bluuebunny/crossref_metadata_2025 huggingface dataset:
FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients
Authors: Xie Ning , Tian Can , Wu Hui , Yang Xiaohong , liu Liping , Li Jing , Xiao Huawu , Gao Jianxiang , Lu Jun , Hu Xuming , Cao Min , Shui Zhengrong , Tang Yu , Wang Xiao , Yang Jianbo , Hu Zhe-Yu , Ouyang Quchang
Published: May 2020

Background:

The survival status of patients with breast cancer and brain metastasis (BCBM) receiving current treatments is poor.

Method:

We designed a real-world study to investigate using patients’ clinical and genetic aberrations to forecast the prognoses of BCBM patients. We recruited 146 BCBM patients and analyzed their clinical features to evaluate the overall survival (OS). For genetic testing, 30 BCBM and 165 non-brain-metastatic (BM) metastatic breast cancer (MBC) patients from Hunan Cancer Hospital, and 86 BCBM and 1416 non-BM MBC patients from the Geneplus database who received circulating tumor DNA testing, were compared and analyzed.

Results:

Ki67 >14% and >3 metastatic brain tumors were significant risk factors associated with poor OS, while chemotherapy and brain radiotherapy were beneficial factors for better OS. Compared with non-BM MBC patients, BCBM patients had more fibroblast growth factor receptor ( FGFR) aberrations. The combination of FGFR, TP53 and FLT1 aberrations plus immunohistochemistry HER2-positive were associated with an increased risk of brain metastasis (AUC = 77.13%). FGFR aberration alone was not only a predictive factor (AUC = 67.90%), but also a significant risk factor for poor progression-free survival (Logrank p = 0.029). FGFR1 aberration was more frequent than other FGFR family genes in BCBM patients, and FGFR1 aberration was significantly higher in BCBM patients than non-BM MBC patients. Most FGFR1-amplified MBC patients progressed within 3 months of the late-line (>2 lines) treatment.

Conclusion:

A group of genetic events, including FGFR, TP53 and FLT1 genetic aberrations, and HER2-positivity, forecasted the occurrence of BM in breast cancers. FGFR genetic aberration alone predicted poor prognosis.
Home Away From Home: The Social and Political Roles of Contemporary Chinese Associations in Zambia
Authors: Li Hangwei , Shi Xuefei
Published: May 2020

This article examines the social and political roles of contemporary Chinese associations in Africa with case studies from Zambia. These associations help Chinese migrants better integrate and promote China’s image in Zambian society. More importantly, they proactively engage in bilateral political relations, working with the embassy and state apparatus, defending China’s overseas interests, and providing public goods to the Chinese community. We argue that, because of the associations, Chinese migrants in Zambia are politicised beyond the fact of their living in economic enclaves. Contemporary Chinese associations should thus be recognised as a significant actor and an indispensable intermediary in the rapid evolution of China–Africa relations.
Nonacosan-10-ol and n-Alkanes in Needles of Pinus halepensis
Authors: Nikolić Biljana , Todosijević Marina , Đorđević Iris , Stanković Jovana , Mitić Zorica S. , Tešević Vele , Marin Petar D.
Published: May 2020

In needle cuticular wax of Pinus halepensis, nonacosan-10-ol is high (77.08% on average). n-Alkanes ranged from C18 to C35 with the most dominant C27 and C29 (32.4% and 25.8%, respectively). The carbon preference index ranged from 3.2 to 5.4 (3.4 on average), while the average chain length ranged from 14.0 to 18.0 (17.2 on average). Long-chain n-alkanes strongly dominated (95.1%).
A Survey of Antifungal Activity of Selected South African Plant Species Used for the Treatment of Skin Infections
Authors: Shikwambana Ndzalama , Mahlo Salome Mamokone
Published: May 2020

Dermatophytosis is a fungal infection of the skin caused by a group of pathogenic fungi known as dermatophytes. Therefore, we investigated those medicinal plants that were being used by local people and traditional healers to treat skin infections in the Mopani District, Limpopo Province. A survey was conducted through the use of a semistructured program to gather information on the common names, plant parts used, methods of preparation, and administration of the medicine. Findings of the survey revealed that over 30 plant species were used for the treatment of skin infections in the area. The most common local mode of medicinal preparation to treat skin was decoction (37%), followed by paste (21%), infusion (19%), poultice (9%), smoke (7%), maceration (5%), and steam (2%). Of the species, only 12 ( Ficus sur L., Peltophorum africanum Sond., Vangueria infausta Burch. subsp. infausta, Diospyros mespilliformis Hochst. ex. A. DC., Ziziphus mucronata Willd. subsp. mucronata, Euclea divinorum Hiern, Ximenia caffra Sond., Dombeya rotundifolia Hochst., Ficus sycomorus L., Sideroxylon inerme L. subsp inerme, Parinari curattellifolia Planch. ex Benth., and Maytenus undata (Thunb.) Blakelock) were selected based on literature and ethnobotanical information. We further investigated the antifungal activity of acetone and aqueous extracts of the above mentioned selected plant species using serial dilution assay against Trichophyton rubrum, Microsporum canis, and Candida albicans. All plant extracts were active against the tested microorganisms with minimum inhibitory concentration (MIC) values ranging between 0.02 mg/mL and 1.25 mg/mL. In the bioautography assay, more active compounds were visible in acetone and water extracts of E. divinorum. No active compounds were observed in some plant extracts with excellent antifungal activity, as shown in the microdilution assay. Findings, in general, suggest that the identified plant species, especially those with extracts showing relatively low MIC values, are playing a big role in treating skin infections in Mopani District.
Pulling Back the Curtain on Moral Reasoning and Ethical Leadership Development for K–12 School Leaders
Authors: Gurley D. Keith , Dagley Amy
Published: May 2020

