bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulated 5-HT1A receptor-mediated currents in the prefrontal cortex layer 5 neurons in the 15q11–13 duplication mouse model of autism
Authors: Saitow Fumihito , Takumi Toru , Suzuki Hidenori 
Published: August 2020

AbstractSerotonin (5-HT) is a well-known modulator of behavioral, physiological, and emotional functions of the forebrain region. We recently discovered alterations of serotonergic synaptic modulations in both, the prefrontal cortex (PFC) and the somatosensory cortex, in the 15q dup mouse model of autism spectrum disorder (ASD). To further understand the roles of the 5-HT system implicated in developmental disorders such as ASD, comparison with model animals exhibiting different phenotypes may be useful. In this study, we investigated the relationship between sociability and the magnitude of 5-HT1A receptor (5-HT1AR) activation-induced outward currents from layer 5 pyramidal neurons in the PFC, because a mouse model of Williams-Beuren syndrome (WBS; another developmental disorder exhibiting low innate anxiety and high sociability) reportedly showed larger 5-HT-induced currents. To investigate whether the 5-HT1AR activation-induced outward currents are involved in the endophenotype determination of social behavior, we examined 15q dup mice with a phenotype opposite to WBS. We found 5-HT elicited significantly larger outward currents in 15q dup mice than in WT controls, regardless of sociability. In contrast, baclofen-induced GABAB receptor-mediated outward currents were not significantly different between genotypes, although GABAB receptor was coupled to Gi/o as well as 5-HT1A. Further, we found the larger 5-HT1AR-mediated currents in 15q dup mice did not affect the magnitude of inhibitory action of NMDA receptor functions. Taken together, our results provide a potential physiological hallmark for developmental disorders that may involve the imbalance of the neuronal circuity in the PFC.
History of global burden of disease assessment at the World Health Organization
Authors: Mathers Colin D. 
Published: August 2020

Abstract
Background
The World Health Organization collaborated in the first Global Burden of Disease Study (GBD), published in the 1993 World Development Report. This paper summarizes the substantial methodological improvements and expanding scope of GBD work carried out by WHO over the next 25 years.

Methods
This review is based on a review of WHO and UN interagency work relating to Global Burden of Disease over the last 20 years, supplemented by a literature review of published papers and commentaries on global burden of disease activities and the production of global health statistics.

Results
WHO development of global burden of disease work in the Millenium Development Goal era resulted in regular publication of time series estimates of deaths by cause, age and sex at country level, consistent with UN population and life table estimates, and with cause-specific statistics produced across UN agencies and interagency collaborations. This positioned WHO as the lead agency to monitor many of the 43 health-related indicators for the UN Sustainable Development Goals.
In 2007, the Institute of Health Metrics and Evaluation (IHME) was established to conduct new global burden of disease and related work, funded by the Bill and Melinda Gates Foundation (BMGF). WHO was a core collaborator in its first GBD2010 study, but withdrew prior to publication as it was unable to obtain full access input data and methods. The publication of global health statistics by IHME resulted in user confusion and in debate over differences and the reasons for them. The new WHO administration of Director General Dr. Tedros Ghebreyesus has sought to make greater use of IHME outputs for its global health statistics and SDG monitoring.

Conclusions
WHO work on global burden of disease has positioned it to be the lead agency for monitoring many of the UN Sustainable Development Goals. Current moves to use IHME analyses raises a number of issues for WHO and for Member States in relation to WHO’s constitutional mandate, its accountability to Member States, the consistency of WHO and UN demographic and health statistics, and the ability of Member States to engage with the results of the complex and computer-intensive modelling procedures used by IHME. As new global health actors and funders have arisen in recent decades, and funding to carry out WHO’s expanding mandate has declined, it is unclear whether WHO has the ability or desire to continue as the lead agency for global health statistics.
Comparison of correction factor for both dynamic total thermal insulation and evaporative resistance between ISO 7933 and ISO 9920
Authors: Ueno Satoru 
Published: August 2020

Abstract
Background
Thermal insulation and evaporative resistance of clothing are the physical parameters to quantify heat transfer and evaporative dissipation from the human body to the environment, respectively. Wind and body movement decrease thermal insulation and evaporative resistance of clothing, which is represented as correction factors for dynamic total thermal insulation (CFi) and evaporative resistance (CFe), respectively. Then, CFi and CFe are parts of the key parameters to predict heat strain of workers by computer simulation. The objective of this study was to elucidate the difference of CFi and CFe between ISO 7933 and ISO 9920 and compare the difference of predicted rectal temperature, water loss, and exposure time limit calculated by using each correction factor.

