bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of long-term treatment of Carvacrol on glucose metabolism in Streptozotocin-induced diabetic mice
Authors: Li Yilang , Mai Yunpei , Qiu Xiaoxia , Chen Xiaoqing , Li Conglin , Yuan Wenchang , Hou Ning
Published: May 2020

Background

Carvacrol is a food additive with various bioactivities, including reducing the blood glucose level as well as improvement of heart function, in diabetic mice. We explored the antihyperglycemic effect of carvacrol and its effect on the key hepatic enzymes accounting for glucose metabolism.

Methods

A streptozotocin (STZ)-induced diabetes-mellitus model in mice was used. Mice were divided randomly into a control group, diabetic group, low dose carvacrol-treated diabetic group (10 mg/kg body weight [BW]), and high dose carvacrol-treated diabetic group (20 mg/kg BW). Carvacrol was injected intraperitoneally (i.p.) in each carvacrol-treated group daily for 4 weeks and 6 weeks, respectively. The level of random plasma glucose, fasting plasma glucose, and plasma insulin was determined at 4 weeks and 6 weeks after carvacrol administration. The plasma level of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and the activity of hepatic key enzymes related to glucose metabolism were determined.

Results

Carvacrol treatment decreased the levels of random plasma glucose and fasting plasma glucose, significantly in a dose-dependent manner. A significant improvement in glucose tolerance and a significant decrease in the plasma level of TG were observed in carvacrol-treated diabetic mice at a dose of 20 mg/kg BW compared with that in vehicle-treated diabetic mice. There was no significant difference in the plasma level of TC and insulin between vehicle-treated diabetic mice and carvacrol-treated diabetic mice. Carvacrol treatment at a dose of 20 mg/kg BW significantly reduced the plasma level of LDH but not AST, ALT, or ALP, compared with that in the vehicle-treated diabetic group. The activity of hexokinase (HK), 6-phosphofructokinase (PFK), and citrate synthetase (CS) was increased by carvacrol treatment in diabetic mice.

Conclusions

Carvacrol exerted an anti-hyperglycemic effect in STZ-induced diabetic mice. This was achieved through regulating glucose metabolism by increasing the activity of the hepatic enzymes HK, PFK, and CS.
Learning radiotherapy: the state of the art
Authors: Walls Gerard M. , Hanna Gerard G. , McAleer James J.
Published: May 2020

Background

The last two decades have seen revolutionary developments in both radiotherapy technology and postgraduate medical training. Trainees are expected to attain competencies using a mix of experiential learning, formal postgraduate teaching, self-directed learning and peer education. Radiation (Clinical) Oncology is a recognised ‘craft specialty’ where the apprenticeship model of training is applicable. This scoping review examines the evidence in relation to how medical trainees learn radiotherapy.

Methods

A systematic search of MEDINE and EMBASE was undertaken to identify studies of trainee and/or trainer experience of radiotherapy learning published 1999–2018. Results pertaining to Medical Oncology, workforce trends, undergraduate radiotherapy exposure, academic training, global health, non-medical staff, health service infrastructure and recruitment to training programmes were not included.

Results

A total of 146 publications were included in the synthesis. Five themes were apparent through careful iterative analysis representing broadly inter-related issues. Most articles studied radiotherapy training from the perspective of the trainee doctor. Most literature reports results of observational, local or national surveys with a tightly defined scope. Considerable variation exists within hospitals, within countries, over time and between different curricular areas.

Conclusions

Medical education has not kept pace with changes in the field of radiotherapy and large differences are demonstrated in experience between trainees in different hospitals, countries and training stages. Interpersonal relationships, departmental organisation, and national curricula impact on training quality. Qualitative and quantitative research examining modern radiotherapy learning has been uncommon and uncoordinated, until recently. To date no single study has been designed to comprehensively assess a department’s training scheme.
An economic evaluation of a specialist preventive care clinician in a community mental health service: a randomised controlled trial
Authors: Fehily Caitlin , Ling Rod , Searles Andrew , Bartlem Kate , Wiggers John , Hodder Rebecca , Wilson Andrew , Colyvas Kim , Bowman Jenny
Published: May 2020

Background

Clinical practice guidelines and policies direct community mental health services to provide preventive care to address chronic disease risks, however, such care is infrequently provided in routine consultations. An alternative model of care is to appoint a clinician to the dedicated role of offering and providing preventive care in an additional consultation: the ‘specialist clinician’ model. Economic evaluations of models of care are needed to determine the cost of adhering to guidelines and policies, and to inform pragmatic service delivery decisions. This study is an economic evaluation of the specialist clinician model; designed to achieve policy concordant preventive care delivery.

Methods

A retrospective analysis of the incremental costs, cost-effectiveness, and budget impact of a ‘specialist preventive care clinician’ (an occupational therapist) was conducted in a randomised controlled trial, where participants were randomised to receive usual care; or usual care plus the offer of an additional preventive care consultation with the specialist clinician. The study outcome was client acceptance of referrals to two free telephone-based chronic disease prevention services. This is a key care delivery outcome mandated by the local health district policy of the service. The base case analysis assumed the mental health service cost perspective. A budget impact analysis determined the annual budget required to implement the model of care for all clients of the community mental health service over 5 years.

