bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis and Therapy of Triple-Negative Breast Cancer (TNBC) – Recommendations for Daily Routine Practice
Authors: Schneeweiss Andreas , Denkert Carsten , Fasching Peter A. , Fremd Carlo , Gluz Oleg , Kolberg-Liedtke Cornelia , Loibl Sibylle , Lück Hans-Joachim
Published: June 2019

The rapid increase in knowledge in tumour biology and tumour pathogenesis of triple-negative breast cancer (TNBC) has resulted in new therapeutic approaches and new therapeutic concepts for treatment. For years, TNBC has been considered to be a difficult-to-treat tumour due to its generally aggressive tumour biology and in view of limited therapeutic options. The risk of recurrence and metastasis is higher than in the case of other breast cancer subtypes of the same stage. In addition to surgery and radiation in the curative situation, systemic chemotherapy with anthracyclines and/or taxanes is still the therapy of choice. New therapeutic approaches are based on the knowledge that TNBC is a molecularly very heterogeneous disease. Research groups are working to classify TNBC better and better on a molecular level and use this molecular subtyping as the basis for new therapeutic strategies. The most promising new approaches and considerations regarding the therapy of TNBCs are shown below. In addition, the current therapeutic strategies are discussed using a fictitious case history, taking the current data and the resultant therapeutic consequence into account.
Von den Tücken der Leitlinienentwicklung und den Lehren der Medizingeschichte
Authors: Singer Dominique
Published: June 2019

Liebe Leserinnen und Leser,

angesichts der Zunahme multiresistenter Erreger in der Bevölkerung und der medialen Aufmerksamkeit für „Killerkeime auf Frühchen-Intensivstationen“ bewegt sich der Umgang mit bakteriellen Infektionen bei Neugeborenen heute mehr denn je im Spannungsfeld zwischen einer präventiven Risikominimierung einerseits und einer präzisen therapeutischen Indikationsstellung andererseits. Dass dieses Spannungsfeld, zumal angesichts begrenzter bzw. uneindeutiger Evidenzen, nicht leicht zu bewältigen ist, davon zeugt allein der Umfang der aktualisierten AWMF-Leitlinie zu diesem Thema, die auf 15 Seiten des vorliegenden Heftes der Zeitschrift für Geburtshilfe und Neonatologie (ZGN) abgedruckt ist.
Strukturelle Prädiktoren der Adhärenz für körperliche Aktivität im betrieblichen Setting – eine systematische Übersichtsarbeit
Authors: Benda Frederike
Published: June 2019

Hintergrund Der Erfolg betrieblicher Gesundheitsprogramme hängt maßgeblich von der Adhärenz der Beschäftigten ab. In betrieblichen Bewegungsprogrammen beträgt diese üblicherweise 25,8 % bis 29,2 %. Determiniert wird die Adhärenz durch demografische, gesundheitsbezogene, arbeitsbezogene und strukturelle Prädiktoren (Robroek, van Lenthe, van Empelen und Burdorf, 2009). Diese Übersichtsarbeit fasst zusammen, unter welchen strukturellen Prädiktoren die Adhärenz für betriebliche Bewegungsprogramme am höchsten ist.

Methode Zur Identifizierung relevanter Artikel wurde eine systematische Literatursuche in den Datenbanken Pubmed, Sportdiscus, Cinahl, Embase, Medline und Business Source Premier durchgeführt. Es konnten 47 relevante Artikel aus der Ergebnismenge extrahiert werden. Diese wurden in Bezug auf ihre methodische Qualität bewertet. Adhärenzdaten sowie Teilnehmerquoten wurden nach thematischen Schwerpunkten ausgewertet.

Ergebnisse Die Qualität der Studien ist gering, da nur wenige Studien die Adhärenz von betrieblichen Bewegungsprogrammen als primäres Zielkriterium auswerten. Die Messung, Operationalisierung und Definition der Adhärenz für körperliche Aktivität variiert sehr stark in den untersuchten Studien und die Ergebnisse sind inkonsistent. Es fehlen randomisierte kontrollierte Versuche, die unterschiedliche strukturelle Aspekte der Betriebe und Programme miteinander vergleichen. Dennoch konnte der Einfluss struktureller Prädiktoren auf die Adhärenz für betriebliche Bewegungsprogramme bestätigt werden.

Diskussion Es besteht die Notwendigkeit, die Adhärenzforschung zu standardisieren, um vergleichbare Ergebnisse liefern zu können. Randomisierte kontrollierte Studien sollten den Einfluss struktureller Prädiktoren auf die Adhärenz genauer spezifizieren. Es ist außerdem von Bedeutung, Strategien zu finden, die die Langzeitadhärenz erhöhen, um das gesundheitsfördernde Potential von Bewegungsprogrammen am Arbeitsplatz besser nutzen zu können. Hierfür muss die Adhärenz als ein komplex determiniertes Verhalten betrachtet werden.
Sitzen macht dick, dumm und krank – warum macht sich die allgegenwärtige Ergonomieberatung dann immer noch Standardgedanken zur Einstellung und Optimierung unseres Sitzens?
Authors: Adomat Sven , Bartosch Sven
Published: June 2019

Das Thema Ergonomie ist im Fokus vieler Beratungen und Angebote im Hinblick auf die Entwicklung und Erhaltung der Gesundheit von Mitarbeitern. In diesem Beitrag wird die notwendige Erweiterung und Veränderung des Blickes von dem eindimensionalen mechanischen Ansatz hin zu einer Mehrdimensionalität weiterentwickelt und ein dementsprechender Analyseweg vorgestellt. Dieses Vorgehen des Umdenkens bildet nach unserer Einschätzung die Basis für eine nachhaltige biopsychosoziale Intervention im Betrieb.
Developing HL7 CDA-Based Data Warehouse for the Use of Electronic Health Record Data for Secondary Purposes
Authors: Pecoraro Fabrizio , Luzi Daniela , Ricci Fabrizio L.
Published: June 2019

Background The growing availability of clinical and administrative data collected in electronic health records (EHRs) have led researchers and policy makers to implement data warehouses to improve the reuse of EHR data for secondary purposes. This approach can take advantages from a unique source of information that collects data from providers across multiple organizations. Moreover, the development of a data warehouse benefits from the standards adopted to exchange data provided by heterogeneous systems.

