bluuebunny/crossref_metadata_2025 huggingface dataset:
A Hybrid Contact Model With Experimental Validation
Authors: Liu Qian , Cheng Jing , Li Delun , Wei Qingqing
Published: March 2021

This brief paper emphasizes on the experimental study of a hybrid contact model combining a traditional physical-based contact model and a data-driven error model in order to provide a more accurate description of a contact dynamics phenomenon. The physical-based contact model is employed to describe the known contact physics of a complex contact case, while the data-driven error model, which is an artificial neural network model trained from experimental data using a machine learning technique, is used to represent the inherent unmodeled factors of the contact case. A bouncing ball experiment is designed and performed to validate the model. The hybrid contact model can duplicate experimental results well, which demonstrates the feasibility and accuracy of the presented approach.
Effects of Turning Angle and Turning Internal Radius on Channel Impingement Cooling for a Novel Internal Cooling Structure
Authors: He Wei , Deng Qinghua , Yang Guoying , Feng Zhenping
Published: March 2021

Leading-edge multi-channel double-wall design, a novel internal cooling structure, has been presented recently to enable higher overall cooling effectiveness with less penalty of coolant and pressure loss. Our previous work has proved the advantages of the design under operating condition relative to conventional internal cooling methods, including impingement cooling and swirl cooling. Channel impingement cooling structure, which is utilized at the turning region of the leading edge, is the critical factor to realize the high cooling performance of the design. Hence, the turning angle and turning internal radius of the cooling channel are two key parameters for the novel design, and this paper focuses on the effects of these two parameters on the flow and heat transfer characteristics of the design. Nine simplified single-channel models with different turning angles (45 deg, 60 deg, and 75 deg) and radii (0.6 mm, 0.9 mm, and 1.2 mm) were adopted to conduct the study, and the jet Reynolds number ranges from 10,000 to 40,000. The results show that the turning angle and turning internal radius affect the jet form significantly for the same mechanism. Small turning angle means large impingement, which leads to stream-wise counter-rotational vortices and high turbulence intensity, but increasing turning internal radius transfers the jet form from impingement jet to laminar layer attaching the target surface with low heat transfer. The turning internal radius has stronger effect than turning angle. With higher jet Reynolds number, both the heat transfer and total pressure loss increase dramatically, and the effects of geometrical parameters are clearer.
Hf1−xZrxO2 and HfO2/ZrO2 gate dielectrics with extremely low density of interfacial defects using low temperature atomic layer deposition on GaN and InP
Authors: Ahadi Kaveh , Cadien Ken
Published: March 2021

Achieving a negative capacitance field effect transistor with a subthreshold swing beyond the Boltzmann limit requires a “defect-free” dielectric-semiconductor interface. We grew alloyed (Hf1−xZrxO2) and stacked (HfO2/ZrO2) gate dielectrics on GaN and InP substrates using low temperature plasma enhanced atomic layer deposition. In situ ellipsometry data show that alloying hafnia with zirconia reduces the refractive index and widens the bandgap. The stacked and alloyed structures reveal very low capacitance-voltage hysteresis of 35 and 45 mV, respectively, on GaN. The density of interfacial traps as low as 1.12 × 1010 cm−2 eV−1 was achieved on GaN mainly due to the combination of very low dielectric growth temperature (100 °C) and high postfabrication heat treatment temperature (510 °C). The conduction and valence band offsets of the alloyed gate dielectrics on InP were measured and compared to pure zirconia using a combination of x-ray photoelectron spectroscopy and ellipsometry. The alloyed structures show a wider bandgap, larger conduction band offset, and smaller valence band offset compared to pure zirconia. This was attributed to the increase in the valence band width with hafnia addition, which reduces the alloyed gate dielectric’s valence band offset. We resolved the band structure alignement to be type I with band offsets of 3.53 eV for electrons and 1.03 eV for holes in Hf0.25Zr0.75O2/InP heterojunctions. The results allow for a clear and detailed picture of two distinct growth procedure that affect the interfacial defect concentration.
Reflections on Developing a Career in Kinesiology and Public Health
Authors: Ainsworth Barbara E.
Published: March 2021