Using the Defining Issues Test of moral reasoning, researchers gathered pre- and posttest data from educational leadership students ( N = 52) and confidence levels in enacting ethical school leadership, before and after completing a master’s degree program in educational leadership. On a 95-point scale, pretest, postconventional moral reasoning abilities were calculated at M = 33.57. Significantly higher posttest, postconventional moral reasoning ( M = 38.80) was determined. Respondent confidence levels in enacting ethical leadership also increased dramatically. Moral reasoning abilities measured far lower than would be expected compared with national norms of adults who had achieved similar levels of education in other professional areas.
Impact of Service Quality on Customer Loyalty and Customer Satisfaction in Islamic Banks in the Sultanate of Oman
Authors: Fida Bashir Ahmad , Ahmed Umar , Al-Balushi Yousuf , Singh Dharmendra
Published: May 2020

This study attempts to examine the impact of service quality on customer loyalty and customer satisfaction using the SERVQUAL model for four main Islamic banks in the Sultanate of Oman. This is a quantitative nature of a study, which involved a structured, self-administered questionnaire based on a convenience sampling method gathering data from 120 customers of Islamic banks in Oman. The study data were analyzed using SPSS, and the reliability coefficient (Cronbach’s alpha) was established. The correlation analysis examined the significant relationships among the study variables. The impact of service quality dimensions on customer satisfaction was captured through regression analysis. The key findings of the study revealed that the respondents showed on average an “Agree” response in the five areas, namely, tangibles, responsiveness, reliability, assurance, and empathy. The correlation results depicted a significant relationship between the three variables: service quality, customer satisfaction, and customer loyalty. Similarly, regression results demonstrated that empathy and responsiveness dimensions have a significant positive impact on customer satisfaction. It is, therefore, recommended that banks should focus more on empathy and responsiveness considering the significant relationship of these two variables on customer satisfaction. However, banks should not neglect the importance of other variables such as reliability, assurance, and tangibles that are revealed as important by responses of the participants for the bank’s provisions.
International Law and Humanitarian Intervention in the Syrian Civil War: The Role of the United States
Authors: Ogunnowo Oluwaseyi Emmanuel , Chidozie Felix
Published: May 2020

This article interrogates the legality of American interventions in the Syrian conflict. The Syrian civil war stands as one of the most controversial conflicts of the 21st century, owing to the mass destruction of lives and properties and the multiplicity of interventions which have created numerous strands of the conflict. The United States as one of the intervening powers has shown support for the rebel forces geared at toppling the Assad government. The research adopts the qualitative method and utilizes the case study research design. The research makes use of secondary data as derived from academic journals, books, book chapters, newspapers, and so on and analyzes these data through the use of thematic analysis. The findings of the study reveal that the interventions of the United States are not legal. The study also finds that the United States possesses certain strategic interests in the Syrian conflict which it aims to achieve.
Why Did You Not Act on Our Suggestion? Regulatory and Growth-Oriented Opportunities During Ethical Review: A Case Study
Authors: Dicks Sean G. , Pieper Ian J. , Northam Holly L. , van Haren Frank M. P. , Boer Douglas P.
Published: May 2020

In Australia, before conducting research with human participants, researchers must have their research plan reviewed by a Human Research Ethics Committee (HREC) to ensure that proposed methods meet ethical requirements and protect the welfare of participants. In addition, it has been proposed that HRECs can contribute to a novice researcher’s ethical mindfulness. To explore this suggestion, the current self-reflective case study examines the dialogue between a PhD candidate and the HREC that reviewed his proposed study of family bereavement in the context of the potential for organ donation. Findings suggest that when a respectful, problem-solving attitude is adopted by both parties, a learning environment evolves where diverse views, differences of opinion, and novel solutions are tolerated. In this context, the research plan is improved and the novice researcher’s ability to apply research ethics is developed. Simultaneously, members of the HREC gain practice in the identification of ethical dilemmas and the application of ethical principles that help resolve those dilemmas.
Great Expectations: A Regional Study of Entrepreneurship Among Romanian Return Migrants
Authors: Croitoru Alin
Published: May 2020

This article examines the main determinants for entrepreneurial activities among return migrants in a regional context within Romania. The analytical framework is based on conceptual tools provided by the intersection of entrepreneurship theory and return migration research. The study aimed to answer a set of research questions regarding migrant individuals’ probability for entrepreneurial careers upon return, and Romania constitutes a fertile European origin country for testing them. Returnees are perceived as one of the main transformational forces within the country, and great expectations are related to their entrepreneurial orientation. We test this general assumption using survey data collected from 840 returnees and several logistic regression models which included variables about employment status before the individuals’ first migration, country of destination, length of stay abroad, return reasons, use of savings, and sociodemographics. Individuals’ characteristics as well as features of the migration experiences were found to be highly relevant for predicting the chances of migrants entering into entrepreneurship upon return.
The benefits and harms of therapeutic exercise on physical and psychosocial outcomes in people with multimorbidity: Protocol for a systematic review
Authors: Bricca Alessio , Harris Lasse K , Saracutu Madalina , Smith Susan M , Juhl Carsten B , Skou Søren T
Published: May 2020

Aim:

The aim of this study is to investigate the benefits and harms of therapeutic exercise in people with multimorbidity defined as the combination of two or more of the following conditions: knee and hip osteoarthritis, hypertension, diabetes type 2, depression, heart failure, ischaemic heart disease and chronic obstructive pulmonary disease, by performing a systematic review of randomized controlled trials (RCTs).

