bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Learning for Computer Vision: A Brief Review
Authors: Voulodimos Athanasios , Doulamis Nikolaos , Doulamis Anastasios , Protopapadakis Eftychios
Published: February 2018

Over the last years deep learning methods have been shown to outperform previous state-of-the-art machine learning techniques in several fields, with computer vision being one of the most prominent cases. This review paper provides a brief overview of some of the most significant deep learning schemes used in computer vision problems, that is, Convolutional Neural Networks, Deep Boltzmann Machines and Deep Belief Networks, and Stacked Denoising Autoencoders. A brief account of their history, structure, advantages, and limitations is given, followed by a description of their applications in various computer vision tasks, such as object detection, face recognition, action and activity recognition, and human pose estimation. Finally, a brief overview is given of future directions in designing deep learning schemes for computer vision problems and the challenges involved therein.
Enhancement of the Comb Filtering Selectivity Using Iterative Moving Average for Periodic Waveform and Harmonic Elimination
Authors: Ferreira José L. , Wu Yan , Aarts Ronald M.
Published: February 2018

A recurring problem regarding the use of conventional comb filter approaches for elimination of periodic waveforms is the degree of selectivity achieved by the filtering process. Some applications, such as the gradient artefact correction in EEG recordings during coregistered EEG-fMRI, require a highly selective comb filtering that provides effective attenuation in the stopbands and gain close to unity in the pass-bands. In this paper, we present a novel comb filtering implementation whereby the iterative filtering application of FIR moving average-based approaches is exploited in order to enhance the comb filtering selectivity. Our results indicate that the proposed approach can be used to effectively approximate the FIR moving average filter characteristics to those of an ideal filter. A cascaded implementation using the proposed approach shows to further increase the attenuation in the filter stopbands. Moreover, broadening of the bandwidth of the comb filtering stopbands around −3 dB according to the fundamental frequency of the stopband can be achieved by the novel method, which constitutes an important characteristic to account for broadening of the harmonic gradient artefact spectral lines. In parallel, the proposed filtering implementation can also be used to design a novel notch filtering approach with enhanced selectivity as well.
Serum Soluble Vascular Cell Adhesion Molecule-1 Overexpression Is a Disease Marker in Patients with First-Time Diagnosed Antinuclear Antibodies: A Prospective, Observational Pilot Study
Authors: Oleszowsky Mara , Seidel Matthias F.
Published: February 2018

Objective. Antinuclear antibodies (ANA) serve as screening tests for connective tissue diseases but have low specificity. In this pilot study, we aimed to identify patients with first-time positive ANA and musculoskeletal complaints and correlate serum soluble vascular adhesion molecules as biomarkers.Methods. Prospective, observational study with 100 ANA-positive patients, comparing them to age- and gender-matched healthy controls (HC,n=75), was conducted. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), endothelial-leukocyte adhesion molecule-1 (sELAM-1), and vascular cell adhesion molecule-1 (sVCAM-1) were measured. A subgroup of patients with systemic sclerosis (SSc) treated with immunosuppressants was followed over 10 months.Results. Patients belonged to three main entities: rheumatoid arthritis (RA,n=32), collagen diseases (CD,n=56) also including systemic sclerosis (SSc,n=11), and other autoimmune diseases (n=12). sICAM-1 was similar among groups. sELAM-1 was elevated by 1.9-fold in only in SSc. sVCAM-1 was elevated by 3.1-fold in RA and by 3.3-fold in CD and in other autoimmune diseases by 3.4-fold. Seven SSc patients with immunosuppression had a 2.7-fold increased sVCAM-1 at baseline and reached the levels of healthy controls after 5 months, while CRP, ESR, and clinical parameters remained unchanged.Conclusion. Our study suggests that sVCAM-1 is a disease marker independent of standard serum parameters in several rheumatic diseases. This study is registered with EU PAS Register number:EUPAS22154.
Visualization of Flow Field: Application of PLIF Technique
Authors: Peng Jiang Bo , Lv Ze Fang , Yu Xin , Meng Song He , Dong Hao , Deng Fan , Chen Lin , Chen De Ying , Fan Rong Wei , Dong Zhi Wei , Li Xu Dong
Published: February 2018

The objective of this paper is to apply planar laser-induced fluorescence (PLIF) technology to flow field visualization. This experiment was carried out in a one-meter wind tunnel to study the wake flow field around a circular cylinder. This experiment studied the method of injecting tracer into the flow field; the frequency of the vortex in the wake field and the vortex speed are quantitatively analyzed. This paper gives the correspondence between the speed of the flow field and the frequency of the laser, which could be used as a rough reference standard for future wind tunnel visualization experiments. The result shows that PLIF diagnostic technology has great potential in visualization of flow field.
Overcoming Resistance to DNA-Targeted Agents by Epigenetic Activation of Schlafen 11 (SLFN11) Expression with Class I Histone Deacetylase Inhibitors
Authors: Tang Sai-Wen , Thomas Anish , Murai Junko , Trepel Jane B. , Bates Susan E. , Rajapakse Vinodh N. , Pommier Yves
Published: February 2018

Purpose: Schlafen 11 (SLFN11), a putative DNA/RNA helicase is a dominant genomic determinant of response to DNA-damaging agents and is frequently not expressed in cancer cells. Whether histone deacetylase (HDAC) inhibitors can be used to release SLFN11 and sensitize SLFN11-inactivated cancers to DNA-targeted agents is tested here.

Experimental Design: SLFN11 expression was examined in The Cancer Genome Atlas (TCGA), in cancer cell line databases and in patients treated with romidepsin. Isogenic cells overexpressing or genetically inactivated for SLFN11 were used to investigate the effect of HDAC inhibitors on SLFN11 expression and sensitivity to DNA-damaging agents.

