bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type II Secretion-Dependent Aminopeptidase LapA and Acyltransferase PlaC Are Redundant for Nutrient Acquisition during
Legionella pneumophila
Intracellular Infection of Amoebas
Authors: White Richard C. , Gunderson Felizza F. , Tyson Jessica Y. , Richardson Katherine H. , Portlock Theo J. , Garnett James A. , Cianciotto Nicholas P. 
Published: April 2018

ABSTRACT

Legionella pneumophila
genes encoding LapA, LapB, and PlaC were identified as the most highly upregulated type II secretion (T2S) genes during infection of
Acanthamoeba castellanii
, although these genes had been considered dispensable on the basis of the behavior of mutants lacking either
lapA
and
lapB
or
plaC
. A
plaC
mutant showed even higher levels of
lapA
and
lapB
transcripts, and a
lapA lapB
mutant showed heightening of
plaC
mRNA levels, suggesting that the role of the LapA/B aminopeptidase is compensatory with respect to that of the PlaC acyltransferase. Hence, we made double mutants and found that
lapA plaC
mutants have an ~50-fold defect during infection of
A. castellanii
. These data revealed, for the first time, the importance of LapA in any sort of infection; thus, we purified LapA and defined its crystal structure, activation by another T2S-dependent protease (ProA), and broad substrate specificity. When the amoebal infection medium was supplemented with amino acids, the defect of the
lapA plaC
mutant was reversed, implying that LapA generates amino acids for nutrition. Since the LapA and PlaC data did not fully explain the role of T2S in infection, we identified, via proteomic analysis, a novel secreted protein (NttD) that promotes infection of
A. castellanii
. A
lapA plaC nttD
mutant displayed an even greater (100-fold) defect, demonstrating that the LapA, PlaC, and NttD data explain, to a significant degree, the importance of T2S. LapA-, PlaC-, and NttD-like proteins had distinct distribution patterns within and outside the
Legionella
genus. LapA was notable for having as its closest homologue an
A. castellanii
protein.

IMPORTANCE
Transmission of
L. pneumophila
to humans is facilitated by its ability to grow in
Acanthamoeba
species. We previously documented that type II secretion (T2S) promotes
L. pneumophila
infection of
A. castellanii
. Utilizing transcriptional analysis and proteomics, double and triple mutants, and crystal structures, we defined three secreted substrates/effectors that largely clarify the role of T2S during infection of
A. castellanii
. Particularly interesting are the unique functional overlap between an acyltransferase (PlaC) and aminopeptidase (LapA), the broad substrate specificity and eukaryotic-protein-like character of LapA, and the novelty of NttD. Linking LapA to amino acid acquisition, we defined, for the first time, the importance of secreted aminopeptidases in intracellular infection. Bioinformatic investigation, not previously applied to T2S, revealed that effectors originate from diverse sources and distribute within the
Legionella
genus in unique ways. The results of this study represent a major advance in understanding
Legionella
ecology and pathogenesis, bacterial secretion, and the evolution of intracellular parasitism.
Trends, geographical variation and factors associated with prescribing of gluten-free foods in English primary care: a cross-sectional study
Authors: Walker Alex J , Curtis Helen J , Bacon Seb , Croker Richard , Goldacre Ben 
Published: April 2018

ObjectivesThere is substantial disagreement about whether gluten-free foods should be prescribed on the National Health Service. We aim to describe time trends, variation and factors associated with prescribing gluten-free foods in England.SettingEnglish primary care.ParticipantsEnglish general practices.Primary and secondary outcome measuresWe described long-term national trends in gluten-free prescribing, and practice and Clinical Commissioning Group (CCG) level monthly variation in the rate of gluten-free prescribing (per 1000 patients) over time. We used a mixed-effect Poisson regression model to determine factors associated with gluten-free prescribing rate.ResultsThere were 1.3 million gluten-free prescriptions between July 2016 and June 2017, down from 1.8 million in 2012/2013, with a corresponding cost reduction from £25.4 million to £18.7 million. There was substantial variation in prescribing rates among practices (range 0 to 148 prescriptions per 1000 patients, IQR 7.3–31.8), driven in part by substantial variation at the CCG level, likely due to differences in prescribing policy. Practices in the most deprived quintile of deprivation score had a lower prescribing rate than those in the highest quintile (incidence rate ratio 0.89, 95% CI 0.87 to 0.91). This is potentially a reflection of the lower rate of diagnosed coeliac disease in more deprived populations.ConclusionGluten-free prescribing is in a state of flux, with substantial clinically unwarranted variation between practices and CCGs.
Targeting Toll-like Receptors in Cancer Prevention
Authors: Sfanos Karen S. 
Published: April 2018

