bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Insights into the Eukaryotic Transcription Initiation Machinery
Authors: Nogales Eva , Louder Robert K. , He Yuan
Published: May 2017

Eukaryotic gene transcription requires the assembly at the promoter of a large preinitiation complex (PIC) that includes RNA polymerase II (Pol II) and the general transcription factors TFIID, TFIIA, TFIIB, TFIIF, TFIIE, and TFIIH. The size and complexity of Pol II, TFIID, and TFIIH have precluded their reconstitution from heterologous systems, and purification relies on scarce endogenous sources. Together with their conformational flexibility and the transient nature of their interactions, these limitations had precluded structural characterization of the PIC. In the last few years, however, progress in cryo–electron microscopy (cryo-EM) has made possible the visualization, at increasingly better resolution, of large PIC assemblies in different functional states. These structures can now be interpreted in near-atomic detail and provide an exciting structural framework for past and future functional studies, giving us unique mechanistic insight into the complex process of transcription initiation.
Knowledge on Irradiation, Medical Imaging Prescriptions, and Clinical Imaging Referral Guidelines among Physicians in a Sub-Saharan African Country (Cameroon)
Authors: Moifo Boniface , Tene Ulrich , Moulion Tapouh Jean Roger , Samba Ngano Odette , Tchemtchoua Youta Justine , Simo Augustin , Gonsu Fotsin Joseph
Published: May 2017

Background. Clinical imaging guidelines (CIGs) are suitable tools to enhance justification of imaging procedures. Objective. To assess physicians’ knowledge on irradiation, their self-perception of imaging prescriptions, and the use of CIGs. Materials and Methods. A questionnaire of 21 items was self-administered between July and August 2016 to 155 referring physicians working in seven university-affiliated hospitals in Yaoundé and Douala (Cameroon). This pretested questionnaire based on imaging referral practices, the use and the need of CIGs, knowledge on radiation doses of 11 specific radiologic procedures, and knowledge of injurious effects of radiation was completed in the presence of the investigator. Scores were allocated for each question. Results. 155 questionnaires were completed out of 180 administered (86.1%). Participants were 90 (58%) females, 63 (40.64%) specialists, 53 (34.20%) residents/interns, and 39 (25.16%) general practitioners. The average professional experience was 7.4 years (1–25 years). The mean knowledge score was 11.5/59 with no influence of sex, years of experience, and professional category. CIGs users’ score was better than nonusers (means 14.2 versus 10.6; p<0.01). 80% of physicians (124/155) underrated radiation doses of routine imaging exams. Seventy-eight (50.3%) participants have knowledge on CIGs and half of them made use of them. “Impact on diagnosis” was the highest justification criteria follow by “impact on treatment decision.” Unjustified requests were mainly for “patient expectation or will” or for “research motivations.” 96% of interviewees believed that making available national CIGs will improve justification. Conclusion. Most physicians did not have appropriate awareness about radiation doses for routine imaging procedures. A small number of physicians have knowledge on CIGs but they believe that making available CIGs will improve justification of imaging procedures. Continuous trainings on radiation protection and implementation of national CIGs are therefore recommended.
Sliding Mode Control of Cable‐Driven Redundancy Parallel Robot with 6 DOF Based on Cable‐Length Sensor Feedback
Authors: Lv Wei , Tao Limin , Ji Zhengnan
Published: May 2017

The sliding mode control of the cable‐driven redundancy parallel robot with six degrees of freedom is studied based on the cable‐length sensor feedback. Under the control scheme of task space coordinates, the cable length obtained by the cable‐length sensor is used to solve the forward kinematics of the cable‐driven redundancy parallel robot in real‐time, which is treated as the feedback for the control system. First, the method of forward kinematics of the cable‐driven redundancy parallel robot is proposed based on the tetrahedron method and Levenberg‐Marquardt method. Then, an iterative initial value estimation method for the Levenberg‐Marquardt method is proposed. Second, the sliding mode control method based on the exponential approach law is used to control the effector of the robot, and the influence of the sliding mode parameters on control performance is simulated. Finally, a six‐degree‐of‐freedom position tracking experiment is carried out on the principle prototype of the cable‐driven redundancy parallel robot. The experimental results show that the robot can accurately track the desired position in six directions, which indicates that the control method based on the cable‐length sensor feedback for the cable‐driven redundancy parallel robot is effective and feasible.
Component Release and Mechanical Properties of Endodontic Sealers following Incorporation of Antimicrobial Agents
Authors: Gjorgievska Elizabeta S. , Nicholson John W. , Coleman Nichola J. , Booth Samantha , Dimkov Aleksandar , Hurt Andrew
Published: May 2017

Root canal sealers with antimicrobial activity are highly beneficial; therefore, their antimicrobial properties could be improved by incorporation of antimicrobial agents. In the present study, the release of the quaternary ammonium compounds from endodontic sealers admixed with either benzalkonium chloride (BC) or cetylpyridinium chloride (CPC) at loadings of 2% wt was monitored. The effect of these additives on the compressive strengths and their release from the sealers was determined after 1 and 4 weeks. All of the materials studied were found to be capable of releasing antimicrobial additive in useful quantities. The release of CPC occurred to a statistically significant greater extent than BC for all materials. The addition of both BC and CPC generally decreased the compressive strength of all the endodontic sealers, with the exception of CPC in AH Plus, where the compressive strength was significantly increased. This suggests that, for these endodontic sealers, the antimicrobial additives alter the setting chemistry. AH Plus is an epoxy-based material cured with an amine, and in this case the increase in compressive strength with CPC is attributed to an enhanced cure reaction with this system. In all other cases, the additive inhibited the cure reaction to a greater or lesser extent.
Effects of Src Kinase Inhibition on Expression of Protein Tyrosine Phosphatase 1B after Brain Hypoxia in a Piglet Animal Model
Authors: Angelis Dimitrios , Delivoria-Papadopoulos Maria
Published: May 2017