Objective This article aims to design and implement a conceptual framework that semiautomatically extracts information collected in Health Level 7 Clinical Document Architecture (CDA) documents stored in an EHR and transforms them to be loaded in a target data warehouse.

Results The solution adopted in this article supports the integration of the EHR as an operational data store in a data warehouse infrastructure. Moreover, data structure of EHR clinical documents and the data warehouse modeling schemas are analyzed to define a semiautomatic framework that maps the primitives of the CDA with the concepts of the dimensional model. The case study successfully tests this approach.

Conclusion The proposed solution guarantees data quality using structured documents already integrated in a large-scale infrastructure, with a timely updated information flow. It ensures data integrity and consistency and has the advantage to be based on a sample size that covers a broad target population. Moreover, the use of CDAs simplifies the definition of extract, transform, and load tools through the adoption of a conceptual framework that load the information stored in the CDA in the data warehouse.
A Clinical and Radiographic Study of Four Different Root Canal Filling Materials in Primary Molars—An In Vivo Study
Authors: Gupta Bhavleen , Singh Inderjeet , Goyal Puneet , Garg Shaveta , Gupta Shivani
Published: June 2019

Introduction Pulpectomy helps in preserving a pulpally involved primary tooth by eliminating bacteria and their products and ensures hermetic seal of the root canals, so that the primary teeth can complete their function until normal exfoliation. For the success of endodontic treatment in primary teeth, the resorption of obturating material plays a vital role. The materials used for obturation in this study included zinc oxide propolis (ZOP) as a new paste, Endoflas, Metapex, and zinc oxide eugenol (ZOE).

Objective To evaluate the success rate of pulpectomy of primary molars using four different root canal filling materials: ZOP as a new paste, Endoflas, Metapex, and ZOE.

Materials and Methods A total of 48 primary molars were divided into four equal groups of 12 molars according to the type of root canal filling paste, that is, ZOE, Endoflas, ZOP, and Metapex.

Results When Tukey’s test was applied, out of the four materials, ZOP was the most significant material as its p-value was < 0.05, whereas other materials showed nonsignificant results as their p-value was > 0.05.

Conclusion Among the four groups, ZOP showed greater clinical success and its resorbability was similar to that of root.
Design considerations for three-dimensional betavoltaics
Authors: Murphy John W. , Voss Lars F. , Frye Clint D. , Shao Qinghui , Kazkaz Kareem , Stoyer Mark A. , Henderson Roger A. , Nikolic Rebecca J.
Published: June 2019

Betavoltaic devices are suitable for delivering low-power over periods of years. Typically, their power density is on the order of nano to micro-Watts per cubic centimeter. In this work we evaluate the potential for using high-aspect ratio three-dimensional semiconductor structures to enhance the power and efficiency of these devices. The Monte Carlo transport code MCNP6 is used to provide realistic estimates of the theoretical levels of charge generation, which is in turn used to make predictions about the power output from three-dimensional betavoltaics. The focus of this work is on silicon and promethium-147, but other semiconductors and radioisotopes are considered as well. In the case of silicon diodes with three-dimensional features that are comparable to what is commercially available we estimate that power densities in the range of 20-25 mW/cm3 can be achieved at efficiencies of 2.9-5.8% when coupled with promethium-147 oxide.
Nanoparticle injector for photonic manipulators using dielectrophoresis
Authors: Maser Jaykob , Rovey Joshua
Published: June 2019

We describe the concept of a dielectrophoretic nanoparticle injector and its use in a plasmonic/photonic-based nanoparticle manipulation system. Particle motion is achieved by generating an electrostatic, non-uniform field between two tilted plates and applying the corresponding dielectrophoretic force to net-neutral nanoparticles. We investigate the dependence the dielectrophoretic force has on the plate angle of the charged plates as well as their separation distance, dielectric filler material, and exit interface membrane. Our results indicate an increasing average and maximum dielectrophoretic force attainable in the axial direction with corresponding decreasing plate angle and gap distance. The model also predicts larger field variation and deviation from the average with smaller plate angle and gap distance. Lastly, we conclude that the nanoparticles must be suspended in a dielectric medium with permittivity greater than their own permittivity so that their net motion is outward through the exit interface membrane and into the manipulator system.
A new model for contact angle hysteresis of superhydrophobic surface
Authors: Zhu Jiyuan , Dai Xuanjun
Published: June 2019

Contact angle hysteresis (CAH) is essential to characterize the wetting properties of a surface. But its underlying causes are not yet understood. A model relating to CAH is presented through mathematical deduction. The calculation results coincide well with several experimental data from previous findings in literatures. Factors affecting CAH are investigated. This study offers new insight into the understanding of CAH and offers useful guidance for the preparation of superhydrophobic surfaces.
Dynamics of hydroxyl dissociation of methanol and water on silicon surfaces
Authors: Liebendorfer Adam
Published: June 2019

Molecular beam techniques show how reaction dynamics depend on bonding of intermediate state and functional groups involved.
Overexpression of Triticum durum TdAnn12 gene confers stress tolerance through scavenging reactive oxygen species in transgenic tobacco
Authors: Ben Saad Rania , Harbaoui Marwa , Ben Romdhane Walid , Zouari Nabil , Giang Khong N. , Ben Hsouna Anis , Brini Faical
Published: June 2019

