bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Analysis of Elderly Patients with Multiple Organ Dysfunction Syndrome Undergoing Invasive Mechanical Ventilation
Authors: Xiao Kun , Liu Bin , Guan Wei , Yan Peng , Song Licheng , Wang Yue , Xie Lixin
Published: March 2020

Objective. To prospectively investigate early prognostic assessments of patients with Multiple Organ Dysfunction Syndrome in the Elderly (MODSE) who were receiving invasive mechanical ventilation (IMV). Methods. The clinical data of 351 patients were enrolled prospectively between January 2013 and January 2018. The Acute Physiology and Chronic Health Evaluation II (APACHE II), APACHE III, Simplified Acute Physiology Score (SAPS II), and Multiple Organ Dysfunction Score (MODS) were calculated. According to the outcome of 28-day, the patients were divided into survivors and nonsurvivors. Additionally, based on whether weaning could be implemented, all patients were divided into a successful-weaning group and a failure-to-wean group. Results. According to the prognosis, the areas under the receiver operating characteristic curve of the APACHE II, APACHE III, SAPS II, and MODS scoring systems were 0.837, 0.833, 0.784, and 0.860, respectively. MODS exhibited the highest sensitivity, whereas APACHE II showed the highest specificity, and successful weaning was conducive to ameliorating patients’ prognosis. Multivariate logistic regression analyses revealed that underlying lung disease, plasma albumin, serum creatinine level, number of failing organs, and IMV duration were related to prognosis of weaning, with odds ratios (ORs) of 1.447, 0.820, 1.603, 2.374, and 3.105, respectively. Conclusions. The APACHE II, APACHE III, SAPS II, and MODS systems could perform excellent prognostic assessment for patients with Multiple Organ Dysfunction Syndrome in the elderly. Underlying lung disease, plasma albumin, serum creatinine, number of failing organs, and IMV duration were independent prognostic factors of weaning in MODSE patients with invasive mechanical ventilation.
Friedman Score in Relation to Compliance and Treatment Response in Nonsevere Obstructive Sleep Apnea
Authors: Berg Lars M. , Ankjell Torun K. S. , Sun Yi-Qian , Trovik Tordis A. , Sjögren Anders , Rikardsen Oddveig G. , Moen Ketil , Hellem Sølve , Bugten Vegard
Published: March 2020

Nonsevere obstructive sleep apnea (OSA) is most often treated with a continuous positive airway pressure (CPAP) device or a mandibular advancement splint (MAS). However, patient compliance with these treatments is difficult to predict. Improvement in apnea-hypopnea index (AHI) is also somewhat unpredictable in MAS treatment. In this study, we investigated the association between Friedman tongue position score (Friedman score) and both treatment compliance and AHI improvement in patients with nonsevere OSA receiving CPAP or MAS treatment. 104 patients with nonsevere OSA were randomly allocated to CPAP or MAS treatment and followed for 12 months. Data were collected through a medical examination, questionnaires, sleep recordings from ambulatory type 3 polygraphic sleep recording devices, and CPAP recordings. Associations between Friedman score, treatment compliance, and AHI improvement were analysed with logistic regression analyses. Friedman score was not associated with treatment compliance (odds ratio [OR]: 0.85, 95% confidence interval [CI]: 0.59–1.23), or AHI improvement (OR: 1.05, 95% CI: 0.62–1.76) in the overall study sample, the CPAP treatment group, or the MAS treatment group. Adjustment for socioeconomic factors, body mass index, and tonsil size did not significantly impact the results. Although Friedman score may predict OSA severity and contribute to the prediction of success in uvulopalatopharyngoplasty, we found no association between Friedman score and treatment compliance in patients with nonsevere OSA receiving CPAP or MAS treatment, nor did we find any association between Friedman score and AHI improvement. Factors other than Friedman score should be considered when deciding whether a patient with nonsevere OSA should be treated with CPAP or MAS.
Influence of Anisotropy and Nonhomogeneity on Stability Analysis of Fissured Slopes Subjected to Seismic Action
Authors: Liu Zhidan , Zhang Jingwu , Chen Weiping , Wu Di
Published: March 2020

Based on the upper bound theorem of limit analysis, this paper presents a procedure for assessment of the influence of the soil anisotropy and nonhomogeneity on the stability of fissured slopes subjected to seismic action. By means of a mathematical optimization procedure written in Matlab software codes, the stability factorsNSandλcφare derived with respect to the best upper bound solutions. A series of stability charts are obtained in this paper, and then the critical locations of cracks are determined for cracks of known depth. The results demonstrate a significant influence of the soil anisotropy and nonhomogeneity on the stability of the fissured slopes and the location distribution of the cracks. In addition, the procedures for getting the factor of safety are put forward. It is shown that a decrease in the nonhomogeneity coefficientn0and an increase in the anisotropy coefficientkcould lead to the fissured slopes becoming unsafe. Finally, this article also illustrates the variation in the safety factor of fissured slopes under the impact of three factors (Kh,H1/H, andλ).
miR-210 in Exosomes Derived from Macrophages under High Glucose Promotes Mouse Diabetic Obesity Pathogenesis by Suppressing NDUFA4 Expression
Authors: Tian Feng , Tang Ping , Sun Zhilian , Zhang Ruifen , Zhu Danhua , He Junying , Liao Jixing , Wan Qinghua , Shen Jie
Published: March 2020