Results

There was a significantly greater increase from baseline to follow-up in the proportion of intervention participants accepting referrals to both telephone services, compared to usual care. The incremental cost-effectiveness ratio was $347 per additional acceptance of a referral (CI: $263–$494). The annual budget required to implement the model of care for all prospective clients was projected to be $711,446 over 5-years; resulting in 2616 accepted referrals.

Conclusions

The evaluation provides key information regarding the costs for the mental health service to adhere to policy targets, indicating the model of care involved a low per client cost whilst increasing key preventive care delivery outcomes. Additional modelling is required to further explore its economic benefits.

Trial registration

ACTRN12616001519448. Registered 3 November 2016,https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371709.
Health care personnel’s perception of guideline implementation for musculoskeletal imaging: a process evaluation
Authors: Gransjøen Ann Mari , Wiig Siri , Lysdahl Kristin Bakke , Hofmann Bjørn Morten
Published: May 2020

Background

The increasing complexity and variability in radiology have significantly fueled the need for guidelines. There are many methods for disseminating and implementing guidelines however; and obtaining lasting changes has been difficult. Implementation outcome is usually measured in a decrease in unwarranted examinations, and qualitative data are rarely used. This study’s aim was to evaluate a guideline implementation process and identify factors influencing implementation outcome using qualitative data.

Methods

Seven general practitioners and five radiological personnel from a Norwegian county participated in four focus group interviews in 2019. The data were analyzed using qualitative content analysis, where some categories were predetermined, while most were drawn from the data.

Results

Four main categories were developed from the data material. 1) Successful/unsuccessful parts of the implementation, 2) perceived changes/lack of changes after the implementation, 3) environment-related factors that affected guideline use, and 4) User related factors that affect guideline use.

Conclusions

Our findings show that clinical guideline implementation is difficult, despite the implementation strategy being tailored to the target groups. Several environment- and user-related factors contributed to the lack of changes experienced in practice for both general practitioners and radiological personnel.
Feasibility of training community health workers to conduct periodontal examinations: a validation study in rural Nepal
Authors: Erchick Daniel J. , Agrawal Nitin K. , Khatry Subarna K. , Katz Joanne , LeClerq Steven C. , Rai Bhola , Reynolds Mark A. , Mullany Luke C.
Published: May 2020

Background

In many low- and middle-income countries, insufficient human resources limit access to oral health services. Shifting clinical tasks to less specialized health professionals, such as community health workers, has been used as a strategy to expand the health workforce, especially in remote or underserved locations. The objective of this study was to evaluate the validity of periodontal examinations conducted by auxiliary nurse midwives in a rural home setting in Nepal.

Methods

Twenty-one pregnant women < 26 weeks gestation from Sarlahi District, Nepal, underwent full mouth periodontal examinations measuring probing depth (PD) and bleeding on probing (BOP) on 6 sites per tooth by one of five auxiliary nurse midwives, who were trained for this study but had no previous training in dentistry. After a 15-min break, each participant was examined again by an experienced dentist. Measures of validity for PD and BOP were calculated comparing the pooled and individual auxiliary nurse midwives to the dentist. A multivariable GEE model estimated the effect of periodontal characteristics on agreement between the auxiliary nurse midwives and the dentist.

Results

Participant mean age was 22 years (SD: ±3 years), mean PD was 1.4 mm (SD: 03 mm), and 86% of women had BOP (according to the dentist). Percent agreement, weighted kappa scores, and intraclass correlation coefficients for PD, with an allowance of ±1 mm, exceeded 99%, 0.7, and 0.9, respectively, indicating an acceptable level of agreement. Auxiliary nurse midwives tended to report higher PD scores relative to the dentist, although this over-estimation was small and unlikely to impact population-based estimates of important indicators of oral health status. GEE regression modeling indicated similar agreement for mandible vs. maxilla, left vs. right side, and PD (≤2 mm, > 2 mm), and lower agreement for posterior teeth and lingual and proximal sites.

Conclusion

Auxiliary nurse midwives were able to accurately conduct periodontal examinations in a rural home setting, suggesting the potential to shift tasks away from highly trained dentists and periodontal examiners in low-resource communities.

Trial registration

ClinicalTrials.gov Identifier: NCT01177111 (Nepal Oil Massage Study); registered on August 6th, 2010.
Barriers to managing and delivery of care to war-injured survivors or patients with non-communicable disease: a qualitative study of Palestinian patients’ and policy-makers’ perspectives
Authors: Mosleh Marwan , Al Jeesh Yousef , Dalal Koustuv , Eriksson Charli , Carlerby Heidi , Viitasara Eija
Published: May 2020

Background

Improving access to optimal quality of care is a core priority and ambitious health policy goal in spite of impediments, threats and challenges in Palestine. Understanding the factors that may impede quality of care is essential in developing an effective healthcare intervention for patient with non-communicable disease (NCD) or war-injured survivors.

Methods

Qualitative interviews were performed using a purposive sampling strategy of 18 political-key informants, 10 patients with NCD and 7 war-injured survivors from different health facilities in Gaza Strip. A semi-structured interview guide was developed for data collection. The interviews were audio recorded and transcribed verbatim. Important field notes of the individual interviews were also reported. Thematic-driven analytic approach was used to identify key themes and patterns.

Results

From the policy maker’s perspective, the following important barriers to accessing optimal healthcare for patients with NCD or war-injured survivors’ treatment were identified; 1) organizational/structural 2) availability 3) communication 4) personnel/lack of staff 5) financial and political barriers. Patient with NCD or war-injury had similar experiences of barriers as the policy makers. In addition, they also identified socioeconomic, physical and psychological barriers for accessing optimal healthcare and treatment.

