bluuebunny/crossref_metadata_2025 huggingface dataset:
Awareness and Vaccine Coverage of Hepatitis B among Cameroonian Medical Students
Authors: Aroke Desmond , Kadia Benjamin Momo , Anutebeh Ephesians Nkwetta , Belanquale Cluade Asaba , Misori Glory Masango , Awa Alfred , Mbanga Clarence M. , Ngek Larry Tangie
Published: September 2018

Background. The endemic nature of the hepatitis B virus (HBV) in Sub-Saharan Africa is a significant public health problem that places health care providers (medical students inclusive) at increased risk of occupational exposure. However vaccination against HBV is not systematic among medical students in Cameroon. Thus, we sought to evaluate awareness and HBV vaccine coverage among medical students in Cameroon. Methods. Using semistructured questionnaire and a cross-sectional approach, medical students from 3 State Universities in Cameroon were evaluated for their knowledge, attitudes, and vaccination status against the HBV. Data were collected over a 3-month period. HBV vaccine status was defined as complete (3 doses), partial (1 and 2 doses), and unvaccinated. Data were entered and analyzed using Epi-info 7. Results. There were 714 respondents among whom 186 (26.05%) had been vaccinated at least once against HBV. Sixty-six (9.24%) were partially vaccinated and 120 (16.81%) completely vaccinated. No student had done postvaccination serologic testing to confirm full immunisation. Eighty-three percent (83.00%) of respondents had adequate knowledge on HBV infection and vaccine, while 90.00% had adequate knowledge on HBV transmission. Most medical students had a positive attitude towards the HBV vaccine. The most common negative attitudes were worries about the side effects and fears of being infected by the vaccine. Conclusion. Despite adequate knowledge on HBV infection and vaccination only about 1 in 6 medical students had completed the HBV vaccination series. This highlights the need for better health policies aimed at increasing access and coverage of the HBV in at-risk populations like medical students.
Antimicrobial Activity ofPiper marginatumJacq andIlex guayusaLoes on Microorganisms Associated with Periodontal Disease
Authors: Gamboa Fredy , Muñoz Camila-Cristina , Numpaque Gloria , Sequeda-Castañeda Luis Gonzalo , Gutierrez Sandra Janeth , Tellez Nohemi
Published: September 2018

Background. Chronic periodontitis is a multifactorial infectious disease, where multiple bacteria, such asPorphyromonas gingivalis,Prevotella intermedia, andFusobacterium nucleatumare implicated. The main purpose of researching natural products is to find substances or compounds with antimicrobial activity.Aim. The objective of this work was to determine antimicrobial activity from extracts and obtained fractions fromPiper marginatumJacq andIlex guayusaLoes onP. gingivalisATCC 33277,F. nucleatumATCC 25586, andP. intermediaATCC 25611.Methods. Total ethanol extracts were obtained from both plants. Fractions were obtained from total ethanol extracts with amberlite as a stationary phase employing hexane, acetone, and ethanol-water as solvents. Qualitative and quantitative phytochemical characterization was performed on total ethanol extracts from both plants. Antimicrobial activity from total ethanol extracts and fractions from both plants were evaluated onP. gingivalisATCC 33277,F. nucleatumATCC 25586, andP. intermediaATCC by the well diffusion method with Wilkins–Chalgren agar.Results.Piper marginatumJacq total ethanol extract presented antimicrobial activity against all three bacteria, whereasIlex guayusaLoes was only efficient againstP. gingivalisATCC 33277 andP. intermediaATCC 25611, with inhibition halos from 9.3 to 30 mm.Ilex guayusaLoes obtained fractions presented antimicrobial activity against all three microorganisms evaluated, with inhibition halos ranging from 9.7 to 18.7 mm. In regards toPiper marginatumJacq fractions, inhibition halos were between 8.3 and 19 mm, against all three microorganisms evaluated; only hexane fraction did not present antimicrobial activity againstF. nucleatumATCC 25586.Conclusion.Piper marginatumJacq andIlex guayusaLoes total ethanol extracts and fractions presented outstanding antimicrobial activity againstP. gingivalisATCC 33277,P. intermediaATCC 25611, andF. nucleatumATCC 25586.
Induction of Labour in Advanced Abdominal Pregnancy with Fetal Demise due to Cord Round Neck: A Case Report of a Missed Diagnosis
Authors: Mforteh Ascensius Achuo , Tchakounte Collince , Sama Carlson-Babila , Eteme-Messi Stephane , Djiognouo Willy , Dohbit Sama , Foumane Pascal
Published: September 2018

Background. There are increasing reports of term live abdominal pregnancies even though the diagnosis of abdominal pregnancy is made preoperatively only in 45% of cases which partly explains the high maternal and perinatal morbidity and mortality associated with abdominal pregnancy. Case Report. We report a rare case of misdiagnosed term abdominal pregnancy complicated by fetal demise due to cord round neck in a 29-year-old G3P2002 at 39-week and 1-day gestation. She noticed reduced fetal movements for which upon examination fetal death was diagnosed. Cervical ripening was started which eventually failed, and surgery was indicated. Findings were an abdominal pregnancy with a third-degree macerated fetus with cord round neck. She was discharged on day 8 postoperation to continue follow-up as an outpatient with regular βHCG and ultrasound checks. Conclusion. This case illustrates the need to effectively confirm an intrauterine location of a pregnancy even in a case of fetal demise and the need to monitor for cord abnormalities in advanced abdominal pregnancy being managed expectantly.
Vibration Characteristics of Heavy‐Duty CNC Machine Tool‐Foundation Systems
Authors: Tian Yang , Shu Qilin , Liu Zhifeng , Ji Yujie
Published: September 2018

