bluuebunny/crossref_metadata_2025 huggingface dataset:
89Zr-labeled Bispecific T-cell Engager AMG 211 PET Shows AMG 211 Accumulation in CD3-rich Tissues and Clear, Heterogeneous Tumor Uptake
Authors: Moek Kirsten L. , Waaijer Stijn J.H. , Kok Iris C. , Suurs Frans V. , Brouwers Adrienne H. , Menke-van der Houven van Oordt C. Willemien , Wind Thijs T. , Gietema Jourik A. , Schröder Carolien P. , Mahesh Shekar V.K. , Jorritsma-Smit Annelies , Lub-de Hooge Marjolijn N. , Fehrmann Rudolf S.N. , de Groot Derk Jan A. , de Vries Elisabeth G.E.
Published: February 2019

Purpose:

Biodistribution of bispecific antibodies in patients is largely unknown. We therefore performed a feasibility study in 9 patients with advanced gastrointestinal adenocarcinomas to explore AMG 211 biodistribution (also known as MEDI-565), an approximately 55 kDa bispecific T-cell engager (BiTE®) directed against carcinoembryonic antigen (CEA) on tumor cells and cluster of differentiation 3 (CD3) on T-cells.

Experimental Design:

89Zr-labeled AMG 211 as tracer was administered alone or with cold AMG 211, for PET imaging before and/or during AMG 211 treatment.

Results:

Before AMG 211 treatment, the optimal imaging dose was 200-μg 89Zr-AMG 211 + 1,800-μg cold AMG 211. At 3 hours, the highest blood pool standardized uptake value (SUV)mean was 4.0, and tracer serum half-life was 3.3 hours. CD3-mediated uptake was clearly observed in CD3-rich lymphoid tissues including spleen and bone marrow (SUVmean 3.2 and 1.8, respectively), and the SUVmean decreased more slowly than in other healthy tissues. 89Zr-AMG 211 remained intact in plasma and was excreted predominantly via the kidneys in degraded forms. Of 43 visible tumor lesions, 37 were PET quantifiable, with a SUVmax of 4.0 [interquartile range (IQR) 2.7–4.4] at 3 hours using the optimal imaging dose. The tracer uptake differed between tumor lesions 5-fold within and 9-fold between patients. During AMG 211 treatment, tracer was present in the blood pool, whereas tumor lesions were not visualized, possibly reflecting target saturation.

Conclusions:

This first-in-human study shows high, specific 89Zr-AMG 211 accumulation in CD3-rich lymphoid tissues, as well as a clear, inter- and intraindividual heterogeneous tumor uptake.
Evaluation of Salivary Exosomal Chimeric GOLM1-NAA35 RNA as a Potential Biomarker in Esophageal Carcinoma
Authors: Lin Yusheng , Dong Hongmei , Deng Weilun , Lin Wan , Li Kai , Xiong Xiao , Guo Yi , Zhou Fuyou , Ma Changchun , Chen Yuping , Ren Hongzheng , Yang Haijun , Dai Ningtao , Ma Lang , Meltzer Stephen J. , Yeung Sai-Ching J. , Zhang Hao
Published: February 2019

Purpose:

Transcriptionally induced chimeric RNAs are an important emerging area of research into molecular signatures for biomarker and therapeutic target development. Salivary exosomes represent a relatively unexplored, but convenient, and noninvasive area of cancer biomarker discovery. However, the potential of cancer-derived exosomal chimeric RNAs in saliva as biomarkers is unknown. Here, we explore the potential clinical utility of salivary exosomal GOLM1-NAA35 chimeric RNA (seG-NchiRNA) in esophageal squamous cell carcinoma (ESCC).

Experimental Design:

In a retrospective study, the prognostic significance of G-NchiRNA was determined in ESCC tissues. The correlation between seG-NchiRNA and circulating exosomal or tumoral G-NchiRNA was ascertained in cultured cells and mice. In multiple prospective cohorts of patients with ESCC, seG-NchiRNA was measured by qRT-PCR and analyzed for diagnostic accuracy, longitudinal monitoring of treatment response, and prediction of progression-free survival (PFS).

Results:

Exosomal G-NchiRNA was readily detectable in ESCC cells and nude mouse ESCC xenografts. SeG-NchiRNA levels reflected tumor burden in vivo and correlated with tumor G-NchiRNA levels. In prospective studies of a training cohort (n = 220) and a validation cohort (n = 102), seG-NchiRNA levels were substantially reduced after ESCC resection. Moreover, seG-NchiRNA was successfully used to evaluate chemoradiation responsiveness, as well as to detect disease progression earlier than imaging studies. Changes in seG-NchiRNA levels also predicted PFS of patients after chemoradiation.

Conclusions:

SeG-NchiRNA constitutes an effective candidate noninvasive biomarker for the convenient, reliable assessment of therapeutic response, recurrence, and early detection.
Autologous Lymphocyte Infusion Supports Tumor Antigen Vaccine–Induced Immunity in Autologous Stem Cell Transplant for Multiple Myeloma
Authors: Cohen Adam D. , Lendvai Nikoletta , Nataraj Sarah , Imai Naoko , Jungbluth Achim A. , Tsakos Ioanna , Rahman Adeeb , Mei Anna Huo-Chang , Singh Herman , Zarychta Katarzyna , Kim-Schulze Seunghee , Park Andrew , Venhaus Ralph , Alpaugh Katherine , Gnjatic Sacha , Cho Hearn J.
Published: February 2019

