bluuebunny/crossref_metadata_2025 huggingface dataset:
Recoupling fire and grazing reduces wildland fuel loads on rangelands
Authors: Starns Heath D. , Fuhlendorf Samuel D. , Elmore R. Dwayne , Twidwell Dirac , Thacker Eric T. , Hovick Torre J. , Luttbeg Barney
Published: January 2019

Fire suppression and exclusion, the historically dominant paradigm of fire management, has resulted in major modifications of fire‐dependent ecosystems worldwide. These changes are partially credited with a recent increase in wildfire number and extent, as well as more extreme fire behavior. Fire and herbivory historically interacted, and research has shown that the interaction creates a unique mosaic of vegetation heterogeneity that each disturbance alone does not create. Because fire and grazing have largely been decoupled in modern times, the degree to which the interaction affects fuels and fire regimes has not yet been quantified. We evaluated effects of fire‐only and pyric herbivory on rangeland fuels and fire behavior simulated using BehavePlus at four sites across the southern Great Plains. We predicted patches managed via pyric herbivory would maintain lower fuel loads, and less intense simulated fire behavior than fire alone. We found that time since fire was a significant predictor of fuel loads and simulated fire behavior characteristics at all sites. Fuel loads and simulated fire behavior characteristics (flame length and rate of spread) increased with increasing time since fire in all simulated weather scenarios. Pyric herbivory mediated fuel accumulation at all sites. Mean fuel loads in fire‐only treatments exceeded 5000 kg/ha within 24 months, but pyric herbivory treatments remained below 5000 kg/ha for approximately 36 months. Simulated flame lengths in fire‐only treatments were consistently higher (up to 3 × ) than in pyric herbivory treatments. Similarly, fire spread rates were higher in fire‐only than in pyric herbivory treatments in all simulated weather conditions. Although all sites had potential to burn in the most extreme weather conditions, pyric herbivory reduced fuel accumulations, flame lengths, and rates of spread across all weather patterns simulated. These reductions extended the amount of time standard wildland firefighting techniques remain effective. Therefore, incorporating pyric herbivory into fuel management practices, in areas of high herbaceous productivity, increases the effectiveness of fuel treatments.
Pancreatic safety of vildagliptin in patients with type 2 diabetes mellitus: A European, noninterventional, postauthorization safety study
Authors: Williams Rachael , Kothny Wolfgang , Serban Carmen , Lopez‐Leon Sandra , Schlienger Raymond
Published: January 2019

This cohort study assessed the pancreatic safety of vildagliptin versus other noninsulin antidiabetic drugs (NIADs) based on data from five European electronic health care databases. Patients with type 2 diabetes aged ≥18 years on NIAD treatment were enrolled. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated separately for acute pancreatitis and pancreatic cancer for vildagliptin (± other NIADs) compared with other NIADs using negative binomial regression. Approximately 2.8% of the enrolled patients (n = 738 054) used vildagliptin during the study, with an average follow‐up time of 1.4 years. For acute pancreatitis, adjusted IRRs ranged between 0.89 andt 2.58 with all corresponding 95% CIs crossing 1. For pancreatic cancer adjusted IRRs ranged from 0.56 to 3.64, with the lower limit of 95% CIs >1 in some analyses. Post hoc sensitivity analyses taking latency time into account markedly lowered the risk estimates with corresponding 95% CIs crossing 1. Overall, the results do not suggest an increased pancreatitis risk with vildagliptin, while the observation for pancreatic cancer have to be interpreted carefully as this study was not designed to assess pancreatic cancer and rather be explained by certain underlying limitations including latency ‐time, chance findings and/or bias and confounding.
Decomposition of N2O at low temperature over Co3O4 prepared by different methods
Authors: Inayat Abrar , Ayoub Muhammad , Abdullah Ahmad Z. , Ullah Sami , Naqvi Salman R.
Published: January 2019

The activity of Co3O4 prepared by different methods was examined for decomposition of N2O in the presence of 2% oxygen concentration. This N2O gas is also a part of NOx gases and it is also nominated as a greenhouse gas that is a big threat for future environment due to very stable compound and having long life many and more than CO2. It is very difficult to make unstable or decompose N2O compound especially at low temperature. Catalytical decomposition is ultimate way to convert N2O into environmental friendly gases. In the present study, Co3O4 was prepared by different methods and used as a catalyst for this purpose. In the preparation of Co3O4, three different methods were used namely sol–gel method (Co3O4‐S), calcination method (Co3O4‐C), and the co‐precipitation method (Co3O4‐P). The prepared materials were well characterized by TEM, TGA, XRD, and BET surface techniques. These three different preparation methods of Co3O4 were performed to optimize for N2O decomposition. The experimental results showed that the catalytic activities of Co3O4 strongly depended on the Na/Co molar ratio and pH of an alkaline solution during Co3O4 preparation other than reaction temperature and time parameters. The optimized catalyst 1% NaOH + 1 M NH4OH/Co3O4‐P was observed highly active at optimum pH value 9.8 and Na/Co molar ratio 0.0120. The highest activity of this optimized catalyst for N2O decomposition was found 98% at 400°C while 95%, 89%, 78%, and 68% were recorded at 350°C, 300°C, 250°C and 200°C, respectively. © 2019 American Institute of Chemical Engineers Environ Prog, 38:e13129, 2019
Rationale and budget impact of bimonthly use of Cetuximab in patients with recurrent and/or metastatic head and neck cancer
Authors: Mennini FS , Marcellusi A , Fabiano G , Platini F , Bossi P
Published: January 2019

Background

In recurrent and/or metastatic head and neck squamous cell cancer, Cetuximab is administered once a week, followed by weekly doses. We present the clinical rationale of a different schedule of maintenance Cetuximab and we estimate the potential economic benefits on the health care budget from a societal perspective in Italy.