Results: SLFN11 expression is suppressed in a broad fraction of common cancers and cancer cell lines. In cancer cells not expressing SLFN11, transfection of SLFN11 sensitized the cells to camptothecin, topotecan, hydroxyurea, and cisplatin but not to paclitaxel. SLFN11 mRNA and protein levels were strongly induced by class I (romidepsin, entinostat), but not class II (roclinostat) HDAC inhibitors in a broad panel of cancer cells. SLFN11 expression was also enhanced in peripheral blood mononuclear cells of patients with circulating cutaneous T-cell lymphoma treated with romidepsin. Consistent with the epigenetic regulation of SLFN11, camptothecin and class I HDAC inhibitors were synergistic in many of the cell lines tested.

Conclusions: This study reports the prevalent epigenetic regulation of SLFN11 and the dominant stimulatory effect of HDAC inhibitors on SLFN11 expression. Our results provide a rationale for combining class I HDAC inhibitors and DNA-damaging agents to overcome epigenetic inactivation of SLFN11-mediated resistance to DNA-targeted agents. Clin Cancer Res; 24(8); 1944–53. ©2018 AACR.
HSF1 Is Essential for Myeloma Cell Survival and A Promising Therapeutic Target
Authors: Fok Jacqueline H.L. , Hedayat Somaieh , Zhang Lei , Aronson Lauren I. , Mirabella Fabio , Pawlyn Charlotte , Bright Michael D. , Wardell Christopher P. , Keats Jonathan J. , De Billy Emmanuel , Rye Carl S. , Chessum Nicola E.A. , Jones Keith , Morgan Gareth J. , Eccles Suzanne A. , Workman Paul , Davies Faith E.
Published: February 2018

Purpose: Myeloma is a plasma cell malignancy characterized by the overproduction of immunoglobulin, and is therefore susceptible to therapies targeting protein homeostasis. We hypothesized that heat shock factor 1 (HSF1) was an attractive therapeutic target for myeloma due to its direct regulation of transcriptional programs implicated in both protein homeostasis and the oncogenic phenotype. Here, we interrogate HSF1 as a therapeutic target in myeloma using bioinformatic, genetic, and pharmacologic means.

Experimental Design: To assess the clinical relevance of HSF1, we analyzed publicly available patient myeloma gene expression datasets. Validation of this novel target was conducted in in vitro experiments using shRNA or inhibitors of the HSF1 pathway in human myeloma cell lines and primary cells as well as in in vivo human myeloma xenograft models.

Results: Expression of HSF1 and its target genes were associated with poorer myeloma patient survival. ShRNA-mediated knockdown or pharmacologic inhibition of the HSF1 pathway with a novel chemical probe, CCT251236, or with KRIBB11, led to caspase-mediated cell death that was associated with an increase in EIF2α phosphorylation, CHOP expression and a decrease in overall protein synthesis. Importantly, both CCT251236 and KRIBB11 induced cytotoxicity in human myeloma cell lines and patient-derived primary myeloma cells with a therapeutic window over normal cells. Pharmacologic inhibition induced tumor growth inhibition and was well-tolerated in a human myeloma xenograft murine model with evidence of pharmacodynamic biomarker modulation.

Conclusions: Taken together, our studies demonstrate the dependence of myeloma cells on HSF1 for survival and support the clinical evaluation of pharmacologic inhibitors of the HSF1 pathway in myeloma. Clin Cancer Res; 24(10); 2395–407. ©2018 AACR.

See related commentary by Parekh, p. 2237
NK Cell–Specific CDK8 Deletion Enhances Antitumor Responses
Authors: Witalisz-Siepracka Agnieszka , Gotthardt Dagmar , Prchal-Murphy Michaela , Didara Zrinka , Menzl Ingeborg , Prinz Daniela , Edlinger Leo , Putz Eva Maria , Sexl Veronika
Published: February 2018

Cyclin-dependent kinase 8 (CDK8) is a member of the transcription-regulating CDK family. CDK8 activates or represses transcription by associating with the mediator complex or by regulating transcription factors. Oncogenic activity of CDK8 has been demonstrated in several cancer types. Targeting CDK8 represents a potential therapeutic strategy. Because knockdown of CDK8 in a natural killer (NK) cell line enhances cytotoxicity and NK cells provide the first line of immune defense against transformed cells, we asked whether inhibiting CDK8 would improve NK-cell antitumor responses. In this study, we investigated the role of CDK8 in NK-cell function in vivo using mice with conditional ablation of CDK8 in NKp46+ cells (Cdk8fl/flNcr1Cre). Regardless of CDK8 expression, NK cells develop and mature normally in bone marrow and spleen. However, CDK8 deletion increased expression of the lytic molecule perforin, which correlated with enhanced NK-cell cytotoxicity in vitro. This translates into improved NK cell–mediated tumor surveillance in vivo in three independent models: B16F10 melanoma, v-abl+ lymphoma, and a slowly developing oncogene-driven leukemia. Our results thereby define a suppressive effect of CDK8 on NK-cell activity. Therapies that target CDK8 in cancer patients may enhance NK-cell responses against tumor cells. Cancer Immunol Res; 6(4); 458–66. ©2018 AACR.
Interaction between Medical Treatment and Minimally Invasive Surgical Treatment for the Malignancies of the Digestive Tract
Authors: Kato Hiroyuki , Ono Hiroyuki , Hamamoto Yasuo , Ishikawa Hitoshi
Published: February 2018

