bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic Reprogramming Strategies to Reverse Global Loss of 5-Hydroxymethylcytosine, a Prognostic Factor for Poor Survival in High-grade Serous Ovarian Cancer
Authors: Tucker Douglass W. , Getchell Christopher R. , McCarthy Eric T. , Ohman Anders W. , Sasamoto Naoko , Xu Shuyun , Ko Joo Yeon , Gupta Mamta , Shafrir Amy , Medina Jamie E. , Lee Jonathan J. , MacDonald Lauren A. , Malik Ammara , Hasselblatt Kathleen T , Li Wenjing , Zhang Hong , Kaplan Samuel J. , Murphy George F. , Hirsch Michelle S. , Liu Joyce F. , Matulonis Ursula A. , Terry Kathryn L. , Lian Christine G. , Dinulescu Daniela M.
Published: December 2017

Purpose: A major challenge in platinum-based cancer therapy is the clinical management of chemoresistant tumors, which have a largely unknown pathogenesis at the level of epigenetic regulation.

Experimental Design: We evaluated the potential of using global loss of 5-hydroxymethylcytosine (5-hmC) levels as a novel diagnostic and prognostic epigenetic marker to better assess platinum-based chemotherapy response and clinical outcome in high-grade serous tumors (HGSOC), the most common and deadliest subtype of ovarian cancer. Furthermore, we identified a targetable pathway to reverse these epigenetic changes, both genetically and pharmacologically.

Results: This study shows that decreased 5-hmC levels are an epigenetic hallmark for malignancy and tumor progression in HGSOC. In addition, global 5-hmC loss is associated with a decreased response to platinum-based chemotherapy, shorter time to relapse, and poor overall survival in patients newly diagnosed with HGSOC. Interestingly, the rescue of 5-hmC loss restores sensitivity to platinum chemotherapy in vitro and in vivo, decreases the percentage of tumor cells with cancer stem cell markers, and increases overall survival in an aggressive animal model of platinum-resistant disease.

Conclusions: Consequently, a global analysis of patient 5-hmC levels should be included in future clinical trials, which use pretreatment with epigenetic adjuvants to elevate 5-hmC levels and improve the efficacy of current chemotherapies. Identifying prognostic epigenetic markers and altering chemotherapeutic regimens to incorporate DNMTi pretreatment in tumors with low 5-hmC levels could have important clinical implications for newly diagnosed HGSOC disease. Clin Cancer Res; 24(6); 1389–401. ©2017 AACR.
A Transgenic Dual-Luciferase Reporter Mouse for Longitudinal and Functional Monitoring of T Cells In Vivo
Authors: Szyska Martin , Herda Stefanie , Althoff Stefanie , Heimann Andreas , Russ Josefine , D'Abundo Daniele , Dang Tra My , Durieux Isabell , Dörken Bernd , Blankenstein Thomas , Na Il-Kang
Published: December 2017

Adoptive T-cell therapy (ATT) efficacy is limited when targeting large solid tumors. The evaluation of ATT outcomes using accessory treatment would greatly benefit from an in vivo monitoring tool, allowing the detection of functional parameters of transferred T cells. Here, we generated transgenic bioluminescence imaging of T cells (BLITC) mice expressing an NFAT-dependent click-beetle luciferase and a constitutive Renilla luciferase, which supports concomitant in vivo analysis of migration and activation of T cells. Rapid transferability of our system to preestablished tumor models was demonstrated in the SV40-large T antigen model via both crossbreeding of BLITC mice into a T-cell receptor (TCR)-transgenic background and TCR transduction of BLITC T cells. We observed rapid tumor infiltration of BLITC CD8+ T cells followed by a burst-like activation that mirrored rejection kinetics. Using the BLITC reporter in the clinically relevant H-Y model, we performed female to male transfers and detected H-Y-specific alloreactivity (graft-versus-host disease) in vivo. In an H-Y solid tumor model, we found migration of adoptively transferred H-Y TCR-transgenic CD4+ T cells into the tumor, marked by transient activation. This suggests a rapid inactivation of infiltrating T cells by the tumor microenvironment, as confirmed by their expression of inhibitory receptors. In summary, the BLITC reporter system facilitates analysis of therapeutic parameters for ATT, is rapidly transferable to models of interest not restricted to tumor research, and is suitable for rapid screening of TCR clones for tumor rejection kinetics, as well as off-target effects. Cancer Immunol Res; 6(1); 110–20. ©2018 AACR.
Consensus on Wound Antisepsis: Update 2018
Authors: Kramer Axel , Dissemond Joachim , Kim Simon , Willy Christian , Mayer Dieter , Papke Roald , Tuchmann Felix , Assadian Ojan
Published: December 2017