Autologous stem cell transplant (autoSCT), the standard consolidation therapy for multiple myeloma, improves disease-free survival, but is not curative. This could be an ideal setting for immunologic therapy. However, the immune milieu is impaired after autoSCT. We hypothesized that autologous lymphocyte infusion would restore immune competence, allowing immunotherapies such as cancer vaccines to elicit tumor antigen–specific immunity in the setting of autoSCT. In this pilot study (NCT01380145), we investigated safety, immunologic, and clinical outcomes of autologous lymphocyte infusion combined with peri-autoSCT immunotherapy with recombinant MAGE-A3 (a multiple myeloma–associated antigen) and adjuvant. Thirteen patients with multiple myeloma undergoing autoSCT were enrolled. Autologous lymphocyte infusion and MAGE vaccination were well tolerated. Combination immunotherapy resulted in high-titer humoral immunity and robust, antigen-specific CD4+ T-cell responses in all subjects, and the responses persisted at least one year post-autoSCT. CD4+ T cells were polyfunctional and Th1-biased. CD8+ T-cell responses were elicited in 3 of 13 subjects. These cells recognized naturally processed MAGE-A3 antigen. Median progression-free survival was 27 months, and median overall survival was not reached, suggesting no differences from standard-of-care. In 4 of 8 subjects tested, MAGE-A protein expression was not detected by IHC in multiple myeloma cells at relapse, suggesting therapy-induced immunologic selection against antigen-expressing clones. These results demonstrated that autologous lymphocyte infusion augmentation of autoSCT confers a favorable milieu for immunotherapies such as tumor vaccines. This strategy does not require ex vivo manipulation of autologous lymphocyte products and is an applicable platform for further investigation into combination immunotherapies to treat multiple myeloma.
Differential CRE Expression in Lhrh-cre and GnRH-cre Alleles and the Impact on Fertility in Otx2-Flox Mice
Authors: Hoffmann Hanne M. , Larder Rachel , Lee Jessica S. , Hu Rachael J. , Trang Crystal , Devries Brooke M. , Clark Daniel D. , Mellon Pamela L.
Published: February 2019

There is an increasing trend in studies utilizing cell-specific deletion of genes through conditional gene deletion by CRE recombination. Despite numerous advantages, this strategy also has limitations such as ectopic CRE-expression and germline recombination. Two commonly used gonadotropin-releasing hormone (Gnrh)-driven CRE-expressing mice both target GnRH neurons. However, a direct comparison of the cells targeted and their phenotypic outcome have not yet been presented. To compare where recombination takes place, we crossed the Gnrh-cre and Lhrh-cre lines with the Rosa26-LacZ reporter mouse. Lhrh-cre allowed recombination of the Rosa26-LacZ gene in ∼700 cells, which is comparable to the GnRH neuronal population. Surprisingly, there were > 20 times more LacZ expressing cells in the adult Gnrh-cre:Rosa26-LacZ than the Lhrh-cre:Rosa26-LacZ brain. The greatest differences in targeting of the Gnrh-cre and Lhrh-cre lines were found in the septum, the suprachiasmatic nucleus, and the septohypothalamic area. This difference in cells targeted was present from embryonic day 12. A prior study using the Gnrh-cre to delete the transcription factor Otx2 found fewer GnRH neurons, leading to male and female subfertility. To recapitulate this study, we performed a fertility assay in Otx2:Lhrh-cre mice. We confirmed the requirement for Otx2 in GnRH neuron development, fertility and correct gonadotropin hormone release in Otx2:Lhrh-cre males, but the subfertility was more modest than in Otx2:Gnrh-cre and absent in female Otx2:Lhrh-cre. This suggests that ectopic expression of Gnrh-cre contributes to the reproductive phenotype observed. Finally, the Cre alleles caused germline recombination of the flox allele when transmitted from either parent, generating embryonic lethal knock-out offspring, producing smaller live litters.
Tensões entre Estado e propriedade nos Dois Tratados Sobre o Governo de Locke
Authors: Gruner Thiago
Published: February 2019

John Locke é frequentemente pensado como pai de um liberalismo que colocou a economia no centro do problema político, contribuindo para o que hoje entendemos por economias de mercado. Porém uma leitura mais problematizante de sua maior obra, Dois tratados sobre o governo, pode desfazer tal clichê e revelar outras respostas: afinal, até aonde pode ir o Estado na gerência da propriedade de seus cidadãos? O presente artigo pretende expor três leituras interpretativas dos Dois tratados que respondem a essa pergunta: uma primeira, de viés libertário, que acredita em direitos irrevogáveis de propriedade justamente adquirida; uma segunda, cunhada como comunalista, que acredita na distribuição inclusiva da propriedade pelo Estado; e uma terceira, que se apresenta como alternativa crítica às suas anteriores. É com esta última que este artigo alinhar-se-á, buscando defender que não há direito absoluto de propriedade nos Dois tratados – seja de bens, ação livre ou vida. Dadas certas condições reiteradas por Locke, o Estado poderia, sim, agir não só nos bens materiais, mas também na vida e na liberdade dos cidadãos, uma vez que existem reivindicações possíveis sobre todos esses direitos.
Fundamento da possibilidade de conhecer: a Analítica dos Conceitos da segunda edição da Crítica da Razão Pura
Authors: Minkovicius Dani Barki
Published: February 2019

O artigo pretende reconstituir os argumentos apresentados na Analítica dos conceitos da segunda edição da Crítica da razão pura, de modo a investigar uma das questões centrais no projeto crítico de Kant: o fundamento da possibilidade de conhecer. Ou seja, mais do que apenas responder a como conhecemos, o objetivo aqui é compreender o que legitima a maneira e a possibilidade pelas quais conhecemos; enfim, o que fundamenta a possibilidade mesma de conhecer.
A questão da técnica e o Humanismo de Martin Heidegger
Authors: Nonaka Álvaro Itie Febrônio
Published: February 2019

