bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of gut and pancreatic hormones, bile acids, and fibroblast growth factor-21 differ to glucose, protein, and fat ingestion after gastric bypass surgery
Authors: Jensen Christian Zinck , Bojsen-Møller Kirstine N. , Svane Maria S. , Holst Line M. , Hermansen Kjeld , Hartmann Bolette , Wewer Albrechtsen Nicolai Jacob , Kuhre Rune Ehrenreich , Kristiansen Viggo B. , Rehfeld Jens Frederik , Clausen Trine R. , Holst Jens J. , Madsbad Sten
Published: February 2020

Postprandial gut hormone responses change after Roux-en-Y gastric bypass (RYGB), and we investigated the impact of glucose, protein, and fat (with and without pancreas lipase inhibition) on plasma responses of gut and pancreas hormones, bile acids, and fibroblast growth factor 21 (FGF-21) after RYGB and in nonoperated control subjects. In a randomized, crossover study 10 RYGB operated and 8 healthy weight-matched control subjects were administered 4 different 4-h isocaloric (200 kcal) liquid meal tests containing >90 energy (E)% of either glucose, protein (whey protein), or fat (butter with and without orlistat). The primary outcome was glucagon-like peptide-1 (GLP-1) secretion (area under the curve above baseline). Secondary outcomes included responses of peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), glicentin, neurotensin, ghrelin, insulin, glucagon, bile acids, and FGF-21. In the RYGB group the responses of GLP-1, GIP, glicentin, FGF-21, and C-peptide were increased after glucose compared with the other meals. The neurotensin and bile acids responses were greater after fat, while the glucagon and CCK responses were greater after protein ingestion. Furthermore, compared with control subjects, RYGB subjects had greater responses of total PYY after glucose, glucagon after glucose and fat, glicentin after glucose and protein, and GLP-1 and neurotensin after all meals, while GIP and CCK responses were lower after fat. Ghrelin responses did not differ between meals or between groups. Orlistat reduced all hormone responses to fat ingestion, except for ghrelin in the RYGB group. In conclusion, after RYGB glucose is a more potent stimulator of most gut hormones, especially for the marked increased secretion of GLP-1 compared with fat and protein.

NEW & NOTEWORTHY We investigated the impact of glucose, protein, and fat meals on intestinal and pancreatic hormones, bile acid, and fibroblast growth factor 21 (FGF-21) secretion in gastric bypass-operated patients compared with matched nonoperated individuals. The fat meal was administered with and without a pancreas lipase inhibitor. We found that the impact of the different meals on gut hormones, bile, and FGF 21 secretion differ and was different from the responses observed in nonoperated control subjects.
Organ-specific lymphatics play distinct roles in regulating HDL trafficking and composition
Authors: Gracia Gracia , Cao Enyuan , Johnston Angus P. R. , Porter Christopher J. H. , Trevaskis Natalie L.
Published: February 2020

Recently, peripheral lymphatic vessels were found to transport high-density lipoprotein (HDL) from interstitial tissues to the blood circulation during reverse cholesterol transport. This function is thought to be critical to the clearance of cholesterol from atherosclerotic plaques. The role of organ-specific lymphatics in modulating HDL transport and composition is, however, incompletely understood. This study aimed to 1) determine the contribution of the lymphatics draining the intestine and liver (which are major sites of HDL synthesis) to total (thoracic) lymph HDL transport and 2) verify whether the HDLs in lymph are derived from specific organs and are modified during trafficking in lymph. The mesenteric, hepatic, or thoracic lymph duct was cannulated in nonfasted Sprague-Dawley rats, and lymph was collected over 5 h under anesthesia. Whole lymph and specific lymph lipoproteins (isolated by ultracentrifugation) were analyzed for protein and lipid composition. The majority of thoracic lymph fluid, protein, and lipid mass was sourced from the mesenteric, and to a lesser extent, hepatic lymph. Mesenteric and thoracic lymph were both rich in chylomicrons and very low-density lipoprotein, whereas hepatic lymph and plasma were HDL-rich. The protein and lipid mass in thoracic lymph HDL was mostly sourced from mesenteric lymph, whereas the cholesterol mass was equally sourced from mesenteric and hepatic lymph. HDLs were compositionally distinct across the lymph sources and plasma. The composition of HDL also appeared to be modified during passage from the mesenteric and hepatic to the thoracic lymph duct. Overall, this study demonstrates that the lipoproteins in lymph are organ specific in composition, and the intestine and liver appear to be the main source of HDL in the lymph.

NEW & NOTEWORTHY High-density lipoprotein in lymph are organ-specific in composition and derive mostly from the intestine and liver. High-density lipoprotein also appears to be remodeled during transport through the lymphatics. These findings have implications to cardiometabolic diseases that involve perturbations in lipoprotein distribution and metabolism.
Juvenile OLFM4-null mice are protected from sepsis
Authors: Stark Julie E. , Opoka Amy M. , Mallela Jaya , Devarajan Prasad , Ma Qing , Levinsky Nick C. , Stringer Keith F. , Wong Hector R. , Alder Matthew N.
Published: February 2020