Vibration characteristics of heavy CNC machine tools are directly affected by their foundations. To analyze vibrations of heavy CNC machine tools caused by internal and external loads, a system dynamics model of a rigid‐flexible coupled heavy‐duty CNC machine tool‐foundation system was established based on the multibody transfer matrix method. Since joint surfaces can seriously affect the accuracy of system mechanics models, the substructure synthesis method was first used to establish a dynamic model of the joint surface. The frequency response function was then used to identify model parameters. Moreover, to improve the accuracy of parameter identification of the joint surface, a residual frequency compensation function was used to reconstruct the frequency response function. Finally, the multibody system model was implemented by combining surface elements. To verify the system dynamics model, an experimental model of the heavy‐duty machine‐foundation system was built, taking into consideration joint surface factors, and the theoretical model was validated by comparing theoretical, simulation, and experimental results. Using the theoretical model, the influence of different forms of concrete foundations, materials, and soil properties on the vibration characteristics of heavy‐duty CNC machine tools was analyzed, thus providing a theoretical basis for optimizing and improving CNC machine tools.
Efficient Synthesis of Glutamate Peptide-Estradiol Conjugate for Imaging Estrogen Receptor-Positive Diseases
Authors: Shih Ming-Chi , Simon Sergio Daniel , Jin Zhiming , Gui Yuan , Xu Bohua , Xu Zhihong , Rosado-de-Castro Paulo Henrique , Silveira Braghirolli Ana Maria , Barbosa da Fonseca Lea Mirian , Inoue Tomio , Yang David J.
Published: September 2018

Molecular imaging of estrogen receptor-positive (ER+) pathway-activated system serves the basis of ER+ disease management such as cancers and endometriosis. ER+ patients have better response to endocrine therapy and survive twice as long as negative ER patients. However, tumor resistance resulting from clinical used aromatase inhibitors and antiestrogens is unpredictable. Radiolabeled ER+ ligand could quantify ER+ tissue uptake which helps to stage and restage of the cancer as well as endometriosis. The differential diagnosis of ER+ lesions by using a labeled ligand helps to select the patients for optimal response to endocrine therapy and to discontinue the treatment when resistance occurs. In addition, radiolabeled ER+ ligand serves as basis for image-guided response follow-up. Glutamate receptors are cell surface receptors which are overexpressed in inflammation and infection. Using glutamate peptide as a drug carrier helps to target intracellular genes via glutamate receptor-mediated process. Reports have shown that polyglutamate is a drug carrier that could alter drug solubility and enhance estrogen receptor-ligand binding pocket. However, polyglutamate was a blend of mixed polymer with a wide range of molecular weight. Thus, the structural confirmation and purity of the conjugates were not optimized. To overcome this problem, the efficient synthesis of glutamate peptide-estradiol (GAP-EDL) conjugate was achieved with high purity. EDL was conjugated site-specific at the first glutamate of GAP. The average cell uptake of 68Ga-GAP-EDL was 5-fold higher than the previous reported synthesis. The efficient synthesis of GAP-EDL has greatly enhanced sensitivity and specificity in cell uptake studies. In vivo PET imaging studies indicated that 68Ga-GAP-EDL could image ER (+) tumors in MCF-7 tumor-bearing mice. Therefore, GAP-EDL makes it possible to image ER-enriched endometriosis and cancer.
Speech Understanding and Sound Localization with a New Nonimplantable Wearing Option for Baha
Authors: Gawliczek Tom , Wimmer Wilhelm , Munzinger Fabio , Caversaccio Marco , Kompis Martin
Published: September 2018

Objective. To measure the audiological benefit of the Baha SoundArc, a recently introduced nonimplantable wearing option for bone conduction sound processor, and to compare it with the known softband wearing option in subjects with normal cochlear function and a purely conductive bilateral hearing loss.Methods. Both ears of 15 normal hearing subjects were occluded for the time of the measurement, yielding an average unaided threshold of 49 dB HL (0.5 – 4 kHz). Soundfield thresholds, speech understanding in quiet and in noise, and sound localization were measured in unaided conditions and with 1 or 2 Baha 5 sound processors mounted on either a softband or a SoundArc device.Results. Soundfield thresholds and speech reception thresholds were improved by 19.5 to 24.8 dB (p<.001), when compared to the unaided condition. Speech reception thresholds in noise were improved by 3.7 to 4.7 dB (p<.001). Using 2 sound processors rather than one improved speech understanding in noise for speech from the direction of the2nddevice and sound localization error by 23° to 28°. No statistically significant difference was found between the SoundArc and the softband wearing options in any of the tests.Conclusions. Bone conduction sound processor mounted on a SoundArc or on a softband resulted in considerable improvements in hearing and speech understanding in subjects with a simulated, purely conductive, and bilateral hearing loss. No significant difference between the 2 wearing options was found. Using 2 sound processors improves sound localization and speech understanding in noise in certain spatial settings.
Durability and Biological Response of a New Posterior Dynamic Stabilization System Using Polyethylene with Vitamin E
Authors: Matsumoto Koji , Tokuhashi Yasuaki
Published: September 2018