Conclusions

The main perceived barriers explored through this study will be very interesting and useful if they are considered seriously and handled carefully, in order to ensure efficient, productive, cost-effective intervention and delivery of a high-standard quality of care and better disease management.
Profiling Italian cat and dog owners’ perceptions of pet food quality traits
Authors: Vinassa Marica , Vergnano Diana , Valle Emanuela , Giribaldi Marzia , Nery Joana , Prola Liviana , Bergero Domenico , Schiavone Achille
Published: May 2020

Background

Over recent years, pet owners have started to demonstrate increased sensitivity toward their companion animals, which includes an increase in the attention paid towards their nutrition, seen as a way of safeguarding their pets’ welfare. The aim of this study was to identify how pet food quality traits are perceived as being the most important by dog and cat owners. To this end, a survey of dog and cat owners was conducted by means of a questionnaire distributed in pet stores and trade fairs throughout Italy.

Results

A total of 935 surveys were collected; 61.8% of which were compiled by female pet owners. The respondents were relatively homogeneously distributed between cat (30.8%), dog (39.4%), and cat and dog (29.8%) owners. A quarter of the owners (25.5%) reported to have asked their veterinarian for advice on which pet food to buy, and almost a third (30.4%) trusted the advice posted on the web sites of well-known brands. “Contains natural ingredients” was the characteristic that obtained the highest mean score (4.3 out of 5).

Elderly owners (> 65 years) placed most importance on whether a product had a high price, and least on feed appearance, animal satisfaction, and stool quality. Young owners (< 35y) paid most attention to the stool quality, the percentage of protein in the feed, and the presence of recyclable packaging, and least attention to feed appearance, smell, and animal satisfaction. Feed appearance, smell, a higher cost, and certain label indications (protein content, presence of fresh meat, grain free) were mostly important among the buyers of wet pet food. Some specific differences also emerged between dog, cat, and dog and cat owners.

Conclusions

In this survey of Italian pet food buyers, the presence of “natural” ingredients was considered to be the most important indicator of pet food quality, whereas characterized by a high price was considered least important. The data obtained from this survey could be used to help pet food companies identify which pet food quality traits are perceived as important by dog and cat owners.
A Gleason score-related outcome model for human prostate cancer: a comprehensive study based on weighted gene co-expression network analysis
Authors: Wang Yongzhi , Yang Zhonghua
Published: May 2020

Background

Prostate cancer (PCa) is the second leading cause of cancer death in men in 2018. Thus, the evaluation of prognosis is crucial for clinical treatment decision of human PCa patients. We aim to establishing an effective and reliable model to predict the outcome of PCa patients.

Methods

We first identified differentially expressed genes between prostate cancer and normal prostate in TCGA-PRAD and then performed WGCNA to initially identify the candidate Gleason score related genes. Then, the candidate genes were applied to construct a LASSO Cox regression analysis model. Numerous independent validation cohorts, time-dependent receiver operating characteristic (ROC), univariate cox regression analysis, nomogram were used to test the effectiveness, accuracy and clinical utility of the prognostic model. Furthermore, functional analysis and immune cells infiltration were performed.

Results

Gleason score-related differentially expressed candidates were identified and used to build up the outcome model in TCGA-PRAD cohort and was validated in MSKCC cohort. We found the 3-gene outcome model (CDC45, ESPL1 and RAD54L) had good performance in predicting recurrence free survival, metastasis free survival and overall survival of PCa patients. Time-dependent ROC and nomogram indicated an ideal predictive accuracy and clinical utility of the outcome model. Moreover, outcome model was enriched in 28 pathways by GSVA and GSEA. In addition, the risk score was positively correlated with memory B cells, native CD4 T cells, activated CD4 memory T cells and eosinophil, and negatively correlated with plasma cells, resting CD4 memory T cells, resting mast cells and neutrophil.

Conclusions

In summary, our outcome model proves to be an effective prognostic model for predicting the risk of prognosis in PCa.
Correction to: LncRNA MEG3 inhibits melanoma growth, metastasis and formation through modulating miR-21/E-cadherin axis
Authors: Wu Liangcai , Zhu Lifei , Li Yanchang , Zheng Zhixin , Lin Xi , Yang Chaoying
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Estimated postnatal p,p’-DDT and p,p’-DDE levels and body mass index at 42 months of age in a longitudinal study of Japanese children
Authors: Plouffe Laurence , Bosson-Rieutort Delphine , Madaniyazi Lina , Iwai-Shimada Miyuki , Nakai Kunihiko , Tatsuta Nozomi , Nakayama Shoji F. , Verner Marc-André
Published: May 2020

Background

Children are exposed top,p’-dichlorodiphenyltrichloroethane (p,p’-DDT) andp,p’-dichlorodiphenyldichloroethylene (p,p’-DDE) through placental and lactational transfer. Some studies have suggested that early-life exposure to these compounds could lead to increased body mass index (BMI) during childhood. Our aim was to assess whether children’s exposure during the first 2 years of life is associated with BMI z-score in Japanese children at 42 months of age.

