bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Potent HER3 Monoclonal Antibody That Blocks Both Ligand-Dependent and -Independent Activities: Differential Impacts ofPTENStatus on Tumor Response
Authors: Xiao Zhan , Carrasco Rosa A. , Schifferli Kevin , Kinneer Krista , Tammali Ravinder , Chen Hong , Rothstein Ray , Wetzel Leslie , Yang Chunning , Chowdhury Partha , Tsui Ping , Steiner Philipp , Jallal Bahija , Herbst Ronald , Hollingsworth Robert E. , Tice David A. 
Published: February 2016

AbstractHER3/ERBB3 is a kinase-deficient member of the EGFR family receptor tyrosine kinases (RTK) that is broadly expressed and activated in human cancers. HER3 is a compelling cancer target due to its important role in activation of the oncogenic PI3K/AKT pathway. It has also been demonstrated to confer tumor resistance to a variety of cancer therapies, especially targeted drugs against EGFR and HER2. HER3 can be activated by its ligand (heregulin/HRG), which induces HER3 heterodimerization with EGFR, HER2, or other RTKs. Alternatively, HER3 can be activated in a ligand-independent manner through heterodimerization with HER2 in HER2-amplified cells. We developed a fully human mAb against HER3 (KTN3379) that efficiently suppressed HER3 activity in both ligand-dependent and independent settings. Correspondingly, KTN3379 inhibited tumor growth in divergent tumor models driven by either ligand-dependent or independent mechanisms in vitro and in vivo. Most intriguingly, while investigating the mechanistic underpinnings of tumor response to KTN3379, we discovered an interesting dichotomy in that PTEN loss, a frequently occurring oncogenic lesion in a broad range of cancer types, substantially blunted the tumor response in HER2-amplified cancer, but not in the ligand-driven cancer. To our knowledge, this represents the first study ascertaining the impact of PTEN loss on the antitumor efficacy of a HER3 mAb. KTN3379 is currently undergoing a phase Ib clinical trial in patients with advanced solid tumors. Our current study may help us optimize patient selection schemes for KTN3379 to maximize its clinical benefits. Mol Cancer Ther; 15(4); 689–701. ©2016 AACR.
Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease
Authors: Wens Stephan C.A. , Schaaf Gerben J. , Michels Michelle , Kruijshaar Michelle E. , van Gestel Tom J.M. , in ‘t Groen Stijn , Pijnenburg Joon , Dekkers Dick H.W. , Demmers Jeroen A.A. , Verdijk Lex B. , Brusse Esther , van Schaik Ron H.N. , van der Ploeg Ans T. , van Doorn Pieter A. , Pijnappel W.W.M. Pim 
Published: February 2016

Background—
Elevated plasma cardiac troponin T (cTnT) levels in patients with neuromuscular disorders may erroneously lead to the diagnosis of acute myocardial infarction or myocardial injury.

Methods and Results—

In 122 patients with Pompe disease, the relationship between cTnT, cardiac troponin I, creatine kinase (CK), CK-myocardial band levels, and skeletal muscle damage was assessed. ECG and echocardiography were used to evaluate possible cardiac disease. Patients were divided into classic infantile, childhood-onset, and adult-onset patients. cTnT levels were elevated in 82% of patients (median 27 ng/L, normal values <14 ng/L). Cardiac troponin I levels were normal in all patients, whereas CK-myocardial band levels were increased in 59% of patients. cTnT levels correlated with CK levels in all 3 subgroups (
P
<0.001). None of the abnormal ECGs recorded in 21 patients were indicative of acute myocardial infarction, and there were no differences in cTnT levels between patients with and without (n=90) abnormalities on ECG (median 28 ng/L in both groups). The median left ventricular mass index measured with echocardiography was normal in all the 3 subgroups. cTnT mRNA expression in skeletal muscle was not detectable in controls but was strongly induced in patients with Pompe disease. cTnT protein was identified by mass spectrometry in patient-derived skeletal muscle tissue.

