bluuebunny/crossref_metadata_2025 huggingface dataset:
Scalp eschar and neck lymphadenopathy after tick bite (SENLAT) caused by Bartonella henselae in Korea: a case report
Authors: Seo Jun-Won , Kim Choon-Mee , Yun Na Ra , Kim Dong-Min , Kim Sung Soon , Choi Sangho , Chu Hyuk
Published: March 2020

Background

Tick-borne lymphadenopathy (TIBOLA) is an infectious disease, mainly caused by species from the spotted fever group rickettsiae and is characterized by enlarged lymph nodes following a tick bite. Among cases of TIBOLA, a case of scalp eschar and neck lymphadenopathy after tick bite (SENLAT) is diagnosed when an eschar is present on the scalp, accompanied by peripheral lymphadenopathy (LAP). Only a few cases of SENLAT caused by Bartonella henselae have been reported.

Case presentation

A 58-year-old male sought medical advice while suffering from high fever and diarrhea. Three weeks before the visit, he had been hunting a water deer, and upon bringing the deer home discovered a tick on his scalp area. Symptoms occurred one week after hunting, and a lump was palpated on the right neck area 6 days after the onset of symptoms. Physical examination upon presentation confirmed an eschar-like lesion on the right scalp area, and cervical palpation revealed that the lymph nodes on the right side were non-painful and enlarged at 2.5 × 1.5 cm. Fine needle aspiration of the enlarged lymph nodes was performed, and results of nested PCR for the Bartonella internal transcribed spacer (ITS) confirmed B. henselae as the causative agent.

Conclusion

With an isolated case of SENLAT and a confirmation of B. henselae in Korea, it is pertinent to raise awareness to physicians in other Asian countries that B. henselae could be a causative agent for SENLAT.
The WHO Safe Childbirth Checklist implementation: impact on the prescription of magnesium sulphate through a one-year longitudinal study
Authors: da Silva Gama Zenewton André , Medeiros Wilton Rodrigues , Saturno-Hernández Pedro Jesus , de Meneses Sousa Kelienny , Mello Matheus Silva , de Lima Vale Érico , de Souza Rosendo Tatyana Maria Silva , da Silva Edna Marta Mendes , de Freitas Marise Reis
Published: March 2020

Background

Preeclampsia is a relatively frequent condition during pregnancy and childbirth. The administration of magnesium sulphate as a prophylactic and treatment measure is an evidence-based practice for eclampsia; however, it is not consistently used, compromising the health of pregnant women. This study aimed to assess compliance with recommendations of the International Society for the Study of Hypertension in Pregnancy (ISSHP) for the use of MgSO4 in pregnant women with preeclampsia, before and after the implementation of the World Health Organization Safe Childbirth Checklist (SCC).

Methods

This quasi-experimental study was conducted between July 2015 and July 2016 at a third-level maternity hospital in northeastern Brazil, where the SCC was implemented. Compliance (underuse and overuse of MgSO4) was assessed in biweekly samples of 30 deliveries assessed 6 months before and 6 months after SCC implementation, using indicators based on international guidelines. A total of 720 deliveries were assessed over 1 year using an ad hoc application for reviewing medical records. Aggregated adequate use was estimated for the study period, and the time series measurements were compared to a control chart to assess change.

Results

The incidence of preeclampsia was 39.9% (287/720). Among these, 64.8% (186/287) had severe signs or symptoms and needed MgSO4. Underuse (no prescription when needed) of MgSO4 was observed in 74.7% (139/186) of women who needed the drug. Considering all women, non-compliance with the prescription protocol (underuse and overuse) was 20.0% (144/720). After introducing the SCC, the use of MgSO4 in women with preeclampsia with severe features increased from 19.1 to 34.2% (p = 0.025). Longitudinal analysis showed a significant (p < 0.05) ascending curve of adequate use of MgSO4 after the SCC was implemented.

Conclusions

Compliance with recommendations for the use of MgSO4 in preeclampsia was low, but improved after implementation of the SCC. Interventions to improve compliance based on diagnosis and treatment reminders may help in the implementation of this good practice.
Estimating racial health disparities among adverse birth outcomes as deviations from the population rates
Authors: Thompson James A. , Suter Melissa A.
Published: March 2020

Background

Despite significant research, the reasons for racial health disparities among adverse birth outcomes (ABO) remain largely unknown. The bulk of research into racial health disparities among ABO in the United States has concentrated on the risk of race and ethnic groups relative to the specific sub-population of non-Hispanic white women and their children. The objective of this study was to estimate the racial and ethnic risks among a set of neonatal and maternal health disparities while minimizing bias attributable to how the baseline risk was established.

Methods

All birth records were obtained from the United States Natality database for the years 2014 to 2017. A Bayesian modeling approach was used to estimate the risk disparity for disorders by race. The estimation of the race-specific risks used a sum-to-zero constraint for the race regression coefficients.

Results

Estimating racial health disparities relative to the overall population rate yielded novel results and identified perinatal health disparities for all the race groups studied.