Wound antisepsis has undergone a renaissance due to the introduction of highly effective wound-compatible antimicrobial agents and the spread of multidrug-resistant organisms (MDROs). However, a strict indication must be set for the application of these agents. An infected or critically colonized wound must be treated antiseptically. In addition, systemic antibiotic therapy is required in case the infection spreads. If applied preventively, the Wounds-at-Risk Score allows an assessment of the risk for infection and thus appropriateness of the indication. The content of this updated consensus recommendation still largely consists of discussing properties of octenidine dihydrochloride (OCT), polihexanide, and iodophores. The evaluations of hypochlorite, taurolidine, and silver ions have been updated. For critically colonized and infected chronic wounds as well as for burns, polihexanide is classified as the active agent of choice. The combination 0.1% OCT/phenoxyethanol (PE) solution is suitable for acute, contaminated, and traumatic wounds, including MRSA-colonized wounds due to its deep action. For chronic wounds, preparations with 0.05% OCT are preferable. For bite, stab/puncture, and gunshot wounds, polyvinylpyrrolidone (PVP)-iodine is the first choice, while polihexanide and hypochlorite are superior to PVP-iodine for the treatment of contaminated acute and chronic wounds. For the decolonization of wounds colonized or infected with MDROs, the combination of OCT/PE is preferred. For peritoneal rinsing or rinsing of other cavities with a lack of drainage potential as well as the risk of central nervous system exposure, hypochlorite is the superior active agent. Silver-sulfadiazine is classified as dispensable, while dyes, organic mercury compounds, and hydrogen peroxide alone are classified as obsolete. As promising prospects, acetic acid, the combination of negative pressure wound therapy with the instillation of antiseptics (NPWTi), and cold atmospheric plasma are also subjects of this assessment.
Quality of Life and Cost-Effectiveness of Cochlear Implants: A Narrative Review
Authors: Crowson Matthew G. , Semenov Yevgeniy R. , Tucci Debara L. , Niparko John K.
Published: December 2017

Objectives: To review evidence regarding the health-related quality of life (HRQoL) and cost-effectiveness of unilateral and bilateral cochlear implantation (CI) among children and adults with severe-to-profound hearing loss. Study Design: Narrative review. Methods: Publications related to quality of life (QoL) and costs of care in CI were acquired through searches in English-language databases. Studies were included if they had identified the HRQoL attainment, cost of care, cost-utility, or cost-effectiveness associated with CI. Results: 57 studies were critically reviewed. The QoL outcome metrics used in these articles were divided into 2 categories - generic and condition specific. In studies investigating children, many reported no significant difference in QoL attainment between CI recipients and normal-hearing peers. In adults, significant improvements in QoL after implantation and higher QoL than in their nonimplanted (hearing-aided) peers were frequently reported. Studies involving an older adult cohort reported significant improvement in QoL after implantation, which was often independent of audiological performance. Overall, the calculated cost-utility ratios consistently met the threshold of cost acceptance, indicating acceptable values for expenditures on CI. Conclusions: Considerable work has been done on the QoL attainment and health economic implications of CI. Unilateral CI across all age groups leads to reported sustained benefits in the recipients' overall and disease-specific QoL. With increased cost associated with bilateral CI, further study is needed to characterize its costs and benefits with respect to the recipients' health, well-being, and contributions to society.
Sacubitril/Valsartan in Clinical Practice: A Report of 2 Cases
Authors: Cosentino Eugenio
Published: December 2017

Following the results of the PARADIGM-HF trial, the European Society of Cardiology (ESC) guidelines recommend sacubitril/valsartan to replace ACE inhibitors in ambulatory patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal therapy and who fit trial criteria. However, the optimal use of sacubitril/valsartan in clinical practice needs further investigation. We report here the cases of 2 patients with HFrEH successfully treated with sacubitril/valsartan in our daily practice. Both subjects presented multiple comorbidities and received an implantable cardioverter defibrillator in primary prevention. In both patients, therapy with sacubitril/valsartan led to prompt (30 days) amelioration of heart function, with a corresponding decrease in NHYA class and without any relevant safety issue.
Management of a Multicomorbid Patient with Heart Failure
Authors: Magri Gianluigi , Bentivenga Crescenzio , Cosentino Eugenio Roberto , Degli Esposti Daniela , Borghi Claudio , Dormi Ada
Published: December 2017

The optimal use of sacubitril/valsartan in clinical practice needs further investigation, in particular for patients with multiple comorbidities, as such patients are usually poorly represented in clinical trials. To this end, well-documented case reports may add further evidence to the bulk of “field practice” experience on sacubitril/valsartan. We report here the case of a patient with heart failure with reduced ejection refraction with multiple comorbidities treated with sacubitril/valsartan. Overall, sacubitril/valsartan led to a prompt (within a few months) improvement in LVEF (+15%, from 38 to 53%), without any noticeable adverse events. This therapy also allowed the patient to discontinue furosemide.
A Case of Advanced Submandibular Gland Cancer in Which Increased Prostate-Specific Antigen and Multiple Bone Metastases Wrongly Suggested Concurrent Prostate Cancer
Authors: Fukasawa Yoko , Honda Takeshi , Natsume Maika , Haruyama Terunobu , Ishihara Masashi , Sakamoto Takahiko , Usui Ryo , Tanzawa Shigeru , Ota Shuji , Ichikawa Yasuko , Watanabe Kiyotaka , Saito Koji , Seki Nobuhiko
Published: December 2017

A 73-year-old man, followed for prostatic hyperplasia, developed submandibular gland cancer. Initially, because of the concurrent presence of elevated serum prostate-specific antigen (PSA) and multiple bone metastases, he was clinically determined as having stage IV prostate cancer in addition to stage II submandibular gland cancer, and radical surgery for his submandibular gland cancer was performed first. However, subsequent detailed examinations of the prostate gland showed no prostate cancer, and a diagnosis of advanced submandibular gland cancer with increased PSA and multiple bone metastases was established. Serum PSA is highly specific for prostate diseases and is widely used as a tumor marker of prostate cancer. However, clinicians should be aware that, in patients with non-prostate cancer, the detection of increased PSA and multiple bone metastases does not necessarily indicate the concurrent presence of prostate cancer.
A Case of Paraneoplastic Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome Improved by Chemotherapy
Authors: Sakamoto Takahiko , Ota Shuji , Haruyama Terunobu , Ishihara Masashi , Natsume Maika , Fukasawa Yoko , Tanzawa Shigeru , Usui Ryo , Honda Takeshi , Ichikawa Yasuko , Watanabe Kiyotaka , Seki Nobuhiko
Published: December 2017

