bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytochrome c Oxidase Sequences of Zambian Wildlife Helps to Identify Species of Origin of Meat
Authors: Syakalima Michelo , Munyeme Musso , Yasuda Jun
Published: November 2016

Accurate species identification is a crucial tool in wildlife conservation. Enforcement of antipoaching law is more achievable with robust molecular identification of poached meat. Determining the region where the animal may have been taken from would also be a useful tool in suppression of cross-border trade of poached meat. We present data from a cytochrome c oxidase “barcoding” study of Zambian ruminants that adequately identifies the species of origin of meat samples. Furthermore, the method demonstrates possible improvement and application in regional variation in sequence identity that has a potential for discriminating meat samples from different subpopulations.
Avulsion Fracture of the Coracoid Process at the Coracoclavicular Ligament Insertion: A Report of Three Cases
Authors: Morioka Takeshi , Ogawa Kiyohisa , Takahashi Masaaki
Published: November 2016

Avulsion fracture at the site of attachment of the coracoid process of the coracoclavicular ligament (CCL) is extremely rare. We presented three adult cases of this unusual avulsion fracture associated with other injuries. Case  1 was a 25-year-old right-handed male with a left distal clavicular fracture with an avulsion fracture of the coracoid attachment of the CCL; this case was treated surgically and achieved an excellent outcome. Case  2 was a 39-year-old right-handed male with dislocation of the left acromioclavicular joint with two avulsion fractures: one at the posteromedial surface of the coracoid process at the attachment of the conoid ligament and one at the inferior surface of the clavicle at the attachment site of the trapezoid ligament; this case was treated conservatively, and unfavorable symptoms such as dull pain at rest and sharp pain during some daily activities remained. Case  3 was a 41-year-old right-handed female with a right distal clavicular fracture with an avulsion fracture of the coracoid attachment of the conoid ligament; this case was treated conservatively, and the distal clavicular fracture became typical nonunion. These three cases corresponded to type I fractures according to Ogawa’s classification as the firm scapuloclavicular connection was destroyed and also to double disruption of the superior shoulder suspensory complex. We recommend surgical intervention when treating patients with this type of acute or subacute injury, especially in those engaging in heavy lifting or overhead work.
Congenital Hypothyroidism: An Unusual Combination of Biochemical Abnormalities
Authors: Mantri Ruchi , Bavdekar S. B. , Save Sushma U.
Published: November 2016

A forty-five-day-old female infant presented with prolonged jaundice with clinical features suggestive of congenital hypothyroidism (CHT). On investigations, the infant was noted to have indirect hyperbilirubinemia (13.8 mg/dl) with increased levels of AST (298 IU/dl) and ALT (174 IU/dl) in the serum. The child had low levels of free T3 (<1 pg/ml) and free T4 (0.4 ng/dl) secondary to thyroid agenesis detected on radionuclide scan and ultrasonography of the neck and raised levels of TSH (>500 microIU/ml) in the serum. The combination of indirect hyperbilirubinemia and raised levels of hepatic transaminases has not been reported in babies with CHT. Following institution of oral thyroxin therapy, the serum bilirubin levels ameliorated (2.9 mg/dl) considerably by 15 days of therapy and the serum levels of AST (40 IU/dl) and ALT (20 IU/dl) got normalized. The case demonstrates that raised levels of hepatic transaminases can occur in infants with CHT and these can resolve just with thyroxin therapy, obviating the need for extensive investigative laboratory work-up.
Preparation of a Modified Nanoalumina Sorbent for the Removal of Alizarin Yellow R and Methylene Blue Dyes from Aqueous Solutions
Authors: Al-Rubayee Wasan T. , Abdul-Rasheed Omar F. , Ali Noor Mustafa
Published: November 2016

A modified form ofγ-alumina nanoparticles prepared by immobilization of 2,4-dinitrophenyl hydrazine onγ-alumina nanoparticles coated with sodium dodecyl sulfate (DNPH-γ-alumina) for the removal of the anionic dye (Alizarin yellow R) and cationic dye (Methylene blue) from aqueous solutions has been investigated. The FTIR, SEM, TEM, XRD, BET, and BJH analysis techniques indicate that the modification reaction has occurred. Batch adsorption study revealed that 0.05 g amount of the modified adsorbent was capable of removing 95.6% and 65.6% of Alizarin yellow (AY) and Methylene blue (MB) dyes, respectively, in 60 min. The experimental equilibrium data showed that Langmuir isotherm applies well for describing the adsorption behavior, and the maximum adsorption capacity was found to be 47.8 mg/g and 32.8 mg/g for AY and MB on DNPH-γ-alumina, respectively. Kinetic studies showed best applicability of the second-order kinetic model. The DNPH-γ-alumina adsorbent proved capability, effectiveness, and selectivity for the removal of Alizarin yellow R dye. Therefore, it is possible to increase the efficiency of an adsorbent for the removal of pollutants by applying a modification to the surface of the adsorbent, and DNPH as a modifier proved efficient for the removal of a wider range of pollutants including metal ions and dye compounds.
Cholecystocolonic Fistulas from Diverticulosis: A Potentially Missable Cause of Liver Abscesses
Authors: Warner Ben , Wong Terry , Berry Philip
Published: November 2016

Cholecystocolonic fistulas (CCF) due to colonic diverticulosis are a rare cause of liver abscesses. It is even rarer to simultaneously have choledocholithiasis, another cause for liver abscesses. In this case report, we found both pathologies and emphasise the need to study cholangiograms carefully so as not to miss alternative diagnoses.
Trend and Cycle Analysis of Annual and Seasonal Precipitation in Liaoning, China
Authors: Chen Taotao , Xia Guimin , Wilson Lloyd T. , Chen Wei , Chi Daocai
Published: November 2016