O artigo analisa a reflexão de Martin Heidegger sobre o Humanismo a partir da leitura de A questão da técnica. Nesse sentido, o texto acompanha a concepção corrente da técnica moderna, como um meio para um fim, que é correta, porém não verdadeira. Heidegger, nesse texto, postula que através e por dentro do correto se pode chegar à verdade; o mesmo se aplica aos diversos modos de Humanismo, que tendem a conceitualizar uma “essência” humana. A jornada através do correto, em direção à verdade, é um passo a mais que nos aproxima da verdade do Ser.
Elemento detetivesco: aproximações entre Sophie Calle e Walter Benjamin
Authors: Politano Stela
Published: February 2019

O objetivo deste ensaio é analisar o trabalho Suite Vénitienne (1981), da artista Sophie Calle (1953), e contrapô-lo a alguns mecanismos estéticos de Walter Benjamin (1892-1940), tais como: conceito de experiência, arte de narrar, fotografia como técnica política e modificadora do sujeito, conceito de fragmento e mimese. O texto é resultado de um exercício inicial de reflexão.
Novel Paracrine Functions of Smooth Muscle Cells in Supporting Endothelial Regeneration Following Arterial Injury
Authors: Ren Jun , Zhou Ting , Pilli Vijaya Satish Sekhar , Phan Noel , Wang Qiwei , Gupta Kartik , Liu Zhenjie , Sheibani Nader , Liu Bo
Published: February 2019

Rationale:

Regeneration of denuded or injured endothelium is an important component of vascular injury response. Cell-cell communication between endothelial cells and smooth muscle cells (SMCs) plays a critical role not only in vascular homeostasis but also in disease. We have previously demonstrated that PKCδ (protein kinase C-delta) regulates multiple components of vascular injury response including apoptosis of SMCs and production of chemokines, thus is an attractive candidate for a role in SMC-endothelial cells communication.

Objective:

To test whether PKCδ-mediated paracrine functions of SMCs influence reendothelialization in rodent models of arterial injury.

Methods and Results:

Femoral artery wire injury was performed in SMC-conditional
Prkcd
knockout mice, and carotid angioplasty was conducted in rats receiving transient
Prkcd
knockdown or overexpression. SMC-specific knockout of
Prkcd
impaired reendothelialization, reflected by a smaller Evans blue-excluding area in the knockout compared with the wild-type controls. A similar impediment to reendothelialization was observed in rats with SMC-specific knockdown of
Prkcd
. In contrast, SMC-specific gene transfer of
Prkcd
accelerated reendothelialization. In vitro, medium conditioned by AdPKCδ-infected SMCs increased endothelial wound closure without affecting their proliferation. A polymerase chain reaction-based array analysis identified
Cxcl1
and
Cxcl7
among others as PKCδ-mediated chemokines produced by SMCs. Mechanistically, we postulated that PKCδ regulates
Cxcl7
expression through STAT3 (signal transducer and activator of transcription 3) as knockdown of STAT3 abolished
Cxcl7
expression. The role of CXCL7 in SMC-endothelial cells communication was demonstrated by blocking CXCL7 or its receptor CXCR2, both significantly inhibited endothelial wound closure. Furthermore, insertion of a
Cxcl7
cDNA in the lentiviral vector that carries a
Prkcd
shRNA overcame the adverse effects of
Prkcd
knockdown on reendothelialization.

Conclusions:

SMCs promote reendothelialization in a PKCδ-dependent paracrine mechanism, likely through CXCL7-mediated recruitment of endothelial cells from uninjured endothelium.
Genetic Characteristics of Aldosterone-Producing Adenomas in Blacks
Authors: Nanba Kazutaka , Omata Kei , Gomez-Sanchez Celso E. , Stratakis Constantine A. , Demidowich Andrew P. , Suzuki Mari , Thompson Lester D. R. , Cohen Debbie L. , Luther James M. , Gellert Lan , Vaidya Anand , Barletta Justine A. , Else Tobias , Giordano Thomas J. , Tomlins Scott A. , Rainey William E.
Published: February 2019

Somatic mutations have been identified in aldosterone-producing adenomas (APAs) in genes that include
KCNJ5
,
ATP1A1
,
ATP2B3
, and
CACNA1D
. Based on independent studies, there appears to be racial differences in the prevalence of somatic
KCNJ5
mutations, particularly between East Asians and Europeans. Despite the high cardiovascular disease mortality of blacks, there have been no studies focusing on somatic mutations in APAs in this population. In the present study, we investigated genetic characteristics of APAs in blacks using a CYP11B2 (aldosterone synthase) immunohistochemistry-guided next-generation sequencing approach. The adrenal glands with adrenocortical adenomas from 79 black patients with primary aldosteronism were studied. Seventy-three tumors from 69 adrenal glands were confirmed to be APAs by CYP11B2 immunohistochemistry. Sixty-five of 73 APAs (89%) had somatic mutations in aldosterone-driver genes. Somatic
CACNA1D
mutations were the most prevalent genetic alteration (42%), followed by
KCNJ5
(34%),
ATP1A1
(8%), and
ATP2B3
mutations (4%).
CACNA1D
mutations were more often observed in APAs from males than those from females (55% versus 29%,
P
=0.033), whereas
KCNJ5
mutations were more prevalent in APAs from females compared with those from males (57% versus 13%,
P
<0.001). No somatic mutations in aldosterone-driver genes were identified in tumors without CYP11B2 expression. In conclusion, 89% of APAs in blacks harbor aldosterone-driving mutations, and unlike Europeans and East Asians, the most frequently mutated aldosterone-driver gene was
CACNA1D
. Determination of racial differences in the prevalence of aldosterone-driver gene mutations may facilitate the development of personalized medicines for patients with primary aldosteronism.
Novel Role of T Cells and IL-6 (Interleukin-6) in Angiotensin II–Induced Microvascular Dysfunction
Authors: Senchenkova Elena Y. , Russell Janice , Yildirim Alper , Granger D. Neil , Gavins Felicity N.E.
Published: February 2019

