bluuebunny/crossref_metadata_2025 huggingface dataset:
Endometrioid adenocarcinoma of the rectovaginal septum with invasion of the rectum: a case report and review of literature
Authors: Yang Hua , Gu Jiao-jiao , Qi Yue , Zhao Wei , Wang Xin-lu
Published: December 2019

Background

Malignant transformation of endometriosis in the rectovaginal septum is rare and usually misdiagnosed as a colorectal or gynecological tumor. We report a rare case of primary endometrioid adenocarcinoma of the rectovaginal septum with invasion of the rectum.

Case presentation

A 57-year-old overweight woman presented with vaginal bleeding and self-reported left lower abdominal pain during the previous 2 weeks. Preoperative imaging showed a large pelvic mass with invasion of the rectum, suggestive of a gynecologic malignancy. Multiple endoscopic biopsies and immunohistochemical analyses of specimens was performed. The patient received joint gynecological-surgical laparotomy, and there were no intra- or postoperative complications. The histopathological diagnosis was rectovaginal endometrioid adenocarcinoma with rectum infiltration. The patient received adjuvant chemotherapy and achieved good treatment response, with no early complications. At 12 months after surgery, there was no evidence of recurrence.

Conclusions

A high index of clinical suspicion is required for the diagnosis of endometrioid adenocarcinoma in the rectovaginal septum. Surgery combined with additional chemotherapy or radiotherapy seems to be a standard treatment, and hormonal therapy is optional. The efficacies of other therapies, including targeted medication and immunotherapy, are unknown.
‘All the stars were aligned’? The origins of England’s National Institute for Health Research
Authors: Atkinson Paul , Sheard Sally , Walley Tom
Published: December 2019

Background

In 2006, the research and development (R&D) activity of England’s national healthcare system, the National Health Service, was reformed. A National Institute for Health Research (NIHR) was established within the Department of Health, the first body to manage this activity as an integrated system, unlocking significant increases in government funding. This article investigates how the NIHR came to be set up, and why it took the form it did. Our goal was a better understanding of ‘how we got here’.

Methods

We conducted oral history interviews with 38 key witnesses, held a witness seminar, and examined published and unpublished documents.

Results

We conclude that the most important forces shaping the origin of NIHR were the growing impact of evidence-based medicine on service policies, the growth of New Public Management ways of thinking, economic policies favouring investment in health R&D and buoyant public funding for healthcare. We note the strong two-way interaction between the health research system and the healthcare system — while beneficial for the use of research, challenges for healthcare (such as stop-go funding) could also produce challenges for health research.

Conclusions

Understanding how and why England came to have a centralised health service research system alongside a long-established funder of biomedical research (the Medical Research Council) helps us interpret the significance of the English health research experience for other countries and helps English policy-makers better understand their present options.

Learning lessons from the features of the English health research system calls for an understanding of the processes which shaped it. Firstly, the publicly funded, nationally organised character of healthcare promoted government interest in evidence-based medicine, made research prioritisation simpler and helped promote the implementation of findings. Secondly, the essential role of leadership by a group who valued research for its health impact ensured that new management methods (such as metrics and competitive tendering) were harnessed to patient benefit, rather than as an end in themselves. A policy window of government willingness to invest in R&D for wider economic goals and buoyant funding of the health system were also effectively exploited.
Circulating levels of GDF15 in patients with myalgic encephalomyelitis/chronic fatigue syndrome
Authors: Melvin A. , Lacerda E. , Dockrell H. M. , O’Rahilly S. , Nacul L.
Published: December 2019

Background

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition characterised by fatigue and post-exertional malaise. Its pathogenesis is poorly understood. GDF15 is a circulating protein secreted by cells in response to a variety of stressors. The receptor for GDF15 is expressed in the brain, where its activation results in a range of responses. Among the conditions in which circulating GDF15 levels are highly elevated are mitochondrial disorders, where early skeletal muscle fatigue is a key symptom. We hypothesised that GDF15 may represent a marker of cellular stress in ME/CFS.

Methods

GDF15 was measured in serum from patients with ME/CFS (n = 150; 100 with mild/moderate and 50 with severe symptoms), “healthy volunteers” (n = 150) and a cohort of patients with multiple sclerosis (n = 50).

Results

Circulating GDF15 remained stable in a subset of ME/CFS patients when sampled on two occasions ~ 7 months (IQR 6.7–8.8) apart, 720 pg/ml (95% CI 625–816) vs 670 pg/ml (95% CI 598–796), P = 0.5. GDF15 levels were 491 pg/ml in controls (95% CI 429–553), 546 pg/ml (95% CI 478–614) in MS patients, 560 pg/ml (95% CI 502–617) in mild/moderate ME/CFS patients and 602 pg/ml (95% CI 531–674) in severely affected ME/CFS patients. Accounting for potential confounders, severely affected ME/CFS patients had GDF15 concentrations that were significantly increased compared to healthy controls (P = 0.01). GDF15 levels were positively correlated (P = 0.026) with fatigue scores in ME/CFS.

Conclusions

Severe ME/CFS is associated with increased levels of GDF15, a circulating biomarker of cellular stress that appears which stable over several months.
Cutis marmorata telangiectatica congenita: a literature review
Authors: Bui Teresa Nu Phuong Trinh , Corap Ayse , Bygum Anette
Published: December 2019

Background

Cutis marmorata telangiectatica congenita (CMTC) is a rare capillary malformation characterised by persistent reticulated marbled erythema. It tends to be associated with cutaneous atrophy, ulcerations and body asymmetry. CMTC is usually reported to be a benign condition; however, associated anomalies are not rare. Here, we have compiled information on published CMTC patients with the aim to evaluate the proposed diagnostic criteria by Kienast et al. and address the clinical manifestations, associated anomalies, differential diagnoses, management and prognosis. Our review is based on a search of the PubMed database which retrieved studies between 1922 and April 2019. The search yielded 148 original articles with a total of 485 patients.