Methods:

This study will be performed according to the recommendations from the Cochrane Collaboration and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We will search for RCTs investigating the effect of therapeutic exercise in multimorbidity, as defined above, in MEDLINE, EMBASE, CENTRAL and CINAHL from 1990. Cochrane reviews on the effect of therapeutic exercise for each of the aforementioned conditions and references of the included studies will be checked for eligible studies and citation tracking will be performed in Web of Science. We will assess the risk of bias of the included studies using the Cochrane ‘Risk of Bias Tool’ 2.0 and the Grading of Recommendations Assessment, Development and Evaluation assessment for judging the overall quality of evidence. Meta-analyses will be performed, if possible, using a random-effects model as heterogeneity is expected due to differences in interventions and participant characteristics and outcome measures. Subgroup and meta-regression analyses will be performed to explore potential predictors of outcomes.

Dissemination:

The results of this systematic review will be published in a peer-review journal, presented at national and international conferences and made available to end users via infographics, podcasts, press releases and videos.
The Influence of Patient–Provider Communication on Cancer Screening
Authors: Kindratt Tiffany B , Atem Folefac , Dallo Florence J , Allicock Marlyn , Balasubramanian Bijal A
Published: May 2020

Few studies have examined how different qualities and modes (face-to-face vs electronic) of patient–provider communication (PPC) influence cancer screening uptake. Our objective was to determine whether receiving a breast, cervical, and colorectal cancer screening is influenced by (1) qualities of face-to-face and (2) the use of e-mail PPC. We analyzed Health Information National Trends Survey 4, cycles 1 to 4 data. To assess qualities of face-to-face PPC, adults reported how often physicians spent enough time with them, explained so they understood, gave them a chance to ask questions, addressed feelings and emotions, involved them in decisions, confirmed understanding, and helped them with uncertainty. Adults reported whether they used e-mail PPC. We used multivariable logistic regression to evaluate the odds of receiving cancer screenings based on face-to-face and e-mail PPC. Adults whose health-care providers involved them in decision-making had highest odds of receiving breast (odds ratio [OR] = 1.38; 95% confidence interval [CI] = 1.11-1.71), cervical (OR = 1.30; 95% CI = 1.06-1.60), and colorectal (OR = 1.25; 95% CI = 1.03-1.51) cancer screenings. No significant associations were observed between e-mail PPC and cancer screenings. More research is needed to explore this association.
Estimations of the moisture content above the fiber saturation point in sugi wood using the correlation between the specific dynamic Young’s modulus and tangent loss
Authors: Fukui Toshiyuki , Yanase Yoshiyuki , Sawada Yutaka , Fujii Yoshihisa
Published: May 2020

A novel method for estimating the wood moisture content above the fiber saturation point (FSP) is proposed, and the method performance is confirmed. Previous studies have highlighted that there is a negative linear correlation between the specific dynamic Young’s modulus (log (E/ρ)) and tangent loss (log (tanδ)) of clear small wood specimens. We confirm that this correlation can be obtained for air-dried commercial lumber from Japanese cedar, or sugi (Cryptomeria japonica), via experimental analysis. The best-fit linear regression line of this correlation only changes by the apparent density above the FSP (i.e., only by the moisture content of the specimen) when E and tanδ are kept constant in this high moisture content range. Here, we derive an equation to calculate the moisture content using log (E/ρ) and log (tanδ) based on the regression line of sugi wood at the FSP. A 45-day drying test was conducted on 23 green lumber specimens, with the E/ρ and tanδ values calculated from the natural resonance frequency fr, the logarithmic decrement λ and dimensions at various drying stages. The estimated moisture contents are in good agreement with the measured values, confirming the performance of proposed moisture content method.
Duodenal perforations secondary to a migrated biliary plastic stent successfully treated by endoscope: case-report and review of the literature
Authors: Wang Xiaopeng , Qu Junwen , Li Kewei
Published: May 2020

Background

Endoscopic retrograde biliary drainage (ERBD) is the most frequently performed procedure for treating benign or malignant biliary obstruction. Although duodenal perforations secondary to the biliary plastic stent are quite rare, they can be life-threatening. The treatment strategies for such perforations are diverse and continue to be debated.

Case presentation

We report three cases of duodenal perforation due to the migration of biliary plastic stents that were successfully managed using an endoscope. The three patients were admitted on complaints of abdominal pain after they underwent ERBD. Abdominal computerized tomography (CT) revealed migration of the biliary plastic stents and perforation of the duodenum. Endoscopy was immediately performed, and perforation was confirmed. All migrated stents were successfully extracted endoscopically by using snares. In two of the three cases, the duodenal defects were successfully closed with haemostatic clips after stent retrieval, and subsequently, endoscopic nasobiliary drainage tubes were inserted. After the endoscopy and medical treatment, all three patients recovered completely.

