bluuebunny/crossref_metadata_2025 huggingface dataset:
SupplementalTrichomonas vaginalistesting is required to maintain control following a transition from Pap smear to HPV DNA testing for cervical screening: a mathematical modelling study
Authors: Regan David Gabriel , Hui Ben B , Guy Rebecca J , Donovan Basil , Hocking Jane S , Law Matthew G
Published: April 2019

Objectives

Using mathematical modelling, we have previously shown that the prevalence of infection withTrichomonas vaginalis(TV) is likely to increase in the general population in Australia with the transition from Pap smear-based cervical screening to human papillomavirus (HPV) DNA testing. Here we use the existing model to estimate the level of supplemental testing required to maintain TV control.

Methods

A compartmental mathematical model describing the transmission of TV in the general heterosexual population in Australia was used to evaluate the impact of a range of screening scenarios on TV prevalence over time following the transition to HPV DNA testing for cervical screening. Scenarios considered were the inclusion of a TV test with the HPV test and the addition of TV testing to routine chlamydia testing conducted in primary care.

Results

Our modelling suggests that with sufficient coverage, inclusion of TV testing with routine chlamydia screening in general practice, TV prevalence can be reduced over time, but at the current reported coverage will gradually increase following the transition to HPV testing. Inclusion of TV testing with HPV testing in the cervical screening programme is preferable to no supplemental testing but is considerably less effective in controlling TV.

Conclusions

These findings support the inclusion of TV testing with routine chlamydia testing of young people.
Resuscitative endovascular balloon occlusion of the aorta (REBOA): indications: advantages and challenges of implementation in traumatic non-compressible torso hemorrhage
Authors: Bekdache Omar , Paradis Tiffany , Shen Yu Bai He , Elbahrawy Aly , Grushka Jeremy , Deckelbaum Dan , Khwaja Kosar , Fata Paola , Razek Tarek , Beckett Andrew
Published: April 2019

Background

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is regaining popularity in the treatment of traumatic non-compressible torso bleeding. Advances in invasive radiology coupled with new damage control measures assisted in the refinement of the technique with promising outcomes. The literature continues to have substantial heterogeneity about REBOA indications, applications, and the challenges confronted when implementing the technique in a level I trauma center. Scoping reviews are excellent platforms to assess the diverse literature of a new technique. It is for the first time that a scoping review is adopted for this topic. Advances in invasive radiology coupled with new damage control measures assisted in the refinement of the technique with promising outcomes. The literature continues to have substantial heterogeneity about REBOA indications, applications, and the challenges confronted when implementing the technique in a level I trauma center. Scoping reviews are excellent platforms to assess the diverse literature of a new technique. It is for the first time that a scoping review is adopted for this topic.

Methods

Critical search from MEDLINE, EMBASE, BIOSIS, COCHRANE CENTRAL, PUBMED and SCOPUS were conducted from the earliest available dates until March 2018. Evidence-based articles, as well as gray literature at large, were analyzed regardless of the quality of articles.

Results

We identified 1176 articles related to the topic from all available database sources and 57 reviews from the gray literature search. The final review yielded 105 articles. Quantitative and qualitative variables included patient demographics, study design, study objectives, methods of data collection, indications, REBOA protocol used, time to deployment, zone of deployment, occlusion time, complications, outcome, and the level of expertise at the concerned trauma center.

Conclusion

Growing levels of evidence support the use of REBOA in selected indications. Our data analysis showed an advantage for its use in terms of morbidities and physiologic derangement in comparison to other resuscitation measures. Current challenges remain in the selective application, implementation, competency assessment, and credentialing for the use of REBOA in trauma settings. The identification of the proper indication, terms of use, and possible advantage of the prehospital and partial REBOA are topics for further research.

Level of evidence

Level III.
A harmonic spectral beamformer for the enhanced localization of propeller-driven aircraft
Authors: Harvey Brendan , O’Young Siu
Published: April 2019

The following paper presents several array processing techniques that may be used to enhance the localization of acoustic source targets, such as UAVs. A review of common methods is first provided, followed by several algorithms developed to reduce computational loads for the application of concern. A beamforming method is proposed that exploits the properties of harmonic narrowband signals, such as that generated by propeller-driven aircraft to enhance direction of arrival accuracy. In addition, a regional contraction search algorithm is proposed to minimize computational loads associated with the presented localization technique. A brief comparison of the proposed method to that of standard frequency domain beamformers is also provided using both theoretical analysis and experimental data. For the case of target localization between two moving fixed-wing UAVs, it was found that the proposed harmonic spectral beamforming method increased localization accuracy by 50% over the standard steered response power approach.
The improvement of thermal conductivity in silica gel composite employing graphene nano-particles
Authors: Lv Jian , Cai Xiaoming , Ye Qianxu , Cai Jinming
Published: April 2019

Heat conducting gel sheets were fabricated with graphene nano-particles (GNPs) filler which was prepared by ball-milling method. The thermal conductivity of GNPs gel sheets (GNPs-GS) with 10 wt.% reaching 0.38 W/(m⋅K) at [Formula: see text] increased by 90% compared with the pure gel sheets (Pure-GS). The conduction of heat-sink device which was made of GNPs-GS with 10 wt.% is much faster than the one which was made of Pure-GS. FE-SEM images show that the GNPs are layered and uniformly distributed in the matrix, which demonstrated the actual exfoliation of GNPs in the process of ball-milling. This handy and cost-efficient method of ball-milling to exfoliate GNPs and further for fabricating heat conducting gel sheets is a feasible program in industrial production.
Experimental Investigation and Parametric Optimization in Abrasive Jet Machining on NICKEL 233 Alloy Using WASPAS
Authors: Prasad S. Rajendra , Ravindranath K. , Devakumar M. L. S.
Published: April 2019