Conclusions

Unbiased risk estimates for racial disparities among ABO are now available for stimulating and initiating more complex causal modeling that can lead to understanding how racial health disparities for ABO are mediated and how they can be prevented.
Alteration in the sensitivity to crizotinib by Na+/H+ exchanger regulatory factor 1 is dependent to its subcellular localization in ALK-positive lung cancers
Authors: Yang Fenglian , Hu Mu , Chang Siyuan , Huang Jing , Si Yang , Wang Jinghui , Cheng Shan , Jiang Wen G.
Published: March 2020

Background

Na+/H+ exchanger regulatory factor 1 (NHERF1) is an important scaffold protein participates in the modulation of a variety of intracellular signal pathways. NHERF1 was able to enhance the effects of chemo-drugs in breast and cervical cancer cells. Anaplastic lymphoma kinase (ALK) fusion mutations are validated molecules targeted therapy in lung cancers, where crizotinib can be used as the specific inhibitor to suppress tumor progression. However, due to the less frequent occurrence of ALK mutations and the complexity for factors to determine drug responses, the genes that could alter crizotinib sensitivity are unclear.

Methods

Both ALK-translocated and ALK-negative lung adenocarcinoma specimens in tissue sections were collected for immunohistochemistry. The possible mechanisms of NHERF1 and its role in the cell sensitivity to crizotinib were investigated using an ALK-positive and crizotinib-sensitive lung adenocarcinoma cell line H3122. Either a NHERF1 overexpression vector or agents for NHERF1 knockdown was used for crizotinib sensitivity measures, in association with cell viability and apoptosis assays.

Results

The expression level of NHERF1 in ALK-translocated NSCLC was significantly higher than that in other lung cancer tissues. NHERF1 expression in ALK positive lung cancer cells was regulated by ALK activities, and was in return able to alter the sensitivity to crizotinib. The function of NHERF1 to influence crizotinib sensitivity was depending on its subcellular distribution in cytosol instead of its nucleus localized form.

Conclusion

Ectopically overexpressed NHERF1 could be a functional protein for consideration to suppress lung cancers. The determination of NHERF1 levels in ALK positive NSCLC tissues might be useful to predict crizotinib resistance, especially by distinguishing cytosolic or nuclear localized NHERF1 for the overexpressed molecules.
Outcomes of patients with initially locally advanced pancreatic adenocarcinoma who did not benefit from resection: a prospective cohort study
Authors: Garnier Jonathan , Ewald Jacques , Marchese Ugo , Gilabert Marine , Launay Simon , Moureau-Zabotto Laurence , Poizat Flora , Giovannini Marc , Delpero Jean-Robert , Turrini Olivier
Published: March 2020

Background

The current study aimed to evaluate the outcomes of patients with unresectable non-metastatic locally advanced pancreatic adenocarcinoma (LAPA) who did not benefit from resection considering the treatment strategy in the clinical settings.

Methods

Between 2010 and 2017, a total of 234 patients underwent induction chemotherapy for LAPA that could not be treated with surgery. After oncologic restaging, continuous chemotherapy or chemoradiation (CRT) was decided for patients without metastatic disease. The Kaplan–Meier method was used to determine overall survival (OS), and the Wilcoxon test to compare survival curves. Multivariate analysis was performed using the stepwise logistic regression method.

Results

FOLFIRINOX was the most common induction regimen (168 patients, 72%), with a median of 6 chemotherapy cycles and resulted in higher OS, compared to gemcitabine (19 vs. 16 months, hazard ratio (HR) = 1.2, 95% confidence interval: 0.86–1.6, P = .03). However, no difference was observed after adjusting for age (≤75 years) and performance status score (0–1). At restaging, 187 patients (80%) had non-metastatic disease: CRT was administered to 126 patients (67%) while chemotherapy was continued in 61 (33%). Patients who received CRT had characteristics comparable to those who continued with chemotherapy, with similar OS. They also had longer progression-free survival (median 13.3 vs. 9.6 months, HR = 1.38, 95% confidence interval: 1–1.9, P < .01) and limited short-term treatment-related toxicity.

Conclusions

The median survival of patients who could not undergo surgery was 19 months. Hence, CRT should not be eliminated as a treatment option and may be useful as a part of optimised sequential chemotherapy for both local and metastatic disease.
Bouldering psychotherapy is more effective in the treatment of depression than physical exercise alone: results of a multicentre randomised controlled intervention study
Authors: Karg Nina , Dorscht Lisa , Kornhuber Johannes , Luttenberger Katharina
Published: March 2020

Background

Recent scientific studies have suggested that climbing/bouldering is effective in alleviating depression when the comparison group was a waitlist control group, even when physical activity and other therapeutic approaches were controlled for. In the present study, we aimed to investigate the effectiveness of a manualised psychotherapeutic bouldering intervention for depressed individuals, compared with an active control group performing physical exercise alone.

Methods

In a multicentre randomised controlled intervention trial, 133 outpatients with depression were assigned to either a bouldering psychotherapy (BPT) group or a home-based supervised exercise programme (EP). Severity of depression as the primary outcome was assessed at baseline and directly after a ten-week intervention period using the Montgomery–Åsberg Depression Rating Scale (MADRS). Secondary outcomes included anxiety, coping skills, self-esteem, body image, and interpersonal sensitivity. We applied t-tests to test for differences within the groups (t0 vs. t1) and between the BPT and the EP and a multiple regression analysis with the post-intervention MADRS score as the dependent variable. The robustness of estimates was investigated with a sensitivity analyses.