Annual and seasonal precipitation data for 49 meteorological stations over the period of 1960–2006 in Liaoning province were analyzed. Liaoning experienced province-wide decreases in precipitation over the 47-year period, with annual precipitation decreasing by 96% of the stations, followed by 92, 84, 63, and 27%, respectively, for summer, autumn, spring, and winter precipitation. Regional trend analysis confirmed the province-wide decrease, which was detected by the site-specific analysis, but a greater number of significant declines were found for annual, summer, and autumn precipitation for Liaoning province and for three of its four subregions. Four significant cycles with alternation patterns were detected mainly at the time scales of 3–5, 10-11, 20–23, and 31.2 years for each of the four subregions (Liaodong Peninsula, Northeastern Mountain, Western Highland, and Central Plain) and the entire Liaoning province, with the dominant periodicities being 10-11 years. The 10-11-year periodic variation of Liaoning annual precipitation was negatively associated with sunspot activity and positively associated with the East Asian Summer Monsoon (EASM) at the same time scale, while the 31.2-year periodic variation of Liaoning annual precipitation was positively correlated with both the EASM and ENSO activities at the 30–33-year time scale.
Proximal Limb Weakness in a Patient with Celiac Disease: Copper Deficiency, Gluten Sensitivity, or Both as the Underlying Cause?
Authors: Avila J. David , Lacomis David
Published: November 2016

Celiac disease has been associated with several neurologic disorders which may result from micronutrient deficiencies, coexisting autoimmune conditions, or gluten sensitivity. Copper deficiency can produce multiple neurologic manifestations. Myeloneuropathy is the most common neurologic syndrome and it is often irreversible, despite copper replacement. We report the case of a 55-year-old man who presented with progressive proximal limb weakness and weight loss in the setting of untreated celiac disease without gastrointestinal symptoms. He had anemia, neutropenia, and severe hypocupremia. The pattern of weakness raised the suspicion that there was an underlying myopathy, although this was not confirmed by electrodiagnostic studies. Weakness and hematologic abnormalities resolved completely within 1 month of total parenteral nutrition with copper supplementation and a gluten-free diet. Myopathy can rarely occur in patients with celiac disease, but the mechanism is unclear. Pure proximal limb weakness has not been previously reported in copper deficiency. We propose that this may represent a novel manifestation of hypocupremia and recommend considering copper deficiency and gluten sensitivity in patients presenting with proximal limb weakness.
Comparison of the Lag Screw Placements for the Treatment of Stable and Unstable Intertrochanteric Femoral Fractures regarding Trabecular Bone Failure
Authors: Celik Talip , Mutlu Ibrahim , Ozkan Arif , Kisioglu Yasin
Published: November 2016

Background.In this study, the cut-out risk of Dynamic Hip Screw (DHS) was investigated in nine different positions of the lag screw for two fracture types by using Finite Element Analysis (FEA).Methods.Two types of fractures (31-A1.1 and A2.1 in AO classification) were generated in the femur model obtained from Computerized Tomography images. The DHS model was placed into the fractured femur model in nine different positions. Tip-Apex Distances were measured using SolidWorks. In FEA, the force applied to the femoral head was determined according to the maximum value being observed during walking.Results.The highest volume percentage exceeding the yield strength of trabecular bone was obtained in posterior-inferior region in both fracture types. The best placement region for the lag screw was found in the middle of both fracture types. There are compatible results between Tip-Apex Distances and the cut-out risk except for posterior-superior and superior region of 31-A2.1 fracture type.Conclusion.The position of the lag screw affects the risk of cut-out significantly. Also, Tip-Apex Distance is a good predictor of the cut-out risk. All in all, we can supposedly say that the density distribution of the trabecular bone is a more efficient factor compared to the positions of lag screw in the cut-out risk.
Impaired Visual Motor Coordination in Obese Adults
Authors: Gaul David , Mat Arimin , O’Shea Donal , Issartel Johann
Published: November 2016

Objective. To investigate whether obesity alters the sensory motor integration process and movement outcome during a visual rhythmic coordination task. Methods. 88 participants (44 obese and 44 matched control) sat on a chair equipped with a wrist pendulum oscillating in the sagittal plane. The task was to swing the pendulum in synchrony with a moving visual stimulus displayed on a screen. Results. Obese participants demonstrated significantly (p<0.01) higher values for continuous relative phase (CRP) indicating poorer level of coordination, increased movement variability (p<0.05), and a larger amplitude (p<0.05) than their healthy weight counterparts. Conclusion. These results highlight the existence of visual sensory integration deficiencies for obese participants. The obese group have greater difficulty in synchronizing their movement with a visual stimulus. Considering that visual motor coordination is an essential component of many activities of daily living, any impairment could significantly affect quality of life.
Multivariate Macdonald Distribution and Its Properties
Authors: Nagar Daya K. , Zarrazola Edwin , Sánchez Luz Estela
Published: November 2016

We give multivariate generalization of Macdonald distribution and study several of its properties. We also define the multivariate Macdonald-gamma distribution and derive a number of results pertaining to it.
Congenital Lumbar Hernia: A 15-Year Experience at a Single Tertiary Centre
Authors: Rattan K. N. , Agarwal Arushi , Dhiman Ankur , Rattan Ananta
Published: November 2016

Aim. Congenital lumbar hernia is an uncommon anomaly with only few cases reported in the English literature. This study was done to study the incidence, age at presentation, sex, associated anomalies, surgical management, and postoperative morbidity and mortality of congenital lumbar hernia in pediatric patients.Methods. Retrospective analysis of all patients of CLH over a period of 15 years (January 2000 to December 2015) was analyzed.Results. A total of 14 patients were encountered in this series. All presented within first 2 years of age. 12 were males and 2 were females. All of them presented with swelling in lumbar region. 13 were unilateral and 1 was bilateral. Left sided hernia was observed in 2 cases only. Lumbocostovertebral syndrome was found in all the patients in addition to other rare anomalies. All cases were managed with open surgical repair. Wound infection was seen in 2 cases. There was no mortality in our series.Conclusion. CLH is very rare among hernias. Surgery should be carried out within 1 year of age. For a defect of <5 cm, primary repair is done. For a defect of >5 cm, meshplasty should be considered. Prognosis is excellent.
Volatility Spillovers in Capesize Forward Freight Agreement Markets
Authors: Gong Xiaoxing , Lu Jing
Published: November 2016

