bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chimeric Hemagglutinin Constructs Induce Broad Protection against Influenza B Virus Challenge in the Mouse Model
Authors: Ermler Megan E. , Kirkpatrick Ericka , Sun Weina , Hai Rong , Amanat Fatima , Chromikova Veronika , Palese Peter , Krammer Florian 
Published: March 2017

ABSTRACT
Seasonal influenza virus epidemics represent a significant public health burden. Approximately 25% of all influenza virus infections are caused by type B viruses, and these infections can be severe, especially in children. Current influenza virus vaccines are an effective prophylaxis against infection but are impacted by rapid antigenic drift, which can lead to mismatches between vaccine strains and circulating strains. Here, we describe a broadly protective vaccine candidate based on chimeric hemagglutinins, consisting of globular head domains from exotic influenza A viruses and stalk domains from influenza B viruses. Sequential vaccination with these constructs in mice leads to the induction of broadly reactive antibodies that bind to the conserved stalk domain of influenza B virus hemagglutinin. Vaccinated mice are protected from lethal challenge with diverse influenza B viruses. Results from serum transfer experiments and antibody-dependent cell-mediated cytotoxicity (ADCC) assays indicate that this protection is antibody mediated and based on Fc effector functions. The present data suggest that chimeric hemagglutinin-based vaccination is a viable strategy to broadly protect against influenza B virus infection.

IMPORTANCE
While current influenza virus vaccines are effective, they are affected by mismatches between vaccine strains and circulating strains. Furthermore, the antiviral drug oseltamivir is less effective for treating influenza B virus infections than for treating influenza A virus infections. A vaccine that induces broad and long-lasting protection against influenza B viruses is therefore urgently needed.
Efficacy of the PARP Inhibitor Veliparib with Carboplatin or as a Single Agent in Patients with Germline BRCA1- or BRCA2-Associated Metastatic Breast Cancer: California Cancer Consortium Trial NCT01149083
Authors: Somlo George , Frankel Paul H. , Arun Banu K. , Ma Cynthia X. , Garcia Agustin A. , Cigler Tessa , Cream Leah V. , Harvey Harold A. , Sparano Joseph A. , Nanda Rita , Chew Helen K. , Moynihan Timothy J. , Vahdat Linda T. , Goetz Matthew P. , Beumer Jan H. , Hurria Arti , Mortimer Joanne , Piekarz Richard , Sand Sharon , Herzog Josef , Van Tongeren Lily R. , Ferry-Galow Katherine V. , Chen Alice P. , Ruel Christopher , Newman Edward M. , Gandara David R. , Weitzel Jeffrey N. 
Published: March 2017

Abstract
Purpose: We aimed to establish the MTD of the poly (ADP-ribose) (PAR) polymerase inhibitor, veliparib, in combination with carboplatin in germline BRCA1- and BRCA2- (BRCA)-associated metastatic breast cancer (MBC), to assess the efficacy of single-agent veliparib, and of the combination treatment after progression, and to correlate PAR levels with clinical outcome.
Experimental Design: Phase I patients received carboplatin (AUC of 5–6, every 21 days), with escalating doses (50-20 mg) of oral twice-daily (BID) veliparib. In a companion phase II trial, patients received single-agent veliparib (400 mg BID), and upon progression, received the combination at MTD. Peripheral blood mononuclear cell PAR and serum veliparib levels were assessed and correlated with outcome.
Results: Twenty-seven phase I trial patients were evaluable. Dose-limiting toxicities were nausea, dehydration, and thrombocytopenia [MTD: veliparib 150 mg po BID and carboplatin (AUC of 5)]. Response rate (RR) was 56%; 3 patients remain in complete response (CR) beyond 3 years. Progression-free survival (PFS) and overall survival (OS) were 8.7 and 18.8 months. The PFS and OS were 5.2 and 14.5 months in the 44 patients in the phase II trial, with a 14% RR in BRCA1 (n = 22) and 36% in BRCA2 (n = 22). One of 30 patients responded to the combination therapy after progression on veliparib. Higher baseline PAR was associated with clinical benefit.
Conclusions: Safety and efficacy are encouraging with veliparib alone and in combination with carboplatin in BRCA-associated MBC. Lasting CRs were observed when the combination was administered first in the phase I trial. Further investigation of PAR level association with clinical outcomes is warranted. Clin Cancer Res; 23(15); 4066–76. ©2017 AACR.
Left Ventricular Dysfunction Switches Mesenchymal Stromal Cells Toward an Inflammatory Phenotype and Impairs Their Reparative Properties Via Toll-Like Receptor-4
Authors: Naftali-Shani Nili , Levin-Kotler La-Paz , Palevski Dahlia , Amit Uri , Kain David , Landa Natalie , Hochhauser Edith , Leor Jonathan 
Published: March 2017