Conclusions—
Elevated plasma cTnT levels in patients with Pompe disease are associated with skeletal muscle damage, rather than acute myocardial injury. Increased cTnT levels in Pompe disease and likely other neuromuscular disorders should be interpreted with caution to avoid unnecessary cardiac interventions.
Meaning of Illness and Cardiovascular Risk Factors in Patients With Type 2 Diabetes
Authors: Lynch Cheryl P. , Williams Joni Strom , Voronca Delia , Walker Rebekah J. , Egede Leonard E. 
Published: February 2016

Purpose The purpose of this study was to examine the relationship between meaning of illness and cardiovascular disease risk factors in patients with type 2 diabetes. Methods The sample population was recruited from primary care clinics in the southeastern United States. The meaning of illness was assessed by a validated questionnaire with 5 subscales. The primary outcomes were cardiovascular disease (CVD) risk factors, assessed by A1C, systolic and diastolic blood pressure (SBP and DBP, respectively), and low-density lipoprotein cholesterol (LDL-C). Multivariate linear regression models investigated associations between the clinical outcomes and the 5 MIQ factors, controlling for possible confounders. Results The sample comprised 302 black and white participants of whom more than half were elderly (65+ years) and the vast majority were male (98%). Systolic blood pressure was positively associated with non-anticipated vulnerability. Diastolic blood pressure was negatively associated with degree of stress/change in commitments and positively associated with challenge/motivation/hope and non-anticipated vulnerability. Low-density lipoprotein cholesterol was significantly and negatively associated with degree of stress/change in commitments. Conclusions Meaning of illness had a significant effect on measured outcomes of CVD risk. The specific factor included in the overarching concept of meaning of illness differed in its influence, with more positive views of stress/commitments associated with lower blood pressure and LDL but more positive views of the challenge/hope/motivation and negative views of non-anticipated vulnerability associated with diabetes associated with higher systolic and diastolic blood pressure.
MiR-205 promotes proliferation, migration and invasion of nasopharyngeal carcinoma cells by activation of AKT signalling
Authors: Mao Yanjiao , Wu Shixiu , Zhao Ruping , Deng Qinghua 
Published: February 2016

Objective To examine the role of microRNA (miR)-205 in proliferation, migration and invasion of nasopharyngeal carcinoma (NPC). Methods The human NPC cell line CNE2 was transfected with miR-205 mimic, anti-miR-205 inhibitor or scrambled oligonucleotide (control). Cell proliferation was assessed via MTT assay. Cell migration and invasion were evaluated by transwell migration and Matrigel® invasion assay, respectively. Radiation induced apoptosis was quantified via Caspase-Glo3/7 assay. Apoptotic proteins and epithelial–mesenchymal transition (EMT) proteins were semiquantified by Western blot analysis. Results Overexpression of miR-205 increased the proliferation, migration and invasion of CNE2 cells, and decreased radiation-induced apoptosis compared with control cells. MiR-205 overexpression downregulated E-cadherin and upregulated Snail expression via downregulation of PTEN and upregulation of AKT. Conclusion MiR-205 plays vital roles in tumourigenesis and tumour progression in NPC, and may be a potential treatment target.
Comparison of effects of intravenous midazolam and ketamine on emergence agitation in children: Randomized controlled trial
Authors: Kim Kyung Mi , Lee Ki Hwa , Kim Yong Han , Ko Myoung Jin , Jung Jae-Wook , Kang Eunsu 
Published: February 2016

Objective A prospective, double-blind, randomized controlled trial to compare the effect of preoperative midazolam or ketamine on the incidence of emergence agitation (EA) following sevoflurane anaesthesia in children. Methods Paediatric patients (2–6 years old) undergoing ophthalmic surgery were allocated to receive premedication with either 0.1 mg/kg midazolam or 1 mg/kg ketamine. Incidence of EA and postoperative pain scores were recorded at 10-min intervals in the postanaesthetic care unit (PACU). The use of EA rescue medications (fentanyl or midazolam) was recorded. Results The incidence of EA was significantly lower in the ketamine group ( n = 33) than the midazolam group ( n = 34) at 10 and 20 min after transfer to PACU. There was no significant difference in overall incidence of EA. The frequency of midazolam use as rescue medication was significantly lower in the katamine group than in the midazolam group. Conclusion Premedication with ketamine is more effective than midazolam in preventing EA during the early emergence period after sevoflurane anaesthesia in children.
Evaluation of Inpatient Influenza and Pneumococcal Vaccination Acceptance Rates With Pharmacist Education
Authors: Queeno Brenda V. 
Published: February 2016