Methods

A budget impact (BI) excel‐based model was developed comparing a base case scenario of 100% weekly administration with a dose of 250 mg/m2 to an every‐other‐week (EOW) administration at 50% or 100% with a dose of 500 mg/m2.

Results

In the EOW, 50% scenario it was calculated a cost reduction of €347 000 of which 70% attributable to indirect costs, increasing to €694 000 after 4 months.

Conclusions

In our analysis, we showed that this simplified schedule could also reduce the costs of treatments both for the health system (direct costs) and for the society (indirect costs).
Alpha‐1 Antitrypsin Deficiency Liver Disease, Mutational Homogeneity Modulated by Epigenetic Heterogeneity With Links to Obesity
Authors: Wang Liguo , Marek George W. , Hlady Ryan A. , Wagner Ryan T. , Zhao Xia , Clark Virginia C. , Fan Alex Xiucheng , Liu Chen , Brantly Mark , Robertson Keith D.
Published: January 2019

Alpha‐1 antitrypsin deficiency (AATD) liver disease is characterized by marked heterogeneity in presentation and progression, despite a common underlying gene mutation, strongly suggesting the involvement of other genetic and/or epigenetic modifiers. Variation in clinical phenotype has added to the challenge of detection, diagnosis, and testing of new therapies in patients with AATD. We examined the contribution of DNA methylation (5‐methylcytosine [5mC]) to AATD liver disease heterogeneity because 5mC responds to environmental and genetic cues and its deregulation is a major driver of liver disease. Using liver biopsies from adults with early‐stage AATD and the ZZ genotype, genome‐wide 5mC patterns were interrogated. We compared DNA methylation among patients with early AATD, and among patients with normal liver, cirrhosis, and hepatocellular carcinoma derived from multiple etiologic exposures, and linked patient clinical/demographic features. Global analysis revealed significant genomic hypomethylation in AATD liver–impacting genes related to liver cancer, cell cycle, and fibrosis, as well as key regulatory molecules influencing growth, migration, and immune function. Further analysis indicated that 5mC changes are localized, with hypermethylation occurring within a background of genome‐wide 5mC loss and with patients with AATD manifesting distinct epigenetic landscapes despite their mutational homogeneity. By integrating clinical data with 5mC landscapes, we observed that CpGs differentially methylated among patients with AATD disease are linked to hallmark clinical features of AATD (e.g., hepatocyte degeneration and polymer accumulation) and further reveal links to well‐known sex‐specific effects of liver disease progression. Conclusion: Our data reveal molecular epigenetic signatures within this mutationally homogeneous group that point to ways to stratify patients for liver disease risk.
The immunomodulatory mechanism of brain injury induced by hyperhomocysteinemia in spontaneously hypertensive rats
Authors: Zhang Yu , Wang Lin , Zhou Xin , Geng Jie , Li Xin
Published: January 2019

Background

Elevated plasma homocysteine (Hcy) concentration is considered as the diagnostic criteria of Hyperhomocysteinemia (HHcy), which is associated with the inflammatory response and blood‐brain barrier disruption. Previous studies have proposed that HHcy with hypertension was associated with the brain injury by enhancing the cerebrovascular permeability, however, the immune mechanism remains obscure. The purpose of the study is to explore the immunomodulatory mechanism of brain injury in spontaneously hypertensive rats (SHRs) induced by HHcy.

Materials and methods

Sixty SHRs were randomly assigned to three groups: SHR‐C (control group), SHR‐M (methionine group) and SHR‐T (treatment group). Physical examination of body weight, systolic blood pressure (SBP) and plasma Hcy content was measured every 4 weeks. Besides, T‐helper cell 17 and regulatory T cells (Treg)‐related inflammatory cytokines (interleukin [IL]‐6, IL‐17, IL‐10, and transforming growth factor beta [TGF‐β]) and genes (RORγt and FoxP3) were detected by enzyme‐linked immunosorbent assay, quantitative polymerase chain reaction , Western blot, and immunohistochemistry.

Results

High methionine diet could cause weight loss, SBP rising, and plasma Hcy content significantly elevated. IL‐16 and IL‐17A levels in peripheral blood and in brain tissue both lifted, while IL‐10 and TGF‐β levels dropped; RORγt expression raised in brain, nevertheless, FoxP3 levels were the opposite. After the intervention with vitamin B6, B12, and folic acid in SHR‐T group, these trends would be eased or completely changed. Furthermore, brain tissue slices showed that IL‐17‐positive cells tended to decrease, and IL‐10‐positive cells increased in SHR‐T group, which was reversed in SHR‐M group.