Background:
Little is known about the potentially unfavorable effects of mesenchymal stromal cell (MSC) activation on the heart. MSCs can respond to tissue injury by anti- or proinflammatory activation. We aimed to study the potential negative interaction between left ventricular dysfunction (LVD) and MSC activation.

Methods:

We isolated MSCs from cardiac and subcutaneous fat tissues of mice with LVD 28 days after myocardial infarction or sham operation. To evaluate the effect of LVD on MSCs, we characterized cardiac MSCs and subcutaneous MSCs in vitro. Subsequently, we injected MSCs or saline into the infarcted myocardium of mice and evaluated LV remodeling and function 28 days after myocardial infarction. To test the hypothesis that toll-like receptor 4 (
TLR4
) mediates proinflammatory polarization of MSCs, we characterized cardiac MSCs from
TLR4
-/-
and wild-type (WT) mice after inflammatory stimulation in vitro. Next, we transplanted cardiac MSCs from
TLR4
-/-
and WT male mice into the infarcted myocardium of female WT mice and evaluated infarct size, MSC retention, inflammation, remodeling, and function after 7 days.

Results:

LVD switched cardiac MSCs toward an inflammatory phenotype, with increased secretion of inflammatory cytokines as well as chemokines. The effect of LVD on subcutaneous MSCs was less remarkable. Although transplantation of cardiac MSCs and subcutaneous MSCs from LVD and sham hearts did not improve LV remodeling and function, cardiac MSCs from LVD exacerbated anterior wall thinning 28 days after myocardial infarction. The inflammatory polarization of cardiac MSCs by LVD was mediated by
TLR4
, as we found less secretion of inflammatory cytokines and higher secretion of anti-inflammatory cytokines from activated cardiac MSCs of
TLR4
-deficient mice, compared with WT cardiac MSCs. Significantly,
TLR4
deficiency preserved the expression of CD47 (don’t eat me signal) on cardiac MSCs after both
TLR4
stimulation in vitro and transplantation into the infarcted heart. Compared with WT cardiac MSCs and saline,
TLR4
-/-
cardiac MSCs survived in the cardiac tissue and maintained their reparative properties, reduced infarct size, increased scar thickness, and attenuated LV dilatation 7 days after myocardial infarction.

Conclusions:

The environment of the failing and infarcted myocardium drives resident and transplanted MSCs toward a proinflammatory phenotype and restricts their survival and reparative effects in a mechanism mediated by
TLR4
.
A Case Study of Observed and Modeled Barrier Flow in the Denmark Strait in May 2015
Authors: DuVivier Alice K. , Cassano John J. , Greco Steven , Emmitt G. David 
Published: March 2017

Abstract
Mesoscale barrier jets in the Denmark Strait are common in winter months and have the capability to influence open ocean convection. This paper presents the first detailed observational study of a summertime (21 May 2015) barrier wind event in the Denmark Strait using dropsondes and observations from an airborne Doppler wind lidar (DWL). The DWL profiles agree well with dropsonde observations and show a vertically narrow (~250–400 m) barrier jet of 23–28 m s−1 near the Greenland coast that broadens (~300–1000 m) and strengthens farther off coast. In addition, otherwise identical regional high-resolution Weather Research and Forecasting (WRF) Model simulations of the event are analyzed at four horizontal grid spacings (5, 10, 25, and 50 km), two vertical resolutions (40 and 60 levels), and two planetary boundary layer (PBL) parameterizations [Mellor–Yamada–Nakanishi–Niino, version 2.5 (MYNN2.5) and University of Washington (UW)] to determine what model configurations best simulate the observed jet structure. Comparison of the WRF simulations with wind observations from satellites, dropsondes, and the airborne DWL scans indicate that the combination of both high horizontal resolution (5 km) and vertical resolution (60 levels) best captures observed barrier jet structure and speeds as well as the observed cloud field, including some convective clouds. Both WRF PBL schemes produced reasonable barrier jets with the UW scheme slightly outperforming the MYNN2.5 scheme. However, further investigation at high horizontal and vertical resolution is needed to determine the impact of the WRF PBL scheme on surface energy budget terms, particularly in the high-latitude maritime environment around Greenland.
Atypical choroid plexus papilloma: clinicopathological and neuroradiological features
Authors: Shi Yu-Zhen , Chen Mao-Zhen , Huang Wei , Guo Li-Li , Chen Xiao , Kong Dan , Zhuang Ying-Ying , Xu Yi-Ming , Zhang Rui-Rui , Bo Gen-Ji , Wang Zhong-Qiu 
Published: March 2017