Methods
CFi of ISO 7933 (CFi7933) and ISO 9920 (CFi9920), and CFe of ISO 7933 (CFe7933) and two kinds of CFe of ISO 9920 (CFe9920a, CFe9920b) were compared in terms of relative air velocity, walking speed for three kinds of thermal insulation of clothing. Next, two modified predicted heat strain (PHS) models were developed: modified PHS integrated with CFi9920 and CFe9920a (PHSmA) and modified PHS integrated with CFi9920 and CFe9920b (PHSmB). We calculated the rectal temperature, water loss, and exposure time limit by PHS, PHSmA, and PHSmB and compared the results.

Results
CFi7933 and CFi9920 were almost similar in terms of Var and walking speed, while CFe9920a and CFe9920b were larger than CFe7933 when Var was more than 1.0 m·s−1. Intrinsic clothing insulation (Icl) diminished the effects of Var on CFi7933, CFi9920, CFe7933, and CFe9920b. However, CFe9920a was not influenced by Icl. The predicted rectal temperature and water loss difference were larger between PHS and PHSmA as CFe difference got larger. The duration time when limit of rectal temperature of 38 °C was reached (DlimTre38) calculated by PHS was significantly longer than PHSmA, PHSmB at higher Var.

Conclusions
Precise correction factors for evaporative resistance are required to predict rectal temperature, water loss, and work-time limits.
An unusual presentation of an extragastrointestinal stromal tumour: a case report
Authors: Oliveira Santos Pedro , Cunha Teresa Margarida , Lemos Maria Manuel 
Published: August 2020

Abstract
Background
Gastrointestinal stromal tumours (GISTs) account for most mesenchymal gastrointestinal tumours, which in turn represent 1% of all gastrointestinal cancers. They mainly affect older adults, with a slight male preponderance. These lesions can be found along the digestive tract and most frequently in the stomach. Extragastrointestinal stromal tumours (EGISTs) are even rarer lesions, with few cases or series reported.

Case presentation
A 51-year-old woman was referred to our hospital due to progressive abdominal volume increase. Evaluation by multidetector computed tomography (MDCT) revealed a large intraperitoneal mixed tumour with few solid components, measuring up to 30 cm and compressing the surrounding structures, thought to be an ovarian tumour. Diagnostic laparotomy showed that the lesion was adherent to the greater gastric curvature and the vesical peritoneum. The lesion was removed without complications.

Conclusions
Imaging plays an essential role in the diagnosis of large intraperitoneal tumours. MDCT is the preferred technique to stage and to follow-up EGISTs.
Clinical features of adolescents diagnosed with eating disorders and at risk for psychosis
Authors: Mensi Martina Maria , Rogantini Chiara , Nacinovich Renata , Riva Anna , Provenzi Livio , Chiappedi Matteo , Balottin Umberto , Borgatti Renato 
Published: August 2020

Abstract

Background.
The presence of subthreshold psychotic symptoms in adolescents with eating disorders is poorly described. This study provides a detailed characterization of adolescents affected by eating disorders in the absence or presence of subthreshold psychotic symptoms, taking into account a wide set of sociodemographic, psychological, and clinical variables.

Methods.
Ninety-four adolescents diagnosed with eating disorders were interviewed, focusing on clinical anamnesis and sociodemographic data collection. The Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to assess the presence (HR+) or absence (HR−) of subthreshold psychosis. The clinicians completed a questionnaire on eating disorders severity, whereas patients provided self-report measures of global social functioning and psychological symptoms associated with eating disorders.

Results.
Attenuated psychotic symptoms were highly frequent (84% of subjects). HR+ patients experienced more frequently purging behaviors and dysmorphophobia and received a greater amount of antipsychotic drugs. Compared to HR− counterparts, HR+ patients reported higher eating disorders severity and psychological symptoms (i.e., ineffectiveness, interpersonal and affective problems) associated with eating disorders. Finally, a significant correlation between global social functioning and eating disorders severity emerged only for HR− subjects.