Objectives: To detail the implementation of a pharmacist-driven education program targeting patients who originally declined pneumococcal or influenza vaccination upon hospital admission and to evaluate the results. Methods: Patients admitted to a small community hospital who qualified to receive pneumococcal polysaccharide or influenza vaccination but declined upon admission were educated in person by pharmacists or pharmacy interns and reoffered vaccination. Patient education sheets were provided. Data were obtained via pharmacy intervention documentation in the pharmacy order entry system. Staff documented the outcome of counseling for each patient. Results: A total of 214 and 83 patients receiving influenza and pneumococcal vaccination counseling, respectively, were evaluated. As a result, 23.4% ( P = .06) and 26.5% (n = 83, P = .18) of patients agreed to receive influenza and pneumococcal vaccines, respectively. An unanticipated subset of patients were undecided after counseling and wanted to consider the information further before making a final decision. Taken together with those who consented to receive the vaccine after counseling, 39.2% ( P = .001) and 45.8% ( P = .01) of patients were influenced by the influenza and pneumococcal vaccination counseling, respectively. Conclusion: Patient education performed by a pharmacist or pharmacy intern showed a trend toward increased pneumococcal and influenza vaccination acceptance rates for inpatients who had initially declined.
Glucose Variability
Authors: Le Floch Jean-Pierre , Kessler Laurence 
Published: February 2016

Background: Glucose variability has been suspected to be a major factor of diabetic complications. Several indices have been proposed for measuring glucose variability, but their interest remains discussed. Our aim was to compare different indices. Methods: Glucose variability was studied in 150 insulin-treated diabetic patients (46% men, 42% type 1 diabetes, age 52 ± 11 years) using a continuous glucose monitoring system (668 ± 564 glucose values; mean glucose value 173 ± 38 mg/dL). Results from the mean, the median, different indices (SD, MAGE, MAG, glucose fluctuation index (GFI), and percentages of low [<60 mg/dL] and high [>180 mg/dL] glucose values), and ratios (CV = SD/m, MAGE/m, MAG/m, and GCF = GFI/m) were compared using Pearson linear correlations and a multivariate principal component analysis (PCA). Results: CV, MAGE/m (ns), GCF and GFI ( P < .05), MAG and MAG/m ( P < .01) were not strongly correlated with the mean. The percentage of high glucose values was mainly correlated with indices. The percentage of low glucose values was mainly correlated with ratios. PCA showed 3 main axes; the first was associated with descriptive data (mean, SD, CV, MAGE, MAGE/m, and percentage of high glucose values); the second with ratios MAG/m and GCF and with the percentage of low glucose values; and the third with MAG, GFI, and the percentage of high glucose values. Conclusions: Indices and ratios provide complementary pieces of information associated with high and low glucose values, respectively. The pairs MAG+MAG/m and GFI+GCF appear to be the most reliable markers of glucose variability in diabetic patients.
Myeloid sarcoma of submandibular salivary gland
Authors: Dagna Federico , Giordano Pamela , Boggio Valeria , Albera Roberto 
Published: February 2016

Objective: To report a rare case of a myeloid sarcoma of submandibular salivary gland. Methods: A 65-year-old woman with a history of successfully treated myelodysplastic syndrome, presenting with periodic painful swelling of her right submandibular area. Results: Physical evaluation, ultrasound and CT scan revealed the presence of a 3-cm mass contiguous to the submandibular salivary gland. A core needle biopsy confirmed the diagnosis of myeloid sarcoma. Bone marrow biopsy was still showing complete remission and the submandibular gland was the only extramedullary site involved. The patient was submitted to chemotherapy. Conclusion: Myeloid sarcoma is a rare extramedullary neoplasm. It can virtually involve any anatomic site, but it usually involves lymph nodes, paranasal sinuses, skin, soft tissue and periostium. Myeloid sarcomas of salivary glands are very rare and ENTs should be aware of this disease in order to include it in the differential diagnosis of a solitary neck mass.
Contrast-enhanced synthetic MRI for the detection of brain metastases
Authors: Hagiwara Akifumi , Hori Masaaki , Suzuki Michimasa , Andica Christina , Nakazawa Misaki , Tsuruta Kouhei , Takano Nao , Sato Shuji , Hamasaki Nozomi , Yoshida Mariko , Kumamaru Kanako Kunishima , Ohtomo Kuni , Aoki Shigeki 
Published: February 2016