Background Atypical choroid plexus papilloma (APP) is a rare, newly introduced entity with intermediate characteristics. To date, few reports have revealed the magnetic resonance (MR) findings. Purpose To analyze the clinicopathological and MR features of APP. Material and Methods The clinicopathological data and preoperative MR images of six patients with pathologically proven APP were retrospectively reviewed. The MR features including tumor location, contour, signal intensity, degree of enhancement, intratumoral cysts, and necrosis; and flow voids, borders, peritumoral edema, and associated hydrocephalus were analyzed. Results The APP were located in the ventricle (n = 4) and cerebellopontine angle (CPA, n = 2). Tumor dissemination along the spinal subarachnoid space was found in one patient. The tumors appeared as milt-lobulated (n = 5) or round mass (n = 1), with slightly heterogeneous signals (n = 5) or mixed signals (n = 1) on T1-weighted and T2-weighted images. Heterogeneous and strong enhancement were found in five cases on contrast-enhanced images. Three of four intraventricular tumors had a partly blurred border with ventricle wall. Four tumors had mild to moderate extent of surrounding edema signals. A slight hydrocephalus was seen in four patients. Incomplete capsule was seen in four tumors at surgery. Histopathologically, mild nuclear atypia was seen in all tumors with a mitotic rate of 2–5 per 10 high-power fields. Conclusion APP should be included in the differential diagnosis when an intraventricular or CPA tumor appearing as a multi-lobulated solid mass with slight heterogeneity, heterogeneous strong enhancement, partly blurred borders, mild to moderate peritumoral edema, or slight hydrocephalus are present.
Microbial alginate dressings show improved binding capacity for pathophysiological factors in chronic wounds compared to commercial alginate dressings of marine origin
Authors: Fischer Melissa , Gebhard Florian , Hammer Timo , Zurek Christian , Meurer Guido , Marquardt Christoph , Hoefer Dirk 
Published: March 2017

Marine alginates are well established in wound management. Compared with different modern wound dressings, marine alginates cannot prove superior effects on wound healing. Alginates from bacteria have never been studied for medical applications so far, although the microbial polymer raises expectations for improved binding of wound factors because of its unique O-acetylation. Due to its possible positive effects on wound healing, alginates from bacteria might be a superior future medical product for clinical use. To prove the binding capacity of microbial alginates to pathophysiological factors in chronic wounds, we processed microbial alginate fibres, produced from fermentation of the soil bacterium Azotobacter vinelandii ATCC 9046, into needle web dressings and compared them with commercial dressings made of marine alginate. Four dressings were assessed: Marine alginate dressings containing either ionic silver or zinc/manganese/calcium, and microbial alginate dressings with and without nanosilver. All dressings were tested in an in vitro approach for influence on chronic wound parameters such as elastase, matrix metalloproteases-2, tumour necrosis factor-α, interleukin-8, and free radical formation. Despite the alginate origin or addition of antimicrobials, all dressings were able to reduce the concentration of the proinflammatory cytokines TNF-α and IL-8. However, microbial alginate was found to bind considerable larger amounts of elastase and matrix metalloproteases-2 in contrast to the marine alginate dressings. The incorporation of zinc, silver or nanosilver into alginate fibres did not improve their binding capacity for proteases or cytokines. The addition of nanosilver slightly enhanced the antioxidant capacity of microbial alginate dressings, whereas the marine alginate dressing containing zinc/manganese/calcium was unable to inhibit the formation of free radicals. The enhanced binding affinity by microbial alginate of Azotobacter vinelandii to pathophysiological factors may be interesting to support optimal conditions for wound healing.
Suspected Synthetic Cannabinomimetic Intoxication: Case Series and Review
Authors: Baum Regan A. , Bailey Abby , Chan Ryan , Blumenschein Karen 
Published: March 2017