Objective. Type 2 diabetes mellitus (T2DM) is featured by insulin resistance and lipid metabolism dysregulation. A large number of miRNAs were identified in exosomes derived from adipose tissue macrophages associated with T2DM pathogenesis, but its pathogenic roles remain unknown. This study is aimed at investigating the function of miR-210 in diabetic obesity. Methods. Exosomes from mouse macrophage RAW264.7 cells were characterized by electron microscopy, combined with biomarker expression by western blot. Expression of miR-210 was determined by quantitative RT-PCR. Glucose uptake was measured by a fluorometric method, and the mitochondrial respiratory chain activity was evaluated by ELISA. The target gene of miR-210 was validated by dual-luciferase reporter and pull-down assays. A mouse obese diabetic model was established by a high-fat diet and streptozocin treatment. Results. miR-210 was highly expressed in exosomes derived from high glucose-induced macrophage RAW264.7 cells. Macrophage-derived exosomes impaired glucose uptake and mitochondrial CIV complex activity and suppressed NADH dehydrogenase ubiquinone 1 alpha subcomplex 4 (NDUFA4) expression in 3T3-L1 adipocytes. miR-210 directly bind with mRNA sequences of NDUFA4 gene. Inhibition of miR-210 mitigated the effects of macrophage-derived exosomes on the glucose uptake and complex IV (CIV) activity in 3T3-L1 adipocytes, and NDUFA4 overexpression offset the inhibition of glucose uptake and CIV activity by macrophage-derived exosomes. Furthermore, mice with miR-210 knockout showed greatly repressed diabetic obesity development. Conclusion. miR-210 derived from adipose tissue macrophages promotes mouse obese diabetes pathogenesis by regulating glucose uptake and mitochondrial CIV activity through targeting NDUFA4 gene expression.
Spectrum Sharing with Vehicular Communication in Cognitive Small-Cell Networks
Authors: Wu Guilu , Chu Hongyun
Published: March 2020

An increasing number of vehicles make spectrum resources face serious challenges in vehicular cognitive small-cell networks. The means of spectrum sharing can greatly alleviate this pressure. In this paper, we introduce a supermodular game theoretic approach to analyze the problem of spectrum sharing. The small-cell BS (primary service provider, PSP) and the vehicle (secondary service provider, SSP) can share the spectrum, where the PSP can sell idle spectrum resources to the SSP. This is taken as a spectrum trading market, and a Bertrand competition model is considered to depict this phenomenon. Different PSPs compete with each other to maximize their individual profits. The Bertrand competition model can be proved as a supermodular game, and the corresponding Nash equilibrium (NE) solution is provided as the optimal price solution. Hence, an improved genetic simulated annealing algorithm is designed to achieve NE. Simulation results demonstrate that the NE point for the price of the primary service provider exists. The change of the exogenous variable is also analyzed on the equilibrium point.
Metastatic Small-Cell Lung Cancer Presenting as Primary Adrenal Insufficiency
Authors: Esperti Shawn , Stoelting Austen , Scibelli Nicolina , Moccia David , Patel Dveet , Haughton Michael , Mangano Andrew
Published: March 2020

A 40-year-old male smoker with HIV was admitted for cough, hypotension, and abdominal pain for 5 days. Chest radiography showed a right lower lobe consolidation. CT of the chest, abdomen, and pelvis revealed paratracheal adenopathy, a 5.8×4.5 cm mass invading the right bronchus intermedius, and dense bilateral adrenal masses, measuring 5.4×4.0 cm on the right and 4.8×2.0 cm on the left. Laboratory studies showed white blood cell count of 18.5 K/mm3, sodium of 131 mmol/L, creatinine of 1.6 mg/dL, and CD4 count of 567 cells/mm3. The random morning cortisol level was 7.0 μg/dL, the ACTH stimulation test yielded inappropriate response, and a random serum ACTH was elevated at 83.4 pg/mL. MRI brain revealed no pituitary adenoma confirming primary adrenal insufficiency. The adrenal CT washout study was consistent with solid mass content, concerning for metastasis. Bronchoscopy with endobronchial mass and paratracheal lymph node biopsy confirmed small-cell lung cancer (SCLC). Intravenous steroids, 100 mg hydrocortisone every 8 hours, improved his hypotension and abdominal pain. PET scan revealed metabolically active right paratracheal mass, right hilar mass, and bilateral adrenal masses. Treatment included palliative chemotherapy consisting of carboplatin/etoposide/atezolizumab and chest radiation. We present this novel case to demonstrate SCLC’s ability to cause primary adrenal insufficiency, as well as evaluate clinical response to chemotherapeutics.
20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats
Authors: Zhou Tong , Sun Lin , Yang Shuo , Lv You , Cao Yue , Gang Xiaokun , Wang Guixia
Published: March 2020

20(S)-Ginsenoside Rg3 (20(S)-Rg3) has been shown to induce apoptosis by interfering with several signaling pathways. Furthermore, it has been reported to have anticancer and antidiabetic effects. In order to detect the protective effect of 20(S)-Rg3 on diabetic kidney disease (DKD), diabetic rat models which were established by administering high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ), and age-matched wild-type (WT) rat were given 20(S)-Rg3 for 12 weeks, with three groups: control group (normal adult rats with saline), diabetic group (diabetic rats with saline), and 20(S)-Rg3 treatment group (diabetic rats with 20(S)-Rg3 (10 mg/kg body weight/day)). The biochemical indicators and the changes in glomerular basement membrane and mesangial matrix were detected. TUNEL staining was used to detect glomerular and renal tubular cell apoptosis. Immunohistochemical staining was used to detect the expression of fibrosis factors and inflammation factors in rat kidney tissues. Through periodic acid-Schiff staining, we observed that the change in renal histology was improved and renal tubular epithelial cell apoptosis decreased significantly by treatment with 20(S)-Rg3. Plus, the urine protein decreased in the rats with the 20(S)-Rg3 treatment. Fasting blood glucose, creatinine, total cholesterol, and triglyceride levels in the 20(S)-Rg3 treatment group were all lower than those in the diabetic group. Mechanistically, 20(S)-Rg3 dramatically downregulated the expression of TGF-β1, NF-κB65, and TNF-α in the kidney. These resulted in a significant prevention of renal damage from the inflammation. The results of the current study suggest that 20(S)-Rg3 could potentially be used as a novel treatment against DKD.
Indole-3-carbaldehyde Semicarbazone Derivatives: Synthesis, Characterization, and Antibacterial Activities
Authors: Carrasco Fernando , Hernández Wilfredo , Chupayo Oscar , Álvarez Celedonio M. , Oramas-Royo Sandra , Spodine Evgenia , Tamariz-Angeles Carmen , Olivera-Gonzales Percy , Dávalos Juan Z.
Published: March 2020