Conclusions

Duodenal perforations due to the migration of biliary stents are rare, and the treatment strategies remain controversial. Our cases and cases in the literature demonstrate that abdominal CT is the preferred method of examination for such perforations, and endoscopic management is appropriate as a first-line treatment approach.
The burden of laboratory-confirmed influenza infection in Lebanon between 2008 and 2016: a single tertiary care center experience
Authors: Assaf-Casals Aia , Saleh Zeina , Khafaja Sarah , Fayad Danielle , Ezzeddine Hady , Saleh Mohammad , Chamseddine Sarah , Sayegh Rouba , Sharara Sima L. , Chmaisse Ahmad , Kanj Souha S. , Kanafani Zeina , Hanna-Wakim Rima , Araj George F. , Mahfouz Rami , Saito Reiko , Suzuki Hiroshi , Zaraket Hassan , Dbaibo Ghassan S.
Published: May 2020

Background

Influenza is a major cause of morbidity and mortality worldwide. Following the 2009 pandemic, there was widened interest in studying influenza burden in all regions. However, since data from the World Health Organization (WHO) Middle East and North Africa (MENA) region remain limited, we aimed to contribute to the understanding of influenza burden in Lebanon.

Methods

A retrospective chart review extending over a period of 8 seasons from Jan 1st, 2008 till June 30th, 2016 at a tertiary care center in Beirut was performed. All cases confirmed to have influenza based on rapid antigen detection or/and polymerase chain reaction on a respiratory sample were included for analysis. Data on epidemiology, clinical presentation, complications, antiviral use and mortality were collected for analysis.

Results

A total of 1829 cases of laboratory-confirmed influenza were identified. Average annual positivity rate was 14% (positive tests over total requested). Both influenza A and B co-circulated in each season with predominance of influenza A. Influenza virus started circulating in December and peaked in January and February. The age group of 19–50 years accounted for the largest proportion of cases (22.5%) followed by the age group of 5–19 years (18%). Pneumonia was the most common complication reported in 33% of cases. Mortality reached 3.8%. The two extremes of age (< 2 years and ≥ 65 years) were associated with a more severe course of disease, hospitalization, intensive care unit (ICU) admission, complications, and mortality rate. Of all the identified cases, 26% were hospitalized. Moderate-to-severe disease was more likely in influenza B cases but no difference in mortality was reported between the two types. Antivirals were prescribed in 68.8% and antibiotics in 41% of cases. There seemed to be an increasing trend in the number of diagnosed and hospitalized cases over the years of the study.

Conclusion

Patients with laboratory-confirmed influenza at our center had a high rate of hospitalization and mortality. A population based prospective surveillance study is needed to better estimate the burden of Influenza in Lebanon that would help formulate a policy on influenza control.
Burnout syndrome among nephrologists - a burning issue – results of the countrywide survey by the Polish Society of Nephrology
Authors: Pawłowicz Ewa , Nowicki Michał
Published: May 2020

Background

Burnout syndrome in physicians is associated with adverse patient safety events, poorer quality of care and reduced patients’ satisfaction. There has been scarce information on the risk factors of burnout affecting professionals working in the renal care settings. As yet the phenomenon has not been studied in the population of Polish nephrologists therefore a nationwide cross-sectional study was established by the Polish Society of Nephrology to assess the prevalence of the syndrome.

Methods

The survey, that consisted of the abbreviated Maslach Burnout Inventory, questions about strategies for dealing with burnout symptoms and demographic data, was distributed during two main national meetings that gather nephrologists in Poland. 177 participants filled out the survey – 64% of participants were women, 88% were specialists and 12% - doctors in training.

Results

52% of participants demonstrated a high level of depersonalization and almost half of the study group showed high level of emotional exhaustion. Reduced personal accomplishment was more pronounced in doctors working mostly in dialysis units compared to other nephrologists (p = 0.017). 37% of participants reported that they treat some patients as they were impersonal objects and 48% felt emotionally drained from their work. 59% of participants would like to take part in the remedy program.

Conclusions

Burnout syndrome seems to be an important problem in the population of Polish nephrologists. Doctors working mostly in dialysis settings might be at increased risk of reduced personal accomplishment. The results of the survey may be useful to prepare burnout remedy program.
Trends in diabetes-related complications in Hong Kong, 2001–2016: a retrospective cohort study
Authors: Wu Hongjiang , Lau Eric S. H. , Yang Aimin , Ma Ronald C. W. , Kong Alice P. S. , Chow Elaine , So Wing-Yee , Chan Juliana C. N. , Luk Andrea O. Y.
Published: May 2020

Background

Nationwide studies on contemporary trends in incidence of diabetes-related complications in Asia are lacking. We describe trends in incident coronary heart disease (CHD), stroke, heart failure, hyperglycaemic crisis, and lower-extremity amputation (LEA) in people with diabetes in Hong Kong between 2001 and 2016.

Methods

The Hong Kong Diabetes Surveillance Database (HKDSD) is a territory-wide diabetes cohort identified from Hong Kong Hospital Authority electronic medical record system. We identified events of CHD, stroke, heart failure and hyperglycaemic crisis using hospital principal diagnosis codes at discharge and that of LEA using inpatient procedure codes. We used Joinpoint regression analysis to describe incidence trends by age and sex.

