bluuebunny/crossref_metadata_2025_split huggingface dataset:
Volume Growth, Curvature, and Buser-Type Inequalities in Graphs
Authors: Benson Brian , Ralli Peter , Tetali Prasad 
Published: October 2019

AbstractWe study the volume growth of metric balls as a function of the radius in discrete spaces and focus on the relationship between volume growth and discrete curvature. We improve volume growth bounds under a lower bound on the so-called Ollivier curvature and discuss similar results under other types of discrete Ricci curvature.Following recent work in the continuous setting of Riemannian manifolds (by the 1st author), we then bound the eigenvalues of the Laplacian of a graph under bounds on the volume growth. In particular, $\lambda _2$ of the graph can be bounded using a weighted discrete Hardy inequality and the higher eigenvalues of the graph can be bounded by the eigenvalues of a tridiagonal matrix times a multiplicative factor, both of which only depend on the volume growth of the graph. As a direct application, we relate the eigenvalues to the Cheeger isoperimetric constant. Using these methods, we describe classes of graphs for which the Cheeger inequality is tight on the 2nd eigenvalue (i.e. the 1st nonzero eigenvalue). We also describe a method for proving Buser’s Inequality in graphs, particularly under a lower bound assumption on curvature.
Substrate-based kinase activity inference identifies MK2 as driver of colitis
Authors: Strasser Samantha Dale , Ghazi Phaedra C , Starchenko Alina , Boukhali Myriam , Edwards Amanda , Suarez-Lopez Lucia , Lyons Jesse , Changelian Paul S , Monahan Joseph B , Jacobsen Jon , Brubaker Douglas K , Joughin Brian A , Yaffe Michael B , Haas Wilhelm , Lauffenburger Douglas A , Haigis Kevin M 
Published: October 2019

Abstract
Inflammatory bowel disease (IBD) is a chronic and debilitating disorder that has few treatment options due to a lack of comprehensive understanding of its molecular pathogenesis. We used multiplexed mass spectrometry to collect high-content information on protein phosphorylation in two different mouse models of IBD. Because the biological function of the vast majority of phosphorylation sites remains unknown, we developed Substrate-based Kinase Activity Inference (SKAI), a methodology to infer kinase activity from phosphoproteomic data. This approach draws upon prior knowledge of kinase-substrate interactions to construct custom lists of kinases and their respective substrate sites, termed kinase-substrate sets that employ prior knowledge across organisms. This expansion as much as triples the amount of prior knowledge available. We then used these sets within the Gene Set Enrichment Analysis framework to infer kinase activity based on increased or decreased phosphorylation of its substrates in a dataset. When applied to the phosphoproteomic datasets from the two mouse models, SKAI predicted largely non-overlapping kinase activation profiles. These results suggest that chronic inflammation may arise through activation of largely divergent signaling networks. However, the one kinase inferred to be activated in both mouse models was mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2 or MK2), a serine/threonine kinase that functions downstream of p38 stress-activated mitogen-activated protein kinase. Treatment of mice with active colitis with ATI450, an orally bioavailable small molecule inhibitor of the MK2 pathway, reduced inflammatory signaling in the colon and alleviated the clinical and histological features of inflammation. These studies establish MK2 as a therapeutic target in IBD and identify ATI450 as a potential therapy for the disease.
DOCK family proteins: key players in immune surveillance mechanisms
Authors: Kunimura Kazufumi , Uruno Takehito , Fukui Yoshinori 
Published: October 2019

Abstract
Dedicator of cytokinesis (DOCK) proteins constitute a family of evolutionarily conserved guanine nucleotide exchange factors (GEFs) for the Rho family of GTPases. Although DOCK family proteins do not contain the Dbl homology domain typically found in other GEFs, they mediate the GTP–GDP exchange reaction through the DOCK homology region-2 (DHR-2) domain. In mammals, this family consists of 11 members, each of which has unique functions depending on the expression pattern and the substrate specificity. For example, DOCK2 is a Rac activator critical for migration and activation of leukocytes, whereas DOCK8 is a Cdc42-specific GEF that regulates interstitial migration of dendritic cells. Identification of DOCK2 and DOCK8 as causative genes for severe combined immunodeficiency syndromes in humans has highlighted their roles in immune surveillance. In addition, the recent discovery of a naturally occurring DOCK2-inhibitory metabolite has uncovered an unexpected mechanism of tissue-specific immune evasion. On the other hand, GEF-independent functions have been shown for DOCK8 in antigen-induced IL-31 production in helper T cells. This review summarizes multifaced functions of DOCK family proteins in the immune system.
Heterogeneity of penicillin-non-susceptible group B streptococci isolated from a single patient in Germany
Authors: van der Linden Mark , Mamede Rafael , Levina Natascha , Helwig Peter , Vila-Cerqueira Pedro , Carriço João André , Melo-Cristino José , Ramirez Mário , Martins Elisabete R 
Published: October 2019