Results

Patients in the BPT group showed a significantly larger decrease in depression scores compared with the EP on the MADRS (drop of 8.4 vs. 3.0 points, p = .002, Cohen’s d = 0.55). In the confounder-adjusted regression analyses, group allocation was found to be the only significant predictor of the post-intervention MADRS score (β = − 5.60, p = .001) besides the baseline MADRS score. Further significant differences in change scores between the BPT and the EP were found for anxiety (p = .046, d = 0.35), body image (p = .018, d = 0.42), and global self-esteem (p = .011, d = 0.45).

Conclusions

The study provides evidence that the manualised BPT is not only effective in alleviating depressive symptoms but even goes beyond the effect of mere physical exercise. Based on these findings, the BPT should be considered as a complementary therapeutic approach.

Trial registration

Trial identification number: ISRCTN12457760: Study KuS (Klettern und Stimmung - Climbing and Mood) combined boulder and psychotherapy against depression, registered retrospectively on July 26th, 2017.
Emotion dysregulation in adults with attention deficit hyperactivity disorder: a meta-analysis
Authors: Beheshti Ashkan , Chavanon Mira-Lynn , Christiansen Hanna
Published: March 2020

Background

Emotional symptoms are increasingly considered a core feature of attention deficit/hyperactivity disorder (ADHD). We aimed to quantify the evidence of emotional dysregulation and its respective facets in individuals with adult ADHD compared to healthy controls using meta-analysis.

Methods

Two electronic databases (PubMed, PsycINFO) were reviewed to identify studies. Studies were eligible for inclusion that had reports on any measure of emotion (dys) regulation in adults (> 18 years of age) in clinically diagnosed patients with ADHD as well as healthy control participants. We included a total of 13 studies (N = 2535) to assess (1) the standardized mean difference in emotion dysregulation (ED) as a general factor and its specific facets (i.e., emotional lability, negative emotional responses, and emotion recognition) between adults with ADHD and healthy controls; and (2) the association between ADHD symptom severity and ED.

Results

Compared to healthy controls, adults with ADHD revealed significantly higher levels of general ED (Hedges’ g = 1.17, p < 0.001; Hedges’ g is the adjusted effect size). With regard to intermediate dimensions of ED, emotional lability exhibited the strongest weighted effect (Hedges’ g = 1.20, CI [0.57, 1.83], p < 0.001). Furthermore, symptom severity and general ED correlated significantly (r = 0.54, p < 0.001). Regarding intermediate dimensions of ED, negative emotional responses correlated closely with ADHD symptom severity (r = 0.63, p < 0.001) and emotional lability (r = 0.52, p < 0.001).

Conclusions

Our findings support ED symptoms as a core feature of ADHD’s psychopathology. With respect to dimensions of ED, emotional lability, and negative emotional responses play a more definitive role in the psychopathology of adults with ADHD. Due to insufficient statistical reports in the included studies, we could not perform meta-regressions to control the role of moderator variables.
The validation of organisational culture assessment instrument in healthcare setting: results from a cross-sectional study in Vietnam
Authors: Van Huy Nguyen , Thu Nguyen Thi Hoai , Anh Nguyen Le Tuan , Au Nguyen Thanh Hai , Phuong Nguyen The , Cham Nguyen Thi , Minh Pham Duc
Published: March 2020

Background

Organisational culture (OC) has increasingly become a crucial factor in defining healthcare practice and management. However, there has been little research validating and adapting OCAI (organisational culture assessment instrument) to assess OC in healthcare settings in developing countries, including Vietnam. The purpose of this study is to validate the OCAI in a hospital setting using key psychometric tests and confirmatory factor analysis (CFA).

Methods

This is a cross-sectional study. Self-administered structured questionnaire was completed by 566 health professionals from a Vietnamese national general hospital, the General Hospital of Quang Nam province. The psychometric tests and CFA were utilized to detect internal reliability and construct validity of the instrument.

Results

The Cronbach’s alpha coefficients (α-reliability statistic) ranged from 0.6 to 0.8. In current culture, the coefficient was 0.80 for clan and 0.60 for adhocracy, hierarchy and market dimension, while in expected culture, the coefficient for clan, adhocracy, hierarchy, and market dimension was 0.70, 0.70, 0.70 and 0.60, respectively. The CFA indicated that most factor loading coefficients were of moderate values ranging from 0.30 to 0.60 in both current and expected culture model. These models are of marginal good fit.

Conclusions

The study findings suggest that the OCAI be of fairly good reliability and construct validity in measuring four types of organisational culture in healthcare setting in resource-constrained countries such as Vietnam. This result is a first step towards developing a valid Vietnamese version of the OCAI which can also provide a strong case for future research in the field of measuring and managing organisational culture.
An assessment of the food safety knowledge and attitudes of food handlers in hospitals
Authors: Teffo Lesiba A. , Tabit Frederick T.
Published: March 2020

Background

The possession of inadequate food safety knowledge (FSK) by food handlers poses a serious threat to food safety in service establishments. The aim of this research was to investigate factors that influenced the FSK and food safety attitudes (FSA) of employees involved in the preparation and/or the serving of food from nine hospitals in the Capricorn District Municipality (CDM) in Limpopo Province, South Africa.

Method

Up to 210 individuals (18–65 years) who were employed in these hospitals, and who were involved in the preparation and serving of food to patients were purposefully selected. Data collection was by means of an interview using a questionnaire design for this study. The FSK and FSA scores of hospital food handlers were obtained by adding the correct response to FSK or FSA questions.