The patient was a 69-year-old male who had started experiencing acute-onset pain in both shoulder joints and edema of both hands and feet. His symptoms progressively worsened within 1 month. Laboratory data indicated elevated CRP and erythrocyte sedimentation rate despite the normal range of antinuclear antibodies and rheumatoid factor and normal organ function. Furthermore, imaging data of the hand indicated synovitis without bone erosions. Meanwhile, chest CT revealed a lung tumor, leading to a diagnosis of primary lung adenocarcinoma with EGFR mutation (cT2aN3M0, stage IIIB). Based on these findings, he was diagnosed as suffering from paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Thereafter, his symptoms disappeared as the tumor size was rapidly decreased by gefitinib therapy for lung adenocarcinoma. Currently, RS3PE syndrome can be classified as a vascular endothelial growth factor (VEGF)-associated disorder. Given that his symptoms improved by chemotherapy, the present case further supported the possible hypothesis that paraneoplastic RS3PE syndrome might be caused by tumor-induced VEGF. Therefore, the present case suggested that the symptoms of acute-onset joint pain accompanied by pitting edema in elderly patients should be considered suspicious for a malignant tumor, thereby warranting a detailed full-body examination.
Integrated Karyotyping of Woodland Strawberry (Fragaria vesca) with Oligopaint FISH Probes
Authors: Qu Manman , Li Kunpeng , Han Yanli , Chen Lei , Li Zongyun , Han Yonghua
Published: December 2017

Chromosome identification is critical for many aspects of cytogenetic research. However, for Fragaria vesca, definite identification of individual chromosomes is almost impossible because of their small size and high similarity. Here, we demonstrate that bulked oligonucleotide (oligo) probes can be used as chromosome-specific DNA markers for chromosome identification in F. vesca. Oligos specific to entire pseudochromosomes in the draft genome of F. vesca were identified and synthesized as libraries. In all, we synthesized 6 oligo libraries corresponding to 6 pseudochromosomes of F. vesca. These libraries were amplified and labeled as probes for fluorescence in situ hybridization (FISH). Two rounds of multicolor FISH analysis were sequentially conducted on the same metaphase cells with each round including 3 probe libraries, which permitted simultaneous identification of all chromosomes of F. vesca. Moreover, 45S and 5S rDNA were mapped to chromosomes 1, 2, and 7, respectively. A karyotype of metaphase chromosomes was constructed, representing the first FISH-based molecular cytogenetic karyotype of F. vesca. Our study can serve as a basis for future comparative cytogenetic research through cross-species chromosome painting using bulked oligo probes and will facilitate the application of breeding technologies that rely on the identification of chromosomes in the genus Fragaria.
Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease
Authors: Lai Silvia , Mastroluca Daniela , Matino Silvia , Panebianco Valeria , Vitarelli Antonio , Capotosto Lidia , Turinese Irene , Marinelli Paolo , Rossetti Marco , Galani Alessandro , Baiocchi Pia , D’Angelo Anna R. , Palange Paolo
Published: December 2017

Background/Aims: Cardiovascular disease is the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients, often before the onset of renal failure, and the pathogenetic mechanism is not yet well elucidated. The aim of the study was to identify early and noninvasive markers of cardiovascular risk in young ADPKD patients, in the early stages of disease. Methods: A total of 26 patients with ADPKD and 24 control group, matched for age and sex, were enrolled, and we have assessed inflammatory indexes, mineral metabolism, metabolic state and markers of atherosclerosis and endothelial dysfunction (carotid intima media thickness (IMT), ankle brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI), left ventricular mass index (LVMI)) and cardiopulmonary exercise testing (CPET), maximal O2 uptake (V’O2max), and O2 uptake at lactic acid threshold (V’O2@LT). Results: The ADPKD patients compared to control group, showed a significant higher mean value of LVMI, RRI, homocysteine (Hcy), Homeostasis Model Assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), Cardiac-troponinT (cTnT) and intact parathyroid hormone (iPTH) (p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, p=0.007, p=0.019; respectively), and a lower value of FMD and 25-hydroxyvitaminD (25-OH-VitD) (p<0.001, p<0.001) with reduced parameters of exercise tolerance, as V’O2max, V’O2max/Kg and V’O2max (% predicted) (p<0.001, p<0.001, p=0.018; respectively), and metabolic response indexes (V’O2@LT, V’O2 @LT%, V’O2@LT/Kg,) (p<0.001, p=0.14, p<0.001; respectively). Moreover, inflammatory indexes were significantly higher in ADPKD patients, and we found a positive correlation between HOMA-IR and C-reactive protein (CRP) (r=0.507, p=0.008), and a negative correlation between HOMA-IR and 25-OH-VitD (r=-0.585, p=0.002). Conclusion: In our study, ADPKD patients, in the early stages of disease, showed a greater insulin resistance, endothelial dysfunction, inflammation and mineral metabolism disorders, respect to control group. Moreover, these patients presented reduced tolerance to stress, and decreased anaerobic threshold to CPET. Our results indicate a major and early cardiovascular risk in ADPKD patients. Therefore early and noninvasive markers of cardiovascular risk and CPET should be carried out, in ADPKD patients, in the early stages of disease, despite the cost implication.
Angiotensin II Facilitates Matrix Metalloproteinase-9-Mediated Myosin Light Chain Kinase Degradation in Pressure Overload-Induced Cardiac Hypertrophy
Authors: Wang Shun , Cheng Mian , Hu Zhengqing , Hu Shan , Zou Qiang , Lai Xin , Liu Beilei , Jiang Hong , Huang Congxin , Wu Gang
Published: December 2017