This paper provides reflections on my academic career in kinesiology and public health from an autobiographical perspective. Themes include the importance of movement and physical activity in my development and career choices, a recognition of the importance of physical activity for health outcomes, experiences in studying physical activity in a public health framework, and observations on kinesiology in higher education. I also reflect on the importance of the physical education and physical activity environment that brought me a sense of belonging, enjoyment, and accomplishment that has lasted throughout my career. As in sports and professional activities, I have tried my best and never given up until I felt the task was done.
Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke
Authors: Lemmerman Luke R. , Balch Maria H. H. , Moore Jordan T. , Alzate-Correa Diego , Rincon-Benavides Maria A. , Salazar-Puerta Ana , Gnyawali Surya , Harris Hallie N. , Lawrence William , Ortega-Pineda Lilibeth , Wilch Lauren , Risser Ian B. , Maxwell Aidan J. , Duarte-Sanmiguel Silvia , Dodd Daniel , Guio-Vega Gina P. , McTigue Dana M. , Arnold W. David , Nimjee Shahid M. , Sen Chandan K. , Khanna Savita , Rink Cameron , Higuita-Castro Natalia , Gallego-Perez Daniel
Published: March 2021

Fibroblasts nonvirally programmed to convert into induced endothelial cells show therapeutic potential for ischemic stroke.
Preventing pores and inflammation
Authors: Pickering Robert J. , Bryant Clare E.
Published: March 2021

Metabolite-directed modification of pore-forming cell death protein limits inflammation
Exploiting albumin as a mucosal vaccine chaperone for robust generation of lung-resident memory T cells
Authors: Rakhra Kavya , Abraham Wuhbet , Wang Chensu , Moynihan Kelly D. , Li Na , Donahue Nathan , Baldeon Alexis D. , Irvine Darrell J.
Published: March 2021

Pulmonary immunization with albumin-binding peptide vaccines promotes resident memory CD8
+
T cell generation in the lung.
Polymorphonuclear Myeloid-Derived Cells That Contribute to the Immune Paralysis Are Generated in the Early Phase of Sepsis via PD-1/PD-L1 Pathway
Authors: Ao Xiang , Yang Yue , Okiji Takashi , Azuma Miyuki , Nagai Shigenori
Published: March 2021

Immune paralysis is a protracted state of immune suppression following the early/acute inflammatory phase of sepsis. CD11b
+
Gr-1
+
cells induced during sepsis are heterogeneous myeloid-derived cells (MDCs).
Defining Stable Reference Genes in HIV Latency Reversal Experiments
Authors: Ceriani Cristina , Streeter Gabrielle S. , Lemu Kena J. , James Katherine S. , Ghofrani Simon , Allard Brigitte , Shook-Sa Bonnie E. , Margolis David M. , Archin Nancie M.
Published: March 2021

Latency-reversing agents (LRAs) are ubiquitously used in the “shock-and-kill” HIV cure strategy, and their performance is often evaluated by
ex vivo
quantification of cell-associated HIV RNA. HIV RNA, measured by quantitative PCR (qPCR), is often normalized to internal reference genes, but the expression of these genes should not be influenced by the experimental settings.
Management considerations in the adult with surgically modified d-transposition of the great arteries
Authors: Gaur Lasya , Cedars Ari , Diller Gerhard Paul , Kutty Shelby , Orwat Stefan
Published: March 2021