Background. Protein tyrosine phosphatases (PTPs) in conjunction with protein tyrosine kinases (PTKs) regulate cellular processes by posttranslational modifications of signal transduction proteins. PTP nonreceptor type 1B (PTP-1B) is an enzyme of the PTP family. We have previously shown that hypoxia induces an increase in activation of a class of nonreceptor PTK, the Src kinases. In the present study, we investigated the changes that occur in the expression of PTP-1B in the cytosolic component of the brain of newborn piglets acutely after hypoxia as well as long term for up to 2 weeks.Methods. Newborn piglets were divided into groups: normoxia, hypoxia, hypoxia followed by 1 day and 15 days in FiO20.21, and hypoxia pretreated with Src kinase inhibitor PP2, prior to hypoxia followed by 1 day and 15 days. Hypoxia was achieved by providing 7% FiO2for 1 hour and PTP-1B expression was measured via immunoblotting.Results. PTP-1B increased posthypoxia by about 30% and persisted for 2 weeks while Src kinase inhibition attenuated the expected PTP-1B-increased expression.Conclusions. Our study suggests that Src kinase mediates a hypoxia-induced increased PTP-1B expression.
A New Approach for Accurate Prediction of Liquid Loading of Directional Gas Wells in Transition Flow or Turbulent Flow
Authors: Ming Ruiqing , He Huiqun
Published: May 2017

Current common models for calculating continuous liquid-carrying critical gas velocity are established based on vertical wells and laminar flow without considering the influence of deviation angle and Reynolds number on liquid-carrying. With the increase of the directional well in transition flow or turbulent flow, the current common models cannot accurately predict the critical gas velocity of these wells. So we built a new model to predict continuous liquid-carrying critical gas velocity for directional well in transition flow or turbulent flow. It is shown from sensitivity analysis that the correction coefficient is mainly influenced by Reynolds number and deviation angle. With the increase of Reynolds number, the critical liquid-carrying gas velocity increases first and then decreases. And with the increase of deviation angle, the critical liquid-carrying gas velocity gradually decreases. It is indicated from the case calculation analysis that the calculation error of this new model is less than 10%, where accuracy is much higher than those of current common models. It is demonstrated that the continuous liquid-carrying critical gas velocity of directional well in transition flow or turbulent flow can be predicted accurately by using this new model.
A Novel Surgical Technique for Fixation of Recurrent Acromioclavicular Dislocations: AC Dog Bone Technique in Combination with Autogenous Semitendinosus Tendon Graft
Authors: Holweg Patrick , Pichler Wolfgang , Gruber Gerald , Tackner Ellen , Seibert Franz Josef , Sadoghi Patrick , Hohenberger Gloria
Published: May 2017

Various surgical techniques have been described for the fixation of acromioclavicular (AC) dislocations. However, recurrent dislocation is one of the main complications associated with the majority of these techniques. We report a case of postoperative AC joint redislocation. In order to overcome recurrent dislocation after revision surgery, a reconstruction of the conoid and trapezoid ligament with the use of a free tendon graft in combination with a FiberTape was provided within a novel surgical technique. After 12 months, the patient was very satisfied with the functional outcome. The patient achieved excellent results in the Constant (98 points), SPADI (0 points), and QuickDASH score (0 points). The described technique results in an anatomic reconstruction of the AC joint. The nonrigid nature of the intervention seems to restore the normal arthrokinematics by reconstructing the coracoclavicular ligaments with an autograft which is then protected by the AC Dog Bone artificial ligaments during the healing period. The arthroscopic approach to the AC joint with minimal exposure reduces the risks and complications of the intervention. This is the first case in literature that utilizes the artificial dog bone ligament securing the autograft in an anatomic AC reconstruction.
Periplaneta americana Extracts Promote Skin Wound Healing via Nuclear Factor Kappa B Canonical Pathway and Extracellular Signal‐Regulated Kinase Signaling
Authors: Song Qin , Gou Qiheng , Xie Yuxin , Zhang Zhen , Fu Chaomei
Published: May 2017

Periplaneta americana extracts (PAEs) exhibit wound healing properties. However, the underlying molecular mechanisms are not well understood. Here, we treated human skin fibroblasts (HSF) with PAE and the proliferation was determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The wound healing and transwell migration assays were used to detect cell migration. Nuclear factor kappa B (NF‐κB) and extracellular signal‐regulated kinase (ERK) pathways were analyzed by Western blot (WB). Immunofluorescence staining was used to detect the key molecular localization in the cells. The results showed that PAE enhanced the proliferation and migration of HSF cells. The expression and activation of key proteins such as RelA and p‐ERK were increased in NF‐κB and ERK pathways followed by nuclear translocation. In vivo, both WB and immunohistochemical (IHC) staining showed that PAE enhanced p‐IκBα and p‐ERK activation and the nuclear translocation of RelA. Our study suggests that the protective function of PAE is mediated via enhanced NF‐κB and ERK signaling.
Pharmacokinetic Comparison of 20(R)‐ and 20(S)‐Ginsenoside Rh1 and 20(R)‐ and 20(S)‐Ginsenoside Rg3 in Rat Plasma following Oral Administration of Radix Ginseng Rubra and Sheng‐Mai‐San Extracts
Authors: Fan Xiaomei , Xu Yan , Zhu Danni , Ji Yibing
Published: May 2017