Background Synthetic magnetic resonance imaging (MRI), a technique that enables creation of various contrast-weighted images from a single MRI quantification scan, is a useful clinical tool. However, there are currently no reports examining the use of contrast-enhanced synthetic MRI for detecting brain metastases. Purpose To assess whether contrast-enhanced synthetic MRI is suitable for detecting brain metastases. Material and Methods Ten patients with a combined total of 167 brain metastases who underwent quantitative MRI and conventional T1-weighted inversion recovery fast spin-echo (conventional T1IR) MRI before and after administration of a contrast agent were included in the study. Synthetic T1IR and T1-weighted (synthetic T1W) images were produced after parameter quantification. Lesion-to-white matter contrast and contrast-to-noise ratio were calculated for each image. The number of visible lesions in each image was determined by two neuroradiologists. Results The mean lesion-to-white matter contrast and mean contrast-to-noise ratio of the synthetic T1IR images were significantly higher than those of the synthetic T1W ( P < 0.001 and P < 0.001, respectively) and conventional T1IR ( P = 0.04 and P = 0.002, respectively) images. Totals of 130 and 124 metastases were detected in the synthetic T1IR images by the first and second radiologists, respectively. The corresponding numbers were 91 and 85 in the synthetic T1W images and 119 and 119 in the conventional T1IR images. Statistical significance was not found among detected numbers of lesions. Conclusion Synthetic T1IR imaging created better contrast compared with synthetic T1W or conventional T1IR imaging. The ability to detect brain metastases was comparable among these imaging.
Spontaneous brain tumor imaging of aged rat by crystal X-ray interferometer-based phase-contrast X-ray CT
Authors: Lwin Thet-Thet , Yoneyama Akio , Hara Atsuko , Ohbu Makoto , Maruyama Hiroko , Taguchi Masaya , Esashi Shogo , Matsushima Tsubasa , Terazaki Kei , Hyodo Kazuyuki , Takeda Tohoru 
Published: February 2016

Background Crystal X-ray interferometer-based phase-contrast X-ray computed tomography (C-PCCT) enables the depiction of internal structures of biological tissue without contrast agents. Purpose To determine the advantage of this technique in visualizing detailed morphological structures of a rare spontaneous brain tumor in an aged rat. Material and Methods An aged rat’s spontaneous brain tumor was imaged by C-PCCT without contrast agent. Three-dimensional (3D) images of the tumor microvasculature were reconstructed and compared with pathological pictures. Results C-PCCT depicted the tumor’s various pathological features clearly, e.g. its cell density and vasculature, and blood clots caused by hemorrhaging and/or hematomas. The obtained images resembled pathological pictures with a magnification of ×20 and were used to reconstruct 3D images of the tumor vascularity up to approximately 26 µm in diameter. Conclusion Since C-PCCT is able to depict various pathological conditions, it might be useful for cancer research.
RETRACTED ARTICLE: Universal minicircle sequence binding protein of Leishmania donovani regulates pathogenicity by controlling expression of cytochrome-b
Authors: Singh Ruby , Purkait Bidyut , Abhishek Kumar , Saini Savita , Das Sushmita , Verma Sudha , Mandal Abhishek , Ghosh Ayan Kr. , Ansari Yousuf , Kumar Ashish , Sardar Abul H. , Kumar Ajay , Parrack Pradeep , Das Pradeep 
Published: February 2016