Results

Of the identified patients, 24.5% had generalised CMTC, 66.8% had localised and 8.7% had a non-specified distribution of CMTC. Associated anomalies were observed in 42.5% of patients, predominantly body asymmetry and neurological defects like seizure and developmental delay. Fewer patients (10.1%) had ophthalmological defects, usually glaucoma. The major criterium “absence of venectasia” was not met in 20.4% of patients.

Conclusion

We suggest that children with CMTC should be referred to an ophthalmologist for regular follow-up, and children with CMTC affecting the legs should be monitored for leg length discrepancy throughout the growth period. Furthermore, we suggest reconsideration of the major criterium “absence of venectasia” from the proposed diagnostic criteria, and instead include body asymmetry.
Treatment needs and expectations for Fabry disease in France: development of a new Patient Needs Questionnaire
Authors: Noël Esther , Dussol Bertrand , Lacombe Didier , Bedreddine Najya , Fouilhoux Alain , Ronco Pierre , Genevaz Delphine , Bekri Soumeya , Hagège Albert , Dupuis-Siméon Frédérique , Derrien Ansquer Valérie , Germain Dominique P. , Lidove Olivier
Published: December 2019

Background

Fabry disease (FD) is a rare, X-linked, inherited lysosomal disease caused by absent or reduced α-galactosidase A activity. Due to the heterogeneity of disease presentation and progression, generic patient-reported outcome (PRO) tools do not provide accurate insight into patients’ daily lives and impact of disease specific treatments. Also, the French National Health Authority, (HAS) actively encourages a patient-centric approach to improve the quality of care throughout the patient journey. In response to this initiative, we aimed to develop and validate a specific, self-reported, Patient Needs Questionnaire for people living with Fabry disease to appraise patient needs and expectations towards their treatment (PNQ Fabry). This endeavour was led with the help of French patient associations (APMF & VML) and dedicated expert centres. PNQ Fabry was developed according to the FDA/EMA methodologies and best practices for the development of PRO tools in rare diseases. Our approach comprised of three steps, as follows: concept elicitation and item generation, item reduction, and final validation of the questionnaire through a two-stage survey.

Results

Intrinsic and extrinsic reliability was established, using a validated benchmark questionnaire. With the invaluable help of patient associations, we recruited a satisfactory population in this rare disease setting, to ensure robust participation to validate our PNQ (final number of questionnaires: 76). At the end of the process, a 26-item patient-reported questionnaire was obtained with excellent psychometric properties, exhibiting very satisfactory measurement outcomes for reliability and validity. The results of this initiative demonstrate that the PNQ Fabry is accurate, suitable and tailored to FD patients, as it addresses themes identified during patient interviews, that were further validated through statistical analyses of quantitative surveys. An ongoing phase IV study is using this tool.

Conclusion

We believe the PNQ Fabry will be a reliable and insightful tool in clinical practice, to improve patient management in FD.
Analgesic effects of optogenetic inhibition of basolateral amygdala inputs into the prefrontal cortex in nerve injured female mice
Authors: Gadotti Vinicius M. , Zhang Zizhen , Huang Junting , Zamponi Gerald W.
Published: December 2019

Peripheral nerve injury can lead to remodeling of brain circuits, and this can cause chronification of pain. We have recently reported that male mice subjected to spared injury of the sciatic nerve undergo changes in the function of the medial prefrontal cortex (mPFC) that culminate in reduced output of layer 5 pyramidal cells. More recently, we have shown that this is mediated by alterations in synaptic inputs from the basolateral amygdala (BLA) into GABAergic interneurons in the mPFC. Optogenetic inhibition of these inputs reversed mechanical allodynia and thermal hyperalgesia in male mice. It is known that the processing of pain signals can exhibit marked sex differences. We therefore tested whether the dysregulation of BLA to mPFC signaling is equally altered in female mice. Injection of AAV-Arch3.0 constructs into the BLA followed by implantation of a fiberoptic cannula into the mPFC in sham and SNI operated female mice was carried out, and pain behavioral responses were measured in response to yellow light mediated activation of this inhibitory opsin. Our data reveal that Arch3.0 activation leads to a marked increase in paw withdrawal thresholds and latencies in response to mechanical and thermal stimuli, respectively. However, we did not observe nerve injury-induced changes in mPFC layer 5 pyramidal cell output in female mice. Hence, the observed light-induced analgesic effects may be due to compensation for dysregulated neuronal circuits downstream of the mPFC.
Effectiveness of message-framing intervention on complementary feeding related behaviors among mothers with infants aged 4–8 months: a 3-arm randomized controlled trial
Authors: Rafieyan-Kopaei Ziba , Fathian-Dastgerdi Zohreh , Tarrahi Mohammad Javad , Zamani-Alavijeh Fereshteh
Published: December 2019

Objective

Complementary feeding from the age of 6 months along with breastfeeding is essential for the health of infants. The effect of educational interventions on preventing the early or late onset of complementary feeding and correcting other relevant behaviors depends on the framing of educational messages. This study aimed to compare different types of message framing on maternal behaviors in complementary feeding of infants.