Conclusions.
These descriptive data are warranted to identify a potential psychotic core in eating disorders, mainly concerning body image and weight as well as specific psychological features. The availability of reliable and valid markers of risk can further increase our capacity to detect the early emergence of psychosis in adolescents with eating disorders, whose outcome might be worsened by the presence of psychotic symptoms.
Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer
Authors: Tutt A. , Robson M. , Garber J. E. , Domchek S. , Audeh M. W. , Weitzel J. N. , Friedlander M. , Carmichael J. 
Published: August 2020

CRA501 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text]
Partial breast irradiation or whole breast radiotherapy for early breast cancer: A meta-analysis of randomized controlled trials
Authors: Valachis A. , Mauri D. , Polyzos N. P. , Mavroudis D. , Georgoulias V. , Casazza G. 
Published: August 2020

CRA532 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. No significant financial relationships to disclose.
HER-2/neu in tissue and serum at time of primary diagnosis of breast cancer
Authors: Dresse M. , Mayr D. , Heinemann V. , Kahlert S. , Bauerfeind I. , Nagel D. , Seidel D. , Stieber P. 
Published: August 2020

e11500 Aim: HER2 in breast cancer tissue is a marker of high prognostic and predictive relevance. Soluble HER-2, the extracellular domain of the HER-2/neu receptor which is shed into the blood, has been suggested to be a helpful tumor marker. We investigated whether there exists a relationship between the concentration of HER-2/neu Shed Antigen in serum (s-HER-2/neu) and HER- 2/neu in breast cancer tissue and whether this relationship could be used for diagnostic purposes. Patients and Methods: s-HER- 2/neu was measured at time of primary diagnosis in the pretherapeutical (presurgical) sera of 525 breast cancer patients with known HER- 2/neu-status in breast cancer tissue. 33 of the patients (6,3%) revealed to have distant metastases (M1). The HER-2/neu- status in tumor tissue was determined by immunhistochemistry, followed by subsequent FISH analysis in case of score 2+. Dako-Score 3+ or 2+ and geneamplification in FISH analysis were regarded as HER-2/neu-positive. HER-2/neu shed antigen was analysed by Immunoassay. Results: For patients without distant metastases (M0) as well as patients with distant metastases (M1) we observed a correlation of s-HER-2/neu with HER-2/neu-status. The median s-HER-2/neu-concentrations were 11.7 ng/ml (13.2 ng/ml) for the HER-2/neu-negative resp. -positive patients in the M0 group (p<0,001) and 11.9 ng/ml (16,0 ng/ml) in the M1 group (p=0,01). In 492 M0-patients we performed a ROC-analysis in order to investigate the diagnostic capacity of s-HER-2/neu concerning its predictive value for the HER-2/neu-status: using a cut off value of 30 ng/ml the HER-2/neu-status was always positive, corresponding to a specificity of 100% and a sensitivity of 7.7 %. Conclusions: There is a correlation between high s-HER-2/neu-values and a positive HER-2/neu-status. Pretherapeutical s-HER- 2/neu-values ≥30 ng/ml were only observed in HER-2/neu-positive patients. HER-2/neu shed antigen in serum can add up to the HER-2/neu-status and might reveal false-negative tissue findings. [Table: see text]
Pharmacogenomic prediction of breast cancer treatment outcome with adjuvant tamoxifen in postmenopausal women with estrogen receptor-positive breast cancer
Authors: Pribylova O. , Petruzelka L. B. , Argalaczova S. , Konopasek B. , Drazdakova J. , Slanar O. , Slanar O. , Zima T. 
Published: August 2020

e11501 Background: The clinical outcome of tamoxifen-treated breast cancer patients may be influenced by the activity of cytochrome P450 enzymes that catalyze the formation of antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. Methods: The AmpliChip CYP450 Test was used to identify CYP2D6 genotypes which have an impaired ability to metabolize tamoxifen into the active metabolite, endoxifen. Results: Our aim is to determine the share of ultrarapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizers in the group of postmenopausal women with estrogen receptor-positive breast cancer. We are presenting first 72 results as the part of long term study on 180 women. It is evident that EM and UM have significantly lower percentage of disease progression (22% respectively 0%) compare to IM (67%). No progression observed at PM needs further monitoring and investigation. Conclusions: The results tentatively support the hypothesis, that the genetic variants associated with activity of CYP2D6 could help to clinicians in determining the therapeutic strategy. [Table: see text] No significant financial relationships to disclose.
Non-sentinel lymph node status and prognosis of the breast cancer patients with micrometastatic sentinel lymph nodes
Authors: Jinno H. , Onishi T. , Takahashi M. , Sakata M. , Kitagawa Y. , Kitamura N. , Nakahara T. , Mukai M. 
Published: August 2020