Methods

We used data from a birth cohort (n = 290) of the Tohoku Study of Child Development.p,p’-DDT andp,p’-DDE levels were measured in breast milk samples collected 1 month after birth, and levels in children were estimated using a toxicokinetic model for three exposure periods (0–6 months, 6–12 months, 12–24 months). Associations between exposure estimates and BMI z-score at 42 months of age were assessed using multivariate linear regression models.

Results

We found no significant association between levels ofp,p’-DDT measured in breast milk or estimated in children and BMI z-score. However, we observed associations between estimatedp,p’-DDE levels in girls during all postnatal exposure periods and BMI z-score; for each log increase in the estimatedp,p’-DDE levels, BMI z-score increased by 0.23 (C.I. 95%: 0.01, 0.45) for the 0–6 months exposure period, 0.26 (C.I. 95%: 0.06, 0.47) for the 6–12 months exposure period, and 0.24 (C.I. 95%: 0.05, 0.43) for the 12–24 months exposure period.

Conclusion

In this study of Japanese children, estimated postnatalp,p’-DDE levels were associated with increased BMI z-score at 42 months of age, mostly in girls. These results are in line with previous studies supporting that early-life exposure top,p’-DDE may be associated with higher BMI during childhood.
Metabolic effects of PCSK9 inhibition with Evolocumab in subjects with elevated Lp(a)
Authors: Zhang Xiang , Stiekema Lotte C. A. , Stroes Erik S. G. , Groen Albert K.
Published: May 2020

Background

Epidemiological studies substantiated that subjects with elevated lipoprotein(a) [Lp(a)] have a markedly increased cardiovascular risk. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) lowers both LDL cholesterol (LDL-C) as well as Lp(a), albeit modestly. Effects of PCSK9 inhibition on circulating metabolites such as lipoprotein subclasses, amino acids and fatty acids remain to be characterized.

Methods

We performed nuclear magnetic resonance (NMR) metabolomics on plasma samples derived from 30 individuals with elevated Lp(a) (> 150 mg/dL). The 30 participants were randomly assigned into two groups, placebo (N = 14) and evolocumab (N = 16). We assessed the effect of 16 weeks of evolocumab 420 mg Q4W treatment on circulating metabolites by running lognormal regression analyses, and compared this to placebo. Subsequently, we assessed the interrelationship between Lp(a) and 14 lipoprotein subclasses in response to treatment with evolocumab, by running multilevel multivariate regression analyses.

Results

On average, evolocumab treatment for 16 weeks resulted in a 17% (95% credible interval: 8 to 26%, P < 0.001) reduction of circulating Lp(a), coupled with substantial reduction of VLDL, IDL and LDL particles as well as their lipid contents. Interestingly, increasing concentrations of baseline Lp(a) were associated with larger reduction in triglyceride-rich VLDL particles after evolocumab treatment.

Conclusions

Inhibition of PCSK9 with evolocumab markedly reduced VLDL particle concentrations in addition to lowering LDL-C. The extent of reduction in VLDL particles depended on the baseline level of Lp(a). Our findings suggest a marked effect of evolocumab on VLDL metabolism in subjects with elevated Lp(a).

Trial registration

Clinical trial registration information is registered at ClinicalTrials.gov on April 14, 2016 with the registration number NCT02729025.
High tumor mutation burden is associated with DNA damage repair gene mutation in breast carcinomas
Authors: Mei Ping , Freitag C. Eric , Wei Lai , Zhang Yunxiang , Parwani Anil V. , Li Zaibo
Published: May 2020

Background

Immunotherapy has demonstrated encouraging clinical benefits in patients with advanced breast carcinomas and Programmed death ligand 1 (PD-L1) expression has been proposed as an immunotherapy biomarker. Challenges with current PD-L1 testing exist and tumor mutation burden (TMB) is emerging as a biomarker to predict clinical response to immunotherapy in melanoma and non-small cell lung cancer patients. However, TMB has not been well characterized in breast carcinomas.

Methods

The study cohort included 62 advanced breast cancer patients (13 primary and 49 metastatic). Genetic alterations and TMB were determined by FoundationOne CDx next generation sequencing (NGS) and the association with clinicopathologic features was analyzed.

Results

High TMB was observed in a relatively low frequency (3/62, 4.8%). TMB levels were positively associated tumor infiltrating lymphocytes and significantly higher TMB was observed in breast carcinomas with DNA damage repair gene mutation(s). There was no significant association between TMB levels and other analyzed clinicopathologic characteristics.

Conclusions

Our data indicate the importance of DNA damage repair proteins in maintaining DNA integrity and immune reaction and breast carcinoma patients with DDR mutation may benefit from immunotherapy.
Mentored training and its association with dissemination and implementation research output: a quasi-experimental evaluation
Authors: Jacob Rebekah R. , Gacad Angeline , Padek Margaret , Colditz Graham A. , Emmons Karen M. , Kerner Jon F. , Chambers David A. , Brownson Ross C.
Published: May 2020

Background

There is a continued need to evaluate training programs in dissemination and implementation (D&I) research. Scientific products yielded from trainees are an important and objective measure to understand the capacity growth within the D&I field. This study evaluates our mentored training program in terms of scientific productivity among applicants.