Objective. The purpose of this study was to evaluate the durability and biological response of a new Posterior Dynamic Stabilization system using polyethylene with vitamin E on the sliding surface. Summary of Background Data. The use of polyethylene with vitamin E on the sliding surface in Posterior Dynamic Stabilization has not been reported previously. Methods. A developed pedicle screw-based Posterior Dynamic system consists of four parts: a set screw, a rod, a ball, and a pedicle screw. The rod is inserted into the through hole of the ball, and the ball is sandwiched by the set screw. (1) Fatigue Wear Test. Testing was conducted under a dynamic compressive load of 50N at a speed of 1 Hz for 1 million cycles. We examined the loss of polyethylene due to abrasion in 3 units. (2) Biological Response in Pigs. In two pigs, a new pedicle screw and a conventional pedicle screw were inserted in L2 and L3/4, and L4 and L2/3, respectively. After breeding for 6 months, autopsies were performed. CT imaging was used to evaluate bone union of the facet joint. Abrasive specimens were prepared, and abrasion powder and inflammatory cell infiltration were evaluated microscopically. Results. The average loss of polyethylene due to abrasion was -0.01 mg. In all units, polyethylene showed a decrease of 0.1 mm or less at the contact point with the set screw. The facet joints between the conventional screws exhibited bone fusion, but the facet joint between the conventional and the new screw retained mobility with no bony fusion. No abrasion powder was found and inflammatory cell infiltration was only minimally observed. Conclusion. The new Posterior Dynamic Stabilization system exhibited a high level of durability and biological safety.
Prevalence of Adjustment Problem and Its Predictors among First-Year Undergraduate Students in Ethiopian University: A Cross-Sectional Institution Based Study
Authors: Belay Ababu Getu , Belete Yigzaw Asmare , Dinku Besene Yihunbelay , Getinet Alemu Wondale
Published: September 2018

Background. Being in a university for the first time is an unpleasant event and time of heavy pressure relating to social things and dissatisfaction for several new faculty students. Adjustment difficulties are the foremost common issues among freshman students; World Health Organization area unit researched a full-of-life adjustment innovation in universities. Despite this reality, there is a few literature that identifies prevalence and factors related to the adjustment downside among university/college students. Methods. Institutional based quantitative cross-sectional study style was conducted from May to June 2016. A total of 537 haphazardly elite students concerned within the study. The result adjustment downside was explained with Student Adjustment to College Questionnaire (SACQ). Data was described using descriptive analysis; logistic regression was used to assess the relation between adjustment downside and associated factors. An odds quantitative relation 95% confidence interval was used to point out the strength of association. Applied mathematics significance was declared as a p value less than 0.05. Result. A total of 537 respondents participate with a response rate of eighty-five percent. the prevalence of adjustment downside among the respondents was 228 ( 42.5%). Of the respondents, 327 (60.9%) were male and therefore the mean (sd) age was 19 (+- 1) years. Being away from home and homesickness (AOR=4.15,95% CI: 2.46,2,99 and AOR=5. 9,95% CI: 2.35,14.76) and difficulties in socializing or making friends (AOR=3.99,95% CI:2.29,6.98) and difficulties in managing time and study skill (AOR=3.02,95% CI: 1.3,7.02) were abundant associated factors with adjustment downside. Conclusion. The study confirms that freshman students joining university do face problems in adjusting themselves at the university. Homesickness, difficulties in socializing or making friends, and difficulties in managing time and study skill were found to be significant factors in adjustment downside.
Multiplex Real-Time Polymerase Chain Reaction for Simultaneous Quantification ofSalmonellaspp.,Escherichia coli, andStaphylococcus aureusin Different Food Matrices: Advantages and Disadvantages
Authors: Lopes Amanda Teixeira Sampaio , Albuquerque George Rêgo , Maciel Bianca Mendes
Published: September 2018

Quantitative real-time polymerase chain reactions (qPCRs) of the most prevalent bacteria causing foodborne diseases worldwide, such asSalmonellaspp.,Escherichia coli, andStaphylococcus aureus,can be an important tool for quantitative microbial risk assessment, which requires numerical data to determine the level of contamination at a specific stage of food production. However, most of qPCR assays described in the literature for these pathogens are qualitative; their objective is pathogen detection and not pathogen quantification. Thus, the aim of our work was to develop a qPCR for the simultaneous quantification ofSalmonellaspp.,E. coli, andS. aureusand to propose its use in the analysis of foods, as a tool for microbiological quality monitoring. For this, a multiplex qPCR was standardized for the simultaneous quantification of specific fragments of target genes (ssf,phoA, andnuc) corresponding to each one of the mentioned bacteria. The limit of detection of the technique was 13, 10, and 12 gene copies forssf,phoA, andnuc, respectively; standard curves showed R2> 0.99, with efficiencies ranging from 99 to 110%, and inter- and intraexperiment reproducibility presented a low coefficient of variation in all trials. This methodology was applied in different food matrices (milk, ground beef, and oyster meat), and the results were compared with official microbiological culture methodology and with ready-to-use test. Advantages and disadvantages of each methodology used in this study are pointed out. We suggest that this multiplex qPCR can be used as a rapid screening technique for the analysis of food microbiological quality.
Spectral Variation and Corresponding Changing Mechanism of Suspended Particulate Material Absorption in Poyang Lake during Flood Periods
Authors: Wang Yuandong , You Xibin , Yu Lianfang , Meng Lihong , Xu Xiangming , Liu Guangxu
Published: September 2018

Remote sensing accuracy of the dynamic water environment under a changing environment due to climate and anthropogenic impacts should be improved by a deep understanding of the absorption properties pertinent to the water body. Spectral variation of suspended particulate material (SPM) absorption and its changing mechanism during flood periods of Poyang Lake were analyzed in this study. Absorption coefficients were measured and determined by spectrophotometry using the quantitative filter techniques (QFTs) based on field samples from July 12 to September 06, 2017. Two main optical active constituents (OACs) of SPM including nonalgal and phytoplankton algal particulates were quantified and analyzed in detail. The results suggested that, during study periods, Poyang Lake exhibits an overall high level of suspended nonalgal detritus and algal concentration and lower water clarity, showing a strong absorption by total suspended sediments that are closely related with the land‐derived nonalgal detritus material which varied significantly with diverse proportions of minerals and organic materials from multiple sources. Due to variations in phytoplankton community pigment composition, concentration, and package effect, there exists a difference between optical absorption capacity on blue (440) and red (675) portions of bands, the former of which had an obvious enhancement due to the increased effect of accessory pigments in suspended phytoplankton particles from July to September. Evidence also presented that the nonlinear dependency of specific phytoplankton particulate absorption on pigment concentration for various trophic statuses in different periods could be unstable due to relative contributions of the package effect and accessory pigments; this could bring uncertainties to the parameterization of optical models and remote sensing algorithms proposed for accurate applications in lake water environment monitoring.
Importance of Mechanical Periodontal Therapy in Patients with Diabetes Type 2 and Periodontitis
Authors: Naiff Priscilla , Carneiro Valéria , Guimarães Maria do Carmo
Published: September 2018