Abstract
There is a pressing need for the development of new prevention strategies for the most common worldwide malignancy, nonmelanoma skin cancer (NMSC), as sun protection efforts have not proven to be completely effective. Interestingly, despite the known circumstance that individuals undergoing chronic immunosuppression are at a substantially increased risk for developing NMSC, in this issue of Cancer Prevention Research, Blohm-Mangone and colleagues provide new evidence that topical application of the Toll-like receptor 4 (TLR4) antagonist resatorvid may be efficacious as a chemopreventive agent in NMSC specifically via blocking UV-induced inflammatory signaling. These new findings highlight a potentially delicate dichotomy between the role of innate immune receptors in the normal, protective immunosurveillance of damaged cells in the skin and the pathogenic UV-induced overstimulation of cutaneous inflammation that promotes photocarcinogenesis. Given the tremendous cancer burden incurred by NMSC, further exploration of the use of TLR4 antagonists in NMSC chemoprevention strategies is certainly warranted. Cancer Prev Res; 11(5); 251–4. ©2018 AACR.
See related article by Blohm-Mangone et al., p. 265
The Commitment to Go on Theorizing “Religion”
Authors: Taira Teemu 
Published: April 2018

AbstractThere are two kinds of scholars in the world, those who do theory and those who do not. This is one of the main organizing binaries inTheory in a Time of Excess(edited by Aaron W. Hughes). All contributors of the volume agree that theory is something that is valuable. In this essay I explore what theory means in this book and how contributors to the volume highlight different aspects of theorizing. This opens up the question of who are the most fruitful conversation partners that potentially maintain and extend a commitment to theorizing.
The Madness of Cambyses: Herodotus and the Problem of Inquiry
Authors: Rathnam Lindsay Mahon 
Published: April 2018

Abstract
In his evaluation of the mad despot Cambyses, Herodotus proclaims that preference for one’s own culture persists after examination. This paper examines how Herodotus’ treatment of Cambyses reveals the insidious ways that thought is bounded by cultural attachments. Blindness to one’s attachments spurs the drive to empire by covering and justifying expansionist appetites. Herodotus’ treatment of Cambyses’ imperialist inquiries will thus not only implicate the Persians, but raise unsettling questions about the Hellenes’ own appetites. Herodotus offers his own methods of inquiry as an alternative. Rather than denying appetite and rendering it subterranean, Herodotus suggests that inquiry must be motivated by the quest for self-knowledge – understanding the diversity of the world helps reveal the fuller contours of human nature. Herodotus’ storytelling engages affect by provoking the intellectual curiosity of his audience. It promises that expansionist appetites can be rehabilitated into genuine curiosity and openness to difference.
The Law in Plato’s Laws: A Reading of the ‘Classical Thesis’
Authors: Hunt Luke William 
Published: April 2018

Abstract
Plato’s Laws include what H.L.A. Hart called the ‘classical thesis’ about the nature and role of law: the law exists to see that one leads a morally good life. This paper develops Hart’s brief remarks by providing a panorama of the classical thesis in Laws. This is done by considering two themes: (1) the extent to which Laws is paternalistic, and (2) the extent to which Laws is naturalistic. These themes are significant for a number of reasons, including because they show how Laws might be viewed as a sophisticated forerunner of natural law theory. The upshot is that Plato’s metaphysical commitments about legal ontology allow him to base the truth of legal propositions on the way they relate to the truth of corresponding moral propositions.
Philosophical Genesis: The Three Waves and the City-Soul Analogy in Republic v
Authors: Thomas Charlotte C.S. , Honeycutt Kevin S. 
Published: April 2018