Ginsenosides Rh1 and Rg3, as the main bioactive components from Ginseng, are effective for prevention and treatment of cardiovascular diseases. Sheng‐Mai‐San (SMS), a classical complex prescription of traditional Chinese medicines, is composed of Radix Ginseng Rubra, Fructus Schisandrae, and Radix Ophiopogonis. In this research, a sensitive and specific liquid chromatography‐mass spectrometric method was developed and validated for stereoselective determination and pharmacokinetic studies of 20(R)‐ and 20(S)‐ginsenoside Rh1 and 20(R)‐ and 20(S)‐ginsenoside Rg3 epimers in rat plasma after oral administration of Radix Ginseng Rubra or SMS extracts. The main pharmacokinetic parameters including Tmax, Cmax, t1/2, and AUC were calculated by noncompartment model. Compared with Radix Ginseng Rubra, SMS could significantly increase the content of ginsenosides Rh1 and Rg3 in the decocting process. Ginsenosides Rh1 and Rg3 following SMS treatment displayed higher Cmax, AUC(0–t), and AUC(0–∞) and longer t1/2 and tmax except for 20(R)‐Rh1 in rat plasma. The results indicated SMS compound compatibility could influence the dissolution in vitro and the pharmacokinetic behaviors in vivo of ginsenosides Rh1 and Rg3, suggesting pharmacokinetic drug‐drug interactions between ginsenosides Rh1 and Rg3 and other ingredients from Fructus Schisandrae and Radix Ophiopogonis. This study would provide valuable information for drug development and clinical application of SMS.
Status and Prospects of Robotic Gastrectomy for Gastric Cancer: Our Experience and a Review of the Literature
Authors: Lee Sejin , Son Taeil , Kim Hyoung-Il , Hyung Woo Jin
Published: May 2017

Since the first report of robotic gastrectomy, experienced laparoscopic surgeons have used surgical robots to treat gastric cancer and resolve problems associated with laparoscopic gastrectomy. However, compared with laparoscopic gastrectomy, the superiority of robotic procedures has not been clearly proven. There are several advantages to using robotic surgery for gastric cancer, such as reduced estimated blood loss during the operation, a shorter learning curve, and a larger number of examined lymph nodes than conventional laparoscopic gastrectomy. The increased operation time observed with a robotic system is decreasing because surgeons have accumulated experience using this procedure. While there is limited evidence, long-term oncologic outcomes appear to be similar between robotic and laparoscopic gastrectomy. Robotic procedures have a significantly greater financial cost than laparoscopic gastrectomy, which is a major drawback. Recent clinical studies tried to demonstrate that the benefits of robotic surgery outweighed the cost, but the overall results were disappointing. Ongoing studies are investigating the benefits of robotic gastrectomy in more complicated and challenging cases. Well-designed randomized control trials with large sample sizes are needed to investigate the benefits of robotic gastrectomy compared with laparoscopic surgery.
Read Range Enhancement of a Sensing RFID Tag by Photovoltaic Panel
Authors: Molina-Farrugia B. , Rivadeneyra A. , Fernández-Salmerón J. , Martínez-Martí F. , Banqueri J. , Carvajal M. A.
Published: May 2017

An RFID tag with energy harvesting and sensing capabilities is presented in this paper. This RFID tag is based on an integrated circuit (SL900A) that incorporates a sensor front-end interface capable of measuring voltages, currents, resistances, and capacitances. The aim of this work is to improve the communication distance from the reader to the tag using energy harvesting techniques. Once the energy source and harvester are chosen according to the environment of work, the conditioning circuit for energy management has to be appropriately designed with respect to the nature of the transductor. As a proof of concept, a photovoltaic panel is used in this work to collect the energy from the environment that is managed by a DC-DC converter and stored in a capacitor acting as battery. Such energy is used to support the power system of the tag, giving autonomy to the device and allowing data logging. In particular, the developed tag monitors the ambient temperature and the power voltage. It would be possible to add external sensors without changing the architecture. An increase in the read range of more than 200% is demonstrated. This feature is especially interesting in environments where the access could be difficult.
Effectiveness of a Commercial Lactic Acid Bacteria Intervention Applied to Inhibit Shiga Toxin-Producing Escherichia coli on Refrigerated Vacuum-Aged Beef
Authors: Kirsch Katie R. , Tolen Tamra N. , Hudson Jessica C. , Castillo Alejandro , Griffin Davey , Taylor T. Matthew
Published: May 2017

Because of their antagonistic activity towards pathogenic and spoilage bacteria, some members of the lactic acid bacteria (LAB) have been evaluated for use as food biopreservatives. The objectives of this study were to assess the antimicrobial utility of a commercial LAB intervention against O157 and non-O157 Shiga-toxigenic E. coli (STEC) on intact beef strip loins during refrigerated vacuum aging and determine intervention efficacy as a function of mode of intervention application. Prerigor strip loins were inoculated with a cocktail (8.9±0.1 log10 CFU/ml) of rifampicin-resistant (100.0 μg/ml; RifR) O157 and non-O157 STEC. Inoculated loins were chilled to ≤4°C and treated with 8.7±0.1 log10 CFU/ml LAB intervention using either a pressurized tank air sprayer (conventional application) or air-assisted electrostatic sprayer (ESS). Surviving STEC were enumerated on tryptic soy agar supplemented with 100.0 μg/ml rifampicin (TSAR) to determine STEC inhibition as a function of intervention application method (conventional, ESS) and refrigerated aging period (14, 28 days). Intervention application reduced STEC by 0.4 log10 CFU/cm2 (p<0.05), although application method did not impact STEC reductions (p>0.05). Data indicate that the LAB biopreservative may assist beef safety protection when utilized within a multi-intervention beef harvest, fabrication, and aging process.
Corrosion and Strength Behaviors in Prestressed Tendon under Various Tensile Stress and Impressed Current Conditions
Authors: Lee Bang-Yeon , Koh K. T. , Ismail M. A. , Ryu H. S. , Kwon S. J.
Published: May 2017