Plant annexins are proteins with multiple functions and roles in plant development and responses to abiotic stresses. We report here the functional analysis of the TdAnn12 annexin protein isolated from Triticum durum Desf. We have previously shown that TdAnn12 expression is highly induced by different abiotic stresses. In the present study, to investigate the physiological and biochemical stress-induced responses, we overexpressed TdAnn12 in tobacco. We demonstrate that transgenic tobacco plants expressing TdAnn12 exhibited enhanced tolerance to salt, osmotic stress and H2O2 at the seedling stage. Under greenhouse conditions, these plants showed tolerance to drought and salt stresses. Moreover, scavenging reactive oxygen species (ROS), higher chlorophyll content, lower lipid peroxidation levels and increased antioxidant activities (peroxidase, catalase and superoxide dismutase) were observed. Finally, accumulation of TdAnn12 in tobacco positively affects the regulation of some stress-related genes (MnSOD, APX1, CAT1, P5CS, NHX1, SOS1 and DREB1A). TdAnn12 interacts directly or indirectly with stress-related genes that could stimulate an adaptive potential to gain tolerance which is not present in non-transgenic (NT) plants. Our results clearly show that overexpression of TdAnn12 in transgenic tobacco improves stress tolerance through the removal of ROS.
從邪牀禪母讀音與古江東方言
Authors: Chen Zhongmin
Published: June 2019

抽象

本文首先分析今北部吳語從邪澄牀（崇船）禪等聲母讀音，指出這些聲母讀擦音是吳語固有讀音層（白讀），讀塞擦音是以後杭州半官話覆蓋層（文讀）；然後再分析這些聲母在南部吳語裡的情形，發現與北部吳語大致相同，只是白讀讀擦音的不包括澄母。作者認為從邪崇船禪讀擦音是直接繼承了《顏氏家訓—音辭篇》裡所說的江東方言從邪不分、牀（崇船）禪不分的特點，據此本文提出鑒別南朝江東方言的一個語音特徵：從邪崇船禪母都讀擦音。以此鑒別特徵為依據，本文再考察了北部吳語、南部吳語、江淮官話、徽語、閩語等方言相關聲母的讀音，指出吳語（不包括杭州話）、徽語嚴州片是古江東方言的範圍。不過這些地區的方言歷經一千多年的語言接觸和自身演變，也覆蓋著來自中原權威官話和地區權威話的塞擦音文讀層次。塞擦音文讀層與擦音白讀層互相競爭，此消彼長，使得這些方言裡讀塞擦音還是擦音「一處一個樣，一筆糊塗賬」。
「數＋量＋之／的＋名」的歷時語義演變
Authors: Zhang Futong , Li Xuping
Published: June 2019

抽象

本文探討上古漢語至近代漢語中「數＋量＋之／的＋名」形式、功能兩個層面的發展演變。形式方面，由先秦時期的「數＋量＋之＋名」發展爲宋元以後的「數＋量＋的＋名」，以及元代出現的「數1＋量1＋數2＋量2＋的＋名」；功能方面，「數＋量＋之／的＋名」由初始的純描寫型結構發展出計量功能。我們認爲，不同類型的數詞和量詞對「數＋量＋的＋名」這一結構的語義變化有重要影響。具體來說，當「數＋量＋之／的＋名」這一結構的數詞爲高位數詞、約數詞時，它一般表描寫功能；低位確數詞進入該結構促使計量功能的產生。個體量詞在該結構的大量使用進一步加速了該結構從描寫到計量的轉化。
早期上海話位移事件的詞化類型
Authors: Lin Sue
Published: June 2019

抽象

早期上海話口語文獻顯示，雖然各類位移事件詞化結構皆有S型框架特徵，但無生自移事件S型框架傾向最強，其次是致移事件，而有生自移事件的V型框架傾向最明顯。位移事件內部詞化結構類型的差異反映了三者所受演變機制或者影響程度之別：雖然雙音節化和語義要素分離成為漢語位移事件向S型框架轉變的重要機制，但早期上海話中致移事件的詞化類型主要受制於連動結構語法化為動趨式的制約，有生自移事件卻借雙音節化使V型框架特徵更為穩定，無生自移事件因語義表達需要更青睞S型框架結構。研究表明，演變機制對詞化類型的制約作用並非均衡的，也非線性的，而是具有複雜性。
A note on the history of the term “pronomenalisation”
Authors: LaPolla Randy J.
Published: June 2019

This short note discusses the origin and development of the use
of the term “pronomenalisation” (pronominalization) in Sino-Tibetan linguistics, pointing out that the concept was originally a typological one, and that the
phenomenon was seen as the result of grammaticalization, i.e. the free pronouns
being copied onto the verb.
The role of floral oils in the evolution of apid bees (Hymenoptera: Apidae)
Authors: Policarová Jana , Cardinal Sophie , Martins Aline Cristina , Straka Jakub
Published: June 2019

Most bees collect pollen and nectar for their larvae, while some also collect other resources. We investigated the evolution of floral oil-collecting behaviour in the Apidae and the evolutionary effects of floral oils on host brood cells for cuckoo bees. Focusing on apid bee phylogeny, we reconstructed the evolution of floral oil collection by females, use of floral oils in cell construction and the inclusion of oils in provisioning immatures. Ancestral character reconstruction demonstrates that floral oil-collecting behaviour arose four times independently. We also found that in cuckoo bees, parasitization of oil-collecting bees arose three times (including one secondary return) in Apidae. Except for Ctenoplectrina, oil cuckoo bees are all closely related to each other, forming an independent clade within the Nomadinae. Analysis of evolutionary transition rates indicates that there is a greater tendency for switching from an oil-collecting host to a non-oil-collecting host than the reverse. In apid bees, evolutionary transition rates are higher for switching to cuckoo behaviour from an ancestral lineage in which females collect floral oils than from other pollen-collecting lineages. We conclude that adaptation to oil collection is advantageous for pollen-collecting bees, and that the origin of oil cuckoo bees from non-oil cuckoo bees is constrained.
Glycogen in the uterus and fallopian tubes is an important source of glucose during early pregnancy†
Authors: Dean Matthew
Published: June 2019