Pediatric sepsis is a leading cause of morbidity and mortality in children. One of the most common and devastating morbidities is sepsis-related acute kidney injury (AKI). AKI was traditionally thought to be related to low perfusion and acute tubular necrosis. However, little acute tubular necrosis can be found following septic AKI, and little is known about the mechanism of septic AKI. Olfactomedin-4 (OLFM4) is a secreted glycoprotein that marks a subset of neutrophils. Increased expression of OLFM4 in the blood is associated with worse outcomes in sepsis. Here, we investigated a pediatric model of murine sepsis using murine pups to investigate the mechanisms of OLFM4 in sepsis. When sepsis was induced in murine pups, survival was significantly increased in OLFM4-null pups. Immunohistochemistry at 24 h after the induction of sepsis demonstrated increased expression of OLFM4 in the kidney, which was localized to the loop of Henle. Renal cell apoptosis and plasma creatinine were significantly increased in wild-type versus OLFM4-null pups. Finally, bone marrow transplant suggested that increased OLFM4 in the kidney reflects local production rather than filtered from the plasma. These results demonstrate renal expression of OLFM4 for the first time and suggest that a kidney-specific mechanism may contribute to survival differences in OLFM4-null animals.
Differential kidney proximal tubule cell responses to protein overload by albumin and its ligands
Authors: Long Kimberly R. , Rbaibi Youssef , Gliozzi Megan L. , Ren Qidong , Weisz Ora A.
Published: February 2020

Albuminuria is frequently associated with proximal tubule (PT) cytotoxicity that can feed back to cause glomerular damage and exacerbate kidney disease. PT cells express megalin and cubilin receptors that bind to and internalize albumin over a broad concentration range. How the exposure to high concentrations of albumin leads to PT cytotoxicity remains unclear. Fatty acids and other ligands bound to albumin are known to trigger production of reactive oxygen species (ROS) that impair PT function. Alternatively or in addition, uptake of high concentrations of albumin may overload the endocytic pathway and elicit downstream responses. Here, we used a well-differentiated PT cell culture model with high endocytic capacity to dissect the effects of albumin versus its ligands on endocytic uptake and degradation of albumin, production of ROS, and cell viability. Cellular responses differed dramatically, depending on the preparation of albumin tested. Knockdown of megalin or cubilin failed to prevent ROS production mediated by albumin ligands, suggesting that receptor-mediated internalization of albumin was not necessary to trigger cellular responses to albumin ligands. Moreover, albumin induced cytotoxic responses when added to the basolateral surface of PT cells. Whereas overnight incubation with high concentrations of fatty acid-free albumin had no overt effects on cell function or viability, lysosomal degradation kinetics were slowed upon longer exposure, consistent with overload of the PT endocytic/degradative pathway. Together, the results of our study demonstrate that the PT responds independently to albumin and to its ligands and suggest that the consequences of albumin overload in vivo may be dependent on metabolic state.
Exploring the role of the metabolite-sensing receptor GPR109a in diabetic nephropathy
Authors: Snelson Matthew , Tan Sih Min , Higgins Gavin C. , Lindblom Runa S. J. , Coughlan Melinda T.
Published: February 2020

Alterations in gut homeostasis may contribute to the progression of diabetic nephropathy. There has been recent attention on the renoprotective effects of metabolite-sensing receptors in chronic renal injury, including the G protein-coupled receptor (GPR)109a, which ligates the short-chain fatty acid butyrate. However, the role of GPR109a in the development of diabetic nephropathy, a milieu of diminished microbiome-derived metabolites, has not yet been determined. The present study aimed to assess the effects of insufficient GPR109a signaling, via genetic deletion of GPR109a, on the development of renal injury in diabetic nephropathy. Gpr109a−/− mice or their wild-type littermates ( Gpr109a+/+) were rendered diabetic with streptozotocin. Mice received a control diet or an isocaloric high-fiber diet (12.5% resistant starch) for 24 wk, and gastrointestinal permeability and renal injury were determined. Diabetes was associated with increased albuminuria, glomerulosclerosis, and inflammation. In comparison, Gpr109a−/− mice with diabetes did not show an altered renal phenotype. Resistant starch supplementation did not afford protection from renal injury in diabetic nephropathy. While diabetes was associated with alterations in intestinal morphology, intestinal permeability assessed in vivo using the FITC-dextran test was unaltered. GPR109a deletion did not worsen gastrointestinal permeability. Furthermore, 12.5% resistant starch supplementation, at physiological concentrations, had no effect on intestinal permeability or morphology. The results of this study indicate that GPR109a does not play a critical role in intestinal homeostasis in a model of type 1 diabetes or in the development of diabetic nephropathy.
A Characterization on Singular Value Inequalities of Matrices
Authors: Dai Wei , Ye Yongsheng
Published: February 2020

We obtain a characterization of pair matrices A and B of order n such that sjA≤sjB, j=1, …, n, where sjX denotes the j-th largest singular values of X. It can imply not only some well-known singular value inequalities for sums and direct sums of matrices but also Zhan’s result related to singular values of differences of positive semidefinite matrices. In addition, some related and new inequalities are also obtained.
Online Intelligent Identification of Modal Parameters for Large Cable-Stayed Bridges
Authors: Wen Peng , Khan Inamullah , Jie He , Qiaofeng Chen , Shiyu Yang
Published: February 2020