Materials and methods

This randomized controlled trial was performed on 96 mothers in three groups of 32 subjects with four-month-old infants in Isfahan (central Iran) during May–September 2018. Data were collected through self-report using a valid researcher-made questionnaire including demographic factors, knowledge, attitude, self-efficacy, and the complementary feeding related behaviors of mothers. For 4 months, the mothers received gain-framed messages in the GF group and loss-framed messages in the LF group from two different channels. The control group only received routine education. Data analysis was performed in SPSS20 using paired t-test, ANOVA, and Chi-square at the significance level of below 0.05.

Results

In this study, all three groups were matched in terms of demographic characteristics and mean scores ofattitude,knowledge, andself-efficacyregarding the complementary feeding of their infants. Following the intervention, the meanknowledgescore increased in all three groups and was more favorable in the intervention groups compared to the control group. However, no difference was observed between the GF and LF groups regarding their knowledge. In addition, the GF and LF groups were similar in terms ofself-efficacyandbehavior of mothers concerning the appropriate onset of complementary feeding. Meanwhile, the mean scores ofattitudeandbehavior of mothers regarding the timely onset,diversity,and appropriateness of continuing complementary feedingwere higher in the LF group compared with the GF group.

Conclusion

Framing messages changes the attitude and knowledge and improves behaviors related to complementary feeding. The interesting point is the different impacts of different types of framing on psychological and behavioral variables. In general, loss-framed messages have more effects on the attitude and certain parts of maternal behaviors.

Trial registration

IRCT, IRCT20180901040919N1. Registered 29 October 2018,https://en.irct.ir/trial/33782
Limited role of DWI with apparent diffusion coefficient mapping in breast lesions presenting as non-mass enhancement on dynamic contrast-enhanced MRI
Authors: Avendano Daly , Marino Maria Adele , Leithner Doris , Thakur Sunitha , Bernard-Davila Blanca , Martinez Danny F. , Helbich Thomas H. , Morris Elizabeth A. , Jochelson Maxine S. , Baltzer Pascal A. T. , Clauser Paola , Kapetas Panagiotis , Pinker Katja
Published: December 2019

Background

Available data proving the value of DWI for breast cancer diagnosis is mainly for enhancing masses; DWI may be less sensitive and specific in non-mass enhancement (NME) lesions. The objective of this study was to assess the diagnostic accuracy of DWI using different ROI measurement approaches and ADC metrics in breast lesions presenting as NME lesions on dynamic contrast-enhanced (DCE) MRI.

Methods

In this retrospective study, 95 patients who underwent multiparametric MRI with DCE and DWI from September 2007 to July 2013 and who were diagnosed with a suspicious NME (BI-RADS 4/5) were included. Twenty-nine patients were excluded for lesion non-visibility on DWI (n = 24: 12 benign and 12 malignant) and poor DWI quality (n = 5: 1 benign and 4 malignant). Two readers independently assessed DWI and DCE-MRI findings in two separate randomized readings using different ADC metrics and ROI approaches. NME lesions were classified as either benign (> 1.3 × 10−3 mm2/s) or malignant (≤ 1.3 × 10−3 mm2/s). Histopathology was the standard of reference. ROC curves were plotted, and AUCs were determined. Concordance correlation coefficient (CCC) was measured.

Results

There were 39 malignant (59%) and 27 benign (41%) lesions in 66 (65 women, 1 man) patients (mean age, 51.8 years). The mean ADC value of the darkest part of the tumor (Dptu) achieved the highest diagnostic accuracy, with AUCs of up to 0.71. Inter-reader agreement was highest with Dptu ADC max (CCC 0.42) and lowest with the point tumor (Ptu) ADC min (CCC = − 0.01). Intra-reader agreement was highest with Wtu ADC mean (CCC = 0.44 for reader 1, 0.41 for reader 2), but this was not associated with the highest diagnostic accuracy.

Conclusions

Diagnostic accuracy of DWI with ADC mapping is limited in NME lesions. Thirty-one percent of lesions presenting as NME on DCE-MRI could not be evaluated with DWI, and therefore, DCE-MRI remains indispensable. Best results were achieved using Dptu 2D ROI measurement and ADC mean.
CGRRF1, a growth suppressor, regulates EGFR ubiquitination in breast cancer
Authors: Lee Yu-Ju , Ho Shiuh-Rong , Graves Joshua D. , Xiao Yang , Huang Shixia , Lin Weei-Chin
Published: December 2019

Background

CGRRF1 is a growth suppressor and consists of a transmembrane domain and a RING-finger domain. It functions as a RING domain E3 ubiquitin ligase involved in endoplasmic reticulum-associated degradation. The expression of CGRRF1 is decreased in cancer tissues; however, the role of CGRRF1 in breast cancer and the mechanism(s) of its growth suppressor function remain to be elucidated.

Methods

To investigate whether CGRRF1 inhibits the growth of breast cancer, we performed MTT assays and a xenograft experiment. Tumors harvested from mice were further analyzed by reverse phase protein array (RPPA) analysis to identify potential substrate(s) of CGRRF1. Co-immunoprecipitation assay was used to verify the interaction between CGRRF1 and its substrate, followed by in vivo ubiquitination assays. Western blot, subcellular fractionation, and reverse transcription quantitative polymerase chain reaction (qRT-PCR) were performed to understand the mechanism of CGRRF1 action in breast cancer. Publicly available breast cancer datasets were analyzed to examine the association between CGRRF1 and breast cancer.

