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Background: Neuroblastoma is the most common extracranial solid tumor in children and accounts for 15% of pediatric cancer related deaths. Targeting neuroblastoma with immunotherapies has proven challenging due to a paucity of immune cells in the tumor microenvironment and the release of immunosuppressive cytokines by neuroblastoma tumor cells. We hypothesized that combining an oncolytic Herpes Simplex Virus (oHSV) with natural killer (NK) cells might overcome these barriers and incite tumor cell death. Methods: We utilized MYCN amplified and non-amplified neuroblastoma cell lines, the IL-12 expressing oHSV, M002, and the human NK cell line, NK-92 MI. We assessed the cytotoxicity of NK cells against neuroblastoma with and without M002 infection, the effects of M002 on NK cell priming, and the impact of M002 and priming on the migratory capacity and CD107a expression of NK cells. To test clinical applicability, we then investigated the effects of M002 and NK cells on neuroblastoma in vivo. Results: NK cells were more attracted to neuroblastoma cells that were infected with M002. There was an increase in neuroblastoma cell death with the combination treatment of M002 and NK cells both in vitro and in vivo. Priming the NK cells enhanced their cytotoxicity, migratory capacity and CD107a expression. Conclusions: To the best of our knowledge, these investigations are the first to demonstrate the effects of an oncolytic virus combined with self-maintaining NK cells in neuroblastoma and the priming effect of neuroblastoma on NK cells. The current studies provide a deeper understanding of the relation between NK cells and neuroblastoma and these data suggest that oHSV increases NK cell cytotoxicity towards neuroblastoma. [ABSTRACT FROM AUTHOR]

Time reverse modeling (TRM) is successfully applied to acoustic signals from a circular microphone array, for mapping of sudden cracking sound events. Numerical feasibility using synthetic acoustic sources followed by an experimental study with steel pendulum impacts on a steel plate is carried out. The mapping results from the numerical and experimental data are compared and verified using a delay-and-sum beamforming technique. Based on the feasibility and experimental study, a mapping error is estimated. In the main experimental study, cracking sound events obtained during a tensile test on a textile-reinforced concrete specimen are mapped with the TRM. The enhanced capability of the TRM to map simultaneously occurring cracking sound events along crack paths is demonstrated. [ABSTRACT FROM AUTHOR]

Abstract Despite the clinical benefit of androgen‐deprivation therapy (ADT), the majority of patients with advanced prostate cancer (PCa) ultimately develop lethal castration‐resistant prostate cancer (CRPC). In this study, we identified thioesterase superfamily member 6 (THEM6) as a marker of ADT resistance in PCa. THEM6 deletion reduces in vivo tumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, we show that the ER membrane‐associated protein THEM6 regulates intracellular levels of ether lipids and is essential to trigger the induction of the ER stress response (UPR). Consequently, THEM6 loss in CRPC cells significantly alters ER function, reducing de novo sterol biosynthesis and preventing lipid‐mediated activation of ATF4. Finally, we demonstrate that high THEM6 expression is associated with poor survival and correlates with high levels of UPR activation in PCa patients. Altogether, our results highlight THEM6 as a novel driver of therapy resistance in PCa as well as a promising target for the treatment of CRPC.

Tolerance gaps in wood connections are unavoidable, for reasons of constructability and the effects of natural shrinkage in timber elements with changing moisture content. During a fire, these gaps may lead to a substantial heat transfer to the metal connectors that are considered heat protected being embedded by the wooden components of the connection. Aluminium connectors are popular due to their ease of production and assembly, but they are particularly vulnerable to elevated temperatures. This study investigates the effects of tolerance gaps on the fire performance of aluminium connectors in beam-to-column/wall shear connections. Reduced-scale experiments were designed to study the temperature evolution of aluminium connectors during standard fire exposure for 1 mm and 6 mm tolerance gaps, as well the mitigation effects of additional intumescent fire protection in a 6 mm tolerance gap connection. For the 6 mm gap, the temperature of the connector increased much faster, reaching 286 ± 36°C after 80 min, at which time the connector with a 1 mm gap had only reached 97 ± 1°C. The addition of intumescent protection in a 6 mm gap case led to lower temperatures in the connection, in comparison to an equivalent tolerance gap without protection. Subsequently, two additional loaded fire tests were performed, for 6 mm and 22 mm tolerance gaps without fire protection, to investigate the critical failure mode of the connectors. In these cases, the failure occurred in the connectors at 87 min and 32 min, respectively, when their average temperatures reached approximately 315°C. This study demonstrates the critical influence of gap size on the fire performance of aluminium-wood joints. [ABSTRACT FROM AUTHOR]

Sexual risk behavior (SRB) includes behavioral (sex without contraception, sexualized substance use, sex work, sexual partner violence, other sexual activities that harm oneself or others) and affective subtypes (sexuality-related feelings of shame/guilt, relationship impairments) and leads to psychosocial and health-related consequences. Young adults comprise a vulnerable group regarding the development of SRB. The study aimed to identify SRB patterns among young adults and their relation to sexuality-related risk factors. A cross-sectional online survey measured behavioral and affective aspects of SRB with nine items. Latent class analysis was conducted to identify patterns of SRB. Gender, sexual orientation, age of first intercourse, number of sexual partners, hypersexuality, and sexual dysfunction were captured as risk factors via multinomial logistic regression. Within this convenience sample (n = 609; nfemale = 365; nmale = 245; Mage = 23.1 years), the SRB patterns unremarkable (67%; low values in all SRB subtypes), shame-ridden (17%; high values in sexual feelings of shame/guilt) and risky sexual behavior (16%; high values in all subtypes of SRB, especially sexualized drug use) were identified. The shame-ridden and risky patterns were strongly associated with higher hypersexuality values, the risky pattern moreover with being non-heterosexual, of younger age at first sexual experience, and a higher number of sexual partners. Male and sexual minority participants demonstrated SRB more often than females and heterosexuals. Within prevention and treatment of SRB, it seems beneficial to address sexuality-related feelings of shame/guilt and addictive patterns (concerning sexual behaviors/substances) via gender- and diversity-sensitive measurements. [ABSTRACT FROM AUTHOR]

A new cleaner micron-sized water-based powder particles (DW) were prepared by physical dispersion method of hydrophobic silica and ultrapure water at different proportions. The effects of chemical composition of metal salts on physical properties of dry water materials such as fluidity and particle size distribution were analyzed. The microscopic morphology of DW particles with different components was observed by optical microscope, and the effects of different filling pressures on their microscopic morphology and fire extinguishing efficiency were analyzed. The thermal decomposition kinetics of different DW were analyzed to get their thermal mechanism to extinguish. The results showed that the size of DW particles is more uniform; the structure edge is clearer, and the structure is more stable when the mass ratio of SiO2 to water is 1:13. The fluidity and filling performance of DW were improved by different metal salinization components at a certain concentration. When the filling pressure is 0.6 MPa, the DW structure can remain stable and the fire extinguishing efficiency is the best. DW material can instantly extinguish the small-size oil pool fire. DW shows the best extinguishing efficiency compared to dry powder and water mist. Combined with the thermal decomposition analysis, the addition of metallic sodium salt would increase the apparent activation energy by more than 10 times; therefore, the fire extinguishing efficiency of sodium carbonate-modified DW shows the most obvious. [ABSTRACT FROM AUTHOR]