Conclusions

HHcy may promote inflammation that can lead to brain lesions and down‐regulate immune response to protect the brain.
Adipose mesenchymal stem cell‐derived exosomes promote cell proliferation, migration, and inhibit cell apoptosis via Wnt/β‐catenin signaling in cutaneous wound healing
Authors: Ma Tao , Fu Bingchuan , Yang Xin , Xiao Yilei , Pan Mengxiong
Published: January 2019

Cutaneous wounds, a type of soft tissue injury, are difficult to heal in aging. Differentiation, migration, proliferation, and apoptosis of skin cells are identified as key factors during wound healing processes. Mesenchymal stem cells have been documented as possible candidates for wound healing treatment because their use could augment the regenerative capacity of many tissues. However, the effects of exosomes derived from adipose‐derived stem cell (ADSC‐exos) on cutaneous wound healing remain to be carefully elucidated. In this present study, HaCaT cells were exposed to hydrogen peroxide (H2O
2) for the establishment of the skin lesion model. Cell Counting Kit‐8 assay, migration assay, and flow cytometry assay were conducted to detect the biological function of ADSC‐exos in skin lesion model. Finally, the possible mechanism was further investigated using Western blot assay. The successful construction of the skin lesion model was confirmed by results of the enhanced cell apoptosis of HaCaT cells induced by H
2O
2, the increased Bax expression and decreased Bcl‐2 expression. CD9 and CD63 expression evidenced the existence of ADSC‐exos. The results of functional experiments demonstrated that ADSC‐exos could prompt cell proliferation and migration of HaCaT cells, and repress cell apoptosis of HaCaT cells. In addition, the activation of Wnt/β‐catenin signaling was confirmed by the enhanced expression of β‐catenin at the protein level. Collectively, our findings suggest that ADSC‐exos play a positive role in cutaneous wound healing possibly via Wnt/β‐catenin signaling. Our study may provide new insights into the therapeutic target for cutaneous wound healing.
Blocking OLFM4/HIF‐1α axis alleviates hypoxia‐induced invasion, epithelial–mesenchymal transition, and chemotherapy resistance in non‐small‐cell lung cancer
Authors: Gao Xian‐Zheng , Wang Guan‐Nan , Zhao Wu‐Gan , Han Jing , Diao Chang‐Ying , Wang Xiao‐Hui , Li Sheng‐Lei , Li Wen‐Cai
Published: January 2019

Hypoxia is a common biological hallmark of solid cancers, which has been proposed to be associated with oncogenesis and chemotherapy resistance. The purpose of the present study was to investigate the role and underlying mechanisms of olfactomedin 4 (OLFM4) in the hypoxia‐induced invasion, epithelial–mesenchymal transition (EMT), and chemotherapy resistance of non‐small‐cell lung cancer (NSCLC). We observed dramatically upregulated expression of OLFM4 in several NSCLC cell lines, and this effect was more pronounced in A549 and H1299 cells. In addition, our data revealed that OLFM4 expression was remarkably increased in both A549 and H1299 cells under hypoxic microenvironment, accompanied by enhanced levels of hypoxia‐inducible factor (HIF)‐1α protein. The HIF‐1α level was elevated in response to hypoxia, resulting in the regulation of OLFM4. Interestingly, OLFM4 was a positive regulator of hypoxia‐driven HIF‐1α production. Moreover, depletion of OLFM4 modulated multiple EMT‐associated proteins, as evidenced by the enhanced E‐cadherin levels along with the diminished expression of N‐cadherin and vimentin in response to hypoxia, and thus blocked invasion ability of A549 and H1299 cells following exposure to hypoxia. Furthermore, ablation of OLFM4 accelerated the sensitivity of A549 cells to cisplatin under hypoxic conditions, implying that OLFM4 serves as a key regulator in chemotherapeutic resistance under hypoxia. In conclusion, OLFM4/HIF‐1α axis might be a potential therapeutic strategy for NSCLC.
Cachexia induced by cancer and chemotherapy yield distinct perturbations to energy metabolism
Authors: Pin Fabrizio , Barreto Rafael , Couch Marion E. , Bonetto Andrea , O'Connell Thomas M.
Published: January 2019

Background

Cancer cachexia is a metabolic disorder involving perturbed energy balance and altered mitochondrial function. Chemotherapy is a primary treatment option for many types of cancer, but there is substantial evidence that some chemotherapeutic agents can also lead to the development and progression of cachexia. In this study, we apply a comprehensive and systems level metabolomics approach to characterize the metabolic perturbations in murine models of cancer‐induced and chemotherapy‐induced cachexia. Knowledge of the unique pathways through which cancer and chemotherapy drive cachexia is necessary in order to develop effective treatments.

Methods

The murine Colon26 (C26) adenocarcinoma xenograft model was used to study the metabolic derangements associated with cancer‐induced cachexia. In vivo administration of Folfiri (5‐fluorouracil, irinotecan, and leucovorin) was used to model chemotherapy‐induced cachexia. Comprehensive metabolic profiling was carried out using both nuclear magnetic resonance‐based and mass spectrometry‐based platforms. Analyses included plasma, muscle, and liver tissue to provide a systems level profiling.

Results

The study involved four groups of CD2F1 male mice (n = 4–5), including vehicle treated (V), C26 tumour hosts (CC), Folfiri treated (F), and C26 tumour hosts treated with Folfiri (CCF). Significant weight loss including skeletal muscle was observed for each of the experimental groups with the tumour hosts showing the most dramatic change (−3.74 g vs. initial body weight in the CC group). Skeletal muscle loss was evident in all experimental groups compared with V, with the CCF combination resulting in the most severe depletion of quadriceps mass (−38% vs. V; P < 0.001). All experimental groups were characterized by an increased systemic glucose demand as evidenced by decreased levels of circulating glucose (−47% in CC vs. V; P < 0.001) and depletion of liver glucose (−51% in CC vs. V; P < 0.001) and glycogen (−74% in CC vs. V; P < 0.001). The cancer‐induced and chemotherapy‐induced cachexia models displayed unique alterations in flux through the tricarboxylic acid cycle and β‐oxidation pathways. Cancer‐induced cachexia was uniquely characterized by a dramatic elevation in low‐density lipoprotein particles (+6.9‐fold vs. V; P < 0.001) and a significant increase in the inflammatory marker, GlycA (+33% vs. V; P < 0.001).