Periodontitis is an infectious and inflammatory disease of high prevalence worldwide and constitutes a significant oral health problem. It can lead to tooth loss. In addition, the local inflammatory process can cause the release of inflammatory mediators in the bloodstream and, consequently, contribute to the emergence of systemic effects as cardiovascular and diabetic complications. The purpose of this mini review is to alert health professionals about the risk that periodontitis represents for the onset or exacerbation of complications in individuals with type 2 diabetes mellitus and to emphasize that the mechanical treatment of periodontal disease and reestablishment of oral health are essential for the metabolic control of these patients. The periodontal therapy may help to reduce the risk of systemic complications in diabetes patients. Proper dental management should be suggested by health professionals, mainly from physicians to their patients, in order to improve the health conditions in these individuals.
Studies on the Interaction between Three Small Flavonoid Molecules and Bovine Lactoferrin
Authors: Huang Junyi , Liu Zhenmin , Ma Qiaorong , He Ziyu , Niu Zhidian , Zhang Mengying , Pan Liu , Qu Xiaosheng , Yu Jun , Niu Bing
Published: September 2018

The interaction between three flavonoids, i.e., Luteolin (LTL), Quercetin (QCT), and Naringenin (NGN) and bovine lactoferrin (BLF) at pH 7.4 was investigated by fluorescence quenching spectra, synchronous fluorescence spectra, and UV-visible absorption spectra. The results indicate the fluorescence of BLF quenched by Luteolin (LTL), Quercetin (QCT), and Naringenin (NGN) via static quenching. The main force between QCT and LTL with BLF was van der Waals interactions and hydrogen bonds. Electrostatic interactions played a major role in the binding process of interaction between NGN and BLF. Synchronous fluorescence was used to study the conformational changes of BLF. The values of binding constant (Ka) and number of binding sites (n) at different temperatures (300K, 305K, 310K) were also calculated, respectively. The results of corresponding thermodynamic parameters as well as binding distance between BLF and LTL, QCT, or GNG were obtained. These results implied that Luteolin (LTL), Quercetin (QCT), and Naringenin (NGN) could provide important guides for compound quantity (e.g., medicine dosage) and the design of new compounds (or drugs).
Two Cases of Dedifferentiated Endometrioid Carcinoma: Case Presentation and Brief Review of the Literature
Authors: Morioka Sachiko , Tanase Yasuhito , Kawaguchi Ryuji , Uchiyama Tomoko , Kobayash Hiroshi
Published: September 2018

Endometrioid carcinoma is the most common histological type of uterine endometrial cancer and particularly dedifferentiated endometrioid carcinomas (DEC) are less commonly observed. Silva et al. reported the biological features of UC based on the undifferentiated component of DEC, although the component represented only 20% of undifferentiated carcinoma. In this study, we report two cases of DEC with different presentation. Case 2 presented with the invasion to the bladder, rectum, and LN metastases. In contrast, the tumor in case 1 advanced into the endometrial cavity, similar to an endometrial polyp, without myometrial invasion. Hence, the diagnosis was established early. While we strive to improve the diagnosis of DEC, it is also crucial to better assess the prognosis and the appropriate treatment for the patients with established diagnosis of DEC.
23 Full Factorial Model for Particle Size Optimization of Methotrexate Loaded Chitosan Nanocarriers: A Design of Experiments (DoE) Approach
Authors: Teja S. P. Surya , Damodharan N.
Published: September 2018

Purpose. To build and inquire a statistically significant mathematical model for manufacturing methotrexate loaded chitosan nanoparticles (CsNP) of desired particle size. The study was also performed to evaluate the effect of formulation variables in the explored design space. Method. Ionotropic gelation technique was followed for chitosan nanocarriers by changing formulation variables suggested as per Design Expert software. Altering the levels of Chitosan, tripolyphosphate, methotrexate by 23 factorial design served the purpose. The CsNP were characterized for nanocarrier formation, particle size, and statistical analysis. Then mathematical model was statistically analyzed for fabricating desired formulation having particle size less than 200nm. Results. FT-IR, XRD reports confirmed the structural change in chitosan which lead to the formation of CsNP. For particle size, linear model was found to be best fit to explain effect of variables. Besides, high R2 (0.9958) defends the constancy of constructed model. Chitosan exhibited higher t-value in Pareto chart and a p-value <0.0001. Based on maximum desirability, optimization was performed and amount of variables for preparing CsNP of 180nm was predicted. The experiment was carried out with software suggested combination and particle size was found to be 176±4nm. Conclusion. Low p-value endorsed the greater dominance of chitosan on particle size. Good model adequacy and small percentage error between predicted and experimented value established the reliability of constructed model for robust preparation of CsNP.
Sertoli-Leydig Cell Tumour and DICER1 Mutation: A Case Report and Review of the Literature
Authors: Wormald B. , Elorbany S. , Hanson H. , Williams J. W. , Heenan S. , Barton D. P. J.
Published: September 2018