Results

Only 29% of the hospital food handlers have attended a food safety-training course. Many food handlers were not knowledgeable on the correct temperature for handling foods, and on the correct minimum internal cooking temperature for poultry, seafood and egg. Only the minority of food handlers knew that Salmonella is the main foodborne bacteria pathogen mostly associated with poultry products (47.1%) and that food borne bacteria will grow quickly in food at a temperature of 37 °C (38.1%). Hospital food handlers with higher academic qualifications do not possess more FSK than those with lower academic qualifications. 51% of the hospital food handlers possessed a Satisfactory FSK while 10% possessed a Good FSK and 39% possessed an Inadequate FSK.

Conclusion

More than 60% of the hospital food handlers possesses either Good FSK or Satisfactory FSK. Higher levels of education, experience in food handling and job position did not lead to better FSK outcome. All the hospital food handlers possess at least a Satisfactory FSA. There was a weak positive but significant correlation between the FSK and FSA of hospital food handlers. It is recommended all employees involved in food handlers be subjected to food safety training programmes on a regular basis irrespective of their academic, employment and training details.
Prostate biopsy techniques and pre-biopsy prophylactic measures: variation in current practice patterns in the Netherlands
Authors: Tops Sofie C. M. , Koldewijn Evert L. , Somford Diederik M. , Huis Anita M. P. , Kolwijck Eva , Wertheim Heiman F. L. , Hulscher Marlies E. J. L. , Sedelaar J. P. Michiel
Published: March 2020

Background

The clinical landscape of prostate biopsy (PB) is evolving with changes in procedures and techniques. Moreover, antibiotic resistance is increasing and influences the efficacy of pre-biopsy prophylactic regimens. Therefore, increasing antibiotic resistance may impact on clinical care, which probably results in differences between hospitals. The objective of our study is to determine the (variability in) current practices of PB in the Netherlands and to gain insight into Dutch urologists’ perceptions of fluoroquinolone resistance and biopsy related infections.

Methods

An online questionnaire was prepared using SurveyMonkey® platform and distributed to all 420 members of the Dutch Association of Urology, who work in 81 Dutch hospitals. Information about PB techniques and periprocedural antimicrobial prophylaxis was collected. Urologists’ perceptions regarding pre-biopsy antibiotic prophylaxis in an era of antibiotic resistance was assessed. Descriptive statistical analysis was performed.

Results

One hundred sixty-one responses (38.3%) were analyzed representing 65 (80.3%) of all Dutch hospitals performing PB. Transrectal ultrasound guided prostate biopsy (TRUSPB) was performed in 64 (98.5%) hospitals. 43.1% of the hospitals (also) used other image-guided biopsy techniques. Twenty-three different empirical prophylactic regimens were reported among the hospitals. Ciprofloxacin was most commonly prescribed (84.4%). The duration ranged from one pre-biopsy dose (59.4%) to 5 days extended prophylaxis. 25.2% of the urologists experienced ciprofloxacin resistance as a current problem in the prevention of biopsy related infections and 73.6% as a future problem.

Conclusions

There is a wide variation in practice patterns among Dutch urologists. TRUSPB is the most commonly used biopsy technique, but other image-guided biopsy techniques are increasingly used. Antimicrobial prophylaxis is not standardized and prolonged prophylaxis is common. The wide variation in practice patterns and lack of standardization underlines the need for evidence-based recommendations to guide urologists in choosing appropriate antimicrobial prophylaxis for PB in the context of increasing antibiotic resistance.
Gain-of-function mutation in the voltage-gated potassium channel gene KCNQ1 and glucose-stimulated hypoinsulinemia - case report
Authors: Zhang Jinyi , Juhl Christian R. , Hylten-Cavallius Louise , Salling-Olsen Morten , Linneberg Allan , Holst Jens Juul , Hansen Torben , Kanters Jørgen K. , Torekov Signe S.
Published: March 2020

Background

The voltage-gated potassium channel Kv7.1 encoded by KCNQ1 is located in both cardiac myocytes and insulin producing beta cells. Loss-of-function mutations in KCNQ1 causes long QT syndrome along with glucose-stimulated hyperinsulinemia, increased C-peptide and postprandial hypoglycemia. The KCNE1 protein modulates Kv7.1 in cardiac myocytes, but is not expressed in beta cells. Gain-of-function mutations in KCNQ1 and KCNE1 shorten the action potential duration in cardiac myocytes, but their effect on beta cells and insulin secretion is unknown.

Case presentation

Two patients with atrial fibrillation due to gain-of-function mutations in KCNQ1 (R670K) and KCNE1 (G60D) were BMI-, age-, and sex-matched to six control participants and underwent a 6-h oral glucose tolerance test (OGTT). During the OGTT, the KCNQ1 gain-of-function mutation carrier had 86% lower C-peptide response after glucose stimulation compared with matched control participants (iAUC360min = 34 pmol/l*min VS iAUC360min = 246 ± 71 pmol/l*min). The KCNE1 gain-of-function mutation carrier had normal C-peptide levels.