Copyright of Gynäkologische Endokrinologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: This study aimed to investigate if social media (SM) impacts a patient's provider choice in the field of reproductive endocrinology and infertility (REI). Methods: This was a survey-based study completed in July 2022. A survey link was distributed using Amazon Mechanical Turk, which directed participants to a Qualtrics-based survey. Participants were 18–50 years old. The primary outcome was to identify the preferred method for finding a REI provider based on time spent on SM (< 1 h, 1–3 h, 3 + h). Results: A total of 336 responses were analyzed. Fifty-four percent of respondents used SM < 1 h, 33.33% used 1–3 h, and 12.80% used 3 + h. The majority (69.05%) of respondents stated that they would seek out a REI provider/clinic if they had difficulty conceiving. Most respondents identified asking their primary care physician (44.64%) as the primary means for finding an REI provider/clinic and did not prefer to use SM. Although Facebook (< 1 h: 30.94%, 1–3 h: 31.25%, 3 + h: 27.91%) was the most utilized SM platform among respondents, YouTube was the preferred SM platform if respondents were to follow a REI clinic with a preference for posts focusing on education (< 1 h: 55.68%, 1–3 h: 43.12%, 3 + h: 58.14%) or stress management (< 1 h: 17.61%, 1–3 h: 29.36%, 3 + h: 20.94%). Conclusion: Most respondents utilize traditional methods when choosing their REI provider or clinic and would not utilize SM. However, SM, primarily through YouTube, may be helpful for educating infertility patients and providing support and stress relief while they undergo treatment. [ABSTRACT FROM AUTHOR]

This paper is dedicated to applying the Fourier amplitude sensitivity test (FAST) method to the problem of mixed extension and inflation of a circular cylindrical tube in the presence of residual stresses. The metafunctions and the Ishigami function are considered in the sensitivity analysis (SA). The effects of the input variables on the output variables are investigated, and the most important parameters of the system under the applied pressure and axial force such as the axial stretch and the azimuthal stretch are determined. [ABSTRACT FROM AUTHOR]

Copyright of Gynäkologische Endokrinologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Modeling piezoelectric elements (piezos) using the finite element method with electro-mechanical coupling requires significant computational resources. The electro-mechanical interaction between piezo and structure in the interface will consume the most computational resources because it needs to be updated for each time step. If many piezos are involved, the wave-propagation-based analysis, including simulations of the wave motion, will be handicapped and might lead to the cancellation of the computation. Therefore, a simplified approach for modeling the piezoelectric response is presented, accounting for a ‘purely’ mechanical interaction between piezo and structure, where the electric potential is calculated analytically by multiplying the first two mechanical principal-strain components with the piezoelectric constants a posteriori. This way, the calculation of the equilibrium of the piezoelectric material is omitted which reduces the computational cost significantly without loss of accuracy in the piezoelectric response. An application case is demonstrated, where steel-ball impacts on an aluminum plate were successfully localized using a wave-propagation-based localization method (time reverse modeling), and the piezos were modeled with a simplified mechanical material behavior. [ABSTRACT FROM AUTHOR]

Objectives: Infertility imposes considerable clinical and economic burden, and the high costs of fertility care are a major barrier to payers. This study assessed the cost differences of highly purified human menopausal gonadotropin (HP-hMG) versus recombinant follicle stimulating hormone (rFSH) for controlled ovarian stimulation (COS) protocols in predicted high-responders from the US payer perspective. Methods: A discrete event simulation model was built to perform a cost-comparison analysis of HP-hMG versus rFSH in a cohort of predicted high-responders undergoing up to three embryo transfer cycles, informed by efficacy data from the MEGASET-HR trial. The model considered an event-based treatment pathway and transition probabilities were derived from MEGASET-HR. A variable time horizon was employed, and deterministic and probabilistic sensitivity analyses conducted. Results: Subjects undergoing COS with HP-hMG and rFSH demonstrated comparable live birth rates following three in vitro fertilization (IVF) cycles, with 161 live births with HP-hMG and 152 live births with rFSH, per 310 high-responders. The total cost saving per live birth in subjects receiving HP-hMG versus rFSH was US$3024. These cost savings were largely driven by the need for fewer embryo transfers to achieve similar efficacy outcomes and a reduced rate of ovarian hyperstimulation syndrome. Following deterministic sensitivity analysis, HP-hMG remained cost saving in all baseline parameter variations. No parameters led to rFSH providing cost savings when compared with HP-hMG. Conclusion: Comparable clinical outcomes can be achieved at a lower cost when using HP-hMG versus rFSH based COS protocols in a cohort of predicted high-responders. Such cost savings may reduce the economic burden infertility currently presents to US healthcare providers and those seeking fertility care. [ABSTRACT FROM AUTHOR]

This research aims to extend the isothermal continuum mechanical modeling framework of hydraulic fracturing in porous materials to account for the non-isothermal processes. Whereas the theory of porous media is used for the macroscopic material description, the phase-field method is utilized for modeling the crack initiation and propagation. We proceed in this study from a two-phase porous material consisting of thermomechanically interacting pore fluid and solid matrix. The heat exchange between the fluid in the crack and the surrounding porous environment through the diffusive fracture edges is carefully studied, and new formulations here are proposed. Besides, temperature-dependent solid and fluid material parameters are taken into account, which is of particular importance in connection with fluid viscosity and its effect on post-cracking pressure behavior. This continuum mechanical treatment results in strongly coupled partial differential equations of the mass, the momentum, and the energy balance of the thermally non-equilibrated constituents. Using the finite element method, two-dimensional initial-boundary-value problems are presented to show, on the one hand, the stability and robustness of the applied numerical algorithm in solving the emerged strongly coupled problem in the convection-dominated heat transport state. On the other hand, they show the capability of the modeling scheme in predicting important instances related to hydraulic fracturing and the role of the temperature field in this process. Additionally, they show the importance of using stabilization techniques, such as adding an artificial thermo-diffusivity term, to mitigate temperature fluctuations at high flow velocity. [ABSTRACT FROM AUTHOR]