Background/Aims: Angiotensin II (Ang II) has been shown to promote cardiac remodeling during the process of hypertrophy. Myosin light chain kinase (MLCK), a specific kinase for the phosphorylation of myosin light chain 2 (MLC2), plays an important role in regulating cardiac muscle contraction and hypertrophy. However, whether Ang II could facilitate cardiac hypertrophy by altering the expression of MLCK remains unclear. This study aimed to investigate this effect and the underlying mechanisms. Methods: Cardiac hypertrophy was induced via pressure overload in rats, which were then evaluated via histological and biochemical measurements and echocardiography. Angiotensin-converting enzyme inhibitor (ACEI) was used to inhibit Ang II. Neonatal rat cardiomyocytes were stimulated with Ang II to induce hypertrophy and were treated with a matrix metalloproteinase 9 (MMP9) inhibitor. Myocyte hypertrophy was evaluated using immunofluorescence and qRT-PCR. Degradation of recombinant human MLCK by recombinant human MMP9 was tested using a cleavage assay. The expression levels of MLCK, MLC2, phospho-myosin light chain 2 (p-MLC2), myosin phosphatase 2 (MYPT2), and calmodulin (CaM) were measured using western blotting. Results: ACEI improved cardiac function and remodeling and increased the levels of MLCK and p-MLC2 as well as reduced the expression of MMP9 in pressure overload-induced cardiac hypertrophy. Moreover, the MMP9 inhibitor alleviated myocyte hypertrophy and upregulated the levels of MLCK and p-MLC2 in Ang II-induced cardiomyocyte hypertrophy. Recombinant human MLCK was concentration- and time-dependently degraded by recombinant human MMP9 in vitro, and this process was prevented by the MMP9 inhibitor. Conclusion: Our results suggest that Ang II is involved in the degradation of MLCK in pressure overload-induced cardiac hypertrophy and that this process was mediated by MMP9.
Benzotriazole Enhances Cell Invasive Potency in Endometrial Carcinoma Through CTBP1-Mediated Epithelial-Mesenchymal Transition
Authors: Wang Yiquan , Dai Chencheng , Zhou Cheng , Li Wenqu , Qian Yujia , Wen Juan , Wang Yang , Han Bing , Ma Jingjing , Xu Juan , Fu Ziyi , Ruan Hongjie , Tong Hua , Jia Xuemei
Published: December 2017

Background/Aims: Benzotriazole (BTR) and its derivatives, such as intermediates and UV stabilizers, are important man-made organic chemicals found in everyday life that have been recently identified as environmental toxins and a threat to female reproductive health. Previous studies have shown that BTR could act as a carcinogen by mimicking estrogen. Environmental estrogen mimics could promote the initiation and development of female cancers, such as endometrial carcinoma, a type of estrogenic-sensitive malignancy. However, there is little information on the relationship between BTR and endometrial carcinoma. In this study, we aimed to demonstrate the biological function of BTR in endometrial carcinoma and explored the underlying mechanism. Methods: The CCK-8 assay was performed to detect cell viability; transwell-filter assay was used to assess cell invasion; gene microarray analysis was employed to determine gene expression patterns in response to BTR treatment; western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were carried out to detect the expression levels of BTR-related genes. Results: Our data showed that BTR could induce the invasion and migration of endometrial carcinoma cells (Ishikawa and HEC-1-B). In addition, BTR increased the expression level of CTBP1, which could enhance the epithelial-mesenchymal transition (EMT) in cancer cells. Moreover, CTBP1 silencing reversed the effect of BTR on EMT progression in endometrial carcinoma cells. Conclusion: This study indicates that BTR could act as a carcinogen to promote the development of endometrial carcinoma mainly through CTBP1-mediated EMT, which deserves more attention.
Dachengqi Decoction Attenuates Intestinal Vascular Endothelial Injury in Severe Acute Pancreatitis in Vitro and in Vivo
Authors: Pan Li-yun , Chen Ya-feng , Li Hong-chang , Bi Li-ming , Sun Wen-jie , Sun Gui-fang , Zhang Xiao-fen , Xu Ke , Feng Dian-xu
Published: December 2017

