months to 14 years with newly diagnosed CD19+CD10− pro-B cell acute lymphoblastic leukemia (pro-B ALL) treated at Beijing Children’s Hospital from March 2003 to October 2018. Genetic abnormalities, immunophenotypic markers, minimal residual disease (MRD) at early treatment stage and long-term outcomes of children treated on two consecutive protocols were analyzed.

Results

KMT2A rearrangements were the most frequent abnormalities (incidence rate 33.06%), and were associated with lower frequency of CD13, CD33, CD22 and CD34 expression and higher frequency of CD7 and NG2 expression. Higher frequency of CD15 and CD133 expression was found in KMT2A-AFF1+ patients, exclusively. Presence of CD15 and absence of CD34 at diagnosis correlated with the high burden of MRD at the early stage of treatment. Outcomes were more favorable in patients older than 1 year, with absence of CD20 expression and KMT2A rearrangements, and with MRD lower than 1% at the end of induction and 0.1% before consolidation. Increased intensity of chemotherapy based on MRD analysis did not improve outcomes significantly (5-year EFS 73.9 ± 6.5% for BCH-2003 and 76.1 ± 5.3% for CCLG-2008, P = 0.975). Independent adverse prognostic factors were MRD ≥ 0.1% before consolidation and presence of KMT2A gene rearrangements (odds ratios [ORs] 9.424 [95% confidence interval (CI) 3.210, 27.662; P < 0.001]; 4.142 [1.535, 11.715, P = 0.005]; respectively).

Conclusions

Pediatric pro-B ALL is a heterogeneous disease. Genetic analysis and MRD evaluation can predict patients with dismal prognosis; however, intensive chemotherapy alone does not improve outcomes of these patients and targeted therapy or hematopoietic stem cell transplantation may be required.
The relationship between vitamin D and risk of atrial fibrillation: a dose-response analysis of observational studies
Authors: Liu Xiao , Wang Wei , Tan Zhaochong , Zhu Xin , Liu Menglu , Wan Rong , Hong Kui
Published: November 2019

Background

The relationship between serum vitamin D and atrial fibrillation (AF) or postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass graft (CABG) is still debated. It is also unclear whether there is a dose-response relationship between circulating vitamin D and the risk of AF or POAF.

Methods

The Cochrane Library, PubMed, and Embase databases were searched for relevant studies. We used a “one-stage approach” with a restricted cubic spline model to summarize the dose-specific relationships between serum vitamin D and AF. Relative risk (RR) was used to measure the effects in this meta-analysis.

Results

In total, 13 studies were included with a total of 6519 cases of AF among 74,885 participants. Vitamin D deficiency (< 20 ng/ml) was associated with increased risks of AF (RR: 1.23, 95% CI: 1.05–1.43). In the dose-response analysis, the summary RR for a 10 ng/ml increased in vitamin D was 0.88 (95% CI: 0.78–0.98) and there was no evidence of a non-linear association, Pnon-linearity = 0.86. In the age subgroup, high vitamin D (per 10 ng/ml increase) reduced the risk of AF in the older group (> 65 years) (RR = 0.68, 95% CI = 0.52–0.89) but not among young individuals (< 65 years) (RR = 0.87, 95% CI = 0.72–1.06). In addition, a strong association was found between a 10 ng/ml increased in vitamin D and POAF incident in the patient after CABG (RR: 0.44, 95% CI: 0.24–0.82).

Conclusion

Our dose-response meta-analysis suggested serum vitamin D deficiency was associated with an increased risk of AF in the general population and POAF in patients after CABG. Further studies are needed to explore the age difference in the association between serum vitamin D level and the risk of AF and whether vitamin D supplements will prevent AF.