Conclusions

The results of this study demonstrated for the first time that cancer‐induced and chemotherapy‐induced cachexia is characterized by a number of distinct metabolic derangements. Effective therapeutic interventions for cancer‐induced and chemotherapy‐induced cachexia must take into account the specific metabolic defects imposed by the pathological or pharmacological drivers of cachexia.
Bcl6aa and bcl6ab are ubiquitously expressed and are inducible by lipopolysaccharide and polyI:C in adult tissues of medaka Oryzias latipes
Authors: Zhang Runshuai , Wu Kongyue , Ke Xiaomei , Zhang Xueyan , Xu Gongyu , Shen Hao , Nibona Emile , Al Hafiz Abdullah , Liang Xiaoting , Wang Zequn , Qi Chao , Zhou Qingchun , Zhong Xueping , Zhao Haobin
Published: January 2019

B‐cell lymphoma‐6 (Bcl6) is a transcriptional repressor that plays important roles in various physiological activities such as innate and adaptive immune response, lymphocyte differentiation, and cell cycle regulation in mammals. Two homologs of Bcl6a, namely Bcl6aa and Bcl6ab, are identified in teleost fish including medaka Oryzias latipes. The expression profiles of bcl6aa and bcl6ab in medaka were studied using reverse‐transcription polymerase chain reaction and in situ hybridization. The transcripts of bcl6aa and bcl6ab were detected from very early embryos such as the four‐cell stage until hatching. Bcl6aa and bcl6ab were clearly detected in the embryonic body from 5 days postfertilization onward by in situ hybridization. Bcl6aa was specifically expressed in the retina, whereas bcl6ab was expressed in entire embryonic body. The results referred to that both bcl6aa and bcl6ab originate maternally in the zygotes and may play major roles in embryogenesis of medaka. The transcripts of bcl6aa and bcl6ab were detected in all examined adult tissues, including immune organs such as the gill, spleen, kidney, liver, and intestine. The expression of bcl6aa and bcl6ab in the liver, spleen, head–kidney, and intestine could be upregulated or downregulated by lipopolysaccharide and polyriboinosinic–polyribocytidylic acid. These results indicate that both bcl6aa and bcl6ab may be involved in immune response in medaka.
Regression‐based regionalization for bias correction of temperature and precipitation
Authors: Moghim Sanaz , Bras Rafael L.
Published: January 2019

Statistical bias correction methods are inferred relationships between inputs and outputs. The constructed functions are based on available observations, which are limited in time and space. This study investigates the ability of regression models (linear and nonlinear) to regionalize a domain by defining a minimum number of training pixels necessary to achieve a good level of bias correction performance. Linear regression is used to divide northern South America into five regions. To correct the biases of temperature and precipitation, an artificial neural network (ANN) model was trained with selected pixels within each region and then used to reproduce bias‐corrected temperature and precipitation at all pixels within the delineated regions. The Community Climate System Model (CCSM) provided the climate model data. Results confirm that it is possible to identify regions in terms of physical features such as land cover, topography, and climatology over which models trained with a few pixels can correct the biases of climate variables with good accuracy over the entire domain. This approach saves computational time and reduces memory usage of using ANNs for correcting biases in climate model outputs.
Ultrasound Evaluation of Biliary Atresia Based on Gallbladder Classification: Is 4 Hours of Fasting Necessary?
Authors: Zhou Wenying , Chen Dan , Jiang Hong , Shan Quanyuan , Zhang Xiaoer , Xie Xiaoyan , Zhou Luyao
Published: January 2019

Objectives

The aim of this study was to evaluate the influence of fasting time on the ultrasound identification and exclusion of biliary atresia in jaundiced infants through the use of the gallbladder classification scheme and to test the value of the gallbladder classification scheme in the diagnosis of biliary atresia in inexperienced individuals.

Methods

A total of 188 jaundiced infants were enrolled in this study. All patients received detailed abdominal sonograms. Diagnoses were confirmed via liver biopsy, surgical findings, or follow‐up. Infants were grouped into either the fasting group (fasting time ≥ 4 h) or the nonfasting group (fasting time < 4 h). According to the gallbladder classification scheme, the gallbladders were classified into 4 types. The accuracy of diagnosing biliary atresia based on the gallbladder classification scheme was compared between the 2 groups. The gallbladders of 177 infants that were detectable by ultrasonography were used to compare the diagnostic performances between a junior radiologist and an experienced radiologist.

Results

The accuracies in the diagnosis of biliary atresia with the gallbladder classification scheme were 86.3% (82 of 95 patients) for the fasting group and 93.5% (87 of 93 patients) for the nonfasting group (P = .100). The diagnostic accuracies of biliary atresia were 88.7% (157 of 177 patients) for the junior radiologist and 90.4% (160 of 177 patients) for the experienced radiologist (P = .250). The κ value for the agreement between the 2 radiologists was 0.859.