We set out to map the (1) living/occupational hazards, (2) health outcomes, and (3) barriers to care that exist for pregnant labor-trafficked people. Eight databases were systematically searched based on inclusion criteria. Five papers were eligible for inclusion. Data on study characteristics, social determinants, hazardous exposures, health outcomes, and barriers to care were extracted and synthesized. Common risk factors and occupational/living hazards were identified. Both were thematically connected with barriers to care and a host of adverse health outcomes. More importantly, a significant gap was discovered with no disaggregated quantitative data on the experience of pregnancy among labor-trafficked people. The interaction of risk factors, occupational/living hazards, and barriers to care experienced by pregnant labor-trafficked people may influence their susceptibility to adverse health outcomes. We need population-based studies, informed by those with lived experience of labor trafficking to examine the experience of pregnancy for labor-trafficked people to improve intervention and support efforts for this population. [ABSTRACT FROM AUTHOR]

Extended-duration cyclic loading of the spine is known to be correlated to lower back pain (LBP). Therefore, it is important to understand how the loading history affects the entire structural behavior of the spine, including the viscoelastic effects. Six human spinal segments (L4L5) were loaded with pure moments up to 7.5 Nm cyclically for half an hour, kept unloaded for 15 min, and loaded with three cycles. This procedure was performed in flexion-extension (FE), axial rotation (AR), and lateral bending (LB) and repeated six times per direction for a total of 18 h of testing per segment. A Long Short-Term Memory (LSTM) Recurrent Neural Network (RNN) was trained to predict the change in the biomechanical response under cyclic loading. A strong positive correlation between the total testing time and the ratio of the third cycle to the last cycle of the loading sequence was found (BT: τ = 0.3469, p = 0.0003, RT: τ =0.1988, p = 0.0377). The moment-range of motion (RoM) curves could be very well predicted with an RNN ( R 2 =0.988), including the correlation between testing time and testing temperature as inputs. This study shows successfully the feasibility of using RNNs to predict changing moment-RoM curves under cyclic moment loading. [ABSTRACT FROM AUTHOR]

Water is a problem in understanding chemical evolution towards life's origins on Earth. Although all known life is being based on water key prebiotic reactions are inhibited by it. The prebiotic plausibility of current strategies to circumvent this paradox is questionable regarding the principle that evolution builds on existing pathways. Here, we report a straightforward way to overcome the water paradox in line with evolutionary conservatism. By utilising a molecular deposition method as a physicochemical probe, we uncovered a synergy between biomolecule assembly and temporal nanofluid conditions that emerge within transient nanoconfinements of water between suspended particles. Results from fluorometry, quantitative PCR, melting curve analysis, gel electrophoresis and computational modelling reveal that such conditions induce nonenzymatic polymerisation of nucleotides and promote basic cooperation between nucleotides and amino acids for RNA formation. Aqueous particle suspensions are a geochemical ubiquitous and thus prebiotic highly plausible setting. Harnessing nanofluid conditions in this setting for prebiotic syntheses is consistent with evolutionary conservatism, as living cells also work with temporal nanoconfined water for biosynthesis. Our findings add key insights required to understand the transition from geochemistry to biochemistry and open up systematic pathways to water-based green chemistry approaches in materials science and nanotechnology. The role of water poses a problem in our understanding of prebiotic chemistry, as some biochemical reactions, such as RNA polymerization, are impeded in aqueous solutions. Here, the authors report the abiotic temporal nanoconfinement of water within aqueous particle suspensions, showing that such conditions can induce and promote prebiotic RNA formation. [ABSTRACT FROM AUTHOR]

Disordered solids are ubiquitous in engineering and everyday use. Although research has made considerable progress in the last decades, our understanding of the mechanics of these materials is, at best, in an embryonic state. Since the nature of disorder complicates the realization of physically meaningful continuum-mechanical models, particle-based molecular descriptions provide a powerful alternative. This paper reviews the numerical realization of classical molecular dynamics from an engineer's perspective, starting with selecting potential functions, boundary conditions, time integration, and thermodynamic ensembles. Then, we discuss the concept of the potential energy landscape and the computational realization of the most suitable minimization methods. Subsequently, we discuss the algorithms necessary to numerically generate disordered materials, considering their thermodynamic properties and structural identification. We comprehensively and critically review computational methods and strategies available to mimic disordered materials on a molecular level and discuss some intriguing phenomena that are, to date, mostly ignored when applying models based on continuum-mechanical frameworks. We present the crucial difference between the shear response of a crystalline and a disordered structure. In this context, we elaborate on why it is beneficial to use an overdamped, athermal description to disentangle the complex deformation mechanics of disordered solids and comprehensively discuss the theory of the mechanics of disordered materials, including the problems of prediction and reversibility. Furthermore, we examine the fracture process on the nanoscale and investigate the response behavior to more complex deformation protocols. Finally, we provide critical conclusions, including challenges and future perspectives for engineers. [ABSTRACT FROM AUTHOR]

Current practices vary widely regarding the immunological work-up and management of patients affected with defects in thymic development (DTD), which include chromosome 22q11.2 microdeletion syndrome (22q11.2del) and other causes of DiGeorge syndrome (DGS) and coloboma, heart defect, atresia choanae, retardation of growth and development, genital hypoplasia, ear anomalies/deafness (CHARGE) syndrome. Practice variations affect the initial and subsequent assessment of immune function, the terminology used to describe the condition and immune status, the accepted criteria for recommending live vaccines, and how often follow-up is needed based on the degree of immune compromise. The lack of consensus and widely varying practices highlight the need to establish updated immunological clinical practice guidelines. These guideline recommendations provide a comprehensive review for immunologists and other clinicians who manage immune aspects of this group of disorders. [ABSTRACT FROM AUTHOR]

The pro-tumourigenic role of epithelial TGFβ signalling in colorectal cancer (CRC) is controversial. Here, we identify a cohort of born to be bad early-stage (T1) colorectal tumours, with aggressive features and a propensity to disseminate early, that are characterised by high epithelial cell-intrinsic TGFβ signalling. In the presence of concurrent Apc and Kras mutations, activation of epithelial TGFβ signalling rampantly accelerates tumourigenesis and share transcriptional signatures with those of the born to be bad T1 human tumours and predicts recurrence in stage II CRC. Mechanistically, epithelial TGFβ signalling induces a growth-promoting EGFR-signalling module that synergises with mutant APC and KRAS to drive MAPK signalling that re-sensitise tumour cells to MEK and/or EGFR inhibitors. Together, we identify epithelial TGFβ signalling both as a determinant of early dissemination and a potential therapeutic vulnerability of CRC's with born to be bad traits. It remains critical to identify colorectal cancers (CRC) that will disseminate as early as possible. Here, the authors identify CRC tumours that are aggressive and prone to early dissemination, characterised by epithelial TGFβ and growth-factor signalling - which could be targeted with MEK/EGFR inhibitors. [ABSTRACT FROM AUTHOR]