Four indole-3-carbaldehyde semicarbazone derivatives, 2-((5-bromo-1H-indol-3-yl)methylene)hydrazinecarboxamide (1), 2-((5-chloro-1H-indol-3-yl)methylene)hydrazinecarboxamide (2), 2-((5-methoxy-1H-indol-3-yl)methylene)hydrazinecarboxamide (3), and 2-((4-nitro-1H-indol-3-yl)methylene)hydrazinecarboxamide (4) were synthesized and characterized by ESI-MS and spectroscopic (FT-IR, 1H NMR, and 13C NMR) techniques. The two-dimensional NMR (in acetone-d6) spectral data revealed that the molecules 1 and 2 in solution are in the cisE isomeric form. This evidence is supported by DFT calculations at the B3LYP/6-311++G(d,p) level of theory where it was shown that the corresponding most stable conformers of the synthesized compounds have a cisE geometrical configuration, in both the gas and liquid (acetone and DMSO) phases. The in vitro antibacterial activity of compounds 1–4 was determined against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria. Among all the tested semicarbazones, 1 and 2 exhibited similar inhibitory activities against Staphylococcus aureus (MIC = 100 and 150 μg/mL, respectively) and Bacillus subtilis (MIC = 100 and 150 μg/mL, respectively). On the other hand, 3 and 4 were relatively less active against the tested bacterial strains compared with 1, 2, and tetracycline.
West Nile Virus Vaccine Design by T Cell Epitope Selection: In Silico Analysis of Conservation, Functional Cross-Reactivity with the Human Genome, and Population Coverage
Authors: Waller Frances M. , Reche Pedro A. , Flower Darren R.
Published: March 2020

West Nile Virus (WNV) causes a debilitating and life-threatening neurological disease in humans. Since its emergence in Africa 50 years ago, new strains of WNV and an expanding geographical distribution have increased public health concerns. There are no licensed therapeutics against WNV, limiting effective infection control. Vaccines represent the most efficacious and efficient medical intervention known. Epitope-based vaccines against WNV remain significantly underexploited. Here, we use a selection protocol to identify a set of conserved prevalidated immunogenic T cell epitopes comprising a putative WNV vaccine. Experimentally validated immunogenic WNV epitopes and WNV sequences were retrieved from the IEDB and West Nile Virus Variation Database. Clustering and multiple sequence alignment identified a smaller subset of representative sequences. Protein variability analysis identified evolutionarily conserved sequences, which were used to select a diverse set of immunogenic candidate T cell epitopes. Cross-reactivity and human leukocyte antigen-binding affinities were assessed to eliminate unsuitable epitope candidates. Population protection coverage (PPC) quantified individual epitopes and epitope combinations against the world population. 3 CD8+ T cell epitopes (ITYTDVLRY, TLARGFPFV, and SYHDRRWCF) and 1 CD4+ epitope (VTVNPFVSVATANAKVLI) were selected as a putative WNV vaccine, with an estimated PPC of 97.14%.
Morphological Aspects of Antennal Sensilla of theRhodnius brethesiMatta, 1919 (Hemiptera: Reduviidae) from the Negro River, Amazon Region of Brazil
Authors: Freitas Simone Patrícia Carneiro , Santos Laura Cristina , de Souza Amanda Coutinho , Junqueira Angela Cristina Verissimo
Published: March 2020

Studies conducted in river Ererê located in the left margin of Negro River, municipality of Barcelos, state of Amazonas, have confirmed thatRhodnius brethesihas as its natural habitat the palm treeLeopoldinia piassaba. By scanning electron microscopy, sensillum type was studied on the antennae ofR. brethesi. The specimens used come from the field and laboratory colony. No differences were observed betweenR. brethesiand other Triatominae studied. In theR. brethesiantennas, differences were observed only between the antennal segments and in the dorsal and ventral portions. Trichobothria sensilla show a difference with a lamellar base, suggesting that this conformation of the base of the sensilla is a synapomorphic feature of the genus. Another important observation is that, considering thatR. brethesiis a specialist, infesting only one type of palm tree, trichoidea sensilla may be involved with plant-derived odorants. The knowledge of such functions could benefit the understanding of the likely biological role of these structures in chemical communication and also provide basic information for future studies of niche recognition, since this species of triatomine is only found in theL. piassabapalm.
Advances in Nanoscale Study of Organomineral Complexes of Termite Mounds and Associated Soils: A Systematic Review
Authors: Eze Peter N. , Kokwe Atlasaone , Eze Juliet U.
Published: March 2020

Termite mounds are replete with natural nanoparticles, and they vary in physicochemical, geochemical, mineralogical, and biological properties from the adjoining soils. Although termite mounds have wide ecological and environmental roles including soil formation, faunal and vegetation growth and diversity, organic matter decomposition, geochemical exploration, water survey, treatment of underground contamination, thermoregulation, gas exchange, and global climate change, their nanoscale structures made by the associated organomineral complexes are still poorly understood because of technical limitations. In this review, we highlight the ecological and environmental significance of termite mounds and the documented techniques that have been successfully used to study nanostructure of termite mounds, namely, midinfrared spectroscopy (MIRS), photogrammetry and cross-sectional image analysis, a combination of transmission electron microscopy (TEM) and pyrolysis field ionization mass spectrometry (Py-FIMS), scanning transmission X-ray microscopy (STXM) using synchrotron radiation in conjunction with near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, and high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) for further appraisals. There is a need to continually develop and integrate nanotechnology with the routine classical soil analysis methods to improve our understanding of the functional mechanisms of nanostructure of termite mounds that are responsible for specific properties. In view of the numerous roles termite mounds play in the environments, agriculture, and engineering, there is no better time to channel much research into understanding how they function at nanoscale.
Association of Cost and Medical Service Satisfaction with Korean and Conventional Medicine Use before and after Surgery in Postsurgical Patients: A Questionnaire Survey of Korean Patients with Postsurgical Pain Visiting Korean Medicine Hospitals
Authors: Lee Ki-Beom , Lee Yoon Jae , Kim Me-riong , Shin Kyung-Min , Ha In-Hyuk
Published: March 2020