Trial registration

This study has been registered with PROSPERO (International prospective register of systematic reviews)-registration number-CRD42019119258.
The regulatory roles of neutrophils in adaptive immunity
Authors: Li Yang , Wang Wei , Yang Fan , Xu Yanan , Feng Chang , Zhao Yong
Published: November 2019

Neutrophils have long been considered as cells playing a crucial role in the immune defence against invading pathogens. Accumulating evidence strongly supported the direct and indirect regulatory effects of neutrophils on adaptive immunity. Exogenous cytokines or cytokines produced in an autocrine manner as well as a cell-to-cell contact between neutrophils and T cells could induce the expression of MHC-II and costimulatory molecules on neutrophils, supporting that neutrophils may function as antigen-presenting cells (APCs) in respects of presenting antigens and activating T cells. In addition to the inflammatory roles, neutrophils also have the propensity and ability to suppress the immune response through different mechanisms. In this review, we will mainly highlight the heterogeneity and functional plasticity of neutrophils and the antigen-presenting capacity of different neutrophil subsets. We also discuss mechanisms relevant to the regulatory effects of neutrophils on adaptive immunity. Understanding how neutrophils modulate adaptive immunity may provide novel strategies and new therapeutic approaches for diseases associated with neutrophils.

Graphical abstract
Screen time and problem behaviors in children: exploring the mediating role of sleep duration
Authors: Guerrero Michelle D. , Barnes Joel D. , Chaput Jean-Philippe , Tremblay Mark S.
Published: November 2019

Background

Previous research examining the relationship between screen time (ST) and psychological health outcomes have primarily focused on one type of ST (i.e., television), while little research has considered other types of screens (e.g., videos, movies, social media), screen content (e.g., violent video games), or potential mediating variables. Therefore, the purpose of the present study was to assess ST types and content and their association with problem behaviors, and to determine whether these relationships were mediated by sleep duration.

Methods

Parents and children provided cross-sectional baseline data (2016–18) as part of the Adolescent Brain Cognitive Development study, a broadly US representative sample of 11,875 children aged 9 to 10 years. Parents self-reported their children’s emotional and behavioral syndromes via the Child Behavior Checklist and sleep duration using one item from the Parent Sleep Disturbance Scale. Children self-reported their ST behavior, which comprised ST types (television/movies, videos, video games, and social media) and content (mature-rated video games and R-rated movies).

Results

Time spent in various ST types was positively associated with problem behaviors: watching television/movies was associated with a 5.9% increase in rule-breaking behavior (incidence rate ratio [IRR] = 1.059), 5% increase in social problems (IRR = 1.050), 4% increase in aggressive behavior (IRR = 1.040), and 3.7% increase in thought problems (IRR = 1.037). Greater time spent playing mature-rated video games was associated with greater somatic complaints (IRR = 1.041), aggressive behavior (IRR = 1.039), and reduced sleep duration (IRR = .938). Sleep duration mediated the relationship between ST (type and content) and problem behaviors, albeit the effect sizes were small. The largest effects were observed between sleep duration and all problem behaviors, with greater sleep duration predicting an 8.8–16.6% decrease in problem behaviors (IRRs ranging from .834 to .905).

Conclusion

Greater time spent in ST behavior was associated with greater problem behaviors among children. There was strong evidence that longer sleep duration was associated with reduced problem behaviors. While sleep duration mediated the effects of ST on problem behaviors, other potential mediating variables need to be investigated in future research.
The OncoLifeS data-biobank for oncology: a comprehensive repository of clinical data, biological samples, and the patient’s perspective
Authors: Sidorenkov Grigory , Nagel Janny , Meijer Coby , Duker Jacko J. , Groen Harry J. M. , Halmos Gyorgy B. , Oonk Maaike H. M. , Oostergo Rene J. , van der Vegt Bert , Witjes Max J. H. , Nijland Marcel , Havenga Klaas , Maduro John H. , Gietema Jourik A. , de Bock Gertruida H.
Published: November 2019

Background

Understanding cancer heterogeneity, its temporal evolution over time, and the outcomes of guided treatment depend on accurate data collection in a context of routine clinical care. We have developed a hospital-based data-biobank for oncology, entitled OncoLifeS (Oncological Life Study: Living well as a cancer survivor), that links routine clinical data with preserved biological specimens and quality of life assessments. The aim of this study is to describe the organization and development of a data-biobank for cancer research.