Results

We show that CGRRF1 inhibits the growth of breast cancer in vitro and in vivo, and the RING-finger domain is important for its growth-inhibitory activity. To elucidate the mechanism of CGRRF1, we identified EGFR as a new substrate of CGRRF1. CGRRF1 ubiquitinates EGFR through K48-linked ubiquitination, which leads to proteasome degradation. In addition to regulating the stability of EGFR, knockout of CGRRF1 enhances AKT phosphorylation after EGF stimulation. By analyzing the breast cancer database, we found that patients with low CGRRF1 expression have shorter survival. As compared to normal breast tissues, the mRNA levels of CGRRF1 are lower in breast carcinomas, especially in HER2-positive and basal-like breast cancers. We further noticed that CGRRF1 promoter methylation is increased in breast cancer as compared to that in normal breast tissue, suggesting that CGRRF1 is epigenetically modified in breast cancer. Treatment of 5-azactidine and panobinostat restored CGRRF1 expression, supporting that the promoter of CGRRF1 is epigenetically modified in breast cancer. Since 5-azactidine and panobinostat can increase CGRRF1 expression, they might be potential therapies for breast cancer treatment.

Conclusion

We demonstrated a tumor-suppressive function of CGRRF1 in breast cancer and identified EGFR as its target.
Afann: bias adjustment for alignment-free sequence comparison based on sequencing data using neural network regression
Authors: Tang Kujin , Ren Jie , Sun Fengzhu
Published: December 2019

Alignment-free methods, more time and memory efficient than alignment-based methods, have been widely used for comparing genome sequences or raw sequencing samples without assembly. However, in this study, we show that alignment-free dissimilarity calculated based on sequencing samples can be overestimated compared with the dissimilarity calculated based on their genomes, and this bias can significantly decrease the performance of the alignment-free analysis. Here, we introduce a new alignment-free tool, Alignment-Free methods Adjusted by Neural Network (Afann) that successfully adjusts this bias and achieves excellent performance on various independent datasets. Afann is freely available at https://github.com/GeniusTang/Afann.
Update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol: statistical analysis plan for a prospective, multicenter, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial
Authors: Lindsell Christopher J. , McGlothlin Anna , Nwosu Samuel , Rice Todd W. , Hall Alex , Bernard Gordon R. , Busse Laurence W. , Ely E. Wesley , Fowler Alpha A. , Gaieski David F. , Hinson Jeremiah S. , Hooper Michael H. , Jackson James C. , Kelen Gabor D. , Levine Mark , Martin Greg S. , Rothman Richard E. , Sevransky Jonathan E. , Viele Kert , Wright David W. , Hager David N.
Published: December 2019

Background

Observational research suggests that combined therapy with Vitamin C, thiamine and hydrocortisone may reduce mortality in patients with septic shock.

Methods and design

The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a multicenter, double-blind, adaptive sample size, randomized, placebo-controlled trial designed to test the efficacy of combination therapy with vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) given every 6 h for up to 16 doses in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. The primary outcome is ventilator- and vasopressor-free days with mortality as the key secondary outcome. Recruitment began in August 2018 and is ongoing; 501 participants have been enrolled to date, with a planned maximum sample size of 2000. The Data and Safety Monitoring Board reviewed interim results at N = 200, 300, 400 and 500, and has recommended continuing recruitment. The next interim analysis will occur when N = 1000.

This update presents the statistical analysis plan. Specifically, we provide definitions for key treatment and outcome variables, and for intent-to-treat, per-protocol, and safety analysis datasets. We describe the planned descriptive analyses, the main analysis of the primary end point, our approach to secondary and exploratory analyses, and handling of missing data. Our goal is to provide enough detail that our approach could be replicated by an independent study group, thereby enhancing the transparency of the study.

Trial registration

ClinicalTrials.gov, NCT03509350. Registered on 26 April 2018.
Progressive structural bone changes and their relationship with treatment in patients with psoriatic arthritis: a longitudinal HR-pQCT study
Authors: Wu Dongze , Griffith James F. , Lam Steven H. M. , Wong Priscilla C. H. , Shi Lin , Li Edmund K. , Cheng Isaac T. , Li Tena K. , Hung Vivian W. , Qin Ling , Tam Lai-Shan
Published: December 2019

Background

Although the short-term effects of tumor necrosis factor alpha (TNF-α) and interleukin-17A (IL-17A) inhibition on the structural changes in psoriatic arthritis (PsA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) have been reported, no studies have investigated the long-term structural changes in PsA patients receiving routine care. We reported longitudinal changes of erosions and enthesiophytes using HR-pQCT and their relationship with treatments in PsA patients over a 5-year period.

Methods

HR-pQCT examination at the second and third metacarpal heads (MCH2 and MCH3) was performed in 60 PsA patients at baseline and after 5 years. The size of each individual lesion was quantified. Erosion and enthesiophyte progression were defined as change exceeding the smallest detectable change (SDC).