Decision of finest machining parameters is very essential factors in any processing of machined parts. This article presents a multi-objective optimization technique, based on WASPAS method toward optimize the machining parameters in abrasive jet machining (AJM) process: pressure, nozzle to tip distance (NTD), and average grain diameter on NICKEL 233 alloy. Three conflicting objectives, Material Removal Rate (MRR), surface roughness (Ra) and taper angle (Ta) are simultaneously considered. The proposed technique weighted aggregated product sum assessment technique is investigation of parametric optimization on AJM process. Its outcome using tool in any ranges of responses in AJM process is the optimal setting of parameters are determined through experiments illustrated. Broad usage of Aerospace industries for NICKEL 233, generating a hole of the machining data first time in this work using AJM will be useful.
Computer Aided Finite Element Simulation of the Developed Driller System for Bone Drilling Process in Orthopedic Surgery
Authors: Gok Kadir , Gok Arif , Kisioglu Yasin
Published: April 2019

Heat reveals during the bone drilling operations in orthopedic surgery because of friction between bone and surgical drill bit. The heating causes extremely important damages in bone and soft tissues. The heating has a critical threshold and it is known as 47∘C. If bone temperature value exceeds 47∘C, osteonecrosis occurs in bones and soft tissues. Many factors such as surgical drill bit geometry and material, drilling parameters, coolant has important roles for the temperature rise. Many methods are used to decrease the temperature rise. The most effective method among them is to use the coolant internally. Numeric simulations of a new driller system to avoid the overheating during the orthopedic operating processes were performed in this study. The numerical simulation with/without coolant was also performed using the finite element based software. Computer aided simulation studies were used to measure the bone temperatures occurred during the bone drilling processes. The outcomes from the simulations were compared with the experimental results. A good temperature level agreement between the experimental results and FEA simulations was found during the bone drilling process.
Deep Reinforcement Scheduling for Mobile Crowdsensing in Fog Computing
Authors: Li He , Ota Kaoru , Dong Mianxiong
Published: April 2019

Mobile crowdsensing becomes a promising technology for the emerging Internet of Things (IoT) applications in smart environments. Fog computing is enabling a new breed of IoT services, which is also a new opportunity for mobile crowdsensing. Thus, in this article, we introduce a framework enabling mobile crowdsensing in fog environments with a hierarchical scheduling strategy. We first introduce the crowdsensing framework that has a hierarchical structure to organize different resources. Since different positions and performance of fog nodes influence the quality of service (QoS) of IoT applications, we formulate a scheduling problem in the hierarchical fog structure and solve it by using a deep reinforcement learning–based strategy. From extensive simulation results, our solution outperforms other scheduling solutions for mobile crowdsensing in the given fog computing environment.
Temporal Constraints in Human--Building Interaction
Authors: Johansen Stine Schmieg , Kjeldskov Jesper , Skov Mikael B.
Published: April 2019

Human--building interaction (HBI) is converging the fields of architecture and interaction design, leading to new and interesting tensions in perspectives and methodological approaches. One such tension is related to temporal constraints. Architecture and interaction design typically produce outcomes with very different lifetime expectancies and, predominantly, use methods with very different pace. As an example, fast, iterative approaches of contemporary interaction design, consisting of frequent updates and redesigns, contrasts with much slower, plan-driven and long-term vision driven approaches within architecture. One question emerging from this tension is how to meaningfully combine perspectives and approaches. One suggestion, among others, has been that interaction design methods such as participatory design can be used to heighten the involvement of inhabitants and other stakeholders in continuous adaptations of the buildings they inhabit. While an interesting proposal, we believe that methodological considerations only partly address the complexity of the tension at play from the different lifetime expectancies of buildings and interactive computer systems. Unfolding this complexity further, we therefore propose a framework of temporal constraints at three levels of abstraction: (1) rationale, (2) method, and (3) outcome. Inspired by previous work, we discuss temporal constraints in HBI at these levels. We argue that designing for HBI requires an understanding of temporally constrained design conventions that apply meaningfully to both the short term and long term.
Probabilistic Feature Selection and Classification Vector Machine
Authors: Jiang Bingbing , Li Chang , Rijke Maarten De , Yao Xin , Chen Huanhuan
Published: April 2019

Sparse Bayesian learning is a state-of-the-art supervised learning algorithm that can choose a subset of relevant samples from the input data and make reliable probabilistic predictions. However, in the presence of high-dimensional data with irrelevant features, traditional sparse Bayesian classifiers suffer from performance degradation and low efficiency due to the incapability of eliminating irrelevant features. To tackle this problem, we propose a novel sparse Bayesian embedded feature selection algorithm that adopts truncated Gaussian distributions as both sample and feature priors. The proposed algorithm, called probabilistic feature selection and classification vector machine (PFCVM
LP
) is able to simultaneously select relevant features and samples for classification tasks. In order to derive the analytical solutions, Laplace approximation is applied to compute approximate posteriors and marginal likelihoods. Finally, parameters and hyperparameters are optimized by the type-II maximum likelihood method. Experiments on three datasets validate the performance of PFCVM
LP
along two dimensions: classification performance and effectiveness for feature selection. Finally, we analyze the generalization performance and derive a generalization error bound for PFCVM
LP
. By tightening the bound, the importance of feature selection is demonstrated.
SAQIP
Authors: Sargaran Sahar , Mohammadzadeh Naser
Published: April 2019