Conclusions

This case story presents a patient with a gain-of-function mutation KCNQ1 R670K with low glucose-stimulated C-peptide secretion, additionally suggesting involvement of the voltage-gated potassium channel KCNQ1 in glucose-stimulated insulin regulation.
Children and parents’ perspectives on the acceptability of three management strategies for dental caries in primary teeth within the ‘Filling Children’s Teeth: Indicated or Not’ (FiCTION) randomised controlled trial – a qualitative study
Authors: El-Yousfi Sarab , Innes Nicola P. T. , Holmes Richard D. , Freeman Ruth , Cunningham Kathryn B. , McColl Elaine , Maguire Anne , Douglas Gail V. A. , Clarkson Janet E. , Marshman Zoe
Published: March 2020

Background

The Filling Children’s Teeth: Indicated Or Not? (FiCTION) randomised controlled trial (RCT) aimed to explore the clinical- and cost-effectiveness of managing dental caries in children’s primary teeth. The trial compared three management strategies: conventional caries management with best practice prevention (C + P), biological management with best practice prevention (B + P) and best practice prevention alone (PA)-based approaches. Recently, the concept of treatment acceptability has gained attention and attempts have been made to provide a conceptual definition, however this has mainly focused on adults. Recognising the importance of evaluating the acceptability of interventions in addition to their effectiveness, particularly for multi-component complex interventions, the trial design included a qualitative component. The aim of this component was to explore the acceptability of the three strategies from the perspectives of the child participants and their parents.

Methods

Qualitative exploration, based on the concept of acceptability. Participants were children already taking part in the FiCTION trial and their parents. Children were identified through purposive maximum variation sampling. The sample included children from the three management strategy arms who had been treated and followed up; median (IQR) follow-up was at 33.8 (23.8, 36.7) months. Semi-structured interviews with thirteen child-parent dyads. Interviews were transcribed verbatim and analysed using a framework approach.

Results

Data saturation was reached after thirteen interviews. Each child-parent dyad took part in one interview together. The participants were eight girls and five boys aged 5–11 years and their parents. The children’s distribution across the trial arms was: C + Pn = 4; B + Pn = 5; PAn = 4. Three key factors influenced the acceptability of caries management in primary teeth to children and parents: i) experiences of specific procedures within management strategies; ii) experiences of anticipatory dental anxiety and; iii) perceptions of effectiveness (particularly whether pain was reduced). These factors were underpinned by a fourth key factor: the notion of trust in the dental professionals – this was pervasive across all arms.

Conclusions

Overall children and parents found each of the three strategies for the management of dental caries in primary teeth acceptable, with trust in the dental professional playing an important role.
Performance analysis of novel toxin-antidote CRISPR gene drive systems
Authors: Champer Jackson , Kim Isabel K. , Champer Samuel E. , Clark Andrew G. , Messer Philipp W.
Published: March 2020

Background

CRISPR gene drive systems allow the rapid spread of a genetic construct throughout a population. Such systems promise novel strategies for the management of vector-borne diseases and invasive species by suppressing a target population or modifying it with a desired trait. However, current homing-type drives have two potential shortcomings. First, they can be thwarted by the rapid evolution of resistance. Second, they lack any mechanism for confinement to a specific target population. In this study, we conduct a comprehensive performance assessment of several new types of CRISPR-based gene drive systems employing toxin-antidote (TA) principles, which should be less prone to resistance and allow for the confinement of drives to a target population due to invasion frequency thresholds.

Results

The underlying principle of the proposed CRISPR toxin-antidote gene drives is to disrupt an essential target gene while also providing rescue by a recoded version of the target as part of the drive allele. Thus, drive alleles tend to remain viable, while wild-type targets are disrupted and often rendered nonviable, thereby increasing the relative frequency of the drive allele. Using individual-based simulations, we show that Toxin-Antidote Recessive Embryo (TARE) drives targeting an haplosufficient but essential gene (lethal when both copies are disrupted) can enable the design of robust, regionally confined population modification strategies with high flexibility in choosing promoters and targets. Toxin-Antidote Dominant Embryo (TADE) drives require a haplolethal target gene and a germline-restricted promoter, but they could permit faster regional population modification and even regionally confined population suppression. Toxin-Antidote Dominant Sperm (TADS) drives can be used for population modification or suppression. These drives are expected to spread rapidly and could employ a variety of promoters, but unlike TARE and TADE, they would not be regionally confined and also require highly specific target genes.

Conclusions

Overall, our results suggest that CRISPR-based TA gene drives provide promising candidates for flexible ecological engineering strategies in a variety of organisms.
Biomarker-defined pathways for incident type 2 diabetes and coronary heart disease—a comparison in the MONICA/KORA study
Authors: Huth Cornelia , Bauer Alina , Zierer Astrid , Sudduth-Klinger Julie , Meisinger Christa , Roden Michael , Peters Annette , Koenig Wolfgang , Herder Christian , Thorand Barbara
Published: March 2020

Background

Biomarkers may contribute to our understanding of the pathophysiology of various diseases. Type 2 diabetes (T2D) and coronary heart disease (CHD) share many clinical and lifestyle risk factors and several biomarkers are associated with both diseases. The current analysis aims to assess the relevance of biomarkers combined to pathway groups for the development of T2D and CHD in the same cohort.

Methods

Forty-seven serum biomarkers were measured in the MONICA/KORA case-cohort study using clinical chemistry assays and ultrasensitive molecular counting technology. The T2D (CHD) analyses included 689 (568) incident cases and 1850 (2004) non-cases from three population-based surveys. At baseline, the study participants were 35–74 years old. The median follow-up was 14 years. We computed Cox regression models for each biomarker, adjusted for age, sex, and survey. Additionally, we assigned the biomarkers to 19 etiological pathways based on information from literature. One age-, sex-, and survey-controlled average variable was built for each pathway. We used the R2PM coefficient of determination to assess the explained disease risk.

