bluuebunny/crossref_metadata_2025 huggingface dataset:
Voting and Bribing in Single-Exponential Time
Authors: Knop Dušan , Koutecký Martin , Mnich Matthias
Published: June 2020

We introduce a general problem about bribery in voting systems. In the
R
-M
ulti
-B
ribery
problem, the goal is to bribe a set of voters at minimum cost such that a desired candidate is a winner in the perturbed election under the voting rule
R
. Voters assign prices for withdrawing their vote, for swapping the positions of two consecutive candidates in their preference order, and for perturbing their approval count to favour candidates.

As our main result, we show that
R
-M
ulti
-B
ribery
is fixed-parameter tractable parameterized by the number of candidates |
C
| with only a single-exponential dependence on |
C
|, for many natural voting rules 
R
, including all natural scoring protocols, maximin rule, Bucklin rule, Fallback rule, SP-AV, and any C1 rule. The vast majority of previous work done in the setting of few candidates proceeds by grouping voters into at most |
C
|! types by their preference, constructing an integer linear program with |
C
|!
2
variables, and solving it by Lenstra’s algorithm in time |
C
|!

|
C
|!

2
, hence double-exponential in |
C
|. Note that it is not possible to encode a large number of different voter costs in this way and still obtain a fixed-parameter algorithm, as that would increase the number of voter types and hence the dimension. These two obstacles of double-exponential complexity and restricted costs have been formulated as “Challenges #1 and #2” of the “Nine Research Challenges in Computational Social Choice” by Bredereck et al.

Hence, our result resolves the parameterized complexity of
R
-S
wap
-B
ribery
for the aforementioned voting rules plus Kemeny’s rule, and for all rules except Kemeny brings the dependence on |
C
| down to single-exponential. The engine behind our progress is the use of a new integer linear programming formulation, using so-called “
n
-fold integer programming.” Since its format is quite rigid, we introduce “extended
n
-fold IP,” which allows many useful modeling tricks. Then, we model
R
-M
ulti
-B
ribery
as an extended
n
-fold IP and apply an algorithm of Hemmecke et al. [Math. Prog. 2013].
Trajectory Outlier Detection
Authors: Belhadi Asma , Djenouri Youcef , Lin Jerry Chun-Wei , Cano Alberto
Published: June 2020

Detecting abnormal trajectories is an important task in research and industrial applications, which has attracted considerable attention in recent decades. This work studies the existing trajectory outlier detection algorithms in different industrial domains and applications, including maritime, smart urban transportation, video surveillance, and climate change domains. First, we review several algorithms for trajectory outlier detection. Second, different taxonomies are proposed regarding application-, output-, and algorithm-based levels. Third, evaluation of 10 trajectory outlier detection algorithms is performed on small, large, and big trajectory databases. Finally, future challenges and open issues with regard to trajectory outliers are derived and discussed. This survey offers a general overview of existing trajectory outlier detection algorithms in industrial informatics applications. As a result, mature solutions may be further developed by data mining and machine learning communities.
Biosynthesis and Export of Bacterial Glycolipids
Authors: Caffalette Christopher A. , Kuklewicz Jeremi , Spellmon Nicholas , Zimmer Jochen
Published: June 2020

Complex carbohydrates are essential for many biological processes, from protein quality control to cell recognition, energy storage, and cell wall formation. Many of these processes are performed in topologically extracellular compartments or on the cell surface; hence, diverse secretion systems evolved to transport the hydrophilic molecules to their sites of action. Polyprenyl lipids serve as ubiquitous anchors and facilitators of these transport processes. Here, we summarize and compare bacterial biosynthesis pathways relying on the recognition and transport of lipid-linked complex carbohydrates. In particular, we compare transporters implicated in O antigen and capsular polysaccharide biosyntheses with those facilitating teichoic acid and N-linked glycan transport. Further, we discuss recent insights into the generation, recognition, and recycling of polyprenyl lipids.
Structural and Mechanistic Principles of ABC Transporters
Authors: Thomas Christoph , Tampé Robert
Published: June 2020

ATP-binding cassette (ABC) transporters constitute one of the largest and most ancient protein superfamilies found in all living organisms. They function as molecular machines by coupling ATP binding, hydrolysis, and phosphate release to translocation of diverse substrates across membranes. The substrates range from vitamins, steroids, lipids, and ions to peptides, proteins, polysaccharides, and xenobiotics. ABC transporters undergo substantial conformational changes during substrate translocation. A comprehensive understanding of their inner workings thus requires linking these structural rearrangements to the different functional state transitions. Recent advances in single-particle cryogenic electron microscopy have not only delivered crucial information on the architecture of several medically relevant ABC transporters and their supramolecular assemblies, including the ATP-sensitive potassium channel and the peptide-loading complex, but also made it possible to explore the entire conformational space of these nanomachines under turnover conditions and thereby gain detailed mechanistic insights into their mode of action.
Long Noncoding RNAs: Molecular Modalities to Organismal Functions
Authors: Rinn John L. , Chang Howard Y.
Published: June 2020