This paper is to investigate spillovers in the Capesize forward freight agreements (FFAs) markets before and after the global financial crisis. The paper chooses four Capesize voyage routes FFAs (C3, C4, C5, and C7), two time-charter routes FFAs (BCIT/C average, BPI T/C average), and spot rates as research subjects, covering the periods 3 January 2006 to 24 December 2015. This paper applies Volatility Spillover Multivariate Stochastic Volatility (VS-MSV) model to analyze volatility spillover effects and estimates the parameters via software of Bayesian inference using Gibbs Sampling (BUGS), the deviance information criterion (DIC) used for goodness-of-fit model. The results suggest that there are volatility spillover effects in certain Capesize FFAs routes, and the effects from spot rates to FFAs take place before crisis, yet they are bilateral after crisis. With the development of shipping markets, the correlations between FFAs and spot rate are enhanced, and it seems that the effects depend on market information and traders’ behavior. So practitioners could make decisions according to the spillovers.
Biocompatible and Biodegradable Ultrafine Nanoparticles of Poly(Methyl Methacrylate-co-Methacrylic Acid) Prepared via Semicontinuous Heterophase Polymerization: Kinetics and Product Characterization
Authors: Saade Henned , Guillén María de Lourdes , Romero Judith Cabello , Cepeda Jesús , Ilyna Anna , Fernández Salvador , Enríquez-Medrano Francisco Javier , López Raúl Guillermo
Published: November 2016

Ultrafine nanoparticles, less than 10 nm in mean diameter, of the FDA approved copolymer methyl methacrylate- (MMA-)co-methacrylic acid (MAA), 2/1 (mol/mol), were prepared. The method used for the preparation of these particles stabilized in a latex containing around 11% solids includes the dosing of the monomers mixture on a micellar solution preserving monomer starved conditions. It is thought that the operation at these conditions combined with the hydrophilicity of MMA and MAA units favors the formation of ultrafine particles; the propagation reaction carried out within so small compartments renders copolymer chains rich in syndiotactic units very likely as consequence of the restricted movements of the end propagation of the chains. Because of their biocompatibility and biodegradability as well as their extremely small size these nanoparticles could be used as vehicles for improved drug delivery in the treatment of chronic-degenerative diseases.
Qualitative Insights from the Osteoporosis Research: A Narrative Review of the Literature
Authors: Bombak A. E. , Hanson H. M.
Published: November 2016

Purpose.Much of the research on osteoporosis has been generated quantitatively. However, the qualitative osteoporosis literature provides valuable information on patient and clinician experiences and perspectives, informing the design and implementation of health research and healthcare services. To identify knowledge gaps and inform the design of future qualitative research, a narrative review was conducted to consolidate and synthesize the existing insights available within the qualitative osteoporosis research.Methods.Search terms reflecting the domains of osteoporosis and qualitative research were entered into the Scopus database to generate a comprehensive survey of qualitative research in the area of osteoporosis. Articles were thematically analysed and the results are presented in the form of a narrative review.Results.Forty-four articles were included in the narrative review. Qualitative research in the field of osteoporosis research can be summarized by 3 thematic areas: the meaning of osteoporosis for patients and the public, the lived experience of an osteoporosis diagnosis, and the programmatic approach to osteoporosis prevention and treatment.Conclusions.Qualitative studies provide clinically valuable insights in how osteoporosis is conceptualized and managed and programmatic aspects of osteoporosis treatment. The findings of this narrative review suggest the need for balance between presenting osteoporosis as a serious health condition and producing unwarranted anxiety and inactivity so as to ensure the best possible outcomes for individuals with osteoporosis.
Combined Overlap Extension PCR Method for Improved Site Directed Mutagenesis
Authors: Hussain Hasnain , Chong Nikson Fatt-Ming
Published: November 2016

The combined overlap extension PCR (COE-PCR) method developed in this work combines the strengths of the overlap extension PCR (OE-PCR) method with the speed and ease of the asymmetrical overlap extension (AOE-PCR) method. This combined method allows up to 6 base pairs to be mutated at a time and requires a total of 40–45 PCR cycles. A total of eight mutagenesis experiments were successfully carried out, with each experiment mutating between two to six base pairs. Up to four adjacent codons were changed in a single experiment. This method is especially useful for codon optimization, where doublet or triplet rare codons can be changed using a single mutagenic primer set, in a single experiment.
Low Grade Lymphoma Mimicking Metastatic Urothelial Carcinoma: When Do We Need Further Histologic Staging?
Authors: Ali Azka , Skelton IV William P. , Akhavan Neeka N. , Nguyen Thu-Cuc , Taylor Zachary A. , Townsend Tabitha , Pathak Prajwol , Hasija Nalini , Li Li , Indrisek Jacqueline , Watson Scott , Nixon Isis , Dang Nam H. , Zlotecki Robert , Crispen Paul , Allan Robert , Abbitt Patricia , Dang Long H.
Published: November 2016

Introduction.Patients with urothelial carcinoma of the bladder often present with metastases to regional lymph nodes, with lymphadenopathy on physical examination or radiographic imaging.Case Presentation.We present the case of a 73-year-old Caucasian man with presumed metastatic urothelial carcinoma of the bladder to regional pelvic and retroperitoneal lymph nodes. He underwent systemic chemotherapy for treatment of urothelial carcinoma and was discovered on restaging to have findings suggestive of disease progression but ultimately was found to have a concurrent secondary malignancy.Conclusion.Our case suggests that in patients with urothelial carcinoma, the concurrent presentation of regional lymphadenopathy may not be metastatic urothelial carcinoma and may warrant further investigation.
Regulatory Mechanisms of the Ihh/PTHrP Signaling Pathway in Fibrochondrocytes in Entheses of Pig Achilles Tendon
Authors: Han Xuesong , Zhuang Yanfeng , Zhang Zhihong , Guo Lin , Wang Wanming
Published: November 2016