Abstract
It is conventional to argue that the city-soul analogy of Plato’s Republic dominates Books ii through iv and viii through x but is absent in Books v through vii. We argue that the analogy remains operative in Books v through vii and that its role there, especially as it is played out in the motif of the three waves, illuminates its function in the dialogue as a whole, particularly with respect to the questions: What are the natural dispositions of soul necessary for philosophy? What are the necessary and sufficient conditions for philosophical education?
Hermetic Influences on the Evolutionary System of Helena Blavatsky’s Theosophy
Authors: Prophet Erin 
Published: April 2018

AbstractHelena Blavatsky (1831–1891) developed a program of salvation that she called “double evolution,” which was elaborated in a system known as root race theory. Human souls were seen as traversing through progressive reincarnation a series of seven “races,” or body types, ranging from gigantic amorphous and ethereal bodies and transitioning through hermaphroditic into gigantic gendered ape-like humans, modern humans, and thereafter adepts and divine beings. Although root race theory drew from the scientific racism of its day, it did not equate root races with human races, but to stages of human emanation from and return to divinity. The sources of root race theory have been sought in Eastern contexts due to its use of Hindu and Buddhist terminology, though scholars have noted its Western esoteric influences. This article argues that the primary structure of root race theory is based in the Corpus Hermeticum. It identifies some of Blavatsky’s Hermetic sources, showing that she referred not only generally to a perennialist “Hermetic philosophy” that incorporated Western esoteric tropes, but also to specific Hermetic texts. These texts provided the organizing matrix of root race theory, specifically its creation mythology, support for prior androgyne human existence, a “fall into matter,” and the initial ensoulment of humans with mind, ornous. It also provided a template for the future transformation of humans into divine beings. The article builds on the suggestions of Nicholas Goodrick-Clarke (2013) and Brendan French (2001) to elaborate on the role of Hermetic influence in Blavatsky’s reconfiguring of evolution as a novel form of salvation for an empirically-oriented nineteenth century audience.
Estimated Cost to a Restaurant of a Foodborne Illness Outbreak
Authors: Bartsch Sarah M. , Asti Lindsey , Nyathi Sindiso , Spiker Marie L. , Lee Bruce Y. 
Published: April 2018

Objectives: Although outbreaks of restaurant-associated foodborne illness occur periodically and make the news, a restaurant may not be aware of the cost of an outbreak. We estimated this cost under varying circumstances. Methods: We developed a computational simulation model; scenarios varied outbreak size (5 to 250 people affected), pathogen (n = 15), type of dining establishment (fast food, fast casual, casual dining, and fine dining), lost revenue (ie, meals lost per illness), cost of lawsuits and legal fees, fines, and insurance premium increases. Results: We estimated that the cost of a single foodborne illness outbreak ranged from $3968 to $1.9 million for a fast-food restaurant, $6330 to $2.1 million for a fast-casual restaurant, $8030 to $2.2 million for a casual-dining restaurant, and $8273 to $2.6 million for a fine-dining restaurant, varying from a 5-person outbreak, with no lost revenue, lawsuits, legal fees, or fines, to a 250-person outbreak, with high lost revenue (100 meals lost per illness), and a high amount of lawsuits and legal fees ($1 656 569) and fines ($100 000). This cost amounts to 10% to 5790% of a restaurant’s annual marketing costs and 0.3% to 101% of annual profits and revenue. The biggest cost drivers were lawsuits and legal fees, outbreak size, and lost revenue. Pathogen type affected the cost by a maximum of $337 000, the difference between a Bacillus cereus outbreak (least costly) and a listeria outbreak (most costly). Conclusions: The cost of a single foodborne illness outbreak to a restaurant can be substantial and outweigh the typical costs of prevention and control measures. Our study can help decision makers determine investment and motivate research for infection-control measures in restaurant settings.
Association of MTHFR C677T gene polymorphism with metabolic syndrome in a Chinese population: a case–control study
Authors: Wang Jin , Xu Lijuan , Xia Hongmiao , Li Ying , Tang Shiqi 
Published: April 2018