This study aimed to assess the costs, health status, and medical service satisfaction with Korean and conventional medicine use before and after surgery of patients visiting Korean medicine hospitals for postsurgical musculoskeletal pain. The study population comprised patients who visited KM hospitals for the first time between June and November 2017 for persistent or recurrent pain and discomfort after low back, neck, shoulder, or knee surgery. Various validated questionnaires were used to collect data. A total of 100 participants were enrolled, and the majority had undergone low back surgery (n = 82). The participants had received 1.3 ± 0.7 magnetic resonance imaging (MRI) examinations and 2.4 ± 2.8 X‐rays before surgery. Conventional interventions used before surgery were physical therapy (43%), medications (34%), and injections (28%), in descending order, while 48% of patients reported having received acupuncture 51.3 ± 81.1 times. The mean satisfaction score for surgery was 5.5 ± 2.8 points based on a 9‐point Likert scale, while that for KM‐based interventions was 6.3 ± 1.7 points. With respect to health‐related information, the mean scores were 6.0 ± 2.2 points on the Numeric Rating Scale (NRS), 0.6 ± 0.2 points on the 5‐Level EuroQol‐5 Dimension (EQ‐5D‐5L), and 15.3 ± 10.2 on Beck’s Depression Index II (BDI‐II). The mean score on the Oswestry Disability Index (ODI) in patients with low back pain was 40.1 ± 19.2 points. Work impairment, as measured using the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI‐GH), was 62.5 ± 47.8%, while activity impairment was 5.9 ± 2.6%. Participants tended to show low satisfaction regarding surgery and high preference for KM‐based interventions. In particular, low back surgery patients reported high ODI scores, indicating high dysfunctional levels and poor prognosis after surgery. It can be inferred that it is therefore important to provide appropriate presurgical and postsurgical care for patients with musculoskeletal pain to improve pain, function, and quality of life.
Thermal Lattice Boltzmann Model for Nonisothermal Gas Flow in a Two-Dimensional Microchannel
Authors: Elguennouni Youssef , Hssikou Mohamed , Baliti Jamal , Alaoui Mohammed
Published: March 2020

In this paper, the Thermal Lattice Boltzmann Method (TLBM) is used for the simulation of a gas microflow. A 2D heated microchannel flow driven by a constant inlet velocity profile Uin and nonisothermal walls is investigated numerically. Two cases of micro-Poiseuille flow are considered in the present study. In the first case, the temperature of the walls is kept uniform, equal to zero; therefore, the gas is driven along the channel under the inlet parameters of velocity and temperature. However, in the second one, the gas flow is also induced by the effect of temperature decreasing applied on the walls. For consistent results, velocity slip and temperature jump boundary conditions are used to capture the nonequilibrium effects near the walls. The rarefaction effects described by the Knudsen number, on the velocity and temperature profiles are evaluated. The aim of this study is to prove the efficiency of the TLBM method to simulate Poiseuille flow in case of nonisothermal walls, based on the average value of the Nusselt number and by comparing the results obtained from the TLBM with those obtained using the Finite Difference Method (FDM). The results also show an interesting sensitivity of velocity and temperature profiles with the rarefaction degree and the imposed temperature gradient of the walls.
On the Dimensional Consistency Aware Fractional Domain Generalization of Simplest Chaotic Circuits
Authors: Banchuin Rawid
Published: March 2020

In this research, we generalize the simplest Chua’s chaotic circuit which is even more simpler than the four-element Chua’s circuit in terms of number of elements and the novel simplest chaotic circuit in the fractional domain by using the fractional circuit elements. Unlike the previous works, the time dimensional consistency aware generalization has been performed for the first time in this work. The dynamics of the generalized fractional nonlinear circuits have been analyzed by means of the fractional calculus based on the modified Riemann–Liouville fractional derivative where the Lyapunov exponents and dimensions have also been numerically calculated. We have found that including the dimensional consistency significantly alters the dynamic of the obtained fractional domain Chua’s circuit from that of the previous dimensional consistency ignored counterpart as different Lyapunov exponents and dimensions can be obtained. The conditions for both fractional domain circuits which cease to be chaotic have also been determined where such condition of Chua's circuit presented in this study is different from that of the previous work. This is because the time dimensionalconsistency has been included. The dynamical analyses of these circuits have also been performed where their conditions for being nonchaotic have been verified. Moreover, their emulators have also been realized.
LncSpA: LncRNA Spatial Atlas of Expression across Normal and Cancer Tissues
Authors: Lv Dezhong , Xu Kang , Jin Xiyun , Li Junyi , Shi Yuchen , Zhang Mengying , Jin Xiaoyan , Li Yongsheng , Xu Juan , Li Xia
Published: March 2020

Long noncoding RNAs (lncRNA) play important roles in maintaining morphology and function of tissues, and their regulatory effectiveness is closely associated with spatial expression. To provide a comprehensive spatial atlas of expression for lncRNA, we propose LncSpA (http://bio-bigdata.hrbmu.edu.cn/LncSpA) to explore tissue-elevated (TE) lncRNA across human normal and adult and pediatric cancer tissues. In total, 71,131 and 12,007 TE lncRNAs and 634 clinical-related TE lncRNAs were identified across 38 normal and 33 adult cancer tissues. Moreover, 4,688 TE and 413 clinical-related lncRNAs were identified in pediatric cancer. By quick searching or query options, users can obtain eight major types of detailed information for lncRNA via various visualization techniques, including qualitative and quantitative spatial expression in different resources, coexpressed mRNAs, predicted function, known disease association, and the potential to serve as diagnostic or prognostic markers. LncSpA will be a valuable resource to understand lncRNA functions across tissues and cancers, leading to enhanced therapeutic strategies in precision oncology.