Realizing online intelligent identification of bridge modal parameters requires not only the adaptive decomposition of structural response signals but also the enforcement of the automatic identification of modal parameters. Therefore, in this paper, the signal decomposition algorithm-ensemble empirical mode decomposition algorithm (EEMD) is improved to fulfill the above task. First, the adaptive matching algorithm is introduced to deal with the endpoint effect; second, the method of classification is used to avoid modal aliasing. Finally, an index for filtering the effective intrinsic mode function (IMF) components is constructed to realize automatic screening and signal reconstruction of the effective IMF components. At the same time, the first derivative of the singular entropy increment is used to automatically determine the order of the system, and then the spectral clustering algorithm is combined with the stochastic subspace algorithm to ultimately reach the goal of automatic identification of modal parameters.
An Optimal Control Problem Governed by a Kirchhoff-Type Variational Inequality
Authors: Wang Chengfu , Wu Pengcheng , Zhou Yuying
Published: February 2020

This paper is concerned with an optimal control problem governed by a Kirchhoff-type variational inequality. The existence of multiplicity solutions for the Kirchhoff-type variational inequality is established by using some nonlinear analysis techniques and the variational method, and the existence results of an optimal control for the optimal control problem governed by a Kirchhoff-type variational inequality are derived.
Serological Detection of Rh-Del Phenotype among Rh-Negative Blood Donors at National Blood Center, Yangon, Myanmar
Authors: Wah Saw Thu , Chi Saung Nay , Kyaing Kyi Kyi , Khin Aye Aye , Aung Thida
Published: February 2020

Background. Red cell Rhesus (Rh) antigen expression is influenced by the genetic polymorphism ofRHDandRHCEgenes and reveals serologically different reactions of RhD variants such as partial D, weak D, and Rh-Del. Serologically, Rh-Del type can only be detected by an adsorption-elution technique, and it might be mistyped as Rh-negative. The prevalence of Rh-Del has not been reported yet in Myanmar.Method. A total of 222 Rh-negative blood donors in the National Blood Center were tested for weak D and Rh-Del by indirect antihuman globulin and adsorption-elution method, respectively. RhCE typing was performed among Rh-negative and Rh-Del.Results. Of them, 75.2% (167/222) were Rh-negative, 15.8% (35/222) were Rh-Del, and 9% (20/222) were weak D. Of 202 blood donors (167 true Rh-negative and 35 Rh-Del), all of the Rh-Del positives were C-antigen-positive with 94.3% Ccee phenotype (33/35) and 5.7% CCee (2/35). Most of the Rh-negative donors (80.2%) were ccee phenotype (134/167).Conclusion. About half of Rh-Del subjects were repeated donors, and attention was needed to avoid transfusion of truly Rh-negative patients to prevent alloimmunization. It is recommended to do Rh-Del typing of Rh-negative donors who are C-antigen-positive and consider moving them to the Rh-positive pool. Further study is needed to clarify the alloimmunization status for transfusion of Rh-Del blood to Rh-negative recipients. Molecular markers for RhD-negative and D variants should be established in the Myanmar population to improve selection of antisera for Rh typing and enhance safety of the transfusion services.
Leflunomide-Induced Hidradenitis Suppurativa
Authors: Machan Achraf , Azendour Hasna , Toufik Hamza , Achemlal Lahsen , Boui Mohammed , Hjira Naoufal
Published: February 2020

Hidradenitis suppurativa is an inflammatory disease of the pilosebaceous unit with a chronic intermittent course and a devastating effect on quality of life. Rare reports of drug-induced hidradenitis suppurativa exist. We report on 2 women on follow-up for rheumatoid arthritis, who presented hidradenitis suppurativa after different periods of treatment with leflunomide and who improved few weeks after discontinuation of the medication.
Bargaining Solution-Based Resource Allocation Scheme for Cloud-Assisted Wireless Body Area Networks
Authors: Kim Sungwook
Published: February 2020

Wireless body area network (WBAN) is an emerging technology that has enormous potentials for continuous health monitoring of various diseases. For different medical and healthcare applications, the collected physiological data from multiple WBANs are further transmitted to the remote medical cloud servers. However, several technical issues and challenges are associated with the integration of WBANs and cloud computing services. In this study, we develop a new cloud-assisted WBAN control scheme to effectively use the limited system resource. By employing the main ideas of Generalized Gini and Choquet bargaining solutions, our approach unfolds into dual stages of bargaining processes while increasing the flexibility and adaptability. In particular, we consider the unique features of cloud-assisted WBAN applications and provide a generalized fair-efficient solution for the resource allocation problem. Numerical simulation results demonstrate that we can verify the superiority of our proposed scheme over the existing protocols. Lastly, major further challenges and future research directions about the cloud-assisted WBAN paradigm are summarized and discussed.
Block-Split Array Coding Algorithm for Long-Stream Data Compression
Authors: Jiancheng Qin , Yiqin Lu , Yu Zhong
Published: February 2020

With the advent of IR (Industrial Revolution) 4.0, the spread of sensors in IoT (Internet of Things) may generate massive data, which will challenge the limited sensor storage and network bandwidth. Hence, the study of big data compression is valuable in the field of sensors. A problem is how to compress the long-stream data efficiently with the finite memory of a sensor. To maintain the performance, traditional techniques of compression have to treat the data streams on a small and incompetent scale, which will reduce the compression ratio. To solve this problem, this paper proposes a block-split coding algorithm named “CZ-Array algorithm,” and implements it in the shareware named “ComZip.” CZ-Array can use a relatively small data window to cover a configurable large scale, which benefits the compression ratio. It is fast with the time complexity O(N) and fits the big data compression. The experiment results indicate that ComZip with CZ-Array can obtain a better compression ratio than gzip, lz4, bzip2, and p7zip in the multiple stream data compression, and it also has a competent speed among these general data compression software. Besides, CZ-Array is concise and fits the hardware parallel implementation of sensors.
Brain Functional Differences in Drug‐Naive Major Depression with Anxiety Patients of Different Traditional Chinese Medicine Syndrome Patterns: A Resting‐State fMRI Study
Authors: Du Yi , Zhao Jingjie , Wang Yongzhi , Han Yu , Deng Ligang , Jia Hongxiao , Zhou Yuan , Su Joyce , Li Li
Published: February 2020