We have known for decades that long noncoding RNAs (lncRNAs) can play essential functions across most forms of life. The maintenance of chromosome length requires an lncRNA (e.g., hTERC) and two lncRNAs in the ribosome that are required for protein synthesis. Thus, lncRNAs can represent powerful RNA machines. More recently, it has become clear that mammalian genomes encode thousands more lncRNAs. Thus, we raise the question: Which, if any, of these lncRNAs could also represent RNA-based machines? Here we synthesize studies that are beginning to address this question by investigating fundamental properties of lncRNA genes, revealing new insights into the RNA structure–function relationship, determining cis- and trans-acting lncRNAs in vivo, and generating new developments in high-throughput screening used to identify functional lncRNAs. Overall, these findings provide a context toward understanding the molecular grammar underlying lncRNA biology.
Changes in the host transcriptome and microbial metatranscriptome of the ileum of dairy calves subjected to artificial dosing of exogenous rumen contents
Authors: Li Wenli , Edwards Andrea , Cox Madison S. , Raabis Sarah M. , Skarlupka Joseph H. , Steinberger Andrew J. , Murphy Brianna , Larsen Anna , Suen Garret
Published: June 2020

Development of a properly functioning gastrointestinal tract (GIT) at an early age is critical for the wellbeing and lifetime productivity of dairy cattle. The role of early microbial colonization on GIT development in neonatal cattle and the associated molecular changes remain largely unknown, particularly for the small intestine. In this study, we performed artificial dosing of exogenous rumen fluid during the early life of the calf, starting at birth through the weaning transition at 8 wk. Six calves were included in this study. At 8 wk of age, tissue from the ileum was collected and subjected to host transcriptome and microbial metatranscriptome analysis using RNA sequencing. A total of 333 genes showed significant differential expression (DE) (fold-change ≥2; adjusted P < 0.1, mean read-count ≥10) between the treated and control calves. Gene ontology analysis indicated that these DE genes are predominantly associated with processes related to the host immune response ( P < 0.0001). Association analysis between the host gene expression and the microbial genus abundance identified 57 genes as having significant correlation with the ileum microbial genera ( P < 0.0001). Of these, three genes showed significant association with six microbial genera: lysozyme 2 ( LYZ2), fatty acid binding protein 5 ( FABP5), and fucosyltransferase (FUT1). Specifically, the profound increase in expression of LYZ2 in treated calves suggests the initiation of antibacterial activity and innate response from the host. Despite the limitation of a relatively small sample size, this study sheds light on the potential impact of early introduction of microbes on the small intestine of calves.
Motorcycle Accidents and Their Outcomes amongst Victims Admitted to Health Facilities in Guinea: A Cross-Sectional Study
Authors: Delamou Alexandre , Kourouma Karifa , Camara Bienvenu Salim , Kolie Delphin , Grovogui Fassou Mathias , El Ayadi Alison M. , Ade Serge , Harries Anthony D.
Published: June 2020

Background. Motorcycle road traffic accidents (RTA) constitute an increasing public health challenge with victims more likely to sustain fatal injuries compared with other types of RTA. The aim of this study was to analyze motorcycle RTA-related morbidity and mortality among victims admitted to hospitals in Guinea from 2015 to 2017. Materials and Methods. This was a cross-sectional study based on hospital records from six districts (Boké, Kindia, Mamou, Faranah, N’Zérékoré, and Siguiri) from January 1, 2015, to December 31, 2017. Bivariate analysis and multivariate logistic regression were used to explore associations between RTA types and mortality. Results. There were 14,962 RTA victims with motorcycle RTA accounting for 58.3% and other RTA 45.3% of hospital admissions. Overall, motorcycle RTA accounted for 77.7%, with young adults (96.2%) and males (73.5%) more affected when compared to victims of other types of RTA. Median age of motorcycle RTA victims was 23 years (IQR: 17–33 years). Students (29.7%), employees (23.6%), and farmers/housewives (23.3%) were the commonest groups affected by motorcycle RTA. The highest burden of motorcycle RTA occurred in the mining zones (Boké and Siguiri). Wounds (39.2% and 27.3%) and multiple injuries (43.8% and 43.8%) were the commonest types of injury sustained by victims of both motorcycle and other types of RTA, respectively. Motorcycle RTA accounted for 54% of overall deaths. Using multivariate logistic regression analysis, sustaining a motorcycle RTA in N’Zérékoré (AOR: 4.2; 95% CI: 1.6–11.2) and being admitted with mild (AOR: 7.4; 95% CI 2.1–25.8) and heavy or deep coma (AOR: 776.1; 95% CI: 340.2–1770.7) were significantly associated with mortality. Conclusions. Motorcycle RTA are an important cause of morbidity and mortality in Guinea. Males, young adult users, students, employees, and people from mining zones are the most affected. Better law enforcement and awareness raising among Guinean young adults are promising prevention strategies.
Melissopalynological Study, Phenolic Compounds, and Antioxidant Properties of Heterotrigona itama Honey from Johor, Malaysia
Authors: Majid Mahani , Ellulu Mohammed S. , Abu Bakar Mohd Fadzelly
Published: June 2020