Proposing an architecture that efficiently compensates for the inefficiencies of physical hardware with extra resources is one of the key issues in quantum computer design. Although the demonstration of quantum systems has been limited to some dozen qubits, scaling the current small-sized lab quantum systems to large-scale quantum systems that are capable of solving meaningful practical problems can be the main goal of much research. Focusing on this issue, in this article a scalable architecture for quantum information processors, called SAQIP, is proposed. Moreover, a flow is presented to map and schedule a quantum circuit on this architecture. Experimental results show that the proposed architecture and design flow decrease the average latency and the average area of quantum circuits by about 81% and 11%, respectively, for the attempted benchmarks.
Transparent Acceleration for Heterogeneous Platforms With Compilation to OpenCL
Authors: Riebler Heinrich , Vaz Gavin , Kenter Tobias , Plessl Christian
Published: April 2019

Multi-accelerator platforms combine CPUs and different accelerator architectures within a single compute node. Such systems are capable of processing parallel workloads very efficiently while being more energy efficient than regular systems consisting of CPUs only. However, the architectures of such systems are diverse, forcing developers to port applications to each accelerator using different programming languages, models, tools, and compilers. Developers not only require domain-specific knowledge but also need to understand the low-level accelerator details, leading to an increase in the design effort and costs.

To tackle this challenge, we propose a compilation approach and a practical realization called

HT
r
OP

that is completely transparent to the user. HT
r
OP is able to automatically analyze a sequential CPU application, detect computational hotspots, and generate parallel OpenCL host and kernel code. The potential of HT
r
OP is demonstrated by offloading hotspots to different OpenCL-enabled resources (currently the CPU, the general-purpose GPU, and the manycore Intel Xeon Phi) for a broad set of benchmark applications. We present an in-depth evaluation of our approach in terms of performance gains and energy savings, taking into account all static and dynamic overheads. We are able to achieve speedups and energy savings of up to two orders of magnitude, if an application has sufficient computational intensity, when compared to a natively compiled application.
Combining Source-adaptive and Oblivious Routing with Congestion Control in High-performance Interconnects using Hybrid and Direct Topologies
Authors: Yebenes Pedro , Rocher-Gonzalez Jose , Escudero-Sahuquillo Jesus , Garcia Pedro Javier , Alfaro Francisco J. , Quiles Francisco J. , Gómez Crispín , Duato Jose
Published: April 2019

Hybrid and direct topologies are cost-efficient and scalable options to interconnect thousands of end nodes in high-performance computing (HPC) systems. They offer a rich path diversity, high bisection bandwidth, and a reduced diameter guaranteeing low latency. In these topologies, efficient deterministic routing algorithms can be used to balance smartly the traffic flows among the available routes. Unfortunately, congestion leads these networks to saturation, where the HoL blocking effect degrades their performance dramatically. Among the proposed solutions to deal with HoL blocking, the routing algorithms selecting alternative routes, such as adaptive and oblivious, can mitigate the congestion effects. Other techniques use queues to separate congested flows from non-congested ones, thus reducing the HoL blocking. In this article, we propose a new approach that reduces HoL blocking in hybrid and direct topologies using source-adaptive and oblivious routing. This approach also guarantees deadlock-freedom as it uses virtual networks to break potential cycles generated by the routing policy in the topology. Specifically, we propose two techniques, called
Source-Adaptive Solution for Head-of-Line Blocking Avoidance
(SASHA) and
Oblivious Solution for Head-of-Line Blocking Avoidance
(OSHA). Experiment results, carried out through simulations under different traffic scenarios, show that SASHA and OSHA can significantly reduce the HoL blocking.
Myocardial ischemia: lack of coronary blood flow, myocardial oxygen supply-demand imbalance, or what?
Authors: Heusch Gerd
Published: April 2019

This opinionated article reviews current concepts of myocardial ischemia. Specifically, the historical background is briefly presented. Then, the prevailing paradigm of myocardial oxygen-supply-demand imbalance is criticized since demand is a virtual parameter that cannot be measured and data on measurements of myocardial blood flow and contractile function rather support matching between flow and function. Finally, a concept of myocardial ischemia that focusses on the reduction of coronary blood flow to below 8–10 µl/g per beat with consequences for myocardial electrical, metabolic, contractile and morphological features is advocated.
Treatment with apolipoprotein A1 protects mice against doxorubicin-induced cardiotoxicity in a scavenger receptor class B, type I-dependent manner
Authors: Durham Kristina K. , Kluck George , Mak Kei Cheng , Deng Yak D. , Trigatti Bernardo L.
Published: April 2019

Doxorubicin, an agent used to treat a variety of cancers, is cardiotoxic by triggering cardiomyocyte apoptosis. We previously showed that treating cultured cardiomyocytes with human high-density lipoprotein in vitro or transgenic overexpression of human apolipoprotein A1, its main structural protein, protects against doxorubicin-induced cardiomyocyte apoptosis in a manner dependent on the scavenger receptor class B type I [Durham KK, Chathely KM, Mak KC, Momen A, Thomas CT, Zhao YY, MacDonald ME, Curtis JM, Husain M, Trigatti BL. HDL protects against doxorubicin-induced cardiotoxicity in a scavenger receptor class B type 1-, phosphatidylinositol 3-kinase-, and Akt-dependent manner. Am J Physiol Heart Circ Physiol 314: H31–H44, 2018]. This was due to high-density lipoprotein-induced activation of Akt signaling in cardiomyocytes. We now demonstrate that mice lacking the scavenger receptor class B, type I exhibit increased sensitivity to doxorubicin-induced cardiomyocyte apoptosis in vivo. Cardiomyocytes expressing scavenger receptor class B, type I are protected from doxorubicin-induced apoptosis by preincubation with high-density lipoprotein isolated from wild-type mice, whereas high-density lipoprotein from scavenger receptor class B, type 1 knockout mice is less effective. Cardiomyocytes from scavenger receptor class B, type I knockout mice, however, are not protected by high-density lipoprotein in vitro, and hearts from knockout mice are more sensitive to doxorubicin in vivo. Pharmacological administration of purified apolipoprotein A1 dramatically protected wild-type mice from doxorubicin-induced cardiotoxicity and left ventricular dysfunction, whereas this protection was lost in scavenger receptor class B, type I-deficient mice. This demonstrates, at least in mice, that high-density lipoprotein therapy can confer protection against doxorubicin-induced cardiomyocyte apoptosis in a manner mediated by the scavenger receptor class B, type I.