Results

Between 2001 and 2016, a total of 390,071 men and 380,007 women aged 20 years or older with diabetes were included in the HKDSD. Event rates of CHD, stroke, heart failure, hyperglycaemic crisis and LEA declined by 69.4% (average annual percent change: − 7.6, 95% CI − 10.2, − 5.0), 70.3% (− 8.7, 95% CI − 9.8, − 7.5), 63.6% (− 6.4, 95% CI − 8.0, − 4.7), 59.1% (− 6.6, 95% CI − 12.4, − 0.44), and 67.5% (− 5.8, 95% CI − 7.2, − 4.4), in men and by 77.5% (− 9.9, 95% CI − 11.8, − 7.9), 74.5% (− 9.0, 95% CI − 9.6, − 8.4), 65.8% (− 7.0, 95% CI − 8.0, − 6.0), 81.7% (− 8.5, 95% CI − 10.5, − 6.5), and 72.7% (− 9.1. 95% CI − 12.2, − 5.8) in women, respectively, over a 16-year period in people with diabetes in Hong Kong. Joinpoint analysis identified greater declines in event rates of the five diabetes-related complications in the earlier one-third of study period and slowed down but remained significant until 2016. Event rates decreased for all age groups above 45 years for both sexes. There was no significant change in event rates in the group aged 20–44 years except for decline in hyperglycaemic crisis.

Conclusions

The event rates of diabetes-related complications have declined substantially with no evidence of stabilization or increase in Hong Kong up to 2016. Improvements in outcome were observed for all age subgroups but not in young people with diabetes, calling for urgent action to improve quality of care to prevent complications in young people at risk.
CRNDE: an oncogenic long non-coding RNA in cancers
Authors: Lu Ya , Sha Huanhuan , Sun Xun , Zhang Yuan , Wu Yang , Zhang Junying , Zhang Hui , Wu Jianzhong , Feng Jifeng
Published: May 2020

Colorectal neoplasia differentially expressed (CRNDE) is a long non-coding RNA which has been proved upregulated in various cancers. Meanwhile, CRNDE has been demonstrated to be involved in multiple biological processes of different cancers according to previous study. Moreover, recent studies suggested CRNDE might be a potential diagnostic biomarker and prognostic predictor due to its high sensitivity and specificity in cancer tissues and plasma. In this review, we summarize the biological function of CRNDE and the relevant mechanisms in cancers to establish a molecular basis for the clinical use of CRNDE in the future.
How is the minimal clinically important difference established in health-related quality of life instruments? Review of anchors and methods
Authors: Mouelhi Yosra , Jouve Elisabeth , Castelli Christel , Gentile Stéphanie
Published: May 2020

Background

The aim of this systematic review is to describe the different types of anchors and statistical methods used in estimating the Minimal Clinically Important Difference (MCID) for Health-Related Quality of Life (HRQoL) instruments.

Methods

PubMed and Google scholar were searched for English and French language studies published from 2010 to 2018 using selected keywords. We included original articles (reviews, meta-analysis, commentaries and research letters were not considered) that described anchors and statistical methods used to estimate the MCID in HRQoL instruments.

Results

Forty-seven papers satisfied the inclusion criteria. The MCID was estimated for 6 generic and 18 disease-specific instruments. Most studies in our review used anchor-based methods (n = 41), either alone or in combination with distribution-based methods. The most common applied anchors were non-clinical, from the viewpoint of patients. Different statistical methods for anchor-based methods were applied and the Change Difference (CD) was the most used one. Most distributional methods included 0.2 standard deviations (SD), 0.3 SD, 0.5 SD and 1 standard error of measurement (SEM). MCID values were very variable depending on methods applied, and also on clinical context of the study.

Conclusion

Multiple anchors and methods were applied in the included studies, which lead to different estimations of MCID. Using several methods enables to assess the robustness of the results. This corresponds to a sensitivity analysis of the methods. Close collaboration between statisticians and clinicians is recommended to integrate an agreement regarding the appropriate method to determine MCID for a specific context.
Chondromesenchymal hamartomas in a 24-year-old male mimicking a posterior mediastinal tumor and a 5-month-old boy with postoperative disseminated intravascular coagulation: two case reports
Authors: Li Yue , Zheng Danyang , Zuo Min , Li Yang , Zhang Huizhong
Published: May 2020

Background

Chondromesenchymal hamartoma of the chest wall is a rare, benign disease that usually presents at birth or in early infancy. It typically involves one or more ribs, forming a unilateral or bilateral extrapleural mass. Patients may be asymptomatic or complain of mild respiratory distress depending on tumor size and location. To the best of our knowledge, only two of the approximately 100 cases reported so far are adults.

Case presentation

We present two cases of chondromesenchymal hamartoma. The first case involved the left fifth rib in a 24-year-old male, in close proximity to the fifth vertebral body in the left posterior mediastinum, mimicking a posterior mediastinal tumor on imaging. The tumor was excised via thoracoscopy and the patient had an uneventful postoperative course. The second case was that of a 5-month-old boy, who had a tumor involving the left fifth and sixth ribs which caused thoracic cage collapse. Following en bloc resection of the tumor and the involved rib segments, the patient was transferred to the intensive care unit for treatment of pulmonary infection and disseminated intravascular coagulation (DIC). He was discharged from the hospital in stable condition 11 days later. On histopathology, the tumor was found to be a chondromesenchymal hamartoma with immature spindle-shaped mesenchymal cells, plate-like hyaline cartilage, areas of woven bone formation, endochondral ossification and calcification, osteoclastic giant cells, and secondary aneurysmal bone cysts.

