bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Chk1 inhibitor SAR-020106 sensitizes human glioblastoma cells to irradiation, to temozolomide, and to decitabine treatment
Authors: Patties Ina , Kallendrusch Sonja , Böhme Lisa , Kendzia Eva , Oppermann Henry , Gaunitz Frank , Kortmann Rolf-Dieter , Glasow Annegret 
Published: October 2019

Abstract

Background
Glioblastoma is the most common and aggressive brain tumour in adults with a median overall survival of only 14 months after standard therapy with radiation therapy (IR) and temozolomide (TMZ). In a novel multimodal treatment approach we combined the checkpoint kinase 1 (Chk1) inhibitor SAR-020106 (SAR), disrupting homologue recombination, with standard DNA damage inducers (IR, TMZ) and the epigenetic/cytotoxic drug decitabine (5-aza-2′-deoxycitidine, 5-aza-dC). Different in vitro glioblastoma models are monitored to evaluate if the impaired DNA damage repair may chemo/radiosensitize the tumour cells.

Methods
Human p53-mutated (p53-mut) and -wildtype (p53-wt) glioblastoma cell lines (p53-mut: LN405, T98G; p53-wt: A172, DBTRG) and primary glioblastoma cells (p53-mut: P0297; p53-wt: P0306) were treated with SAR combined with TMZ, 5-aza-dC, and/or IR and analysed for induction of apoptosis (AnnexinV and sub-G1 assay), cell cycle distribution (nuclear PI staining), DNA damage (alkaline comet or gH2A.X assay), proliferation inhibition (BrdU assay), reproductive survival (clonogenic assay), and potential tumour stem cells (nestinpos/GFAPneg fluorescence staining). Potential treatment-induced neurotoxicity was evaluated on nestin-positive neural progenitor cells in a murine entorhinal-hippocampal slice culture model.

Results
SAR showed radiosensitizing effects on the induction of apoptosis and on the reduction of long-term survival in p53-mut and p53-wt glioblastoma cell lines and primary cells. In p53-mut cells, this effect was accompanied by an abrogation of the IR-induced G2/M arrest and an enhancement of IR-induced DNA damage by SAR treatment. Also TMZ and 5-aza-dC acted radioadditively albeit to a lesser extent. The multimodal treatment achieved the most effective reduction of clonogenicity in all tested cell lines and did not affect the ratio of nestinpos/GFAPneg cells. No neurotoxic effects were detected when the number of nestin-positive neural progenitor cells remained unchanged after multimodal treatment.

Conclusion
The Chk1 inhibitor SAR-020106 is a potent sensitizer for DNA damage-induced cell death in glioblastoma therapy strongly reducing clonogenicity of tumour cells. Selectively enhanced p53-mut cell death may provide stronger responses in tumours defective of non-homologous end joining (NHEJ). Our results suggest that a multimodal therapy involving DNA damage inducers and DNA repair inhibitors might be an effective anti-tumour strategy with a low risk of neurotoxicity.
Infants and young children feeding practice and associated factors among HIV positive mothers of children 0–23 months in health centers of Gulele sub-city, Addis Ababa, Ethiopia
Authors: Negash Samuel , Mesfin Firehiwot , Egata Gudina 
Published: October 2019

Abstract

Objective
A health facility based cross sectional study design was conducted among 358 randomly selected HIV positive mothers attending at four health centers from February 1 to 28, 2018. Magnitude of HIV positive mothers’ child feeding practice and associated factors was assessed according to WHO recommendation. Data were collected using structured pretested questionnaire and entered into EPI data version 3.1 and exported to SPSS version 20 computer software for analysis.

Result
The magnitude of recommended way of infant feeding practice among HIV positive mothers attending public health centers in Gulele sub-city is 37.4%, 95% CI (32.26–42.67). Statistically significant correlates of HIV exposed infant feeding practice of mothers in this study were knowledge of mother on HIV exposed infant feeding practice (AOR = 1.80 (95% CI 1.04–3.01)), head of family being father (AOR = 0.17 (95% CI 0.03–0.87)), having family (relatives) support (AOR = 2.05 (95% CI 1.00–4.18)) and information on HIV exposed infant feeding, practice (AOR = 1.77 (95% CI 1.07–2.93)).
Angiotensin II receptor blocker LCZ696 attenuates cardiac remodeling through the inhibition of the ERK signaling pathway in mice with pregnancy-associated cardiomyopathy
Authors: Wang Yi , Guo Zhiheng , Gao Yongmei , Liang Ping , Shan Yanhong , He Jin 
Published: October 2019