Major depressive disorder (MDD), especially combined with anxiety, has a high incidence and low detection rate in China. Literature has shown that patients under major depression with anxiety (MDA) are more likely to nominate a somatic, rather than psychological, symptom as their presenting complaint. In the theory of Traditional Chinese Medicine (TCM), clinical symptoms of MDD patients are mainly categorized into two different syndrome patterns: Deficiency and Excess. We intend to use resting‐state functional magnetic resonance imaging (rs‐fMRI) to investigate their brain functional differences and hopefully to find their brain function mechanism. For our research, 42 drug‐naive MDA patients were divided into two groups (21 for Deficiency and 21 for Excess), with an additional 19 unaffected participants in the normal control (NC) group. We took Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), and brain fMRI scan for each group and analyzed the data. We first used Degree Centrality (DC) to map the functional differences in brain regions, utilized these regions as seed points, and used a seed‐based functional connectivity (FC) analysis to identify the specific functional connection between groups. The Deficiency group was found to have higher HAMD scores, HAMA scores, and HAMD somatic factor than the Excess group. In the DC analysis, significant decreases were found in the right precuneus of both the Deficiency and Excess groups compared to the NC group. In the FC analysis, the right precuneus showed significant decreased network connectivity with the bilateral cuneus, as well as the right lingual gyrus in the Deficiency group when compared to the NC group and the Excess group. Through our research, it was found that precuneus dysfunction may have a relationship with MDA and Deficiency patients have more severe physical and emotional symptoms, and we realized that a larger sample size and multiple brain mode observations were needed in further research.
Experimental Study on Bond Performance and Damage Detection of Corroded Reinforced Concrete Specimens
Authors: Tian Yubin , Liu Junran , Xiao Hengheng , Zhang Yi , Mo Qingcheng , Shen Jiyang , Shi Jun
Published: February 2020

This paper presents the results of an experimental research designed to investigate the combined effects of corrosion rate, concrete cover thickness, and stirrup spacing on the bond performance between reinforcement and concrete of reinforced concrete (RC) specimens. The RC specimens were immersed into sodium chloride solution to eliminate the passivation film on reinforcement. Then, an accelerated corrosion method was applied to corrode reinforcement embedded in concrete specimens. Pullout test was carried out to establish empirical formulas for ultimate slip and ultimate bond strength of RC specimens with three different corrosion rates, different concrete cover thicknesses, and different stirrup spacings. In addition, the bond‐slip relation model was developed to predict and evaluate the bond performance of RC specimens. Finally, the ultrasonic technology was used to detect the damage of RC specimens, and the corresponding nonlinear coefficient β was proposed to characterize the damage degree of RC specimens. The susceptibility of β on the damage of specimens was compared with that of ultrasonic velocity, indicating β was more appropriate to evaluate the damage of RC specimens.
Trends and Factors Associated with Healthcare Utilization for Childhood Diarrhea and Fever in Ethiopia: Further Analysis of the Demographic and Health Surveys from 2000 to 2016
Authors: Woldeamanuel Berhanu Teshome
Published: February 2020

Background. Healthcare use for childhood illness reduces the risk of under-five deaths from common preventable diseases. However, rates of healthcare seeking for childhood diarrhea and fever remain low in most low- and middle-income countries including Ethiopia. This study aimed to assess the trends and factors for healthcare diarrhea and fever in Ethiopia from 2000 to 2016. Methods. Analysis of healthcare use for diarrhea and fever trends was done using data from four Ethiopian Demographic Health Surveys. Descriptive statistics were used to report sample characteristics and healthcare use for diarrhea and fever trends, and chi-square tests were used to assess associations between independent variables and healthcare utilization in each survey. Binary logistic regression analysis was fitted to find the factors related to healthcare utilization for diarrhea and fever. All variables with odds ratio p values <0.05 were considered as significant determinants of the outcome. Results. Healthcare seeking for diarrheal illness significantly increased from 13% (95% CI: 12.5–13.5) in 2000 to 44% (95% CI: 43.2–44.78) in 2016, while healthcare uses for fever significantly increased from 22% (95% CI: 16.7–27.3) in 2000 to 35% (95% CI: 34.3–35.7) in 2016. Factors of healthcare seeking for diarrhea in 2000–2016 were as follows: maternal age <30 years, urban residence, being a male child, nonexposure to mass media and not hearing information about oral rehydration, no desire to have more children, poor wealth index, and region. Meanwhile, factors for healthcare seeking for fever in 2000–2016 were as follows: a long distance from the nearest health facilities, first birth order, nonexposure to mass media, no desire to have more children, maternal age <30 years, urban residence, region, absence of antenatal and postnatal care utilization, poor wealth index, and being born from uneducated mothers (p values < 0.05). Conclusions. Factors associated with healthcare utilization for diarrhea and fever differed between 2000 and 2016. Though Ethiopia has achieved a significant reduction in under-five mortality, it needs to accelerate the reduction through strengthening healthcare utilization for common childhood illness to avoid deaths from preventable diseases.
Quality Prediction of Web Services Based on a Covering Algorithm
Authors: Jin Ying , Cui Guangming , Zhang Yiwen
Published: February 2020