Corrosion occurs more rapidly under high tensile stress and this leads to several problems like degradation of serviceability and structural performance in PSC (prestressed concrete) structures. In this paper, impressed current method, so-called ICM, was applied to tendons under tensile loadings of 0.0, 20.0, 40.0, and 60.0% of ultimate load. With induction of 20 volts for 24 hours to tendon under tensile stress, loading was induced to failure and the ultimate load was evaluated with varying corrosion behaviors. The changing mechanical behaviors in the same corrosive conditions were evaluated under different initial prestressing levels. With increasing initial prestressing load, corrosion occurred more rapidly and corrosion amount also increased linearly. The ultimate load accordingly decreased with increasing initial prestressing and corrosion amount. The relationships between prestressing levels and corrosion behaviors were quantitatively obtained through regression analysis. The measured current during applied voltage and the related corrosion amounts were also dealt with in this work.
Seed Oil ofMorinda citrifoliaL. as a Surfactant for Deinking Flotation
Authors: Trismawati Trismawati , Wardana I. N. G. , Hamidi Nurkholis , Sasongko Mega Nur
Published: May 2017

Surfactants are essential in the pulp recovery process for the removal of ink on paper to be recycled. In order to create a “green” surfactant, seed oil was extracted fromMorinda citrifoliaL. by Soxhlet extraction for 4–8 h and its composition evaluated by gas chromatography-mass spectrometry (GC-MS). The total ion chromatogram (TIC) of fatty acids ofMorinda citrifoliaL. (FAMC) indicated that extraction yields the largest amount of unsaturated fatty acids (UFA), specifically C19H34O2and C21H38O2, at 6 h. All FAMC fractions were evaluated for their suitability as a surfactant for deinking flotation. FAMC isolated after 6 h of extraction yields fatty acids that are the most suitable surfactants, as the fraction consists of mostly unsaturated fatty acids that show good interactions with the structure of common ink molecules. Our results show that the performance of the FAMC taken after 6 h of extraction approaches that of a synthetic surfactant (SS). The appropriate viscous force for deinking flotation was found to be 1.5–2.0 × 10−4 mg/mm s2when the synthetic surfactant is used compared to 1.0–1.5 × 10−4 mg/mm s2for FAMC. The higher intermolecular bonding strength in the synthetic surfactant-ink particle system requires higher viscous force.
Elemental Characterization of Romanian Crop Medicinal Plants by Neutron Activation Analysis
Authors: Haidu Daniela , Párkányi Dénes , Moldovan Radu Ioan , Savii Cecilia , Pinzaru Iulia , Dehelean Cristina , Kurunczi Ludovic
Published: May 2017

The metallic elements concentrations of medicinal plants (coriander, dill,Echinacea, lavender, chamomile, mint, and plantain, used for phytopharmaceutical products), cultivated in unpolluted region, were analyzed by neutron activation analysis. The essential nutrients, macro-, micro-, and trace elements (K, Ca, Mg, Na, Fe, Mn, Rb, Sr, and Zn), potentially toxic elements (Al, As, Ba, Co, Sb, Cr, and V), and rare earth elements were monitored and were compared with those presented in the literature. An estimation of their contributions to intake and toxicity for a person was made, which revealed that (a) teas prepared from the examined plants represent useful contribution to the food provided intake of three essential macronutrients (K, Ca, and Mg); (b) the Cu, Mn, Rb, Sr, Zn, and rare earths levels are normal or low; (c) the quantities of As, Ba, Co, Sb, Cr, and V do not represent toxicological concerns; (d) the examination of the estimated Al and Fe quantities recovered in infusions in the conditions of usual daily tea consumption is below the Tolerable Daily Intake values. The strategy of cultivation of medicinal plants in unpolluted areas is efficient and beneficial. However, individual plants ability to concentrate preferentially certain elements suggests controlling the contamination level of raw materials.
VHL Inactivation in Precancerous Kidney Cells Induces an Inflammatory Response via ER Stress–Activated IRE1α Signaling
Authors: Kuo Chan-Yen , Lin Chih-Hung , Hsu Tien
Published: May 2017

Mutations and epigenetic inactivation of the tumor suppressor gene von Hippel-Lindau (VHL) are major causes of clear-cell renal cell carcinoma (ccRCC) that may originate from chronic inflammation. However, the role of VHL loss of function in the development of ccRCC via inflammation remains poorly understood. VHL-mutant cells exhibit metabolic abnormalities that can cause chronic endoplasmic reticulum (ER) stress and unfolded protein response. We hypothesize that unresolved ER stress induces the inflammatory responses observed in ccRCC. ER stress markers including BiP and XBP1s were significantly increased in cultured and primary VHL loss-of-function kidney cells. In epithelial cells, the kinase activity of IRE1α was required for the induction of NF-κB and JNK and for the recruitment of macrophages. IRE1α kinase activity was also important for the development of fibrotic phenotype in conditional Vhlh knockout mice. Our results offer insights into the therapeutic potential against ccRCC development by relieving metabolic stress. Such cancer prevention strategy may be critical for high-risk cohorts such as the familial VHL disease patients. Cancer Res; 77(13); 3406–16. ©2017 AACR.
IGF1R Protein Expression Is Not Associated with Differential Benefit to Concurrent Trastuzumab in Early-Stage HER2+ Breast Cancer from the North Central Cancer Treatment Group (Alliance) Adjuvant Trastuzumab Trial N9831
Authors: Reinholz Monica M. , Chen Beiyun , Dueck Amylou C. , Tenner Kathleen , Ballman Karla , Riehle Darren , Jenkins Robert B. , Geiger Xochiquetzal J. , McCullough Ann E. , Perez Edith A.
Published: May 2017

Background: Preclinical evidence indicates that increased insulin-like growth factor receptor-1 (IGF1R) signaling interferes with the action of trastuzumab suggesting a possible mechanism of trastuzumab resistance. Thus, we evaluated IGF1R prevalence, relationship with demographic data, and association with disease-free survival (DFS) of patients randomized to chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C) in the prospective phase III HER2+ adjuvant N9831 trial.