Background/Aims: Dachengqi decoction (DCQD) is a well-known traditional Chinese herbal drug with strong anti-inflammatory effects. Angiopoietin-1 (Ang-1) plays a vital role in maintaining the stability and integrity of the vascular wall and prevents vascular leakage due to inflammatory mediators. Our previous work found that DCQD protects against pancreatic injury in rats with severe acute pancreatitis (SAP). This study aims to investigate the effects of DCQD on intestinal endothelial damage in both damaged human umbilical vein endothelial cells (HUVECs) and SAP rats. Methods: HUVECs were randomly divided into four groups: control group, TNF-α group, TNF-α plus Ang-1 group (Ang-1 group), and TNF-α plus DCQD group (DCQD group). Cells were incubated for 6 h, 12 h, and 24 h, before collection. The treatment concentration of DCQD was decided based on a Cell Counting Kit-8 (CCK-8) assay. The monolayer permeability of the HUVECs was assessed by measuring the transendothelial electrical resistance (TEER). Apoptosis was analyzed by flow cytometry. mRNA and protein expression of aquaporin 1 (AQP-1), matrix metalloproteinase 9 (MMP9), and junctional adhesion molecule-C (JAM-C) was evaluated by RT-PCR, immunocytofluorescence, and western blot. Forty male Sprague-Dawley rats were randomized into a control group, SAP group, SAP plus Ang-1 group (Ang-1 group), and SAP plus DCQD group (DCQD group). SAP was induced by intraperitoneal injection of cerulein and lipopolysaccharide (LPS), while the control group received 0.9% saline solution. Evans blue was injected through the penile vein and the rats were then sacrificed 12 h after modeling. Levels of serum amylase, TNF-α, IL-1β, IL-2, and IL-6 were determined by using ELISA. Intestinal tissue was analysed by histology, and capillary permeability in the tissues was evaluated by Evans blue extravasation assay. Protein and mRNA expression of AQP-1, MMP9, and JAM-C were assessed by immunohistofluorescence, western blot, and RT-PCR. Results: DCQD reduced the permeability of HUVEC induced by TNF-α in vitro. Furthermore, DCQD altered the mRNA and protein levels of JAM-C, MMP9, and AQP-1 in HUVECs after TNF-α induction. SAP intestinal injury induced by cerulein combined with lipopolysaccharides was concomitant with increased expression of JAM-C and MMP9, and reduced expression of AQP-1 in intestinal tissue. Pretreatment with DCQD attenuated SAP intestinal injury and lowered the levels of serum amylase, TNF–α, IL-1β, IL-2, and IL-6 effectively. Our study demonstrated that DCQD decreased the expression of JAM-C and MMP9 and increased the expression of AQP-1 both in vitro and in vivo. Conclusion: DCQD can reduce capillary endothelial damage in acute pancreatitis-associated intestinal injury and the mechanism may be associated with the regulation of endothelial barrier function-associated proteins AQP-1, MMP9, and JAM-C.
Extremely Long Survival under Combined Immunotherapy in a Metastatic Functional Neuroendocrine Neoplasia Patient
Authors: Schmidt Daniel , Wiedenmann Bertram
Published: December 2017

Treatment and prognosis of neuroendocrine neoplasia depends on tumor size, stage, grade, resectability, and extent of distant metastasis. In most cases a multimodality approach including surgical, locally invasive procedures, peptide-guided radioreceptor therapy (PRRT), and medical therapies represent the mainstay of treatment in advanced disease. In the reported case, a 68-year-old man was diagnosed in 2010 with an initially functional (histamine) neuroendocrine tumor of gastric type III, G2, stage IVB, cT4cN1cM1 (hepatic, peritoneal, nodal, osseous), including a hepatic tumor load of 25%. Intensive multimodality approaches including combined immunotherapy (vaccination and PD-1/CTLA-4 blockade) led to a survival of 8 years until now with a high quality of life and minimal residual disease (only a single, small paragastric recurrence) despite the dedifferentiation of the tumor into a neuroendocrine carcinoma G3 (Ki-67 of 80%) including a nonfunctional stage.
Nebulized Heparin Attenuates Pulmonary Coagulopathy and Inflammation through Alveolar Macrophages in a Rat Model of Acute Lung Injury
Authors: Chimenti Laura , Camprubí-Rimblas Marta , Guillamat-Prats Raquel , Gomez Maria , Tijero Jessica , Blanch Lluis , Artigas Antonio
Published: December 2017

Objective Alveolar macrophages play a key role in the development and resolution of acute respiratory distress syndrome (ARDS), modulating the inflammatory response and the coagulation cascade in lungs. Anti-coagulants may be helpful in the treatment of ARDS. This study investigated the effects of nebulized heparin on the role of alveolar macrophages in limiting lung coagulation and inflammatory response in an animal model of acute lung injury (ALI).

Methods Rats were randomized to four experimental groups. In three groups, ALI was induced by intratracheal instillation of lipopolysaccharide (LPS) and heparin was nebulized at constant oxygen flow: the LPS/Hep group received nebulized heparin 4 and 8 hours after injury; the Hep/LPS/Hep group received nebulized heparin 30 minutes before and 4 and 8 hours after LPS-induced injury; the LPS/Sal group received nebulized saline 4 and 8 hours after injury. The control group received only saline. Animals were exsanguinated 24 hours after LPS instillation. Lung tissue, bronchoalveolar lavage fluid (BALF) and alveolar macrophages isolated from BALF were analysed.

Results LPS increased protein concentration, oedema and neutrophils in BALF as well as procoagulant and proinflammatory mediators in lung tissue and alveolar macrophages. In lung tissue, nebulized heparin attenuated ALI through decreasing procoagulant (tissue factor, thrombin–anti-thrombin complexes, fibrin degradation products) and proinflammatory (interleukin 6, tumour necrosis factor alpha) pathways. In alveolar macrophages, nebulized heparin reduced expression of procoagulant genes and the effectors of transforming growth factor beta (Smad 2, Smad 3) and nuclear factor kappa B (p-selectin, CCL-2). Pre-treatment resulted in more pronounced attenuation.

Conclusion Nebulized heparin reduced pulmonary coagulopathy and inflammation without producing systemic bleeding, partly by modulating alveolar macrophages.
Clinical Decision Rules for Pulmonary Embolism in Hospitalized Patients: A Systematic Literature Review and Meta-analysis
Authors: Bass Anne , Fields Kara , Goto Rie , Turissini Gregory , Dey Shirin , Russell Linda
Published: December 2017

Background Clinical decision rules (CDRs) for pulmonary embolism (PE) have been validated in outpatients, but their performance in hospitalized patients is not well characterized.

Objectives The goal of this systematic literature review was to assess the performance of CDRs for PE in hospitalized patients.