Hypertension is an established risk factor for subsequent cardiovascular diseases, with Ang II (angiotensin II) playing a major role in mediating thrombotic and inflammatory abnormalities. Although T cells and IL-6 (interleukin-6) play an important role in adaptive immune responses, little is known about their role(s) in the thromboinflammatory responses associated with Ang II. Here we show using intravital microscopy coupled with the light/dye injury model that Rag-1 deficient (Rag-1
−/−
) and IL-6 deficient (IL-6
−/−
) mice are afforded protection against Ang II–induced thrombosis. Blocking IL-6 receptors (using CD126 and gp130 antibodies) significantly diminished Ang II–mediated thrombosis and inflammatory cell recruitment in mice. Furthermore, the adoptive transfer of IL-6
−/−
-derived T cells into Rag-1
−/−
mice failed to accelerate Ang II–induced thrombosis compared with Rag-1
−/−
mice reconstituted with wild-type–derived T cells, suggesting T cell IL-6 mediates the thrombotic abnormalities associated Ang II hypertension. Interestingly, adoptive transfer of WT T cells into Rag-1
−/
−
/Ang II mice resulted in increased numbers of immature platelets, which constitutes a more active platelet population, that is, prothrombotic and proinflammatory. To translate our in vivo findings, we used clinical samples to demonstrate that IL-6 also predisposes platelets to an interaction with collagen receptors, thereby increasing the propensity for platelets to aggregate and cause thrombosis. In summary, we provide compelling evidence for the involvement of IL-6, IL-6R, and T-cell–dependent IL-6 signaling in Ang II–induced thromboinflammation, which may provide new therapeutic possibilities for drug discovery programs for the management of hypertension.
MG53 Protein Protects Aortic Valve Interstitial Cells From Membrane Injury and Fibrocalcific Remodeling
Authors: Adesanya T. M. Ayodele , Russell Melanie , Park Ki Ho , Zhou Xinyu , Sermersheim Matthew A. , Gumpper Kristyn , Koenig Sara N. , Tan Tao , Whitson Bryan A. , Janssen Paul M. L. , Lincoln Joy , Zhu Hua , Ma Jianjie
Published: February 2019

Background

The aortic valve of the heart experiences constant mechanical stress under physiological conditions. Maladaptive valve injury responses contribute to the development of valvular heart disease. Here, we test the hypothesis that
MG
53 (mitsugumin 53), an essential cell membrane repair protein, can protect valvular cells from injury and fibrocalcific remodeling processes associated with valvular heart disease.

Methods and Results

We found that
MG
53 is expressed in pig and human patient aortic valves and observed aortic valve disease in aged
Mg53−/−
mice. Aortic valves of
Mg53−/−
mice showed compromised cell membrane integrity. In vitro studies demonstrated that recombinant human
MG
53 protein protects primary valve interstitial cells from mechanical injury and that, in addition to mediating membrane repair, recombinant human
MG
53 can enter valve interstitial cells and suppress transforming growth factor‐β‐dependent activation of fibrocalcific signaling.

Conclusions

Together, our data characterize valve interstitial cell membrane repair as a novel mechanism of protection against valvular remodeling and assess potential in vivo roles of
MG
53 in preventing valvular heart disease.
Living in Food Deserts and Adverse Cardiovascular Outcomes in Patients With Cardiovascular Disease
Authors: Kelli Heval M. , Kim Jeong Hwan , Samman Tahhan Ayman , Liu Chang , Ko Yi‐An , Hammadah Muhammad , Sullivan Samaah , Sandesara Pratik , Alkhoder Ayman A. , Choudhary Fahad K. , Gafeer M. Mazen , Patel Keyur , Qadir Saqib , Lewis Tené T. , Vaccarino Viola , Sperling Laurence S. , Quyyumi Arshed A.
Published: February 2019

Background

Food deserts (
FDs
), defined as low‐income communities with limited access to healthy food, are a growing public health concern. We evaluated the impact of living in
FDs
on incident cardiovascular events.

Methods and Results

We recruited 4944 subjects (age 64±12, 64% male) undergoing cardiac catheterization into the Emory Cardiovascular Biobank. Using the US Department of Agriculture definition of
FD
, we determined whether their residential addresses had (1) poor access to healthy food, (2) low income, or (3) both (=
FD
). Subjects were prospectively followed for a median of 3.2 years for myocardial infarction (MI) and death. Fine and Gray's subdistribution hazard models for
MI
and Cox proportional hazard models for death/
MI
were used to examine the association between area characteristics (
FD
, poor access, and low income) and the rates of adverse events after adjusting for traditional risk factors. A total of 981 (20%) lived in
FDs
and had a higher adjusted risk of
MI
(subdistribution hazard ratio, 1.44 [95%
CI,
1.06–1.95]) than those living in non‐
FDs
. In a multivariate analysis including both food access and area income, only living in a low‐income area was associated with a higher adjusted risk of
MI
(subdistribution hazard ratio, 1.40 [1.06–1.85]) and death/
MI
(hazard ratio, 1.18 [1.02–1.35]) while living in a poor‐access area was not significantly associated with either (subdistribution hazard ratio, 1.05 [0.80–1.38] and hazard ratio, 0.99 [0.87–1.14], respectively).