Conclusions

The performance of gallbladder diagnoses was not influenced by the fasting time with the use of the gallbladder classification scheme. Additionally, the gallbladder classification scheme may help junior radiologists to more effectively identify biliary atresia and nonbiliary atresia.
Computational analysis of six optical coherence tomography systems for vocal fold imaging: A comparison study
Authors: Pham Tiffany T. , Chen Lily , Heidari Andrew E. , Chen Jason J. , Zhukhovitskaya Alisa , Li Yan , Patel Urja , Chen Zhongping , Wong Brian J.F.
Published: January 2019

Objectives

There have been many advancements in laryngeal imaging using optical coherence tomography (OCT), with varying system design and probes for use in research, office, and operating room settings. We evaluated the performance of six distinct OCT systems in imaging porcine vocal folds (cords) using computational image processing and segmentation.

Methods

Porcine vocal folds were scanned using six OCT systems. Imaging system and probe performance were quantitatively assessed for signal penetration, layer differentiation, and epithelium (EP) measurement. Fitted exponential decay curves with corresponding α constant and intensity thresholding segmentation were utilized to quantify the aforementioned parameters.

Results

The smallest average α constant and deepest signal penetration was of the SS‐OCT 1700 nm 90 kHz microscope system (α = −1.74), followed by the SS‐OCT 1310 nm 200 kHz VCSEL microscope system (α = −1.99), and SS‐OCT 1310 nm 50 kHz rigid forward viewing endoscope system (α = −2.23). The EP was not readily visualized for three out of six systems, but was detected using automated segmentation. Average EP thickness (mean ± SD) was calculated as 55.79 ± 31.86 μm which agrees favorably with previous literature.

Conclusion

Comparisons of OCT systems are challenging, as they encompass different probe design, optical path, and lasers, depending on application. Practical evaluation of different systems using computer based quantitative image processing and segmentation revealed basic, constructive information, such as EP measurements. To further validate the comparisons of system performance with clinical usability, in vivo human laryngeal imaging will be conducted. Further development of automated image processing and segmentation can be useful in rapid analysis of information. Lasers Surg. Med. 51:412–422, 2019. © 2019 Wiley Periodicals, Inc.
Investigation of passive layer formation on steel rebars in foamed concrete
Authors: Bagheri Alireza , Rastegar Mohammad Mahdi
Published: January 2019

Foamed concrete is a versatile lightweight material which is increasingly being considered for structural and semi structural applications. This would inevitably involve incorporation of steel reinforcement inside foamed concrete. The presence of large volume of air voids in the vicinity of steel could unfavorably affect its electrochemical behavior and jeopardize the formation of the passive layer. In the current study the passive layer formation of steel embedded in foam concrete with 55% air content was investigated and compared to that of steel embedded in the same mix without foam incorporation, that is, the base mix. The electrochemical tests included half‐cell potential, linear polarization resistance (LPR), potentiodynamic test, and electrochemical impedance spectroscopy (EIS). The results of half‐cell potential and the LPR test show that a passive layer forms within 3 weeks of casting steel inside foamed concrete which is similar to that observed for the steel in the base mix. The results of the potentiodynamic and the EIS tests which were carried out at the age of 28 days confirmed the passivity of reinforcement embedded in both foamed concrete and the base mix
The effect of simulated in‐service heat impact on the microstructure and corrosion properties of a high Cu containing Al‐Mg‐Si alloy
Authors: Schnatterer Christian , Altenbach Christoph , Zander Daniela
Published: January 2019

The effect of long‐term heat treatments in air at 135 °C for up to 42 days on the microstructure and the corrosion properties of the AA6056 aluminum alloy was investigated. The material was studied in the solution annealed (T4) and peak‐aged (T6) condition as well as after long‐term heat impact at 135 °C of up to 42 days (∼1008 h) of the initial T4 and T6 states. The increase of hardness during artificial aging was attributed to β” formation, whereas β’ and/or Q’ phases were found to be formed during over‐aging. The T4‐treated material suffer pitting corrosion, whereas the T6‐treated material was susceptible to intergranular corrosion (IGC) when tested according to ISO 11846 B. The initially T4‐treated material exhibited a complete change from pitting to IGC after 24 h at 135 °C, whereas further aging did not cause any change of the corrosion morphology. The corrosion properties of the T6‐treated material remained unaffected during heat impact up to 42 days.
A Sort & Search method for multicriteria optimization problems with applications to scheduling theory
Authors: Shang Lei , T'Kindt Vincent
Published: January 2019

This paper focuses on the Sort & Search method to solve a particular class of single criterion optimization problems called multiple constraints problems. This general method enables to derive exponential‐time algorithms for
‐hard optimization problems. In this paper, this method is further extended to the class of multicriteria multiple constraints problems for which the set of Pareto optima is enumerated. Then, the application of this new method on some multicriteria scheduling problems is proposed, leading to new exponential‐time algorithms for those problems.
Changes in DNA methylation and imprinting disorders in E9.5 mouse fetuses and placentas derived from vitrified eight‐cell embryos
Authors: Ma Yuan , Ma Yefei , Wen Liang , Lei Hui , Chen Shuqiang , Wang Xiaohong
Published: January 2019