Purpose: The purpose of this work was to retrospectively review patient cases presenting to the University of Kentucky Chandler Medical Center (UKCMC) emergency department (ED) with symptoms of suspected synthetic cannabinomimetic (SC) intoxication. These drugs, currently undetected by standard urine drug screen tests, comprise a structurally diverse group of compounds designed to mimic the psychoactive effects of Δ9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive cannabinoid in marijuana. Summary: Fourteen cases of suspected SC intoxication were identified between July 1, 2015, through September 30, 2015. The median patient age was 25.5 years (range: 13-45 years), and most (64%) patients were males. The most common psychoactive symptom was agitation (n = 6, 42.9%), while the most common physical symptoms were altered level of consciousness (n = 9, 64.3%) and mydriasis (n = 3, 21.4%). Most cases resolved without complication in 24 hours; 2 patients required hospitalization. Conclusion: Recent legislation has failed to curb the public health concerns emanating from SC misuse. Education about the risks of SC use along with additional regulation may be required to remove the false sense of safety that some individuals, especially adolescents and young adults, may associate with these compounds, which are often misconstrued as “herbal marijuana.” Clinicians need to be prepared to identify and treat symptoms of SC intoxication as incidents of toxicity continue to rise.
Acute acalculous cholecystitis in patients with systemic lupus erythematosus: A unique form of disease flare
Authors: Yang H , Bian S , Xu D , Zhang F , Zhang X 
Published: March 2017

Objective We aimed to investigate the clinical features of acute acalculous cholecystitis (AAC) in patients with systemic lupus erythematosus (SLE). Methods SLE patients with AAC hospitalized in the Peking Union Medical College Hospital (PUMCH) from January 2001 to September 2015 were retrospectively analyzed. Their medical records were systematically reviewed. The diagnosis of AAC was based on clinical manifestations and confirmed by radiologic findings including a distended gallbladder with thickened wall, pericholecystic fluid and absence of gallstones. Results Among the 8411 hospitalized SLE patients in PUMCH, 13 (0.15%) were identified to have SLE-AAC. Eleven (84.6%) of them were female, with a mean age of 30.1 ± 8.6 years. AAC was the initial manifestation of SLE in four (30.8%) cases. Eleven (84.6%) patients complained of fever and abdominal pain, four (30.8%) had positive Murphy’s sign and six (46.2%) had elevated liver enzymes. The median SLE Disease Activity Index was 8.0 (range 0–20.0) at the time of AAC. Other affected organs in SLE-AAC included kidney (11, 84.6%) and hematologic system (11, 84.6%), followed by mucocutaneous (seven, 53.8%), musculoskeletal (seven, 53.8%) and neuropsychiatric (two, 15.4%) systems. All patients received treatment of glucocorticoids and immunosuppressants but none underwent surgical intervention. During a median follow-up of 28 months (range, 2–320 months), 12 cases (92.4%) responded to treatment with no relapse and one patient (7.6%) died of septic shock. Conclusion Our study suggests that AAC is a relatively uncommon and underestimated gastrointestinal involvement of SLE that is often associated with active disease. For patients with AAC in SLE, treatment with aggressive glucocorticoids could result in a good prognosis.
Direct oral anticoagulants: an alternative treatment for thrombotic antiphospholipid syndrome?
Authors: Resseguier A S , Pereira B , Rieu V , Le Guenno G , Grobost V , Ruivard M 
Published: March 2017