Abstract
Pregnancy-associated cardiomyopathy (PAH) represents a pregnancy-associated myocardial disease that is characterized by the progression of heart failure due to marked left ventricular systolic dysfunction. Compelling evidence has highlighted the potential of angiotensin (Ang) receptor inhibitors as therapeutic targets in PAH treatment. The present study aims to elucidate the molecular mechanisms underlying Ang II receptor inhibitor LCZ696 treatment in PAH. Initially, a PAH mouse model was induced, followed by intraperitoneal injection of LCZ696. Subsequently, cardiomyocytes and fibroblasts were isolated, cultured, and treated with Ang II and LCZ696, followed by detection of the total survival rate, cardiac injury, cardiac fibrosis and apoptosis. Moreover, in order to quantify the cardiac hypertrophy and fibrosis degree of cardiac fibroblasts, the expression levels of markers of cardiac hypertrophy (ANP, βMHC and TIMP2) and markers of fibrosis (collagen I, collagen III and TGF-β) were evaluated. Furthermore, the potential effect of LCZ696 on the extracellular signal-regulated kinase (ERK) signaling pathway was examined. The acquired findings revealed that LCZ696 increased the total survival rate of PAH mice, but decreased cardiac injury, cardiac fibrosis, and apoptosis in vitro. LCZ696 attenuated cardiac injury induced by Ang II through the inhibition the expression of markers of cardiac hypertrophy, fibrosis and apoptosis by inhibiting ERK phosphorylation in vivo and in vitro. Altogether, LCZ676 could potentially alleviate cardiac remodeling in mice with PAH via blockade of the ERK signaling pathway activation. Our findings suggest that LCZ696 could be a potential target for PAH therapy.
Patients’ experiences from basic body awareness therapy in the treatment of binge eating disorder -movement toward health: a phenomenological study
Authors: Albertsen Marit Nilsen , Natvik Eli , Råheim Målfrid 
Published: October 2019

Abstract

Background
Binge Eating Disorder (BED) is the most common eating disorder. Patients with BED are often not diagnosed, nor offered adequate specific treatment. A great number of those who receive recommended treatment do not recover over time. More knowledge about central aspects of BED, and treatments that specifically target such aspects is needed. Previous research has linked body experience to the development and maintenance of eating disorders, as well as influencing treatment results and the risk of relapse. The aim of this study was to explore how patients with BED experience Basic Body Awareness Therapy (BBAT), which is a psychomotor physiotherapy treatment addressing body experience.

Method
In this phenomenological study, we interviewed two patients with BED in depth during and after treatment. Video observations of treatment sessions and logs written by the patients were used as supporting data. The analysis was guided by Van Manen’s hermeneutic phenomenology.

Results
A meaning structure was identified: “On the way from the body as a problem to the body as a possibility.” The two participants that besides BED also had a history of childhood trauma, perceived BBAT as a process of getting to know their own bodies in new ways, and described that the way they related to their own body changed as did aspects of their way of being. These changes were prominent when the participants described emotions, movement, pain, calmness, and self-experience, and interwoven with relational aspects as well as practices in everyday life.

Conclusion
The present results indicate that BBAT stimulated body experience in a way that opened new possibilities for two participants with BED, and hence that BBAT can improve the health status of BED patients also suffering from childhood trauma.
Comparison of a tridimensional cephalometric analysis performed on 3T-MRI compared with CBCT: a pilot study in adults
Authors: Maspero Cinzia , Abate Andrea , Bellincioni Francesca , Cavagnetto Davide , Lanteri Valentina , Costa Antonella , Farronato Marco 
Published: October 2019

Abstract

Objective
Since the introduction of cone-beam computed tomography (CBCT) in dentistry, this technology has enabled distortion-free three-dimensional cephalometric analysis for orthodontic and orthognathic surgery diagnosis. However, CBCT is associated with significantly higher radiation exposure than traditional routine bidimensional examinations for orthodontic diagnosis, although low-dose protocols have markedly reduced radiation exposure over time.
The objective of this preliminary feasibility study is to compare the accuracy and diagnostic capabilities of an already-validated three-dimensional cephalometric analysis on CBCT to those of an analysis on 3-T magnetic resonance imaging (3T-MRI) to assess whether the latter can deliver a comparable quality of information while avoiding radiation exposure.