NEW & NOTEWORTHY We show that scavenger receptor class B, type I (SR-B1) mediates HDL-dependent protection against doxorubicin-induced cardiomyocyte apoptosis and that this is a property of SR-B1 in cardiomyocytes in vitro and in hearts in vivo. We also demonstrate that pharmacological treatment with apolipoprotein A1, the major HDL structural protein, protects mice against doxorubicin-induced cardiomyocyte apoptosis and left ventricular dysfunction in an SR-B1-dependent manner. This suggests that HDL-targeted pharmacological therapy may hold promise for protecting against the deleterious, cardiotoxic side effects of this commonly used chemotherapeutic drug.
Chemotherapy acutely impairs neurovascular and hemodynamic responses in women with breast cancer
Authors: Sales Allan Robson Kluser , Negrão Marcelo Vailati , Testa Laura , Ferreira-Santos Larissa , Groehs Raphaela Villar Ramalho , Carvalho Bruna , Toschi-Dias Edgar , Rocha Natalia Galito , Laurindo Francisco Rafael Martins , Debbas Victor , Rondon Maria Urbana P. B. , Mano Max Sena , Hajjar Ludhmila Abrahao , Hoff Paulo Marcelo Gehm , Filho Roberto Kalil , Negrão Carlos Eduardo
Published: April 2019

The purpose of the present study was to test the hypothesis that doxorubicin (DX) and cyclophosphamide (CY) adjuvant chemotherapy (CHT) acutely impairs neurovascular and hemodynamic responses in women with breast cancer. Sixteen women (age: 47.0 ± 2.0 yr; body mass index: 24.2 ± 1.5 kg/m) with stage II-III breast cancer and indication for adjuvant CHT underwent two experimental sessions, saline (SL) and CHT. In the CHT session, DX (60 mg/m2) and CY (600 mg/m2) were administered over 45 min. In the SL session, a matching SL volume was infused in 45 min. Muscle sympathetic nerve activity (MSNA) from peroneal nerve (microneurography), calf blood flow (CBF; plethysmography) and calf vascular conductance (CVC), heart rate (HR; electrocardiography), and beat-to-beat blood pressure (BP; finger plethysmography) were measured at rest before, during, and after each session. Venous blood samples (5 ml) were collected before and after both sessions for assessment of circulating endothelial microparticles (EMPs; flow cytometry), a surrogate marker for endothelial damage. MSNA and BP responses were increased ( P < 0.001), whereas CBF and CVC responses were decreased ( P < 0.001), during and after CHT session when compared with SL session. Interestingly, the vascular alterations were also observed at the molecular level through an increased EMP response to CHT ( P = 0.03, CHT vs. SL session). No difference in HR response was observed ( P > 0.05). Adjuvant CHT with DX and CY in patients treated for breast cancer increases sympathetic nerve activity and circulating EMP levels and, in addition, reduces muscle vascular conductance and elevates systemic BP. These responses may be early signs of CHT-induced cardiovascular alterations and may represent potential targets for preventive interventions.

NEW & NOTEWORTHY It is known that chemotherapy regimens increase the risk of cardiovascular events in patients treated for cancer. Here, we identified that a single cycle of adjuvant chemotherapy with doxorubicin and cyclophosphamide in women treated for breast cancer dramatically increases sympathetic nerve activity and circulating endothelial microparticle levels, reduces the muscle vascular conductance, and elevates systemic blood pressure.
Human genotyping and an experimental model reveal NPR-C as a possible contributor to morbidity in coarctation of the aorta
Authors: LaDisa John F. , Tomita-Mitchell Aoy , Stamm Karl , Bazan Kathleen , Mahnke Donna K. , Goetsch Mary A. , Wegter Brandon J. , Gerringer Jesse W. , Repp Kathryn , Palygin Oleg , Zietara Adrian P. , Krolikowski Mary M. , Eddinger Thomas J. , Alli Abdel A. , Mitchell Michael E.
Published: April 2019