Objective To investigate the association of the MTHFR C677T gene polymorphism with metabolic syndrome (MetS) in people in Hubei Province, China. Methods A case–control study was conducted with 651 subjects with MetS (MetS group) and 727 healthy controls (control group) at Renmin Hospital of Wuhan University between January and December 2016. The MTHFR C677T genotype was detected by the gene chip technique and clinical data were collected. Results Body mass index, waist circumference, the waist-hip-ratio, systolic and diastolic blood pressure, fasting blood glucose, fasting insulin, triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and homocysteine levels, and the homeostasis model assessment of insulin resistance were higher in the MetS group than in controls. The risk of MetS was higher for the TT genotype and T allele carriers than for the CC genotype and C allele carriers. With MetS, the TT genotype increased the risk of elevated blood pressure, fasting glucose levels, and triglyceride levels. Patients with MetS and the TT genotype showed more severe abdominal obesity, dyslipidaemia, insulin resistance, elevated blood pressure, elevated fasting glucose levels, and hyperhomocysteinaemia compared with those with the CC genotype. Conclusions In this population, MTHFR C677T gene polymorphism may be a risk factor for MetS.
Adrenocorticotropic Hormone Secreting Pituitary Adenomas: Analysis of Growth Fraction Using the MIB-1 Antibody
Authors: Mastronardi Luciano , Guiducci Antonio , Spera Cristina , Puzzilli Fabrizio , Liberati Fabrizio , Ruggeri Andrea , Peciarolo Antonella 
Published: April 2018

Aims and background Pituitary adenomas are usually considered well differentiated tumors, even if in about one third of cases they invade surrounding tissues, with the possibility of postoperative relapse after complete surgical removal. Adrenocorticotropic hormone (ACTH) secreting adenomas seem to be the most infiltrating subtype, with a higher incidence of recurrence. Ki-67 is a nuclear antigen which is easily detectable by means of the MIB-1 monoclonal antibody, and the labeling index (LI) obtained can be considered a marker of tumor proliferation. Methods In order to identify the growth fraction of these tumors we used the MIB-1 antibody to evaluate the expression of Ki-67 antibody in 11 ACTH secreting pituitary adenomas and to compare it with the LI obtained in 98 other hormone secreting or non-functioning pituitary adenomas consecutively operated on during a 40-month period. Results In relation to surgically verified infiltration of the sellar floor dura and bone, we identified eight non-invasive and three invasive ACTH secreting pituitary adenomas. All invasive tumors infiltrated the wall of the cavernous sinus (CS). The mean Ki-67 LI was 5.88 ± 9.13% versus 2.33 ± 2.40% in non-ACTH secreting adenomas (P = 0.0025). It was 13.27 ± 15.42% in invasive and 3.11 ± 4.37% in non-invasive ACTH adenomas, and 18.40 ± 17.82% in patients over 50 years versus 3.10 ± 4.09% in younger subjects (P = 0.02). Conclusions Ki-67 LI is a useful marker in the determination of proliferative activity and invasiveness of anterior pituitary adenomas. Our data seem to confirm that ACTH secreting adenomas have a higher growth fraction than other pituitary adenomas and this observation presumably explains the higher incidence of relapse of these tumors even after macroscopically total removal.
Detection of Melanoma Cells in Peripheral Blood and Sentinel Lymph Nodes by RT-PCR Analysis: A Comparative Study with Immunohistochemistry
Authors: Pellegrino Daniela , Bellina Calogero Riccardo , Manca Gianpiero , Boni Giuseppe , Grosso Mariano , Volterrani Duccio , Desideri lelizza , Bianchi Francesca , Bottoni Antonio , Ciliberti Vincenzo , Salimbeni Grazia , Gandini Daniele , Castagna Maura , Zucchi Vanna , Romanini Antonella , Bianchi Romano 
Published: April 2018