Materials and methods
In order to test the feasibility of three-dimensional cephalometry on 3T-MRI, 18 subjects (4 male; 14 female) with mean age 37.8 ± SD 10.2, who had undergone both maxillofacial CBCT and maxillofacial 3T-MRI for various purposes within 1 month, were selected from the archive of the Department of Dentistry and Maxillofacial Surgery of Fondazione Ospedale Policlinico Maggiore, IRCCS, Milano, Italy.
A three-dimensional cephalometric analysis composed of ten midsagittal and four bilateral landmarks and 24 measurements (11 angular, 13 linear) was performed on both scans using Mimics Research® v. 17.0 (NV, Technologielaan 15, 3001 Leuven, Belgium). Cephalometric analysis was performed twice by two independent orthodontists for each scan, and each orthodontist repeated the measurements 3 weeks later. Statistical analysis was performed with SPSS® 20.00 for Windows (IBM® Corporation, Sommers, NY, USA). A Bland-Altman test for each cephalometric value was performed to assess the agreement between the procedures. The intraclass correlation coefficient (ICC) was used to assess interobserver and intraobserver reliability. The coefficient of variation was used to evaluate precision.

Results
Both procedures showed good reliability, with mean intraobserver ICCs of 0.977/0.971 for CBCT and 0.881/0.912 for MRI. The average interobserver ICCs were 0.965 for CBCT and 0.833 for MRI. A Bland-Altman analysis for the cephalometric tracing revealed a similar range of agreement between the two modalities; the bias range (mean ± SD) was − 0.25–0.66 mm (0.174 ± 0.31) for distances and − 0.41–0.54° (0.12 ± 0.33) for angles.

Conclusions
Within the main limitation of this pilot study, that is, the small sample, it is possible to state that cephalometric measurements on 3T-MRI seem to possess adequate reliability and repeatability and that they show satisfying agreement with values measured on CBCTs. An MRI examination does not expose patients to ionizing radiation and could provide an alternative to CBCT for three-dimensional cephalometrics in the future.
Electronic nicotine delivery system (ENDS) liquid nicotine exposure in young children presenting to US emergency departments, 2018
Authors: Chang Joanne T. , Rostron Brian L. 
Published: October 2019

Abstract

Background
Increased use of electronic nicotine delivery systems (ENDS) in the United States (U.S.) has been related to acute adverse events from liquid nicotine exposure. Previous studies have reported on these events through 2017.

Findings
We used 2018 National Emergency Injury Surveillance System data to generate national estimates with 95% confidence intervals (CIs) of ENDS liquid nicotine-related poisonings among children under age 5 treated in U.S. hospital emergency departments (EDs). In 2018, an estimated 885 (95% CI: 397–1374) poisoning cases related to liquid nicotine among children under 5 were treated in U.S. EDs, which was a non-statistically signficant increase from 2017 (411 poisoning cases, 95% CI: 84–738). The most common route of exposure was through ingestion (99.4%). The majority of cases were treated and released from the hospital (90.0%), 8.9% of the cases left the hospital without being seen, and 1.1% of the cases were treated and admitted to the hospital.

Conclusions
This study provides updated national estimates of poisoning events related to liquid nicotine exposure that occurred in 2018 among children under age 5. Updated information from this study may complement public education efforts and prevent liquid nicotine exposure among children.
Temporary loss of consciousness during cetuximab treatment of a patient with metastatic colon cancer: a case report
Authors: Fukui Taro , Suzuki Koichi , Tamaki Sawako , Abe Iku , Endo Yuhei , Ishikawa Hideki , Kakizawa Nao , Watanabe Fumiaki , Saito Masaaki , Tsujinaka Shingo , Futsuhara Kazushige , Miyakura Yasuyuki , Noda Hiroshi , Rikiyama Toshiki 
Published: October 2019

Abstract

Background
Anti-epidermal growth factor receptor (EGFR) antibody is widely used for the treatment of patients with metastatic colorectal cancer. Hypomagnesemia is a comparatively frequent adverse event of this drug, which is likely overlooked because it occurs later in treatment without symptoms. Furthermore, hypomagnesemia and hypomagnesemia-induced corrected QT (QTc) prolongation may lead to loss of consciousness (LOC), the onset of which is not generally considered associated with the treatment of anti-EGFR antibody because of its rare occurrence. Here, we present a colorectal cancer patient treated with anti-EGFR antibody, who suffered LOC during treatment while severe hypomagnesemia or QTc prolongation was not observed.