This study is aimed at exploring the effect of stress stimulation on the proliferation and differentiation of fibrochondrocytes in entheses mediated via the Indian hedgehog (Ihh)/parathyroid hormone‐related protein (PTHrP) signaling pathway. Differential stress stimulation on fibrochondrocytes in entheses was imposed. Gene expression and protein levels of signaling molecules including collagen type I (Col I), Col II, Col X, Ihh, and PTHrP in the cytoplasm of fibrochondrocytes were detected. Ihh signal blocking group was set up using Ihh signaling pathway‐specific blocking agent cyclopamine. PTHrP enhancement group was set up using PTHrP reagent. Ihh/PTHrP double intervention group, as well as control group, was included to study the regulatory mechanisms of the Ihh/PTHrP signaling pathway in fibrochondrocytes. Under low cyclic stress tensile (CTS), PTHrP, Col I, and Col II gene expression and protein synthesis increased. Under high CTS, Ihh and Col X gene expression and protein synthesis increased. Blocking Ihh signaling with cyclopamine resulted in reduced PTHrP gene expression and protein synthesis and increased Col X gene expression and protein synthesis. Ihh and PTHrP coregulate fibrochondrocyte proliferation and differentiation in entheses through negative feedback regulation. Fibrochondrocyte is affected by the CTS. This phenomenon is regulated by stress stimulation through the Ihh/PTHrP signaling pathway.
Comparison of Surface and Structural Properties of Carbonaceous Materials Prepared by Chemical Activation of Tomato Paste Waste: The Effects of Activator Type and Impregnation Ratio
Authors: Ozbay Nurgul , Yargic Adife Seyda
Published: November 2016

Activated carbons were prepared by carbonization of tomato paste processing industry waste at 500°C followed by chemical activation with KOH, K2CO3, and HCl in N2 atmosphere at low temperature (500°C). The effects of different activating agents and impregnation ratios (25, 50, and 100 wt.%) on the materials’ characteristics were examined. Precursor, carbonized tomato waste (CTW), and activated carbons were characterized by using ultimate and proximate analysis, thermogravimetric analysis (TG/DTG), Fourier transform-infrared (FT-IR) spectroscopy, X-ray fluorescence (XRF) spectroscopy, point of zero charge measurements (pHPZC), particle size analyzer, scanning electron microscopy (SEM), energy dispersive X-ray (EDX) spectroscopy, nitrogen adsorption/desorption isotherms, and X-ray diffraction (XRD) analysis. Activation process improved pore formation and changed activated carbons’ surface characteristics. Activated carbon with the highest surface area (283 m3/g) was prepared by using 50 wt.% KOH as an activator. According to the experimental results, tomato paste waste could be used as an alternative precursor to produce low-cost activated carbon.
Dilated Cardiomyopathy Induced by Chronic Starvation and Selenium Deficiency
Authors: Dasgupta Soham , Aly Ashraf M.
Published: November 2016

Protein energy malnutrition (PEM) has been rarely documented as a cause of cardiovascular abnormalities, including dilated cardiomyopathy. Selenium is responsible for antioxidant defense mechanisms in cardiomyocytes, and its deficiency in the setting of PEM and disease related malnutrition (DRM) may lead to exacerbation of the dilated cardiomyopathy. We report a rare case of a fourteen-year-old boy who presented with symptoms of congestive heart failure due to DRM and PEM (secondary to chronic starvation) along with severe selenium deficiency. An initial echocardiogram showed severely depressed systolic function consistent with dilated cardiomyopathy. Aggressive nutritional support and replacement of selenium and congestive heart failure medications that included diuretics and ACE inhibitors with the addition of carvedilol led to normalization of the cardiac function within four weeks. He continues to have significant weight gain and is currently completely asymptomatic from a cardiovascular standpoint.
Multiplicity of Solutions for Schrödinger Equations with Concave-Convex Nonlinearities
Authors: Wu Dong-Lun , Tang Chun-Lei , Wu Xing-Ping
Published: November 2016

We study the multiplicity of solutions for a class of semilinear Schrödinger equations: -Δu+V(x)u=gx,u,  for  x∈RN;  u(x)→0,  as  u→∞, where V satisfies some kind of coercive condition and g involves concave-convex nonlinearities with indefinite signs. Our theorems contain some new nonlinearities.
Efficiency of Polyphenol Extraction from Artificial Honey Using C18 Cartridges and Amberlite® XAD-2 Resin: A Comparative Study
Authors: Yung An Chua , Hossain Md. Murad , Alam Fahmida , Islam Md. Asiful , Khalil Md. Ibrahim , Alam Nadia , Gan Siew Hua
Published: November 2016

A comparative study of the extraction efficiency of nine known polyphenols [phenolic acids (benzoic acid, dihydroxybenzoic acid, gallic acid, trans-cinnamic acid, and vanillic acid) and flavonoids (naringenin, naringin, quercetin, and rutin)] was conducted by deliberately adding the polyphenols to an artificial honey solution and performing solid phase extraction (SPE). Two SPE methods were compared: one using Amberlite XAD-2 resin and another one using a C18 cartridge. A gradient high performance liquid chromatography system with an RP18 column and photodiode array detector was utilized to analyze the extracted polyphenols. The mean percent of recovery from the C18 cartridges was 74.2%, while that from the Amberlite XAD-2 resin was 43.7%. The recoveries of vanillic acid, naringin, and rutin were excellent (>90%); however, gallic acid was not obtained when C18 cartridges were used. Additionally, the reusability of Amberlite XAD-2 resin was investigated, revealing that the mean recovery of polyphenols decreased from 43.7% (1st extraction) to 29.3% (3rd extraction). It was concluded that although Amberlite XAD-2 resin yielded a higher number of compounds, C18 cartridges gave a better extraction recovery. The lower recovery seen for the Amberlite XAD-2 resin also cannot be compensated by repeated extractions due to the gradual decrease of extraction recovery when reused.
Acute Myocardial Infarction in a Patient with Two-Vessel Occlusion and a Large Lambl’s Excrescence
Authors: Pizzuti Alfredo , Parisi Francesco , Mosso Luciano , Cali’ Quaglia Francesca , Tomasello Antonino
Published: November 2016