Conclusions

Living in an FD is associated with a higher risk of adverse cardiovascular events in those with coronary artery disease. Specifically, low area income of
FDs
, not poor access to food, was significantly associated with worse outcomes.
Indistinguishable from Magic: Perception, Knowledge, Technology, Art
Authors: Benjamin Garfield
Published: February 2019

The term magic has long been associated with both technology and art. Whether an illusion performed on stage or the search for the supernatural, magic is concerned with changing either reality itself or our perception of it. Each new technology takes on a magical role by increasing humans' power to manipulate the world around them. Similarly, magical practices are often labeled arts, and the manipulation of our perceptions by artists often creates quasi-magical experiences. Four approaches to magic in relation to digital art practice—illusionist, alchemist, necromancer and sorcerer—offer a mode of understanding the manipulation of perceptual reality by artists using digital technologies. The framework will then be applied to five such practitioners—Pascal Dombis, Anne-Sarah Le Meur, Antoine Schmitt, Dmitry Morozov and Zaven Paré—who demonstrate the quest for the unknown and the manipulation of knowledge to create a new reality.
A Layered, Bounded, Integrated Approach to Research on the Arts across Disciplines
Authors: Lopes Dominic McIver
Published: February 2019

Cooperation among arts scholars is thought to be hampered by the division of research on the arts into two cultures, one scientific, one humanistic. This article proposes an alternative model for arts research, wherein multiple levels of explanation focused on well-bounded phenomena integrate research across academic disciplines. Two case studies of research that fit the model are presented.
Resisting Clarity/Highlighting Form: Comparing Vanguard Approaches in Poetry and Programming
Authors: Lyubchenko Irina
Published: February 2019

This article contributes to the study of an esoteric programming language, brainfuck. It proposes a novel view that brainfuck embodies a poetic turn in computer programming, which could be viewed in relationship to Giambattista Vico's historical concept of ricorso—return to an earlier age that Vico, without derogation, identified as barbaric and characterized by the prevalence of poetic forms. Ricorso presupposes a previous existence of an analogous form of communication, which resurfaces in a transformed but recognizable shape in the current time. This article suggests that this older form of poetics is the Russian Futurists' Zaum poetry theorized by the Russian formalist Viktor Shklovsky among others.
Intimate Visions: Representations of the Imperfect Body in the Age of Digital Medicine
Authors: Monahon Catherine , Jameson Elizabeth
Published: February 2019

The authors explore the work of artists looking at the relationship between illness, identity, the brain and imagery produced by medical imaging technology. Digital images of the brain generated by magnetic resonance imaging (MRI) technology represent a powerful unveiling, making visible that which was invisible until the creation of the CT scanner and, shortly after, the more refined MRI technology. At the intersection of fine art and clinical medical images, the authors discover a resistance and a reshaping of the experience of illness. In their focus on the brain, illness and identity, the authors feature specific works of artists impacted by diseases of the brain and spinal cord, specifically Laura Ferguson, Katherine Sherwood, Marilène Oliver, Kelly Haydon, Darian Goldin Stahl and Elizabeth Jameson.
Molecular and morphological phylogenetic analysis and taxonomic revision of the genus Orleanesia (Laeliinae, Epidendroideae, Orchidaceae)
Authors: GONÇALVES GABRIEL F. , MAUAD ANNA VICTORIA S. R. , TAQUES GIULIANA , SMIDT ERIC C. , DE BARROS FÁBIO
Published: February 2019

In order to evaluate the monophyly of the genus Orleanesia (Orchidaceae) and to assess its position within Laeliinae, a phylogenetic analysis was performed using molecular (nuclear ITS and plastid matK DNA sequences) and morphological data. A taxonomic revision of Orleanesia was also performed, with a description of the genus and its species using fresh living plants and 115 exsiccates from 31 herbaria. All phylogenetic analyses were highly congruent, and thus the sequence data from all three data sets were combined. The resulting phylogeny corroborated the monophyly of Orleanesia, with two strongly supported clades, and confirmed Caularthron as its sister group. Character analysis was not very informative due to a high degree of homoplasy. Two lectotypifications and three new synonyms were proposed for the genus, thereby reducing the number of accepted species to six. Although none of the species of Orleanesia are considered endangered, it is clear that some populations are threatened with deforestation and habitat reduction.
Transferring two names of Chlamydogramme to Tectaria (Pteridophyta: Tectariaceae)
Authors: ZHANG XIN , ZHANG LIANG , ZHANG LI-BING
Published: February 2019

Following recent taxonomic treatment we here transfer two species of ferns from Chlamydogramme to Tectaria (Tectariaceae). We also lectotypify Gymnopteris hollrungii Kuhn.
Fifteen new species and a new country record of Labomimus Sharp from China, with a checklist of world species (Coleoptera: Staphylinidae: Pselaphinae)
Authors: ZHANG YU-QING , LI LI-ZHEN , YIN ZI-WEI
Published: February 2019

The diversity of the ‘Pselaphodes complex’ of genera from Asia remains fragmentally documented. Herein we describe fifteen new species of the genus Labomimus Sharp from China: L. assingi sp. nov. and L. dilatatus sp. nov. from Shaanxi, L. longnan sp. nov. and L. minshanus sp. nov. from Gansu, L. chouwenii sp. nov. from Taiwan, L. yue sp. nov. from Guangdong, L. howaichuni sp. nov. from Hong Kong, L. jinfomontis sp. nov. from Chongqing, L. niger sp. nov. from Sichuan, L. maolan sp. nov. from Guizhou, L. corpulentus sp. nov., L. dulongensis sp. nov., and L. wuchaoi sp. nov. from Yunnan, and L. medogensis sp. nov. and L. qiujianyuae sp. nov. from Xizang. A little known species, L. torticornis (Champion), originally described from Assam, northeastern India, is newly recorded in Yunnan, southwestern China. Illustrations of the habitus and major diagnostic characters of all treated species are provided. A checklist and a distributional map of world species are given.
Adjunctive Perampanel Oral Suspension in Pediatric Patients From ≥2 to <12 Years of Age With Epilepsy: Pharmacokinetics, Safety, Tolerability, and Efficacy
Authors: Renfroe J. Ben , Mintz Mark , Davis Ronald , Ferreira Jose , Dispoto Sharon , Ferry Jim , Umetsu Yuko , Rege Bhaskar , Majid Oneeb , Hussein Ziad , Laurenza Antonio
Published: February 2019