Pregnancy loss is common during the peri-implantation period in mammals when glucose is required for both embryonic development and decidualization of the endometrium. As the uterus cannot synthesize glucose, all glucose must come directly from maternal circulation as needed or transiently stored as the macromolecule glycogen. Glycogen acts as a glucose reservoir, storing up to 55 000 glucose moieties per molecule. Endometrial glycogen concentrations are correlated with fertility in humans, indicating that glycogen is an essential source of glucose during early pregnancy. In humans and primates, endometrial glycogen concentrations peak during the luteal phase due to progesterone. In contrast, in rats and mink, estradiol triggers an accumulation of uterine glycogen during proestrus and estrus. In mated rats, the glycogen content of the endometrium increases again after implantation due to high levels of glycogen stored in the decidua. In mink, endometrial glycogen reserves are localized in the uterine epithelia at estrus. These reserves are mobilized before implantation, suggesting they are used to support embryonic growth. Uterine glycogen concentrations continue to decrease after implantation in mink, probably due to a lack of decidualization. How ovarian steroids stimulate glycogenesis in the endometrium is unclear, but current evidence suggests that estradiol/progesterone interacts with insulin or insulin-like growth factor signaling. In summary, endometrial glycogen is an essential source of glucose during the peri-implantation period. More work is needed to characterize differences among species, elucidate the fate of the glucose liberated from glycogen, and understand how ovarian steroids regulate glycogen metabolism in the uterus.
Genital Human Immunodeficiency Virus–1 RNA and DNA Shedding in Virologically Suppressed Individuals Switching From Triple- to Dual- or Monotherapy: Pooled Results From 2 Randomized, Controlled Trials
Authors: Hocqueloux Laurent , Gubavu Camélia , Prazuck Thierry , De Dieuleveult Barbara , Guinard Jérôme , Sève Aymeric , Mille Catherine , Gardiennet Elise , Lopez Pauline , Rouzioux Christine , Lefeuvre Sandrine , Avettand-Fènoël Véronique
Published: June 2019

Background

Increasingly, people living with human immunodeficiency virus (HIV) benefit from lower drug regimens (LDRs). Exploring viral genital shedding during LDRs is crucial to ensure their safety.

Methods

We pooled genital sub-studies from 2 clinical trials in this area. Patients were randomized 1:1 to continue abacavir/lamivudine/dolutegravir or switch to dolutegravir (MONCAY trial), or to continue tenofovir/emtricitabine + a third agent or switch to tenofovir/emtricitabine (TRULIGHT trial). Participants whose plasma HIV-RNA remained <50 copies/mL had sperm or cervicovaginal lavage collected between Weeks 24 and 48. HIV-RNA and HIV-DNA were amplified by ultrasensitive polymerase chain reaction. The main objective was to measure the proportion of participants who had no detectable HIV in genital fluids, both according to each strategy and then in an aggregated analysis (LDR versus triple therapies).

Results

There were 64 participants (35 males, 29 females) included: 16 received dual therapies and 16 received triple therapies in TRULIGHT; and 16 received monotherapies and 16 received triple therapies in MONCAY. In TRULIGHT, 13/15 (87%) of evaluable participants on dual therapy had no detectable HIV in their genital fluid, versus 14/15 (93%) under triple therapy (P = 1.0). In MONCAY, these figures were 12/15 (80%) on monotherapy versus 13/16 (81%) on triple therapy (P = 1.0). In the pooled analysis, a similar proportion of participants in the LDR and triple therapy groups had no detectable HIV: 25/30 (83%) and 27/31 (87%), respectively (P = .73).

Conclusions

There was no evidence of increased HIV-RNA and/or -DNA shedding in the genital fluids of people who maintained undetectable plasma HIV-RNA during LDRs.

Clinical Trials Registration

NCT02302547 and NCT02596334
Staring into the void: demystifying microbial metabolomics
Authors: Grim Cynthia M , Luu Gordon T , Sanchez Laura M
Published: June 2019

Metabolites give us a window into the chemistry of microbes and are split into two subclasses: primary and secondary. Primary metabolites are required for life whereas secondary metabolites have historically been classified as those appearing after exponential growth and are not necessarily needed for survival. Many microbial species are estimated to produce hundreds of metabolites and can be affected by differing nutrients. Using various analytical techniques, metabolites can be directly detected in order to elucidate their biological significance. Currently, a single experiment can produce anywhere from megabytes to terabytes of data. This big data has motivated scientists to develop informatics tools to help target specific metabolites or sets of metabolites. Broadly, it is imperative to identify clear biological questions before embarking on a study of metabolites (metabolomics). For instance, studying the effect of a transposon insertion on phenazine biosynthesis in Pseudomonas is a very different from asking what molecules are present in a specific banana-derived strain of Pseudomonas. This review is meant to serve as a primer for a ‘choose your own adventure’ approach for microbiologists with limited mass spectrometry expertise, with a strong focus on liquid chromatography mass spectrometry based workflows developed or optimized within the past five years.
Effect of Prescribed Fire on Timber Volume and Grade in the Hoosier National Forest
Authors: Stanis Shannon , Wiedenbeck Jan , Saunders Mike R
Published: June 2019