Coarctation of the aorta (CoA) is a common congenital cardiovascular (CV) defect characterized by a stenosis of the descending thoracic aorta. Treatment exists, but many patients develop hypertension (HTN). Identifying the cause of HTN is challenging because of patient variability (e.g., age, follow-up duration, severity) and concurrent CV abnormalities. Our objective was to conduct RNA sequencing of aortic tissue from humans with CoA to identify a candidate gene for mechanistic studies of arterial dysfunction in a rabbit model of CoA devoid of the variability seen with humans. We present the first known evidence of natriuretic peptide receptor C ( NPR-C; aka NPR3) downregulation in human aortic sections subjected to high blood pressure (BP) from CoA versus normal BP regions (validated to PCR). These changes in NPR-C, a gene associated with BP and proliferation, were replicated in the rabbit model of CoA. Artery segments from this model were used with human aortic endothelial cells to reveal the functional relevance of altered NPR-C activity. Results showed decreased intracellular calcium ([Ca2+]i) activity to C-type natriuretic peptide (CNP). Normal relaxation induced by CNP and atrial natriuretic peptide was impaired for aortic segments exposed to elevated BP from CoA. Inhibition of NPR-C (M372049) also impaired aortic relaxation and [Ca2+]i activity. Genotyping of NPR-C variants predicted to be damaging revealed that rs146301345 was enriched in our CoA patients, but sample size limited association with HTN. These results may ultimately be used to tailor treatment for CoA based on mechanical stimuli, genotyping, and/or changes in arterial function.
Signatures of B-cell receptor diversity in B lymphocytes following Epstein-Barr virus transformation
Authors: Lai Meimei , Wang Qiongdan , Lu Yutian , Xu Xi , Xia Ying , Tu Mengyun , Liu Yanqing , Zhang Qi , Peng Ying , Zheng Xiaoqun
Published: April 2019

Epstein-Barr virus (EBV) is a widespread human virus that establishes latent infection, potentially leading to tumors, hematological disorders, and other severe diseases. EBV infections are associated with diverse symptoms and affect various organs; therefore, early diagnosis and treatment are crucial. B cell receptor (BCR) repertoires of B cell surface immunoglobulins have been widely studied for their association with various infectious diseases. However, the specific genetic changes that modulate the BCR repertoires after an EBV infection are still poorly understood. In this study, we employed high-throughput sequencing (HTS) to investigate the diversity of BCR repertoires in an EBV-transformed lymphoblastic cell line (LCL). Compared with the noninfected control B cell line, the LCL exhibited a decrease in overall BCR diversity but displayed an increase in the expansion of some dominant rearrangements such as IGHV4-31/IGHJ4, IGHV4-59/IGHJ4, IGHV5-51/IGHJ3, and IGHV3-74/IGHJ3. A higher frequency of occurrence of these rearrangement types was confirmed in patients with EBV infection. Interestingly, the IGHV3-74 rearrangement was only detected in EBV-infected children, suggesting that our experimental observations were not coincidental. In addition, we identified a highly dominant consensus motif, CAR(xRx)YGSG(xYx)FD, in complementarity-determining region 3 (CDR3) sequences of the heavy chain in the LCL. Our findings demonstrated the utility of HTS technology for studying the variations in signature motifs of the BCR repertoires after EBV infection. We propose that the analysis of BCR repertoire sequences represents a promising method for diagnosing early EBV infections and developing novel antibody- and vaccine-based therapies against such infections.
Cutting Edge: Probiotics and Fecal Microbiota Transplantation in Immunomodulation
Authors: Zeng Wenjie , Shen Jie , Bo Tao , Peng Liangxin , Xu Hongbo , Nasser Moussa Ide , Zhuang Quan , Zhao Mingyi
Published: April 2019

Probiotics are commensal or nonpathogenic microbes that confer beneficial effects on the host through several mechanisms such as competitive exclusion, antibacterial effects, and modulation of immune responses. Some probiotics have been found to regulate immune responses via immune regulatory mechanisms. T regulatory (Treg) cells, T helper cell balances, dendritic cells, macrophages, B cells, and natural killer (NK) cells can be considered as the most determinant dysregulated mediators in immunomodulatory status. Recently, fecal microbiota transplantation (FMT) has been defined as the transfer of distal gut microbial communities from a healthy individual to a patient’s intestinal tract to cure some immune disorders (mainly inflammatory bowel diseases). The aim of this review was followed through the recent literature survey on immunomodulatory effects and mechanisms of probiotics and FMT and also efficacy and safety of probiotics and FMT in clinical trials and applications.
A Clinically Applicable Gene-Expression Classifier Reveals Intrinsic and Extrinsic Contributions to Consensus Molecular Subtypes in Primary and Metastatic Colon Cancer
Authors: Piskol Robert , Huw Ling , Sergin Ismail , Kljin Christiaan , Modrusan Zora , Kim Doris , Kljavin Noelyn , Tam Rachel , Patel Rajesh , Burton Jeremy , Penuel Elicia , Qu Xueping , Koeppen Hartmut , Sumiyoshi Teiko , de Sauvage Frederic , Lackner Mark R. , de Sousa e Melo Felipe , Kabbarah Omar
Published: April 2019

Purpose:

Four consensus molecular subtypes (CMS1–4) of colorectal cancer were identified in primary tumors and found to be associated with distinctive biological features and clinical outcomes. Given that distant metastasis largely accounts for colorectal cancer–related mortality, we examined the molecular and clinical attributes of CMS in metastatic colorectal cancer (mCRC).

Experimental Design:

We developed a colorectal cancer–focused NanoString-based CMS classifier that is ideally suited to interrogate archival tissues. We successfully used this panel in the CMS classification of formalin-fixed paraffin-embedded (FFPE) tissues from mCRC cohorts, one of which is composed of paired primary tumors and metastases. Finally, we developed novel mouse implantation models to enable modeling of colorectal cancer in vivo at relevant sites.

Results:

Using our classifier, we find that the biological hallmarks of mCRC, including CMS, are in general highly similar to those observed in nonmetastatic early-stage disease. Importantly, our data demonstrate that CMS1 has the worst outcome in relapsed disease, compared with other CMS. Assigning CMS to primary tumors and their matched metastases reveals mostly concordant subtypes between primary and metastasis. Molecular analysis of matched discordant pairs reveals differences in stromal composition at each site. The development of two novel in vivo orthotopic implantation models further reinforces the notion that extrinsic factors may impact on CMS identification in matched primary and metastatic colorectal cancer.