Methods

Post-doctoral and early-career cancer researchers were recruited and applied to the R25 Mentored Training for Dissemination and Implementation Research in Cancer (MT-DIRC) between 2014 and 2017. Using application details and publicly available bibliometric and funding data, we compared selected fellows with unsuccessful applicants (nonfellows). We extracted Scopus citations and US federal grant funding records for all applicants (N= 102). Funding and publication abstracts were de-identified and coded for D&I focus and aggregated to the applicant level for analysis. Logistic regression models were explored separately for the odds of (1) a D&I publication and (2) US federal grant funding post year of application among fellows (N= 55) and nonfellows (N= 47). Additional models were constructed to include independent variables that attenuated the program’s association by 5% or more. Only US-based applicants (N= 87) were included in the grant funding analysis.

Results

Fellows and nonfellows were similar across several demographic characteristics. Fellows were more than 3 times more likely than nonfellows to have grant funding after MT-DIRC application year (OR 3.2; 95% CI 1.1–11.0) while controlling for time since application year; the association estimate was 3.1 (95% CI 0.98–11.0) after adjusting for both cancer research area and previous grant funding. For publications, fellows were almost 4 times more likely to publish D&I-focused work adjusting for time (OR 3.8; 95% CI 1.7–9.0). This association lessened after adjusting for previous D&I publication and years since undergraduate degree (OR 2.9; 95% CI 1.2–7.5).

Conclusions

We document the association of a mentored training approach with built-in networks of peers to yield productive D&I researchers. Future evaluation efforts could be expanded to include other forms of longer-term productivity such as policy or practice change as additional objective measures. D&I research trainings in the USA and internationally should consider common evaluation measures.
Design and fabrication of a Nano-based neutron shield for fast neutrons from medical linear accelerators in radiation therapy
Authors: Afkham Younes , Mesbahi Asghar , Alemi Abdolali , Zolfagharpour Farhad , Jabbari Nasrollah
Published: May 2020

Background

Photo-neutrons are produced at the head of the medical linear accelerators (linac) by the interaction of high-energy photons, and patients receive a whole-body-absorbed dose from these neutrons. The current study aimed to find an efficient shielding material for fast neutrons.

Methods

Nanoparticles (NPs) of Fe3O4 and B4C were applied in a matrix of silicone resin to design a proper shield against fast neutrons produced by the 18 MeV photon beam of a Varian 2100 C/D linac. Neutron macroscopic cross-sections for three types of samples were calculated by the Monte Carlo (MC) method and experimentally measured for neutrons of an Am-Be source. The designed shields in different concentrations were tested by MCNPX MC code, and the proper concentration was chosen for the experimental test. A shield was designed with two layers, including nano-iron oxide and a layer of nano-boron carbide for eliminating fast neutrons.

Results

MC simulation results with uncertainty less than 1% showed that for discrete energies and 50% nanomaterial concentration, the macroscopic cross-sections for iron oxide and boron carbide at the energy of 1 MeV were 0.36 cm− 1 and 0.32 cm− 1, respectively. For 30% nanomaterial concentration, the calculated macroscopic cross-sections for iron oxide and boron carbide shields for Am-Be spectrum equaled 0.12 cm− 1 and 0.15 cm− 1, respectively, while they are 0.15 cm− 1 and 0.18 cm− 1 for the linac spectrum. In the experiment with the Am-Be spectrum, the macroscopic cross-sections for 30% nanomaterial concentration were 0.17 ± 0.01 cm− 1 for iron oxide and 0.21 ± 0.02 cm− 1 for boron carbide. The measured transmission factors for 30% nanomaterial concentration with the Am-Be spectrum were 0.71 ± 0.01, 0.66 ± 0.02, and 0.62 ± 0.01 for the iron oxide, boron carbide, and double-layer shields, respectively. In addition, these values were 0.74, 0.69, and 0.67, respectively, for MC simulation for the linac spectrum at the same concentration and thickness of 2 cm.

Conclusion

Results achieved from MC simulation and experimental tests were in a satisfactory agreement. The difference between MC and measurements was in the range of 10%. Our results demonstrated that the designed double-layer shield has a superior macroscopic cross-section compared with two single-layer nanoshields and more efficiently eliminates fast photo-neutrons.
Anterior mediastinal metastasis of primary fallopian tube adenocarcinoma: a case report
Authors: Zhang Bo , Liu Renwang , Li Tong , Chen Feng , Huo Huandong , Ren Dian , Ren Fan , Xu Song , Xu Xiaohong , Song Zuoqing
Published: May 2020

Background

Primary fallopian tube carcinoma (PFTC) is a malignant tumor of the female genital tract that mostly presents intraperitoneal dissemination in clinical practice. The incidence of upper anterior mediastinal metastasis in PFTCs is extremely rare. We herein report a rare case of PFTC mediastinal metastasis after radical resection. When anterior mediastinal metastasis of an unknown origin is encountered, the possibility of PFTC should be considered.

Case presentation

A 68-year-old female who was previously diagnosed with PFTC after radical resection of a primary tumor in the fallopian tube was admitted to our department with a right anterior mediastinum mass. Radical resection of the mediastinal mass was performed, and poorly differentiated metastatic adenocarcinoma of the fallopian tube was confirmed. There was no recurrence in the 24 months after the curative operation.