Six honey samples produced by the stingless bee Heterotrigona itama were analyzed for their plant sources, phenolic compositions, and antioxidant activities. The honey samples were acetolyzed and identified microscopically, and the phenolic compounds were identified by using HPLC-DAD. The antioxidant activities were evaluated using three different assays (FRAP, DPPH, and ABTS) by spectrophotometry. The melissopalynological analysis showed that 26 pollen types from 14 plant families were identified in the honey. Cocos nucifera and Rhizophora mucronata presented as predominant pollen. A total of 6 phenolic acids such as catechin, chlorogenic acid, epicatechin, protocatechuic acid, p-coumaric acid, and rutin were identified. Rhizophora mucronata honey possessed the highest antioxidant activity in all assays. The result showed the influence of plant sources on the phenolic compounds and the antioxidant properties of stingless bee honey. These findings could be significant contributions for the sustainability of stingless bee industry as well as to promote Malaysian stingless bee honey worldwide.
Digital Biomimetic Architecture between Art and Dynamic Structure: Case Study—Wings in Flight
Authors: Wu Shi-Yen , Wagiri Felicia , Huang Yen-Fen , Shih Shen-Guan
Published: June 2020

Architecture as a multirelated field is influenced and connected by many subjects. Among those subjects, the role of art and natural science is the most dominant frame without ignoring the development of advanced technology. By using technology, the impossible becomes possible such as to capture the body motion of humans as the subject of art and science at the same time. Body motion is a potential research of movement over the time. This does not only involve the aesthetic, but also even more the scientific aspect of a dynamic motion of an organism that can be investigated through a biomimetic approach. In order to understand the biomimetic term, we investigated the physical morphogenesis and geometrical principle of an organism. The term morphogenesis is a process in which the natural system produces and regulates the configuration of a material in space and over time. Based on that, we tried to design a dynamic structure using butterfly’s motion as a subject of study with morphological and biomimetic approaches. Butterflies show a simultaneous aspect of movement over time characterized by fragmentation. This idea also summarizes many aspects of modern art such as portrayal of body movements by futurists, space-time continuum, cinematic freeze frame, and time-lapse photography. A futurist represents a movement that is emphasized on the factors of speed, technology, modernisms, and objects. This indicates an alternative position that may be relevant to the system of butterfly wings. This can only be achieved by utilizing a digital design and its parametric tools that help generate functions and form dynamic structures with high complexity and precision. Throughout the development of the system, there will be many changes to the form which will be constantly tested and evaluated using a series of prototype and visual digital design.
The Relationship between C-Reactive Protein/Albumin Ratio and Disease Activity in Patients with Inflammatory Bowel Disease
Authors: Chen Yi-Han , Wang Li , Feng Shu-Yi , Cai Wei-Min , Chen Xiao-Fu , Huang Zhi-Ming
Published: June 2020

Objectives. The aims of this study were to evaluate the C-reactive protein/albumin ratio (CRP/ALB), inflammatory markers, and parameters from the complete blood count (CBC) in patients with inflammatory bowel disease (IBD) and their associations with disease activity. Methods. A total of 876 IBD patients, composed of 275 patients with ulcerative colitis (UC) and 601 patients with Crohn’s disease (CD), were included in this retrospective study, and the serum C-reactive protein (CRP), albumin (ALB), erythrocyte sedimentation rate (ESR), and CBC parameters were measured. To explore the disease activity, the Mayo score and Crohn disease activity index were used to assess UC and CD patients, respectively. Results. The CRP/ALB ratio, CRP, ESR, platelet to lymphocyte ratio (PLR), red blood cell distribution width (RDW), and neutrophil to lymphocyte ratio (NLR) levels in active IBD patients were significantly higher than those in inactive IBD patients, whereas ALB and lymphocyte to monocyte ratio (LMR) levels were significantly decreased (P<0.001). The receiver operating characteristic analysis showed that the optimum cut-off values of the CRP/ALB ratio for active UC and CD were 0.18 and 0.43, with sensitivities of 67.8% and 75.8% and specificities of 86.7% and 92.0%, respectively. Multivariable logistic analysis revealed that after adjusting for these inflammatory markers (ESR, NLR, PLR, and LMR), the CRP/ALB ratio was a statistically significant parameter capable of differentiating the disease activity of UC and CD. Conclusions. This study indicated that the CRP/ALB ratio was closely related to the IBD disease activity. Compared with CBC parameters, the CRP/ALB ratio had a higher discriminative capacity for active IBD.
Fixed Point Theorems for Noncyclic Monotone Relativelyρ-Nonexpansive Mappings in Modular Spaces
Authors: El Harmouchi Nour-eddine , Chaira Karim , Marhrani El Miloudi
Published: June 2020

In this paper, we obtain some fixed point results for noncyclic monotoneρ-nonexpansive mappings in uniformly convex modular spaces and uniformly convex in every direction modular spaces. As an application, we prove the existence of the solution of an integral equation.
A Review on Model and Control of Electromagnetic Active Engine Mounts
Authors: Zhang Henghai , Shi Wenku , Ke Jun , Feng Guoyu , Qu Junlong , Chen Zhiyong
Published: June 2020

The isolation of the body from engine vibration is the most challenging and disruptive vibrational problem. Active engine mounts (AEMs), especially electromagnetic AEMs, achieve a significant performance improvement in decreasing the wide frequency band vibration. Increasing research interest is necessary to provide the academic community with a guideline for electromagnetic AEMs. Therefore, the current review aims to comprehensively supplement the review of AEMs. The key reviews of electromagnetic AEMs focus on (1) general considerations of electromagnetic AEMs, (2) models, and (3) control strategies. This paper presents a review of the current status and developmental progress of AEMs. A theoretical model, a finite-element model, and the identification (or experimental modelling) of electromagnetic AEMs during the last 2 decades are then studied. Finally, control strategies, such as classical control, adaptive control, and two degree of freedom (2DOF) control, are discussed and compared. The main purpose of this paper is to meet the needs of researchers and engineers engaged in electromagnetic AEM analysis and control.
Examination of Molecular Effects ofMYLKDeletion in a Patient with Extensive Aortic, Carotid, and Abdominal Dissections That Underlie the Genetic Dysfunction
Authors: Macklin Sarah K. , Bruno Katelyn A. , Vadlamudi Charitha , Helmi Haytham , Samreen Ayesha , Mohammad Ahmed N. , Hines Stephanie , Atwal Paldeep S. , Caulfield Thomas R.
Published: June 2020