Methods We performed a structured literature search using Medline, EMBASE and the Cochrane library for articles published on or before January 18, 2017. Two authors reviewed all titles, abstracts and full texts. We selected prospective studies of symptomatic hospitalized patients in which a CDR was used to estimate the likelihood of PE. The diagnosis of PE had to be confirmed using an accepted reference standard. Data on hospitalized patients were solicited from authors of studies in mixed populations of outpatients and hospitalized patients. Study characteristics, PE prevalence and CDR performance were extracted. The methodological quality of the studies was assessed using the QUADAS instrument.

Results Twelve studies encompassing 3,942 hospitalized patients were included. Studies varied in methodology (randomized controlled trials and observational studies) and reference standards used. The pooled sensitivity of the modified Wells rule (cut-off ≤ 4) in hospitalized patients was 72.1% (95% confidence interval [CI], 63.7–79.2) and the pooled specificity was 62.2% (95% CI, 52.6–70.9). The modified Wells rule (cut-off ≤ 4) plus D-dimer testing had a pooled sensitivity 99.7% (95% CI, 96.7–100) and pooled specificity 10.8% (95% CI, 6.7–16.9). The efficiency (proportion of patients stratified into the ‘PE unlikely’ group) was 8.4% (95% CI, 4.1–16.5), and the failure rate (proportion of low likelihood patients who were diagnosed with PE during follow-up) was 0.1% (95% CI, 0–5.3).

Conclusion In symptomatic hospitalized patients, use of the Wells rule plus D-dimer to rule out PE is safe, but allows very few patients to forgo imaging.
Frog assemblage associated with bromeliads in a sandy coastal plain in the state of Espírito Santo, southeastern Brazil
Authors: Mageski Marcio Marques , Ferreira Rodrigo Barbosa , Costa Larissa Corteletti da , Jesus Paulo Roberto , Ferreira Paulo Dias
Published: December 2017

Amphibians may use bromeliads for reproduction (i.e., bromeligenous species) or only for refuge and foraging (i.e., bromelicolous species). The partition of bromeliad resources is essential to maintain the coexistence of the associated assemblages. We sampled 913 bromeliads in a sandy coastal plain (i.e., restinga habitat) in southeastern Brazil and found 234 frogs belonging to seven species. One of the frog species was bromeligenous and the other six were facultative bromelicolous. The bromeliads of the genus Aechmea were the most frequently used by frogs. The low degree of frog occupancy of bromeliads (26%) suggests habitat segregation. Our study highlights the importance of maintenance of bromeliad species for conservation of the associated frog assemblages.
Mandibular allometry in Hydrochoerus hydrochaeris (Linnaeus, 1766) (Hydrocherinae, Caviidae)
Authors: Parés-Casanova Pere Miquel
Published: December 2017

The mammalian masticatory apparatus is a highly plastic region of the skull and thus subjected to singular ontogenetic trajectories. Here we present the first descriptive allometric pattern study of mandible among the capybara (Hydrochoerus hydrochaeris), based on the study of 37 specimens. Allometric changes in shape were analyzed using geometric morphometrics techniques and the pattern of allometry was visualized. A multivariate regression of the shape component on size, estimated by the logarithm of centroid size, appeared as highly significant. Therefore, a major component of shape variation in these mandibles is related to the attainment of adult size (i.e., growth).
Actividad reproductiva y dieta de Hemidactylus frenatus (Sauria: Gekkonidae) en el norte de Colombia
Authors: Díaz-Pérez Jorge A. , Sampedro-Marín Alcides C. , Ramírez-Pinilla Martha P.
Published: December 2017

Despite its success as an invasive species, little is known about the ecological aspects of the gekkonid lizard Hemidactylus frenatus in Colombia. In the present study the size at maturity, sexual dimorphism, reproductive activity, and diet composition of a population of this species in an urban locality of Northern Colombia were determined. We conducted eleven samplings from September 2011 to August 2012 in buildings of the municipality of Sincelejo. A total of 264 specimens H. frenatus were captured, 112 were adult females, 133 adult males and 19 juveniles. Males reach sexual maturity at a smaller size (snout-vent length) than females (males: 35.7 mm; females: 42.7 mm), also they are larger and have proportionally larger heads and mouths than females. Males were reproductive throughout the year; although testicular volume varied significantly between samples, this variation was not associated with body size and precipitation in the study area. Reproductive adult females were found during all the sampling period. Females have an invariable clutch size of two eggs and we found no differences in the diameter and weight of eggs in each oviduct. The diet of H. frenatus is varied, with Diptera, Hemiptera and Formicidae being the prey types with the greatest relative importance values. Individuals of both sexes consume a similar volume and number of prey. Thus, the studied population of H. frenatus has continuous reproductive activity and a generalist-opportunistic feeding behavior. The climatic conditions of the study area, environmental availability of prey and intrinsic features of this species appear to be responsible for their abundance and colonizing success in this and other localities.
First record of Gryllophila skrjabini Sergiev, 1923 and Cephalobellus magalhaesi Schwenk, 1926 (Nematoda: Thelastomatidae) parasites of Neocurtilla claraziana Saussure, 1874 (Orthoptera: Gryllotalpidae) in Argentina
Authors: Rusconi José Matias , Achinelly Maria Fernanda , Camino Nora Beatriz
Published: December 2017

Thelastomatidae is one of the largest families parasitizing insects, within the order Oxyurida. In this work we reported parasitism in nymphs and adults of Neocurtilla claraziana by two different thelastomatid species as a part of a field survey on agricultural pests. Nymphs and adults of this insect were isolated from grasslands of Buenos Aires State, Argentina using a tensio-active solution. The nematode species Gryllophila skrjabini Sergiev, 1923 and Cephalobellus magalhaesi Schwenk, 1926 are briefly described and measurements are given. Both nematodes are reported for the first time in Argentina with C. magalhaesi being the second isolation of this species in the world. Neocurtilla clarziana is a new host record for G. skrjabini.
Visadas cubistas: Carl Einstein, Daniel-Henry Kahnweiler e Vincenc Kramář
Authors: O'Neill Elena
Published: December 2017