Conclusion

To our knowledge, no mediastinal metastasis of PFTC has been reported yet. Thus, we presented this rare case indicating the heterogeneity of this malignant disease and to draw attention to the occasional distant metastasis of PFTC in clinical practice.
Incidentally discovered cold hemagglutinin disease with massive blood clots in the cardioplegia line and coronary artery, during coronary artery bypass graft
Authors: Chung Euysuk , Park Sungjoon , Lee Jaehoon
Published: May 2020

Background

Cold hemagglutinin disease (CHAD) is a rare autoimmune disease, in which patients manifest symptoms when the body temperature decreases. It causes critical problems with blood clotting and hemolysis during hypothermia in cardiac surgery. Although various methods are recommended, the CHAD discovered incidentally during cardiac surgery is still a clinical challenge.

Case presentation

A 76-year-old male visited our hospital for chest pain. Angiography revealed unstable angina, left-main and three-vessel disease. We performed coronary artery bypass graft (CABG) with cardiopulmonary bypass after heparin injection. Shortly after aorta cross-clamping (ACC) and infusion of cold blood cardioplegia, we found massive blood clots in the cardioplegia line. Upon suspicion of CHAD, we raised the temperature and infused warm blood cardioplegia in a retrograde manner. After performing cardiac arrest, we opened the coronary artery and found blood clots in the coronary artery. We eliminated the clots and washed with warm crystalloid cardioplegia simultaneously in an antegrade and retrograde manner. During the ACC, warm cardioplegia was infused every 15 min, via retrograde and antegrade techniques simultaneously. After distal anastomosis of the saphenous venous graft (SVG) to the coronary artery, we performed a direct SVG warm cardioplegia infusion. Finally, before the proximal SVG anastomosis to the aorta, we used warm cardioplegia to eliminate the remaining microemboli. The cold reactive protein test showed a positive result. The patient was discharged without any complications.

Conclusion

In this rare case, we incidentally discovered CHAD associated with massive blood clots in the cardioplegia line and the coronary artery, during CABG. However, we performed CABG without any complications using a reasonable and appropriate cardioplegia infusion technique, including direct SVG warm cardioplegia infusion.
Reduced complement of dopaminergic neurons in the substantia nigra pars compacta of mice with a constitutive “low footprint” genetic knockout of alpha-synuclein
Authors: Goloborshcheva Valeria V. , Chaprov Kirill D. , Teterina Ekaterina V. , Ovchinnikov Ruslan , Buchman Vladimir L.
Published: May 2020

Previous studies of the alpha-synuclein null mutant mice on the C57Bl6 genetic background have revealed reduced number of dopaminergic neurons in their substantia nigra pars compacta (SNpc). However, the presence in genomes of the studied mouse lines of additional genetic modifications that affect expression of genes located in a close proximity to the alpha-synuclein-encoding Snca gene makes these data open to various interpretations. To unambiguously demonstrate that the absence of alpha-synuclein is the primary cause of the observed deficit of dopaminergic neurons, we employed a recently produced constituent alpha-synuclein knockout mouse line B6(Cg)-Sncatm1.2Vlb/J. The only modification introduced to the genome of these mice is a substitution of the first coding exon and adjusted short intronic fragments of the Snca gene by a single loxP site. We compared the number of dopaminergic neurons in the SNpc of this line, previously studied B6(Cg)-Sncatm1Rosl/J line and wild type littermate mice. A similar decrease was observed in both knockout lines when compared with wild type mice. In a recently published study we revealed no loss of dopaminergic neurons following conditional inactivation of the Snca gene in neurons of adult mice. Taken together, these results strongly suggest that alpha-synuclein is required for efficient survival or maturation of dopaminergic neurons in the developing SNpc but is dispensable for survival of mature SNpc dopaminergic neurons.
ULK1 inhibition as a targeted therapeutic strategy for FLT3-ITD-mutated acute myeloid leukemia
Authors: Hwang Doh Yu , Eom Ju-In , Jang Ji Eun , Jeung Hoi-Kyung , Chung Haerim , Kim Jin Seok , Cheong June-Won , Min Yoo Hong
Published: May 2020

Background

In acute myeloid leukemia (AML), internal tandem duplication mutations in the FLT3 tyrosine kinase receptor (FLT3-ITD) are associated with a dismal outcome. Although uncoordinated 51-like kinase 1 (ULK1), which plays a central role in the autophagy pathway, has emerged as a novel therapeutic target for various cancers, its role in FLT3-ITD AML remains elusive. In this study, we evaluated the effects of ULK1 inhibition on leukemia cell death in FLT3-ITD AML.

Method

We evaluated ULK1 expression and the levels of apoptosis and autophagy following ULK1 inhibition in FLT3-ITD AML cell lines and investigated the mechanism underlying apoptosis induced by ULK1 inhibition. Statistical analysis was performed using GraphPad Prism 4.0 (GraphPad Software Inc).

Results

FLT3-ITD AML cells showed significantly higher ULK1 expression than FLT3-wild-type (WT) AML cells. Two ULK1 inhibitors, MRT 68921 and SBI-0206965, induced apoptosis in FLT3-ITD AML cells, with relatively minimal effects on FLT3-WT AML cells and normal CD34-positive cells. Apoptosis induction by ULK1 inhibition was associated with caspase pathway activation. Interestingly, ULK1 inhibition paradoxically also induced autophagy, showing synergistic interaction with autophagy inhibitors. Hence, autophagy may act as a prosurvival mechanism in FLT3-ITD AML cells. FLT3-ITD protein degradation and inhibition of the ERK, AKT, and STAT5 pathways were also observed in FLT3-ITD AML cells following treatment with ULK1 inhibitors.