Significance:

LncSpA is a new interactive resource that provides the spatial expression pattern of lncRNA across thousands of normal and cancer samples representing major tissue types.
The Evolutionary Origins of Recurrent Pancreatic Cancer
Authors: Sakamoto Hitomi , Attiyeh Marc A. , Gerold Jeffrey M. , Makohon-Moore Alvin P. , Hayashi Akimasa , Hong Jungeui , Kappagantula Rajya , Zhang Lance , Melchor Jerry P. , Reiter Johannes G. , Heyde Alexander , Bielski Craig M. , Penson Alexander V. , Gönen Mithat , Chakravarty Debyani , O'Reilly Eileen M. , Wood Laura D. , Hruban Ralph H. , Nowak Martin A. , Socci Nicholas D. , Taylor Barry S. , Iacobuzio-Donahue Christine A.
Published: March 2020

Surgery is the only curative option for stage I/II pancreatic cancer; nonetheless, most patients will experience a recurrence after surgery and die of their disease. To identify novel opportunities for management of recurrent pancreatic cancer, we performed whole-exome or targeted sequencing of 10 resected primary cancers and matched intrapancreatic recurrences or distant metastases. We identified that recurrent disease after adjuvant or first-line platinum therapy corresponds to an increased mutational burden. Recurrent disease is enriched for genetic alterations predicted to activate MAPK/ERK and PI3K–AKT signaling and develops from a monophyletic or polyphyletic origin. Treatment-induced genetic bottlenecks lead to a modified genetic landscape and subclonal heterogeneity for driver gene alterations in part due to intermetastatic seeding. In 1 patient what was believed to be recurrent disease was an independent (second) primary tumor. These findings suggest routine post-treatment sampling may have value in the management of recurrent pancreatic cancer.

Significance:

The biological features or clinical vulnerabilities of recurrent pancreatic cancer after pancreaticoduodenectomy are unknown. Using whole-exome sequencing we find that recurrent disease has a distinct genomic landscape, intermetastatic genetic heterogeneity, diverse clonal origins, and higher mutational burden than found for treatment-naïve disease.

See related commentary by Bednar and Pasca di Magliano, p. 762.

This article is highlighted in the In This Issue feature, p. 747
Desensitization in Iron Product Allergy
Authors: Di Girolamo Attilio , Albanesi Marcello , Loconte Filomena , Di Bona Danilo , Caiaffa Maria Filomena , Macchia Luigi
Published: March 2020

Iron deficiency is the main cause of anemia in both sexes, with women being more commonly affected. Iron therapy is currently considered an effective and safe remedy to replenish the iron storages. Iron can be administrated both orally and intravenously. In particular, intravenous (IV) iron therapy is widely used when oral iron preparations are either not tolerated or ineffective. Indeed, IV iron improves iron stores more rapidly. Two main immunological responses have been described for iron hypersensitivity reactions (HSRs): IgE-mediated allergy and complement activation-related pseudo-allergy. Here, we report 3 cases of adult patients with iron allergy, who were successfully treated with two different desensitization procedures, respectively. Analysis of these cases demonstrates that, in the presence of HSRs to iron products, desensitization is an effective and safe procedure that prevents treatment discontinuation and hence allows therapeutic target achievement.
Efficacy of Laparoscopic Partial Cystectomy with a Transurethral Resectoscope in Patients with Bladder Endometriosis: See-Through Technique
Authors: Endo Yuki , Akatsuka Jun , Obayashi Kotaro , Takeda Hayato , Hayashi Tatsuro , Nakayama Satoko , Suzuki Yasutomo , Hamasaki Tsutomu , Kondo Yukihiro
Published: March 2020

Purpose: Bladder endometriosis (BE) is rare. Deep invasive endometriosis is difficult to control with medications alone; such cases need surgical treatment. Good results of laparoscopic partial cystectomy with a transurethral (TU) resectoscope by the see-through technique for patients with BE are reported. Materials and Methods: From January 2008 to February 2016, 12 cases of symptomatic BE were seen in our institution. The chief complaints of 9 cases were micturition pain during menstruation. Preoperative cystoscopy showed a bladder mass with blueberry spots. All surgeries were performed under general anesthesia. Laparoscopic surgery was performed with a fan of 4 ports in the lower abdomen. First, the uterus and bilateral ovaries were checked. Then, the TU resectoscope was inserted. When the affected bladder wall was identified, it was again observed with the laparoscopic light source off, which made it possible to observe the twilight leaking inside from the bladder. This twilight came from the light source of the TU resectoscope via the unaffected bladder wall. In contrast, the thickness of the affected wall prevented the light from inside the bladder from passing through it. We call this the “see-through technique.” The tumor was then safely dissected with both laparoscopic and TU resection procedures. Finally, the bladder was sutured by laparoscopic procedures using absorbable sterile surgical suture. The urethral catheter was removed after cystography 7 days after the operation. Results: The surgical margins of all cases were negative. There has been no recurrence of BE so far in any patients. There were no major adverse events perioperatively and the urinary symptoms improved in all cases. Conclusions: By laparoscopic partial cystectomy assisted with a TU resectoscope and see-through technique, the edge of BE could be easily and precisely identified. These procedures are effective and safe for BE surgical treatment.
Increased Quinolone-Resistant Mutations of gyrA and parC Genes after Pouchitis Treatment with Ciprofloxacin
Authors: Fukushima Kouhei , Saito Takashi , Kohyama Atsushi , Watanabe Kazuhiro
Published: March 2020