Recently, endoscopic diagnosis and treatment methods for early cancer in the digestive tract have made rapid progress. As for surgery, laparoscopic and thoracoscopic techniques have achieved rapidly advancing development in the last 2 decades. Early detection of the malignant lesion and the evolution of endoscopic and surgical device enabled in performing the minimally invasive surgery. Collaboration of medical treatment and minimally invasive surgery for advanced cancer is ongoing in the case of some conditions and in a few institutes. In this review, the contents of the core symposia on “Interaction between medical treatment and minimally invasive surgical treatment for the malignancies of the digestive tract", held at the 11, 12 and 13th annual meeting of the Japanese Gastroenterological Association, are summarized. At each annual meeting, the core symposium focused primarily on gastric, colorectal, and esophageal cancer treatment. For gastric cancer, endoscopic resection and laparoscopic surgery were 2 important key words. For colorectal cancer, multidisciplinary therapy was a major key word. And for esophageal cancer, endoscopic resection, chemoradiotherapy, thoracoscopic surgery and salvage surgery were key words. Patients’ survival and quality of life are expected to further advance as a result of the collaboration of such therapeutic modalities.
Clinical Utility of Capsule Endoscopy and Double-Balloon Enteroscopy in the Management of Obscure Gastrointestinal Bleeding
Authors: Otani Koji , Watanabe Toshio , Shimada Sunao , Hosomi Shuhei , Nagami Yasuaki , Tanaka Fumio , Kamata Noriko , Taira Koichi , Yamagami Hirokazu , Tanigawa Tetsuya , Shiba Masatsugu , Fujiwara Yasuhiro
Published: February 2018

Background: Obscure gastrointestinal bleeding (OGIB) is a common but embarrassing problem for gastroenterologists. Most bleeding lesions associated with OGIB are present in the small intestine and sometimes cannot be identified due to the difficulty associated with physical accessibility. Capsule endoscopy (CE) and double-balloon enteroscopy (DBE) have enabled in the process of diagnosing and have evolved to become approaches to treating OGIB. Summary: CE is a minimally invasive procedure and has a high diagnostic yield in patients with OGIB. DBE offers additional advantage of biopsy collection for pathological diagnosis and therapeutic intervention, but it should be noted that it sometimes causes severe adverse events such as acute pancreatitis, intestinal bleeding, and intestinal perforation. CE should be performed early in the workup course of OGIB. Positive CE findings enhance the diagnostic yield of subsequent DBE, and the effective therapeutic intervention improves the clinical outcomes of OGIB patients. On the contrary, there are no clear guidelines for further investigation of patients with negative CE findings at the present. Although patients in stable general condition may only require follow-up, repeated CE is useful to detect positive findings in patients with evidence of sustained bleeding and progressing anemia. We have revealed that repeated CE has higher positive finding rate than DBE in OGIB patients with negative CE findings in a preliminary study. Key Messages: CE and DBE have complementary roles in the management of OGIB, and the precise timing and proper sequence may be important for the approach to treating OGIB.
Correlation of Fecal Markers with Magnifying Endoscopic Stratification in Patients with Ulcerative Colitis Who Are in Clinical Remission
Authors: Mine Shoichiro , Takeshima Fuminao , Akazawa Yuko , Matsushima Kayoko , Minami Hitomi , Yamaguchi Naoyuki , Ohnita Ken , Isomoto Hajime , Nakao Kazuhiko
Published: February 2018

Background: Maintenance of mucosal healing is recommended during the treatment of ulcerative colitis (UC). However, symptoms of UC often do not reflect mucosal disease activity. Fecal markers such as calprotectin, lactoferrin, and hemoglobin have been reported to correlate well with the Mayo endoscopic subscore (MES) and are being considered alternative monitoring tools in endoscopy. Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is a new and more detailed endoscopic scoring system compared to MES. Furthermore, magnifying endoscopic stratification (ME) based on alterations in the mucosal surface pit patterns is noted in UC. However, the association between fecal markers and UCIES and magnifying endoscopy is relatively unexplored. Summary: This study investigated the association between the aforementioned fecal markers and MES, UCEIS, and ME in patients with UC in clinical remission. This prospective study included 60 patients with UC in clinical remission who underwent colonoscopy at the Nagasaki University Hospital between June 2015 and November 2016. A significant correlation was observed between MES and all fecal markers. Notably, the fecal markers correlated well with UCEIS (calprotectin Spearman’s correlation coefficient [r] = 0.54, p < 0.0001; lactoferrin r = 0.56, p < 0.0001; and hemoglobin r = 0.43, p < 0.001). Furthermore, ME findings correlated significantly with calprotectin (r = 0.50, p = 0.0002) and lactoferrin (r = 0.46, p = 0.0006) levels and slightly with hemoglobin (r = 0.28, p = 0.043) levels. Moreover, each cutoff level of fecal calprotectin, lactoferrin, or hemoglobin had a high sensitivity and specificity for the detection of MES = 0, UCEIS = 0, ME = A, for predicting mucosa healing. Key Messages: Fecal markers correlated not only with MES but also with UCEIS and ME and should be useful for monitoring patients with UC in clinical remission.
Human Embryonic Kidney 293 Cells: A Vehicle for Biopharmaceutical Manufacturing, Structural Biology, and Electrophysiology
Authors: Hu Jianwen , Han Jizhong , Li Haoran , Zhang Xian , Liu Lan lan , Chen Fei , Zeng Bin
Published: February 2018

Mammalian cells, e.g., CHO, BHK, HEK293, HT-1080, and NS0 cells, represent important manufacturing platforms in bioengineering. They are widely used for the production of recombinant therapeutic proteins, vaccines, anticancer agents, and other clinically relevant drugs. HEK293 (human embryonic kidney 293) cells and their derived cell lines provide an attractive heterologous system for the development of recombinant proteins or adenovirus productions, not least due to their human-like posttranslational modification of protein molecules to provide the desired biological activity. Secondly, they also exhibit high transfection efficiency yielding high-quality recombinant proteins. They are easy to maintain and express with high fidelity membrane proteins, such as ion channels and transporters, and thus are attractive for structural biology and electrophysiology studies. In this article, we review the literature on HEK293 cells regarding their origins but also stress their advancements into the different cell lines engineered and discuss some significant aspects which make them versatile systems for biopharmaceutical manufacturing, drug screening, structural biology research, and electrophysiology applications.
Convulsive Seizures as Presenting Symptom of Metronidazole-Induced Encephalopathy: A Case Report
Authors: Sørensen Caspar Godthaab , Karlsson William Kristian , Amin Faisal Mohammad , Lindelof Mette
Published: February 2018