Experimental Design: IGF1R protein expression was determined in tissue microarray sections (three cores per block; N = 1,197) or in whole tissue sections (WS; N = 537) using IHC (rabbit polyclonal antibody against IGF1R β-subunit). A tumor was considered positive (IGF1R+) if any core or WS had ≥1+ membrane staining in >0% invasive cells. Median follow-up was 8.5 years.

Results: Of 1,734 patients, 708 (41%) had IGF1R+ breast tumors. IGF1R+ was associated with younger age (median 48 vs. 51, P = 0.007), estrogen receptor/progesterone receptor positivity (78% vs. 35%, P < 0.001), nodal positivity (89% vs. 83%, P < 0.001), well/intermediate grade (34% vs. 24%, P < 0.001), tumors ≥2 cm (72% vs. 67%, P = 0.02) but not associated with race or tumor histology. IGF1R did not affect DFS within arms. Between Arms A and C, patients with IGF1R+ and IGF1R− tumors had DFS HRs of 0.48 (P ≤ 0.001) and 0.68 (P = 0.009), respectively (Pinteraction = 0.17). Between Arms A and B, patients with IGF1R+ and IGF1R− tumors had DFS HRs of 0.83 (P = 0.25) and 0.69 (P = 0.01), respectively (Pinteraction = 0.42).

Conclusions: In contrast to preclinical studies that suggest a decrease in trastuzumab sensitivity in IGF1R+ tumors, our adjuvant data show benefit of adding trastuzumab for patients with either IGF1R+ and IGF1R− breast tumors. Clin Cancer Res; 23(15); 4203–11. ©2016 AACR.
Converting Lymphoma Cells into Potent Antigen-Presenting Cells for Interferon-Induced Tumor Regression
Authors: Liao Jing , Luan Yan , Ren Zhenhua , Liu Xiaojuan , Xue Diyuan , Xu Hairong , Sun Zhichen , Yang Kaiting , Peng Hua , Fu Yang-Xin
Published: May 2017

Anti-hCD20 is a therapeutic mAb that is clinically used to treat B-cell lymphoma. Some lymphomas are resistant to anti-hCD20; others relapse after treatment with anti-hCD20. Using a syngeneic immunocompetent mouse model, we observed that targeting lymphoma with interferon-α (IFNα) abolished resistance of B-cell lymphoma to anti-CD20 while limiting interferon (IFN)-associated systemic toxicity in the host. Control of tumors by a fusion of anti-CD20 and IFNα (anti–CD20-IFNα) depended on existing tumor-infiltrating CD8+ T cells. Although lymphomas were resistant to IFN-directed killing, IFN-exposed tumor cells became the dominant antigen-presenting cells (APC) for the reactivation of tumor-infiltrating CD8+ T cells that then controlled those lymphomas. Anti–CD20-IFNα also abolished checkpoint blockade resistance in advanced B-cell lymphoma. Our findings indicate that anti–CD20-IFNα eradicates B-cell lymphoma by employing tumor cells as APCs to reactivate tumor-infiltrating CD8+ T cells and synergizing with anti–PD-L1 treatment. Cancer Immunol Res; 5(7); 560–70. ©2017 AACR.
Characterization of an Animal Model to Study Risk Factors and New Therapies for the Cardiorenal Syndrome, a Major Health Issue in Our Aging Population
Authors: Verhulst Anja , Neven Ellen , D'Haese Patrick C.
Published: May 2017

Background: The cardiorenal syndrome (CRS) is a major health problem in our aging population. The term was introduced to cover disorders of the kidneys and heart, whereby dysfunction of one organ may induce dysfunction of the other. As the natural history of the CRS is mostly slow, hence difficult to explore in clinical trials, adequate animal models combining cardiovascular and renal disease are required. Therefore, we developed and characterized a usable model for CRS type 4, i.e. chronic kidney disease (CKD) causing cardiac dysfunction. Methods: CKD was induced in rats by supplementing the diet with adenine. During 8 weeks, several aspects of CRS were studied: CKD, mineral-bone disorder (MBD), cardiovascular disease, and (iron-deficiency) anemia. Hereto, the following parameters were monitored: serum creatinine, calcium, phosphate, FGF23, dynamic bone parameters, aortic Ca deposits, heart weight, serum NT-proANP, Hct, Hb, reticulocytes, spleen iron, and serum hepcidin. Results: Animals developed a severe CKD together with a disturbed mineral balance as reflected by the increased serum creatinine and phosphorus levels and decreased serum calcium levels; and in association herewith aberrations in hormonal levels of FGF-23. In turn, the well-known and highly undesirable complications of CKD, i.e. high turnover bone disease and pathological vessel calcification were induced. Furthermore (iron-deficiency) anemia developed quickly. Conclusion: The animal model described in this article in many aspects mimics the human situation of the CRS type 4 and will be useful to concomitantly evaluate the effects of new treatment strategies on the various aspects of CRS.
Can DMCO Detect Visual Field Loss in Neurological Patients? A Secondary Validation Study
Authors: Olsen Ane Sophie , Steensberg Alvilda Thougaard , la Cour Morten , Kjaer Troels Wesenberg , Damato Bertil , Pinborg Lars Hageman , Kolko Miriam
Published: May 2017