Background: Oral antibiotics, such as ciprofloxacin (CFX), are widely used for the treatment of acute and chronic pouchitis. Most bacterial mutations that confer quinolone resistance are at Ser-83 and Asp-87 in the gyrA gene and Ser-80 and Glu-84 in the parC gene. Methods: We obtained 51 stool samples from 43 patients who were diagnosed with ulcerative colitis and underwent ileal pouch-anal anastomosis. Patients were divided into 2 groups: 13 patients with CFX treatment of pouchitis and 30 patients without pouchitis. After extraction of fecal DNA, the amount of Escherichia coli 16S rRNA, gyrA, and parC gene DNA were measured using real-time polymerase chain reaction (PCR). Possible mutations at gyrA 83 and 87 and at parC 80 and 84 were investigated by PCR cloning and sequencing, and mutation rates were quantified by rapid PCR-restriction fragment length polymorphism. Results: Samples from both CFX-treated and -untreated patients had comparable levels of gyrA and parC gene DNA. Nucleic acid and amino acid mutations were identified at gyrA 83 and 87, and at parC 80 and 84. We successfully quantified mutation rates at gyrA 83 and 87, and at parC 84, all of which were significantly higher in samples from CFX-treated patients (70, 84, and 38%) than from CFX-untreated patients (13, 11, and 5%). Conclusion: E. coli in patient pouches may have mutations in their gyrA and parC genes that produce CFX resistance. Mutation rates of these genes were significantly higher in samples from CFX-treated patients. This study contributes to understanding the decrease and loss of CFX effectiveness against pouchitis.
Evaluation of Systemic Inflammatory Response and Nutritional Biomarkers as Predictive Factors in Patients with Recurrent Gastric Cancer
Authors: Namikawa Tsutomu , Yokota Keiichiro , Yamaguchi Sachi , Iwabu Jun , Munekage Masaya , Uemura Sunao , Tsujii Shigehiro , Maeda Hiromichi , Kitagawa Hiroyuki , Kumon Masamitsu , Kobayashi Michiya , Hanazaki Kazuhiro
Published: March 2020

Background: The present study sought to evaluate host-related factors as predictors in patients receiving chemotherapy for recurrent advanced gastric cancer. Methods: Sixty-three patients were enrolled in the study and received chemotherapy for recurrent gastric cancer at the Kochi Medical School from 2008 to 2015. Clinicopathological information and systemic inflammatory response data were obtained retrospectively to investigate associations between baseline cancer-related prognostic variables and survival outcomes. Results: The median survival time was significantly higher for patients with a Glasgow prognostic score (GPS) of 0 compared to a GPS of 1 or 2 (18.2 vs. 7.1 months; p = 0.006), and for patients in the normal range for carbohydrate antigen-125 (CA125) compared to higher levels (17.9 vs. 4.1 months; p = 0.003). There was no significant influence on overall survival by age, gender, disease status, metastatic site, time to recurrence, carcinoembryonic antigen level, CA19–9 level, prognostic nutrition index, or neutrophil to lymphocyte ratio according to the results of the univariate log-rank tests. Multivariate survival analysis identified a GPS of 1 or 2 (hazard ratio, 3.520; 95% confidence interval, 1.343–9.227; p = 0.010) and a high CA125 level (hazard ratio, 3.135; 95% confidence interval, 1.276–7.697; p = 0.013) as significant independent predictors associated with a poorer prognosis in the studied group of cancer patients. Conclusions: A GPS of 1 or 2 and a high level of CA125 are independent predictors of a poorer prognosis in patients receiving chemotherapy for recurrent gastric cancer.
Relapsing and Progressive Complications of Severe Hypertriglyceridemia: Effective Long-Term Treatment with Double Filtration Plasmapheresis
Authors: Grupp Clemens , Beckermann Johannes , Köster Eric , Zewinger Stephen , Knittel Markus , Walek Tilman , Hohenstein Bernd , Jaeger Beate , Spitthöver Ralf , Klingel Reinhard , Fassbender Cordula M. , Tyczynski Bartosz
Published: March 2020

Background: Severe hypertriglyceridemia (HTG) is associated with major complications such as acute or relapsing pancreatitis (AP) and atherosclerotic cardiovascular disease (ASCVD). Rapid elimination of triglyceride (TG)-rich lipoproteins (LP) with double filtration plasmapheresis (DFPP) without need for substitution has been found to be effective for the acute, short-term treatment of HTG-induced AP. Data on the long-term use of DFPP to prevent HTG-associated complications are scarce. Objectives: To evaluate the use and efficacy of regular DFPP treatment in clinical practice for preventing recurrence of HTG-associated complications in thera­py refractory patients. Methods: Retrospective multicenter study in patients with severe symptomatic drug and diet refractory HTG with regular DFPP treatment. Patients’ incidence of HTG-associated pancreatic or cardiovascular complications was compared before treatment and with regular DFPP treatment. Results: Ten patients (3 female) were identified with baseline maximal TG concentrations of 2,587–28,090 mg/dL (median 5,487 mg/dL; interquartile range [IQR] 4,340–12,636). The mean observation period was 3.9 ± 3.4 years before and 3.8 ± 3.0 years after commencement of DFPP. In 5 patients, severe HTG was related to chylomicronemia, 2 patients had familial partial lipodystrophy Dunnigan, and 1 patient had additional LP(a)-hyperlipoproteinemia. The main HTG-associated complication was recurrent AP in 8 patients, including 1 patient treated during pregnancy. Two patients presented severe progressive ASCVD. With long-term DFPP treatment, the annual rate of HTG-associa­ted pancreatic or cardiovascular complications declined from median 1.4 (IQR 0.7–2.6) to 0 (IQR 0.0–0.4; p < 0.005). The absolute number of events was reduced by 77%. In 6 patients (60%) episodes of AP did not occur, nor was progression of ASCVD detected clinically or by routine imaging techniques. DFPP was effective in the elimination of TG-rich LP from plasma, and was safe and well-tolerated. Conclusion: Long-term, regular DFPP treatment resulted in stabilization of patients with severe HTG and related recurrent AP or progression of ASCVD, who were refractory to conventional dietary and drug therapy.
Subepithelial Spread of Early Gastric Signet Ring Cell Carcinoma: How Far They Can Reach?
Authors: Lee Yong Moon , Kang Sun Hyung , Kim Ju Seok , Eun Hyuk Soo , Joo Jong Seok , Rou Woo Sun , Park Jae Ho , Moon Hee Seok , Lee Eaum Seok , Kim Seok Hyun , Sung Jae kyu , Lee Byung Seok , Jeong Hyun Yong , Yeo Min Kyung , Song Kyu Sang , Yoo Hee Min
Published: March 2020