A 59-year-old man underwent an echocardiography study after myocardial infarction and it showed a thin, mobile mass attached to the aortic valve. A diagnosis of Lambl’s excrescence (LE) was suspected. Coronary occlusion as a consequence of embolism of LE’s material could not be excluded and the patient underwent surgical excision. Histology confirmed the diagnosis; however a differential diagnosis with papillary fibroelastoma could not be established because both of these structures are histologically indistinguishable. A brief survey of the literature is presented. Evidence-based recommendations for treatment have not been established yet.
Gastric Adenocarcinoma of the Fundic Gland Type Treated by Endoscopic Mucosal Resection: A Case Report and Review of the Literature
Authors: Lewin Eleanor , Daroca Philip , Sikka Sanjay , Wu Tong , Nakanishi Yukihiro
Published: November 2016

Gastric adenocarcinoma of the fundic gland type (GA-FG) is a rare entity that has only recently been described and defined. There is ongoing controversy regarding the malignant potential of this lesion. We report the case of a GA-FG in a 49-year-old Caucasian man who was referred to endoscopy for management of an incidentally found gastric polyp. Endoscopy showed a single polypoid lesion in the gastric fundus which was successfully removed with endoscopic resection. Grossly, the polyp measured 1.1 cm in greatest dimension. Microscopic examination showed irregularly branched neoplastic glands covered with a nonneoplastic foveolar epithelium. The continuity between the neoplastic glands and the fundic glands is clearly identified, indicating the tumor arose from the fundic glands. The tumor cells exhibited occasional oxyntic cytoplasm with enlarged atypical nuclei. The tumor invaded the submucosa with complete disruption of the muscularis mucosae and mild lymphocytic and fibroblastic stromal reaction. No necrosis, mitosis, or lymph-vascular invasion was identified. Although some authors have proposed reclassification of GA-FGs as oxyntic gland polyps/adenomas, in light of several reported cases with submucosal invasion as well as lymphatic invasion, we maintain that this neoplasm is best categorized as an extremely well-differentiated adenocarcinoma to reflect its invasive potential.
Spatiotemporal Changes of Reference Evapotranspiration in Mongolia during 1980–2006
Authors: Yu Wenjun , Wu Tonghua , Wang Weizhen , Li Ren , Wang Tianye , Qin Yanhui , Wang Weihua , Zhu Xiaofan
Published: November 2016

Reference evapotranspiration (RET) plays an important role in the terrestrial hydrological cycle. Applying the Penman-Monteith method, the RET over Mongolia was estimated from 1980 to 2006. The changing trends and magnitude of RET were detected by the Mann-Kendall test and Theil-Sen’s slope methods. Meanwhile, aridity indices were estimated using two different indices. The impacts of meteorological variables on RET were assessed through sensitive analysis by comparing the resulting RETs from artificially disturbed meteorological variables. The results indicated that the RET for 16 stations in Mongolia showed an increasing trend, particularly in the center and south. The calculated RET was higher than precipitation, which means severe droughts in Mongolia. The spatial patterns of RET are significantly influenced by climatic conditions as well as characteristics of the underlying surface (e.g., elevation and vegetation). The mean annual RET decreased from the south to the north, owing to sparse vegetation in the south of Mongolia. The sensitivity analysis revealed that the changes of RET were strongly affected by air temperature and relative humidity.
Morbidity and Mortality in Preterm Infants following Antacid Use: A Retrospective Audit
Authors: Singh Natasha , Dhayade Aparna , Mohamed Abdel-Latif , Chaudhari Tejasvi Vasant
Published: November 2016

Background and Objectives. Antacids are often prescribed to preterm infants due to misdiagnosis of gastro-oesophageal reflux. This suppresses gastric acidity, a major defence mechanism against infection. This study aims to determine if ranitidine and omeprazole use in very low birth weight (VLBW) neonates, <1500 grams, is associated with increased risk of late onset sepsis, necrotising enterocolitis (NEC), and mortality.Methods. Retrospective analysis was conducted on neonates, <1500 grams, born and admitted into theNeonatal Intensive Care UnitatThe Canberra Hospitalduring the period from January 2008 to December 2012. Information regarding late onset sepsis, NEC, mortality, ranitidine/omeprazole use, and other neonatal/hospital factors was collected for each neonate.Results. 360 neonates were evaluated, 64 received ranitidine and/or omeprazole, and 296 had not. There were no statistically significant differences in incidence of late onset sepsis (OR = 0.52, CI = 0.24–1.1, andp= 0.117), NEC Stage 2 and above (OR = 0.4, CI = 0.05–3.2, andp= 0.7), or mortality (OR = 0.35, CI = 0.08–1.5, andp= 0.19) between the two groups. After adjusting significant differences in neonatal and hospital factors, risk of late onset sepsis was significantly lower in those that received ranitidine/omeprazole (OR = 0.28, CI = 0.13–0.65, andp= 0.003).Conclusions. Ranitidine and omeprazole use in VLBW preterm infants may not be associated with an increased risk of infection, NEC, and mortality.
T Cells Redirected to a Minor Histocompatibility Antigen Instruct Intratumoral TNFα Expression and Empower Adoptive Cell Therapy for Solid Tumors
Authors: Manzo Teresa , Sturmheit Tabea , Basso Veronica , Petrozziello Elisabetta , Hess Michelini Rodrigo , Riba Michela , Freschi Massimo , Elia Angela R. , Grioni Matteo , Curnis Flavio , Protti Maria Pia , Schumacher Ton N. , Debets Reno , Swartz Melody A. , Corti Angelo , Bellone Matteo , Mondino Anna
Published: November 2016