We describe the phenotype of a patient with extensive aortic, carotid, and abdominal dissections. The proband was found to have a heterozygous deletion of exons 21–34 inMYLK, which is a rare finding, as deletions in this gene have been infrequently reported. We describe this finding following detection in a proband with an extensive history of aortic, carotid, and abdominal dissections. Neoteric molecular modeling techniques to help determine the impact of this deletion on protein function indicated loss of function due to lack of any kinase domain. We also provide the electrostatics calculations from the wild type and mutant variant. Through a combined multiomic approach of clinical, functional, and protein informatics, we arrive at a data fusion for determination of pathogenicity embedded within the genetic code for this particular genetic variant, which, as a platform, continues to broaden its scope across the field of variants of uncertain significance classification.
A Rare Paraneoplastic Syndrome of Lung Cancer
Authors: Azzeddine R. , Herrak L. , Rhanim A. , Jniene A. , Elftouh M. , Achachi L.
Published: June 2020

Achalasia is a neurodegenerative motor disease of the esophagus resulting mainly from a loss of function of the lower esophageal sphincter, the pathophysiology of which is still poorly understood. Its incidence is rare—it is 1.6 per 100,000—and its occurrence in the context of paraneoplastic syndrome has been rarely described in the literature. We report a rare case of paraneoplastic achalasia associated with lung cancer.
Perturbation Analysis of Population Growth Rates in Taiwan
Authors: Hsieh Shun-Chieh
Published: June 2020

The total fertility rate in Taiwan has fallen below 1.3 since 2003. The objective of the study is to use perturbation analysis with census data from 1992 to 2017 to identify which demographic parameters are most important to target for population management. The research shows that the fertility of older ages plays an important role for declining population in Taiwan. From a practical viewpoint, population management policy having a substantial impact on the survival of prereproductive females and the fertility of order females is likely to produce the most dramatic change in population trends. Therefore, the perturbation analysis is useful in understanding the relative importance of vital rates to increase management effectiveness.
Listeria monocytogenes Meningoencephalitis and Cerebral Abscess in a Heart Transplant Recipient
Authors: Adjei Paul C.
Published: June 2020

A 54-year-old male, five months postorthotopic heart transplantation, presented with intermittent fevers, headaches, and “soupy” stools. Prior to presentation, he had low-level cytomegalovirus (CMV) viremia for two straight weeks. Given his immunosuppression, diarrhea, and low-level CMV viremia, he was presumed to have cytomegalovirus and/or C. difficile colitis and treated empirically for both on hospital day one. However, he developed neck pain/stiffness, diaphoresis, and worsening fevers on hospital day three. Blood cultures eventually grew Listeria monocytogenes; MRI of the brain with gadolinium showed left brain meningoencephalitis with early cerebral abscess formation. Lumbar puncture revealed elevated opening pressure, CSF neutrophilic pleocytosis, and elevated CSF protein and lactate but negative gram stain and cultures. First-line agent for Listeria meningoencephalitis is ampicillin. However, he reported amoxicillin allergy. Desensitization to ampicillin failed because ampicillin was too unstable per the allergist. He was therefore treated with penicillin monotherapy for eight weeks with complete resolution of his brain lesions and without any residual neurologic deficits.
Determination of the Contents of Antioxidants and Their Degradation Products in Sodium Chloride Injection for Blood Transfusion
Authors: Tao Bo , Wang Gang , Yin Zongning , Pu Xiaocong , Jiang Yan , Zhang Luohong , Cheng Jie , Li Yong , Zhang Jiayu
Published: June 2020

The infusion bag is mainly made up of polyolefin polymer. Antioxidants are usually added to these polymer materials in the production process to prevent the materials from aging and enhance the stability of the materials. Because of the potential harm of antioxidants to human body, it is necessary to limit the amount of antioxidants migrating to the pharmaceutical solutions. In the present study, we developed and validated the HPLC method for the simultaneous quantification of antioxidants and their degradation products migrating to sodium chloride solution for injection. A total of six antioxidants and six their degradation products were separated and simultaneously determined by using a Waters Symmetry RP18 column (250 × 4.6 mm, 5 μm) and gradient elution of methanol/acetonitrile/acetic acid-water (1 : 99, v/v) at a flow rate of 1.0 mL/min. The detective wavelength was set at 277 nm, and the column temperature was maintained at 35°C. The method was validated in terms of limit of detection (LOD, 0.011–0.151 μg/mL), limit of quantification (LOQ, 0.031–0.393 μg/mL), intraday precision (0.25%–3.17%), interday precision (0.47%–3.48%), linearity (0.1–46.8 μg/mL, r > 0.9994), stability (0.35%–3.29%), and accuracy (80.39%–104.31%). In the extraction experiment, antioxidants, BHT, 1010, 1330, 1076, and 168, and their degradation products, 1310 and DBP, were detected in the packaging materials. Only 1310 was detected in the migration experiment. The maximum daily dosage of sodium chloride for blood transfusion is three bags, and the content of 1310 in long-term testing samples is from 0 to 12 months ranging from 37.44 μg/3 bags to 48.71 μg/3 bags. The daily intake of 1310 did not exceed 48.71 μg, which was much lower than its permitted daily exposure (PDE, 300 μg/day). Therefore, the antioxidants and their degradation products migrating into the drug solution would not cause drug safety risks.
Tube Length Adjustment and Tube Trimming Technique in Refractory Glaucoma
Authors: Soebijantoro Iwan , Noor Nina Asrini
Published: June 2020