Conclusions:

We describe the utility of a NanoString panel for CMS classification of FFPE clinical samples. Our work reveals the impact of intrinsic and extrinsic factors on colorectal cancer heterogeneity during disease progression.
A Constitutional Activating MET Mutation Makes the Genetic Link between Malignancies and Chronic Inflammatory Diseases
Authors: El Bouchtaoui Morad , Do Cruzeiro Marcio , Leboeuf Christophe , Loisel-Ferreira Irmine , Fedronie Carèle , Ferreira Chrystophe , Ait El Far Rachida , Ziol Marianne , Espié Marc , Falgarone Géraldine , Cassinat Bruno , Kiladjian Jean-Jacques , Feugeas Jean-Paul , Janin Anne , Bousquet Guilhem
Published: April 2019

Purpose:

The genesis of all cancers results from an accumulation of mutations, constitutional and/or acquired when induced by external mutagenic factors. High-speed technologies for genome sequencing have completely changed the study of disease genetics, but with limited knowledge of the functional value of most genetic changes.

Experimental Design:

Here, we proposed an innovative individual approach by studying tissue samples from a young woman with an unusual association of breast cancer, polycythemia vera, and rheumatoid arthritis. We performed genomic analyses for copy number variations and point mutations on laser-microdissected tumor cells from the breast cancer, and on CD34+ cells sorted from bone marrow aspiration, to identify gene abnormalities common to these two types of cell populations.

Results:

Using ONCOSCAN technology, we identified a constitutional pR988C, c2962C>T mutation of MET. Using CRISPR-Cas9 technology, we established pR988C MET-mutated transgenic mice, which reproduced the autoimmune diseases and myeloproliferation found in our index-case; one of the transgenic mice spontaneously developed a skin squamous cell carcinoma. We also showed that additional mutagenic factors were required to induce cancers, including skin squamous cell carcinoma and thyroid cancer. Using an anti-MET drug, cabozantinib, we demonstrated for the first time the functional role of this mutation in the maintenance of myeloproliferation and rheumatoid arthritis, and in cancer genesis.

Conclusions:

Our study opens a considerable field of application in the domain of constitutional genetics, to establish genetic links between cancers and other very different severe diseases.
Comparative Analysis of AR Variant AR-V567es mRNA Detection Systems Reveals Eminent Variability and Questions the Role as a Clinical Biomarker in Prostate Cancer
Authors: Bernemann Christof , Humberg Verena , Thielen Barbara , Steinestel Julie , Chen Xin , Duensing Stefan , Schrader Andres J. , Boegemann Martin
Published: April 2019

Purpose:

Androgen receptor splice variants are known to facilitate resistance of prostate cancer cells toward antihormonal therapies. However, detection of the most prominent variant, AR-V7, on its own, is not sufficiently accurate for prediction of response. Thus, simultaneous detection of other variants might improve prediction. AR-V567es has been shown to be expressed in late stages of prostate cancer. Yet, there have been discrepant results regarding incidence of AR-V567es. We therefore aimed to perform a comprehensive comparison of different detection approaches for AR-V567es mRNA.

Experimental Design:

We compared a custom-made, probe-based PCR assay with 6 published AR-V567es detection PCR assays in distinct samples, that is, cancer cell lines, LuCaP xenografts, primary and metastatic tumor samples, and circulating tumor cells (CTC).

Results:

Using distinct approaches, we concordantly detected expression of AR-V567es in only three of 45 samples (LuCaP xenografts 86.2 and 136s2 as well as one CTC sample). We observed varying results in all other samples. Specificity analysis displayed nonspecific binding of 5 previously published PCR assays to AR full-length mRNA in the absence of AR-V567es.

Conclusions:

Validation of biomarker detection approaches is one of the most critical steps before transfer into clinical application. By performing comparative analysis of different detection approaches, we revealed eminent variability among previously described systems. Furthermore, we demonstrate an overestimation of AR-V567es in prostate cancer, presumably due to nonspecific detection of AR-FL mRNA. Therefore, any correlation between AR-V567es expression and clinical responses is highly doubtful and does not reflect the biological nature of the disease.
Phenotypic and Genomic Determinants of Immunotherapy Response Associated with Squamousness
Authors: Goodman Aaron M. , Kato Shumei , Chattopadhyay Ranajoy , Okamura Ryosuke , Saunders Ila M. , Montesion Meagan , Frampton Garrett M. , Miller Vincent A. , Daniels Gregory A. , Kurzrock Razelle
Published: April 2019

Advanced and metastatic squamous cell carcinomas (SCC) are common and difficult-to-treat malignancies. We assessed 75 immunotherapy-treated patients with SCC from a clinically annotated database of 2,651 patients, as well as 9,407 patients from a deidentified database for molecular features that might influence checkpoint blockade response. SCCs had higher tumor mutational burdens (TMB) than non-SCCs (P < 0.0001). Cutaneous SCCs had the highest TMB (P < 0.0001), with 41.3% demonstrating a very high TMB (≥50 mutations/Mb). In immunotherapy-treated patients with SCC, higher TMB (≥12 mutations/Mb) correlated with a trend to higher clinical benefit rate [stable disease ≥ 6 months or partial/complete remission; 60% vs. 29%; (high vs. low TMB); P = 0.06] and significantly longer median time-to-treatment failure (TTF; 9.9 vs. 4.4 months; P = 0.0058). Cutaneous SCCs had the highest clinical benefit [11/15 patients (73%) vs. 20/60 (33%) non-cutaneous (P = 0.008)], TTF (P = 0.0015), and overall survival (P = 0.06) with immunotherapy treatment. In conclusion, among a diverse set of SCCs, higher TMB and cutaneous disease associated with better immunotherapy outcome.
Assessing Cerebral Metabolism in the Immature Rodent: From Extracts to Real-Time Assessments
Authors: Mikrogeorgiou Alkisti , Xu Duan , Ferriero Donna M. , Vannucci Susan J.
Published: April 2019