Results

A total of 108 bone erosions and 99 enthesiophytes were detected at baseline. Three new bone erosions but no new enthesiophytes were evident at 5 years. A significant increase in mean (±SD) erosion (0.58 ± 1.50 mm3,P < 0.001) and enthesiophyte (0.47 ± 0.76 mm3,P < 0.001) volume was observed. Erosion and enthesiophyte progression were found in 37/111 (33.3%) and 50/99 (50.5%) lesions, respectively. During this 5-year period, 26 (43%) out of the 60 patients achieved sustained Disease Activity index for PSoriatic Arthritis (DAPSA) low disease activity (LDA) (SDL group, defined as achieving DAPSA-LDA at both baseline and 5 years). Fourteen (23%) out of 60 patients received a TNF inhibitor throughout the 5-year period (TNFi group). Fewer erosions progressed (12/51 [23.5%] vs 25/60 [41.7%],P = 0.047) and the increased in enthesiophyte volume was significantly less (0.28 ± 0.67 vs 0.61 ± 0.80 mm3,P = 0.048) in the SDL group than in the non-SDL group. However, no significant difference between the TNFi and non-TNFi groups was detected in terms of the change in volume or progression of bone erosion and enthesiophyte.

Conclusion

Damage accrual in terms of bone erosion and enthesiophyte was observed in PsA patients over a period of 5 years despite receiving routine clinical care. Nonetheless, sustained control of disease activity may be able to prevent these bony damages.
Epigenetic therapy of novel tumour suppressor ZAR1 and its cancer biomarker function
Authors: Deutschmeyer Verena , Breuer Janina , Walesch Sara K. , Sokol Anna M. , Graumann Johannes , Bartkuhn Marek , Boettger Thomas , Rossbach Oliver , Richter Antje M.
Published: December 2019

Background

Cancer still is one of the leading causes of death and its death toll is predicted to rise further. We identified earlier the potential tumour suppressor zygote arrest 1 (ZAR1) to play a role in lung carcinogenesis through its epigenetic inactivation.

Results

We are the first to report that ZAR1 is epigenetically inactivated not only in lung cancer but also across cancer types, and ZAR1 methylation occurs across its complete CpG island. ZAR1 hypermethylation significantly correlates with its expression reduction in cancers. We are also the first to report that ZAR1 methylation and expression reduction are of clinical importance as a prognostic marker for lung cancer and kidney cancer. We further established that the carboxy (C)-terminally present zinc-finger of ZAR1 is relevant for its tumour suppression function and its protein partner binding associated with the mRNA/ribosomal network. Global gene expression profiling supported ZAR1's role in cell cycle arrest and p53 signalling pathway, and we could show that ZAR1 growth suppression was in part p53 dependent. Using the CRISPR-dCas9 tools, we were able to prove that epigenetic editing and reactivation of ZAR1 is possible in cancer cell lines.

Conclusion

ZAR1 is a novel cancer biomarker for lung and kidney, which is epigenetically silenced in various cancers by DNA hypermethylation. ZAR1 exerts its tumour suppressive function in part through p53 and through its zinc-finger domain. Epigenetic therapy can reactivate the ZAR1 tumour suppressor in cancer.
ZMYND10, an epigenetically regulated tumor suppressor, exerts tumor-suppressive functions via miR145-5p/NEDD9 axis in breast cancer
Authors: Wang Yan , Dan Liangying , Li Qianqian , Li Lili , Zhong Lan , Shao Bianfei , Yu Fang , He Sanxiu , Tian Shaorong , He Jin , Xiao Qian , Putti Thomas C. , He Xiaoqian , Feng Yixiao , Lin Yong , Xiang Tingxiu
Published: December 2019

Background

Recent studies suggested that ZMYND10 is a potential tumor suppressor gene in multiple tumor types. However, the mechanism by which ZMYND10 inhibits breast cancer remains unclear. Here, we investigated the role and mechanism of ZMYND10 in breast cancer inhibition.

Results

ZMYND10 was dramatically reduced in multiple breast cancer cell lines and tissues, which was associated with promoter hypermethylation. Ectopic expression of ZMYND10 in silenced breast cancer cells induced cell apoptosis while suppressed cell growth, cell migration and invasion in vitro, and xenograft tumor growth in vivo. Furthermore, molecular mechanism studies indicated that ZMYND10 enhances expression of miR145-5p, which suppresses the expression of NEDD9 protein through directly targeting the 3'-untranslated region of NEDD9 mRNA.

Conclusions

Results from this study show that ZMYND10 suppresses breast cancer tumorigenicity by inhibiting the miR145-5p/NEDD9 signaling pathway. This novel discovered signaling pathway may be a valid target for small molecules that might help to develop new therapies to better inhibit the breast cancer metastasis.
What to expect, and how to improve online discussion forums: the instructors’ perspective
Authors: de Lima Dhanielly P. R. , Gerosa Marco A. , Conte Tayana U. , de M. Netto José Francisco
Published: December 2019

Online discussion forums are asynchronous communication tools that are widely used in Learning Management Systems. However, instructors and students face various difficulties, and instructors lack a guide on what strategies they can use to achieve a more participatory forum environment. This work aims to identify benefits and difficulties of using online discussion forums from the instructors’ point of view, and to provide a list of strategies and improvements that can mitigate the challenges and lead to a more participatory forum. We used coding procedures to analyze data collected through semi-structured interviews. The results of our exploratory analysis are relevant to the distance learning community and can inform instructors, developers, and researchers to help them improve the quality of mediation and use of forums.
Comparison and analysis of two forms of harvesting functions in the two-prey and one-predator model
Authors: Liu Xinxin , Huang Qingdao
Published: December 2019