Secondary glaucoma may develop after vitreoretinal surgery as it is a known risk factor for its development. When the risk factors are more than one, for instance along with neovascular glaucoma (NVG), the secondary glaucoma may become recalcitrant and very difficult to manage. Surgical intervention is often warranted to control intraocular pressure (IOP) and prevent progressive glaucomatous damage in patients with refractory glaucoma, and glaucoma drainage implant may be preferred as the primary choice. We describe a patient who develop secondary glaucoma after vitrectomy and silicone oil (SO) injection due to unresolved vitreous hemorrhage in proliferative diabetic retinopathy (PDR) and subsequent NVG. Baerveldt glaucoma implant (BGI) was carried out and placed in the superotemporal quadrant with longer anterior chamber tube placement to prevent escape of SO through the tube. Qualified success was achieved with additional one fixed-drug combination (FDC). However, 3 years later, the tube was blocked by the iris tissue at the inferior edge of the pupil. Tube trimming was performed efficiently using a simple technique. The distal end of the tube was pulled out of the anterior chamber through a paracentesis just next to the tube entrance and trimmed to the appropriate length. More than a year after the surgery, IOP was still well controlled with the same FDC. Unfortunately, the visual acuity could not be recovered due to advanced PDR.
Shenmai Injection Supresses Glycolysis and Enhances Cisplatin Cytotoxicity in Cisplatin‐Resistant A549/DDP Cells via the AKT‐mTOR‐c‐Myc Signaling Pathway
Authors: Sun Ye , Chen Yushi , Xu Ming , Liu Chunying , Shang Hai , Wang Chun
Published: June 2020

Tumor cells, especially drug‐resistant cells, predominately support growth by glycolysis even under the condition of adequate oxygen, which is known as the Warburg effect. Glucose metabolism reprogramming is one of the main factors causing tumor resistance. Previous studies on Shenmai injection (SMI), a Chinese herbal medicine, have shown enhanced efficacy in the treatment of tumors in combination with chemotherapy drugs, but the mechanism is not clear. In this study, we investigated the effect of SMI combined with cisplatin on cisplatin‐resistant lung adenocarcinoma A549/DDP cells. Our results showed that cisplatin‐resistant A549/DDP cells exhibited increased glucose consumption, lactate production, and expression levels of key glycolytic enzymes, including hexokinase 2 (HK2), pyruvate kinase M1/2 (PKM1/2), pyruvate kinase M2 (PKM2), glucose transporter 1 (GLUT1), and lactate dehydrogenase A (LDHA), compared with cisplatin‐sensitive A549 cells. SMI combined with cisplatin in A549/DDP cells, led to significantly lower expression levels of key glycolytic enzymes, such as HK2, PKM1/2, GLUT1, and pyruvate dehydrogenase (PDH). In addition, we found that the combination of SMI and cisplatin could inhibit cell proliferation and promote apoptosis by reducing the expression levels of p‐Akt, p‐mTOR, and c‐Myc, and then, it reduced the glycolysis level. These results suggest that SMI enhances the antitumor effect of cisplatin via glucose metabolism reprogramming. Therefore, the combination of SMI and cisplatin may be a potential therapeutic strategy to treat cisplatin‐resistant nonsmall cell lung cancer.
Mineral Composition of Traditional Non-GMO Soybean Cultivars in relation to Nitrogen Fertilization
Authors: Szostak Bogdan , Głowacka Aleksandra , Klebaniuk Renata , Kiełtyka-Dadasiewicz Anna
Published: June 2020

Soybean is widely used as food. Genetic factors, as well as agrotechnical procedures, affect the yield and quality of soybeans. The subject of our research was the synchronization between soil N supply (from both mineralization and fertilization) and crop N demand. The aim of the research was to determine the effect of the cultivar and nitrogen application on the seed yield and mineral content in soybeans. Two non-GMO soybean cultivars (Amandine and Merlin) and four mineral nitrogen fertilizers ((A) N 0, control; (B) N 30:0, 30 kg N ha−1 before sowing; (C) N 0:30, 30 kg N ha−1 at BBCH 73–75; (D) N 30:30, 30 kg N ha−1 before sowing and 30 kg N ha−1 at BBCH 73–75) were tested. The highest soybean yield was obtained following nitrogen application at a rate of 60 kg ha−1. The genetic factor was found to significantly influence the content of some macronutrients (P, K, and Mg) and micronutrients (Cu, Mn, and Fe). In general, the Merlin cultivar had better macronutrient parameters except nitrogen, while Amandine had a higher content of Cu and Fe. Nitrogen fertilization decreased the content of P, K, and Zn in the soybeans but significantly increased the content of Ca, Mg, Cu, and Mn.
The Interaction Test of Binary Mixtures of Endocrine-Disrupting Chemicals Using In Vitro Bioassays
Authors: Tang Qianqian , Lei Bingli , Liu Yun , Zhang Xiaolan , Liu Qian , Sun Su
Published: June 2020