The presence of lymph node metastases is the best prognostic factor for predicting relapse or survival in melanoma patients. It has been demonstrated that melanoma metastases spread through the first lymph node(s) draining the tumor (sentinel lymph node, SN) to the lymphatic system and that detection of melanoma cells in peripheral blood directly correlates with prognosis in melanoma. To identify lymph node metastases and circulating melanocytes, we developed a single-step reverse transcriptase-polymerase chain reaction assay (RT-PCR) for detection of two melanoma-specific markers: the tyrosinase gene, which encodes an enzyme associated with melanin synthesis, and melanoma antigen-related T-cells, which are present in tumor infiltrating T-lymphocytes. This method detects two tumor cells in a background of 107 lymphocytes. Thirty patients with stage I–IV cutaneous melanoma entered the study. Blood samples were taken preoperatively, one month after excision of the primary melanoma lesion and the SN or total lymphadenectomy, and before the start of chemotherapy and every three months thereafter in metastatic patients. SNs were collected from 22 patients, bisected and analyzed by RT-PCR and routine pathological and immunohistochemical tests. The preliminary results indicate that RT-PCR for melanoma markers is a sensitive and valuable method for the detection of micrometastases and for early diagnosis and staging of melanoma.
Detection of Sentinel Nodes by Lymphoscintigraphy and Gamma Probe Guided Surgery in Vulvar Neoplasia
Authors: Sideri Mario , De Cicco Concetta , Maggioni Angelo , Colombo Nicoletta , Bocciolone Luca , Trifirò Giuseppe , De Nuzzo Maria , Mangioni Costantino , Paganelli Giovanni 
Published: April 2018

Background Pathologic lymph node status is the most important prognostic factor in vulvar cancer; however, complete inguinofemoral node dissection is associated with significant morbidity. Intraoperative lymphoscintigraphy associated with gamma detecting probe-guided surgery has proved to be reliable in the detection of sentinel node (SN) involvement in melanoma and breast cancer patients. The present study evaluates the feasibility of the surgical identification of inguinal sentinel nodes using lymphoscintigraphy and a gamma detecting probe in patients with early vulvar cancer. Methods Technetium-99-labeled colloid human albumin was administered perilesionally in 44 patients. Twenty patients had T1 and 23 had T2 invasive epidermoid vulvar cancer; one patient had a lower-third vaginal cancer. An intraoperative gamma detecting probe was used to identify SNs during surgery. Complete inguinofemoral node dissection was subsequently performed. SNs underwent separate pathologic evaluation. Results A total of 77 groins were dissected in 44 patients. SNs were identified in all the studied groins. Thirteen cases had positive nodes: the SN was positive in all of them; in 10 cases the SN was the only positive node. Thirty-one patients showed negative SNs: all of them were negative for lymph node metastasis. Conclusions Lymphoscintigraphy and SN biopsy under gamma detecting probe guidance proved to be an easy and reliable method for detection of SNs in early vulvar cancer. If these preliminary data will be confirmed, the technique would represent a real progress towards less aggressive treatment in patients with vulvar cancer.
Use of Surgical Gamma Probe for the Detection of Lymph Node Metastases in Differentiated Thyroid Cancer
Authors: Lippi Francesco , Capezzone Marco , Miccoli Paolo , Traino Claudio , Di Martino Francesco , Angelini Fabrizio , Spinelli Claudio , Iacconi Pietro , Pinchera Aldo , Pacini Furio 
Published: April 2018

Background Patients with differentiated thyroid cancer (DTC) after total or near-total thyroidectomy require 131l therapy. After surgery the persistence of lymph node metastases in our series of patients was frequent (30%). Such patients are preferentially treated with radioiodine and shifted to surgical re-intervention when the nodal lesions persist after two 131I treatments. Aim Use of an intraoperative radioactive probe (C-TraK) to allow a more radical surgical approach in thyroid cancer patients submitted to surgery for lymph node metastases. Methods and results After adequate withdrawal of L-thyroxine suppressive therapy six patients were given high 131l doses followed by post-therapy WBS which demonstrated cervical activity in 5 patients and peri-jugular activity in 1. Surgery with the help of a gamma probe allowed to detect and remove all metastatic nodes. After excision all surgical specimens showed higher radioactive counts with respect to the background. The post-surgical scan showed the disappearance of all areas of 131I uptake. Histology confirmed the presence of metastatic lesions from papillary thyroid cancer. Conclusions We conclude that the use of a gamma probe can be successful in patients with metastatic neck lesions resistant to 131I treatment, particularly in patients with nonpalpable lesions.