Sertoli-Leydig cell tumours of the ovary (SLCT) are rare tumours predominantly caused by mutations in the DICER1 gene. We present a patient with a unilateral SLCT who had an underlying germline DICER1 gene mutation. We discuss the underlying pathology, risks, and screening opportunities available to those with a mutation in this gene as SLCT is only one of a multitude of other tumours encompassing DICER1 syndrome. The condition is inherited in an autosomal dominant fashion. As such, genetic counselling is a key component of the management of women with SLCT.
Late-Life Presentation of Unsuspected G6PD Deficiency
Authors: Benchimol Marcos , Madeira Laura Bernardo , de Oliveira-Souza Ricardo
Published: September 2018

Deficiency of glucose-6-phosphate dehydrogenase (G6PD) is the commonest enzyme deficiency in humans with a wide range of possible clinical manifestations depending on the specific genetic variant in each case. Here we present the case of an 86-year-old male of African descent who acutely developed symptoms of G6PD deficiency immediately after he received methylene blue for treating methemoglobinemia. The contrast between a low SO2 on pulse oximetry and a normal arterial gas sampling raised the possibility of methemoglobinemia. The patient was treated with packed red blood cells and folic acid, and a rapid clinical improvement followed by normalization of the red blood cell count ensued. In view of the patient’s advanced age, the lack of a history of similar episodes in the past, and the normal laboratory results during the hemolytic crisis, this case remained a diagnostic challenge for over three months, when a follow-up measure of G6DP activity eventually confirmed the diagnosis. A latent deficiency of G6PD may become clinically manifest under the appropriate triggering conditions even in elderly patients and in the absence of past or current clinical and laboratory evidence of G6PD deficiency.
Severe Symptomatic Hypocalcemia from HIV Related Hypoparathyroidism
Authors: Sandhu Sartaj , Desai Akshata , Batra Manav , Girdhar Robin , Chatterjee Kaushik , Kemp E. Helen , Makdissi Antoine , Chaudhuri Ajay
Published: September 2018

We report the case of a 54-year-old Caucasian female who presented with a two-year history of persistent hypocalcemia requiring multiple hospitalizations. Her medical history was significant for HIV diagnosed four years ago. She denied any history of prior neck surgery or radiation. Her vital signs were stable with an unremarkable physical exam. Pertinent medications included calcium carbonate, vitamin D3, calcitriol, efavirenz, emtricitabine, tenofovir disoproxil, hydrochlorothiazide, and inhaled budesonide/formoterol. Laboratory testing showed total calcium of 5.7 mg/dL (normal range: 8.4-10.2 mg/dL), ionized calcium of 2.7 mg/dL (normal range: 4.5-5.5 mg/dL), serum phosphate of 6.3 mg/dL (normal range: 2.7-4.5 mg/dL), and intact PTH of 7.6 pg/mL (normal range: 15-65 pg/mL). She was diagnosed with primary hypoparathyroidism. Anti-calcium-sensing receptor antibodies and NALP5 antibodies were tested and found to be negative. During subsequent clinic visits, doses of calcium supplements and calcitriol were titrated. Last corrected serum calcium level was 9.18 mg/dL. She was subsequently lost to follow-up. This case gives insight into severe symptomatic hypocalcemia from primary hypoparathyroidism attributed to HIV infection. We suggest that calcium levels should be closely monitored in patients with HIV infection.
Fatal Septic Shock in a Patient with Hemophagocytic Lymphohistiocytosis Associated with an Infectious Mononucleosis
Authors: Berlot Giorgio , Tomasini Ariella , Zandonà Lorenzo , Leonardo Eugenio , Bussani Rossana , Zarrillo Nadia
Published: September 2018

The authors describe the case of a young woman who developed a clinical pictures resembling a septic shock-related multiple organ dysfunction syndrome a couple of months after having been diagnosed suffering from a hemophagocytic lymphohistiocytosis associated with an infectious mononucleosis. Despite the aggressive treatment, which included antibiotics, vasopressors, IV immunoglobulins, and the use of an extracorporeal device aimed to remove mediators released both during sepsis and the cytokine storm determined by the hemophagocytic lymphohistiocytosis, the patient died. At the autopsy, an extremely uncommon aggressive lymphoma of Epstein-Barr virus-positive T-lymphocytes with systemic involvement was discovered.
Prognostic Value of SYNTAX Score II in Patients with Acute Coronary Syndromes Referred for Invasive Management: A Subanalysis from the SPUM and COMFORTABLE AMI Cohorts
Authors: Obeid Slayman , Frangieh Antonio H. , Räber Lorenz , Yousif Nooraldaem , Gilhofer Thomas , Yamaji Kyohei , Jaguszewski Milosz , Aghlmandi Soheila , Adams James , Bockhorn Yannik , Templin Christian , Stähli Barbara E. , Jüni Peter , Rodondi Nicolas , Mach François , Roffi Marco , Windecker Stephan , Maier Willibald , Nietlispach Fabian , Matter Christian M. , Klingenberg Roland , Lüscher Thomas F.
Published: September 2018