A new way to study the harvested predator–prey system is presented by analyzing the dynamics of two-prey and one-predator model, in which two teams of prey are interacting with one team of predators and the harvesting functions for two prey species takes different forms. Firstly, we make a brief analysis of the dynamics of the two subsystems which include one predator and one prey, respectively. The positivity and boundedness of the solutions are verified. The existence and stability of seven equilibrium points of the three-species model are further studied. Specifically, the global stability analysis of the coexistence equilibrium point is investigated. The problem of maximum sustainable yield and dynamic optimal yield in finite time is studied. Numerical simulations are performed using MATLAB from four aspects: the role of the carrying capacity of prey, the simulation about the model equations around three biologically significant steady states, simulation for the yield problem of model system, and the comparison between the two forms of harvesting functions. We obtain that the new form of harvesting function is more realistic than the traditional form in the given model, which may be a better reflection of the role of human-made disturbance in the development of the biological system.
Correction to: Impact of intensive care unit supportive care on the physiology of Ebola virus disease in a universally lethal non-human primate model
Authors: Poliquin Guillaume , Funk Duane , Jones Shane , Tran Kaylie , Ranadheera Charlene , Hagan Mable , Tierney Kevin , Grolla Allen , Dhaliwal Amrinder , Bello Alexander , Leung Anders , Nakamura Cory , Kobasa Darwyn , Falzarano Darryl , Garnett Lauren , Bovendo Hugues Fausther , Feldmann Heinz , Kesselman Murray , Hansen Gregory , Gren Jason , Risi George , Biondi Mia , Mortimer Todd , Racine Trina , Deschambault Yvon , Aminian Sam , Edmonds Jocelyn , Saurette Ray , Allan Mark , Rondeau Lauren , Hadder Sharron , Press Christy , DeGraff Christine , Kucas Stephanie , Cook Bradley W. M. , Hancock B. J. , Kumar Anand , Soni Reeni , Schantz Daryl , McKitrick Jarrid , Warner Bryce , Griffin Bryan D. , Qiu Xiangguo , Kobinger Gary P. , Safronetz Dave , Stein Derek , Cutts Todd , Kenny James , Soule Geoff , Kozak Robert , Theriault Steven , Menec Liam , Vendramelli Robert , Higgins Sean , Banadyga Logan , Liu Guodong , Rahim Md Niaz , Kasloff Samantha , Sloan Angela , He Shihua , Tailor Nikesh , Albietz Alixandra , Pickering Brad , Wong Gary , Gray Michael , Strong James E.
Published: December 2019

Please note that four authors (Logan Banadyga, Alixandra Albietz, Brad Pickering, and Gary Wong) have been erroneously omitted from the author list in the published original article [1].
Diagnostic performance in T staging for patients with esophagogastric junction cancer using high-resolution MRI: a comparison with conventional MRI at 3 tesla
Authors: Yuan Yuan , Chen Luguang , Ren Shengnan , Wang Zhen , Chen Yukun , Jin Aiguo , Li Shuai , Fang Xu , Wang Tiegong , Bian Yun , Yang Qingsong , Bai Chenguang , Hao Qiang , Lu Jianping
Published: December 2019

Background

To investigate and compare the diagnostic performance in T staging for patients with esophagogastric junction cancer using high-resolution magnetic resonance imaging (HR MRI), as compared with conventional MRI at 3 Tesla.

Methods

A total of 118 patients with pathologically confirmed esophagogastric junction cancer were included and underwent multiparameter HR MRI (Cohort 1, 62 patients) or conventional MRI (Cohort 2, 56 patients). T2-weighted, T1-weighted, diffusion-weighted and contrast-enhanced T1-weighted images of each patient were evaluated by two radiologists who determined the preoperative T staging by consensus. Using pathologic staging as the gold standard, the consistency between HR MRI and pathology and between conventional MRI and pathology in T staging was calculated and compared. The overall accuracy, overstatement and understatement of HR MRI and conventional MRI in T staging of patients with esophagogastric junction cancer were computed and compared. Moreover, the diagnostic performance of HR MRI and conventional MRI in T staging (≤ T1 and ≥ T4) of patients with esophagogastric junction cancer were evaluated.

Results

There were no significant differences in age (p = 0.465) and sex (p = 0.175) between Cohorts 1 and 2. Excellent agreement was observed in the T staging of patients with esophagogastric junction cancer between pathology and HR MRI (kappa = 0.813), while moderate agreement was observed between pathology and conventional MRI (kappa = 0.486). Significant differences were observed in overall accuracy (88.7% vs 64.3%, p = 0.002) and understatement (1.6% vs 26.8%, p < 0.001) but not for overstatement (9.7% vs 8.9%, p = 0.889) in T staging between HR MRI and conventional MRI techniques. For differentiating the T stages of ≤ T1 from ≥ T2 and the T stages of ≤ T3 from ≥ T4, no significant differences were observed between the imaging techniques.

Conclusions

HR MRI has good diagnostic performance and may serve as an alternative technique in the T staging of patients with esophagogastric junction cancer in clinical practice.
Regeneration patterns in Mexican pine-oak forests
Authors: Alfaro Reyna Teresa , Martínez-Vilalta Jordi , Retana Javier
Published: December 2019

Background

Global change is causing an increase in the incidence of natural and anthropogenic disturbances on forests, which frequently interact synergistically and promote changes in forest structure, composition and functioning. In this study we evaluate the regeneration of Pinaceae and Fagaceae species in pure and mixed stands in Mexico to determine if current regeneration patterns are indicative of changes in the relative dominance of these two tree families, as observed in other temperate regions. We also identify the environmental factors that determine the regeneration patterns of Pinaceae and Fagaceae species in these forests.