Conclusions

Although the presently reported cases have morphological characteristics similar to previously reported ones, they had distinct radiological and clinical characteristics. Patient 1 is only the third report of an adult with chondromesenchymal hamartoma. His case was characterized by its radiological appearance mimicking a posterior mediastinal tumor. Patient 2 represents the first documentation of DIC as a postoperative complication following excision of a chondromesenchymal hamartoma. We present these two cases to provide clinicopathological insights regarding this extremely rare tumor that are relevant to both pathologists and clinicians.
A novel bispecific antibody targeting CD3 and prolactin receptor (PRLR) against PRLR-expression breast cancer
Authors: Zhou Yuexian , Zong Huifang , Han Lei , Xie Yueqing , Jiang Hua , Gilly John , Zhang Baohong , Lu Huili , Chen Jie , Sun Rui , Pan Zhidi , Zhu Jianwei
Published: May 2020

Background

Prolactin receptor (PRLR) is highly expressed in a subset of human breast cancer and prostate cancer, which makes it a potential target for cancer treatment. In clinical trials, the blockade of PRLR was shown to be safe but with poor efficacy. It is therefore urgent to develop new therapies against PRLR target. Bispecific antibodies (BsAbs) could guide immune cells toward tumor cells, and produced remarkable effects in some cancers.

Methods

In this study, a bispecific antibody targeting both tumor antigen PRLR and T cell surface CD3 antigen (PRLR-DbsAb) was constructed by split intein mediated protein transsplicing (BAPTS) system for the first time. Its binding activity was determined by Biacore and Flow cytometry, and target-dependent T cell mediated cytotoxicity was detected using LDH release assay. ELISA was utilized to study the secretion of cytokines by immune cells. Subcutaneous tumor mouse models were used to analyze the in vivo anti-tumor effects of PRLR-DbsAb.

Results

PRLR-DbsAb in vitro could recruit and activate T cells to promote the release of Th1 cytokines IFN-γand TNF-α, which could kill PRLR expressed breast cancer cells. In xenograft models with breast cancer cell line T47D, NOD/SCID mice intraperitoneally injected with PRLR-DbsAb exhibited significant inhibition of tumor growth and a longer survival compared to mice treated with PRLR monoclonal antibody (PRLR mAb).

Conclusions

Both in vitro and in vivo experiments showed PRLR-DbsAb had a potential therapy of cancer treatment potential therapy for cancer. Immunotherapy may be a promising treatment against the tumor target of PRLR.
Drug repurposing against COVID-19: focus on anticancer agents
Authors: Ciliberto Gennaro , Mancini Rita , Paggi Marco G.
Published: May 2020

Background

The very limited time allowed to face the COVID-19 pandemic poses a pressing challenge to find proper therapeutic approaches. However, synthesis and full investigation from preclinical studies to phase III trials of new medications is a time-consuming procedure, and not viable in a global emergency, such as the one we are facing.

Main Body

Drug repurposing/repositioning, a strategy effectively employed in cancer treatment, can represent a valid alternative. Most drugs considered for repurposing/repositioning in the therapy of the COVID-19 outbreak are commercially available and their dosage and toxicity in humans is well known, due to years (or even decades) of clinical use. This can allow their fast-track evaluation in phase II–III clinical trials, or even within straightforward compassionate use.

Several drugs being re-considered for COVID-19 therapy are or have been used in cancer therapy. Indeed, virus-infected cells are pushed to enhance the synthesis of nucleic acids, protein and lipid synthesis and boost their energy metabolism, in order to comply to the “viral program”. Indeed, the same features are seen in cancer cells, making it likely that drugs interfering with specific cancer cell pathways may be effective as well in defeating viral replication.

Short Conclusion

To our knowledge, cancer drugs potentially suitable for facing SARS-CoV-2 infection have not been carefully reviewed. We present here a comprehensive analysis of available information on potential candidate cancer drugs that can be repurposed for the treatment of COIVD-19.
Association of helicopter transportation and improved mortality for patients with major trauma in the northern French Alps trauma system: an observational study based on the TRENAU registry
Authors:   for the TRENAU Group, Ageron Francois-Xavier , Debaty Guillaume , Savary Dominique , Champly Frederic , Albasini Francois , Usseglio Pascal , Vallot Cécile , Galvagno Samuel , Bouzat Pierre
Published: May 2020

Background

Prompt prehospital triage and transportation are essential in an organised trauma system. The benefits of helicopter transportation on mortality in a physician-staffed pre-hospital trauma system remains unknown. The aim of the study was to assess the impact of helicopter transportation on mortality and prehospital triage.

Methods

Data collection was based on trauma registry for all consecutive major trauma patients transported by helicopter or ground ambulance in the Northern French Alps Trauma system between 2009 and 2017. The primary endpoint was in-hospital death. We performed multivariate logistic regression to compare death between helicopter and ground ambulance.