Abstract

Objectives
Streptococcus agalactiae [group B streptococci (GBS)] have been considered uniformly susceptible to penicillin. However, increasing reports from Asia and North America are documenting penicillin-non-susceptible GBS (PRGBS) with mutations in pbp genes. Here we report, to the best of our knowledge, the first two PRGBS isolates recovered in Europe (AC-13238-1 and AC-13238-2), isolated from the same patient.

Methods
Two different colony morphologies of GBS were noted from a surgical abscess drainage sample. Both were serotyped and antimicrobial susceptibility testing was performed by different methodologies. High-throughput sequencing was done to compare the isolates at the genomic level, to identify their capsular type and ST, to evaluate mutations in the pbp genes and to compare the isolates with the genomes of other PRGBS isolates sharing the same serotype and ST.

Results
Isolates AC-13238-1 and AC-13238-2 presented MICs above the EUCAST and CLSI breakpoints for penicillin susceptibility. Both shared the capsular type Ia operon and ST23. Genomic analysis uncovered differences between the two isolates in seven genes, including altered pbp genes. Deduced amino acid sequences revealed critical substitutions in PBP2X in both isolates. Comparison with serotype Ia clonal complex 23 PRGBS from the USA reinforced the similarity between AC-13238-1 and AC-13238-2, and their divergence from the US strains.

Conclusions
Our results support the in-host evolution of β-lactam-resistant GBS, with two PRGBS variants being isolated from one patient.
In vitro selection of aztreonam/avibactam resistance in dual-carbapenemase-producing Klebsiella pneumoniae
Authors: Niu Siqiang , Wei Jie , Zou Chunhong , Chavda Kalyan D , Lv Jingnan , Zhang Haifang , Du Hong , Tang Yi-Wei , Pitout Johann D D , Bonomo Robert A , Kreiswirth Barry N , Chen Liang 
Published: October 2019

AbstractObjectivesTo examine the in vitro selection of aztreonam/avibactam resistance among MBL-producing Klebsiella pneumoniae and to understand the mechanism of increased resistance.MethodsThe MICs of aztreonam were determined with and without avibactam (4 mg/L) using a broth microdilution method. Single-step and multi-step mutant selection was conducted on five MBL-producing K. pneumoniae strains, including two dual carbapenemase producers. Genomic sequencing and gene cloning were performed to investigate the mechanism of increased resistance.ResultsWe examined the MICs for 68 MBL-producing K. pneumoniae isolates, including 13 dual carbapenemase producers. Compared with aztreonam alone, the addition of avibactam (4 mg/L) reduced the MICs for all isolates by &gt;128-fold, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively. One NDM-1-, OXA-48-, CTX-M-15- and CMY-16-positive ST101 K. pneumoniae strain was selected to be resistant to aztreonam/avibactam, with a &gt;16-fold increase in MIC (&gt;128 mg/L). WGS revealed that the resistant mutants lost the blaNDM-1 gene, but acquired amino acid substitutions in CMY-16 (Tyr150Ser and Asn346His). Construction of blaCMY-16 mutants confirmed that the substitutions (Tyr150Ser and Asn346His) were primarily responsible for the decreased susceptibility to aztreonam/avibactam. In addition, transfer of blaCMY-16 mutant (Tyr150Ser and Asn346His) plasmid constructs into certain clinical carbapenemase-producing isolates demonstrated &gt;64-fold increased MICs of aztreonam/avibactam and aztreonam/avibactam/ceftazidime.ConclusionsAztreonam in combination with avibactam showed potent in vitro activity against MBL-producing K. pneumoniae. However, our study suggested the likelihood of aztreonam/avibactam resistance among MBL- and AmpC-co-producing strains and clinical practice should beware of the possibility of the emerging resistance.
Segmental Analysis of R/S-Methamphetamine and R/S-Amphetamine in Abusers’ Head Hair
Authors: Wang Ting , Shen Baohua , Wu Hejian , Gu Jun , Shen Min , Xiang Ping 
Published: October 2019