Low-intensity surface fire is prescribed in eastern North American hardwood stands prior to overstory harvest in order to improve regeneration and recruitment of oak and other fire-tolerant and fire-adapted species. However, this use of prescribed fire potentially can reduce timber value. We inventoried overstory trees (>10 in. diameter at breast height) in 54 oak-dominated stands with varied prescribed fire histories and aspects in southern Indiana. We then documented the extent of prescribed fire damage (i.e., wounds) to overstory trees and quantified both the relative stand volume of timber loss and the proportion of trees that had tree grade reductions because of prescribed fire. Generally, as a stand received more prescribed fires, more trees were scarred, the relative volume lost increased, and a higher proportion of trees declined in grade. Overall, burned stands experienced less than 10 percent sawtimber volume loss, regardless of the number of prescribed fires and aspect. Less than 3 percent of trees, study-wide, had reduced grade because of prescribed fire. Grade and volume reductions varied by species, however. Our results suggest that prescribed fire has a minor economic impact on standing timber, particularly when timber is harvested within two decades of the first fire.
The Anatomy and Ultrastructure of the Digestive Tract and Salivary Glands of Hishimonus lamellatus (Hemiptera: Cicadellidae)
Authors: Dai Lizhen , Yang Baodong , Wang Jinzhong , Zhang Zhiyong , Yang Rui , Zhang Tieqiang , Ren Zhengguang , Lin Caili
Published: June 2019

In recent years, we found that Hishimonus lamellatus Cai et Kuoh is a potential vector of jujube witches’-broom phytoplasma. However, little is known about the anatomy and histology of this leafhopper. Here, we examined histology and ultrastructure of the digestive system of H. lamellatus, both by dissecting and by semi- and ultrathin sectioning techniques. We found that the H. lamellatus digestive tract consists of an esophagus, a filter chamber, a conical midgut and midgut loop, Malpighian tubules, an ileum, and a rectum. Furthermore, both the basal region of the filter chamber epithelium and the apical surface of the midgut epithelium have developed microvilli. We also identify the perimicrovillar membrane, which ensheaths the microvilli of midgut loop enterocyte, and the flame-like luminal membrane, which covers the microvilli of the conical midgut epithelium. In addition, H. lamellatus has the principal and accessory salivary glands. Our observations also showed that the endoplasmic reticulum, mitochondria, and secretory granules were all highly abundant in the secretory cells of the principal salivary glands, while the accessory glands consist of only one ovate or elbow-like acinus. We also briefly contrast the structure of the gut of H. lamellatus with those of other leafhopper species. These results intend to offer help for the future study on the histological and subcellular levels of phytopathogen–leafhopper relationships, including transmission barriers and the binding sites of pathogens and other microorganisms within their leafhopper vectors.
Risk of Second Primary Bone and Soft–Tissue Sarcomas Among Young Adulthood Cancer Survivors
Authors: Schonfeld Sara J , Merino Diana M , Curtis Rochelle E , Berrington de González Amy , Herr Megan M , Kleinerman Ruth A , Savage Sharon A , Tucker Margaret A , Morton Lindsay M
Published: June 2019

Excess sarcoma risks after childhood cancer are well established, but risks among young adulthood cancer survivors are poorly understood. Using US population-based cancer registry data, we compared bone and soft-tissue sarcoma risk vs the general population among 186 351 individuals who were diagnosed with nonsarcoma first primary malignancies at ages 20–39 years from 1975 to 2014 (follow-up through 2015) and survived at least 1 year. Bone sarcomas were rare (n = 50), but risk was statistically significantly elevated overall (2.9-fold) and greater than fivefold after Hodgkin lymphoma, non-Hodgkin lymphoma, and central nervous system tumors. Soft-tissue sarcomas were more common (n = 284) and risks were statistically significantly elevated approximately twofold overall and after melanoma and carcinomas of the breast, thyroid, and testis, and greater than fourfold after Hodgkin lymphoma and central nervous system tumors. Risks varied markedly by subtype, with the highest risks (greater than fourfold) for osteosarcoma and the soft-tissue subtypes of rhabdomyosarcoma and blood vessel and nerve sheath sarcomas. These data demonstrate elevated risk for sarcoma after a range of young adulthood cancers.
Interleukin-6 Promotes Murine Estrogen Deficiency-Associated Cerebral Aneurysm Rupture
Authors: Wajima Daisuke , Hourani Siham , Dodd William , Patel Devan , Jones Chad , Motwani Kartik , Fazal Hanain Z , Hosaka Koji , Hoh Brian L
Published: June 2019

BACKGROUND

Estrogen deficiency is associated with cerebral aneurysm rupture, but the precise mechanism is unknown.

OBJECTIVE

To test the hypothesis that IL-6 is required for the increase in aneurysm rupture rate observed in estrogen-deficient mice.

METHODS

We analyzed IL-6 expression in human cerebral aneurysms. We induced cerebral aneurysms in estrogen-deficient female C57BL/6 mice that had undergone 4-vinylcyclohexene diepoxide (VCD) treatment or bilateral ovariectomy (OVE). Mice were blindly randomized to selective IL-6 inhibition (IL-6 receptor [IL-6R] neutralizing antibody, n = 25) or control (isotype-matched IgG, n = 28). Murine cerebral arteries at the circle of Willis were assessed for aneurysm rupture and macrophage infiltration.

RESULTS

IL-6 is expressed in human cerebral aneurysms, but not in control arteries. Serum IL-6 is elevated in ovariectomized female mice compared to sham control (14.3 ± 1.7 pg/mL vs 7.4 ± 1.5 pg/mL, P = .008). Selective IL-6R inhibition suppressed cerebral aneurysm rupture in estrogen-deficient mice compared with control (VCD: 31.6% vs 70.0%, P = .026; OVE: 28.6% vs 65.2%, P = .019). IL-6R inhibition had no effect on formation or rupture rate in wild-type mice. IL-6R neutralizing antibody significantly reduced macrophage infiltration at the circle of Willis (1.9 ± 0.2 vs 5.7 ± 0.6 cells/2500 μm2; n = 8 vs n = 15; P < .001).