Case presentation
A 69-year-old man with metastatic colon cancer was treated with cetuximab (anti-EGFR antibody) plus irinotecan as third-line chemotherapy. His serum magnesium level gradually decreased, and grade 2 hypomagnesemia (a serum magnesium level of 0.9 mg/dL) was observed at the 12th administration of cetuximab. In light of this development, intravenous supplementation of 20 mEq magnesium sulfate began with careful blood monitoring despite the lack of clinical symptoms. Electrocardiogram (ECG) showed prolonged QT or corrected QT (QTc) intervals (grade 1). His serum magnesium level remained at 0.9 mg/dL, and no hypomagnesemia symptoms were observed by the 17th administration of cetuximab. After the treatment, however, he suddenly lost consciousness without symptoms related to infusion or allergic reactions. Circulatory collapse following dermatological reactions and respiratory events were not evident. Intravenous supplementation of magnesium sulfate was administered again. He awakened 2 min after the onset of temporary LOC without any other symptoms related to hypomagnesemia, such as lethargy, tremor, tetany, and seizures. No other etiology outside of the low level of serum magnesium was confirmed in further examinations. Cetuximab was discontinued, and his serum magnesium level returned to a level within the normal range after 6 weeks. Because of tumor progression, regorafenib and TAS-102 (trifluridine tipiracil hydrochloride) were introduced sequentially for 6 months. Five months after the final treatment of TAS-102, he died of his primary disease, which reflected a survival period of 4 years and 6 months since the beginning of treatment.

Conclusions
This case report reminds clinicians that LOC can be induced without severe hypomagnesemia or QTc prolongation, during anti-EGFR antibody treatment for metastatic colorectal cancer even while under carefully monitored magnesium supplementation.
A pathological complete response by chemotherapy with S-1 and oxaliplatin for a locally advanced duodenal adenocarcinoma in Lynch syndrome: a case report
Authors: Yasuda Satoshi , Harada Suzuka , Tsujimoto Akinori , Aoki Satoko , Takei Takeshi , Migita Kazuhiro , Ueno Masato , Tatsumi Mitsutoshi , Watanabe Akihiko 
Published: October 2019

Abstract

Background
Although primary duodenal adenocarcinoma (DA) is a rare malignancy representing ~ 0.5% of all gastrointestinal cancers, the incidence of DA is more frequent in Lynch syndrome. Because of its rarity, treatment strategies or optimal chemotherapeutic regimens have not been clearly defined for advanced DA.

Case presentation
A 72-year-old woman with Lynch syndrome visited our hospital with a right upper abdominal pain. Computed tomography (CT) showed wall thickness with enhancement in the second portion of the duodenum and adjacent abdominal wall, which suggested direct tumor invasion to the abdominal wall. Upper gastrointestinal endoscopy (UGE) showed a large ulcerative tumor in the second portion of the duodenum, and histological analysis revealed a poorly differentiated adenocarcinoma. A cT4N0M0, cStage IIB (Union for International Control Cancer TNM staging) DA was diagnosed. After three courses of chemotherapy with S-1 and oxaliplatin (SOX), follow-up CT and UGE showed shrinkage of the duodenal tumor. Therefore, the patient underwent pancreaticoduodenectomy with lymph node dissection with curative intent. Histological examination showed a pathological complete response to SOX therapy. The postoperative course was uneventful, and the patient was discharged on postoperative day 29. The patient received no adjuvant chemotherapy, and there has been no evidence of recurrence 6 months after the operation.

Conclusions
SOX therapy provided a remarkable response and can be an optimal chemotherapeutic regimen for advanced DA in Lynch syndrome.
Prognosis of lymphotropic invasive micropapillary breast carcinoma analyzed by using data from the National Cancer Database
Authors: Lewis Gary D. , Xing Yan , Haque Waqar , Patel Tejal , Schwartz Mary , Chen Albert , Farach Andrew , Hatch Sandra S. , Butler E. Brian , Chang Jenny , Teh Bin S. 
Published: October 2019

