bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundIn 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.MethodsA 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.ResultsIn 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.ConclusionsIn 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).
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

AbstractBackgroundElevated 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 methodsSixty 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.ResultsHigh 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.ConclusionsHHcy 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

AbstractCutaneous 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

AbstractHypoxia 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

AbstractBackgroundCancer 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.MethodsThe 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.ResultsThe 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).ConclusionsThe 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

AbstractB‐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.
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

ObjectivesThe 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.MethodsA 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.ResultsThe 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.ConclusionsThe 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

ObjectivesThere 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.MethodsPorcine 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.ResultsThe 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.ConclusionComparisons 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.
A Sort & Search method for multicriteria optimization problems with applications to scheduling theory
Authors: Shang Lei , T'Kindt Vincent 
Published: January 2019

AbstractThis 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

AbstractVitrification 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

ABSTRACTIntroduction: 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

ABSTRACTIntroduction: 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

Abstract
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.