Results

We have enrolled 3704 patients aged ≥ 18 years diagnosed with cancer, of which 45 with hereditary breast-ovarian cancer (70% participation rate) as of October 24th, 2019. The average age is 63.6 ± 14.2 years and 1892 (51.1%) are female. The following data are collected: clinical and treatment details, comorbidities, lifestyle, radiological and pathological findings, and long-term outcomes. We also collect and store various biomaterials of patients as well as information from quality of life assessments.

Conclusion

Embedding a data-biobank in clinical care can ensure the collection of high-quality data. Moreover, the inclusion of longitudinal quality of life data allows us to incorporate patients’ perspectives and inclusion of imaging data provides an opportunity for analyzing raw imaging data using artificial intelligence (AI) methods, thus adding new dimensions to the collected data.
Targeting of tolerogenic dendritic cells to heat-shock proteins in inflammatory arthritis
Authors: Spiering Rachel , Jansen Manon A. A. , Wood Matthew J. , Fath Anshorulloh A. , Eltherington Oliver , Anderson Amy E. , Pratt Arthur G. , van Eden Willem , Isaacs John D. , Broere Femke , Hilkens Catharien M. U.
Published: November 2019

Background

Autologous tolerogenic dendritic cells (tolDC) are a promising therapeutic strategy for inflammatory arthritis (IA) as they can regulate autoantigen-specific T cell responses. Here, we investigated two outstanding priorities for clinical development: (i) the suitability of using heat-shock proteins (HSP), abundant in inflamed synovia, as surrogate autoantigens to be presented by tolDC and (ii) identification of functional biomarkers that confirm tolDC regulatory activity.

Methods

Cell proliferation dye-labelled human peripheral blood mononuclear cells of IA (rheumatoid arthritis (RA) and psoriatic arthritis (PsA)) patients or healthy donors were cultured with HSP40-, HSP60- and HSP70-derived peptides or recall antigens (e.g. tuberculin purified protein derivative (PPD)) in the presence or absence of tolDC or control DC for 9 days. Functional characteristics of proliferated antigen-specific T-cells were measured using flow cytometry, gene expression profiling and cytokine secretion immunoassays. Repeated measures analysis of variance (ANOVA) with Bonferroni correction for comparisons between multiple groups and paired Studentttest for comparisons between two groups were used to determine significance.

Results

All groups showed robust CD4+T-cell responses towards one or more HSP-derived peptide(s) as assessed by a stimulation index > 2 (healthy donors: 78%, RA: 73%, PsA: 90%) and production of the cytokines IFNγ, IL-17A and GM-CSF. Addition of tolDC but not control DC induced a type 1 regulatory (Tr1) phenotype in the antigen-specific CD4+T-cell population, as identified by high expression of LAG3, CD49b and secretion of IL-10. Furthermore, tolDC inhibited bystander natural killer (NK) cell activation in a TGFβ dependent manner.

Conclusions

HSP-specific CD4+T-cells are detectable in the majority of RA and PsA patients and can be converted into Tr1 cells by tolDC. HSP-loaded tolDC may therefore be suitable for directing T regulatory responses to antigens in inflamed synovia of IA patients. Tr1 markers LAG3, CD49b and IL-10 are suitable biomarkers for future tolDC clinical trials.
The 164 K, 165 K, and 167 K residues of VP1 are vital for goose parvovirus proliferation in GEFs based on PCR-based reverse genetics system
Authors: Liu Peng , Yang Liqin , Zhang Jingyue , Wang Tao , Wu Yuanyuan , Wang Mingshu , Jia Renyong , Zhu Dekang , Liu Mafeng , Zhao Xinxin , Yang Qiao , Wu Ying , Zhang Shaqiu , Liu Yunya , Yu Yanling , Zhang Ling , Pan Leichang , Chen Shun , Cheng Anchun
Published: November 2019

Background

Goose parvovirus (GPV) is the etiological agent of Derzsy’s disease and is fatal for gosling. Research on the molecular basis of GPV pathogenicity has been hampered by the lack of a reliable reverse genetics system. At present, the GPV infectious clone has been rescued by transfection in the goose embryo, but the growth character of it is unclear in vitro.