Results

We use data from two consecutive surveys of the National Inventory of Forests and Soils of Mexico (INFyS), obtained in 2004–2009 and 2009–2014. Our results show that the spatial patterns of regeneration are affected by forest structure, by climate, by the type and intensity of disturbances and by land tenure. Importantly, the presence and abundance of Fagaceae regeneration is generally higher than that of Pinaceae, and tends to be favoured (relative to Pinaceae) under warmer climates and by the presence of wildfires.

Conclusions

The higher regeneration of Fagaceae relative to Pinaceae under warmer and fire-prone conditions could have important impacts on the composition and functioning of Mexican temperate forests under ongoing climate change, as well as affect their resilience to future disturbances.
IVF outcomes after hysteroscopic metroplasty in patients with T- shaped uterus
Authors: Uyar Esra , Usal Deniz , Selam Belgin , Cincik Mehmet , Bagis Tayfun
Published: December 2019

Background

T- shaped uterus may be associated with infertility and adverse pregnancy outcomes. Hysteroscopic metroplasty may improve the reproductivity for these cases. To our knowledge, there is no data in literature about the clinical consequences of in vitro fertilization (IVF) in patients undergoing hysteroscopic metroplasty for T-shaped uterus. The principal objective of the current study is to assess the impact of hysteroscopic metroplasty for T-shaped uterus on the reproductive outcomes of IVF.

Methods

IVF outcomes of 74 patients who underwent hysteroscopic metroplasty for T- shaped uterus and 148 patients without any uterine abnormalities and with diagnosis of unexplained infertility (control group) were retrospectively analyzed.

Results

Patients in metroplasty and control groups were comparable with respect to age, BMI, partner’s age and duration of infertility. Number of patients with a history of pregnancy beyond 20 weeks of gestation was significantly lower in the metroplasty group (4.1% vs 18.2%; p < 0.05). Number of previous unsuccessful cycles and percentage of patients with ≥3 unsuccessful IVF cycles (35.1% vs 17.6%; p < 0.05) were significantly higher in the metroplasty group. There were no significant differences in the reproductive outcomes such as the pregnancy rate, clinical pregnancy or live birth rate between the metroplasty and control groups. There were non-significant trends for higher rates of miscarriage (18.8% vs 8%, p > 0.05) and biochemical pregnancy (20.0% vs 10.7%, p > 0.05) in the metroplasty group compared to the control group.

Conclusions

Reproductive results of the IVF cycles after hysteroscopic correction of T-shaped uterus were comparable to those of the patients without any uterine abnormalities and with diagnosis of unexplained infertility. Hysteroscopic metroplasty may contribute to improved IVF outcomes in patients with T-shaped uterus.
True brachial artery aneurysm after arteriovenous fistula closure following renal transplantation: a case report and literature review
Authors: Toyota Satoshi , Inoue Kentaro , Kurose Shun , Yoshino Shinichiro , Nakayama Ken , Yamashita Sho , Morisaki Koichi , Furuyama Tadashi , Mori Masaki
Published: December 2019

Background

A brachial artery aneurysm (BAA) is a rare condition accounting for 5% of all peripheral arterial aneurysms. More cases of true BAAs after arteriovenous fistula (AVF) closure have been reported in the past two decades.

Case presentation

A 60-year-old man who underwent AVF closure after renal transplantation had a true BAA on his left elbow that had grown within the past 6 months. We successfully performed an open repair with end-to-end anastomosis. No complications occurred for 1 year.

Conclusions

High flow due to AVF and some collateral factors such as the use of steroids and immunosuppressants after renal transplantation, arteriosclerosis, and chronic mechanical stimulation might contribute to BAA formation.
Comparing videos and a 3D virtual environment for teaching school-related functional skills and behaviors to students with ADHD or developmental dyslexia, displaying challenging behaviors: a case study
Authors: Fokides Emmanuel , Chronopoulou Maria-Ioanna , Kaimara Polyxeni
Published: December 2019

The study presents the results of a comparative study in which videos and a 3D virtual environment were used for teaching school-related functional skills to students with ADHD or developmental dyslexia, displaying challenging behaviors. The participating students (sixteen 8 to 9 years old) were divided into two groups. To the first, videos were used and the second used the virtual environment. To both, a school environment was presented, students observed how they were expected to behave, and had to demonstrate what they have learned. Each student attended a total of three two-hour sessions. Data were collected by means of observations. The results indicated that students in the second group significantly improved their functional skills in terms of the number of behaviors that were retained and manifested in the real school environment. Thus, it can be argued that virtual environments are a promising tool for teaching functional skills to students with ADHD or developmental dyslexia, displaying challenging behaviors. Implications for research and practice are also discussed.
Development of the Health Awareness and Behaviour Tool (HABiT): reliability and suitability for a Canadian older adult population
Authors: Agarwal Gina , Pirrie Melissa , Angeles Ricardo , Marzanek Francine , Parascandalo Jenna
Published: December 2019

Background

Determining the effectiveness of community-based health promotion and disease prevention programs requires an appropriate data collection tool. This study aimed to develop a comprehensive health questionnaire for older adults, called the HABiT, and evaluate its reliability, content validity, and face validity in assessing individual health-related items (e.g., health status, healthcare utilization) and five specific scales: knowledge, current health behaviors (risk factors), health-related quality of life (HRQoL), perceived risk and understanding, and self-efficacy.

Methods

Iterative survey development and evaluation of its psychometric properties in a convenience sample of 28 older adults (≥ 55 years old), half from a low-income population. Following item generation, the questionnaire was assessed for content validity (expert panel), face validity (participant feedback), internal consistency of each scale (Cronbach’s alpha), and test-retest reliability for each item and scale (Pearson’srand phi correlations, as appropriate).