Vitrification is increasingly used in assisted reproductive technology (ART) laboratories worldwide, and potential vitrification‐induced risks require further exploration. The effect of vitrification on changes in DNA methylation and imprinting disorders was investigated in E9.5 mouse fetuses and placentas. Fetus and placental tissues were collected from the natural mating (nautural conception [NC]) group, in vitro culture (IVC) group and vitrified embryo transfer (VET) group. The fetal crown‐rump length at E9.5 in both the IVC (0.210 ± 0.059 mm) and VET (0.205 ± 0.048 mm) groups was significantly reduced compared with the NC group (0.288 ± 0.083 mm). The global methylation levels of fetuses were decreased in the IVC group compared with the NC group and it was increased after vitrification compared with IVC (p < 0.05), similar to what was observed in the NC group (p > 0.05). The changes could be attributed to the disorders of DNA methyltransferases and ten‐eleven translocations. In the IVC and VET fetuses, a majority of maternally expressed genes were upregulated, which repressed fetal growth. Furthermore, vitrification led to a change in the methylation level of KvDMR1, which resulted in the disturbance of gene imprinting. According to our results, vitrification could contribute to increased methylation compared with IVC and contributes to a gene imprinting disorder rather than recovery. Despite the routine use of embryo vitrification in clinical settings, the effect that this procedure may have on genomic imprinting deserves much greater attention.
Nerve high‐resolution ultrasonography in tangier disease
Authors: Pasquale Antonella Di , Leonardi Luca , Fionda Laura , Vanoli Fiammetta , Garibaldi Matteo , Inghilleri Maurizio , Ceccanti Marco , Cambieri Chiara , Onesti Emanuela , Antonini Giovanni
Published: January 2019

Introduction: Tangier disease (TD) is an autosomal recessive disorder characterized by severe reduction in high‐density lipoprotein and accumulation of cholesterol esters in peripheral nerves and other tissues. The aim of this study was to evaluate whether nerve high‐resolution ultrasonography (HRUS) can detect morphological nerve changes in TD. Methods: Three related patients of a previously reported Italian family with Tangier disease, carrying the Y1698X mutation in ABCA1, underwent clinical, neurophysiological, and quantitative nerve HRUS evaluation. Nerve HRUS data were compared with normal controls. Results: Despite neurophysiological abnormalities, no quantitative HRUS abnormality was detected in peripheral nerves. Discussion: Normalcy of HRUS in neurophysiologically abnormal nerves suggests possible subtle abnormalities that escape quantitative HRUS detection. Systematic studies in larger TD cohorts with different mutations are needed to confirm our findings. Muscle Nerve 59:587–587, 2019
Use of collision tests to identify physiological differences between the median and ulnar nerves
Authors: Koszewicz Magdalena , Szydlo Mariusz , Gosk Jerzy , Wieczorek Malgorzata , Budrewicz Slawomir
Published: January 2019

Introduction: Median and ulnar nerves are used in comparative electrophysiological studies. We analyzed the conduction values in these hand nerves in healthy volunteers to find any physiological differences between them. Methods: We performed standard conduction studies and conduction velocity distribution (CVD) tests with estimation of 3 quartiles in 31 healthy right‐handed volunteers (17 women, 14 men) with a mean age of 44.8 ± 15.5 years. Results: The conduction velocities in all quartiles of CVD tests were statistically faster in the ulnar nerve (P < 0.00001), with no differences in the spread of conduction values and no differences between sides. In the ulnar nerve, CVD velocities in all quartiles were faster in the female group (P < 0.05). Discussion: The ulnar nerve has more fibers conducting with high velocities than does the median nerve. Electrophysiological comparisons between hand nerves must be performed carefully. Muscle Nerve 59:470–474, 2019
Effects of Angler Harvest on Adult Muskellunge Growth and Survival in Escanaba Lake, Wisconsin, 1956–2016
Authors: Shaw S. L. , Sass G. G. , Eslinger L. D.
Published: January 2019

The behavior of anglers targeting Muskellunge Esox masquinongy in Wisconsin has changed over time from being harvest oriented to catch-and-release oriented. Our objectives were to use the long-term tagging data set (1956–2016) available on the Muskellunge population of Escanaba Lake, Wisconsin, to characterize sex-specific age structure, length at age, and survival in relation to a potential change in angler harvest. We hypothesized that (1) angler harvest has changed over time, (2) age structure and length at age have changed in relation to the change in angler harvest, and (3) annual survival has changed over time in relation to changes in angler harvest. A breakpoint analysis revealed distinct changes in angler total harvest over time, occurring in 1995 and 2011. Muskellunge harvest (1956–1994) was significantly higher (29.7 ± 15.9 fish/year [mean ± SD]) than that observed during 1995–2010 (6.5 ± 2.9 fish/year) and 2011–2016 (0.83 ± 1.1 fish/year). Sex-specific growth did not differ between fishery type (i.e., high and low harvest). However, there was evidence that the asymptotic length of female Muskellunge was higher during the high harvest fishery. The top model in program MARK suggested that survival (S) differed by fishery type; i.e., Shigh ± SD = 0.72 ± 0.01 and Slow ± SD = 0.99 ± 0.006. Exploitation was the primary component of annual mortality. Natural and discard mortality could not be differentiated. Natural and discard mortality was 9.2 ± 11%/year during the high harvest fishery and 4.9 ± 5.9%/year during the low harvest fishery. Reductions in Muskellunge exploitation led to increased survival and no apparent change in length at age. These results from Escanaba Lake suggest that the lack of harvest leading to an unexploited Muskellunge fishery may result in population stability, improved age structure distribution, and adult survival, but could potentially hinder management actions meant to further increase population density or growth potential to trophy size.
International continence society white paper regarding female genital mutilation/cutting
Authors: Payne Christopher K. , Abdulcadir Jasmine , Ouedraogo Charlemagne , Madzou Sebastien , Kabore Fasnéwindé Aristide , De Elise JB ,   Ethics Committee if the International Continence Society
Published: January 2019