Introduction: Encephalopathy and convulsive seizures are rare manifestations of metronidazole toxicity. The incidence is unknown, but the condition has most frequently been reported in patients in their fifth to sixth decades. Usually, this condition is regarded as reversible, but permanent deficits and even death have been reported. Case Report: A 66-year-old female patient undergoing metronidazole treatment for pleural empyema was admitted to our institution after her second episode of seizure. Over the course of 1 week after admittance, the patient developed several convulsive seizures along with progressive cerebellar dysfunction and cognitive impairment. MRI revealed bilateral, symmetrical hyperintense signal changes in the pons and dentate nuclei. EEG, ECG, lumbar puncture, and blood samples were normal. The patient improved already 2–3 days after discontinuation of metronidazole and was discharged fully recovered after 17 days. Follow-up clinical assessment and MRI were unremarkable. Conclusion: Metronidazole-induced encephalopathy is a rare condition, and due to a general lack of awareness the diagnosis is often delayed. This condition should be considered in metronidazole-treated patients presenting with unprovoked seizures, myoclonus, cerebellar signs, and encephalopathy. Characteristic MRI lesions may support the clinical suspicion.
Acute Lymphoblastic Leukemia Presenting as Fanconi Syndrome
Authors: Yoshida Tatsunori , Tsujimoto Hiroshi , Ichikawa Takayuki , Kounami Shinji , Suzuki Hiroyuki
Published: February 2018

Acute lymphoblastic leukemia (ALL) presenting as Fanconi syndrome (FS) is extremely rare. Here, we report a case of ALL presenting as bilateral nephromegaly following FS. A 2-year-old girl was unexpectedly diagnosed with bilateral nephromegaly. After 2 weeks, she developed general fatigue, thirst, and polyuria. Laboratory examinations revealed renal tubular acidosis, hypokalemia, hypophosphatemia, and aminoaciduria, and FS was diagnosed. Replacement of bicarbonate and potassium did not improve her condition. Two weeks after the onset of FS, leukemic cells appeared on a peripheral blood smear, and the patient was diagnosed with precursor B-cell ALL presenting as nephromegaly and FS. Chemotherapy brought about a prompt resolution of acidosis and electrolyte abnormalities, without renal dysfunction. The patient remains well 4 years after the onset of the disease. Although extremely rare, FS should be recognized as one of the emerging renal complications of ALL.
Restless Legs Syndrome: An Unresolved Uremic Disorder after Renal Transplantation
Authors: Calviño Jesús , Cigarrán Secundino , Gonzalez-Tabares Lourdes , Guijarro Monica , Millán Beatriz , Cobelo Carmen , Cillero Sonia , Sobrido María-Jesús
Published: February 2018

Background: Restless legs syndrome (RLS) is a common complication of uremia that may improve after transplantation. Its frequency might not be as low as expected, as some uremic disturbances may continue even after a successful graft. Our aim was to investigate the prevalence and related conditions for RLS in renal transplant patients. Methods: We carried out a cross-sectional, observational study. A self-administered questionnaire following the International Restless Legs Syndrome Study Group diagnostic criteria was administered to 129 patients (82 men and 47 women) aged 57 ± 12.8 years followed up for at least 1 year, with stable renal function (Cr 1.5 ± 0.54 mg/dL). Patients with probable RLS according to the screening questionnaire underwent comprehensive neurological examination to exclude RLS mimics. Results: The frequency of RLS according to questionnaires was 29.5% (18 men/20 women). After neurological exam, RLS was confirmed in 19 patients providing an overall frequency of 14.8% (higher than the prevalence in the general population). A definitive diagnosis of RLS was established for 6 men (7.3%) and 13 women (27.7%), indicating a positive predictive value for the screening questionnaire of 65% for women and 33% for men. There were fewer patients under renin-angiotensin aldosterone system (RAAS) blocking treatment in the RLS group (21.1 vs. 47.3%). Women with RLS had poorer renal function (52 ± 17.5 vs. 42 ± 13.9 mL/min) and phosphate-reabsorption rate (75 ± 10.5 vs. 65 ± 9.2). There was no difference in age, comorbidities, anticalcineurin therapy, renal function, anemia and time since transplantation between transplant patients with and without RLS. Conclusion: The prevalence of RLS after transplantation remains high (14.8%). This condition is twice more prevalent for females. Contribution of RAAS, graft function and phosphate overload requires further investigation.
Low Expression of FUS1 Is Negatively Correlated with miR-378 and May Predict Adverse Prognoses in Acute Myeloid Leukemia
Authors: Tang Xi , Zhou Jiao , Zhang Jing , Zhou Ling-Yu , Zhai Ling-Ling  , Vanessa Minse Evola-Deniz , Yi Jing , Yi Yun-Yun , Lin Jiang , Deng Zhao-Qun
Published: February 2018

FUS1 is a tumor suppressor gene that has been found to be frequently lost in a variety of solid tumors. In this study, we aimed to investigate the expression status of the FUS1 gene in acute myeloid leukemia (AML), as well as its clinical significance. We further explored the correlation between the expression of FUS1 and miR-378 in AML. We detected expression of the FUS1 transcript in bone marrow mononuclear cells from 23 controls and 158 newly diagnosed AML patients by real-time quantitative polymerase chain reaction. Downregulated FUS1 expression was found in 139 out of 158 (87.97%) AML cases; this rate was significantly lower than that in all 23 controls (p = 0.012). Receiver operating characteristic curve analysis revealed that the FUS1 transcript level could discriminate AML patients from controls effectively (area under the ROC curve = 0.663). Kaplan-Meier analysis demonstrated that non-M3-AML patients with a low FUS1 expression had a shorter overall survival (p = 0.049) and leukemia-free survival (p = 0.051) than those with a high FUS1 expression. Furthermore, we studied the correlation between the expression of FUS1 and miR-378 in 53 newly diagnosed AML patients. We found that the correlation coefficient was –0.346, which showed that FUS1 and miR-378 were negatively correlated in AML patients (p = 0.011). These results indicate that the low expression of FUS1 is a common molecular event in AML.
ПАЛІАТИВНА ДОПОМОГА В НЕОНАТОЛОГЇЇ ТА ШЛЯХИ ЇЇ РОЗВИТКУ
Authors: Slobodyuk Z. O. , Haliyash N. B.
Published: February 2018