Aims. To assess the incremental prognostic value of SYNTAX score II (SxSII) as compared to anatomical SYNTAX Score (SxS) and GRACE risk score in patients with acute coronary syndromes who underwent percutaneous coronary intervention. Methods and results. SxSII and SxS were determined in 734 ACS patients. Patients were enrolled in the prospective Special Program University Medicine ACS and the COMFORTABLE AMI cohorts and later on stratified according to tertiles of SxSII (SxSIILow ≤21.5 (n=245), SxSIIMid 21.5–30.6 (n=245), and SxSIIHigh ≥30.6 (n=244). The primary endpoint of adjudicated all-cause mortality and secondary endpoints of MACE (cardiac death, repeat revascularization, and myocardial infarction) and MACCE (all-cause mortality, cerebrovascular events, MI, and repeat revascularization) were determined at 1-year follow-up. SxSII provided incremental predictive information for risk stratification when compared to SxS and GRACE risk score (AUC 0.804, 95% CI 0.77–0.84, p<0.001 versus 0.67, 95% CI 0.63–0.72, p=0.007 versus 0.69, 95% CI 0.6–0.8, p=0.002), respectively. In a multivariable Cox regression analysis, we found that unlike SxS (adjusted HR 1.013, 95% CI (0.96–1.07), p=0.654), SxSII was significantly associated with all-cause mortality (HR = 1.095, 95% CI (1.06–1.11), p<0.001). This was also true for the prediction of both secondary outcomes MACE (n=60) and MACCE (n=70) with an adjusted HR = 1.055, 95% CI (1.03–1.08), p<0.001, and HR = 1.065, 95% CI (1.04–1.09), p<0.001. Conclusion. In patients with ACS who underwent PCI, SxSII is an independent predictor of mortality during 1-year follow-up. SxSII shows superiority in discriminating risk compared to conventional SxS and GRACE for all-cause mortality.
Genomic Characterization of Six Virus-Associated Cancers Identifies Changes in the Tumor Immune Microenvironment and Altered Genetic Programs
Authors: Varn Frederick S. , Schaafsma Evelien , Wang Yue , Cheng Chao
Published: September 2018

Viruses affect approximately 20% of all human cancers and induce expression of immunogenic viral oncoproteins that make these tumors potent targets for immune checkpoint inhibitors. In this study, we apply computational tools to The Cancer Genome Atlas (TCGA) and other genomic datasets to define how virus infection shapes the tumor immune microenvironment and genetic architecture of 6 virus-associated tumor types. Across cancers, the cellular composition of the microenvironment varied by viral status, with virus-positive tumors often exhibiting increased infiltration of cytolytic cell types compared with their virus-negative counterparts. Analyses of the infiltrating T-cell receptor repertoire in these patients revealed that Epstein–Barr virus infection was associated with decreased receptor diversity in multiple cancers, suggesting an antigen-driven clonal T-cell response. Tissue-specific gene-expression signatures capturing virus-associated transcriptomic changes successfully predicted virus status in independent datasets and were associated with both immune- and proliferation-related features that were predictive of patient prognosis. Together, the analyses presented suggest viruses have distinct effects in different tumors, with implications for immunotherapy.

Significance: This study utilizes TCGA and other genomic datasets to further our understanding of how viruses affect the tumor immune response in different cancer types.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/22/6413/F1.large.jpg. Cancer Res; 78(22); 6413–23. ©2018 AACR.
Semaphorin 7A Promotes Macrophage-Mediated Lymphatic Remodeling during Postpartum Mammary Gland Involution and in Breast Cancer
Authors: Elder Alan M. , Tamburini Beth A.J. , Crump Lyndsey S. , Black Sarah A. , Wessells Veronica M. , Schedin Pepper J. , Borges Virginia F. , Lyons Traci R.
Published: September 2018

Postpartum mammary gland involution is a tissue remodeling event that occurs in all mammals in the absence of nursing or after weaning to return the gland to the pre-pregnant state. The tissue microenvironment created by involution has proven to be tumor promotional. Here we report that the GPI-linked protein semaphorin 7A (SEMA7A) is expressed on mammary epithelial cells during involution and use preclinical models to demonstrate that tumors induced during involution express high levels of SEMA7A. Overexpression of SEMA7A promoted the presence of myeloid-derived podoplanin (PDPN)-expressing cells in the tumor microenvironment and during involution. SEMA7A drove the expression of PDPN in macrophages, which led to integrin- and PDPN-dependent motility and adherence to lymphatic endothelial cells to promote lymphangiogenesis. In support of this mechanism, mammary tissue from SEMA7A-knockout mice exhibited decreased myeloid-derived PDPN-expressing cells, PDPN-expressing endothelial cells, and lymphatic vessel density. Furthermore, coexpression of SEMA7A, PDPN, and macrophage marker CD68 predicted for decreased distant metastasis-free survival in a cohort of over 600 cases of breast cancer as well as in ovarian, lung, and gastric cancers. Together, our results indicate that SEMA7A may orchestrate macrophage-mediated lymphatic vessel remodeling, which in turn drives metastasis in breast cancer.

Signficance: SEMA7A, which is expressed on mammary cells during glandular involution, alters macrophage biology and lymphangiogenesis to drive breast cancer metastasis. Cancer Res; 78(22); 6473–85. ©2018 AACR.
Cyclin F-Dependent Degradation of RBPJ Inhibits IDH1R132H-Mediated Tumorigenesis
Authors: Deshmukh Ruhi S. , Sharma Shalakha , Das Sanjeev
Published: September 2018

Cyclin F is a substrate recognition subunit of Skp1-Cul1-F-box protein (SCF) E3 ubiquitin ligase complex. Although there have been reports describing the role of cyclin F in the genotoxic stress response, its function under conditions of altered metabolic homeostasis remain unexplored. Here we report that cyclin F is induced upon metabolic stress in a FOXO1-dependent manner. Under metabolic stress conditions, cyclin F mediated polyubiquitylation of RBPJ at Lys315, leading to its proteasomal degradation. RBPJ regulated the expression of IDH1, which is often mutated to an oncogenic form IDH1R132H in cancers. Thus, metabolic stress–induced cyclin F attenuated the oncogenic functions of IDH1R132H in an RBPJ-dependent manner. Studies in mouse tumor models indicated that abrogation of cyclin F expression facilitates IDH1R132H-mediated tumorigenesis and metastasis. In addition, increased IDH1R132H levels correlated with reduced cyclin F levels in increasing grades of glioma. These findings highlight a novel aspect of cyclin F functions in inhibiting tumorigenesis and provide mechanistic insights into regulation of IDH1R132H.