Study 232, an open-label pilot study with an extension phase, evaluated the pharmacokinetics and preliminary safety/tolerability and efficacy of adjunctive perampanel oral suspension (≤0.18 mg/kg/d) in epilepsy patients aged ≥2 to <12 years. Patients were grouped into cohorts 1 (aged ≥7 to <12 years) and 2 (aged ≥2 to <7 years). The Core Study included pretreatment (≤2 weeks) and treatment phases (7-week titration; 4-week maintenance; 4-week follow-up [for those not entering the extension]). The extension phase consisted of 41-week maintenance and 4-week follow-up periods. Pharmacokinetic data were pooled with adolescent pharmacokinetic data from phase II/III studies. Population pharmacokinetic analysis showed that perampanel pharmacokinetics was independent of age, weight, or liver function, suggesting age- or weight-based dosing is not required and that the same dose can be given to adults and children to achieve exposures shown to be efficacious. Perampanel was well tolerated and efficacious for ≤52 weeks.
Role of neutrophil-to-lymphocyte ratio as a prognostic indicator for hemodialysis arteriovenous fistula failure
Authors: Wongmahisorn Yuthapong
Published: February 2019

Objective:

To evaluate the role of preoperative peripheral blood neutrophil-to-lymphocyte ratio in predicting early arteriovenous fistula failure. The impact of postoperative neutrophil-to-lymphocyte ratio on arteriovenous fistula failure was also investigated.

Methods:

Medical records from 470 patients who underwent first-time arteriovenous fistula creation were studied. Demographic, clinical, and laboratory data were obtained. Receiver operating characteristic curves were constructed to determine the optimal cutoff values of preoperative and postoperative neutrophil-to-lymphocyte ratios for predicting early arteriovenous fistula failure. Univariate and multivariate analyses were performed to evaluate whether the neutrophil-to-lymphocyte ratio parameters were prognostic indicators for arteriovenous fistula failure.

Results:

Complete data from 396 patients were studied. The prevalence of early arteriovenous fistula failure was 30.6%. The optimal cutoff values of preoperative and postoperative neutrophil-to-lymphocyte ratios for predicting early arteriovenous fistula failure were 2.7 (82.6% sensitivity and 52.0% specificity) and 2.9 (78.5% sensitivity and 73.1% specificity), respectively. By univariate and multivariate analyses, high preoperative and postoperative neutrophil-to-lymphocyte ratios were significantly associated with early arteriovenous fistula failure. The adjusted odds ratios were 5.46 (95% confidence interval: 3.15–9.48) and 7.19 (95% confidence interval: 4.12–12.55), respectively.

Conclusions:

High preoperative and postoperative neutrophil-to-lymphocyte ratios significantly predict early arteriovenous fistula failure.
Professional Backgrounds in State Legislatures, 1993‐2012
Authors: Makse Todd
Published: February 2019

In this paper, I introduce a new dataset of individual-level professional background data for state legislators in 98 chambers from 1993 to 2012. Using this data, I examine trends in the professional backgrounds of state legislators over the period of the study, with attention to institutional factors such as professionalism and legislative turnover and individual-level factors such as political party and gender. In addition, I briefly illustrate three applications of the data. First, I analyze the extent to which district-level demographic and political factors affect the probability that a district will elect a legislator from certain backgrounds. Second, I examine the relationship between occupational background and ideology, identifying the backgrounds that identify moderate and extreme members in each party. Third, I contrast the occupational backgrounds of legislators who hold leadership positions with the membership at large. Taken together, these examples speak to some of the ways in which the composition of state legislatures can reveal interesting and relevant information underlying legislative behavior and institutions.
Why People Living With and Beyond Cancer Use the Internet
Authors: Holmes Michelle Marie
Published: February 2019

People living with and beyond cancer suffer with a wide range of physical and psychological symptoms. To manage the challenges associated with cancer, patients use a variety of self-management resources, including the Internet. People living with and beyond cancer use the Internet to make decisions regarding their self-care, through information provision, online communities, and support groups. Using the Internet may empower patients, enabling them to feel they have the required knowledge to discuss complementary and alternative treatment options with their health care team. Patients use the Internet because of its practicality; however, there are also several barriers affecting patients with cancer using the Internet, such as lack of information technology skills, lack of computer access, and concerns over the quality of information. Health care professionals need to be aware that the information available on the Internet plays a factor in the decision-making processes regarding using complementary and alternative medicine for self-management. With the use of the Internet as a tool for self-management continuing to grow, it is recommended that more emphasis is placed on health care professionals discussing the role the Internet plays in the decision-making process, to further support their patients regarding self-management for living with and beyond cancer.
Introduction: Memories of joy
Authors: Sindbæk Andersen Tea , Ortner Jessica
Published: February 2019

This introduction argues that the field of memory studies needs to pay more attention to the role of joyful and positive types of memory. Quoting recent discussions, we propose that the dominant focus on traumatic and dark pasts within memory studies carries the risks that the research field ignores important aspects of collective memory and eclipses group memories that differ from societies’ hegemonic discourse about the past. Contemporary societies also need positive or hopeful memories in order to create alternative imaginaries for the future. This special issue sets out to explore what memories of joy may look like and how they can be studied.
Modularization as a system life cycle management strategy: Drivers, barriers, mechanisms and impacts
Authors: Micheli Guido JL , Trucco Paolo , Sabri Yasmine , Mancini Mauro
Published: February 2019

This literature-grounded research contributes to a deeper understanding of modularization as a system life cycle management strategy, by providing a comprehensive view of its key barriers, drivers, possible mechanisms of implementation and impact. This comprehensive view, arranged into a decision-making–driven ontology, enables a decision maker to systematically identify modularization implementation opportunities in different industrial and service domains. The proposed ontology transforms modularization into a fully operationalizable strategy and contributes to a paradigm shift in the understanding of modularization, from a pure design option (i.e. modularity) to a fully strategic choice that, by nature, impacts on many of the system’s life cycle phases and involves a number of stakeholders.
Nasal dermoid cyst with intracranial extension in a cat
Authors: Brady Stacey , Bell Erin , Courtman Natalie , Chevoir Matthias Le
Published: February 2019

Case summary

An 11-month-old female neutered Ragdoll cat was presented for focal seizures, aggression and altered behaviour. A diagnosis of a nasal dermoid cyst with intracranial extension was made following MRI, cytology and histopathology. The cyst was surgically excised with a resolution of clinical signs, with the exception of ongoing seizure activity requiring anti-seizure medication.