CONCLUSION

IL-6 is increased in the serum of estrogen-deficient mice and appears to play a role in promoting murine estrogen deficiency-associated cerebral aneurysm rupture via enhanced macrophage infiltration at the circle of Willis. Inhibition of IL-6 signaling via IL-6 receptor neutralizing antibody inhibits aneurysm rupture in estrogen-deficient mice. IL-6 receptor inhibition had no effect on aneurysm formation or rupture in wild-type animals.
Why Spirituality Matters for Law: An Explanation
Authors: Domingo Rafael
Published: June 2019

In this article, I explore potential connections between law and spirituality as well as some of the legal implications of these connections. After arguing that spirituality is conceptually autonomous from religion and morality, I explain why the spiritual triad of love, communion, and gift is deeply interconnected with the legal triad of justice, agreement, and right. I also make clear why individual and collective intentions and cultural values are the main channels of interaction between law and spirituality. In the second part of the article, I argue that legal systems evolve through spiritualization, among other ways, promoting the dematerialization of the legal system, encouraging the limitation of domination, inspiring the reduction of coercion, stimulating communion and consensus in society, or increasing respect for the law and the legal systems. Spiritualization demands a recognition of the higher dimension of the law and, therefore, helps rethink, reorient, renew, reform, and reimagine law and legal systems. Finally, I sketch a pattern of five levels to measure the degree of spiritualization of concrete legal systems. This pattern can also be applied to legal actors and institutions.
THE RECENT SUCCESS OF MICRODOSIMETRY
Authors: Horowitz Y S
Published: June 2019

Recent successful microdosimetric calculations of heavy charged particle efficiencies are evaluated with suggestion for future research.
Phylogenomics Uncovers Confidence and Conflict in the Rapid Radiation of Australo-Papuan Rodents
Authors: Roycroft Emily J , Moussalli Adnan , Rowe Kevin C
Published: June 2019

The estimation of robust and accurate measures of branch support has proven challenging in the era of phylogenomics. In data sets of potentially millions of sites, bootstrap support for bifurcating relationships around very short internal branches can be inappropriately inflated. Such overestimation of branch support may be particularly problematic in rapid radiations, where phylogenetic signal is low and incomplete lineage sorting severe. Here, we explore this issue by comparing various branch support estimates under both concatenated and coalescent frameworks, in the recent radiation Australo-Papuan murine rodents (Muridae: Hydromyini). Using nucleotide sequence data from 1245 independent loci and several phylogenomic inference methods, we unequivocally resolve the majority of genus-level relationships within Hydromyini. However, at four nodes we recover inconsistency in branch support estimates both within and among concatenated and coalescent approaches. In most cases, concatenated likelihood approaches using standard fast bootstrap algorithms did not detect any uncertainty at these four nodes, regardless of partitioning strategy. However, we found this could be overcome with two-stage resampling, that is, across genes and sites within genes (using -bsam GENESITE in IQ-TREE). In addition, low confidence at recalcitrant nodes was recovered using UFBoot2, a recent revision to the bootstrap protocol in IQ-TREE, but this depended on partitioning strategy. Summary coalescent approaches also failed to detect uncertainty under some circumstances. For each of four recalcitrant nodes, an equivalent (or close to equivalent) number of genes were in strong support ($>$ 75% bootstrap) of both the primary and at least one alternative topological hypothesis, suggesting notable phylogenetic conflict among loci not detected using some standard branch support metrics. Recent debate has focused on the appropriateness of concatenated versus multigenealogical approaches to resolving species relationships, but less so on accurately estimating uncertainty in large data sets. Our results demonstrate the importance of employing multiple approaches when assessing confidence and highlight the need for greater attention to the development of robust measures of uncertainty in the era of phylogenomics.
First Report of Tomato Spotted Wilt Virus Identified in Tulbaghia violacea in Florida
Authors: Dey K. K. , Li C. , Sellers M. C. , McVay John , Whilby L. , Hodges G. , Smith T. R.
Published: June 2019

Tulbaghia violacea Harv., also known as society garlic, belongs to the genus Tulbaghia (Amaryllidaceae). It is diversely used for medicinal, culinary, and ornamental purposes. In June 2018, T. violacea plants from Lake County, FL, with typical tospovirus-like symptoms of chlorotic ring patterns, were submitted to the Florida Department of Agriculture and Consumer Services, Division of Plant Industry (Gainesville, FL) for identification. Representative leaf tissue from four plants tested positive in a serological assay and reverse transcription-polymerase chain reaction. Amplicons of the expected size were produced using the tomato spotted wilt virus (TSWV) nucleocapsid (N) gene primers. They were directly sequenced and deposited in GenBank (MK567883). The 777-bp N gene sequence had 98 to 99% nucleotide identity with the corresponding region of previously described Florida TSWV isolates and 96 to 99% nucleotide identity with all TSWV isolates in GenBank. Epidemics of TSWV occur frequently in numerous crops in Florida, chiefly tomato, pepper, tobacco, and ornamentals. The western flower thrip, Frankliniella occidentalis (Pergande), is the most efficient vector of TSWV and has become established in Florida. This is the first report of TSWV infection in T. violacea.
Modulating physical properties of porcine urethra with injection of novel biomimetic proteoglycans
ex vivo
Authors: Kriete Alicia S. , Prudnikova Katsiaryna , Marcolongo Michele S.
Published: June 2019