Abstract
In this study, the relationships between the concentrations of R/S-methamphetamine (MA) and its metabolite R/S-amphetamine (AP), the AP/MA ratio in hair samples, and MA dependence were investigated by performing segmental hair analysis in MA users. Authentic hair samples collected from 10 chronic MA abusers were cut into 1-cm sections (a total of 120 segments). The concentrations of MA and AM enantiomers were quantitatively measured by the LC–MS-MS method. The S-MA concentrations ranged from 1.17 to 256.41 ng/mg and the S-AP concentrations ranged from 0.11 to 23.31 ng/mg in the 120 segments. S-MA and S-AP were the most common analytes identified in hair; no R-MA or R-AP was found. The S-AP/S-MA ratios ranged from 0.03 to 0.32, indicating that the subjects primarily consumed S-MA rather than R-MA or AP. The S-AP/S-MA ratios in the long hair of all chronic MA abusers showed some variation, but there was an overall trend of gradual increase from the distal to the proximal end. This trend was independent of the drug concentrations. Therefore, we could conclude that the AP/MA ratios increased with the duration of MA abuse, and a higher AP/MA ratio suggested high MA dependence. There was no chiral conversion of MA or AP in the hair matrix. The segmental hair analysis showed that all subjects continuously used S-MA, and some users showed an increase in drug dose or the frequency of use.
Candidatus Rickettsia senegalensis in Cat Fleas (Siphonaptera: Pulicidae) Collected from Dogs and Cats in Cauca, Colombia
Authors: Betancourt-Ruiz Paola , Martínez-Díaz Heidy-C , Gil-Mora Juliana , Ospina Catalina , Olaya-M Luz-Adriana , Benavides Efraín , Bolaños Eliana , Cuervo Claudia , Blanton Lucas , Hidalgo Marylin 
Published: October 2019

AbstractRickettsia typhi and Rickettsia felis (Rickettsiales: Rickettsiaceae) are flea-transmitted pathogens. They are important causes of acute febrile illness throughout the world. We, therefore, sought to identify the rickettsial species present in the fleas of dogs and cats in the department of Cauca, Colombia. In this study, we collected 1,242 fleas from 132 dogs and 43 fleas from 11 cats. All fleas were morphologically identified as Ctenocephalides felis (Bouché) adults and organized in pools for DNA extraction (234 pools from dogs and 11 from cats). The gltA gene from rickettsiae was targeted for screening amplification using conventional PCR. In total, 144 of the 245 pools (58.7%) were positive. The positive samples were then processed for the amplification of the 17kDa antigen gene (144/144; 100% positive) and sca5 gene (140/144; 97.2% positive). In addition, restriction enzyme length polymorphism analysis using NlaIV on the amplified product of the sca5 gene demonstrated several organisms: 21/140 (15%) were R. felis, 118/140 (84.3%) were Rickettsia asemboensis, and 1/140 (0.7%) were Candidatus Rickettsia senegalensis. Subsequent sequencing confirmed Candidatus Rickettsia senegalensis in C. felis collected from dogs the first reported from Colombia.
The Power Puzzle: When Exclusion Increases Security and Inclusion Reduces It
Authors: Hazelton Jacqueline L 
Published: October 2019

AbstractThe empirical research in this issue explores sources of security and insecurity to reveal paradoxical relationships and dangerous assumptions. Drawing on this research and earlier findings about international and intra-state security, I argue that inclusion can drive insecurity and exclusion can support security. It is normatively appealing to believe that inclusion increases security in ways that benefit humans and polities and that exclusion decreases security. Authors here, however, find that it is not necessarily so. The key to increasing security as a positive good lies in understanding the actors' interests and goals. Some states and non-state actors may want to increase security in ways that do not benefit all. Others may profit by increasing insecurity. Some actors may seek inclusion while others prefer exclusion of self or other. The articles in this issue underline the importance of accurately identifying and examining assumptions in scholarship and policymaking.
Examining Differences in Parent Knowledge About Pediatric Food Allergies
Authors: Luke Anna K , Flessner Christopher A 
Published: October 2019

Abstract

Objective
Pediatric food allergy (FA) is a serious health condition that has become increasingly prevalent. Parents often play a primary role in assessing and managing risk for their child’s FAs, making it critical that they remain informed of the most recent guidelines for FA management. This study aimed to examine if diagnostic source (i.e., pediatrician vs. allergist) and child- and parent-level variables predicted parental FA knowledge using a comprehensive measure.

Methods
The Food Allergy Knowledge Test (FAKT) was administered to parents (N = 518) of children aged 3–17 years with (n = 349) and without (n = 169; i.e., control group) FAs using internet-sampling procedures. The sample was further partitioned into parents of children diagnosed by an allergist or a pediatrician, and control group parents who did or did not endorse knowing someone with an FA.