Donor-derived allogeneic T cells evoke potent graft versus tumor (GVT) effects likely due to the simultaneous recognition of tumor-specific and host-restricted minor histocompatibility (H) antigens. Here we investigated whether such effects could be reproduced in autologous settings by TCR gene–engineered lymphocytes. We report that T cells redirected either to a broadly expressed Y-encoded minor H antigen or to a tumor-associated antigen, although poorly effective if individually transferred, when simultaneously administered enabled acute autochthonous tumor debulking and resulted in durable clinical remission. Y-redirected T cells proved hyporesponsive in peripheral lymphoid organs, whereas they retained effector function at the tumor site, where in synergy with tumor-redirected lymphocytes, they instructed TNFα expression, endothelial cell activation, and intratumoral T-cell infiltration. While neutralizing TNFα hindered GVT effects by the combined T-cell infusion, a single injection of picogram amounts of NGR-TNF, a tumor vessel–targeted TNFα derivative currently in phase III clinical trials, substituted for Y-redirected cells and enabled tumor debulking by tumor-redirected lymphocytes. Together, our results provide new mechanistic insights into allogeneic GVT, validate the importance of targeting the tumor and its associated stroma, and prove the potency of a novel combined approach suitable for immediate clinical implementation. Cancer Res; 77(3); 658–71. ©2016 AACR.
MIF-Induced Stromal PKCβ/IL8 Is Essential in Human Acute Myeloid Leukemia
Authors: Abdul-Aziz Amina M. , Shafat Manar S. , Mehta Tarang K. , Di Palma Federica , Lawes Matthew J. , Rushworth Stuart A. , Bowles Kristian M.
Published: November 2016

Acute myeloid leukemia (AML) cells exhibit a high level of spontaneous apoptosis when cultured in vitro but have a prolonged survival time in vivo, indicating that tissue microenvironment plays a critical role in promoting AML cell survival. In vitro studies have shown that bone marrow mesenchymal stromal cells (BM-MSC) protect AML blasts from spontaneous and chemotherapy-induced apoptosis. Here, we report a novel interaction between AML blasts and BM-MSCs, which benefits AML proliferation and survival. We initially examined the cytokine profile in cultured human AML compared with AML cultured with BM-MSCs and found that macrophage migration inhibitory factor (MIF) was highly expressed by primary AML, and that IL8 was increased in AML/BM-MSC cocultures. Recombinant MIF increased IL8 expression in BM-MSCs via its receptor CD74. Moreover, the MIF inhibitor ISO-1 inhibited AML-induced IL8 expression by BM-MSCs as well as BM-MSC–induced AML survival. Protein kinase C β (PKCβ) regulated MIF-induced IL8 in BM-MSCs. Finally, targeted IL8 shRNA inhibited BM-MSC–induced AML survival. These results describe a novel, bidirectional, prosurvival mechanism between AML blasts and BM-MSCs. Furthermore, they provide biologic rationale for therapeutic strategies in AML targeting the microenvironment, specifically MIF and IL8. Cancer Res; 77(2); 303–11. ©2016 AACR.
Regeneration of CD8αβ T Cells from T-cell–Derived iPSC Imparts Potent Tumor Antigen-Specific Cytotoxicity
Authors: Maeda Takuya , Nagano Seiji , Ichise Hiroshi , Kataoka Keisuke , Yamada Daisuke , Ogawa Seishi , Koseki Haruhiko , Kitawaki Toshio , Kadowaki Norimitsu , Takaori-Kondo Akifumi , Masuda Kyoko , Kawamoto Hiroshi
Published: November 2016

Although adoptive transfer of cytotoxic T lymphocytes (CTL) offer a promising cancer therapeutic direction, the generation of antigen-specific CTL from patients has faced difficulty in efficient expansion in ex vivo culture. To resolve this issue, several groups have proposed that induced pluripotent stem cell technology be applied for the expansion of antigen-specific CTL, which retain expression of the same T-cell receptor as original CTL. However, in these previous studies, the regenerated CTL are mostly of the CD8αα+ innate type and have less antigen-specific cytotoxic activity than primary CTL. Here we report that, by stimulating purified iPSC-derived CD4/CD8 double-positive cells with anti-CD3 antibody, T cells expressing CD8αβ were generated and exhibited improved antigen-specific cytotoxicity compared with CD8αα+ CTL. Failure of CD8αβ T-cell production using the previous method was found to be due to killing of double-positive cells by the double-negative cells in the mixed cultures. We found that WT1 tumor antigen-specific CTL regenerated by this method prolonged the survival of mice bearing WT1-expressing leukemic cells. Implementation of our methods may offer a useful clinical tool. Cancer Res; 76(23); 6839–50. ©2016 AACR.
A Novel Platinum(II)–Based Bifunctional ADC Linker Benchmarked Using 89Zr-Desferal and Auristatin F–Conjugated Trastuzumab
Authors: Sijbrandi Niels J. , Merkul Eugen , Muns Joey A. , Waalboer Dennis C.J. , Adamzek Kevin , Bolijn Marije , Montserrat Veronica , Somsen Govert W. , Haselberg Rob , Steverink Paul J.G.M. , Houthoff Hendrik-Jan , van Dongen Guus A.M.S.
Published: November 2016