Female genital mutilation/cutting (FGM/C)—also known as Female Genital Cutting or Mutilation—is defined as the partial or total removal of the female external genitalia for non‐therapeutic reasons. This White Paper, prepared under the auspices of the International Continence Society (ICS), is intended by the ICS as a statement promoting the abandonment of this practice. The ICS also supports the respectful and evidence‐based care or treatment of women and girls already affected by FGM/C, in keeping with the World Health Organization (WHO) Guidelines on the Management of Health Complications from Female Genital Mutilation.Our members specialize in pelvic floor disorders from perspectives within a range of specialties; we encounter and treat women living with FGM/C and its consequences—particularly incontinence, infections, voiding dysfunction, sexual dysfunction, chronic pelvic pain, and obstetric trauma. Understanding the ethical, sociocultural, medical and surgical factors surrounding FGM/C is central to caring for women and girls with a history of FGM/C. The ICS voices herein state strong opposition to FGM/C. We encourage members to apply their skills to improve prevention strategies and the management of those affected.
Classical and Reverse Substituent Effects in Substituted Anthrol Derivatives
Authors: Szatylowicz Halina , Domanski Mateusz A. , Krygowski Tadeusz M.
Published: January 2019

The substituent effect in 1‐, 2‐, and 9‐anthrols is studied by means of B3LYP/6‐311++G(d,p) computation, taking into account substituents (X): NO2, CN, OH and NH2 located in all positions except the adjacent ones. The substituent effect is characterized by approaches based on quantum chemistry: The charge of the substituent active region (cSAR), substituent effect stabilization energy (SESE) and the charge flow index (CFI) describing flow of the charge from X to the fixed group (or vice versa) as well as substituent constants σ. Changes in properties observed in the fixed group (OH) are described by cSAR(OH). Mutual interdependences are found between these descriptors. The HOMA index is used to describe an effect of a substituent on aromaticity of an anthrol hydrocarbon skeleton and of individual rings. In all cases, the classical (influence of X on the properties of OH) and reverse (influence of OH on the properties of X) substituent effects are studied. The latter is clearly documented by the cSAR approach.
Identifying patients using antidepressants for the treatment of depression: A predictive algorithm for use in pharmaceutical and medical claims data
Authors: Havard Alys , Straka Peter , Sara Grant , Lujic Sanja , Tran Duong T. , Jorm Louisa R.
Published: January 2019

Purpose

Records of antidepressant dispensings are often used as a surrogate measure of depression. However, as antidepressants are frequently prescribed for indications other than depression, this is likely to result in misclassification. This study aimed to develop a predictive algorithm that identifies patients using antidepressants for the treatment of depression.

Methods

Pharmaceutical Benefits Scheme (PBS) and Medicare Benefits Schedule (MBS) claims data were linked to follow‐up questionnaires (completed in 2012‐2013) for participants of the 45 and Up Study—a cohort study of residents of New South Wales, Australia, aged 45 years and older. The sample composed participants who were dispensed an antidepressant in the 30 days prior to questionnaire completion (n = 3162). An algorithm based on patient characteristics, pharmaceutical dispensings, and claims for mental health services was built using group‐lasso interaction network (glinternet), with self‐reported receipt of treatment for depression as the outcome. The predictive performance of the algorithm was assessed via bootstrap resampling.

Results

The algorithm composes 15 main effects and 11 interactions, with type of antidepressant dispensed and claims for mental health services the strongest predictors. The ability of the algorithm to discriminate between antidepressant users with and without depression was 0.73. At a predicted probability cut‐off of 0.6, specificity was 93.8% and sensitivity was 23.6%.

Conclusions

Using this algorithm with a high probability cut‐off yields high specificity and facilitates the exclusion of individuals using antidepressants for indications other than depression, thereby mitigating the risk of confounding by indication when evaluating the outcomes of antidepressant use.
A randomized controlled trial of 24 weeks of varenicline for tobacco use among cancer patients: Efficacy, safety, and adherence
Authors: Schnoll Robert , Leone Frank , Veluz‐Wilkins Anna , Miele Andrew , Hole Anita , Jao Nancy C. , Paul Wileyto E. , Carroll Allison J. , Kalhan Ravi , Patel Jyoti , Langer Corey , Lubitz Su Fen , Hitsman Brian
Published: January 2019

Objective

Continuing to smoke after a cancer diagnosis undermines prognosis. Yet few trials have tested Food and Drug Administration (FDA)‐approved tobacco use medications in this population. Extended use varenicline may represent an effective treatment for cancer patients who smoke given barriers to cessation including a prolonged time line for relapse.

Methods

A placebo‐controlled randomized trial tested 12 weeks of varenicline plus 12 weeks of placebo (standard [ST]) vs 24 weeks of varenicline (extended [ET]) with seven counseling sessions for treatment‐seeking cancer patients who smoke (N = 207). Primary outcomes were 7‐day biochemically confirmed abstinence at weeks 24 and 52. Treatment adherence and side effects, adverse and serious adverse events, and blood pressure were assessed.

Results

Point prevalence and continuous abstinence quit rates at weeks 24 and 52 were not significantly different across treatment arms (P's > 0.05). Adherence (43% of sample) significantly interacted with treatment arm for week 24 point prevalence (odds ratio [OR] = 2.31; 95% confidence interval [CI], 1.15‐4.63; P = 0.02) and continuous (OR = 5.82; 95% CI, 2.66‐12.71; P < 0.001) abstinence. For both outcomes, adherent participants who received ET reported higher abstinence (60.5% and 44.2%) vs ST (44.7% and 27.7%), but differences in quit rates between arms were not significant for nonadherent participants (ET: 9.7% and 4.8%; ST: 12.7% and 10.9%). There were no significant differences between treatment arms on side effects, adverse and serious adverse events, and rates of high blood pressure (P's > 0.05).