Três textos centrais sobre Cubismo escritos nas primeiras décadas do século XX se distinguem pelo esforço de acompanhar de modo original as descobertas e formulações de Picasso, Braque, Léger e Juan Gris. Seus autores, Carl Einstein, Daniel-Henry Kahnweiler e Vincenc Kramář, fizeram leituras criativas do cubismo e defenderam a busca dos pintores por estabelecer novas compreensões do espaço baseadas na experiência vivenciada. Eles descartaram a concepção metafísica do espaço enquanto medida de valor espiritual, se esforçaram por evitar descrições baseadas em sentimentos e entenderam a experiência da arte a partir da interpenetração de elementos físicos e psíquicos. Apresentamos aqui algumas características desses três textos.
Retratos em movimento
Authors: Oliveira Junior Luiz Carlos
Published: December 2017

O artigo aborda aspectos da relação do cinema com a arte do retrato. Buscamos, em primeiro lugar, uma definição estética do que seria um retrato cinematográfico, sempre em tensão com os critérios formais e padrões estilísticos que historicamente constituíram o retrato pictórico. Em seguida, relacionamos essa questão com a importância que se deu à representação do close-up de rosto nas primeiras décadas do cinema, quando foi atribuído aos filmes um papel inédito no estudo da fisionomia e da expressão facial. Por fim, apresentamos exemplos de autorretratos na pintura e no cinema para expor a forma como a autorrepresentação põe em crise as noções de subjetividade e identidade em que a definição clássica do retrato se apoiava.
A intencionalidade das formas expressivas: estilo e método em Bordwell e Baxandall
Authors: Pirajá Tess Chamusca
Published: December 2017

Com o intuito de estimular a apropriação entre pesquisadores de diferentes produções audiovisuais, este artigo sistematiza os recursos metodológicos usados por Bordwell e Baxandall para a análise de questões estilísticas em dois tipos de produções artísticas: filmes e quadros. O texto aponta proximidades e complementaridades entre os dois autores. Entre elas figuram o desenvolvimento de análises focadas nas formas expressivas dos objetos de estudo, o uso do paradigma problema/solução, a recusa das teorias generalizantes, uma atenta perspectiva histórica e a preocupação em não impor o método à produção analisada, respeitando os modos de composição de cada obra.
Diccionario de semiótica y narrativas de cine y televisión
Authors: Vilches Lorenzo
Published: December 2017

Este artículo-homenaje a Algirdas Greimas tiene como objetivo resaltar la contribución del Diccionario de semiótica de Greimas y Courtés a la teoría narrativa y sus aplicaciones, entre ellas, las teorías del cine y de la televisión. En la teoría narrativa se pueden distinguir dos campos bien delimitados: la teoría narratológica propiamente tal como ciencia de referencia —por ejemplo, de Aristóteles a Greimas, pasando por Propp, Bajtin, Todorov, Barthes, Genet— y las teorías narrativas aplicadas a la literatura, al cine y a la televisión. En este trabajo, relacionamos algunas de las entradas claves del Diccionario de semiótica con la narrativa fílmica y televisiva.
Estratégias enunciativas em Google Spotlight Stories: o olhar da semiótica de Greimas nos vídeos 360°
Authors: Médola Ana Silvia Lopes Davi , Oliveira Bruno Jareta de
Published: December 2017

As lógicas de linearidade e práticas de fruição e interação introduzidas pelos vídeos 360° para dispositivos móveis e aparelhos de realidade virtual constituem um marco na forma expressiva audiovisual. Ao subverter a dinâmica da montagem como elemento fundante dos efeitos de continuidade, os vídeos 360° introduzem nova racionalidade na representação do espaço e conferem ao espectador parte do poder de decisão sobre o que ver. Sistema de significação próprio das tecnologias digitais, a visualidade inaugurada nos vídeos 360° recebe neste trabalho o olhar da semiótica greimasiana sobre as estratégias enunciativas que regem novas formas de espacialização e efeitos de imersão no audiovisual.
Cinema e circulações culturais em Salvador nos anos 1970
Authors: Seliprandy Fernando
Published: December 2017

“Cinema é mais que filme”: uma história das Jornadas de Cinema da Bahia (1972-1978), de Izabel de Fátima Cruz Melo, joga luz sobre as circulações culturais que gravitavam esse evento cinematográfico em plena ditadura. O texto oferece uma vívida imagem das trocas e tensões desse circuito, desde o fomento à produção local curta-metragista, passando pela exibição de títulos de outras paragens, pelas mobilizações de classe e pelas divergências entre realizadores de distintas bitolas (35 mm, 16 mm, super-8), até chegar aos embates com a censura oficial. O descentramento do olhar é o grande saldo do livro, ao descortinar outros horizontes da história das práticas audiovisuais no Brasil.
Picture ahead: a Kodak e a construção do turista-fotógrafo
Authors: Foster Lila
Published: December 2017

Picture ahead: a Kodak e a construção do turista fotógrafo investigates the history of visual culture in the 20th century by considering the constitution of an imaginary that has linked amateur photography and tourism. Kodak company was central in promoting such imagery through advertisements and intense marketing campaigns, establishing modes of production and consumption of the photographic image. Anchored in the concept of apparatus, the book makes explicit the many ways the company portrayed the tourist photographer without abandoning references from different sources and contemporary visual culture.
A institucionalização do ensino de Arquitetura Paisagística no Rio de Janeiro
Authors: Ferreira Alda Azevedo , Ono Fernando Pedro Carvalho , Nóbrega Claudia Carvalho Leme
Published: December 2017