Background Direct oral anticoagulants (DOACs) demonstrate a lower risk–benefit ratio than vitamin K antagonists (VKAs) for secondary thromboprophylaxis of thrombotic events. But there are no data on the efficacy of DOACs for the prevention of thrombotic recurrence in patients with antiphospholipid syndrome (APS). In this study, we evaluated the efficacy of DOACs to prevent recurrences of thrombotic events in patients with APS. Methods This was a single-center pilot, using a multi-step Fleming design. If seven or fewer patients presented treatment failure with rivaroxaban, the study could conclude efficacy. Results A total of 23 patients were included. APS involved the veins only ( n = 19), arteries only ( n = 2) or both ( n = 1) and 1 patient exhibited catastrophic antiphospholipid syndrome (CAPS). Overall, two patients were positive for lupus anticoagulant, anti-beta-2 glycoprotein I antibodies and anticardiolipid antibodies (triple positivity). The mean duration of follow up was 35.6 (range, 29–40) months. A total of six treatment failures were reported: one patient, with triple positivity, developed bilateral distal pulmonary embolism (PE) after 20 months of treatment with rivaroxaban, two patients refused to take rivaroxaban, the treatment was stopped in three other patients: two with adverse effects and one with chronic iron-deficiency anemia. Conclusions Rivaroxaban may represent an alternative for secondary thromboprophylaxis for thrombo-embolism in patients with APS, in particular, those with poor international normalized ratio (INR) control and those who are not at the highest risk of recurrent thrombosis, such as those with triple positivity.
Study of Image Qualities From 6D Robot–Based CBCT Imaging System of Small Animal Irradiator
Authors: Sharma Sunil , Narayanasamy Ganesh , Clarkson Richard , Chao Ming , Moros Eduardo G. , Zhang Xin , Yan Yulong , Boerma Marjan , Paudel Nava , Morrill Steven , Corry Peter , Griffin Robert J. 
Published: March 2017

Purpose: To assess the quality of cone beam computed tomography images obtained by a robotic arm-based and image-guided small animal conformal radiation therapy device. Method and Materials: The small animal conformal radiation therapy device is equipped with a 40 to 225 kV X-ray tube mounted on a custom made gantry, a 1024 × 1024 pixels flat panel detector (200 μm resolution), a programmable 6 degrees of freedom robot for cone beam computed tomography imaging and conformal delivery of radiation doses. A series of 2-dimensional radiographic projection images were recorded in cone beam mode by placing and rotating microcomputed tomography phantoms on the “palm’ of the robotic arm. Reconstructed images were studied for image quality (spatial resolution, image uniformity, computed tomography number linearity, voxel noise, and artifacts). Results: Geometric accuracy was measured to be 2% corresponding to 0.7 mm accuracy on a Shelley microcomputed tomography QA phantom. Qualitative resolution of reconstructed axial computed tomography slices using the resolution coils was within 200 μm. Quantitative spatial resolution was found to be 3.16 lp/mm. Uniformity of the system was measured within 34 Hounsfield unit on a QRM microcomputed tomography water phantom. Computed tomography numbers measured using the linearity plate were linear with material density ( R2 > 0.995). Cone beam computed tomography images of the QRM multidisk phantom had minimal artifacts. Conclusion: Results showed that the small animal conformal radiation therapy device is capable of producing high-quality cone beam computed tomography images for precise and conformal small animal dose delivery. With its high-caliber imaging capabilities, the small animal conformal radiation therapy device is a powerful tool for small animal research.
Gender’s Effects to the Early Symptoms of Alzheimer’s Disease in 5 Asian Countries
Authors: Yang Yuan-Han , Meguro Kenichi , Dominguez Jacqueline , Chen Christopher Li-Hsian , Wang Huali , Ong Paulus Anam 
Published: March 2017

Background: Asia has the greatest population and more patients with dementia in the world. Early recognition of clinical symptoms of Alzheimer’s disease (AD) is crucial for dementia care. In order to foster collaboration in AD care, a uniformed manner to report the early clinical symptoms of AD is necessary. Methods: We have recruited clinically diagnosed patients with AD at their very mild stage with Clinical Dementia Rating (CDR) 0.5 in Taiwan, Japan, China, Philippines, and Singapore. Demographic characteristics and psychometrics including Ascertain of Dementia-8 (AD8) questionnaire were administrated to collect and report the clinical presentation in these countries. Results: In total, 713 clinically diagnosed patients with AD at very mild stage, CDR 0.5, have been recruited from these 5 countries. “Repeats questions, stories, or statements” were consistently the frequently reported symptom across these countries. Taiwan, China, and Singapore have the higher AD8 total score compared to that in Japan and Philippines. Japan and Philippines have the gender-related differences in clinical presentation of early AD. Conclusion: Difficulties in using small trouble appliance and in handling complicated financial affairs were frequently reported in Japan female, compared to male, patients with AD. Identifying the clinical symptom of AD and the gender-related issues would be crucial in the dementia care in Asia.