Typical environmental endocrine-disrupting chemicals (EDCs) such as estradiol valerate (EV), diethylstilbestrol (DES), di-2-ethylhexyl phthalate (DEHP), mono-2-ethylhexyl phthalate (MEHP), and bisphenol A (BPA) have a strong reproductive and developmental toxicity at low concentrations. However, information on their joint toxicity is scarce. In this study, we evaluated the combined effects of EV and other four EDCs (DES, DEHP, MEHP, and BPA) on the human breast MCF-7 cells by detecting the cell proliferation, intracellular reactive oxygen species (ROS) levels, and estrogen receptor alpha (ERα) protein expression using equal concentration ratio method. The results showed that, after exposure for 24, 48, and 72 h, single EV, DES, and BPA can promote the proliferation of MCF-7 human breast cancer cells, and EV has the strongest effect in inducing cell proliferation. DEHP and MEHP cannot induce MCF-7 cell proliferation for all exposure time, while cell proliferation induced by EV was significantly attenuated by DES, BPA, DEHP, and MEHP when they mixed with EV. For intracellular ROS, single EV, BPA, DES, DEHP, and MEHP elevated intracellular ROS levels for different exposure time. Similar to the cell proliferation, DES and BPA decreased intracellular ROS levels induced by EV when they mixed with EV for 24 h. EV, DES, and BPA exposed alone or combined with EV upregulated the ERα protein expression. However, DEHP and MEHP exposed alone or combined with EV had no effect on ERα protein expression, indicating that DEHP or MEHP could attenuate ERα protein expression upregulated by EV. These results showed that the joint toxicity of binary mixtures of EV and other EDCs do not interact in a synergistic fashion in inducing cell proliferation, intracellular ROS levels, and ERα protein expression. These findings have important implications in the human risk assessments of EV mixed with other EDCs in the environment.
Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition
Authors: Ngo Bryan , Kim Eugenie , Osorio-Vasquez Victoria , Doll Sophia , Bustraan Sophia , Liang Roger J. , Luengo Alba , Davidson Shawn M. , Ali Ahmed , Ferraro Gino B. , Fischer Grant M. , Eskandari Roozbeh , Kang Diane S. , Ni Jing , Plasger Ariana , Rajasekhar Vinagolu K. , Kastenhuber Edward R. , Bacha Sarah , Sriram Roshan K. , Stein Benjamin D. , Bakhoum Samuel F. , Snuderl Matija , Cotzia Paolo , Healey John H. , Mainolfi Nello , Suri Vipin , Friedman Adam , Manfredi Mark , Sabatini David M. , Jones Drew R. , Yu Min , Zhao Jean J. , Jain Rakesh K. , Keshari Kayvan R. , Davies Michael A. , Vander Heiden Matthew G. , Hernando Eva , Mann Matthias , Cantley Lewis C. , Pacold Michael E.
Published: June 2020

A hallmark of metastasis is the adaptation of tumor cells to new environments. Metabolic constraints imposed by the serine and glycine–limited brain environment restrict metastatic tumor growth. How brain metastases overcome these growth-prohibitive conditions is poorly understood. Here, we demonstrate that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the rate-limiting step of glucose-derived serine synthesis, is a major determinant of brain metastasis in multiple human cancer types and preclinical models. Enhanced serine synthesis proved important for nucleotide production and cell proliferation in highly aggressive brain metastatic cells. In vivo, genetic suppression and pharmacologic inhibition of PHGDH attenuated brain metastasis, but not extracranial tumor growth, and improved overall survival in mice. These results reveal that extracellular amino acid availability determines serine synthesis pathway dependence, and suggest that PHGDH inhibitors may be useful in the treatment of brain metastasis.

Significance:

Using proteomics, metabolomics, and multiple brain metastasis models, we demonstrate that the nutrient-limited environment of the brain potentiates brain metastasis susceptibility to serine synthesis inhibition. These findings underscore the importance of studying cancer metabolism in physiologically relevant contexts, and provide a rationale for using PHGDH inhibitors to treat brain metastasis.

This article is highlighted in the In This Issue feature, p. 1241
Trajectories of Waist-to-Hip Ratio and Adverse Outcomes in Heart Failure with Mid-Range Ejection Fraction
Authors: Gao Feng , Wan Jindong , Xu Banglong , Wang Xiaochen , Lin Xianhe , Wang Peijian
Published: June 2020