Introduction: Although signet ring cell carcinoma (SRC) is a poorly differentiated cancer subtype, recent studies suggest that endoscopic resection can be applied in small, mucosal early gastric SRC. However, other studies report frequent positive lines at the lateral resection margin after endoscopic treatment. Subepithelial spread beneath normal mucosa can exist in SRC, and such lesions may be the cause of positive margins after endoscopic resection. Thus, we conducted a retrospective study in order to evaluate the significance of subepithelial spread in early gastric SRC. Method: Medical records of early gastric SRC patients who underwent surgery or endoscopic resection from January 2011 to December 2016 at a single tertiary hospital (Daejeon, South Korea) were reviewed to examine subepithelial spread and clinical datum. Two expert pathologists reviewed all pathologic specimens, and only patients showing a pure SRC component were included. Results: Eighty-six patients were initially enrolled, and subepithelial spread existed in 62 patients (72.1%). The mean distance of subepithelial spread was 1,132.1 µm, and the maximal distance was 6,000 μm. Only discoloration was significantly associated with the presence of a subepithelial spread (p < 0.05, χ2 test, and logistic regression test). Distance of subepithelial spread did not correlate with total lesion size. Conclusion: Subepithelial spread of early gastric SRC occurs frequently and can reach up to 6 mm. Lesion discoloration may be associated with the presence of subepithelial spread. Our results suggest that careful decision of the margin is needed when performing endoscopic resection of early gastric SRC.
Acetaminophen (Paracetamol) Metabolites Induce Vasodilation and Hypotension by Activating Kv7 Potassium Channels Directly and Indirectly
Authors: van der Horst Jennifer , Manville Rian W. , Hayes Katie , Thomsen Morten B. , Abbott Geoffrey W. , Jepps Thomas A.
Published: March 2020

Objective:

Intravenous acetaminophen/paracetamol (APAP) is well documented to cause hypotension. Since the patients receiving intravenous APAP are usually critically ill, any severe hemodynamic changes, as with those associated with APAP, can be life-threatening. The mechanism underlying this dangerous iatrogenic effect of APAP was unknown.

Approach and Results:

Here, we show that intravenous APAP caused transient hypotension in rats, which was attenuated by the Kv7 channel blocker, linopirdine. APAP metabolite N-acetyl-p-benzoquinone imine caused vasodilatation of rat mesenteric arteries ex vivo. This vasodilatation was sensitive to linopirdine and also the calcitonin gene-related peptide antagonist, BIBN 4096. Further investigation revealed N-acetyl-p-benzoquinone imine stimulates calcitonin gene-related peptide release from perivascular nerves, causing a cAMP-dependent activation of Kv7 channels. We also show that N-acetyl-p-benzoquinone imine enhances Kv7.4 and Kv7.5 channels overexpressed in oocytes, suggesting that it can activate Kv7.4 and Kv7.5 channels directly, to elicit vasodilatation.

Conclusions:

Direct and indirect activation of Kv7 channels by the APAP metabolite N-acetyl-p-benzoquinone imine decreases arterial tone, which can lead to a drop in blood pressure. Our findings provide a molecular mechanism and potential preventive intervention for the clinical phenomenon of intravenous APAP-dependent transient hypotension.
A Role for MMP-10 (Matrix Metalloproteinase-10) in Calcific Aortic Valve Stenosis
Authors: Matilla Lara , Roncal Carmen , Ibarrola Jaime , Arrieta Vanessa , García-Peña Amaia , Fernández-Celis Amaya , Navarro Adela , Álvarez Virginia , Gainza Alicia , Orbe Josune , Cachofeiro Victoria , Zalba Guillermo , Sádaba Rafael , Rodríguez José A. , López-Andrés Natalia
Published: March 2020

Objective:

Aortic valve (AV) calcification plays an important role in the progression of aortic stenosis (AS). MMP-10 (matrix metalloproteinase-10 or stromelysin-2) is involved in vascular calcification in atherosclerosis. We hypothesize that MMP-10 may play a pathophysiological role in calcific AS.

Approach and Results:

Blood samples (n=112 AS and n=349 controls) and AVs (n=88) from patients undergoing valve replacement were analyzed. Circulating MMP-10 was higher in patients with AS compared with controls (
P
<0.001) and correlated with TNFα (tumor necrosis factor α; r
S
=0.451;
P
<0.0001). MMP-10 was detected by immunochemistry in AVs from patients with AS colocalized with aortic valve interstitial cells markers α-SMA (α-smooth muscle actin) and vimentin and with calcification markers Runx2 (Runt-related transcription factor 2) and SRY (sex-determining region Y)-box 9. MMP-10 expression in AVs was further confirmed by RT-qPCR and western blot. Ex vivo, MMP-10 was elevated in the conditioned media of AVs from patients with AS and associated with interleukin-1β (r
S
=0.5045,
P
<0.001) and BMP (bone morphogenetic protein)-2 (r
S
=0.5003,
P
<0.01). In vitro, recombinant human MMP-10 induced the overexpression of inflammatory, fibrotic, and osteogenic markers (interleukin-1β, α-SMA, vimentin, collagen, BMP-4, Sox9, OPN [osteopontin], BMP-9, and Smad 1/5/8;
P
<0.05) and cell mineralization in aortic valve interstitial cells isolated from human AVs, in a mechanism involving Akt (protein kinase B) phosphorylation. These effects were prevented by TIMP-1 (tissue inhibitor of metalloproteinases type 1), a physiological MMP inhibitor, or specifically by an anti-MMP-10 antibody.