Significance: These findings reveal mechanistic insights into the key role of the cyclin F-RBPJ axis in response to metabolic stress in cancer cells. Cancer Res; 78(22); 6386–98. ©2018 AACR.
An ATM/TRIM37/NEMO Axis Counteracts Genotoxicity by Activating Nuclear-to-Cytoplasmic NF-κB Signaling
Authors: Wu Geyan , Song Libing , Zhu Jinrong , Hu Yameng , Cao Lixue , Tan Zhanyao , Zhang Shuxia , Li Ziwen , Li Jun
Published: September 2018

Blocking genotoxic stress-induced NF-κB activation would substantially enhance the anticancer efficiency of genotoxic chemotherapy. Unlike the well-established classical NF-κB pathway, the genotoxic agents-induced “nuclear-to-cytoplasmic” NF-κB pathway is initiated from the nucleus and transferred to the cytoplasm. However, the mechanism linking nuclear DNA damage signaling to cytoplasmic IKK activation remains unclear. Here, we report that TRIM37, a novel E3 ligase, plays a vital role in genotoxic activation of NF-κB via monoubiquitination of NEMO at K309 in the nucleus, consequently resulting in nuclear export of NEMO and IKK/NF-κB activation. Clinically, TRIM37 levels correlated positively with levels of activated NF-κB and expression of Bcl-xl and XIAP in esophageal cancer specimens, which also associated positively with clinical stage and tumor-node-metastasis classification and associated inversely with overall and relapse-free survival in patients with esophageal cancer. Overexpression of TRIM37 conferred resistance to the DNA-damaging anticancer drug cisplatin in vitro and in vivo through activation of the NF-κB pathway. Genotoxic stress-activated ATM kinase directly interacted with and phosphorylated TRIM37 in the cytoplasm, which induced translocation of TRIM37 into the nucleus, where it formed a complex with NEMO and TRAF6 via a TRAF6-binding motif (TBM). Importantly, blocking the ATM/TRIM37/NEMO axis via cell-penetrating TAT-TBM peptide abrogated genotoxic agent-induced NEMO monoubiquitination and NF-κB activity, resulting in hypersensitivity of cancer cells to genotoxic drugs. Collectively, our results unveil a pivotal role for TRIM37 in genotoxic stress and shed light on mechanisms of inducible chemotherapy resistance in cancer.

Significance: In response to genotoxic stress, TRIM37 activates NF-κB signaling via monoubiquitination of NEMO, which subsequently promotes cisplatin chemoresistance and tumor relapse in cancer. Cancer Res; 78(22); 6399–412. ©2018 AACR.
Harnessing Androgen Receptor Pathway Activation for Targeted Alpha Particle Radioimmunotherapy of Breast Cancer
Authors: Thorek Daniel L.J. , Ku Anson T. , Mitsiades Nicholas , Veach Darren , Watson Philip A. , Metha Dipti , Strand Sven-Erik , Sharma Sai Kiran , Lewis Jason S. , Abou Diane S. , Lilja Hans G. , Larson Steven M. , McDevitt Michael R. , Ulmert David
Published: September 2018

Purpose:

The impact of androgen receptor (AR) activity in breast cancer biology is unclear. We characterized and tested a novel therapy to an AR-governed target in breast cancer.

Experimental Design: We evaluated the expression of prototypical AR gene products human kallikrein 2 (hK2) and PSA in breast cancer models. We screened 13 well-characterized breast cancer cell lines for hK2 and PSA production upon in vitro hormone stimulation by testosterone [dihydrotestosterone (DHT)]. AR-positive lines were further evaluated by exposure to estrogen (17β-Estradiol) and the synthetic progestin D-Norgestrel. We then evaluated an anti-hK2–targeted radiotherapy platform (hu11B6), labeled with alpha (α)-particle emitting Actinium-225, to specifically treat AR-expressing breast cancer xenografts under hormone stimulation.

Results:

D-Norgestrel and DHT activated the AR pathway, while 17β-Estradiol did not. Competitive binding for AR protein showed similar affinity between DHT and D-Norgestrel, indicating direct AR–ligand interaction. In vivo production of hK2 was sufficient to achieve site-specific delivery of therapeutic radionuclide to tumor tissue at >20-fold over background muscle uptake; effecting long-term local tumor control.

Conclusions:

[225Ac]hu11B6 targeted radiotherapy was potentiated by DHT and by D-Norgestrel in murine xenograft models of breast cancer. AR activity in breast cancer correlates with kallikrein-related peptidase-2 and can be activated by D-Norgestrel, a common contraceptive, and AR induction can be harnessed for hK2-targeted breast cancer α-emitter radiotherapy.
Carbonic Anhydrase XII Inhibitors Overcome P-Glycoprotein–Mediated Resistance to Temozolomide in Glioblastoma
Authors: Salaroglio Iris C. , Mujumdar Prashant , Annovazzi Laura , Kopecka Joanna , Mellai Marta , Schiffer Davide , Poulsen Sally-Ann , Riganti Chiara
Published: September 2018