Results

Overall, 9458 major trauma patients were included. 37% (n = 3524) were transported by helicopter, and 56% (n = 5253) by ground ambulance. Prehospital time from the first call to the arrival at hospital was longer in the helicopter group compared to the ground ambulance group, respectively median time 95 [72–124] minutes and 85 [63–113] minutes (P < 0.001). Median transport time was similar between groups, 20 min [13–30] for helicopter and 21 min [14–32] for ground ambulance. Using multivariate logistic regression, helicopter was associated with reduced mortality compared to ground ambulance (adjusted OR 0.70; 95% CI, 0.53–0.92; P = 0.01) and with reduced undertriage (OR 0.69 95% CI, 0.60–0.80; P < 0.001).

Conclusion

Helicopter was associated with reduced in-hospital death and undertriage by one third. It did not decrease prehospital and transport times in a system with the same crew using both helicopter or ground ambulance. The mortality and undertriage benefits observed suggest that the helicopter is the proper mode for long-distant transport to a regional trauma centre.
Nitrous oxide/oxygen plus acetaminophen versus morphine in ST elevation myocardial infarction: open-label, cluster-randomized, non-inferiority study
Authors:   for the SCADOL II investigators, Charpentier Sandrine , Galinski Michel , Bounes Vincent , Ricard-Hibon Agnès , El-Khoury Carlos , Elbaz Meyer , Ageron François-Xavier , Manzo-Silberman Stéphane , Soulat Louis , Lapostolle Frédéric , Gérard Alexandre , Bregeaud Delphine , Bongard Vanina , Bonnefoy-Cudraz Eric
Published: May 2020

Background

Studies have shown disparate results on the consequences of morphine use in ST-segment elevation myocardial infarction (STEMI). No study has evaluated alternative treatments that could be at least non-inferior to morphine without its potentially damaging consequences for myocardial function and platelet reactivity. The aim of this study was to evaluate whether nitrous oxide/oxygen plus intravenous acetaminophen (NOO-A) is non-inferior to morphine to control chest pain in STEMI patients.

Methods

This multicenter, open-label, cluster-randomized, controlled, non-inferiority study compared NOO-A with morphine in 684 prehospital patients with ongoing suspected STEMI of < 12 h duration and a pain rating score ≥ 4. The primary endpoint was the proportion of patients achieving pain relief (numeric rating score ≤ 3) after 30 min. Secondary safety endpoints included serious adverse events and death at 30 days.

Results

The median baseline pain score was 7.0 in both groups. The primary endpoint occurred in 51.7% of the NOO-A group and 73.6% of the morphine group (absolute risk difference − 21.7%; 95% confidence interval − 29.6 to − 13.8). At 30 days, the rate of serious adverse events was 16.0 and 18.8% in the NOO-A and morphine groups respectively (p = NS). The rate of death was 1.8% (NOO-A group) and 3.8% (morphine group) (p = NS).

Conclusion

Analgesia provided by NOO-A was inferior to morphine at 30 min in patients with acute STEMI in the prehospital setting. Rates of serious adverse events did not differ between groups.

Trial registration

ClinicalTrials.gov: NCT02198378.
Terminating contamination: large-scale search identifies more than 2,000,000 contaminated entries in GenBank
Authors: Steinegger Martin , Salzberg Steven L.
Published: May 2020

Genomic analyses are sensitive to contamination in public databases caused by incorrectly labeled reference sequences. Here, we describe Conterminator, an efficient method to detect and remove incorrectly labeled sequences by an exhaustive all-against-all sequence comparison. Our analysis reports contamination of 2,161,746, 114,035, and 14,148 sequences in the RefSeq, GenBank, and NR databases, respectively, spanning the whole range from draft to “complete” model organism genomes. Our method scales linearly with input size and can process 3.3 TB in 12 days on a 32-core computer. Conterminator can help ensure the quality of reference databases. Source code (GPLv3):https://github.com/martin-steinegger/conterminator
An antibiotic stewardship programme to reduce inappropriate antibiotic prescribing for acute respiratory infections in rural Chinese primary care facilities: study protocol for a clustered randomised controlled trial
Authors: Zhuo Chao , Wei Xiaolin , Zhang Zhitong , Hicks Joseph Paul , Zheng Jinkun , Chen Zhixu , Haldane Victoria , Walley John , Guan Yubao , Xu Hongyan , Zhong Nanshan
Published: May 2020

Background

Inappropriate prescribing of antibiotics for acute respiratory infections at the primary care level represents the major source of antibiotic misuse in healthcare, and is a major driver for antimicrobial resistance worldwide. In this study we will develop, pilot and evaluate the effectiveness of a comprehensive antibiotic stewardship programme in China’s primary care hospitals to reduce inappropriate prescribing of antibiotics for acute respiratory infections among all ages.

Methods

We will use a parallel-group, cluster-randomised, controlled, superiority trial with blinded outcome evaluation but unblinded treatment (providers and patients). We will randomise 34 primary care hospitals from two counties within Guangdong province into the intervention and control arm (1:1 overall ratio) stratified by county (8:9 within-county ratio). In the control arm, antibiotic prescribing and management will continue through usual care. In the intervention arm, we will implement an antibiotic stewardship programme targeting family physicians and patients/caregivers. The family physician components include: (1) training using new operational guidelines, (2) improved management and peer-review of antibiotic prescribing, (3) improved electronic medical records and smart phone app facilitation. The patient/caregiver component involves patient education via family physicians, leaflets and videos. The primary outcome is the proportion of prescriptions for acute respiratory infections (excluding pneumonia) that contain any antibiotic(s). Secondary outcomes will address how frequently specific classes of antibiotics are prescribed, how frequently key non-antibiotic alternatives are prescribed and the costs of consultations. We will conduct a qualitative process evaluation to explore operational questions regarding acceptability, cultural appropriateness and burden of technology use, as well as a cost-effectiveness analysis and a long-term benefit evaluation. The duration of the intervention will be 12 months, with another 24 months’ post-trial long-term follow-up.