Background: Waist-to-hip ratio (WHR) is a strong predictor of mortality in patients with heart failure (HF). However, common WHR trajectories are not well established in HF with mid-range ejection fraction (HFmrEF) persons, and their relationship to clinical outcomes remains uncertain. Method: We prospectively enrolled 1,396 participants with HFmrEF (left ventricular ejection fraction 40–49%) from April 2013 through April 2017. The waist and hip circumferences of the subjects were measured at regular intervals, and the WHR was calculated as waist circumference divided by hip circumference. Latent mixture modeling was performed to identify WHR trajectories. We then used Cox proportional-hazard models to examine the association between WHR trajectory patterns and incident HF, incident cardiovascular disease (CVD), and all-cause mortality. Results: We identified four distinct WHR trajectory patterns: lean-moderate increase (9.2%), medium-stable/increase (32.7%), heavy-stable/increase (48.0%), and heavy-moderate decrease (10.1%). After multivariable adjustment, the heavy-stable/increase and heavy-moderate decrease patterns were associated with an increased all-cause mortality risk (heavy-stable/increase: adjusted hazard ratio [HR] 3.18, 95% confidence interval [CI] 2.75–4.62; heavy-moderate decrease: adjusted HR 2.32, 95% CI 1.71–3.04), incident CVD risk (heavy-stable/increase: adjusted HR 4.03, 95% CI 2.39–4.91; heavy-moderate decrease: adjusted HR 3.05, 95% CI 2.34–4.09), and incident HF risk (heavy-stable/increase: adjusted HR 2.72, 95% CI 2.05–3.28; heavy-moderate decrease: adjusted HR 2.39, 95% CI 1.80–3.03) with reference to the lean-moderate increase pattern. Conclusion: Among patients with HFmrEF, the trajectories of WHR gain are associated with poor outcomes. These findings highlight the importance of abdominal fat accumulation management during the progression of HFmrEF.
Endoscopic Ultrasound-Guided Ablation of Focal Pancreatic Lesions: The GRUPUGE Perspective
Authors: Bispo Miguel , Caldeira Ana , Leite Sílvia , Marques Susana , Moreira Teresa , Moutinho-Ribeiro Pedro , Nunes Nuno ,   Portuguese Group for Ultrasound in Gastroenterology (GRUPUGE)
Published: June 2020

Focal pancreatic lesions include a heterogeneous group of solid and cystic lesions, with different natures and variable clinical, imagiological, and pathological characteristics. Several endoscopic ultrasound (EUS)-guided ablative techniques have been tested during the last decade for the treatment of these pancreatic lesions, mostly consisting of the injection of ablative agents and, more recently, radiofrequency ablation. The most encouraging EUS-guided ablation outcomes are being reached in the treatment of some pancreatic cystic neoplasms and small (≤2 cm) pancreatic neuroendocrine tumours (pNETs). Data supporting a potential role of ablative therapies in the treatment of pancreatic ductal adenocarcinoma is still lacking. In this article, GRUPUGE presents an updated perspective of the potential role of EUS-guided ablation for the treatment of pancreatic cystic neoplasms and pNETs, addressing the selection criteria and technical issues of different techniques and analysing recent data on their safety and efficacy.
Mouse Models of Rheumatoid Arthritis for Studies on Immunopathogenesis and Preclinical Testing of Fc Receptor-Targeting Biologics
Authors: Lewis Bonnie J.B. , Branch Donald R.
Published: June 2020

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation, swelling, and pain in the joints and involves systemic complications. Mouse models of RA have been extensively used to model the pathogenesis of RA and to develop effective therapies. Although many components of the immune system have been studied in these models, the role of crystallizable fragment (Fc) gamma receptors (FcγRs) in RA has been sorely neglected. The aim of this review was to introduce the different mouse models of RA and to describe the different drug development strategies that have been tested in these models to target FcγR function, with the focus being on drugs that have been made from the Fc of immunoglobulin G (IgG). Summary: Evidence suggests that FcγRs play a major role in immune complex-induced inflammation in autoimmune diseases, such as RA. However, there is limited knowledge on the importance of FcγRs in the human disease even though there has been extensive work in mouse models of RA. Numerous mouse models of RA are available, with each model depicting certain aspects of the disease. Induced models of RA have nonspecific immune activation with cartilage-directed autoimmunity, whereas spontaneous models of RA develop without immunization, which results in a more chronic form of arthritis. These models have been used to test FcγR-targeting monoclonal antibodies, intravenous immunoglobulin (IVIg), subcutaneously administered IVIg, and recombinant Fcs for their ability to interact with and modify FcγR function. Recombinant Fcs avidly bind FcγRs and exhibit enhanced therapeutic efficacy in mouse models of RA. Key Message: The therapeutic utility of targeting FcγRs with recombinant Fcs is great and should be explored in human clinical trials for autoimmune diseases, such as RA.
The Clinical Importance of Androgen Receptor Status in Response to Neoadjuvant Chemotherapy in Turkish Patients with Local and Locally Advanced Breast Cancer
Authors: Arici Serdar , Sengiz Erhan Selma , Geredeli Caglayan , Cekin Ruhper , Sakin Abdullah , Cihan Sener
Published: June 2020

Purpose: To investigate whether androgen receptor (AR) status affects neoadjuvant chemotherapy (NACT) in stage II and III Turkish breast cancer patients. Methods: The histological response for breast and axilla was assessed according to the Miller-Payne grading system. In light microscopy, nuclear staining in tumor cells was evaluated, and nuclear staining above 1% was accepted as positive for AR expression. The patients were divided into 3 groups according to the intensity of AR staining: low, moderate, and high. Results: In total, 71 women with breast cancer were included in the study. In univariate analysis, age, menopause status, tumor diameter, stage, histological grade, Ki-67, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER-2) status were tested to determine which of these factors were associated with >90% responsiveness. AR negativity was found to be the only statistically significant factor. In multivariate analysis, AR positivity at each intensity was found to be the single important factor affecting decreasing pathologic response in patients receiving NACT for breast cancer. Conclusion: Our results show that AR positivity is associated with poor response to NACT in Turkish breast cancer patients and that AR positivity is independent of stage, hormone receptor status, HER-2 status, and disease stage.
Single-Center Noninferiority Randomized Trial on the Efficacy and Safety of Low- and High-Dose Rush Oral Milk Immunotherapy for Severe Milk Allergy
Authors: Takaoka Yuri , Yajima Yuko , Ito Yoichi M. , Kumon Junko , Muroya Takahiro , Tsurinaga Yuki , Shigekawa Amane , Takahashi Shinichi , Iba Norihito , Tsuji Taisuke , Nishikido Tomoki , Yoshida Yukinori , Doi Satoru , Kameda Makoto
Published: June 2020