У статті розглянуто становлення та сучасний стан паліативної допомоги в неонатології в Україні, а також проаналізовано можливі шляхи її подальшого розвитку. Зростання потреби у розв’язанні складного комплексу фізичних, психосоціальних і духовних проблем невиліковно хворих дітей і членів їхніх родин стало новим викликом для системи охорони здоров’я та поштовхом до розвитку інституцій паліативної допомоги.
ПЕРСОНАЛІСТИЧНА МОДЕЛЬ БІОЕТИКИ ЯК ЕТИЧНА ЗАСАДА МЕДСЕСТРИНСТВА
Authors: Boyeva O. I.
Published: February 2018

Сучасні вимоги до якості медичних послуг, реформування і удосконалення вітчизняної медичної служби спонукало нас вивчити роль біоетичної обізнаності медичного персоналу лікарні у забезпеченні належної якості медичної допомоги. Один раз на місяць проводилося анонімне анкетування стаціонарних пацієнтів щодо дотримання етики та деонтології медпрацівниками у стаціонарних відділеннях, щодо якості надання медичної допомоги хворим стаціонарних відділень, щодо якості харчування хворих стаціонарних відділень. Результати анкетування показують, що успішна медсестринська практика має грунтуватися на етичних засадах персоналістичної моделі біоетики.
ПРОФЕСІЙНА АДАПТАЦІЯ ФЕЛЬдШЕРІВ-ПОЧАТКІВЦІВ НА РОБОЧОМУ МІСЦІ НА СТАНЦІЇ НЕВІДКЛАДНОЇ ДОПОМОГИ
Authors: Rozhelyuk O. V.
Published: February 2018

У статті висвітлено основні проблеми у професійній адаптації випускників зі спеціальності «Лікувальна справа» на станції невідкладної допомоги.
РОЛЬ МЕДИЧНОЇ СЕСТРИ У НАВЧАННІ ХВОРИХ ПО ДОГЛЯДУ ЗА ДІАБЕТИЧНИМИ СТОПАМИ
Authors: Berkela I. O. , Naumova L. V.
Published: February 2018

У статті наведено дані щодо необхідності проведення навчання хворих із діабетичною стопою з метою  кращої компенсації  цукрового діабету. Доведено, що правильний догляд за стопами дозволяє сповільнити прогресування мікросудинних уражень при цукровому діабеті та скоротити час перебування пацієнта в стаціонарі.
ОСОБЛИВОСТІ СТАНОВЛЕННЯ ТА РОЗВИТКУ ПАЛІАТИВНО-ХОСПІСНОЇ ДОПОМОГИ В УКРАЇНІ
Authors: Bugaevskaya N. A.
Published: February 2018

У статті проаналізовано процес становлення та розвитку системи паліативно-хоспісної допомоги в Україні за останні роки, а також фактори, що йому сприяють чи гальмують.
Distinct Pathogenesis of Pancreatic Cancer Microvesicle–Associated Venous Thrombosis Identifies New Antithrombotic Targets In Vivo
Authors: Stark Konstantin , Schubert Irene , Joshi Urjita , Kilani Badr , Hoseinpour Parandis , Thakur Manovriti , Grünauer Petra , Pfeiler Susanne , Schmidergall Tobias , Stockhausen Sven , Bäumer Markus , Chandraratne Sue , von Brühl Marie-Luise , Lorenz Michael , Coletti Raffaele , Reese Sven , Laitinen Iina , Wörmann Sonja Maria , Algül Hana , Bruns Christiane J. , Ware Jerry , Mackman Nigel , Engelmann Bernd , Massberg Steffen
Published: February 2018

Objective—

Cancer patients are at high risk of developing deep venous thrombosis (DVT) and venous thromboembolism, a leading cause of mortality in this population. However, it is largely unclear how malignant tumors drive the prothrombotic cascade culminating in DVT.

Approach and Results—

Here, we addressed the pathophysiology of malignant DVT compared with nonmalignant DVT and focused on the role of tumor microvesicles as potential targets to prevent cancer-associated DVT. We show that microvesicles released by pancreatic adenocarcinoma cells (pancreatic tumor–derived microvesicles [pcMV]) boost thrombus formation in a model of flow restriction of the mouse vena cava. This depends on the synergistic activation of coagulation by pcMV and host tissue factor. Unlike nonmalignant DVT, which is initiated and propagated by innate immune cells, thrombosis triggered by pcMV was largely independent of myeloid leukocytes or platelets. Instead, we identified externalization of the phospholipid phosphatidylethanolamine as a major mechanism controlling the prothrombotic activity of pcMV. Disrupting phosphatidylethanolamine-dependent activation of factor X suppressed pcMV-induced DVT without causing changes in hemostasis.