Results

The associations of many biomarkers, such as several cytokines or the iron marker soluble transferrin receptor (sTfR), were similar in strength for T2D and CHD, but we also observed important differences. Lipoprotein (a) (Lp(a)) and N-terminal pro B-type natriuretic peptide (NT-proBNP) even demonstrated opposite effect directions. All pathway variables together explained 49% of the T2D risk and 21% of the CHD risk. The insulin-like growth factor binding protein 2 (IGFBP-2, IGF/IGFBP system pathway) best explained the T2D risk (about 9% explained risk, independent of all other pathway variables). For CHD, the myocardial-injury- and lipid-related-pathways were most important and both explained about 4% of the CHD risk.

Conclusions

The biomarker-derived pathway variables explained a higher proportion of the T2D risk compared to CHD. The ranking of the pathways differed between the two diseases, with the IGF/IGFBP-system-pathway being most strongly associated with T2D and the myocardial-injury- and lipid-related-pathways with CHD. Our results help to better understand the pathophysiology of the two diseases, with the ultimate goal of pointing out targets for lifestyle intervention and drug development to ideally prevent both T2D and CHD development.
Adenovirus-mediated anti-AEG-1 ScFv expression driven by stathmin promoter inhibits tumor growth in cervical cancer
Authors: Long Min , Lin Fang , Wang Xi , Chen Xi , Liu Li , Zhang Huizhong , Dong Ke
Published: March 2020

Background

Astrocyte-elevated gene-1 (AEG-1) is over-expressed in many cancer cells and has multiple key functions in tumor initiation and progression. Currently, targeted-AEG-1 siRNA is one of the most common techniques to down-regulate AEG-1 expression, but the lack of tumor specificity and available delivery system make it difficult to enter clinical trials.

Methods

In this study, we creatively developed an adenovirus-mediated anti-AEG-1 single-chain antibody fragment (ScFv) expression system driven by a tumor specific promoter, and experimented with it in human cervical carcinoma cells to investigate the effect on tumor’s proliferation and apoptosis.

Results

The results showed that of HeLa and SiHa cells treated with this recombinant anti-AEG-1 ScFv adenovirus not only inhibited cell growth, but induced apoptosis both in vitro and in vivo. Furthermore, we also observed that the expressions of several apoptosis-related genes like Akt 1 and c-Myc decreased, while NF-κB (p65) and cleaved caspase 3 increased on protein levels in vivo.

Conclusion

We concluded that stathmin promoter-driving anti-AEG-1 ScFv adenoviral system may be a breakthrough for its dual-specificity, and serve as an adjuvant tumor specific therapy method in the treatment for human cervical cancers.
Circ_0072083 interference enhances growth-inhibiting effects of cisplatin in non-small-cell lung cancer cells via miR-545-3p/CBLL1 axis
Authors: Li Huiping , Liu Fangfang , Qin Wenjing
Published: March 2020

Background

Non-small-cell lung cancer (NSCLC) is one of the common cancers in the world. Circular RNA 0072083 (circ_0072083, circZFR) has been reported to be associated with the progression of NSCLC. In this study, we intended to explore the role and the potential mechanism of circ_0072083 in NSCLC.

Methods

Quantitative real time polymerase chain reaction (qRT-PCR) was performed to detect the expression of circ_0072083, its matching linear RNA (zinc finger RNA binding protein (ZFR)) and microRNA-545-3p (miR-545-3p) in NSCLC cells. The ability of colony formation in NSCLC cells was detected by colony formation assay. The apoptosis and cell cycle were measured by flow cytometry. The metastasis was determined by transwell migration and invasion assays. The protein expression of E-cadherin, N-cadherin, Vimentin and Cbl proto-oncogene like 1 (CBLL1) was examined by western blot assay. The interaction between miR-545-3p and circ_0072083 or CBLL1 was predicted by starBase or Targetscan software. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to validate these interactions. Nude mice bearing tumors were used to confirm the role of circ_0072083 and cisplatin (DDP) in vivo.

Results

The level of circ_0072083 was higher in NSCLC tissues and cells relative to that in adjacent non-tumor tissues and normal lung cells. The transfection of si-circ_0072083 inhibited colony formation, cell cycle and metastasis while promoted the apoptosis of NSCLC cells stimulated by DDP. MiR-545-3p was a direct functional target of circ_0072083 in NSCLC cells. CBLL1 could bind to miR-545-3p in NSCLC cells. Circ_0072083 promoted the progression of NSCLC induced by DDP through sponging miR-545-3p and enhancing the enrichment of CBLL1 in vivo and in vitro.

Conclusion

Circ_0072083 depletion contributed to DDP-triggered inhibition of NSCLC tumor through miR-545-3p/CBLL1 axis.
CircMRPS35 suppresses gastric cancer progression via recruiting KAT7 to govern histone modification
Authors: Jie Mengmeng , Wu Yaran , Gao Mengyuan , Li Xinzhe , Liu Cheng , Ouyang Qin , Tang Qingyun , Shan Changyu , Lv Yangfan , Zhang Kebin , Dai Qian , Chen Yang , Zeng Shuo , Li Chenglin , Wang Liting , He Fengtian , Hu Changjiang , Yang Shiming
Published: March 2020

Background

Aberrant expression of circular RNAs contributes to the initiation and progression of cancers, but the underlying mechanism remains elusive.