Conclusions:

MMP-10, which is overexpressed in aortic valve from patients with AS, seems to play a central role in calcification in AS through Akt phosphorylation. MMP-10 could be a new therapeutic target for delaying the progression of aortic valve calcification in AS.
İSLAMİ HİSSE SENEDİ ENDEKSLERİ ARASINDAKİ OYNAKLIK İLİŞKİ YAPISI
Authors: KAMIŞLI Serap , ESEN Ethem
Published: March 2020

İslami hisse senedi endeksleri,
İslami kurallara uygun olarak belirlenen alanlarda faaliyet gösteren şirketler
baz alınarak oluşturulan endekslerdir. İslami finansal araçlara yatırım yapan
yatırımların temel amacı, geleneksel finansal araçlara yatırım yapan
yatırımcılara benzer şekilde minimum risk ile maksimum getiriyi sağlamaktır. Bu
amaçla yatırımcılar karar süreçlerinde varlıklara ve piyasalara ilişkin
analizler yapmaktadır. Bu analizlerden biri de varlıklar arasındaki oynaklık
ilişkilerinin yapısının belirlenmesidir. Oynaklık ilişkileri sabit veya dinamik
yapıda olabilmektedir. Bu durum ise yatırım stratejilerinin belirlenmesinde
dikkate alınması gereken bir faktördür. Oynaklık ilişkilerinin yapısının
belirlenmesinde kullanılan testlerden biri Engle ve Sheppard (2001) tarafından
geliştirilen dinamik korelasyon model testidir. Bu bağlamda çalışmada
15.09.2008 - 06.06.2019 tarihleri kapsamında ABD, Hindistan, İngiltere,
Japonya, Kuveyt, Malezya, Sri Lanka ve Türkiye İslami hisse senedi endeks
getirileri arasındaki oynaklık ilişki yapısı, Engle ve Sheppard (2001) dinamik
korelasyon model testi ile sınanmıştır. Çalışma sonucunda, söz konusu endeks
getirileri arasında genellikle dinamik oynaklık ilişkisi bulunduğu tespit
edilmiştir.
TÜKETİCİLERİN PLASTİK MARKET POŞETLERİYLE İLGİLİ ALGILARINI ETKİLEYEN FAKTÖRLERİN SENARYO BAZLI DENEY YÖNTEMİYLE İNCELENMESİ
Authors: TAŞÇIOĞLU Mertcan
Published: March 2020

Günümüzde çevreyi korumaya yönelik uygulamalar ve sürdürülebilirlik kavramı giderek artan bir öneme sahiptir. Birçok ülke plastik atıkları azaltmada yeni uygulamaları yürürlüğe sokmakta, bu bağlamda 1 Ocak 2019 tarihinden itibaren Türkiye’de de plastik poşetler 25 kuruşa satılmaya başlanmıştır. Satılan plastik poşetlerin yasalarla düzenlenen belirli minimum sınırları olmasına karşın poşetin dayanıklılığı, üzerinde marketin logosunun olup olmaması ve poşetin doğada yüzde yüz çözünüp çözünememesi konuları farklılık göstermektedir. Literatürde çevresel sürdürülebilirlik bağlamında birçok araştırma yer alsa da özellikle parayla satılan poşetlere tüketicilerin tepkisi konusunda araştırmalar yeterli değildir. Bu çalışmada senaryo bazlı deney yönteminden yararlanılarak tüketicilerin plastik poşetlerin çeşidine göre davranışları incelenmiştir. Sonuçlar tüketicilerin aldıkları poşet kalınsa üzerinde market logosunun olup olmamasının tüketicilerin tatminleri ve alışveriş niyeti üzerinde çok farkı yokken, inceyse market logosunun olmamasının tüketicilerin tatminlerini ve alışveriş niyetlerini artırdığını göstermektedir. Ayrıca poşetler doğada yüzde yüz çözünemiyorsa üzerinde market logosunun olup olmamasının tüketicilerin alışveriş niyeti üzerinde çok farkı yokken poşetler doğada yüzde yüz çözünebiliyorsa üzerinde market logosu olmaması tüketicilerin alışveriş niyetini artırmaktadır.
GÜNEY AVRUPA REFAH REJİMİ VE SOSYAL KORUMA: KAMU SOSYAL HARCAMALARI AÇISINDAN KARŞILAŞTIRMALI BİR ANALİZ
Authors: ÖZGÜL Burcu Çağla
Published: March 2020

Refah devleti, vatandaşlarına en iyi hayat standartlarını sunmayı hedefleyen, ekonomik ve sosyal alanda koruma sunan devlettir. Başka bir deyişle, refah devletlerinin temel işlevi toplumsal risklere karşı bir güvence olarak nitelendirilebilecek sosyal koruma sağlama işlevidir. Sosyal koruma toplumsal adalet, refah ve barışın gerçekleştirilmesine katkı sağlar. Refah devletinin anlamı ve refah devleti uygulamaları ülkelerin sosyal, kültürel, ekonomik ve siyasi temellerine göre başkalaşmaktadır. Anlayış ve uygulamalardaki bu farklılıklar ve ortaklıklar ise refah rejimi türlerine ilişkin tartışmaları doğurmuştur. Bu çalışmanın amacı, refah devleti rejimleri çerçevesinde Güney Avrupa refah rejimi içerisinde sınıflandırılan refah devletlerini sosyal koruma bakımından sosyal harcamalar kıstasıyla değerlendirmek ve karşılaştırmak, Türkiye’nin bu devletler içindeki durumunu ortaya koymaktır.