Conclusions—

Together, we show here that the pathophysiology of pcMV-associated experimental DVT differs markedly from innate immune cell–promoted nonmalignant DVT and is therefore amenable to distinct antithrombotic strategies. Targeting phosphatidylethanolamine on tumor microvesicles could be a new strategy for prevention of cancer-associated DVT without causing bleeding complications.
Anticoagulant Protein S Targets the Factor IXa Heparin-Binding Exosite to Prevent Thrombosis
Authors: Plautz William E. , Sekhar Pilli Vijaya Satish , Cooley Brian C. , Chattopadhyay Rima , Westmark Pamela R. , Getz Todd , Paul David , Bergmeier Wolfgang , Sheehan John P. , Majumder Rinku
Published: February 2018

Objective—

PS (protein S) is a plasma protein that directly inhibits the coagulation FIXa (factor IXa) in vitro. Because elevated FIXa is associated with increased risk of venous thromboembolism, it is important to establish how PS inhibits FIXa function in vivo. The goal of this study is to confirm direct binding of PS with FIXa in vivo, identify FIXa amino acid residues required for binding PS in vivo, and use an enzymatically active FIXa mutant that is unable to bind PS to measure the significance of PS–FIXa interaction in hemostasis.

Approach and Results—

We demonstrate that PS inhibits FIXa in vivo by associating with the FIXa heparin-binding exosite. We used fluorescence tagging, immunohistochemistry, and protein–protein crosslinking to show in vivo interaction between FIXa and PS. Importantly, platelet colocalization required a direct interaction between the 2 proteins. FIXa and PS also coimmunoprecipitated from plasma, substantiating their interaction in a physiological milieu. PS binding to FIXa and PS inhibition of the intrinsic Xase complex required residues K132, K126, and R170 in the FIXa heparin-binding exosite. A double mutant, K132A/R170A, retained full activity but could not bind to PS. Crucially, Hemophilia B mice infused with FIXa K132A/R170A displayed an accelerated rate of fibrin clot formation compared with wild-type FIXa.

Conclusions—

Our findings establish PS as an important in vivo inhibitor of FIXa. Disruption of the interaction between PS and FIXa causes an increased rate of thrombus formation in mice. This newly discovered function of PS implies an unexploited target for antithrombotic therapeutics.
Hyperoxia Causes Mitochondrial Fragmentation in Pulmonary Endothelial Cells by Increasing Expression of Pro-Fission Proteins
Authors: Ma Cui , Beyer Andreas M. , Durand Matthew , Clough Anne V. , Zhu Daling , Norwood Toro Laura , Terashvili Maia , Ebben Johnathan D. , Hill R. Blake , Audi Said H. , Medhora Meetha , Jacobs Elizabeth R.
Published: February 2018

Objective—

We explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia.

Approach and Results—

Mitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot. Mitochondrial oxidative state was determined using mito-roGFP. Tetramethylrhodamine methyl ester estimated mitochondrial polarization in treatment groups. The role of mitochondrially derived reactive oxygen species in mt-fragmentation was investigated with mito-TEMPOL and mitochondrial DNA (mtDNA) damage studied by using ENDO III (mt-tat-endonuclease III), a protein that repairs mDNA damage. Drp-1 (dynamin-related protein 1) was overexpressed or silenced to test the role of this protein in cell survival or transwell resistance. Hyperoxia increased fragmentation of PEC mitochondria in a time-dependent manner through 48 hours of exposure. Hyperoxic PECs exhibited increased phosphorylation of Drp-1 (serine 616), decreases in Mfn1 (mitofusion protein 1), but increases in OPA-1 (optic atrophy 1). Pro-autophagy proteins p62 (LC3 adapter–binding protein SQSTM1/p62), PINK-1 (PTEN-induced putative kinase 1), and LC3B (microtubule-associated protein 1A/1B-light chain 3) were increased. Returning cells to normoxia for 24 hours reversed the increased mt-fragmentation and changes in expression of pro-fission proteins. Hyperoxia-induced changes in mitochondrial structure or cell survival were mitigated by antioxidants mito-TEMPOL, Drp-1 silencing, or inhibition or protection by the mitochondrial endonuclease ENDO III. Hyperoxia induced oxidation and mitochondrial depolarization and impaired transwell resistance. Decrease in resistance was mitigated by mito-TEMPOL or ENDO III and reproduced by overexpression of Drp-1.

Conclusions—

Because hyperoxia evoked mt-fragmentation, cell survival and transwell resistance are prevented by ENDO III and mito-TEMPOL and Drp-1 silencing, and these data link hyperoxia-induced mt-DNA damage, Drp-1 expression, mt-fragmentation, and PEC dysfunction.
New Insights Into the Role of mTOR Signaling in the Cardiovascular System
Authors: Sciarretta Sebastiano , Forte Maurizio , Frati Giacomo , Sadoshima Junichi
Published: February 2018

The mTOR (mechanistic target of rapamycin) is a master regulator of several crucial cellular processes, including protein synthesis, cellular growth, proliferation, autophagy, lysosomal function, and cell metabolism. mTOR interacts with specific adaptor proteins to form 2 multiprotein complexes, called mTORC1 (mTOR complex 1) and mTORC2 (mTOR complex 2). In the cardiovascular system, the mTOR pathway regulates both physiological and pathological processes in the heart. It is needed for embryonic cardiovascular development and for maintaining cardiac homeostasis in postnatal life. Studies involving mTOR loss-of-function models revealed that mTORC1 activation is indispensable for the development of adaptive cardiac hypertrophy in response to mechanical overload. mTORC2 is also required for normal cardiac physiology and ensures cardiomyocyte survival in response to pressure overload. However, partial genetic or pharmacological inhibition of mTORC1 reduces cardiac remodeling and heart failure in response to pressure overload and chronic myocardial infarction. In addition, mTORC1 blockade reduces cardiac derangements induced by genetic and metabolic disorders and has been reported to extend life span in mice. These studies suggest that pharmacological targeting of mTOR may represent a therapeutic strategy to confer cardioprotection, although clinical evidence in support of this notion is still scarce. This review summarizes and discusses the new evidence on the pathophysiological role of mTOR signaling in the cardiovascular system.
Cardioprotective Role of Myeloid-Derived Suppressor Cells in Heart Failure
Authors: Zhou Ling , Miao Kun , Yin Bingjiao , Li Huaping , Fan Jiahui , Zhu Yazhen , Ba Hongping , Zhang Zunyue , Chen Fang , Wang Jing , Zhao Chunxia , Li Zhuoya , Wang Dao Wen
Published: February 2018

Background:

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that expand in cancer, inflammation, and infection and negatively regulate inflammation and the immune response. Heart failure (HF) is a complex clinical syndrome wherein inflammation induction and incomplete resolution can potentially contribute to HF development and progression. However, the role of MDSCs in HF remains unclear.