Results
Significant group differences were found with respect to the overall FAKT score and diagnostic source. Among the FA group, parental relationship to child, income, identification with a minority status, parental anxiety, and child possession of an emergency action plan were significant predictors of FAKT scores.

Conclusions
Knowledge of FA was poor across all groups. Education for caregivers both with and without food-allergic children is important to ensure FA safety in multiple settings. Future directions and limitations are discussed.
Prognostic impact of immunohistopathologic features in definitive radiation therapy for nasopharyngeal cancer patients
Authors: Murakami Naoya , Mori Taisuke , Kubo Yuko , Yoshimoto Seiichi , Ito Kimiteru , Honma Yoshitaka , Ueno Takao , Kobayashi Kenya , Okamoto Hiroyuki , Boku Narikazu , Takahashi Kana , Inaba Koji , Okuma Kae , Igaki Hiroshi , Nakayama Yuko , Itami Jun 
Published: October 2019

ABSTRACT
Our previous study by Murakami N, Mori T, Nakamura S, Yoshimoto S, Honma Y, Ueno T, Kobayashi K, Kashihara T, Takahashi K, Inaba K, Okuma K, Igaki H, Nakayama Y, Itami J. (J Radiat Res. 2019 Jul 30. pii: rrz053. doi: 10.1093/jrr/rrz053. [Epub ahead of print]) showed that strong expression of epithelial cell adhesion molecule (EpCAM) was associated with radiation resistance in head and neck squamous cell cancer patients (SCC). In this study, the prognostic impact of histopathologic features including EpCAM for nasopharyngeal cancer (NPC) patients was investigated. Since 2009, our institution has performed chemoradiation for locally advanced NPC patients with intensity modulated radiation therapy (IMRT). Tri-weekly adjuvant cisplatin (CDDP, 80 mg/m2) was administered concurrently with definitive radiation therapy 70 Gy in 35 fractions. One month after radiation therapy, adjuvant chemotherapy of three cycles of CDDP/5 fluorouracil (5-FU) was administered. Using a pretreatment biopsy specimen, EBV-encoded small RNA in situ hybridization (EBER-ISH), EpCAM, p16 and p53 were assessed by immunohistochemical analysis. Between May 2009 and September 2017, 51 NPC patients received definitive radiation therapy. Five, 13, 17 and 16 patients were staged as I, II, III and IV, respectively. The median follow-up period for alive patients was 31.1 months (12.4–109.7 months). Three-year overall survival (OS), progression-free survival (PFS) and locoregional control (LRC) were 87.1, 57.1 and 85.7%, respectively. EpCAM, p16 and p53 were not associated with PFS, OS nor LRC. Three-year PFS for patients with keratinizing and non-keratinizing SCC were 25 and 60.5%, respectively (P = 0.033, hazard ratio 4.851 (95% confidence interval 1.321–17.814)).Prognosis of NPC patients with keratinizing SCC was worse than non-keratinizing SCC patients, suggesting a biological difference between the two types of tumor.
Transcriptome sequencing reveals hotspot mutation regions and dwarfing mechanisms in wheat mutants induced by γ-ray irradiation and EMS
Authors: Xiong Hongchun , Zhou Chunyun , Guo Huijun , Xie Yongdun , Zhao Linshu , Gu Jiayu , Zhao Shirong , Ding Yuping , Liu Luxiang 
Published: October 2019

ABSTRACTInduced mutation is an important approach for creating novel plant germplasms. The introduction of dwarf or semi-dwarf genes into wheat has led to great advancements in yield improvement. In this study, four elite dwarf wheat mutants, named dm1–dm4, induced from γ-ray irradiation or ethyl methanesulfonate (EMS) mutagenesis, were used to identify transcriptome variations and dwarfing mechanisms. The results showed that the hotspot regions of mutations distributed on the chromosomes were consistent among the four mutant lines and these regions were mainly located around the 50, 360 and 400 Mb positions of chromosome 1A and the distal regions of chromosomes 2A and 2BL. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that ‘protein processing in endoplasmic reticulum’ was the most common significantly enriched pathway based on the differentially expressed genes (DEGs) between wildtype (WT) and the mutants. Notably, 18 out of 20 genes involved in this process encode heat shock proteins (HSPs). The results implied that HSPs might participate in wheat dwarfism response and function in the dwarfism process through protein folding and/or degradation. Moreover, seven genes in dm4 involved in modulating auxin levels were down-regulated and dm4 was more sensitive to auxin treatment compared with WT, indicating the important roles of auxin in regulation of dwarf phenotype in dm4. This study not only identified transcriptome sequence variation induced by physical and chemical mutagenesis but also revealed potential dwarfing mechanisms in the wheat mutant lines.
The Effect of Information Technology on the Information Exchange between Laboratories and Ambulatory Care Centers: A Systematic Review
Authors: Seyyedi Negisa , Moghaddasi Hamid , Asadi Farkhondeh , Hamidpour Mohsen , Shoaie Kamal 
Published: October 2019