Patients presenting with metastatic hepatoblastoma have limited treatment options and survival rates as low as 25%. We previously demonstrated that Proviral Integration site in Maloney murine leukemia virus 3 (PIM3) kinase promotes tumorigenesis and cancer cell stemness in hepatoblastoma. In this study, we assessed the role of PIM3 kinase in promoting hepatoblastoma metastasis. We utilized a tail vein injection model of metastasis to evaluate the effect of CRISPR/Cas9-mediated PIM3 knockout, stable overexpression of PIM3, and pharmacologic PIM inhibition on the formation of lung metastasis. In vivo studies revealed PIM3 knockout impaired the formation of lung metastasis: 5 out of 6 mice injected with wild type hepatoblastoma cells developed lung metastasis while none of the 7 mice injected with PIM3 knockout hepatoblastoma cells developed lung metastasis. PIM3 overexpression in hepatoblastoma increased the pulmonary metastatic burden in mice and mechanistically, upregulated the phosphorylation and cell surface expression of CXCR4, a key receptor in the progression of cancer cell metastasis. CXCR4 blockade with AMD3100 decreased the metastatic phenotype of PIM3 overexpressing cells, indicating that CXCR4 contributed to PIM3's promotion of hepatoblastoma metastasis. Clinically, PIM3 expression correlated positively with CXCR4 expression in primary hepatoblastoma tissues. In conclusion, we have shown PIM3 kinase promotes the metastatic phenotype of hepatoblastoma cells through upregulation of CXCR4 cell surface expression and these findings suggest that targeting PIM3 kinase may provide a novel therapeutic strategy for metastatic hepatoblastoma. [ABSTRACT FROM AUTHOR]

Eukaryotes may experience oxygen deprivation under both physiological and pathological conditions. Because oxygen shortage leads to a reduction in cellular energy production, all eukaryotes studied so far conserve energy by suppressing their metabolism. However, the molecular physiology of animals that naturally and repeatedly experience anoxia is underexplored. One such animal is the marine nematode Laxus oneistus. It thrives, invariably coated by its sulfur-oxidizing symbiont Candidatus Thiosymbion oneisti, in anoxic sulfidic or hypoxic sand. Here, transcriptomics and proteomics showed that, whether in anoxia or not, L. oneistus mostly expressed genes involved in ubiquitination, energy generation, oxidative stress response, immune response, development, and translation. Importantly, ubiquitination genes were also highly expressed when the nematode was subjected to anoxic sulfidic conditions, together with genes involved in autophagy, detoxification and ribosome biogenesis. We hypothesize that these degradation pathways were induced to recycle damaged cellular components (mitochondria) and misfolded proteins into nutrients. Remarkably, when L. oneistus was subjected to anoxic sulfidic conditions, lectin and mucin genes were also upregulated, potentially to promote the attachment of its thiotrophic symbiont. Furthermore, the nematode appeared to survive oxygen deprivation by using an alternative electron carrier (rhodoquinone) and acceptor (fumarate), to rewire the electron transfer chain. On the other hand, under hypoxia, genes involved in costly processes (e.g., amino acid biosynthesis, development, feeding, mating) were upregulated, together with the worm's Toll-like innate immunity pathway and several immune effectors (e.g., bactericidal/permeability-increasing proteins, fungicides). In conclusion, we hypothesize that, in anoxic sulfidic sand, L. oneistus upregulates degradation processes, rewires the oxidative phosphorylation and reinforces its coat of bacterial sulfur-oxidizers. In upper sand layers, instead, it appears to produce broad-range antimicrobials and to exploit oxygen for biosynthesis and development. [ABSTRACT FROM AUTHOR]

Covid-19 has been a global concern since 2019, crippling the world economy and health. Biological diagnostic tools have since been developed to identify the virus from bodily fluids and since the virus causes pneumonia, which results in lung inflammation, the presence of the virus can also be detected using medical imaging by expert radiologists. The success of each diagnostic method is measured by the hit rate for identifying Covid infections. However, the access for people to each diagnosis tool can be limited, depending on the geographic region and, since Covid treatment denotes a race against time, the diagnosis duration plays an important role. Hospitals with X-ray opportunities are widely distributed all over the world, so a method investigating lung X-ray images for possible Covid-19 infections would offer itself. Promising results have been achieved in the literature in automatically detecting the virus using medical images like CT scans and X-rays using supervised artificial neural network algorithms. One of the major drawbacks of supervised learning models is that they require enormous amounts of data to train, and generalize on new data. In this study, we develop a Swish activated, Instance and Batch normalized Residual U-Net GAN with dense blocks and skip connections to create synthetic and augmented data for training. The proposed GAN architecture, due to the presence of instance normalization and swish activation, can deal with the randomness of luminosity, that arises due to different sources of X-ray images better than the classical architecture and generate realistic-looking synthetic data. Also, the radiology equipment is not generally computationally efficient. They cannot efficiently run state-of-the-art deep neural networks such as DenseNet and ResNet effectively. Hence, we propose a novel CNN architecture that is 40% lighter and more accurate than state-of-the-art CNN networks. Multi-class classification of the three classes of chest X-rays (CXR), ie Covid-19, healthy and Pneumonia, is performed using the proposed model which had an extremely high test accuracy of 99.2% which has not been achieved in any previous studies in the literature. Based on the mentioned criteria for developing Corona infection diagnosis, in the present study, an Artificial Intelligence based method is proposed, resulting in a rapid diagnostic tool for Covid infections based on generative adversarial and convolutional neural networks. The benefit will be a high accuracy of lung infection identification with 99% accuracy. This could lead to a support tool that helps in rapid diagnosis, and an accessible Covid identification method using CXR images. [ABSTRACT FROM AUTHOR]

Background: A variety of anthropogenic stressors influences the ecological status of rivers wordwide. Important stressors include elevated concentrations of nutrients, salt ions, heavy metals and other pollutants, habitat degradation and flow alteration. Some stressors tend to remain underrepresented in multiple-stressor studies, which in particular is apparent for micropollutants (e.g. pesticides, pharmaceuticals) and alterations of the flow regime. This case study analysed and compared the effects of 19 different stressor variables on benthic macroinvertebrates in the two German rivers Erft and Niers (Federal State of North Rhine-Westphalia, Germany). The stressors variables were assigned to four stressor groups (physico-chemical stress, mixture toxicity of 42 micropollutants, hydrological alteration and morphological degradation) and were put into a hierarchical context according to their relative impact on the macroinvertebrate community using redundancy analysis and subsequent variance partitioning. Results: The results suggest a strong and unique effect of physico-chemical stress, yet at the same time reveal also a strong joint effect of physico-chemical and hydrological stressor variables. Morphological degradation showed subordinate effects. Notably, only a minor share of the explained variance was attributed to the mixture toxicity of micropollutants in these specific catchments. Conclusions: The stressor hierarchy indicates that management measures for improving the ecological status still need to address water quality issues in both rivers. The strong joint effect of physico-chemical stress and hydrological alteration might imply a common source of both stressor groups in these two catchment areas: lignite mining drainage, urban area and effluents of wastewater treatment plants. The findings point at the important role of alterations in the flow regime, which often remain unconsidered in hydro-morphological surveys. [ABSTRACT FROM AUTHOR]