Service-oriented architecture (SOA) is widely used, which has fueled the rapid growth of Web services and the deployment of tremendous Web services over the last decades. It becomes challenging but crucial to find the proper Web services because of the increasing amount of Web services. However, it proves unfeasible to inspect all the Web services to check their quality values since it will consume a lot of resources. Thus, developing effective and efficient approaches for predicting the quality values of Web services has become an important research issue. In this paper, we propose UIQPCA, a novel approach for hybrid User and Item-based Quality Prediction with Covering Algorithm. UIQPCA integrates information of both users and Web services on the basis of users’ ideas on the quality of coinvoked Web services. After the integration, users and Web services which are similar to the target user and the target Web service are selected. Then, considering the result of integration, UIQPCA makes predictions on how a target user will appraise a target Web service. Broad experiments on WS-Dream, a web service dataset which is widely used in real world, are conducted to evaluate the reliability of UIQPCA. According to the results of experiment, UIQPCA is far better than former approaches, including item-based, user-based, hybrid, and cluster-based approaches.
Iodine Content of Salt Use after Years of Universal Iodization Policy and Knowledge on Iodized Salt among Households in the Sissala East Municipality in Upper West Region of Ghana
Authors: Appiah Prince Kubi , Yanbom Clement Tiimim , Ayanore Martin Amogre , Bapula Alex
Published: February 2020

Background. Iodine deficiency is a global public health concern as it leads to inadequate production of thyroid hormone in the body, causing too many destructive consequences on the roles and functions of different human organs and muscles including brain growth and can manifest into many damaging effects such as intestinal cerebral impedance, cancer of intestine, breast disorders, and physical deformities like goitre and cretinism to one’s body. Despite all these negative effects, there are several important public health programs including universal salt iodization (USI) to improve on households’ iodine intake, notwithstanding this, countless families are still eating foods containing less iodine or no iodine at all. Hence, this study examined the intake of iodized salt after years of universal salt iodization and the knowledge on iodized salt among households in the Sissala East Municipality. Method. A descriptive cross-sectional study was adopted to collect data for the study. Data were collected from women in charge of household meal preparation using a semistructured questionnaire and rapid field iodine test kits. The Statistical Package for Social Sciences (SPSS) version 20 was used for the data analysis and presented in tables and graphs. p value <0.05 was considered as statistically significant. Findings. Only 41.4% of the households have good knowledge on benefits of iodized salt and dangers associated with iodine deficiency. It was realized that the health workers (46.6%) and television were the main sources of information on iodized salt. Household salt usage with adequate (>15 ppm) levels of iodine was 44.0%; however 85.9% of the salts were stored in covered containers. The study showed significant associations between knowledge on iodized salt and educational level (p≤0.001), occupation (p=0.043), religion (p=0.027), and ethnic lineage (p=0.046). Also, the use of iodized salt showed associations with the educational level (p≤0.001), occupation (p=0.003), religion (p=0.042), and knowledge on iodized salt (p≤0.001). Conclusions. Only about 4 in 10 households were consuming salt with adequate iodine, and this coverage is very low compared with the 90% or more coverage recommended by WHO/UNICEF/ICCIDD. Having secondary and tertiary education and having good knowledge of iodized salt has a great influence on the use of iodized salt; however, with this low level of knowledge of importance of iodized salt among women responsible for house food preparations, there is the need for health professionals to intensify education and promotion on iodized salt in the area and to monitor and verify iodine content of salts produced and sold in the market all times, as the source of the salt might have contributed to the low levels of iodine in the household salt.
Results of a Randomized Phase IIb Trial of Nelipepimut-S + Trastuzumab versus Trastuzumab to Prevent Recurrences in Patients with High-Risk HER2 Low-Expressing Breast Cancer
Authors: Clifton G. Travis , Hale Diane , Vreeland Timothy J. , Hickerson Annelies T. , Litton Jennifer K. , Alatrash Gheath , Murthy Rashmi K. , Qiao Na , Philips Anne V. , Lukas Jason J. , Holmes Jarrod P. , Peoples George E. , Mittendorf Elizabeth A.
Published: February 2020

Purpose:

Preclinical data provide evidence for synergism between HER2-targeted peptide vaccines and trastuzumab. The efficacy of this combination was evaluated in patients with HER2 low-expressing breast cancer in the adjuvant setting.

Patients and Methods:

A phase IIb, multicenter, randomized, single-blinded, controlled trial enrolled disease-free patients after standard therapy completion (NCT01570036). Eligible patients were HLA-A2, A3, A24, and/or A26+, and had HER2 IHC 1+/2+, FISH nonamplified breast cancer, that was node positive and/or hormone receptor–negative [triple-negative breast cancer (TNBC)]. Patients received trastuzumab for 1 year and were randomized to placebo (GM-CSF, control) or nelipepimut-S (NPS) with GM-CSF. Primary outcome was 24-month disease-free survival (DFS). Secondary outcomes were 36-month DFS, safety, and immunologic response.