Urinary incontinence is a significant challenge for women who are affected by it. We propose augmenting the tissue structure to restore normal biomechanics by molecularly engineering the tissue using a novel family of biomimetic proteoglycans (BPGs). This work examines the ability of BPGs to modulate the mechanical and physical properties of porcine urethras
ex vivo
to determine the feasibility of BPGs to be implemented as molecular treatment for stress urinary incontinence (SUI). We investigated compliance by performing a unique radial expansion testing method using urethras from six- to nine-month-old pigs. The urethras were injected with 0.5 ml BPG solution at three sites every approximately 120° (conc.: 25 mg ml
−1
, 50 mg ml
−1
and 75 mg ml
−1
in 1× phosphate-buffered saline (PBS);
n
= 4 per group) and compared them with PBS-injected controls. Young's modulus was calculated by treating the urethra as a thin-walled pressure vessel. A water uptake study was performed by soaking 10 mm urethra biopsy samples that were injected with 0.1 ml BPG solution (conc.: 50 mg ml
−1
, 100 mg ml
−1
and 200 mg ml
−1
in 1× PBS;
n
= 6 per group) in 5 ml PBS for 24 h. Although there was no significant difference in Young's modulus data, there were differences between groups as can be seen in the raw radial expansion testing data. Results showed that BPGs have the potential to increase hydration in samples, and that there was a significant difference in water uptake between BPG-injected samples and the controls (100 mg ml
−1
samples versus PBS samples,
p
< 0.05). This work shows that BPGs have the potential to be implemented as a molecular treatment for SUI, by restoring the diminished proteoglycan content and subsequently increasing hydration and improving the compliance of urethral tissue.
Engineering and women's health: a slow start, but gaining momentum
Authors: Grimm Michele J.
Published: June 2019

While biomedical engineers have participated in research studies that focus on understanding aspects particular to women's health since the 1950s, the depth and breadth of the research have increased significantly in the last 15–20 years. It has been increasingly clear that engineers can lend important knowledge and analysis to address questions that are key to understanding physiology and pathophysiology related to women's health. This historical survey identifies some of the earliest contributions of engineers to exploring aspects of women's health, from the behaviour of key tissues, to issues of reproduction and breast cancer. In addition, some of the more recent work in each area is identified and areas deserving additional attention are described. The interdisciplinary nature of this area of engineering, along with the growing interest within the field of biomedical engineering, promise to bring exciting new discoveries and expand knowledge that will positively impact women's health in the near future.
Daily bilateral pudendal nerve electrical stimulation improves recovery from stress urinary incontinence
Authors: Deng Kangli , Balog Brian M. , Lin Dan Li , Hanzlicek Brett , Song Qi-Xiang , Zhu Hui , Damaser Margot S.
Published: June 2019

Stress urinary incontinence (SUI) in women is strongly associated with childbirth which injures the pudendal nerve (PN) and the external urethral sphincter (EUS) during delivery. Electrical stimulation (ES) can increase brain-derived neurotrophic factor (BDNF) expression in injured neurons, activate Schwann cells and promote neuroregeneration after nerve injury. The aim of this study was to determine if more frequent ES would increase recovery from SUI in a rat model. Forty female Sprague–Dawley rats underwent either sham injury or pudendal nerve crush (PNC) and vaginal distention (VD) to establish SUI. Immediately after injury, electrodes were implanted at the pudendal nerve bilaterally. Each injured animal underwent sham ES, twice per week ES (2/week), or daily ES of 1 h duration for two weeks. Urethral and nerve function were assessed with leak point pressure (LPP), EUS electromyography and pudendal nerve sensory branch potential (PNSBP) recordings two weeks after injury. LPP was significantly increased after daily ES compared to 2/week ES. EUS neuromuscular junction innervation was decreased after injury with sham ES, but improved after 2/week or daily ES. This study demonstrates that daily bilateral ES to the pudendal nerve can accelerate recovery from SUI. Daily ES improved urethral function more than 2/week ES.
Smooth muscle regional contribution to vaginal wall function
Authors: Clark Gabrielle L. , Pokutta-Paskaleva Anastassia P. , Lawrence Dylan J. , Lindsey Sarah H. , Desrosiers Laurephile , Knoepp Leise R. , Bayer Carolyn L. , Gleason Rudolph L. , Miller Kristin S.
Published: June 2019

Pelvic organ prolapse is characterized as the descent of the pelvic organs into the vaginal canal. In the USA, there is a 12% lifetime risk for requiring surgical intervention. Although vaginal childbirth is a well-established risk factor for prolapse, the underlying mechanisms are not fully understood. Decreased smooth muscle organization, composition and maximum muscle tone are characteristics of prolapsed vaginal tissue. Maximum muscle tone of the vaginal wall was previously investigated in the circumferential or axial direction under uniaxial loading; however, the vaginal wall is subjected to multiaxial loads. Further, the contribution of vaginal smooth muscle basal (resting) tone to mechanical function remains undetermined. The objectives of this study were to determine the contribution of smooth muscle basal and maximum tone to the regional biaxial mechanical behaviour of the murine vagina. Vaginal tissue from C57BL/6 mice was subjected to extension–inflation protocols (
n
= 10) with and without basal smooth muscle tone. Maximum tone was induced with KCl under various circumferential (
n
= 5) and axial (
n
= 5) loading conditions. The microstructure was visualized with multiphoton microscopy (
n
= 1), multiaxial histology (
n
= 4) and multiaxial immunohistochemistry (
n
= 4). Smooth muscle basal tone decreased material stiffness and increased anisotropy. In addition, maximum vaginal tone was decreased with increasing intraluminal pressures. This study demonstrated that vaginal muscle tone contributed to the biaxial mechanical response of murine vaginal tissue. This may be important in further elucidating the underlying mechanisms of prolapse, in order to improve current preventative and treatment strategies.
Bioengineering in women's health: part I
Authors: Miller Kristin S. , Myers Kristin , Oyen Michelle
Published: June 2019