Introduction: Oral immunotherapy (OIT) has been reported to be effective but associated with a risk of severe symptoms. Thus, an OIT method with decreased risk is required. Objectives: We aimed to evaluate the efficacy and safety of low- and high-dose OIT regimens in children with severe milk allergy. Methods: Overall, 33 participants (median age, 9 years; median final dose of the milk oral food challenge [OFC], 2 mL) were included. The participants were randomly assigned to groups that received either a low (20 mL; n = 19) or high (100 mL; n = 14) maintenance target dose of OIT. The dose was gradually increased to the target dose in the rush escalation phase and was then maintained daily at home. The primary endpoint was the final OFC dose at 6 months of OIT. Adverse events during OIT were evaluated. Results: The final OFC dose after OIT was significantly higher than that before OIT in both groups (low-dose, p = 0.000; high-dose, p = 0.006), but there was no significant difference in the final OFC dose between the 2 groups (p = 0.767). In the maintenance phase, the high-dose group had significantly more severe symptoms than did the low-dose group (0.5%, 11/2,355 total intake events vs. 0.1%, 4/3,230 total intake events; p = 0.018). Conclusions: An equally increased dose effect was observed for maintenance OIT doses of 20 and 100 mL in children with severe milk allergy. The risk of severe symptoms in the maintenance phase was lower in the low-dose group. A low-dose OIT regimen is recommended for severe milk allergy.
Nuclear Morphology and the Biology of Cancer Cells
Authors: Fischer Edgar G.
Published: June 2020

Background: For more than a century, diagnostic pathologists have used morphologic abnormalities of the nucleus as essential diagnostic features to distinguish benign from malignant cells. These features include nuclear enlargement and increased nuclear-to-cytoplasmic ratio, nuclear membrane irregularities, hyperchromasia, and abnormal chromatin distribution. As our knowledge about the genetic and epigenetic abnormalities of cancer cells has increased in recent decades, the pathophysiologic mechanisms that underlie these morphologic abnormalities remain incompletely understood. Summary: This review attempts to summarize biologic abnormalities in malignant cells related to these morphologic changes. The molecular anatomy of the nuclear envelope in normal and malignant cells is discussed as well as regulation of nuclear size and shape, regulation of signal transduction pathways by molecules of the nuclear envelope, chromatin distribution, and the effects of HPV infection on dysplastic cells in the uterine cervix. Key Message: Causes of morphologic nuclear abnormalities in malignant cells are likely multifactorial. They probably include mutations, dysregulation of signal transduction pathways, abnormal gene expression patterns, alterations of nuclear envelope proteins and chromatin, and aneuploidy.
Self-Measured Blood Pressure Monitoring at Home: A Joint Policy Statement From the American Heart Association and American Medical Association
Authors: Shimbo Daichi , Artinian Nancy T. , Basile Jan N. , Krakoff Lawrence R. , Margolis Karen L. , Rakotz Michael K. , Wozniak Gregory ,   On behalf of the American Heart Association and the American Medical Association
Published: June 2020

The diagnosis and management of hypertension, a common cardiovascular risk factor among the general population, have been based primarily on the measurement of blood pressure (BP) in the office. BP may differ considerably when measured in the office and when measured outside of the office setting, and higher out-of-office BP is associated with increased cardiovascular risk independent of office BP. Self-measured BP monitoring, the measurement of BP by an individual outside of the office at home, is a validated approach for out-of-office BP measurement. Several national and international hypertension guidelines endorse self-measured BP monitoring. Indications include the diagnosis of white-coat hypertension and masked hypertension and the identification of white-coat effect and masked uncontrolled hypertension. Other indications include confirming the diagnosis of resistant hypertension and detecting morning hypertension. Validated self-measured BP monitoring devices that use the oscillometric method are preferred, and a standardized BP measurement and monitoring protocol should be followed. Evidence from meta-analyses of randomized trials indicates that self-measured BP monitoring is associated with a reduction in BP and improved BP control, and the benefits of self-measured BP monitoring are greatest when done along with cointerventions. The addition of self-measured BP monitoring to office BP monitoring is cost-effective compared with office BP monitoring alone or usual care among individuals with high office BP. The use of self-measured BP monitoring is commonly reported by both individuals and providers. Therefore, self-measured BP monitoring has high potential for improving the diagnosis and management of hypertension in the United States. Randomized controlled trials examining the impact of self-measured BP monitoring on cardiovascular outcomes are needed. To adequately address barriers to the implementation of self-measured BP monitoring, financial investment is needed in the following areas: improving education and training of individuals and providers, building health information technology capacity, incorporating self-measured BP readings into clinical performance measures, supporting cointerventions, and enhancing reimbursement.