Results:

Overall, 275 patients were randomized; 136 received NPS with GM-CSF, and 139 received placebo with GM-CSF. There were no clinicopathologic differences between groups. Concurrent trastuzumab and NPS with GM-CSF was safe with no additional overall or cardiac toxicity compared with control. At median follow-up of 25.7 (interquartile range, 18.4–32.7) months, estimated DFS did not significantly differ between NPS and control [HR, 0.62; 95% confidence interval (CI), 0.31–1.25; P = 0.18]. In a planned exploratory analysis of patients with TNBC, DFS was improved for NPS versus control (HR, 0.26; 95% CI, 0.08–0.81, P = 0.01).

Conclusions:

The combination of NPS with trastuzumab is safe. In HER2 low-expressing breast cancer, no significant difference in DFS was seen in the intention-to-treat analysis; however, significant clinical benefit was seen in patients with TNBC. These findings warrant further investigation in a phase III randomized trial.
External Validation of Risk Prediction Models Incorporating Common Genetic Variants for Incident Colorectal Cancer Using UK Biobank
Authors: Saunders Catherine L. , Kilian Britt , Thompson Deborah J. , McGeoch Luke J. , Griffin Simon J. , Antoniou Antonis C. , Emery Jon D. , Walter Fiona M. , Dennis Joe , Yang Xin , Usher-Smith Juliet A.
Published: February 2020

The aim of this study was to compare and externally validate risk scores developed to predict incident colorectal cancer that include common genetic variants (SNPs), with or without established lifestyle/environmental (questionnaire-based/classical/phenotypic) risk factors. We externally validated 23 risk models from a previous systematic review in 443,888 participants ages 37 to 73 from the UK Biobank cohort who had 6-year prospective follow-up, no prior history of colorectal cancer, and data for incidence of colorectal cancer through linkage to national cancer registries. There were 2,679 (0.6%) cases of incident colorectal cancer. We assessed model discrimination using the area under the operating characteristic curve (AUC) and relative risk calibration. The AUC of models including only SNPs increased with the number of included SNPs and was similar in men and women: the model by Huyghe with 120 SNPs had the highest AUC of 0.62 [95% confidence interval (CI), 0.59–0.64] in women and 0.64 (95% CI, 0.61–0.66) in men. Adding phenotypic risk factors without age improved discrimination in men but not in women. Adding phenotypic risk factors and age increased discrimination in all cases (P < 0.05), with the best performing models including SNPs, phenotypic risk factors, and age having AUCs between 0.64 and 0.67 in women and 0.67 and 0.71 in men. Relative risk calibration varied substantially across the models. Among middle-aged people in the UK, existing polygenic risk scores discriminate moderately well between those who do and do not develop colorectal cancer over 6 years. Consideration should be given to exploring the feasibility of incorporating genetic and lifestyle/environmental information in any future stratified colorectal cancer screening program.
Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker
Authors: Kim Chang Min , Hwang Shin , Keam Bhumsuk , Yu Yun Suk , Kim Ji Hoon , Kim Dong-Sik , Bae Si Hyun , Kim Gun-Do , Lee Jong Kyu , Seo Yong Bae , Nam Soon Woo , Kang Koo Jeong , Buonaguro Luigi , Park Jin Young , Kim Yun Soo , Wang Hee Jung
Published: February 2020

Background/Aim: Uniform treatment of hepatocellular carcinoma (HCC) with molecular targeted drugs (e.g., sorafenib) results in a poor overall tumor response when tumor subtyping is absent. Patient stratification based on actionable gene expression is a method that can potentially improve the effectiveness of these drugs. Here we aimed to identify the clinical application of actionable genes in predicting response to sorafenib. Methods: Through quantitative real-time reverse transcription PCR, we analyzed the expression levels of seven actionable genes (VEGFR2, PDGFRB, c-KIT, c-RAF, EGFR, mTOR, and FGFR1) in tumors versus noncancerous tissues from 220 HCC patients treated with sorafenib. Our analysis found that 9 responders did not have unique clinical features compared to nonresponders. A receiver operating characteristic curve evaluated the predictive performance of the treatment benefit score (TBS) calculated from the actionable genes. Results: The responders had significantly higher TBS values than the nonresponders. With an area under the curve of 0.779, a TBS combining mTOR with VEGFR2, c-KIT, and c-RAF was the most significant predictor of response to sorafenib. When used alone, sorafenib had a 0.7–3% response rate among HCC patients, but when stratifying the patients with actionable genes, the tumor response rate rose to 15.6%. Furthermore, actionable gene expression is significantly correlated with tumor response. Conclusions: Our findings on patient stratification based on actionable molecular subtyping potentially provide a therapeutic strategy for improving sorafenib’s effectiveness in treating HCC.
Pneumocystis Pneumonia and Acute Kidney Injury Induced by Everolimus Treatment in a Patient with Metastatic Breast Cancer
Authors: Nakamura Mayuko , Matsunuma Ryoichi , Yamaguchi Kei , Hayami Ryosuke , Tsuneizumi Michiko
Published: February 2020

Everolimus, an inhibitor of the rapamycin pathway, is administered with the combination of an aromatase inhibitor for the treatment of metastatic estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancers. Interstitial lung disease is a well-known major adverse event associated with everolimus treatment, but it is often difficult to distinguish between interstitial lung disease and Pneumocystis pneumonia, a lung infection. Acute kidney injury is another adverse event that is associated with everolimus use. In this article, we report a case of Pneumocystis pneumonia without respiratory symptoms and acute kidney injury induced by everolimus treatment in a patient with ER-positive and HER2-negative metastatic breast cancer.
Identification of Circulating Proteins Associated With Blood Pressure Using Mendelian Randomization
Authors: Thériault Sébastien , Sjaarda Jennifer , Chong Michael , Hess Sibylle , Gerstein Hertzel , Paré Guillaume
Published: February 2020

Background:

Hypertension is a common modifiable risk factor for cardiovascular disease and mortality. Pathophysiological mechanisms leading to hypertension remain incompletely understood. Mendelian randomization (MR) allows the evaluation of the causal role of markers by minimizing the risk of biases such as reverse causation and confounding. We aimed to identify novel circulating proteins associated with blood pressure through a comprehensive screen of 227 blood biomarkers using MR.