Results

Questions were drawn from 15 sources, but primarily three surveys: Canadian Community Health Survey, Canadian Diabetes Risk Questionnaire (CANRISK), and a survey by the Canadian Hypertension Education Program. Expert consensus was attained for item inclusion and representation of the desired constructs. Participants completing the questionnaire deemed the questions to be clear and appropriate. Test-retest reliability for many individual items was moderate-to-high, with some exceptions for items that can reasonably change in a short period (e.g., perceived day-to-day stress). Of the five potential scales evaluated, two had acceptable internal consistency (Cronbach’s alpha ≥ 0.60) and a subset of one scale also had acceptable internal consistency. Test-retest reliability was high (correlation ≥ 0.80) for all scales and sub-scales.

Conclusions

The HABiT is a reliable and suitable comprehensive tool with content and face validity that can be used to evaluate health promotion and chronic disease prevention programs in older adults, including low-income older adults. Some noted limitations are discussed. Data collected using this tool also provides a diabetes risk score, health literacy score, and quality-adjusted life years (QALYs) for economic analysis.
Review of modeling and control strategy of thermostatically controlled loads for virtual energy storage system
Authors: Xie Kang , Hui Hongxun , Ding Yi
Published: December 2019

The increasing penetration of renewable energy sources (RESs) brings more power generation fluctuations into power systems, which puts forward higher requirement on the regulation capacities for maintaining the power balance between supply and demand. In addition to traditional generators for providing regulation capacities, the progressed information and communication technologies enable an alternative method by controlling flexible loads, especially thermostatically controlled loads (TCLs) for regulation services. This paper investigates the modeling and control strategies of aggregated TCLs as the virtual energy storage system (VESS) for demand response. First, TCLs are modeled as VESSs and compared with the traditional energy storage system (ESS) to analyze their characteristic differences. Then, the control strategies of VESS are investigated in microgrid and main grid aspects, respectively. It shows that VESS control strategies can play important roles in frequency regulation and voltage regulation for power systems’ stability. Finally, future research directions of VESS are prospected, including the schedulable potential evaluation, modeling of TCLs, hierarchical control strategies of VESS considering ESSs and RESs and reliability and fast response in frequency control for VESS.
Optimising dual-energy CT scan parameters for virtual non-calcium imaging of the bone marrow: a phantom study
Authors: Müller Felix C. , Børgesen Henrik , Gosvig Kasper , Rodell Anders , Booz Christian , Schmidt Bernhard , Krauss Bernhard , Boesen Mikael
Published: December 2019

Background

We investigated the influence of dose, spectral separation, pitch, rotation time, and reconstruction kernel on accuracy and image noise of virtual non-calcium images using a bone marrow phantom.

Methods

The phantom was developed at our institution and scanned using a third-generation dual-source dual-energy CT scanner at five different spectral separations by varying the tube-voltage combinations (70 kV/Sn150 kV, 80 kV/Sn150 kV, 90 kV/Sn150 kV, and 100 kV/Sn150 kV, all with 0.6-mm tin filter [Sn]; 80 kV/140 kV without tin filter) at six different doses (volume computed tomography dose index from 1 to 80 mGy). In separate experiments, rotation times, pitch, and reconstruction kernels were varied at a constant dose and tube voltage. Accuracy was determined by measuring the mean error between virtual non-calcium values in the fluid within and outside of the bone. Image noise was defined as the standard deviation of virtual non-calcium values.

Results

Spectral separation, dose, rotation time, or pitch did not significantly correlate (p > 0.083) with mean error. Increased spectral separation (rs-0.96, p < 0.001) and increased dose (rs-0.98, p < 0.001) correlated significantly with decreased image noise. Increasing sharpness of the reconstruction kernel correlated with mean error (rs 0.83, p = 0.015) and image noise (rs 1.0, p < 0.001).

Conclusions

Increased dose and increased spectral separation significantly lowered image noise in virtual non-calcium images but did not affect the accuracy. Virtual non-calcium reconstructions with similar accuracy and image noise could be achieved at a lower tube-voltage difference by increasing the dose.
Management of the Egyptian alfalfa weevil, Hypera brunneipennis (Boheman) (Coleoptera: Curculionidae), in the alfalfa, Medicago sativa L., using the entomopathogenic fungus, Beauveria bassiana (Balsamo) Vuillemin
Authors: El Husseini Monir M. M.
Published: December 2019

Larval and adult populations of the Egyptian alfalfa weevil (EAW) Hypera brunneipennis (Boheman) (Coleoptera: Curculionidae) was monitored after application of the entomopathogenic fungus Beauveria bassiana in the alfalfa field (Medicago sativa L.) in two successive seasons 2014/2015 and 2015/2016. The second and last generation of the weevil on April 10, 2016, was controlled by only one application with the conidiospores of the entomopathogenic fungus B. bassiana (3 × 108 spores/ml). Accordingly, the larval population decreased from 16.07 ± 1.09 in season 2015/2016 to 7.37 ± 0.05 individuals/50 sweep net double strokes in season 2016/2017. Also, the adult weevil’s population decreased from 5.66 ± 0.8 to 2.55 ± 0.6 individuals/50 sweep net double strokes in the two seasons, respectively. 39.66% mortality rate was recorded in the Hypera brunneipennis adults aestivated under loose bark of the surrounding eucalyptus trees, which received the application of B. bassiana in the field. Another application with the fungus, targeting the second generation of the pest adults in alfalfa each season, will undoubtedly lead to a further decrease in the pest population.