Unrecognized visual field loss is caused by a range of blinding eye conditions as well as serious brain diseases. The commonest cause of asymptomatic visual field loss is glaucoma. No screening tools have been proven cost-effective. Damato Multifixation Campimetry Online (DMCO), an inexpensive online test, has been evaluated as a future cost-beneficial tool to detect glaucoma. To further validate DMCO, this study aimed to test DMCO in a preselected population with neurological visual field loss. Methods: The study design was an evaluation of a diagnostic test. Patients were included if they had undergone surgery for epilepsy during 2011-2014, resulting in visual field loss. They were examined with DMCO and results were compared with those obtained with the Humphrey Field Analyzer (30:2 SITA-Fast). DMCO sensitivity and specificity were estimated with 95% confidence intervals. Results: The cohort comprised 40 patients (25 female and 15 male) with a mean age of 39 years (range 17-60 years). The mean visual acuity was >1.0 and all eyes had an intraocular pressure <21 mm Hg. Sensitivity and specificity of DMCO compared to the reference standard were 72.7 and 96.3%, respectively. Conclusions: DMCO detects moderate-to-severe homonymous quadrantanopia; it can be useful in settings where the current practice is confrontation visual field examination, and where standard conventional perimetry is not available.
Anastomotic Leakage after Upper Gastrointestinal Surgery: Surgical Treatment
Authors: Hummel Richard , Bausch Dirk
Published: May 2017

Background: Anastomotic leakage after upper gastrointestinal surgery is associated with major morbidity and mortality. In recent years, there was a major paradigm shift in the management of leakage after upper gastrointestinal surgery from surgical towards conservative and endoscopic treatment approaches as first-line treatment options. Methods: We conducted a PubMed literature search using combinations of the keywords ‘leakage', ‘complication', ‘esophagectomy', ‘gastrectomy', and ‘pancreatectomy' to identify relevant publications. Results: Surgical re-intervention after esophagectomy, gastrectomy, or pancreatectomy is still indicated in selected patients, depending on the severity of symptoms, the condition of the patient, and failure of initiated treatment. Furthermore, surgical revision after esophagectomy and gastrectomy is indicated for early leakage and depends on the extent of anastomotic disruption and the condition of tissue. Conclusion: Surgical re-intervention still plays a crucial role in the management of leakage after upper gastrointestinal surgery, especially in critically ill patients and after failure of conservative or endoscopic treatment.
Determining an Upper Reference Value for the Urinary Fluoride-Creatinine Ratio in Healthy Children Younger than 7 Years
Authors: Zohoori F. Vida , Maguire A.
Published: May 2017

The urinary fluoride/creatinine ratio (UF/Cr) in a spot urine sample could be a useful systemic F exposure monitoring tool. No reference value for UF/Cr currently exists, therefore this study aimed to establish an upper reference value for a UF/Cr, corresponding to excessive systemic F exposure, i.e., >0.07 mg F/kg body weight (b.w.)/day, in children. Subsidiary aims were to examine the relationship between (i) total daily F intake (TDFI) and 24-h urinary F excretion (DUFE); (ii) DUFE and UF/Cr, and (iii) TDFI and UF/Cr. Simultaneously collected TDFI, DUFE, and urinary creatinine (UCr) data in children <7 years were taken from UK studies conducted from 2002 to 2014 in order to calculate UF/Cr (mg/g) for each child. For the 158 children (mean age 5.8 years) included in the data analysis, mean TDFI and DUFE were 0.049 (SD 0.033) and 0.016 (SD 0.008) mg/kg b.w./day, respectively, and the mean UF/Cr was 1.21 (SD 0.61) mg/g. Significant (p < 0.001) positive linear correlations were found between TDFI and DUFE, DUFE and UF/Cr, and TDFI and UF/Cr. The estimated upper reference value for UF/Cr was 1.69 mg/g; this was significantly (p = 0.019) higher than the UF/Cr (1.29) associated with optimal F exposure (0.05-0.07 mg/kg b.w./day). In conclusion, the strong positive correlation between TDFI and UF/Cr confirms the strong association of these 2 F exposure variables and the value of a spot urine sample for prediction of TDFI (i.e., the most important risk factor in determining fluorosis occurrence and severity) in young children. Establishing an estimation of an upper reference value of 1.69 mg/g for UF/Cr in spot urine samples could simplify and facilitate their use as a valuable tool in large epidemiological studies.
Comparison of Intravitreal Ranibizumab, Aflibercept, and Dexamethasone Implant after Bevacizumab Failure in Macular Edema Secondary to Retinal Vascular Occlusions
Authors: Hanhart Joel , Rozenman Yaacov
Published: May 2017

Purpose: To compare the visual and anatomic outcomes of macular edema secondary to retinal vein occlusion after switching from bevacizumab to ranibizumab, aflibercept, or dexamethasone implant. Methods: Fifteen eyes were switched to ranibizumab, 12 to aflibercept, and 10 to dexamethasone. At 3, 6, 9, and 12 months, the outcome measures were visual acuity (VA) and central macular thickness (CMT). Results: One year after the switch, CMT decreased from 430.11 ± 91.21 to 291.86 ± 43.87 μm (p < 0.001). VA increased in 59.5% of the eyes. No difference between the groups was found in those outcomes at 1 year, but the number of injections varied: 3.30 ± 0.95 for dexamethasone, 6.50 ± 2.11 for aflibercept, and 8.27 ± 2.37 for ranibizumab (p < 0.001). Conclusions: Most of the eyes that failed initial bevacizumab therapy benefit from switching to another modality. The number of required injections during the first year after the switch varies.
Case of Ovarian Cancer in a Woman with Undiagnosed Graves’ Disease: A Case Report and Review of the Literature
Authors: Markman Timothy M. , Markman Maurie , Clark Bennett W.
Published: May 2017