This contribution presents a proper generalized decomposition-based nonlinear solver for an efficient solution of geometrically nonlinear dynamic problems. The solution is built as a sum of dyadic products of space and time modes, and this sum of so-called enrichments is truncated when the required accuracy is achieved. In the proposed algorithm, we apply a consistent linearization of the residual vectors around the currently known solution over the whole space-time domain. At first, the set of vectorized tangent stiffness matrices is separated in space and time using the singular value decomposition. Then, the left and right singular vectors are reshaped into matrices to separate the space-time stiffness operator. The latter can be incorporated into the alternating fixed-point algorithm to compute couples of space and time modes. Numerical examples of a two-dimensional geometrically exact beam model demonstrate the accuracy, efficiency, and limits of the method. [ABSTRACT FROM AUTHOR]

Manufacturing is a critical component of the economy of industrialized nations. Training of the workforce is vital for the survival and competitiveness of manufacturing. New paradigms are needed to satisfy the demand for knowledge workers in this field. This paper presents the development of a training program for teachers who are trainers of competencies for Industry 4.0. Given the pace of technological change, the challenge was to reach the highest number of individuals in the shortest possible time. The program was divided into three stages. In the first one, conception stage, professors from different Tecnologico de Monterrey (Tec) campuses were selected to take an Industry 4.0 course that was adapted from existing courses at RWTH Aachen. In the second stage, training, the Tec teachers designed a course for other instructors that was adapted to the conditions in Mexico. In the third stage, replication, two more groups of professors were trained. To facilitate dissemination, we created a series of videos to facilitate non synchronous learning. The course was delivered using CANVAS. A laboratory session complemented the activities, and participants developed a project as part of their course work. This work describes the design and implementation of the program. In all, this program has helped 68 professors develop competencies related to the needs of Industry 4.0. Results of surveys show that participants felt that the program helped them develop competences that were later introduced in classes and projects. [ABSTRACT FROM AUTHOR]

Purpose: Primary Central Nervous System Lymphoma (PCNSL) is an aggressive tumor that is confined to the CNS. Although the provision of high-dose methotrexate (HD-MTX) has remarkably improved outcomes in PCNSL patients, the optimal treatment regimens and standard MTX dose for induction therapy have been largely controversial. Herein, we sought to explore the impact of adjuvant rituximab and different dosages of induction HD-MTX on survival outcomes of immunocompetent patients with PCNSL. Methods: In this study, we examined patients with PCNSL treated at a single NCI-designated comprehensive cancer center to evaluate their survival outcomes. We conducted a retrospective analysis of 51 immunocompetent patients with PCNSL who received their induction chemotherapy at the University of Alabama at Birmingham (UAB) between 2001 and 2019. Only adult patients with a confirmed diagnosis of PCNSL who had either HD-MTX alone or in combination with rituximab were included. Patients' demographics, clinical characteristics, and survival data were collected and analyzed. Results: There is no significant difference in survival among patients who received MTX alone versus MTX plus rituximab (HR = 0.996 (95% CI: 0.398–2.493), p = 0.994). Lower doses of MTX were associated with worse survival outcomes (HR = 0.680 (95% CI: 0.530–0.872), p = 0.002); however, this difference in survival was not significant when adjusted to age (HR = 0.797 (95% CI: 0.584–1.088), p = 0.153). Conclusion: Our experience challenges the role of rituximab in PCNSL during induction therapy. Our study also highlights the shorter survival in elderly patients with PCNSL which can be related, to some extent, to the relatively lower doses of HD-MTX. There is an unmet need to establish a consensus on the most effective upfront regimen in PCNSL through prospective studies. [ABSTRACT FROM AUTHOR]

Purpose: There is a paucity of studies on new vertebral body tethering (VBT) surgical constructs especially regarding their potentially motion-preserving ability. This study analyses their effects on the ROM of the spine. Methods: Human spines (T10-L3) were tested under pure moment in four different conditions: (1) native, (2) instrumented with one tether continuously connected in all vertebrae from T10 to L3, (3) additional instrumented with a second tether continuously connected in all vertebrae from T11 to L3, and (4) instrumented with one tether and one titanium rod (hybrid) attached to T12, L1 and L2. The instrumentation was inserted in the left lateral side. The intersegmental ROM was evaluated using a magnetic tracking system, and the medians were analysed. Please check and confirm the author names and initials are correct. Also, kindly confirm the details in the metadata are correct. The mentioned information is correct Results: Compared to the native spine, the instrumented spine presented a reduction of less than 13% in global ROM considering flexion–extension and axial rotation. For left lateral bending, the median global ROM of the native spine (100%) significantly reduced to 74.6%, 66.4%, and 68.1% after testing one tether, two tethers and the hybrid construction, respectively. In these cases, the L1-L2 ROM was reduced to 68.3%, 58.5%, and 38.3%, respectively. In right lateral bending, the normalized global ROM of the spine with one tether, two tethers and the hybrid construction was 58.9%, 54.0%, and 56.6%, respectively. Considering the same order, the normalized L1-L2 ROM was 64.3%, 49.9%, and 35.3%, respectively. Conclusion: The investigated VBT techniques preserved global ROM of the spine in flexion–extension and axial rotation while reduced the ROM in lateral bending. [ABSTRACT FROM AUTHOR]

Summary: Background: The incidence of aneurysms is steadily increasing in older patients due to the aging population. This study compared radiological parameters as well as clinical outcomes between patients younger than 65 years and those over 65 years of age, with special respect to individual treatment options. Methods: Retrospective data were obtained for patients with cerebral aneurysms at a single academic institution within a 7-year period. Data reviewed included admission protocols, patient charts, operating reports as well as outpatient clinic charts. Aneurysmal characteristics as well as surgical outcome were compared between older patients, defined as patients older than 65 years of age, and a control group of patients younger than 65 years of age. To evaluate and compare individual clinical characteristics various scores including the Hunt and Hess score, the Fisher score, and the Glasgow outcome scale were used. Results: A total of 347 patients were included in the final analysis. The control group included 290 patients, while 57 patients were in the older patient group. Neither the Hunt and Hess scores nor Fisher scores were significantly correlated to patient age. The Glasgow outcome scale was significantly lower in the older group after clipping of ruptured aneurysms (p < 0.000) but not significantly different after clipping of unruptured aneurysms (p = 0.793). Conclusion: Postoperative Glasgow outcome scale scores were not significantly different after clipping of unruptured cerebral aneurysms approximately 1 cm in diameter in older patients compared to the younger age group. Therefore, clipping of unruptured cerebral aneurysms may also be a valuable treatment option for older patients. [ABSTRACT FROM AUTHOR]