AbstractBackgroundLeishmaniacontains a concatenated mitochondrial DNA, kDNA. Universal minicircle sequence binding protein (UMSBP), a mitochondrial protein, initiates kDNA replication by binding with a conserved universal minicircle sequence (UMS) of kDNA. Here, we describe first time inL. donovanithe regulation of DNA binding activity of UMSBP and the role of UMSBP in virulence.MethodsInsilco and EMSA study were performed to show UMS-binding activity of UMSBP. Tryparedoxin(TXN)-tryparedoxin peroxidase(TXNPx) assay as well as co-overexpression of cytochrome-b5 reductase-like protein (CBRL) and tryparedoxin inL. donovaniwere done to know the regulation of DNA binding activity of UMSBP. Knockout and episomal-expression constructs of UMSBP were transfected inL. donovani. The cell viability assay and immunofluorescence study to know the status of kDNA were performed. Macrophages were infected with transfected parasites. mRNA level of cytochrome b, activity of complex-III, intracellular ATP level of both transfected promastigotes and amastigotes as well as ROS concentration and the level of apoptosis of transfected promastigotes were measured. Level of oxidative phosphorylation of both transfected and un-transfected amastigotes were compared. Burden of transfected amastigotes in both macrophages and BALB/c mice were measured.ResultsL. donovaniUMSBP is capable of binding with UMS, regulated by redox through mitochondrial enzymes, TXN, TXNPx and CBRL. Depletion of UMSBP (LdU−/−) caused kDNA loss, which decreased cytochrome-b expression [component of complex-III of electron transport chain (ETC)] and leads to the disruption of complex-III activity, decreased ATP generation, increased ROS level and promastigotes exhibited apoptosis like death. Interestingly, single knockout of UMSBP (LdU−/+) has no effect on promastigotes survival. However, single knockout in intracellular amastigotes demonstrate loss of mRNA level of cytochrome-b, disruption in the activity of complex-III and reduced production of ATP in amastigotes than wild type. This process interfere with the oxidative-phosphorylation and thereby completely inhibit the intracellular proliferation of LdU−/+amastigotes in human macrophages and in BALB/c mice. Amastigotes proliferation was restored as wild type after episomal expression of LdUMSBP in LdU−/+parasites (LdU−/+AB).ConclusionThe LdUMSBP regulates leishmanial mitochondrial respiration and pathogenesis. So, LdUMSBP may be an attractive target for rational drug designing and LdU−/+parasites could be considered as a live attenuated vaccine candidate against visceral leishmaniasis.
Hospital treatment, mortality and healthcare costs in relation
to socioeconomic status among people with bipolar affective
disorder
Authors: Pan Yi-Ju. , Yeh Ling-Ling , Chen Yu-Chun , Kuo Kuei-Hong , Chang Chin-Kuo 
Published: February 2016

BackgroundEvidence regarding the relationships between the socioeconomic status and
long-term outcomes of individuals with bipolar affective disorder (BPD)
is lacking.AimsWe aimed to estimate the effects of baseline socioeconomic status on
longitudinal outcomes.MethodA national cohort of adult participants with newly diagnosed BPD was
identified in 2008. The effects of personal and household socioeconomic
status were explored on outcomes of hospital treatment, mortality and
healthcare costs, over a 3-year follow-up period (2008–2011).ResultsA total of 7987 participants were recruited. The relative risks of
hospital treatment and mortality were found elevated for the ones from
low-income households who also had higher healthcare costs. Low premium
levels did not correlate with future healthcare costs.ConclusionsSocioeconomic deprivation is associated with poorer outcome and higher
healthcare costs in BPD patients. Special care should be given to those
with lower socioeconomic status to improve outcomes with potential
benefits of cost savings in the following years.
Thermal biology of the sub-polar–temperate estuarine crabHemigrapsus crenulatus(Crustacea: Decapoda: Varunidae)
Authors: Cumillaf Juan P. , Blanc Johnny , Paschke Kurt , Gebauer Paulina , Díaz Fernando , Re Denisse , Chimal María E. , Vásquez Jorge , Rosas Carlos 
Published: February 2016

ABSTRACTOptimum temperatures can be measured through aerobic scope, preferred temperatures or growth. A complete thermal window, including optimum, transition (Pejus) and critical temperatures (CT), can be described if preferred temperatures and CT are defined. The crustacean Hemigrapsus crenulatus was used as a model species to evaluate the effect of acclimation temperature on: (i) thermal preference and width of thermal window, (ii) respiratory metabolism, and (iii) haemolymph proteins. Dependant on acclimation temperature, preferred temperature was between 11.8°C and 25.2°C while CT was found between a minimum of 2.7°C (CTmin) and a maximum of 35.9°C (CTmax). These data and data from tropical and temperate crustaceans were compared to examine the association between environmental temperature and thermal tolerance. Temperate species have a CTmax limit around 35°C that corresponded with the low CTmax limit of tropical species (34–36°C). Tropical species showed a CTmin limit around 9°C similar to the maximum CTmin of temperate species (5–6°C). The maximum CTmin of deep sea species that occur in cold environments (2.5°C) matched the low CTmin values (3.2°C) of temperate species. Results also indicate that the energy required to activate the enzyme complex (Ei) involved in respiratory metabolism of ectotherms changes along the latitudinal gradient of temperature.