e11504 Background: Sentinel lymph node biopsy (SLNB) has become a standard therapy for clinically node-negative breast cancer patients and improvements of histopathological and molecular analysis of sentinel lymph node (SLN) have increased the rate of micrometastases identified. However it remains controversial whether to perform axillary lymph node dissection (ALND) for patients with micrometastases in SLNs and their prognostic significance is also a matter of debate. The purpose of this study is to determine the non- sentinel lymph node (NSLN) status and prognosis of the patients with micrometastatic SLNs. Methods: A prospective database of 666 breast cancer patients with the tumor size less than 3cm and clinical negative node, who underwent SLNB from January 2002 to July 2007 at Keio University Hospital was analyzed. SLNs were detected using a combined method of isosulfun blue dye and small-sized technetium-99m-labeled tin colloid. SLNs were diagnosed with standard hematoxylin and eosin (HE) staining and immunohistochemical (IHC) analysis. Results: Micrometastases in SLNs were found in 50 (7.5%) of 666 patients. Twenty nine (58.0%) of 50 patients with micrometastatic SLNs underwent ALND and revealed no NSLN metastasis. Among 21 (42.0%) patients with micrometastatic SLNs who skipped ALND, no axillary lymph node recurrence has been observed in the median follow-up time of 43 months, although 20 patients (95.2%) in 21 patients received adjuvant systemic therapy. There is no significant difference in recurrence free survival between the patients with micrometastatic and negative SLNs (98.0% vs. 95.7%, respectively). Conclusions: These date suggested that it may not be necessary to perform ALND for the patients with micrometastases in SLNs and the presence of micrometastases in SLNs may not be associated with prognosis. No significant financial relationships to disclose.
Prognostic value of serum level of HER-2 extracellular domain (ECD) at diagnosis of HER-2 overexpressed primary breast cancer (BC)
Authors: Thureau S. , Clatot F. , Pillé J. , Laberge-Le-Couteulx S. , Rigal O. , Veyret C. , Basuyau J. , Blot E. 
Published: August 2020

e11508 Background: Serum level of HER2 ECD is an adverse prognostic factor in HER2 over-expressed metastatic BC. We analyzed the prognostic value of serum level of HER2 ECD at the diagnostic of HER2 over-expressed primary BC. Methods: Patients with HER2 over-expressed primary BC treated with adjuvant trastuzumab in 2005 and 2006 were retrospectively analyzed. Serum level of HER2 ECD was assessed on frozen sera collected for CA15–3 measurement before initial treatment. Serum level of HER2 ECD was measured with an Elisa commercial kit (Oncogene Science, Cambridge, MA). The cut-off was 15μg/l as recommended. Results: Pre-treatment serum was available for 65 patients treated for non metastatic HER2 over-expressed BC. Seven patients (11%) had initially an elevated serum level of HER2 ECD (mean 25μg/l, range 15.1–38.9). After an average follow-up of 30 months, 4 patients (57%) out of the 7 with initially elevated serum level of HER2 ECD had a metastatic relapse of BC. In contrast, only 3 patients (5%) out of 58 with initially low serum level of HER2 ECD experienced relapse (p=0.004). Median of serum level of HER2 ECD was 17μg/l in patients who experienced relapse during follow-up whereas it was 8.4μg/l in patients who remained relapse-free (p=0.03). Univariate analysis showed that only elevated serum level of HER2 ECD and absence of hormone receptors expression were linked with metastatic relapse (p=0.0004 and p=0.02, respectively). Multivariate analysis showed that elevated serum level of HER2 ECD and absence of hormone receptors expression were linked with metastatic relapse (p=0.02 and p=0.04, respectively). Survival curves showed also that elevated serum level of HER2 ECD was related with a worse disease-free survival (p=0.0004). Conclusions: In this small series, elevated serum level of HER2 ECD was an adverse prognostic factor for HER2 over- expressed non metastatic primary BC. It was also a predictive factor for early failure of adjuvant treatment with trastuzumab. No significant financial relationships to disclose.
A phase II trial of a neoadjuvant platinum-containing regimen for locally advanced breast cancer: Pathologic response, long-term follow-up, and correlation with biomarkers
Authors: Shenkier T. N. , Hayes M. , Gelmon K. A. , Chia S. , Bajdik C. , Norris B. , Caroline S. , Hassell P. , O’Reilly S. E. , Allan S. , Yerushalmi R. 
Published: August 2020