Methods:

The percentage of MDSCs in patients with HF and in mice with pressure overload–induced HF using isoproterenol infusion or transverse aortic constriction (TAC) was detected by flow cytometry. The effects of MDSCs on isoproterenol- or TAC-induced HF were observed on depleting MDSCs with 5-fluorouracil (50 mg/kg) or gemcitabine (120 mg/kg), transferring purified MDSCs, or enhancing endogenous MDSCs with rapamycin (2 mg·kg
−1
·d
−1
). Hypertrophic markers and inflammatory factors were detected by ELISA, real-time polymerase chain reaction, or Western blot. Cardiac functions were determined by echocardiography and hemodynamic analysis.

Results:

The percentage of human leukocyte antigen-D–related (HLA-DR)
−
CD33
+
CD11b
+
MDSCs in the blood of patients with HF was significantly increased and positively correlated with disease severity and increased plasma levels of cytokines, including interleukin-6, interleukin-10, and transforming growth factor–β. Furthermore, MDSCs derived from patients with HF inhibited T-cell proliferation and interferon-γ secretion. Similar results were observed in TAC- and isoproterenol-induced HF in mice. Pharmaceutical depletion of MDSCs significantly exacerbated isoproterenol- and TAC-induced pathological cardiac remodeling and inflammation, whereas adoptive transfer of MDSCs prominently rescued isoproterenol- and TAC-induced HF. Consistently, administration of rapamycin significantly increased endogenous MDSCs by suppressing their differentiation and improved isoproterenol- and TAC-induced HF, but MDSC depletion mostly blocked beneficial rapamycin-mediated effects. Mechanistically, MDSC-secreted molecules suppressed isoproterenol-induced hypertrophy and proinflammatory gene expression in cardiomyocytes in a coculture system. Neutralization of interleukin-10 blunted both monocytic MDSC- and granulocytic MDSC–mediated anti-inflammatory and antihypertrophic effects, but treatment with a nitric oxide inhibitor only partially blocked the antihypertrophic effect of monocytic MDSCs.

Conclusions:

Our findings revealed a cardioprotective role of MDSCs in HF by their antihypertrophic effects on cardiomyocytes and anti-inflammatory effects through interleukin-10 and nitric oxide. Pharmacological targeting of MDSCs by rapamycin constitutes a promising therapeutic strategy for HF.
Liver X Receptor–Binding DNA Motif Associated With Atherosclerosis‐Specific DNA Methylation Profiles of
Alu
Elements and Neighboring CpG Islands
Authors: Tristán‐Flores Fabiola E. , Guzmán Plinio , Ortega‐Kermedy Melany S. , Cruz‐Torres Gabriela , de la Rocha Carmen , Silva‐Martínez Guillermo A. , Rodríguez‐Ríos Dalia , Alvarado‐Caudillo Yolanda , Barbosa‐Sabanero Gloria , Sayols Sergi , Lund Gertrud , Zaina Silvio
Published: February 2018

Background

The signals that determine atherosclerosis‐specific
DNA
methylation profiles are only partially known. We previously identified a 29‐bp
DNA
motif (differential methylation motif [
DMM]
) proximal to CpG islands (
CGI
s) that undergo demethylation in advanced human atheromas. Those data hinted that the
DMM
docks modifiers of
DNA
methylation and transcription.

Methods and Results

We sought to functionally characterize the
DMM
. We showed that the
DMM
overlaps with the
RNA
polymerase
III
–binding B box of
Alu
short interspersed nuclear elements and contains a
DR
2 nuclear receptor response element. Pointing to a possible functional role for an
Alu
DMM
,
CGI
s proximal (<100 bp) to near‐intact
DMM
–harboring
Alu
are significantly less methylated relative to
CGI
s proximal to degenerate
DMM
–harboring
Alu
or to
DMM
‐devoid mammalian‐wide interspersed repeat short interspersed nuclear elements in human arteries. As for
DMM
‐binding factors, LXRB (liver X receptor β) binds the
DMM
in a
DR
2‐dependent fashion, and LXR (liver X receptor) agonists induce significant hypermethylation of the bulk of
Alu
in
THP
‐1 cells. Furthermore, we describe 3 intergenic long noncoding
RNA
s that harbor a
DMM
, are under transcriptional control by
LXR
agonists, and are differentially expressed between normal and atherosclerotic human aortas. Notably,
CGI
s adjacent to those long noncoding
RNA
s tend to be hypomethylated in symptomatic relative to stable human atheromas.

Conclusions

Collectively, the data suggest that a
DMM
is associated with 2 distinct methylation states: relatively low methylation of
in cis
CGI
s and
Alu
element hypermethylation. Based on the known atheroprotective role of
LXR
s, we propose that
LXR
agonist–induced
Alu
hypermethylation, a landmark of atherosclerosis, is a compensatory rather than proatherogenic response.
Jews and Judaism in Classical Sufi Literature
Authors: Russ-Fishbane Elisha
Published: February 2018