Conclusion

ULK1 is a viable drug target and ULK1 inhibition may represent a promising therapeutic strategy against FLT3-ITD AML.
Activated CAMKKβ-AMPK signaling promotes autophagy in a spheroid model of ovarian tumour metastasis
Authors: Laski Jeremi , Singha Bipradeb , Wang Xu , Valdés Yudith Ramos , Collins Olga , Shepherd Trevor G.
Published: May 2020

Background

A hallmark of epithelial ovarian cancer (EOC) metastasis is the process of spheroid formation, whereby tumour cells aggregate into 3D structures while in suspension in the peritoneal cavity. EOC spheroids are subjected to bioenergetic stress, thereby activating AMP-activated protein kinase (AMPK) signaling to enter a metabolically quiescent state, which can facilitate cell survival under nutrient-limiting conditions. Independently, we have also demonstrated that EOC spheroids induce autophagy, a process that degrades and recycles intracellular components to restore energy and metabolites. Herein, we sought to examine whether AMPK controls autophagy induction as a cell survival mechanism in EOC spheroids.

Results

We observed a co-ordinate increase in phosphorylated AMPK and the autophagy marker LC3-II during EOC spheroid formation. Reduced AMPK expression by siRNA-mediated knockdown ofPRKAA1 and PRKAA2blocked autophagic flux in EOC spheroids as visualized by fluorescence microscopy using the mCherry-eGFP-LC3B reporter. A complementary approach using pharmacologic agents Compound C and CAMKKβ inhibitor STO-609 to inhibit AMPK activity both yielded a potent blockade of autophagic flux as well. However, direct activation of AMPK in EOC cells using oligomycin and metformin was insufficient to induce autophagy. STO-609 treatment of EOC spheroids resulted in reduced viability in 7 out of 9 cell lines, but with no observed effect in non-malignant FT190 cell spheroids.

Conclusions

Our results support the premise that CAMKKβ-mediated AMPK activity is required, at least in part, to regulate autophagy induction in EOC spheroids and support cell viability in this in vitro model of EOC metastasis.
Brain natriuretic peptide to predict successful liberation from mechanical ventilation in critically ill patients: a systematic review and meta-analysis
Authors: Deschamps Jean , Andersen Sarah K. , Webber Jordan , Featherstone Robin , Sebastianski Meghan , Vandermeer Ben , Senaratne Janek , Bagshaw Sean M.
Published: May 2020

Background

Predicting successful liberation from mechanical ventilation (MV) in critically ill patients is challenging. Brain natriuretic peptide (BNP) has been proposed to help guide decision-making for readiness to liberate from MV following a spontaneous breathing trial (SBT).

Methods

We performed a systematic review and meta-analysis of randomized and prospective observational studies that measured BNP levels at the time of SBT in patients receiving MV. The primary endpoint was successful liberation from MV (absence of reintubation or non-invasive ventilation at 48 h). Statistical analyses included bi-variate and Moses-Littenberg models and DerSimonian-Laird pooling of areas under ROC curve (AUROC).

Results

A total of 731 articles were screened. Eighteen adult and 2 pediatric studies were fulfilled pre-specified eligibility. The measure of the relative variation of BNP during SBT (ΔBNP%) after exclusion of SBT failure by clinical criteria in adults yielded a sensitivity and specificity of 0.889 [0.831–0.929] and 0.828 [0.730–0.896] for successful liberation from MV, respectively, with a pooled AUROC of 0.92 [0.88–0.97]. The pooled AUROC for any method of analysis for absolute variation of BNP (ΔBNP), pre-SBT BNP, and post-SBT BNP were 0.89 [0.83–0.95], 0.77 [0.63–0.91], and 0.85 [0.80–0.90], respectively.

Conclusion

The relative change in BNP during a SBT has potential value as an incremental tool after successful SBT to predict successful liberation from MV in adults. There is insufficient data to support the use of BNP in children or as an alternate test to clinical indices of SBT, or the use of ΔBNP, BNP-pre, and BNP-post as an alternate or incremental test.

Trial registration

PROSPERO CRD42018087474 (6 February 2018)
Investigation of the adolescent female breast transcriptome and the impact of obesity
Authors: Burkholder Adam , Akrobetu Dennis , Pandiri Arun R. , Ton Kiki , Kim Sue , Labow Brian I. , Nuzzi Laura C. , Firriolo Joseph M. , Schneider Sallie S. , Fenton Suzanne E. , Shaw Natalie D.
Published: May 2020

Background

Early life environmental exposures affect breast development and breast cancer risk in adulthood. The breast is particularly vulnerable during puberty when mammary epithelial cells proliferate exponentially. In overweight/obese (OB) women, inflammation increases breast aromatase expression and estrogen synthesis and promotes estrogen-receptor (ER)-positive breast cancer. In contrast, recent epidemiological studies suggest that obesity during childhood decreases future breast cancer risk. Studies on environmental exposures and breast cancer risk have thus far been limited to animal models. Here, we present the first interrogation of the human adolescent breast at the molecular level and investigate how obesity affects the immature breast.

Methods

We performed RNA-seq in 62 breast tissue samples from adolescent girls/young women (ADOL; mean age 17.8 years) who underwent reduction mammoplasty. Thirty-one subjects were non-overweight/obese (NOB; mean BMI 23.4 kg/m2) and 31 were overweight/obese (OB; BMI 32.1 kg/m2). We also compared our data to published mammary transcriptome datasets from women (mean age 39 years) and young adult mice, rats, and macaques.