Relevance and novel information

To our knowledge, this is the first reported case of a nasal dermoid cyst in a cat, and the first reported case in the veterinary literature of any species with a nasal dermoid cyst presenting with neurological signs.
Beyond palatable: White privilege and Western immigrant restaurateurs in postcolonial Taiwan
Authors: Tzeng Rueyling
Published: February 2019

Unlike immigrants who must struggle with discrimination, some middle-class Westerners who move to Taiwan use their white privilege to open mid- to high-end restaurants, competing with existing Western-style restaurants whose Taiwanese owners generally use chefs trained locally or in Japan. The author reviews this situation based on evidence drawn from the current literature and in-depth interviews. After more than two centuries of Western imperialism in Asia, whites and Western cuisine continue to be perceived by Taiwanese as symbols of modernity that deserve respect. White privilege, a form of racial capital, grants Westerners the freedom to enter Taiwan and quickly achieve a relatively high status. Compared to restaurateurs in their home countries, white Westerners who open restaurants in Taiwan benefit from lower startup and operating costs, fewer regulations, free local media coverage and, in some cases, a more vibrant national economy. However, they encounter limitations to white privilege in terms of entrenched Taiwanese taste preferences and dining practices. For some white Western migrant restaurateurs, catering to those preferences conflicts with their desire to use authenticity as a personal goal and business strategy.
Patients' perspectives on COPD: findings from a social media listening study
Authors: Cook Nigel S. , Kostikas Konstantinos , Gruenberger Jean-Bernard , Shah Bhavik , Pathak Purnima , Kaur Vinay Preet , Mudumby Alaknanda , Sharma Rajat , Gutzwiller Florian S.
Published: February 2019

We utilised social media listening (SML) to obtain patients' perspectives on symptoms, diagnosis and comorbidities associated with chronic obstructive pulmonary disease (COPD) and its impact on patients' quality of life (QoL).

A comprehensive search on social media platforms was performed for English language content posted between July 2016 and January 2018 using COPD-related terms. Social Studio, a social media data aggregator tool, was used to capture relevant records. The content was manually curated to analyse and map psychological aspects with descriptive statistics applied on aggregated findings.

A total of 849 posts from patients or caregivers (“patient insights”) were considered for the analysis, corresponding to postings of 695 unique individuals. Based on 734 mentions of symptoms from 849 posts by potential patients/caregivers, cough (27%), mucus (25%) and shortness of breath (21%) were the most frequent; analysis by perceived COPD severity indicated these to be common across all severities. Difficulty in mucus clearance (24% of 268 mentions) and sadness (40% of 129 mentions) were top among the aspects impacting physical and emotional QoL, respectively.

SML from patients with COPD indicated that relief from cough, mucus production and shortness of breath would be the most desirable aspects of disease management from a patient's perspective.
The evolutionary genetics of lactase persistence in seven ethnic groups across the Iranian plateau
Authors: Charati Hadi , Peng Min-Sheng , Chen Wei , Yang Xing-Yan , Jabbari Ori Roghayeh , Aghajanpour-Mir Mohsen , Esmailizadeh Ali , Zhang Ya-Ping
Published: February 2019

Background

The ability to digest dietary lactose is associated with lactase persistence (LP) in the intestinal lumen in human. The genetic basis of LP has been investigated in many populations in the world. Iran has a long history of pastoralism and the daily consumption of dairy products; thus, we aim to assess how LP has evolved in the Iranian population. We recruited 400 adult individuals from seven Iranian ethnic groups, from whom we investigated their lactose tolerance and screened the genetic variants in their lactase gene locus.

Results

The LP frequency distribution ranged from 0 to 29.9% in the seven Iranian ethnic groups with an average value of 9.8%. The variants, − 13910*T and − 22018*A, were significantly associated with LP phenotype in Iranians. We found no evidence of hard selective sweep for − 13910*T and − 22018*A in Persians, the largest ethnic group of Iran. The extremely low frequency of − 13915*G in the Iranian population challenged the view that LP distribution in Iran resulted from the demic diffusion, especially mediated by the spread of Islam, from the Arabian Peninsula.

Conclusions

Our results indicate the distribution of LP in seven ethnic groups across the Iranian plateau. Soft selective sweep rather than hard selective sweep played a substantial role in the evolution of LP in Iranian populations.
Hematopoietic Stem-Cell Transplantation Does Not Improve the Poor Outcome of Children With Hypodiploid Acute Lymphoblastic Leukemia: A Report From Children’s Oncology Group
Authors: McNeer Jennifer L. , Devidas Meenakshi , Dai Yunfeng , Carroll Andrew J. , Heerema Nyla A. , Gastier-Foster Julie M. , Kahwash Samir B. , Borowitz Michael J. , Wood Brent L. , Larsen Eric , Maloney Kelly W. , Mattano Leonard , Winick Naomi J. , Schultz Kirk R. , Hunger Stephen P. , Carroll William L. , Loh Mignon L. , Raetz Elizabeth A.
Published: February 2019

Purpose

Children and young adults with hypodiploid B-lymphoblastic leukemia (B-ALL) fare poorly and hematopoietic stem-cell transplantation (HSCT) is often pursued in first complete remission (CR1). We retrospectively reviewed the outcomes of children and young adults with hypodiploid B-ALL who were enrolled in recent Children’s Oncology Group (COG) trials to evaluate the impact of HSCT on outcome.