Methods

RNA-seq and qRT-PCR were performed to screen differential expressed circRNAs between gastric cancer tissues and adjacent normal tissues. Candidate circRNA (circMRPS35) was screened out and validated by qRT-PCR. Cell proliferation and invasion ability were determined by CCK-8 and cell invasion assays. RNA-seq, GO-pathway, RNA pull-down and ChIRP were further applied to search for detailed mechanism.

Results

Here, a novel circRNA named circMRPS35, was screened out by RNA-seq in gastric cancer tissues, whose expression is related to clinicopathological characteristics and prognosis in gastric cancer patients. Biologically, circMRPS35 suppresses the proliferation and invasion of gastric cancer cells in vitro and in vivo. Mechanistically, circMRPS35 acts as a modular scaffold to recruit histone acetyltransferase KAT7 to the promoters of FOXO1 and FOXO3a genes, which elicits acetylation of H4K5 in their promoters. Particularly, circMRPS35 specifically binds to FOXO1/3a promoter regions directly. Thus, it dramatically activates the transcription of FOXO1/3a and triggers subsequent response of their downstream target genes expression, including p21, p27, Twist1 and E-cadherin, resulting in the inhibition of cell proliferation and invasion. Moreover, circMRPS35 expression positively correlates with that of FOXO1/3a in gastric cancer tissues.

Conclusions

Our findings not only reveal the pivotal roles of circMRPS35 in governing histone modification in anticancer treatment, but also advocate for triggering circMRPS35/KAT7/FOXO1/3a pathway to combat gastric cancer.
The psychometric properties of the Italian adaptation of the Health Orientation Scale (HOS)
Authors: Masiero M. , Oliveri S. , Cutica I. , Monzani D. , Faccio F. , Mazzocco K. , Pravettoni G.
Published: March 2020

Background

A novel approach suggested that cognitive and dispositional features may explain in depth the health behaviors adoption and the adherence to prevention programs. The Health Orientation Scale (HOS) has been extensively used to map the adoption of health and unhealthy behaviors according to cognitive and dispositional features. Coherently, the main aim of the current research was to assess the factor structure of the Italian version of the HOS using exploratory and confirmatory factor analysis and testing the construct validity of the scale by assessing differences in health orientations between tobacco cigarette smokers and nonsmokers.

Method

The research protocol was organized in two studies.Study 1evaluated the dimensionality of the HOS in a sample of Northern Italian healthy people. Three hundred and twenty-one participants were enrolled; they were 229 women (71.3%) and 92 men (28.7%). InStudy 2, the factor structure and construct validity of the HOS Italian version was assessed trough confirmatory factor analysis using a tobacco cigarette smokers and nonsmokers population. Two hundred and nineteen participants were enrolled; they were 164 women (75.2%) and 55 men (24.8%).

Results

InStudy 1, a seven factors solution was obtained explaining 60% of cumulative variance instead of 10 factors solution of the original version of the HOS. InStudy 2,the factor structure of the Italian version of the HOS was confirmed and applied to the smokers and nonsmokers; nonsmokers reported higher values than smokers in Factor 1 (MHPP) [t (208) = − 2.739p < .007] (CI 95–4.96% to −.809), Factor 2 (HES) [t (209) = − 3.387p < .001] (CI 95–3.93% to -. 1.03), Factor 3 (HIC) [t(213) = − 2.468p < .014] (CI 95–2.56% to −.28) and Factor 7 (HEX) [t(217) = − 3.451p < .001] (CI 95%- 1.45 to .39).

Conclusions

Results of the Italian adaptation of HOS lead to a partial redistribution of items and confirmed 7 subscales to distinguish psycho-cognitive dispositional dimensions involved in health orientation styles.
Fondazione Italiana Linfomi (FIL) expert consensus on the use of intensity-modulated and image-guided radiotherapy for Hodgkin’s lymphoma involving the mediastinum
Authors:   on behalf of the Fondazione Italiana Linfomi (FIL) Radiotherapy Committee, Filippi Andrea Riccardo , Meregalli Sofia , DI Russo Anna , Levis Mario , Ciammella Patrizia , Buglione Michela , Guerini Andrea Emanuele , De Marco Giuseppina , De Sanctis Vitaliana , Vagge Stefano , Ricardi Umberto , Simontacchi Gabriele
Published: March 2020

Aim

Advances in therapy have resulted in improved cure rates and an increasing number of long-term Hodgkin's lymphoma (HL) survivors. However, radiotherapy (RT)-related late effects are still a significant issue, particularly for younger patients with mediastinal disease (secondary cancers, heart diseases). In many Centers, technological evolution has substantially changed RT planning and delivery. This consensus document aims to analyze the current knowledge of Intensity-Modulated Radiation Therapy (IMRT) and Image-Guided Radiation Therapy (IGRT) for mediastinal HL and formulate practical recommendations based on scientific evidence and expert opinions.