Abstract
Laboratory services form an integral part of medical care in the decision-making of physicians, including those working at ambulatory care centers. Information exchange is essential between ambulatory care centers and laboratories. Inevitable errors have always existed in the exchange of such information on paper, which can be to some extent avoided by developing appropriate computer-based interfaces. Therefore, this review aimed to examine studies conducted to determine the effect of electronic communication between ambulatory care centers and laboratories. This systematic review was conducted on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were searched in the PubMed, Embase, Cochrane, and Web of Science, and those written in English and published between 2000 and February 2019 with full texts available were selected. From a total of 3898 papers retrieved from the studied databases, 24 papers were eligible for entering this study after removing similar and nonrelated studies. Electronic exchanges between ambulatory care centers and laboratories can have numerous benefits in terms of financial, organizational, and quality. This evidence for the value of electronic communications is an important factor contributing to its local investment and adoption.
Abdominal Surgery
Authors: Banerjee Ashis , Jafar Anisa J. N. , Mukherjee Angshuman , Solomonides Christian , Witt Erik 
Published: October 2019

Abstract
This chapter on abdominal surgery contains eight clinical Short Answer Questions (SAQs) with explanations and sources for further reading. Possible causes and accompanying symptoms of abdominal pain that may present in the emergency department include appendicitis, cholecystitis, cholangitis, ingested foreign body, rectal bleeding, gastric or sigmoid volvulus and post-laparoscopy complications.. It will be up to the emergency doctor to assess, diagnose, and decide upon a treatment path for each patient. The cases described in this chapter are all situations any emergency doctor is likely to encounter at some point in his or her career. The materials in this chapter will greatly aid revision for the Final FRCEM examination.
Dermatology
Authors: Banerjee Ashis , Jafar Anisa J. N. , Mukherjee Angshuman , Solomonides Christian , Witt Erik 
Published: October 2019

Abstract
This chapter on dermatology contains six clinical Short Answer Questions (SAQs) with explanations and sources for further reading. Rashes (which may be itchy or painful, or both), swelling of the lips (e.g. angioedema), cellulitis of the lower limb, and erythroderma may be indicative of potentially serious conditions, and it will be up to the emergency doctor to assess, diagnose, and decide upon a treatment path for each patient. The cases described in this chapter are all situations any emergency doctor is likely to encounter at some point in his or her career. The material in this chapter will greatly aid revision for the Final FRCEM examination.
Endocrinology
Authors: Banerjee Ashis , Jafar Anisa J. N. , Mukherjee Angshuman , Solomonides Christian , Witt Erik 
Published: October 2019

Abstract
This chapter on endocrinology contains six clinical Short Answer Questions (SAQs) with explanations and sources for further reading. Possible disorders and accompanying symptoms of endocrine origin that may present in the emergency department include hypoglycaemia, diabetic ketoacidosis, and thyroid storm, among others. It will be up to the emergency doctor to assess, diagnose, and decide upon a treatment path for each patient. The cases described in this chapter are all situations any emergency doctor is likely to encounter at some point in his or her career. The material in this chapter will greatly aid revision for the Final FRCEM examination.
ENT Surgery
Authors: Banerjee Ashis , Jafar Anisa J. N. , Mukherjee Angshuman , Solomonides Christian , Witt Erik 
Published: October 2019

Abstract
This chapter on ear, nose, and throat (ENT) surgery contains seven clinical Short Answer Questions (SAQs) with explanations and sources for further reading. Possible disorders and accompanying symptoms of ENT origin that may present in the emergency department include epistaxis, vertigo, peritonsillar abscess, nasal fracture, foreign bodies, and otitis externa. It will be up to the emergency doctor to assess, diagnose, and decide upon a treatment path for each patient. The cases described in this chapter are all situations any emergency doctor is likely to encounter at some point in his or her career. The material in this chapter will greatly aid revision for the Final FRCEM examination.