O ensino de arquitetura paisagística foi instituído pela primeira vez no Rio de Janeiro na década de 1930. Iniciado na Escola Nacional de Belas Artes a partir de reforma promovida por Lucio Costa entre os anos 1930 e 1931 a disciplina foi introduzida junto com a de urbanismo, originando a cátedra ‘Urbanismo e Arquitetura Paisagística’. Este artigo objetivou entender esse processo a partir de informações colhidas em fontes primárias, fundamentado pelos conceitos de campo e habitus, de Pierre Bourdieu. Descobriu-se que o arquiteto e urbanista Attílio Corrêa Lima foi o primeiro professor da disciplina e que o ato da inclusão disciplinar estava inserido na construção de um campo paisagístico na cidade do Rio de Janeiro naquele momento, propagado não só no campo da arquitetura, como articulado às esferas política, econômica, e social.
Effect of different spatial normalization approaches on tractography and structural brain networks
Authors: Greene Clint , Cieslak Matt , Grafton Scott T.
Published: December 2017

To facilitate the comparison of white matter morphologic connectivity across target populations, it is invaluable to map the data to a standardized neuroanatomical space. Here, we evaluated direct streamline normalization (DSN), where the warping was applied directly to the streamlines, with two publically available approaches that spatially normalize the diffusion data and then reconstruct the streamlines. Prior work has shown that streamlines generated after normalization from reoriented diffusion data do not reliably match the streamlines generated in native space. To test the impact of these different normalization methods on quantitative tractography measures, we compared the reproducibility of the resulting normalized connectivity matrices and network metrics with those originally obtained in native space. The two methods that reconstruct streamlines after normalization led to significant differences in network metrics with large to huge standardized effect sizes, reflecting a dramatic alteration of the same subject’s native connectivity. In contrast, after normalizing with DSN we found no significant difference in network metrics compared with native space with only very small-to-small standardized effect sizes. DSN readily outperformed the other methods at preserving native space connectivity and introduced novel opportunities to define connectome networks without relying on gray matter parcellations.
Evaluating directionality in the internal reconstruction of pre-Old Irish copular clauses
Authors: Lash Elliott
Published: December 2017

This article reconstructs the syntax of pre-Old Irish copular clauses using relic or anomalous formations within Old Irish. It is therefore an exercise in syntactic internal reconstruction. The two patterns that are reconstructed are (a) the word order of subject and predicate, which was Predicate Subject in Old Irish but is argued to have been Subject Predicate in pre-Old Irish; (b) the order of negation, the clause-typing enclitic *de, the relative pronoun and the copula which is argued to be NEG+REL+de+COP. Furthermore, It is argued that a change from a fully verbal copula *issi in pre-Old Irish to a clause-typing particle is in Old Irish is implicated in the innovation of both (a) and (b). The reconstruction is evaluated using the technique of ‘local directionality’, by examining detailed feature/phrase-structure analyses of the constructions in at least two languages and hypothesizing the most economical and plausible relation between the two.
A new species of the genus Macrorhyncolus Wollaston, 1873 (Coleoptera: Curculionidae: Cossoninae) from China
Authors: OMAR YOUSSEF M. , ZHANG RUNZHI , DAVIS STEVEN R.
Published: December 2017

Following recent taxonomic study, Macrorhyncolus spinosus sp. nov. is described from China. Earlier, Macrorhyncolus included four species, M. crassiusculus, M. crassitarsis, M. littoralis and M. ventilaginis. A key is presented to all known species of Macrorhyncolus in the Palaearctic Region and China. Illustrations of diagnostic characters of the new species are provided. Macrorhyncolus spinosus is winged, has larger eyes, the rostrum is longer than wide and has a median furrow in the basal half, extending to the vertex, and striae 9 and 10 remain separate from base to apex.
Mobile X-Pol Radar: A New Tool for Investigating Pyroconvection and Associated Wildfire Meteorology
Authors: McCarthy Nicholas , McGowan Hamish , Guyot Adrien , Dowdy Andrew
Published: December 2017

The process of pyroconvection occurs when fire-released heat, moisture, and/or aerosols induce or augment convection in the atmosphere. Prediction of pyroconvection presents a set of complex problems for meteorologists and wildfire managers. In particular, the turbulent characteristics of a pyroconvective plume exert bidirectional feedback on fire behavior, often with resulting severe impacts on life and property. Here, we present the motivation, field strategy, and initial results from the Bushfire Convective Plume Experiment, which through the use of mobile radar aims to quantify the kinematics of pyroconvection and its role in fire behavior. The case studies presented include world-first observations from two wildfires and one prescribed burn using the University of Queensland’s portable, dual-polarized X-band Doppler radar (UQ-XPOL). The initial analyses of reflectivity, Doppler winds, polarimetric variables, and spectrum width data provide insights into these relatively unexplored datasets within the context of pyroconvection. Weather radar data are supported by mesonet observations, time-lapse photography, airborne multispectral imaging, and spot-fire mapping. The ability to combine ground-validated fire intensity and progression at an hourly scale with quantitative data documenting the evolution of the convective plume kinematics at the scale of hundreds of meters represents a new capability for advancing our understanding of wildfires. The results demonstrate the suitability of portable, dual-polarized X-band Doppler radar to investigate pyroconvection and associated plume dynamics.