Epithelial ovarian cancer (OC) is a leading cause of death among females in the United States, due in part to challenges of diagnosis in the early stages of the disease. While efforts are underway to develop a high-quality screening test, it is equally important to consider whether high-risk populations are appropriate to screen. One such population may be females with hyperthyroidism, as epidemiologic studies have shown an association between this condition and OC. In this report, we present a case of a female with OC and Graves’ disease to highlight the potential significance of this association.
Heat Shock Protein A12B Protects Vascular Endothelial Cells Against Sepsis-Induced Acute Lung Injury in Mice
Authors: Chen Yi , Wang Lei , Kang Qiuxiang , Zhang Xu , Yu Guifang , Wan Xiaojian , Wang Jiafeng , Zhu Keming
Published: May 2017

Background: Pulmonary endothelial injury is a critical process in the pathogenesis of acute lung injury (ALI) during sepsis. Heat shock protein A12B (HSPA12B) is mainly expressed in endothelial cells and protects against several harmful factors. However, the effects of HSPA12B in sepsis-induced ALI and its potential mechanisms of action remain unclear. Methods: For in vivo experiments, C57BL/6 mice were randomly divided into four groups (n=15): a sham operation group, a cecal ligation and puncture (CLP) group, a HSPA12B siRNA-CLP group and a negative control (NC) siRNA-CLP group. The mice were treated by nasal inhalation of 2-OMe-modified HSPA12B siRNA or NC siRNA. Sepsis was induced by CLP. Samples were harvested 24 and 48 hours post-CLP surgery. Pathological changes and scoring of lung tissue samples were monitored using hematoxylin and eosin staining. Levels of pro-inflammatory cytokines (e.g., interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6) and myeloperoxidase activity in bronchoalveolar lavage fluid were analyzed by ELISA. Pulmonary edema was assessed using a wet-to-dry weight ratio. Neutrophils and alveolar macrophages were counted using flow cytometry. Pulmonary endothelial cell apoptosis was detected by TUNEL staining. Expression levels of MAPK family signaling molecules and caspase-3 were measured by Western blot analysis. In addition, 7-day survival was recorded. For in vitro experiments, human umbilical vein endothelial cells were pre-transfected with HSPA12B siRNA or pIRES2-EGFP-HSPA12B-Flag plasmid and treated with lipopolysaccharide; subsequently, the expression levels of MAPK family signaling molecules and caspase-3 were measured by Western blotting. Results: Nasal inhalation of nano-polymer-encapsulated HSPA12B siRNA specifically downregulated mRNA and protein expression levels of HSPA12B in lung tissues. The administration of HSPA12B siRNA aggravated lung pathological injury, upregulated pro-inflammatory cytokine (e.g., IL-1β, TNF-α, and IL-6) expression, and increased myeloperoxidase activity, neutrophil infiltration, pulmonary edema, and pulmonary endothelial cell apoptosis. Additionally, HSPA12B knockdown worsened survival after CLP surgery. The potential protective mechanisms of HSPA12B may involve the inhibition of ERK phosphorylation and caspase-3 activation in vivo and in vitro. Conclusion: HSPA12B protected against sepsis-induced ALI. The potential mechanism may be partly due to the inhibition of ERK phosphorylation and caspase-3 activation. These findings provide a potential therapeutic target for treating sepsis.
The Role of 5-HTR6 in Mossy Fiber Sprouting: Activating Fyn and p-ERK1/2 in Pilocarpine-Induced Chronic Epileptic Rats
Authors: Lin Wanhui , Huang Wenli , Chen Shenggen , Lin Mingxing , Huang Qingyu , Huang Huapin
Published: May 2017

Objective: Our primary objective is to verify whether 5-HTR6 is involved in the development of mossy fiber sprouting (MFS), and to determine how the progression of MFS is affected by 5-HTR6. Methods: A total of 90 male adult Sprague-Dawley rats were allocated into either the control group (n=36) or the epileptic group (n=54). Status epilepticus (SE) of rats was induced by the intraperitoneal (i.p.) injection of LiCl-pilocarpine. We conducted our experiments in two stages. The first stage involves equally dividing 36 epileptic rats into three groups with treatments of none, 5-HTR6 antagonist SB-27104 (SB) and vehicle DMSO. Then behavior and electroencephalogram (EEG) of rats were monitored by video-EEG. The second stage involves dividing 126 epileptic rats into seven groups with treatments of none, 10% DMSO, SB (100 µg/kg), Fyn antagonist PP2 (50 µg/kg), p-ERK1/2 antagonist PD-98059 (30 µg/kg), SB (100 µg/ kg) + PP2 (50 µg/kg); SB (100 µg/kg) + PD-98059 (30 µg/kg). We also treated 18 rats in the control group of the first stage with 100 µg/kg 5-HTR6 agonist WAY-181187 (WAY). MFS of rats was detected through the approach of Timm’s staining. Finally, expressions of 5-HTR6, Fyn, p-ERK1/2 and GAP-3 were qualified and semi-quantified via western blotting or RT-PCR. Results: Induction of SE could stimulate formation of MFS and increased GAP-43 expressions. Expressions of 5-HTR6, Fyn and p-ERK1/2 were also up-regulated with increasing time after establishment of SE models. The development of MFS was remarkably inhibited by SB, PP2 and PD. Compared to the single antagonist, such an inhibitory effect was enhanced by SB+PD or SB+PP. Moreover, treatment of healthy rats with WAY would contribute to up-regulated Fyn and p-ERK1/2 expressions, as well as development of MFS (P < 0.05). Suppression of Fyn triggered a down-regulating trend of p-ERK1/2 (P < 0.05), however, suppressed p-ERK1/2 did not have such a significant effect on Fyn expression. Conclusion: HTR6 may affect the progression of MFS by activating both p-ERK1/2 and Fyn, which further modulate the expression of GAP-43.
Transient Receptor Potential Vanilloid 5 Mediates Ca2+ Influx and Inhibits Chondrocyte Autophagy in a Rat Osteoarthritis Model
Authors: Wei Yingliang , Wang Yanfang , Wang Yutong , Bai Lunhao
Published: May 2017