Brain development is an energy-expensive process. Although glucose is irreplaceable, the developing brain utilizes a variety of substrates such as lactate and the ketone bodies, β-hydroxybutyrate and acetoacetate, to produce energy and synthesize the structural components necessary for cerebral maturation. When oxygen and nutrient supplies to the brain are restricted, as in neonatal hypoxia-ischemia (HI), cerebral energy metabolism undergoes alterations in substrate use to preserve the production of adenosine triphosphate. These changes have been studied by in situ biochemical methods that yielded valuable quantitative information about high-energy and glycolytic metabolites and established a temporal profile of the cerebral metabolic response to hypoxia and HI. However, these analyses relied on terminal experiments and averaging values from several animals at each time point as well as challenging requirements for accurate tissue processing.More recent methodologies have focused on in vivo longitudinal analyses in individual animals. The emerging field of metabolomics provides a new investigative tool for studying cerebral metabolism. Magnetic resonance spectroscopy (MRS) has enabled the acquisition of a snapshot of the metabolic status of the brain as quantifiable spectra of various intracellular metabolites. Proton (1H) MRS has been used extensively as an experimental and diagnostic tool of HI in the pursuit of markers of long-term neurodevelopmental outcomes. Still, the interpretation of the metabolite spectra acquired with 1H MRS has proven challenging, due to discrepancies among studies, regarding calculations and timing of measurements. As a result, the predictive utility of such studies is not clear. 13C MRS is methodologically more challenging, but it provides a unique window on living tissue metabolism via measurements of the incorporation of 13C label from substrates into brain metabolites and the localized determination of various metabolic fluxes. The newly developed hyperpolarized 13C MRS is an exciting method for assessing cerebral metabolism in vivo, that bears the advantages of conventional 13C MRS but with a huge gain in signal intensity and much shorter acquisition times. The first part of this review article provides a brief description of the findings of biochemical and imaging methods over the years as well as a discussion of their associated strengths and pitfalls. The second part summarizes the current knowledge on cerebral metabolism during development and HI brain injury.
СИНТЕЗ ТА ПРОТИПУХЛИННА АКТИВНІСТЬ 2-(1H-БЕНЗІМІДАЗОЛ-2-ІЛ)- І 2-БЕНЗТІАЗОЛ-2-ІЛ-3-(5-АРИЛФУРАН-2-ІЛ)АКРИЛОНІТРИЛІВ
Authors: Matiichuk Yu. Е. , Ogurtsov V. V. , Matiychuk V. S.
Published: April 2019

Мета роботи. Синтез та дослідження протипухлинної активності 2-(1H-бензімідазол-2-іл)- і 2-бензтіазол-2-іл-3-(5-арилфуран-2-іл)акрилонітрилів.

Матеріали і методи. Органічний синтез, 1Н ЯМР спектроскопія, елементний аналіз, фармакологічний скринінг.

Результати  й  обговорення. Взаємодією 5-арилфурфуролів з (1H-бензімідазол-2-іл)- та бензтіазол-2-ілацетонітрилом отримано ряд нових 2-(1H-бензімідазол-2-іл)- та 2-бензтіазол-2-іл-3-(5-арилфуран-2-іл)акрилонітрилів. Структуру синтезованих сполук підтверджено елементним аналізом та спектроскопією 1Н ЯМР. Здійснено дослідження біологічної активності синтезованих сполук. Встановлено, що вони проявляють протипухлинну дію різного рівня зі значеннями  mean GP = 32.11 – 102.31%.

Висновки. Розроблено методику синтезу 2-(1H-бензімідазол-2-іл)- та 2-бензтіазол-2-іл-3-(5-арилфуран-2-іл)акрилонітрилів. Досліджено протипухлинну активність синтезованих сполук. Ідентифіковано сполуку-хіт – 2-(1H-бензімідазол-2-іл)-3-[5-(4-хлорофеніл)фуран-2-іл]-акрилонітрил, перспективну для подальшої оптимізації.
A Pragmática comunicativa em uma feira de Belém
Authors: Xavier Fábio Rodrigo de Moraes , Castro Marina Ramos Neves de , Castro Fábio Fonseca de
Published: April 2019

Este artigo objetiva refletir sobre a pragmática comunicativa existente na feira do Guamá, localizada em Belém do Pará, na Amazônia brasileira. Nós procuramos observar, a partir de uma aproximação etnográfica, a movimentação social e as práticas de interação comunicativa  os sujeitos ali presentes em relação às dinâmicas de ocupação do espaço e à disposição dos produtos ali vendidos. A investigação evidencia a estruturação organizacional em sua dinâmica intersubjetiva e, a partir dessa perspectiva, observamos o desenvolvimento da ideia de lugar e a identificação que as pessoas desenvolvem com a localidade dentro de processos estéticos. Para reflexão, neste artigo utilizamos textos do teórico Maffesoli em que trata de localidade e práticas sociais no cotidiano. Também utilizamos a obra de Schutz quando interpretamos as práticas sociais através de tipificação nas estruturas sociais; assim como usamos a compreensão de forma social de Simmel.
Amendment of Articles 8, 9, 10, 21 and 78 of the International Code of Zoological Nomenclature to expand and refine methods of publication
Authors: On Zoological Nomenclature International Commission
Published: April 2019