The role of carbonic anhydrase XII (CAXII) in the chemoresistance of glioblastoma is unexplored. We found CAXII and P-glycoprotein (Pgp) coexpressed in neurospheres derived from 3 of 3 patients with different genetic backgrounds and low response to temozolomide (time to recurrence: 6–9 months). CAXII was necessary for the Pgp efflux of temozolomide and second-line chemotherapeutic drugs, determining chemoresistance in neurospheres. Psammaplin C, a potent inhibitor of CAXII, resensitized primary neurospheres to temozolomide by reducing temozolomide efflux via Pgp. This effect was independent of other known temozolomide resistance factors present in the patients. The overall survival in orthotopic patient-derived xenografts of temozolomide-resistant neurospheres, codosed with Psammaplin C and temozolomide, was significantly increased over temozolomide-treated (P < 0.05) and untreated animals (P < 0.02), without detectable signs of systemic toxicity. We propose that a CAXII inhibitor in combination with temozolomide may provide a new and effective approach to reverse chemoresistance in glioblastoma stem cells. This novel mechanism of action, via the interaction of CAXII and Pgp, ultimately blocks the efflux function of Pgp to improve glioblastoma patient outcomes.
Preoperative Serum Thyroglobulin Level as a Useful Predictive Marker to Differentiate Thyroid Cancer
Authors: Kars Ayhan , Aktan Bülent , Kilic Korhan , Sakat M. Sedat , Gözeler M. Sıtkı , Yörük Özgür , Mutlu Vahit , Yılmaz Sinan
Published: September 2018

Introduction: Thyroid cancer is the most common endocrine system cancer. Although fine-needle aspiration biopsy is the most commonly used method for diagnosis, it is not always sufficient. The aim of this study was to investigate the influence of preoperative serum thyroglobulin (Tg) concentration on differentiated thyroid cancer risk. Material and Methods: A total of 133 patients who underwent total thyroidectomy due to various indications at the Ear-Nose-Throat Department, Ataturk University Medical School, between April 2015 and December 2015, were included in this prospective study. Histopathological diagnosis and preoperative Tg levels were compared. Receiver operating characteristic (ROC) analysis was used for detection of the cut-off to discriminate malignant from benign thyroid masses using preoperative Tg as a variable. Results: Malignant pathology (differentiated thyroid carcinoma) was detected in 59 out of 133 patients (44.4%) and benign pathology in 74 (55.6%). A statistically significant difference in preoperative Tg value was detected between malignant and benign cases (p < 0.05). Conclusion: The prevalence of differentiated thyroid carcinoma was higher among patients with a preoperative serum Tg value > 188.5 ng/mL, and this may thus be used as a marker for the diagnosis of this malignancy.
Chimeric Antigen Receptor-T Cells with 4-1BB Co-Stimulatory Domain Present a Superior Treatment Outcome than Those with CD28 Domain Based on Bioinformatics
Authors: Zhong Qi , Zhu Yang-min , Zheng Li-ling , Shen Hui-juan , Ou Rui-ming , Liu Zhi , She Yan-ling , Chen Rui , Li Cheng , Huang Jing , Yao Meng-dong , Zhang Qing , Liu Shuang
Published: September 2018

Background: The second-generation CD19-chimeric antigen receptor (CAR)-T co-stimulatory domain that is commonly used in clinical practice is CD28 or 4-1BB. Previous studies have shown that the persistence of CAR-T in the 4-1BB co-stimulatory domain appears to be longer. Methods: The expression profile data of GSE65856 were obtained from GEO database. After data preprocessing, the differentially expressed genes (DEGs) between the mock CAR versus CD19-28z CAR T cells and mock CAR versus CD19-BBz CAR T cells were identified using the limma package. Subsequently, functional enrichment analysis of DEGs was performed using the DAVID tool. Then, the protein-protein international (PPI) network of these DEGs was visualized by Cytoscape, and the miRNA-target gene-disease regulatory networks were predicted using Webgestal. Results: A total of 18 common DEGs, 6 CD19-28z specific DEGs and 206 CD19-BBz specific DEGs were identified. Among CD19-28z specific DEGs, down-regulated PAX5 might be an important node in the PPI network and could be targeted by miR-496. In CD19-BBz group, JUN was a hub node in the PPI network and involved in the regulations of miR520D – early growth response gene 3 (EGR3)-JUN and mi-R489-AT-rich interaction domain 5A (ARID5A)-JUN networks. Conclusion: The 4-1BB co-stimulatory domain might play in important role in the treatment of CAR-T via miR-520D-EGR3-JUN and miR489-ARID5A-JUN regulation network, while CD28 had a negative effect on CAR-T treatment.
Current Status and Future Perspectives of Axillary Management in the Neoadjuvant Setting
Authors: Kühn Thorsten , Classe Jean-Marc , Gentilini Oreste David , Tinterri Corrado , Peintinger Florentia , de Boniface Jana
Published: September 2018

Axillary surgery has undergone considerable changes in recent years, especially in relation to patients who undergo neoadjuvant chemotherapy (NACT). Due to constantly decreasing rates of recurrence and death from breast cancer, modern surgical strategies aim at de-escalating the extent of local treatment and avoiding unnecessary procedures. This relates especially to lymph node surgery which is associated with considerable morbidity. In patients who initially present with clinically node-negative disease, sentinel lymph node biopsy (SLNB) is increasingly performed after NACT. The determination of the post-NACT nodal status does not only spare patients from additional surgery but also allows the assessment of pathologic complete response which is increasingly becoming an important tool for treatment planning. Since more than 70% of these patients have a ypN0 status after NACT, future trials will aim to identify patients who might be spared any axillary surgery after NACT. In patients who initially present with positive lymph nodes, the success rates of SLNB in terms of detection and accuracy are less favorable compared to those in patients who undergo primary surgery. The clinical significance of this is unclear. To reduce unnecessary axillary dissection in patients with cN1ycN0 status, prospective outcome data after SLNB without further lymph node removal are urgently needed. Improvements in surgical technique by localizing positive nodes at the time of diagnosis and removing them in a targeted surgical procedure (targeted axillary dissection) are under evaluation. Risk assessment and patient selection (including gene expression profiles) might be other ways of safely omitting axillary dissection.