e11510 Background: To determine the response, tolerability, and long-term outcome of a neoadjuvant platinum-containing regimen for locally advanced breast cancer (LABC). To search for correlation between pathologic complete response (pCR) and predefined biomarkers in this cohort. Patients and Methods: Patients with LABC received eight cycles of either sequence A or B. Sequence A was doxorubicin 60 mg/m2 and paclitaxel 175 mg/m2 (AT) q3w X 4 followed by cisplatin (C) 60 mg/m2 and paclitaxel 90 mg/m2 (CT) q2w X 4. Sequence B was CT x 4 followed by AT x 4. In addition to estrogen receptor and HER2, immunohistochemistry (IHC) for MDR-1, MRP-1, topoisomerase IIα(topoIIα) and p53 was performed. Results: 88 patients were evaluable for response and toxicity. Median follow-up was 97 months. The overall pCR rate was 21.5%. For subgroups ER+/HER2-, HER2 +, and double negative (ER-/ HER2-) disease the pCR was 5.9%,23.3% and 35% respectively, p=0.006. Five year(y) overall survival for the entire cohort was 71.1%. Five y overall survival was 88.1% (CI 77.1%, 99.1%) for the ER positive HER2 negative group compared to 68.5% (CI 51.3%, 85.7%) and 49.5 (CI 27.4%, 71.6%) in the HER2 positive and “double negative” group respectively (p=0.0077). Over-expression of topo IIα was correlated with pCR (p<0.001). There were no toxic deaths. Conclusions: A platinum-containing neoadjuvant regimen was well tolerated and achieved a pCR rate which compares favorably to other recent studies of multi-agent chemotherapy. Further studies tailored for specific breast cancer subtypes are required. No significant financial relationships to disclose.
Measurement of quality of life in women with breast cancer before and after adjuvant chemotherapy: A structural equation modelling
Authors: Choudhury J. B. , Beadle G. , Mengersen K. 
Published: August 2020

e11513 Background: This study examines breast cancer patients’ individual changes in health related quality of life (HRQOL) measures over time and the relationships between these measures within the framework of Structural equation modeling (SEM). Methods: One hundred and fifty five Australian women with breast cancer were asked to complete the Functional Assessment of Cancer Therapy Breast, Version 4 (FACT-B) pre- and post-chemotherapy as measures of HRQOL. In SEM, growth curve modelling was required for the estimation of individual differences in developmental changes of HRQOL scales over time. A growth mixture model was also used for identifying the cross-group differences in the pattern of changes in a given population over time. Results: Reliability and validity of the FACT-G including the fatigue subscale and breast cancer subscale for evaluating Australian breast cancer patients was determined to be sufficient for research purposes. After adjustment for covariates, two subgroups of women were identified with respect of patterns of response, representing largely increasing and decreasing trends in HRQOL respectively. In the former group, on average 85% of breast cancer women reported changes over time with respect to individual HRQOL measures and 78% reported such changes with respect to combined HRQOL Scores. A small group of women reported changes with respect to HRQOL measures in the decreasing group. The greatest contribution to variation in HRQOL measures was in the breast cancer subscale for both individual and combined scores. Subsequent factor analysis of the breast cancer subscale revealed that with one exception, all items loaded onto three separate factors described as self-esteem, physical and psychological. The latter two improved over time, but self- esteem was largely unchanged. Conclusions: The study presents a technique that allows us to identify potential subgroups of study subjects that experience different trajectories of responses. The results of this study provide greater insight into HRQOL changes over time and can help to plan interventions in a better way, ultimately contributing to improvement in HRQOL of women with breast cancer. No significant financial relationships to disclose.