The International Commission on Zoological Nomenclature has voted in favour of a revised version of the amendment to the International Code of Zoological Nomenclature that was proposed in 2008. The purpose of the amendment is to expand and refine the methods of publication allowed by the Code, particularly in relation to electronic publication. The amendment establishes an Official Register of Zoological Nomenclature (with ZooBank as its online version), allows electronic publication after 2011 under certain conditions, and disallows publication on optical discs after 2012. The requirements for electronic publications are that the work be registered in ZooBank before it is published, that the work itself state the date of publication and contain evidence that registration has occurred, and that the ZooBank registration state both the name of an electronic archive intended to preserve the work and the ISSN or ISBN associated with the work. Registration of new scientific names and nomenclatural acts is not required. The Commission has confirmed that ZooBank is ready to handle the requirements of the amendment.
A review of the western Pacific species of the crangonid genus Metacrangon Zarenkov, 1965 (Decapoda: Caridea), with descriptions of seven new species
Authors: KOMAI TOMOYUKI
Published: April 2019

A review of species of the crangonid genus Metacrangon Zarenkov, 1965 (Decapoda: Caridea) from the Northwest andtropical Southwest Pacific Ocean is presented. Twenty-one species, including seven new to science, are recognized: M.asiaticus (Kobjakova, 1955) from the Kuril Islands and Komandor Islands; M. bythos n. sp. from Japan; M. clevai n. sp.from the Solomon Islands and Vanuatu; M. cornuta Komai & Komatsu, 2009 from Japan; M. holthuisi Komai, 2010 fromJapan; M. karubar n. sp. from Indonesia to Solomon Islands; M. laevis (Yokoya, 1933) from northern Japan and the Rus-sian Far East; M. longirostris (Yokoya, 1933) from Japan; M. miyakei Kim, 2005 from Japan; M. monodon (Birshtein &Vinogradov, 1951) from the North Kuril Islands; M. nipponensis (Yokoya, 1933) from Japan; M. obliqua n. sp. from Ja-pan; M. ochotensis (Kobjakova, 1955) from the South Kuril Islands; M. proxima Kim, 2005 from Japan; M. punctata n.sp. from Indonesia, Solomon Islands and New Caledonia; M. robusta (Kobjakova, 1935) from the Sea of Japan and theSea of Okhotsk; M. similis Komai, 1997 from Japan; M. sinensis Fujino & Miyake, 1970 from the northern part of the EastChina Sea; M. trigonorostris (Yokoya, 1933) from Japan; M. tropis n. sp. from Japan; and M. tsugaruensis n. sp. fromJapan. These species are classified into two informal species groups. The new species are fully described and illustrated.Some previously known species, for which detailed descriptions along modern standards are deemed necessary, are rede-scribed. Metacrangon asiaticus is elevated from a subspecies of M. variabilis to full species status. A key to aid in theidentification of the western Pacific species is provided. Bathymetrical and geographical distributions of the treated spe-cies are summarized. It is strongly suggested that each species is highly localized. The species richness is highest in waters around the Japanese Archipelago (17 of the 41 known species occur in the areas).
Catalogue of the mite family Rhodacaridae Oudemans, with notes on the classification of the Rhodacaroidea (Acari: Mesostigmata)
Authors: CASTILHO RAPHAEL C. , DE MORAES GILBERTO J. , HALLIDAY BRUCE
Published: April 2019

The Rhodacaridae Oudemans are free-living, cosmopolitan, edaphic mites, generally reported in the literature aspredators. The taxonomic concept of the family has changed considerably over time, making it very difficult for non-taxonomists and even sometimes for taxonomists to decide on the correct placement of many species. A historic reviewof the literature on the classification of the Rhodacaridae is presented. Brief differential diagnoses are given for thefamilies of Rhodacaroidea, followed by a checklist of genera and sub-genera for each family. The families included areDigamasellidae, Halolaelapidae, Laelaptonyssidae, Ologamasidae, Rhodacaridae and Teranyssidae. Revised diagnosesare given for the genera of Rhodacaridae, and a key for their identification, derived from a standardised database ofcharacter states. Finally, a list of species within each genus of this family was compiled, giving relevant taxonomicinformation about the respective types, and providing references to nomenclatural changes, synonymy, and redescriptionsof each species. In total, 151 rhodacarid species and one subspecies are listed in this work, arranged in 15 genera. Themost diverse genera are Afrodacarellus Hurlbutt and Rhodacarus Oudemans, each with about 20% of the valid species.Five of the genera are monotypic. Taxonomic confusion surrounds some groups of species, especially in the genusRhodacarus. It appears that Rhodacarus calcarulatus Berlese, R. coronatus Berlese, R. pallidus Hull, R. reconditusAthias-Henriot and R. roseus Oudemans have often been misidentified, and these species are in need of detailed revision.A detailed taxonomic or phylogenetic revision of the family was not an objective of this paper. Future efforts to determinesynapomorphies within the group may facilitate a thorough examination of the present status of the family in relation tothe generic placement of species. Regardless, twelve new combinations are proposed in this paper: Afrogamasellus(Foliogamasellus) Karg, 1977 and Afrogamasellus (Latogamasellus) Karg, 1977 are newly synonymised underAfrodacarellus Hurlbutt, 1974 and Laelaptonyssus Womerlsey, 1956 (Laelaptonyssidae) is newly synonymised under Starkovia Lombardini, 1947.