Greater control is desirable in the stochastic conjugation technology used to synthesize antibody–drug conjugates (ADC). We have shown recently that a fluorescent dye can be stably conjugated to a mAb using a bifunctional platinum(II) linker. Here, we describe the general applicability of this novel linker technology for the preparation of stable and efficacious ADCs. The ethylenediamine platinum(II) moiety, herein called Lx, was coordinated to Desferal (DFO) or auristatin F (AF) to provide storable “semifinal” products, which were directly conjugated to unmodified mAbs. Conjugation resulted in ADCs with unimpaired mAb-binding characteristics, DAR in the range of 2.5 to 2.7 and approximately 85% payload bound to the Fc region, presumably to histidine residues. To evaluate the in vivo stability of Lx and its effect on pharmacokinetics and tumor targeting of an ADC, Lx-DFO was conjugated to the HER2 mAb trastuzumab, followed by radiolabeling with 89Zr. Trastuzumab-Lx-DFO-89Zr was stable in vivo and exhibited pharmacokinetic and tumor-targeting properties similar to parental trastuzumab. In a xenograft mouse model of gastric cancer (NCI-N87) or an ado-trastuzumab emtansine-resistant breast cancer (JIMT-1), a single dose of trastuzumab-Lx-AF outperformed its maleimide benchmark trastuzumab-Mal-AF and FDA-approved ado-trastuzumab emtansine. Overall, our findings show the potential of the Lx technology as a robust conjugation platform for the preparation of anticancer ADCs. Cancer Res; 77(2); 257–67. ©2016 AACR.
Natural Killer Cells to the Attack: Combination Therapy against Neuroblastoma
Authors: Zenarruzabeitia Olatz , Vitallé Joana , Astigarraga Itziar , Borrego Francisco
Published: November 2016

TGFβ in the tumor microenvironment diminishes natural killer (NK) cell–mediated anti-disialoganglioside (anti-GD2) mAb elimination of neuroblastoma cells. Consequently, blockade of TGFβ signaling with galunisertib in combination with the anti-GD2 mAb dinutuximab plus adoptively transferred NK cells is a promising tool for the treatment of neuroblastoma. Clin Cancer Res; 23(3); 615–7. ©2016 AACR.

See related article by Tran et al., p. 804
ОПИС КОРИСНОЇ МОДЕЛІ НА КЛІНІЧНИХ КАФЕДРАХ (ДЛЯ ОТРИМАННЯ ПАТЕНТУ УКРАЇНИ): АВТОРСЬКІ ПОГЛЯДИ)
Authors: Chopyak V. V. , Verhun A. R. , Yavorska O. Ya. , Verhun O. M.
Published: November 2016

Формулювання структурної схеми опису для отримання Патенту України на корисну модель на клінічних кафедрах здійснене згідно з вимогами  Державної служби інтелектуальної власності на основі стилістичного аналізу описів 12 патентів України, отриманих працівниками кафедр Львівського національного медичного університету імені Данила Галицького. Запропонований нами опис корисної моделі на клінічних кафедрах (для отримання Патенту України) сприятиме подоланню об’єктивних труднощів щодо адекватного послідовного описання клінічних спостережень, способів діагностики та лікування окремих захворювань згідно з вимогами, задекларованими для патентування.
ПРОБЛЕМА АКАДЕМІЧНОЇ ЧЕСНОСТІ В НАВЧАЛЬНОМУ ПРОЦЕСІ ТА НАУЦІ: ДОСВІД НАЦІОНАЛЬНОГО МЕДИЧНОГО УНІВЕРСИТЕТУ ІМЕНІ О. О. БОГОМОЛЬЦЯ
Authors: Stechenko O. V.
Published: November 2016

У статті проаналізовано досвід Національного медичного університету імені О. О. Богомольця з розробки та впровадження Положення про академічну чесність як важливого документа в рамках функціонування внутрішньовузівської системи управління якістю освіти. Наведено результати аналізу анонімного анкетування 412 респондентів щодо рівня  академічної культури та розповсюдження академічного шахрайства в різних формах. Виявлено, що 55 % студентів Університету самостійно складають підсумковий контроль з дисциплін навчального плану, в той час як визнали несамостійність у складанні сесії 16 % респондентів. Визначено важливість трансформації академічної культури науково-педагогічних працівників та студентів для забезпечення успішності євроінтеграційних змін освітнього процесу в країні.
A Estada em Pernambuco, em 1666, de François de Lopis, marquês de Mondevergue, segundo o relato de Souchu de Rennefort (1688): habitantes, costumes, escravidão, tapuias, comércio, animais e frutos, e a conjuração contra Jerônimo de Mendonça Furtado
Authors:   Universidade de São Paulo. Museu de Zoologia, Papavero Nelson , Almeida Argus Vasconcelos de ,   Universidade Federal Rural de Pernambuco, Teixeira Dante Martins ,   Universidade Federal do Rio de Janeiro. Museu Nacional
Published: November 2016

Relato da expedição da Companhia das Índias Orientais (Compagnie Françoise – ou Royale – des Indes Orientales).
Heart Rate Turbulence Is a Powerful Predictor of Cardiac Death and Ventricular Arrhythmias in Postmyocardial Infarction and Heart Failure Patients
Authors: Disertori Marcello , Masè Michela , Rigoni Marta , Nollo Giandomenico , Ravelli Flavia
Published: November 2016

Background—

Heart rate turbulence (HRT) has been proposed as a candidate marker of altered autonomic tone, and some studies showed its prognostic value for both cardiac death (CD) and sudden death. Nevertheless, HRT is not currently used in the clinical practice.