Results

The ADOL breast transcriptome showed limited (30%) overlap with other species, but 88% overlap with adult women for the 500 most highly expressed genes in each dataset; only 43 genes were shared by all groups. In ADOL, there were 120 differentially expressed genes (DEG) in OB compared with NOB samples (padj < 0.05). Based on these DEG, Ingenuity Pathway Analysis (IPA) identified the cytokines CSF1 and IL-10 and the chemokine receptor CCR2 as among the most highly activated upstream regulators, suggesting increased inflammation in the OB breast. Classical ER targets (e.g., PR, AREG) were not differentially expressed, yet IPA identified the ER and PR and growth factors/receptors (VEGF, HGF, HER3) and kinases (AKT1) involved in hormone-independent ER activation as activated upstream regulators in OB breast tissue.

Conclusions

These studies represent the first investigation of the human breast transcriptome during late puberty/young adulthood and demonstrate that obesity is associated with a transcriptional signature of inflammation which may augment estrogen action in the immature breast microenvironment. We anticipate that these studies will prompt more comprehensive cellular and molecular investigations of obesity and its effect on the breast during this critical developmental window.
Constrained expectation maximisation algorithm for estimating ARMA models in state space representation
Authors: Galka Andreas , Moontaha Sidratul , Siniatchkin Michael
Published: May 2020

This paper discusses the fitting of linear state space models to given multivariate time series in the presence of constraints imposed on the four main parameter matrices of these models. Constraints arise partly from the assumption that the models have a block-diagonal structure, with each block corresponding to an ARMA process, that allows the reconstruction of independent source components from linear mixtures, and partly from the need to keep models identifiable. The first stage of parameter fitting is performed by the expectation maximisation (EM) algorithm. Due to the identifiability constraint, a subset of the diagonal elements of the dynamical noise covariance matrix needs to be constrained to fixed values (usually unity). For this kind of constraints, so far, no closed-form update rules were available. We present new update rules for this situation, both for updating the dynamical noise covariance matrix directly and for updating a matrix square-root of this matrix. The practical applicability of the proposed algorithm is demonstrated by a low-dimensional simulation example. The behaviour of the EM algorithm, as observed in this example, illustrates the well-known fact that in practical applications, the EM algorithm should be combined with a different algorithm for numerical optimisation, such as a quasi-Newton algorithm.
A new deep sparse autoencoder for community detection in complex networks
Authors: Fei Rong , Sha Jingyuan , Xu Qingzheng , Hu Bo , Wang Kan , Li Shasha
Published: May 2020

Feature dimension reduction in the community detection is an important research topic in complex networks and has attracted many research efforts in recent years. However, most of existing algorithms developed for this purpose take advantage of classical mechanisms, which may be long experimental, time-consuming, and ineffective for complex networks. To this purpose, a novel deep sparse autoencoder for community detection, named DSACD, is proposed in this paper. In DSACD, a similarity matrix is constructed to reveal the indirect connections between nodes and a deep sparse automatic encoder based on unsupervised learning is designed to reduce the dimension and extract the feature structure of complex networks. During the process of back propagation, L-BFGS avoid the calculation of Hessian matrix which can increase the calculation speed. The performance of DSACD is validated on synthetic and real-world networks. Experimental results demonstrate the effectiveness of DSACD and the systematic comparisons with four algorithms confirm a significant improvement in terms of three indexFsame,NMI, and modularityQ. Finally, these achieved received signal strength indication (RSSI) data set can be aggregated into 64 correct communities, which further confirms its usability in indoor location systems.
Data assessment and prioritization in mobile networks for real-time prediction of spatial information using machine learning
Authors: Shinkuma Ryoichi , Nishio Takayuki , Inagaki Yuichi , Oki Eiji
Published: May 2020

A new framework of data assessment and prioritization for real-time prediction of spatial information is presented. The real-time prediction of spatial information is promising for next-generation mobile networks. Recent developments in machine learning technology have enabled prediction of spatial information, which will be quite useful for smart mobility services including navigation, driving assistance, and self-driving. Other key enablers for forming spatial information are image sensors in mobile devices like smartphones and tablets and in vehicles such as cars and drones and real-time cognitive computing like automatic number/license plate recognition systems and object recognition systems. However, since image data collected by mobile devices and vehicles need to be delivered to the server in real time to extract input data for real-time prediction, the uplink transmission speed of mobile networks is a major impediment. This paper proposes a framework of data assessment and prioritization that reduces the uplink traffic volume while maintaining the prediction accuracy of spatial information. In our framework, machine learning is used to estimate the importance of each data element and to predict spatial information under the limitation of available data. A numerical evaluation using an actual vehicle mobility dataset demonstrated the validity of the proposed framework. Two extension schemes in our framework, which use the ensemble of importance scores obtained from multiple feature selection methods, are also presented to improve its robustness against various machine learning and feature selection methods. We discuss the performance of those schemes through numerical evaluation.
Some inequalities for the multilinear singular integrals with Lipschitz functions on weighted Morrey spaces
Authors: Gürbüz Ferit
Published: May 2020

The aim of this paper is to prove the boundedness of the oscillation and variation operators for the multilinear singular integrals with Lipschitz functions on weighted Morrey spaces.