The formation of a reliable joint between a large number of aluminum strands for battery applications is crucial in automotive industry, especially in the technology of autonomous vehicles. Therefore, in this study, mechanical deformations and diffusion patterns of the mating interface in ultrasonic welding of aluminum were investigated using molecular dynamics simulations. Furthermore, microscopic observations of the joints between aluminum strands from ultrasonic welding illustrating the influence of two process parameters were done. To study the nanomechanics of the joint formation, two aluminum crystallites of different orientations were built. The impact of the sliding velocity and the compression rate of the upper crystal block on the diffusion pattern at the interface of the two crystallites were quantified via the diffusion coefficient. Tensile deformations of several joint configurations were performed to investigate the load-bearing capacity of the solid state bond, taking into account the compression rate, the sliding velocity and the crystallite orientation. The atomic scale simulations revealed that the orientations of the crystallites govern the interface diffusion and the tensile strength of the joint significantly. Furthermore, interface atom diffusion increased with increasing the sliding velocity. Additionally, it was observed that a higher sliding velocity enhances the friction heat generation between the crystallites and significantly increases the interface temperature. [ABSTRACT FROM AUTHOR]

The fusion welding process of metallic components, such as using gas tungsten arc welding (GTAW), is often accompanied by detrimental deformations and residual stresses, which affect the strength and functionality of these components. In this work, a phase-field model, usually used to track the states of phase-change materials, is embedded in a thermo-elastoplastic finite element model to simulate the GTAW process and estimate the residual stresses. This embedment allows to track the moving melting front of the metallic material induced by the welding heat source and, thus, splits the domain into soft and hard solid regions with a diffusive interface between them. Additionally, temperature- and phase-field-dependent material properties are considered. The J2 plasticity model with isotropic hardening is considered. The coupled system of equations is solved in the FE package FEniCS, whereas two- and three-dimensional initial-boundary-value problems are introduced and the results are compared with reference data from the literature. [ABSTRACT FROM AUTHOR]

Vancomycin plus piperacillin–tazobactam (VPT) is a commonly used antimicrobial regimen for septic patients. VPT is more nephrotoxic than other regimens such as vancomycin plus cefepime (VC) when given over several days. This risk of nephrotoxicity is less clear when VPT is given for initial empiric therapy in sepsis and de-escalated quickly based on evolving clinical information. The objective of this study was to assess nephrotoxicity among septic patients empirically treated with either VPT or VC at initial clinical presentation. We conducted a retrospective study of septic patients who received VPT or VC within 12 h of presentation to the emergency department. The primary outcomes were acute kidney injury (AKI) and renal recovery 72 h after presentation. For the total of 418 patients, 306 received VPT and 112 received VC. Rates of AKI at 72 h were 15.2% for VPT patients and 11.0% for VC patients [p = 0.44]. Among patients with AKI at presentation, 16.3% of VPT patients had AKI at 72 h compared to 8.9% of VC patients [p = 0.19]. Among those without AKI at presentation, 14.2% VPT patients and 16.7% VC patients had AKI at 72 h [p = 0.71]. Renal recovery rates for patients with AKI at presentation were 42.3% for VPT patients versus 40.3% for VC patients [p = 0.78]. In-hospital renal replacement therapy occurred in 6.2% VPT patients and 0.9% VC patients [p = 0.024]. Therefore, initial empiric therapy with VPT in sepsis may not confer increased risk of AKI when de-escalated appropriately. [ABSTRACT FROM AUTHOR]

This research work presents an experimental and numerical study of the coupled thermo-hydro-mechanical (THM) processes that occur during soil freezing. With focusing on the artificial ground freezing (AGF) technology, a new testing device is built, which considers a variety of AGF-related boundary conditions and different freezing directions. In the conducted experiments, a distinction is made between two thermal states: (1) The thermal transient state, which is associated with ice penetration, small deformations, and insignificant water suction. (2) The thermal (quasi-) steady state, which has a much longer duration and is associated with significant ice lens formation due to water suction. In the numerical modeling, a special focus is laid on the processes that occur during the thermal transient state. Besides, a demonstration of the micro-cryo-suction mechanism and its realization in the continuum model through a phenomenological retention-curve-like formulation is presented. This allows modeling the ice lens formation and the stiffness degradation observed in the experiments. Assuming a fully saturated soil as a biphasic porous material, a phase-change THM approach is applied in the numerical modeling. The governing equations are based on the continuum mechanical theory of porous media (TPM) extended by the phase-field modeling (PFM) approach. The model proceeds from a small-strain assumption, whereas the pore fluid can be found in liquid water or solid ice state with a unified kinematics treatment of both states. Comparisons with the experimental data demonstrate the ability and usefulness of the considered model in describing the freezing of saturated soils. [ABSTRACT FROM AUTHOR]

Chemotherapeutic drugs such as the alkylating agent Temozolomide (TMZ), in addition to reducing tumor mass, can also sensitize tumors to immune recognition by transient upregulation of multiple stress induced NKG2D ligands (NKG2DL). However, the potential for an effective response by innate lymphocyte effectors such as NK and γδ T cells that recognize NKG2DL is limited by the drug's concomitant lymphodepleting effects. We have previously shown that modification of γδ T cells with a methylguanine DNA methyltransferase (MGMT) transgene confers TMZ resistance via production of O6-alkylguanine DNA alkyltransferase (AGT) thereby enabling γδ T cell function in therapeutic concentrations of TMZ. In this study, we tested this strategy which we have termed Drug Resistant Immunotherapy (DRI) to examine whether combination therapy of TMZ and MGMT-modified γδ T cells could improve survival outcomes in four human/mouse xenograft models of primary and refractory GBM. Our results confirm that DRI leverages the innate response of γδ T cells to chemotherapy-induced stress associated antigen expression and achieves synergies that are significantly greater than either individual approach. [ABSTRACT FROM AUTHOR]

Electrospray ionization (ESI) generates bare analyte ions from charged droplets, which result from spraying a liquid in a strong electric field. Experimental observations available in the literature suggest that at least a significant fraction of the initially generated droplets remain large, have long lifetimes, and can thus aspirate into the inlet system of an atmospheric pressure ionization mass spectrometer (API-MS). We report on the observation of fragment signatures from charged droplets penetrating deeply the vacuum stages of three commercial mass spectrometer systems with largely different ion source and spray configurations. Charged droplets can pass through the ion source and pressure reduction stages and even into the mass analyzer region. Since droplet signatures were found in all investigated instruments, the incorporation of charged droplets is considered a general phenomenon occurring with common spray conditions in ESI sources. [ABSTRACT FROM AUTHOR]