Methods:

Genetic determinants of 227 biomarkers were identified in ORIGIN (Outcome Reduction With Initial Glargine Intervention; URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00069784) participants (N=4147) and combined with genetic effects on systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure from the International Consortium for Blood Pressure (74 064 individuals) using MR. Results were replicated in the UK Biobank (up to 319 103 individuals) and using another biomarker dataset (N=3301). MR analyses with cardiovascular risk factors and outcomes as well as other biomarkers were performed to further evaluate the mechanisms involved.

Results:

Six biomarkers were associated with blood pressure using MR after adjustment for multiple hypothesis testing. Relationships between NT-proBNP (N-terminal Pro-B-type natriuretic peptide), systolic blood pressure, and diastolic blood pressure confirmed previous reports. Novel circulating proteins associated with blood pressure were also identified. uPA (urokinase-type plasminogen activator) was related to systolic blood pressure; ADM (adrenomedullin) was related to systolic blood pressure and pulse pressure; IL (interleukin) 16 was related to diastolic blood pressure; cFn (cellular fibronectin) and IGFBP3 (insulin-like growth factor-binding protein 3) were related to pulse pressure. With the exception of IL16 and diastolic blood pressure (
P
=0.58), these relationships were validated in the UK Biobank (
P
<0.0001). Further MR analyses with cardiovascular risk factors and outcomes showed relationships between NT-proBNP and large-artery atherosclerotic stroke, IGFBP3 and diabetes mellitus as well as cFn and body mass index.

Conclusions:

We identified novel biomarkers associated with blood pressure using MR. These markers could prove useful for risk assessment and as potential therapeutic targets.
Negation-Licensed Commands
Authors: Iatridou Sabine
Published: February 2020

The main goal of this article is to argue for the existence and crosslinguistic stability of a phenomenon that I call “negation-licensed commands” (NLCs), in which commands can be interpreted as such only in the presence of negation. The article explores morphosyntactic properties of NLCs in a small number of unrelated languages. It stops short of an analysis of the phenomenon, which will have to await future research.
Online Learning Based on Online DCA and Application to Online Classification
Authors: Le Thi Hoai An , Ho Vinh Thanh
Published: February 2020

We investigate an approach based on DC (Difference of Convex functions) programming and DCA (DC Algorithm) for online learning techniques. The prediction problem of an online learner can be formulated as a DC program for which online DCA is applied. We propose the two so-called complete/approximate versions of online DCA scheme and prove their logarithmic/sublinear regrets. Six online DCA-based algorithms are developed for online binary linear classification. Numerical experiments on a variety of benchmark classification data sets show the efficiency of our proposed algorithms in comparison with the state-of-the-art online classification algorithms.
Feature Extraction of Surface Electromyography Based on Improved Small-World Leaky Echo State Network
Authors: Xi Xugang , Jiang Wenjun , Miran Seyed M. , Hua Xian , Zhao Yun-Bo , Yang Chen , Luo Zhizeng
Published: February 2020

Surface electromyography (sEMG) is an electrophysiological reflection of skeletal muscle contractile activity that can directly reflect neuromuscular activity. It has been a matter of research to investigate feature extraction methods of sEMG signals. In this letter, we propose a feature extraction method of sEMG signals based on the improved small-world leaky echo state network (ISWLESN). The reservoir of leaky echo state network (LESN) is connected by a random network. First, we improved the reservoir of the echo state network (ESN) by these networks and used edge-added probability to improve these networks. That idea enhances the adaptability of the reservoir, the generalization ability, and the stability of ESN. Then we obtained the output weight of the network through training and used it as features. We recorded the sEMG signals during different activities: falling, walking, sitting, squatting, going upstairs, and going downstairs. Afterward, we extracted corresponding features by ISWLESN and used principal component analysis for dimension reduction. At the end, scatter plot, the class separability index, and the Davies-Bouldin index were used to assess the performance of features. The results showed that the ISWLESN clustering performance was better than those of LESN and ESN. By support vector machine, it was also revealed that the performance of ISWLESN for classifying the activities was better than those of ESN and LESN.
Novelties in Microlicia (Melastomataceae: Microlicieae) from the Bolivian Cerrado

Authors: PACIFICO RICARDO , ALMEDA FRANK , RODRIGUES LORENA JULIA GALI , FIDANZA KARINA
Published: February 2020