This theme issue of
Interface Focus
is the first of two sets of articles on the topic of bioengineering in women's health. Although there is a long history of collaboration between engineers and medical professionals in orthopaedics and cardiovascular medicine, there has been growing interest in the last decade for interdisciplinary collaborations in other areas of medical science. This growth is particularly true in the case of women's health, a traditionally underserved area of research in the scientific community where fundamental knowledge of female physiology is still needed. Women's health is a broad category encompassing reproduction, fertility, maternal health, normal and abnormal pregnancy and the sequelae associated with a difficult childbirth. Women's health also includes sex-associated pathology associated with cancer, pain, cardiac disease, osteoporosis and other diseases. This list is not exhaustive with new scientific frontiers developing based on the evolving discourse of medicine for all. This first issue in the series focuses on bioengineering advances in the study of the non-pregnant woman, and the articles highlight important developments in pelvic floor disorders, biomedical devices, fertility, breast implant failure and breast cancer. The second issue in the series focuses on pregnancy.
Clostridium prolinivorans sp. nov., a thermophilic bacterium isolated from an anaerobic reactor degrading propionate
Authors: Huang Yan , Wei Zhixian , Cong Lulu , Qiu Zhongwei , Chen Rui , Deng Yu , Zhang Yinggang , Fan Hui , Ma Shichun
Published: June 2019

An anaerobic, Gram-stain-positive, spore-forming bacterium, designated strain PYR-10T, was isolated from a mesophilic methanogenic consortium. Cells were 0.7–1.2×6.0–6.3 µm, straight or slightly curved rods, with flagellar motility. Growth was observed in PYG (peptone-yeast glucose) medium at pH 5.5–8.0 (optimum, pH 6.5), 30–55 °C (45 °C) and in NaCl concentrations of 0–15 g l−1 (0 g l−1). Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain PYR-10T belongs to the genus

Clostridium

. The strain showed 95.4, 93.7, 93.5 and 93.0 % 16S rRNA gene sequence similarity to

Clostridium swellfunianum

DSM 27788T,

Clostridium pascui

DSM 10365T,

Clostridium pasteurianum

DSM 525T and

Clostridium punense

DSM 28650T, respectively. The genomic DNA G+C content was 27.7 mol%. The major cellular fatty acids of strain PYR-10T were iso-C15 : 0, C16 : 0, C16 : 0 DMA, anteiso-C15 : 0 and C14 : 0. The main polar lipids were glycolipid, phosphoaminoglycolipid, diphosphatidylglycerol, phosphatidylglycerol, phospholipids, phosphatidylethanolamine and lipids. An unknown menaquinone was detected. 2,6-Diaminopimelic acid was not detected. The whole-cell sugars contained ribose and lower amounts of glucose. Based on the results of phylogenetic, chemotaxonomic and phenotypic analyses, strain PYR-10T represents a novel species of the genus

Clostridium

, for which the name

Clostridium
prolinivorans sp. nov. is proposed. The type strain is strain PYR-10T (=JCM 33161T=CCAM 531T=CGMCC 1.5286T).
Activation of MAIT cells plays a critical role in viral vector vaccine immunogenicity
Authors: Provine Nicholas M. , Amini Ali , Garner Lucy C. , Dold Christina , Hutchings Claire , FitzPatrick Michael E.B. , Reyes Laura Silva , Chinnakannan Senthil , Oguti Blanche , Raymond Meriel , Capone Stefania , Folgori Antonella , Rollier Christine S. , Barnes Eleanor , Pollard Andrew J. , Klenerman Paul
Published: June 2019

Mucosal-associated invariant T (MAIT) cells can be activated by viruses through a cytokine-dependent mechanism, and thereby protect from lethal infection. Given this, we reasoned MAIT cells may have a critical role in the immunogenicity of replication-incompetent adenovirus vectors, which are novel and highly potent vaccine platforms. In vitro, ChAdOx1 (Chimpanzee Adenovirus Ox1) induced potent activation of MAIT cells. Activation required transduction of monocytes and plasmacytoid dendritic cells to produce IL-18 and IFN-α, respectively. IFN-α-induced monocyte-derived TNF-α was identified as a novel intermediate in this activation pathway, and activation required combinatorial signaling of all three cytokines. Furthermore, ChAdOx1-induced in vivo MAIT cell activation in both mice and human volunteers. Strikingly, MAIT cell activation was necessary in vivo for development of ChAdOx1-induced HCV-specific CD8 T cell responses. These findings define a novel role for MAIT cells in the immunogenicity of viral vector vaccines, with potential implications for future design.

One sentence summary

Robust immunogenicity of candidate adenovirus vaccine vectors requires the activation of unconventional T cells.
The genomic architecture of blood metabolites based on a decade of genome-wide analyses
Authors: Hagenbeek Fiona A. , Pool René , van Dongen Jenny , Draisma Harmen H.M. , Hottenga Jouke Jan , Willemsen Gonneke , Abdellaoui Abdel , Fedko Iryna O. , Braber Anouk den , Visser Pieter Jelle , de Geus Eco J.C.N. , van Dijk Ko Willems , Verhoeven Aswin , Suchiman H. Eka , Beekman Marian , Slagboom P. Eline , van Duijn Cornelia M. ,   BBMRI Metabolomics Consortium, Harms Amy C. , Hankemeier Thomas , Bartels Meike , Nivard Michel G. , Boomsma Dorret I.
Published: June 2019

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes and lipid species. We performed a review of all genetic association studies, and identified > 800 class-specific metabolite loci that influence metabolite levels. In a twin-family cohort (N= 5,117), these metabolite loci were leveraged to simultaneously estimate total heritability (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study revealed significant differences inh2Metabolite-hitsamong different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation had higherh2Metabolite-hitsestimates than phosphatidylcholines with a low degree of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes and lipid species.