Background: Autophagy, a self-protective mechanism of chondrocytes, has become a promising target to impede the progress of osteoarthritis (OA). Autophagy is regulated by cytosolic Ca2+ activity and may thus be modified by the Ca2+ permeable transient receptor potential channel vanilloid 5 (TRPV5). Therefore, we investigated the potential role of TRPV5 in mediating Ca2+ influx and in inhibiting chondrocyte autophagy in a rat OA model. Methods: The rat OA model was assessed by macroscopic and histological analyses. light chain 3B (LC3B) immunolocalization was detected by immunohistochemistry. TRPV5, LC3B and calmodulin in OA articular cartilage were assessed by real time polymerase chain reaction (RT-PCR) and western blotting. TRPV5 small interfering RNA (TRPV5 siRNA) were transfected into rat primary chondrocyte then the calmodulin and LC3B was detected by immunofluorescence. The functionality of the TRPV5 was assessed by Ca2+ influx. Western blot was used to measure autophagy-related proteins. Results: We constructed a monosodium iodoacetate (MIA) -induced rat OA model and found that ruthenium red (TRPV5 inhibitor) slowed the progression of joint destruction. We found that the TRPV5 and calmodulin were up-regulated but LC3B was down-regulated in articular cartilage following prolonged progression of OA. Furthermore, the up-regulated TRPV5 channel caused an increase in the Ca2+ influx in chondrocytes. The up-regulation of TRPV5 stimulated Ca2+ influx, which inhibited autophagy by increasing the production of calmodulin, phosphorylation of calmodulin dependent protein kinases II (p-CAMK II), phosphorylation of Beclin1 (p-Beclin1), and protein of B-cell lymphoma-2 (Bcl-2), and attenuating ratio of LC3-II/ LC3-. Conclusion: Up-regulated TRPV5 as an initiating factor inhibited chondrocyte autophagy via the mediation of Ca2+ influx.
MicroRNA-181a-5p Impedes IL-17-Induced Nonsmall Cell Lung Cancer Proliferation and Migration through Targeting VCAM-1
Authors: Cao Yang , Zhao Dan , Li Ping , Wang Lanrong , Qiao Bingli , Qin Xiaoyan , Li Lei , Wang Yang
Published: May 2017

Aim: The contribution of the inflammatory mediator interleukin-17 (IL-17) in nonsmall cell lung cancer (NSCLC) malignancy has been reported in the literature. MicroRNA-181a-5p (miR-181a-5p) acts as a tumor suppressor which can regulate target gene at the posttranscriptional level. Our study aimed to investigate the interaction between IL-17 and miR-181a-5p in NSCLC. Methods: 35 patients with NSCLC and 24 COPD controls were selected and examined in our study. In vitro, H226 and H460 cell lines were exposed to different doses (20, 40, 60, and 80 ng/mL) of IL-17 to examine the effect of IL-17 on miR-181a-5p and vascular cell adhesion molecule 1 (VCAM-1) expression. MiR-181 mimic and miR-181a-5p inhibitor were transfected to explore the regulation of VCAM-1 as well as tumor cell proliferation and migration. Results: miR-181a-5p expression was downregulated, and IL-17 and VCAM-1 expression was upregulated in NSCLC tissues. Furthermore, IL-17 decreased miR-181a-5p expression but increased VCAM-1 expression in H226 and H460 cells. MiR-181 regulated VCAM-1 expression through binding to 3’-UTR sequence. MiR-181 attenuated tumor cell proliferation and migration. IL-17 modulated miR-181a-5p expression through activating NF-κB but not Stat3. Conclusion: Taken together, our data show the regulation of VCAM-1 expression by miR-181a-5p under IL-17 exposure, predicting a potential way for counteracting cancer metastasis.
A ressonância magnética no diagnóstico e estadiamento dos gliomas cerebrais: a aplicação da técnica da espectroscopia de prótons
Authors: Brisson Rodrigo Tavares , Santos Alair Augusto Sarmet M. D. dos
Published: May 2017

Objetiva-se, com este trabalho, realizar uma revisão de literatura de estudos primários que abordaram a aplicação da espectroscopia de prótons por ressonância magnética (1H-MRS) como método diagnóstico e de estadiamento nos gliomas cerebrais. Todos os artigos analisados, através do PubMed mostraram significância estatística na correlação entre 1H-MRS com a histopatologia da lesão. Dos 26 estudos analisados, 9 mostraram diferenças entre gliomas de outras lesões do Sistema Nervoso Central (SNC) e 23 avaliaram a diferença entre gliomas de baixo grau e gliomas de alto grau. Procurou-se mostrar que as linhas de pesquisa que usaram 1H-RMS apresentaram resultados mais refinados quanto ao diagnóstico destes tumores. Destes estudos, conclui-se que a 1H-MRS associada à MRI é um método diagnóstico com boa acurácia quando comparado com a análise histopatológica. Os metabólitos detectados pela espectroscopia se correlacionam bem com a gradação dos gliomas e fornecem fortes evidências de que este método possa ser mais utilizado para avaliação e seguimento de pacientes no pré e no pós-operatório.