Methods and Results—

We performed a systematic review and meta-analysis of the predictive value of HRT for the end points of total mortality, CD, and fatal and nonfatal ventricular arrhythmias in postacute myocardial infarction and heart failure patients. MEDLINE and The Cochrane Library databases were systematically searched to identify studies, which analyzed the predictive value of abnormal HRT for the defined end points. Twenty studies (25 cohorts: 12 832 patients) were identified by the systematic review, and 15 studies (20 cohorts: 11 499 patients) were included in the meta-analyses. Abnormal HRT was a predictive marker for all the end points in heart failure patients and more markedly in postacute myocardial infarction patients, where 9 out of the 10 cohorts had an ejection fraction >30%. In postacute myocardial infarction patients, HRT had pooled risk ratios of 3.53 (95% confidence interval [CI], 2.54–4.90), 4.82 (95% CI, 3.12–7.45), and 4.48 (95% CI, 3.04–6.60), and positive likelihood ratios of 3.5 (95% CI, 2.6–4.8), 4.1 (95% CI, 3.0–5.7), and 2.7 (95% CI, 2.2–3.3) for total mortality, CD, and arrhythmic events, respectively. The combination of abnormal HRT and T-wave alternans (5 cohorts: 1516 patients) increased the predictive power for CD and arrhythmic events.

Conclusions—

HRT is a powerful predictor of both CD and arrhythmic events, particularly in postacute myocardial infarction patients with ejection fraction >30%. HRT power increases in combination with T-wave alternans analysis.
Contribution of K
V
1.5 Channel to Hydrogen Peroxide–Induced Human Arteriolar Dilation and Its Modulation by Coronary Artery Disease
Authors: Nishijima Yoshinori , Cao Sheng , Chabowski Dawid S. , Korishettar Ankush , Ge Alyce , Zheng Xiaodong , Sparapani Rodney , Gutterman David D. , Zhang David X.
Published: November 2016

Rationale:

Hydrogen peroxide (H
2
O
2
) regulates vascular tone in the human microcirculation under physiological and pathophysiological conditions. It dilates arterioles by activating large-conductance Ca
2+
-activated K
+
channels in subjects with coronary artery disease (CAD), but its mechanisms of action in subjects without CAD (non-CAD) when compared with those with CAD remain unknown.

Objective:

We hypothesize that H
2
O
2
-elicited dilation involves different K
+
channels in non-CAD versus CAD, resulting in an altered capacity for vasodilation during disease.

Methods and Results:

H
2
O
2
induced endothelium-independent vasodilation in non-CAD adipose arterioles, which was reduced by paxilline, a large-conductance Ca
2+
-activated K
+
channel blocker, and by 4-aminopyridine, a voltage-gated K
+
(K
V
) channel blocker. Assays of mRNA transcripts, protein expression, and subcellular localization revealed that K
V
1.5 is the major K
V
1 channel expressed in vascular smooth muscle cells and is abundantly localized on the plasma membrane. The selective K
V
1.5 blocker diphenylphosphine oxide-1 and the K
V
1.3/1.5 blocker 5-(4-phenylbutoxy)psoralen reduced H
2
O
2
-elicited dilation to a similar extent as 4-aminopyridine, but the selective K
V
1.3 blocker phenoxyalkoxypsoralen-1 was without effect. In arterioles from CAD subjects, H
2
O
2
-induced dilation was significantly reduced, and this dilation was inhibited by paxilline but not by 4-aminopyridine, diphenylphosphine oxide-1, or 5-(4-phenylbutoxy)psoralen. K
V
1.5 cell membrane localization and diphenylphosphine oxide-1–sensitive K
+
currents were markedly reduced in isolated vascular smooth muscle cells from CAD arterioles, although mRNA or total cellular protein expression was largely unchanged.

Conclusions:

In human arterioles, H
2
O
2
-induced dilation is impaired in CAD, which is associated with a transition from a combined large-conductance Ca
2+
-activated K
+
- and K
V
(K
V
1.5)-mediated vasodilation toward a large-conductance Ca
2+
–activated K
+
–predominant mechanism of dilation. Loss of K
V
1.5 vasomotor function may play an important role in microvascular dysfunction in CAD or other vascular diseases.
Experimental, Systems, and Computational Approaches to Understanding the MicroRNA-Mediated Reparative Potential of Cardiac Progenitor Cell–Derived Exosomes From Pediatric Patients
Authors: Agarwal Udit , George Alex , Bhutani Srishti , Ghosh-Choudhary Shohini , Maxwell Joshua T. , Brown Milton E. , Mehta Yash , Platt Manu O. , Liang Yaxuan , Sahoo Susmita , Davis Michael E.
Published: November 2016

Rationale
:

Studies have demonstrated that exosomes can repair cardiac tissue post–myocardial infarction and recapitulate the benefits of cellular therapy.

Objective
:

We evaluated the role of donor age and hypoxia of human pediatric cardiac progenitor cell (CPC)–derived exosomes in a rat model of ischemia–reperfusion injury.

Methods and Results
:

Human CPCs from the right atrial appendages from children of different ages undergoing cardiac surgery for congenital heart defects were isolated and cultured under hypoxic or normoxic conditions. Exosomes were isolated from the culture-conditioned media and delivered to athymic rats after ischemia–reperfusion injury. Echocardiography at day 3 post–myocardial infarction suggested statistically improved function in neonatal hypoxic and neonatal normoxic groups compared with saline-treated controls. At 28 days post–myocardial infarction, exosomes derived from neonatal normoxia, neonatal hypoxia, infant hypoxia, and child hypoxia significantly improved cardiac function compared with those from saline-treated controls. Staining showed decreased fibrosis and improved angiogenesis in hypoxic groups compared with controls. Finally, using sequencing data, a computational model was generated to link microRNA levels to specific outcomes.

Conclusions
:

CPC exosomes derived from neonates improved cardiac function independent of culture oxygen levels, whereas CPC exosomes from older children were not reparative unless subjected to hypoxic conditions. Cardiac functional improvements were associated with increased angiogenesis, reduced fibrosis, and improved hypertrophy, resulting in improved cardiac function; however, mechanisms for normoxic neonatal CPC exosomes improved function independent of those mechanisms. This is the first study of its kind demonstrating that donor age and oxygen content in the microenvironment significantly alter the efficacy of human CPC-derived exosomes.