Microlicia woodii is described as a new species from the Meseta de Motacú, Santiago de Chiquitos, eastern Bolivia, a region rich in endemic plants. The new species seems to be closely related to Microlicia sphagnicola, and can be recognized by a combination of elliptic leaf blades 8–10 × 3.2–5 mm, glandular-punctate on both surfaces, petioles 0.2–0.4 mm long, rectangular and dorso-ventrally flattened, solitary 5–6-merous flowers, external and internal intercalycine eglandular trichomes ca. 1–2 mm long, pink petals, and dimorphic, bicolored and polysporangiate anthers. Line drawings, photographs, a distribution map, and notes on its conservation status are provided. Additionally, we designate a lectotype for Microlicia insignis and document the first records for this species in Bolivia, at Parque Nacional Noel Kempff Mercado.
The identity and typification of two endemic taxa of Carex (Cyperaceae) from Eastern Himalaya

Authors: GHOSH ASOK , MALLICK TANMOY , MAJUMDER SUBRATA , MAITI GAUR GOPAL , NASKAR SAIKAT
Published: February 2020

The names Carex crassipes and C. daltoni are lectotypified. The dwarf C. crassipes was considered by Boeckeler as a species different from C. daltoni. However most authors did not recognize its independence, and synonymized it to C. daltoni. We discussed the identity and independence of both taxa using herbarium preserved specimens and recent collection.
Distribution of Iliac Artery Calcification on Unenhanced Computed Tomography Scans Performed on Potential Recipients Prior to Renal Transplantation
Authors: Marcuzzi Adrian , Wang Stella , Tyrrell Pascal N. , Ravichandran Pradeep , Marcuzzi Danny , Prabhudesai Vikramaditya , Stewart Robert
Published: February 2020

Purpose:

To investigate whether a significant difference exists between the calcification of the common iliac arteries (CIAs) and the external iliac arteries (EIAs) and test for associations between clinical factors and the distribution of calcification.

Methods:

A retrospective review of renal transplant candidates who underwent a routine preoperative unenhanced computed tomography yielded 214 patients. Agatston scores for the patients’ left CIA, left EIA, right CIA, and right EIA were assigned. A retrospective search of patient records screened for 5 clinical factors (diabetes, hypertension, coronary artery disease [CAD], smoking, and dialysis). Data were assessed using a 2-sided t test, odds ratio, and a multivariate linear regression calculated through generalized estimating equation (GEE).

Results:

The log-transformed Agatston scores in the CIA were found to be significantly greater than that in the EIA ( t = 9.57, P < .0001), with a mean difference of 1.5078 (95% confidence interval: 1.1962-1.8194), indicating relative EIA sparing. There were no significant differences in calcification between the right and left sides. Generalized estimating equation found that CAD and smoking demonstrated independent positive associations with EIA sparing (GEE = 2.6464 [ P = .0197] and 1.9092 [ P = .0470], respectively). Age was also significantly associated and indicated that EIA sparing remained relatively constant throughout patients’ lives (GEE = 1.0711 [ P < .0001]).

Conclusion:

This study has demonstrated statistically significant EIA sparing in end-stage renal disease patients and identified CAD and smoking as associated factors. This phenomenon warrants further investigation into its biological mechanisms and the impact of EIA sparing on outcomes following transplants.
The Effect of Social Work Services on a Self-Reported Functional Outcome
Authors: Knoop Tobias , Meyer Thorsten
Published: February 2020

Social work is a common service in medical rehabilitation in Germany. However, studies show inconsistent effects of social work interventions. This study aims to compare a self-reported rehabilitation outcome, which covered all functioning domains of the International Classification of Functioning, Disability and Health, in patients with and without social work interventions. The analysis is based on administrative data comprising individuals admitted to medical rehabilitation services due to an orthopedic ( n = 54,056) or cardiac ( n = 16,955) diagnosis between 2007 and 2011. The intervention and control groups were matched by propensity scores (PS) controlling for sociodemographic, clinical, and sociomedical characteristics. A sufficient overlap of the PS allowed a successful matching in both samples. Orthopedic and cardiac patients receiving social work interventions had a worse outcome compared to the control group ( d = −.20, p = .000). The results indicate a clear-cut need for in-depth analysis of social work practice in medical rehabilitation and implementation of controlled studies.
Minicircle DNA vector expressing interferon-lambda-3 inhibits hepatitis B virus replication and expression in hepatocyte-derived cell line
Authors: Guo Xiaoyan , Chen Dianke , Cai Qingxian , Huang Zhanlian , Xu Wenxiong , Peng Liang , Chen Ping
Published: February 2020

Background

Interferon-alpha (IFNα) is a first-line treatment option for chronic hepatitis B virus (HBV) infection, but the severe systemic side-effects limited its clinical application. Interferon-lambda (IFNλ) with comparable antiviral activity and less toxic side-effects is thought to be a good alternative interferon to IFNα. Additionally, the gene vector mediated sustainably expression of therapeutic product in the target cells/tissue may overcome the shortcomings resulted from the short half-life of IFNs.

Results

We constructed a liver-specific IFNλ3-expressing minicircle (MC) vector under the control of a hepatocyte-specific ApoE promoter (MC.IFNλ3) and investigated its anti-HBV activity in a HBV-expressing hepatocyte-derived cell model (HepG2.2.15). As expected, the MC.IFNλ3 vector capable of expressing IFNλ3 in the recipient hepatocytes has demonstrated robust anti-HBV activity, in terms of suppressing viral antigen expression and viral DNA replication, via activation the interferon-stimulated gene (ISG) expression in HepG2.2.15 cells.

Conclusions

Given the MC vector can be easily delivered into liver, the liver-targeted IFN gene-transfer (MC.IFNλ3), instead of systemic administrating IFN repeatedly, provides a promising concept for the treatment of chronic HBV infection.