Conclusions

Compared with ST, ET varenicline does not increase patient risk and increases smoking cessation rates among patients who adhere to treatment. Studies are needed to identify effective methods to increase medication adherence to treat patient tobacco use effectively.
Proteomics in Kidney Allograft Transplantation—Application of Molecular Pathway Analysis for Kidney Allograft Disease Phenotypic Biomarker Selection
Authors: Marx David , Metzger Jochen , Olagne Jérôme , Belczacka Iwona , Faguer Stanislas , Colombat Magali , Husi Holger , Mullen William , Gwinner Wilfried , Caillard Sophie
Published: January 2019

There is a need for accurate, robust, non‐invasive methods to provide early diagnosis of graft lesions after kidney transplantation. A multitude of proteomic biomarkers for the major kidney allograft disease phenotypes defined by the BANFF classification criteria have been described in literature. None of these biomarkers have been established in the clinic. A key reason for this is the lack of clinical validation which is difficult, as even the gold standard of diagnosis, kidney biopsy, is often ambiguous.

The semantic clustering by ReviGO on top of transcriptomic pathway analysis is evaluated to connect histological and transcriptomic kidney allograft disease characteristics with proteomic biomarker qualification.

By using public data generated in microarray studies of kidney allograft tissue, biological processes and key molecules specifically associated with the different kidney allograft disease phenotypes are identified.

Semantic clustering holds the promise to guide adaptation of proteomic marker panels to molecular pathology. This can support the development of noninvasive tests (e.g. in urine, by capillary electrophoresis mass spectrometry) that simultaneously detect diverse kidney allograft phenotypes with high accuracy and sensitivity.
Effect of manual physiotherapy in homogeneous individuals with subacromial shoulder impingement: A randomized controlled trial
Authors: Land Helen , Gordon Susan , Watt Kerrianne
Published: January 2019

Objective

To compare the effect of specific interventions aimed at (1) the upper thoracic spine (passive mobilization) and (2) the posterior shoulder (massage, passive mobilization, and stretching) to (3) an active control intervention in a homogeneous group with extrinsic subacromial shoulder impingement (SSI).

Study Design

Single‐centre, prospective, double‐blinded, randomized controlled trial.

Method

Eligible individuals with clearly defined extrinsic SSI were randomized to each group. Treatment duration was 12 consecutive weeks consisting of nine treatments over 6 weeks, followed by 6 weeks when one home exercise was performed daily. Outcomes included (1) active thoracic flexion/extension range of motion, (2) passive glenohumeral internal rotation and posterior shoulder range, (3) pain rating, and (4) shoulder pain and function disability index. Data were analysed at baseline, 6 and 12 weeks. Shoulder pain and function disability index scores were investigated via email 6 months after commencement of treatment.

Results

Twenty participants completed treatment in each group. No differences were identified between groups at baseline. Upper thoracic and posterior shoulder interventions, with a targeted home exercise, both significantly decreased pain and increased function scores and increased posterior shoulder range compared with active control at 12 weeks, and 6 months following cessation of the trial.

Conclusion

Manual therapy treatment that addresses these extrinsic factors, of thoracic spine or posterior shoulder tightness, decreases the signs and symptoms of SSI.

The trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR; 12615001303538).
Nanoscale flow cytometry to distinguish subpopulations of prostate extracellular vesicles in patient plasma
Authors: Padda Ranjit S. , Deng Florence K. , Brett Sabine I. , Biggs Colleen N. , Durfee Paul N. , Brinker Charles J. , Williams Karla C. , Leong Hon S.
Published: January 2019

Objective

To determine if prostate‐derived extracellular vesicles (EVs) present in patient plasma samples are of exocytotic origin (exosomes) or released by the cell membrane (microparticles/microvesicles). Both malignant and normal prostate cells release two types of EVs into the circulation, exosomes, and microparticles/microvesicles which differ in size, origin, and mode of release. Determining what proportion of prostate‐derived EVs are of exosomal versus microparticle/microvesicle EV subtype is of potential diagnostic significance.

Materials and Methods

Multi‐parametric analytical platforms such as nanoscale flow cytometry (nFC) were used to analyze prostate derived extracellular vesicles. Plasmas from prostate cancer (PCa) patient plasmas representing benign prostatic hyperplasia (BPH), low grade prostate cancer (Gleason Score 3 + 3) and high grade prostate cancer (Gleason Score ≥4 + 4) were analyzed for various exosome markers (CD9, CD63, CD81) and a prostate specific tissue marker (prostate specific membrane antigen/PSMA).

Results

By using nanoscale flow cytometry, we determine that prostate derived EVs are primarily of cell membrane origin, microparticles/microvesicles, and not all PSMA expressing EVs co‐express exosomal markers such as CD9, CD63, and CD81. CD9 was the most abundant exosomal marker on prostate derived EVs (12‐19%). There was no trend observed in terms of more PSMA + CD9 or PSMA + CD63 co‐expressing EVs versus increasing grade of prostate cancer.

Conclusion

The majority of prostate derived EVs present in plasmas are from the cell membrane as evidenced by their size and most importantly, lack of co‐expression of exosomal markers such as CD9/CD63/CD81. In fact, CD81 was not present on any prostate derived EVs in patient plasmas whereas CD9 was present on a minority of prostate derived EVs. The addition of an exosomal marker for detection of prostate‐derived EVs does not provide greater clarity in distinguishing EVs released by the prostate.