Methods

A dedicated working group was set up within the Fondazione Italiana Linfomi (FIL) Radiotherapy Committee in May 2018. After a first meeting, the group adopted a dedicated platform to share retrieved articles and other material. Two group coordinators redacted a first document draft, that was further discussed and finalized in two subsequent meetings. Topics of interest were: 1) Published data comparing 3D-conformal radiotherapy (3D-CRT) and IMRT 2) dose objectives for the organs at risk 3) IGRT protocols and motion management.

Results

Data review showed that IMRT might allow for an essential reduction in the high-dose regions for all different thoracic OAR. As very few studies included specific dose constraints for lungs and breasts, the low-dose component for these OAR resulted slightly higher with IMRT vs. 3D-CRT, depending on the technique used. We propose a set of dose objectives for the heart, breasts, lungs, and thyroid. The use of IGRT is advised for margin reduction without specific indications, such as the use of breath-holding techniques. An individual approach, including comparative planning and considering different risk factors for late morbidity, is recommended for each patient.

Conclusions

As HL therapy continues to evolve, with an emphasis on treatment reduction, radiation oncologists should use at best all the available tools to minimize the dose to organs at risk and optimize treatment plans. This document provides indications on the use of IMRT/IGRT based on expert consensus, providing a basis for clinical implementation and future development.
Clinical validation of a graphical method for radiation therapy plan quality assessment
Authors: Ventura Tiago , Dias Joana , Khouri Leila , Netto Eduardo , Soares André , da Costa Ferreira Brigida , Rocha Humberto , Lopes Maria do Carmo
Published: March 2020

Background

This work aims at clinically validating a graphical tool developed for treatment plan assessment, named SPIDERplan, by comparing the plan choices based on its scoring with the radiation oncologists (RO) clinical preferences.

Methods

SPIDERplan validation was performed for nasopharynx pathology in two steps. In the first step, three ROs from three Portuguese radiotherapy departments were asked to blindly evaluate and rank the dose distributions of twenty pairs of treatment plans. For plan ranking, the best plan from each pair was selected. For plan evaluation, the qualitative classification of ‘Good’, ‘Admissible with minor deviations’ and ‘Not Admissible’ were assigned to each plan. In the second step, SPIDERplan was applied to the same twenty patient cases. The tool was configured for two sets of structures groups: the local clinical set and the groups of structures suggested in international guidelines for nasopharynx cancer. Group weights, quantifying the importance of each group and incorporated in SPIDERplan, were defined according to RO clinical preferences and determined automatically by applying a mixed linear programming model for implicit elicitation of preferences. Intra- and inter-rater ROs plan selection and evaluation were assessed using Brennan-Prediger kappa coefficient.

Results

Two-thirds of the plans were qualitatively evaluated by the ROs as ‘Good’. Concerning intra- and inter-rater variabilities of plan selection, fair agreements were obtained for most of the ROs. For plan evaluation, substantial agreements were verified in most cases. The choice of the best plan made by SPIDERplan was identical for all sets of groups and, in most cases, agreed with RO plan selection. Differences between RO choice and SPIDERplan analysis only occurred in cases for which the score differences between the plans was very low. A score difference threshold of 0.005 was defined as the value below which two plans are considered of equivalent quality.

Conclusion

Generally, SPIDERplan response successfully reproduced the ROs plan selection. SPIDERplan assessment performance can represent clinical preferences based either on manual or automatic group weight assignment. For nasopharynx cases, SPIDERplan was robust in terms of the definitions of structure groups, being able to support different configurations without losing accuracy.
A population-based propensity-matched study of regional dissections in patients with metastatic osteosarcoma
Authors: Wang Wenjuan , Ding Hongzhi , Sun Zhenyu , Jin Chen , Zhu Yanhui , Wang Xiang
Published: March 2020

Background

The survival rates of patients with metastatic osteosarcoma are poor, and the prognosis is closely related to the choice of treatment, especially surgery. This study aimed to evaluate the survival outcomes of patients with metastatic osteosarcoma undergoing regional dissections.

Methods

We collected data on patients with metastatic osteosarcoma between 2004 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier curves were used to compare overall survival (OS) and cancer-specific survival (CSS), while univariate and multivariate Cox regression analyses were used to evaluate outcomes. Propensity score matching (PSM) was used to minimize the effects of confounding factors.

Results

The SEER database had records of 2768 patients diagnosed with osteosarcoma, of whom 398 were included in our study. Of the included patients, 116 (29.15%) underwent regional dissections, while 282 (70.85%) underwent non-regional dissections. The univariate and multivariate Cox regression analyses, prior to PSM, showed that OS (hazard ratio (HR): 0.34, 95% confidence interval (CI): 0.26–0.44, P<0.001 and HR: 0.47, 95% CI: 0.35–0.64, P<0.001, respectively) and CSS (HR: 0.33, 95% CI: 0.25–0.43, P<0.001 and HR: 0.46, 95% CI: 0.34–0.63, P<0.001, respectively) were better in patients who underwent regional dissections than those who underwent non-regional dissections. Compared with non-regional dissections, regional dissections, which included both primary tumour resection (PTR) and primary tumour and metastatic site resection (PTMR), were associated with better OS (P<0.001) and CSS (P<0.001) . However, the survival outcomes following PTR and PTMR showed no significant difference. After PSM, patients in the regional dissection group still had a higher OS (P<0.001) and CSS (P<0.001) than those in the non-regional dissection group.

Conclusions

Compared with non-regional dissection, regional dissection resulted in better survival in patients with metastatic osteosarcoma.