Patients and Methods

Cytogenetic analyses and DNA index were performed at COG-approved laboratories, and hypodiploidy was defined as modal chromosome number less than 44 and/or DNA index less than 0.81. Minimal residual disease (MRD) was determined centrally using flow cytometry at two reference laboratories. Patients with hypodiploid ALL came off protocol therapy postinduction and we retrospectively collected details on their subsequent therapy and outcomes. Event-free survival (EFS) and overall survival (OS) were estimated for the cohort.

Results

Between 2003 and 2011, 8,522 patients with National Cancer Institute standard-risk and high-risk B-ALL were enrolled in COG AALL03B1 ( ClinicalTrials.gov identifier: NCT00482352). Hypodiploidy occurred in 1.5% of patients (n = 131), 98.3% of whom achieved CR after induction therapy. Five-year EFS and OS were 52.2% ± 4.9% and 58.9% ± 4.8%, respectively. Outcomes for patients undergoing CR1 HSCT were not significantly improved: 5-year EFS and OS were 57.4% ± 7.0% and 66.2% ± 6.6% compared with 47.8% ± 7.5% and 53.8% ± 7.6%, respectively ( P = .49 and .34, respectively) for those who did not undergo transplantation. Patients with MRD of 0.01% or greater at the end of induction had 5-year EFS and OS of 26.7% ± 9.3% and 29.3% ± 10.1%, respectively, and HSCT had no significant impact on outcomes.

Conclusion

Children and young adults with hypodiploid B-ALL continue to fare poorly and do not seem to benefit from CR1 HSCT. This is especially true for patients with MRD of 0.01% or greater at the end of induction. New treatment strategies are urgently needed for these patients.
Interpreting Oncology Care Model Data to Drive Value-Based Care: A Prostate Cancer Analysis
Authors: Ennis Ronald D. , Parikh Anish B. , Sanderson Mark , Liu Mark , Isola Luis
Published: February 2019

PURPOSE:

The Oncology Care Model (OCM) must be clinically relevant, accurate, and comprehensible to drive value-based care.

METHODS:

We studied OCM data detailing observed and expected expenses for 6-month-long episodes of care for patients with prostate cancer. We constructed seven disease state–treatment dyads into which we grouped each episode on the bases of diagnoses, procedures, and medications in OCM claims data. We used this clinical-administrative stratification model to facilitate a comparative cost analysis, and we evaluated emergency department and hospital utilization and drug therapy as potential drivers of cost.

RESULTS:

We examined 377 episodes of care, pertaining to 210 patients, that took place within our health system from January 2012 to June 2015. Ninety-six percent of episodes were assigned to clinically meaningful dyads. Excessive expenses were seen in metastatic, castration-resistant dyads containing second-line hormone therapy (ratio of observed to expected expenses [O/E], 2.66), chemotherapy (O/E, 2.09), and radium-223/sipuleucel-T (O/E, 3.01). An OCM update correcting for castration-resistant prostate cancer led to small differences in observed expenses (0% to +2%) but large changes in expected expenses (−17% to −27% for hormone-sensitive dyads and +136% to +141% for castration-resistant dyads). O/E increased up to 38% for hormone-sensitive dyads and decreased up to 58% for castration-resistant dyads. Emergency department and hospital utilization seems to drive cost for castration-resistant dyads but not for hormone-sensitive dyads. In the revised OCM model, overall O/E for all episodes improved by 22%, from 1.48 to 1.15.

CONCLUSION:

Our experience with OCM highlights the limitations of administrative claims data within this model and illustrates a method of translating these data into clinically meaningful information to improve value.
Identifying Potentially Avoidable Hospitalizations in Medicare Patients With Prostate Cancer: A Retrospective Analysis
Authors: Parikh Anish B. , Smith William , Sanderson Mark , Dharmarajan Kavita , Liu Mark , Isola Luis , Ennis Ronald D.
Published: February 2019

PURPOSE:

If identifiable, potentially avoidable hospitalizations (PAHs) can serve as an important target for cost containment efforts in oncology.

METHODS:

PAHs among a cohort of Medicare patients with prostate cancer were identified using a two-stage consensus-driven review process. In stage 1, two clinicians independently evaluated admissions records using a case review form, which we modified from a previous study to assess for PAHs. In stage 2, any admissions that the reviewers disagreed on or were unsure of were re-examined in a larger group of clinicians to yield a consensus determination regarding avoidability. Univariable and multivariable regression analyses were performed to identify factors predictive of PAH.

RESULTS:

There were 160 admissions among this cohort of 210 patients from January 2012 to June 2015, of which 99 were evaluable. Consensus-driven clinical review yielded an overall PAH rate of 28.3%. Factors associated with increased PAH risk were admission for symptoms related to cancer (odds ratio [OR], 7.33; P < .001), presence of a social contributor to admission (OR, 4.40; P = .014), and history of alcohol or drug abuse (OR, 4.93; P = .025). Admission for a noncancer condition was associated with decreased PAH risk (OR, 0.32; P = .011). On multivariable analysis, presence of a social contributor to admission (OR, 9.35; P = .002) and admission as a result of a noncancer condition (OR, 0.16; P = .038) remained predictive of PAH risk.

CONCLUSION:

A significant proportion of hospitalizations among patients with prostate cancer are potentially avoidable. Understanding factors predictive of risk for PAH can help inform programs aimed at avoiding such admissions to improve overall care quality and value.