Discussion

Our study is one of the first trials to evaluate the effect of an antibiotic stewardship programme in primary care settings in a low- or middle-income country (LMIC). All interventional activities will be designed to be embedded into routine primary care with strong local ownership. Through the trial we intend to impact on clinical practice and national policy in antibiotic prescription for primary care facilities in rural China and other LMICs.

Trial registration

ISRCTN, ID: ISRCTN96892547. Registered on 18 August 2019.
Transgenerational epigenetic effects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals
Authors: Van Cauwenbergh Olivia , Di Serafino Alessandra , Tytgat Jan , Soubry Adelheid
Published: May 2020

Assessing long-term health effects from a potentially harmful environment is challenging. Endocrine-disrupting compounds (EDCs) have become omnipresent in our environment. Individuals may or may not experience clinical health issues from being exposed to the increasing environmental pollution in daily life, but an issue of high concern is that also the non-exposed progeny may encounter consequences of these ancestral exposures. Progress in understanding epigenetic mechanisms opens new perspectives to estimate the risk of man-made EDCs. However, the field of epigenetic toxicology is new and its application in public health or in the understanding of disease etiology is almost non-existent, especially if it concerns future generations. In this review, we investigate the literature on transgenerational inheritance of diseases, published in the past 10 years. We question whether persistent epigenetic changes occur in the male germ line after exposure to synthesized EDCs. Our systematic search led to an inclusion of 43 articles, exploring the effects of commonly used synthetic EDCs, such as plasticizers (phthalates and bisphenol A), pesticides (dichlorodiphenyltrichloroethane, atrazine, vinclozin, methoxychlor), dioxins, and polycyclic aromatic hydrocarbons (PAHs, such as benzo(a)pyrene). Most studies found transgenerational epigenetic effects, often linked to puberty- or adult-onset diseases, such as testicular or prostate abnormalities, metabolic disorders, behavioral anomalies, and tumor development. The affected epigenetic mechanisms included changes in DNA methylation patterns, transcriptome, and expression of DNA methyltransferases. Studies involved experiments in animal models and none were based on human data. In the future, human studies are needed to confirm animal findings. If not transgenerational, at least intergenerational human studies and studies on EDC-induced epigenetic effects on germ cells could help to understand early processes of inheritance. Next, toxicity tests of new chemicals need a more comprehensive approach before they are introduced on the market. We further point to the relevance of epigenetic toxicity tests in regard to public health of the current population but also of future generations. Finally, this review sheds a light on how the interplay of genetics and epigenetics may explain the current knowledge gap on transgenerational inheritance.
Promoter methylation changes in ALOX12 and AIRE1: novel epigenetic markers for atherosclerosis
Authors: Kim Jee Yeon , Choi Bong-Geun , Jelinek Jaroslav , Kim Dae Hyun , Lee Seo Hyun , Cho Kwangjo , Rha Seo Hee , Lee Young Ho , Jin Hyo Sun , Choi Dae-Kyoung , Kim Geun-Eun , Kwon Sun U. , Hwang Junha , Cha Jae Kwan , Lee Sukhoon , Issa Jean-Pierre J. , Kim Jei
Published: May 2020

Background

Atherosclerosis is the main cause of cardiovascular diseases such as ischemic stroke and coronary heart disease. Gene-specific promoter methylation changes have been suggested as one of the causes underlying the development of atherosclerosis. We aimed to identify and validate specific genes that are differentially expressed through promoter methylation in atherosclerotic plaques. We performed the present study in four steps: (1) profiling and identification of gene-specific promoter methylation changes in atherosclerotic tissues; (2) validation of the promoter methylation changes of genes in plaques by comparison with non-plaque intima; (3) evaluation of promoter methylation status of the genes in vascular cellular components composing atherosclerotic plaques; and (4) evaluation of promoter methylation differences in genes among monocytes, T cells, and B cells isolated from the blood of ischemic stroke patients.

Results

Upon profiling, AIRE1, ALOX12, FANK1, NETO1, and SERHL2 were found to have displayed changes in promoter methylation. Of these, AIRE1 and ALOX12 displayed higher methylation levels in plaques than in non-plaque intima, but lower than those in the buffy coat of blood. Between inflammatory cells, the three genes were significantly less methylated in monocytes than in T and B cells. In the vascular cells, AIRE1 methylation was lower in endothelial and smooth muscle cells. ALOX12 methylation was higher in endothelial, but lower in smooth muscle cells. Immunofluorescence staining showed that co-localization of ALOX12 and AIRE1 was more frequent in CD14(+)-monocytes than in CD4(+)-T cell in plaque than in non-plaque intima.

Conclusions

Promoter methylation changes in AIRE1 and ALOX12 occur in atherosclerosis and can be considered as novel epigenetic markers.