Methods

In this study, we identified the full-length genome of GPV RC16 from the clinical sample, which was cloned into the pACYC177, generating the pIRC16. The recombinant virus (rGPV RC16) was rescued by the transfection of pIRC16 into goose embryo fibroblasts (GEFs). The rescued virus was characterized by whole genome sequencing, indirect immunofluorescence assays (IFA) and western blot (WB) using rabbit anti-GPV Rep polyclonal antibody as the primary antibody. Previously, we found the 164 K, 165 K, and 167 K residues in the 160YPVVKKPKLTEE171 are required for the nuclear import of VP1 (Chen S, Liu P, He Y, et al. Virology 519:17–22). According to that, the GPV infectious clones with mutated K164A, K165A, or K167A in VP1 were constructed, rescued and passaged.

Results

The rGPV RC16 has been successfully rescued by transfection of pIRC16 into the GEFs and can proliferate in vitro. Furthermore, the progeny virus produced by pIRC16 transfected cells was infectious in GEFs. Moreover, mutagenesis experiments showed that the rGPV RC16 with mutated 164 K, 165 K and 167 K in VP1 could not proliferate in GEFs based on the data of IFA and WB in parental virus and progeny virus.

Conclusions

The rGPV RC16 containing genetic maker and the progeny virus are infectious in GEFs. The 164 K, 165 K, and 167 K of VP1 are vital for the proliferation of rGPV RC16 in vitro.
The prevalence of alcohol use disorders among people living with HIV/AIDS: a systematic review and meta-analysis
Authors: Duko Bereket , Ayalew Mohammed , Ayano Getinet
Published: November 2019

Background

Alcohol use disorder (AUD) is common among people living with HIV/AIDS (PLWHA) and associated with a greater risk of poor medication adherence, unsafe sexual behaviors as well as poor quality of life. To our knowledge, there is no previous systematic review and meta-analysis that reported the pooled prevalence estimate of AUD among PLWHA. Therefore, this review aimed to systematically review the available studies on the prevalence of AUD among PLWHA and forward possible recommendations for future clinical practice and research.

Methods

PubMed, EMBASE, Psych INFO and SCOPUS databases were searched to identify the relevant studies. We have also scanned the reference lists of the eligible studies to supplement our electronic search. We used the Comprehensive Meta-Analysis software versions 3.0 to conduct a meta-analysis. Subgroup and sensitivity analysis were performed and Cochran’s Q- and the I2- test were employed to see the heterogeneity. The presence of publication bias was explored by utilizing Egger’s test and visual inspection of the symmetry in funnel plots.

Results

A total of 25 studies with 25,154 participants across developed and developing countries were included in the final analysis. Our meta-analysis revealed that the pooled prevalence estimate of AUD among PLWHA was found to be 29.80% (95% CI; 24.10–35.76). The prevalence of AUD was higher in males (26.90%) than female (13.37%) HIV patients. In this study, the pooled prevalence of AUD was considerably higher (31.52%) when measured by Alcohol Use Disorders Identification Test (AUDIT) as compared to Composite International Diagnostic Interview (CIDI) (13.51%). In addition, the pooled prevalence of AUD was higher in the developed countries (42.09%) while lower for developing countries (24.52%).

Conclusion

In the current study, the pooled prevalence estimates of AUD among PLWHA was considerably high (29.80%). Screening and appropriate management of AUD among PLWHA are recommended.