Determination of treatment response to immunotherapy in glioblastoma multiforme (GBM) is a process which can take months. Detection of CD8+ T cell recruitment to the tumor with a noninvasive imaging modality such as positron emission tomography (PET) may allow for tumor characterization and early evaluation of therapeutic response to immunotherapy. In this study, we utilized 89Zr-labeled anti-CD8 cys-diabody-PET to provide proof-of-concept to detect CD8+ T cell immune response to oncolytic herpes simplex virus (oHSV) M002 immunotherapy in a syngeneic GBM model. Immunocompetent mice (n = 16) were implanted intracranially with GSC005 GBM tumors, and treated with intratumoral injection of oHSV M002 or saline control. An additional non-tumor bearing cohort (n = 4) receiving oHSV M002 treatment was also evaluated. Mice were injected with 89Zr-labeled anti-CD8 cys-diabody seven days post oHSV administration and imaged with a preclinical PET scanner. Standardized uptake value (SUV) was quantified. Ex vivo tissue analyses included autoradiography and immunohistochemistry. PET imaging showed significantly higher SUV in tumors which had been treated with M002 compared to those without M002 treatment (p = 0.0207) and the non-tumor bearing M002 treated group (p = 0.0021). Accumulation in target areas, especially the spleen, was significantly reduced by blocking with the non-labeled diabody (p < 0.001). Radioactive probe accumulation in brains was consistent with CD8+ cell trafficking patterns after oHSV treatment. This PET imaging strategy could aid in distinguishing responders from non-responders during immunotherapy of GBM. [ABSTRACT FROM AUTHOR]

Objectives: To analyse prenatal parameters predicting biventricular (BV) outcome in pulmonary atresia with intact ventricular septum/critical pulmonary stenosis (PAIVS/CPS). Methods: We evaluated 82 foetuses from 01/08 to 10/18 in 3 centres in intervals 1 (< 24 weeks), 2 (24–30 weeks) and 3 (> 30 weeks). Results: 61/82 (74.4%) were livebirths, 5 (8.2%) lost for follow-up, 3 (4.9%) had compassionate care leaving 53 (64.6% of the whole cohort and 86.9% of livebirths) with intention to treat. 9 died, 44/53 (83.0%) survived. 24/38 (63.2%) with information on postnatal outcome had BV outcome, 14 (36.8%) non-BV outcome (2 × 1.5 circulation). One with BV outcome had prenatal valvuloplasty. Best single parameter for BV outcome was tricuspid/mitral valve (TV/MV) ratio (AUC 0.93) in intervals 2 and 3 (AUC 0.92). Ventriculo-coronary-arterial communications (VCAC) were present in 11 (78.6%) in non-BV outcome group vs. 2 (8.3%) in BV outcome group (p < 0.001). Tricuspid insufficiency (TI)-Vmax > 2.5 m/s was present in BV outcome group in75.0% (18/24) vs. 14.3% (2/14) in non-BV outcome group. Including the most predictive markers (VCAC presence, TI- Vmax < 2.5 m/s, TV/MV ratio < cutoff) to a score, non-BV outcome was correctly predicted when > 1 criterion was fulfilled in all cases. After recently published criteria for foetal intervention, only 4/9 (44.4%) and 5/14 (35.7%) in our interval 2 + 3 with predicted non-BV outcome would have been candidates for intervention. Two (1 × intrauterine intervention) in interval 2, two in interval 3 reached BV outcome and one 1.5 circulation without intervention. Conclusion: TV/MV ratio as simple parameter has high predictive value. After our score, non-BV outcome was correctly predicted in all cases. Criteria for foetal intervention must further be evaluated. [ABSTRACT FROM AUTHOR]

Background: Children with complete DiGeorge anomaly (cDGA) have congenital athymia plus a myriad of other challenging clinical conditions. The term cDGA encompasses children with congenital athymia secondary to 22q11.2DS, CHARGE syndrome (coloboma, heart defects, choanal atresia, growth or mental retardation, genital abnormalities, and ear abnormalities and/or deafness), and other genetic abnormalities. Some children have no known genetic defects. Since 1993, more than 100 children with congenital athymia have been treated with cultured thymus tissue implantation (CTTI). Naïve T cells develop approximately 6 to 12 months after CTTI. Most of the children had significant comorbidities such as heart disease, hypoparathyroidism, and infections requiring complex clinical care post cultured thymus tissue implantation (CTTI). Objective: The purpose of this guidance is to assist multidisciplinary teams in caring for children with cDGA both before and after CTTI. Methods: Thirty-one specialists, in addition to the authors, were asked to share their experience in caring for children with cDGA at Duke University Health System, before and after CTTI. These specialists included physicians, nurses, dentists, therapists, and dieticians. Results: The goal of a multidisciplinary approach is to have children in the best possible condition for receiving CTTI and provide optimal care post CTTI through development of naïve T cells and beyond. The CTT (cultured thymus tissue) must be protected from high doses of steroids which can damage CTT. Organs must be protected from adverse effects of immunosuppression. Conclusion: Creating a multidisciplinary team and a detailed plan of care for children with cDGA is important for optimal outcomes. [ABSTRACT FROM AUTHOR]

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Introduction: Current electroencephalography (EEG) practice relies on interpretation by expert neurologists, which introduces diagnostic and therapeutic delays that can impact patients' clinical outcomes. As EEG practice expands, these experts are becoming increasingly limited resources. A highly sensitive and specific automated seizure detection system would streamline practice and expedite appropriate management for patients with possible nonconvulsive seizures. We aimed to test the performance of a recently FDA-cleared machine learning method (Claritγ, Ceribell Inc.) that measures the burden of seizure activity in real time and generates bedside alerts for possible status epilepticus (SE). Methods: We retrospectively identified adult patients (n = 353) who underwent evaluation of possible seizures with Rapid Response EEG system (Rapid-EEG, Ceribell Inc.). Automated detection of seizure activity and seizure burden throughout a recording (calculated as the percentage of ten-second epochs with seizure activity in any 5-min EEG segment) was performed with Claritγ, and various thresholds of seizure burden were tested (≥ 10% indicating ≥ 30 s of seizure activity in the last 5 min, ≥ 50% indicating ≥ 2.5 min of seizure activity, and ≥ 90% indicating ≥ 4.5 min of seizure activity and triggering a SE alert). The sensitivity and specificity of Claritγ's real-time seizure burden measurements and SE alerts were compared to the majority consensus of at least two expert neurologists. Results: Majority consensus of neurologists labeled the 353 EEGs as normal or slow activity (n = 249), highly epileptiform patterns (HEP, n = 87), or seizures [n = 17, nine longer than 5 min (e.g., SE), and eight shorter than 5 min]. The algorithm generated a SE alert (≥ 90% seizure burden) with 100% sensitivity and 93% specificity. The sensitivity and specificity of various thresholds for seizure burden during EEG recordings for detecting patients with seizures were 100% and 82% for ≥ 50% seizure burden and 88% and 60% for ≥ 10% seizure burden. Of the 179 EEG recordings in which the algorithm detected no seizures, seizures were identified by the expert reviewers in only two cases, indicating a negative predictive value of 99%. Discussion: Claritγ detected SE events with high sensitivity and specificity, and it demonstrated a high negative predictive value for distinguishing nonepileptiform activity from seizure and highly epileptiform activity. Conclusions: Ruling out seizures accurately in a large proportion of cases can help prevent unnecessary or aggressive over-treatment in critical care settings, where empiric treatment with antiseizure medications is currently prevalent. Claritγ's high sensitivity for SE and high negative predictive value for cases without epileptiform activity make it a useful tool for triaging treatment and the need for urgent neurological consultation. [ABSTRACT FROM AUTHOR]