This paper addresses a paradox at the heart of the classical Sufi tradition. On the one hand, key Sufi writers express a radical universalism or ‘transconfessionalism’ in their mystical verse. This has led a variety of modern scholars to identify Sufism as an ecumenical and non-dogmatic tradition. On the other hand, in other writings the selfsame authors conduct a vigorous literary polemic and celebrate missionary efforts against unbelievers of all stripes, yet with a notable emphasis on Jewish unbelievers. This article examines the image of Jews and Judaism in key Sufi texts in both Arabic and Persian between the tenth and thirteenth centuries through a variety of motifs, including the construction of the Jew as embodiment of the demonic and as archetypal unbeliever. These images become critical to the literary function of the Jew in classical Sufi texts with little connection to their historical role in Near Eastern societies.
Sufi Poetry in Twentieth-Century Nigeria
Authors: Brigaglia Andrea
Published: February 2018

This article presents the translation and analysis of two poems (the first in Arabic, the second in Hausa) authored by one of the most famous twentieth-century Islamic scholars and Tijānī Sufis of Kano (Nigeria), Abū Bakr al-ʿAtīq b. Khiḍr (1909–74). As examples of two genres of Sufi poetry that are rather unusual in West Africa (the khamriyya or wine ode and the ghazal or love ode), these poems are important literary and religious documents. From the literary point of view, they are vivid testimonies of the vibrancy of the Sufi qaṣīda tradition in West Africa, and of the capacity of local authors to move across its various genres. From the religious point of view, they show the degree to which the West African Sufis mastered the Sufi tradition, both as a set of spiritual practices and techniques and as a set of linguistic tools to speak of the inner.
A new species of Cleistocybe (Agaricales, Basidiomycota) from the Tibetan Plateau, China
Authors: WU HONG-MEI , LUO JIA-QI , WANG KE , ZHANG RUN-CHAO , LI YI , WU HAI-JUN , WANG YONG-HUI , WEI XIAO-DAN , YAO YI-JIAN
Published: February 2018

During field expeditions to the Tibetan Plateau, a collection of an undescribed species with several basidiomes was found. Morphological observation and DNA sequence analyses of the collection revealed a close relationship with Cleistocybe vernalis, the type species of the genus Cleistocybe. Therefore, a new species is proposed for the fungus with full morphological description accompanied by phylogenetic analyses. The discovery of the species extends the reported distribution of the genus from the north of America and Europe to Asia.
Nomenclatural novelties in Cheiridopsis (Ruschieae: Aizoaceae)
Authors: POWELL ROBYN F. , BOATWRIGHT JAMES S. , KLAK CORNELIA , MAGEE ANTHONY R.
Published: February 2018

The recent study by Powell et al. (2017) showed that the species previously included in the genera Odontophorus N.E.Brown (1927: 12) and Ihlenfeldtia H.E.K.Hartmann (1992: 47) should be recognized under the Southern African endemic genus Cheiridopsis N.E.Brown (1925: 412) (Ruschieae Schwant. ex Ihlenf., Schwant. & Straka, Aizoaceae Martinov). In the new circumscription of Powell et al. (2017), Cheiridopsis comprises of 38 species which belong to three subgenera, i.e. subgen. Cheiridopsis N.E.Brown (1925: 412), subgen. Aequifoliae (1983: 59), and subgen. Odontophoroides H.E.K.Hartmann (1983: 59) (see Hartmann & Dehn 1987, Powell et al. 2017).
Two new species of Marphysa Quatrefages, 1865 (Polychaeta: Eunicida: Eunicidae) from northern coast of China and redescription for Marphysa orientalis Treadwell, 1936
Authors: LIU YUBIN , HUTCHINGS PAT , KUPRIYANOVA ELENA
Published: February 2018

Two new species of Marphysa Quatrefages, 1865 (Polychaeta: Eunicida: Eunicidae), M. bulla n. sp. and M. maxidenticulata n. sp., are described from the northern coast of China with comments on the usefulness of pectinate chaetae to separate species. A redescription of Marphysa orientalis Treadwell, 1936 originally described from China is given. The genus Marphysa is widely collected for bait for recreational fishermen and anglers in China and is also exported to Australia and Japan, yet the number of species involved or their native distribution are currently unknown. It is critical that aquaculture programs know which species they are attempting to breed and their native distributional ranges. A key to all described species of Marphysa from China, including two new species described in this paper is given.
Relationship Between Kinematic and Physiological Indices During Braking Events of Different Intensities
Authors: Musicant Oren , Botzer Assaf , Laufer Ilan , Collet Christian
Published: February 2018

Objective

To study the relationship between physiological indices and kinematic indices during braking events of different intensities.

Background

Based on mental workload theory, driving and other task demands may generate changes in physiological indices, such as the driver’s heart rate and skin conductance. However, no attempts were made to associate changes in physiological indices with changes in vehicle kinematics that result from the driver attempts to meet task demands.

Method

Twenty-five drivers participated in a field experiment. We manipulated braking demands using roadside signs to communicate the speed (km/h) before braking (50 or 60) and the target speed for braking (30 or to a complete stop). In an additional session, we asked drivers to brake as if they were responding to an impending collision. We analyzed the relationship between the intensities of braking events as measured by deceleration values (g) and changes in heart rate, heart rate variability, and skin conductance.

Results

All physiological indices were associated with deceleration intensity. Especially salient were the differences in physiological indices between the intensive (|g| > 0.5) and nonintensive braking events. The strongest relationship was between braking intensity and skin conductance.

Conclusions

Skin conductance, heart rate, and heart rate variability can mirror the mental workload elicited by varying braking intensities.

Application

Associating vehicle kinematics with physiological indices related to short-term driving events may help improve the performance of driver assistance systems.
The psychiatrist as advocate
Authors: Diamond Bernard L.
Published: February 2018

The ideal psychiatric expert witness is generally conceived of as objective, unbiased and uninvolved in the outcome of the trial in which he is testifying. Nevertheless, the expert witness must inevitably act as advocate, either willingly or unwillingly, either with or without awareness. To accept the advocate role and to pursue it intentionally from the witness stand is honest and ethical if done without deceit. Such advocacy may result in important legal reforms, in benefits to the participants in the trial process and in improvements in the relations between psychiatry and the law.