AbstractBackgroundInvasive micropapillary carcinoma (IMPC) is an uncommon subtype of breast cancer. Previous studies of this subtype demonstrated a higher propensity for lymph node metastases as compared with invasive ductal carcinoma (IDC). The purpose of the present study was to determine the clinical characteristics, outcomes, and propensity for lymph node metastasis of patients with IMPC of the breast recorded in the National Cancer Database (NCDB).MethodsRecords of patients with IMPC diagnosed between 2004 and 2014 were retrieved from the NCDB. Log‐rank test was performed to evaluate associations of clinical characteristics with overall survival (OS). Cox proportional hazards model was used to determine variables associated with OS.ResultsOverall, 2660 patients with IMPC met the selection criteria; the 5‐year OS rate was 87.5% and 24.9% of patients had nodal involvement at presentation. Patients with ≥ 4 positive lymph nodes had shorter OS than node‐negative patients, whereas patients with 1–3 positive nodes had similar OS to node‐negative patients. Age < 65 years, receipt of radiotherapy, and estrogen receptor positivity were also associated with prolonged OS. The benefit of radiotherapy was limited to IMPC patients undergoing lumpectomy; there was no benefit for the patients undergoing mastectomy (regardless of nodal positivity/negativity).ConclusionsFavorable prognostic factors of IMPC patients included age < 65 years, < 4 positive lymph nodes, receipt of radiotherapy, and estrogen receptor positivity. The results presented herein suggest a survival benefit associated with radiotherapy in IMPC treatment, though this may be limited to the patients treated with lumpectomy.
Planting and harvesting innovation - an analysis of Samsung Electronics
Authors: Jang Seung Hoon , Lee Sang M. , Kim Taewan , Choi Donghyun 
Published: October 2019

Abstract
This study explores how firms manage the entire life cycle of innovation projects based on the framework of harvesting and planting innovation. While harvesting innovation seeks new products in the expectation of financial performance in the short term, planting innovation pursues creating value over a long time period. Without proper management of the process of planting and harvesting innovation, firms with limited resources may not be successful in launching innovative new products to seize a momentum in high tech industries. To examine this issue, the case of Samsung Electronics (SE), now an electronics giant originated from a former developing country, is analyzed. SE has shown to effectively utilize co-innovation to maintain numerous planting and harvesting innovation projects. Both researchers and practitioners would be interested in learning about how SE shared risks of innovation investment with external partners at the early stage of innovation cycles.
In vitro differentiation of cGMP-grade retinal pigmented epithelium from human embryonic stem cells
Authors: Lojudice Fernando H. , Fernandes Rodrigo A. Brant , Innocenti Francesco , Franciozi Carlos E. , Cristovam Priscila , Maia Maurício , Sogayar Mari C. , Belfort Rubens 
Published: October 2019

Abstract

Background
The World Health Organization (WHO) estimates that the number of individuals who lose their vision due to retinal degeneration is expected to reach 6 million annually in 2020. The retinal degenerative diseases affect the macula, which is responsible for central and detailed vision. Most macular degeneration, i.e., age-related macular degeneration (AMD) develops in the elderly; however, certain hereditary diseases, such as the Stargardt disease, also affect young people. This degeneration begins with loss of retinal pigmented epithelium (RPE) due to formation of drusen (atrophic) or abnormal vessels (exudative). In wet AMD, numerous drugs are available to successful treat the disease; however, no proven therapy currently is available to treat dry AMD or Stargardt. Since its discovery, human embryonic stem cells (hESCs) have been considered a valuable therapeutic tool. Some evidence has shown that transplantation of RPEs differentiated from hESCs cells can result in recovery of both RPE and photoreceptors and prevent visual loss.

Methods
The human embryonic WA-09 stem cell lineage was cultured under current Good Manufacturing Practices (cGMP) conditions using serum-free media and supplements. The colonies were isolated manually and allowed to spontaneously differentiate into RPE cells.

Results
This simple and effective protocol required minimal manipulation and yielded more than 10e8 RPE cells by the end of the differentiation and enrichment processes, with cells exhibiting a cobblestone morphology and displaying cellular markers and a gene expression profile typical of mature RPE cells. Moreover, the differentiated cells displayed phagocytic activity and only a small percentage of the total cells remained positive for the Octamer-binding transcriptions factor 4 (OCT-4) pluripotency cell marker.

Conclusions
These results showed that functional RPE cells can be produced efficiently and suggested the possibility of scaling-up to aim at therapeutic protocols for retinal diseases associated with RPE degeneration.