Purpose: Several roles are attributed to the myometrium including sperm and embryo transport, menstrual discharge, control of uterine blood flow, and labor. Although being a target of diabetes complications, the influence of high glucose on this compartment has been poorly investigated. Both miRNAs and IGF1R are associated with diabetic complications in different tissues. Herein, we examined the effects of high glucose on the expression of miRNAs and IGF1R signaling pathway in the human myometrium. Methods: Human myometrial explants were cultivated for 48 h under either high or low glucose conditions. Thereafter, the conditioned medium was collected for biochemical analyses and the myometrial samples were processed for histological examination as well as miRNA and mRNA expression profiling by qPCR. Results: Myometrial structure and morphology were well preserved after 48 h of cultivation in both high and low glucose conditions. Levels of lactate, creatinine, LDH and estrogen in the supernatant were similar between groups. An explorative screening by qPCR arrays revealed that 6 out of 754 investigated miRNAs were differentially expressed in the high glucose group. Data validation by single qPCR assays confirmed diminished expression of miR-215-5p and miR-296-5p, and also revealed reduced miR-497-3p levels. Accordingly, mRNA levels of IGF1R and its downstream mediators FOXO3 and PDCD4, which are potentially targeted by miR-497-3p, were elevated under high glucose conditions. In contrast, mRNA expression of IGF1, PTEN, and GLUT1 was unchanged. Conclusions: The human myometrium responds to short-term exposure (48 h) to high glucose concentrations by regulating the expression of miRNAs, IGF1R and its downstream targets. [ABSTRACT FROM AUTHOR]

Microplastic particles have been found in all the world's oceans. Since their surfaces are microbially colonised, research is currently determining whether microbes are able to degrade the synthetic polymers. We show that their contribution to the biodegradation of plastics seems to be extremely limited. Also, it is unlikely that microbes specialise in plastic degradation through evolutionary adaptation. This is not only due to the great diversity and simultaneous very low bioavailability of microplastics in the oceans, but also because it is energetically disadvantageous. [ABSTRACT FROM AUTHOR]

In this contribution, we present a space-time formulation of the Newmark integration scheme for linear damped structures under both harmonic and transient excitations. The incremental set of equations of motion and the Newmark approximations are transformed into their corresponding space-time equivalents. The dynamic system is then represented by one algebraic space-time equation only. This equation is projected into a coupled pair of space-time equations, which is solved via the fixed point algorithm. The solution is iteratively assembled by enrichments, each of which is decomposed by a dyadic product of spatial and temporal enrichment vectors. The evolution of the spatial enrichment vectors is investigated during convergence and interpreted by comparing them to the set of linear modes of vibration. The new method is demonstrated by means of four numerical examples, presenting not only the excellent convergence behavior and the numerical efficiency but also the limits of the proposed approach. [ABSTRACT FROM AUTHOR]

The signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive cellular responses occur is unclear. Here, we report development of 3-Dimensional culture analyses to separately quantify growth and invasion. We identify that alternate variants of IQSEC1, an ARF GTPase Exchange Factor, act as switches to promote invasion over growth by controlling phosphoinositide metabolism. All IQSEC1 variants activate ARF5- and ARF6-dependent PIP5-kinase to promote PI(3,4,5)P3-AKT signalling and growth. In contrast, select pro-invasive IQSEC1 variants promote PI(3,4,5)P3 production to form invasion-driving protrusions. Inhibition of IQSEC1 attenuates invasion in vitro and metastasis in vivo. Induction of pro-invasive IQSEC1 variants and elevated IQSEC1 expression occurs in a number of tumour types and is associated with higher-grade metastatic cancer, activation of PI(3,4,5)P3 signalling, and predicts long-term poor outcome across multiple cancers. IQSEC1-regulated phosphoinositide metabolism therefore is a switch to induce invasion over growth in response to the same external signal. Targeting IQSEC1 as the central regulator of this switch may represent a therapeutic vulnerability to stop metastasis. The signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive responses occur is unclear. Here, the authors show that alternate isoforms of the ARF GTPase exchange factor IQSEC1 direct phosphoinositide metabolism to control this switch. [ABSTRACT FROM AUTHOR]

Distress in oncology patients (pts) has a negative impact on quality of life, survival, and healthcare satisfaction. Higher distress leads to lower compliance with treatment and follow-up [1-8]. The 2012 American College of Surgeons Commission on Cancer (CoC) standard of care for oncology pts included an assessment for distress [1]. A screening process for distress allows the healthcare team to address these issues early and refer to appropriate resources [2-9]. This project was initiated to meet National Comprehensive Cancer Network (NCCN) and CoC standard of care, identify distress in veterans with cancer, and address these concerns. Patients who attended the Tuesday oncology clinic at the Dayton VAMC were given the NCCN Distress Thermometer (DT) during triage. The treating physician addressed problems identified. The Wilcoxon signed rank test and the Friedman test were used. DTs were completed by 296 pts from March to December 2016. Mean age was 68, 93% male, 83% white, 55% married, and 93% without PTSD. The distress level was not different from T1 through T3. Number of problems decreased over three time periods. Referrals to nutrition, mental health, and social work services increased over time. Although over time periods we found no decrease in distress scores, there was a decline in number of problems. The mean distress score at all but time 4 was < 4, which is considered mild distress. The mean distress score at T4 was 4.36 (n = 14), suggesting that the few pts who return to clinic more than three times may be experiencing more difficult personal and environmental circumstances. Patient sample ranged from those undergoing intensive cancer treatment (e.g., chemotherapy) to less intensive treatment (e.g., hormone injections) to those who completed treatment. [ABSTRACT FROM AUTHOR]