Dextro-transposition of the great arteries (D-TGA) has undergone a significant evolution in surgical repair, leading to survivors with vastly different postsurgical anatomy which in turn guides their long-term cardiovascular morbidity and mortality. Atrial switch repair survivors are limited by a right ventricle in the systemic position, arrhythmia and atrial baffles prone to obstruction or leak. Functional assessment of the systemic right ventricle is complex, requiring multimodality imaging to include specialised echocardiography and cross-sectional imaging (MRI and CT). In the current era, most neonates undergo the arterial switch operation with increasing understanding of near-term and long-term outcomes specific to their cardiac anatomy. Long-term observations of the Lecompte manoeuvre or coronary stenoses following transfer continue, with evolving understanding to improve surveillance. Ultimately, an understanding of postsurgical anatomy, specialised imaging techniques and interventional and electrophysiological procedures is essential to comprehensive care of D-TGA survivors.
Reovirus-induced cell-mediated immunity for the treatment of multiple myeloma within the resistant bone marrow niche
Authors: Müller Louise M E , Migneco Gemma , Scott Gina B , Down Jenny , King Sancha , Askar Basem , Jennings Victoria , Oyajobi Babatunde , Scott Karen , West Emma , Ralph Christy , Samson Adel , Ilett Elizabeth J , Muthana Munitta , Coffey Matt , Melcher Alan , Parrish Christopher , Cook Gordon , Lawson Michelle , Errington-Mais Fiona
Published: March 2021

Background

Multiple myeloma (MM) remains an incurable disease and oncolytic viruses offer a well-tolerated addition to the therapeutic arsenal. Oncolytic reovirus has progressed to phase I clinical trials and its direct lytic potential has been extensively studied. However, to date, the role for reovirus-induced immunotherapy against MM, and the impact of the bone marrow (BM) niche, have not been reported.

Methods

This study used human peripheral blood mononuclear cells from healthy donors and in vitro co-culture of MM cells and BM stromal cells to recapitulate the resistant BM niche. Additionally, the 5TGM1-Kalw/RijHSD immunocompetent in vivo model was used to examine reovirus efficacy and characterize reovirus-induced immune responses in the BM and spleen following intravenous administration. Collectively, these in vitro and in vivo models were used to characterize the development of innate and adaptive antimyeloma immunity following reovirus treatment.

Results

Using the 5TGM1-Kalw/RijHSD immunocompetent in vivo model we have demonstrated that reovirus reduces both MM tumor burden and myeloma-induced bone disease. Furthermore, detailed immune characterization revealed that reovirus: (i) increased natural killer (NK) cell and CD8+T cell numbers; (ii) activated NK cells and CD8+T cells and (iii) upregulated effector-memory CD8+T cells. Moreover, increased effector-memory CD8+T cells correlated with decreased tumor burden. Next, we explored the potential for reovirus-induced immunotherapy using human co-culture models to mimic the myeloma-supportive BM niche. MM cells co-cultured with BM stromal cells displayed resistance to reovirus-induced oncolysis and bystander cytokine-killing but remained susceptible to killing by reovirus-activated NK cells and MM-specific cytotoxic T lymphocytes.

Conclusion

These data highlight the importance of reovirus-induced immunotherapy for targeting MM cells within the BM niche and suggest that combination with agents which boost antitumor immune responses should be a priority.
Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: cohort A report in a multicenter phase Ib/II trial
Authors: Mei Kuimin , Qin Shukui , Chen Zhendong , Liu Ying , Wang Linna , Zou Jianjun
Published: March 2021

Background

Emerging clinical data suggest that an immune checkpoint inhibitor in combination with an antiangiogenic agent is a reasonable strategy for multiple malignancies. We assessed the combination of camrelizumab with apatinib in pretreated advanced primary liver cancer (PLC, cohort A) from a multicohort phase Ib/II trial.

Methods

Patients with PLC after prior systemic treatment(s) were administered camrelizumab (3 mg/kg, once every 2 weeks) plus apatinib (125, 250, 375, or 500 mg; once per day) in a 3+3 dose-escalation stage and subsequent expansion stage. The primary endpoints were tolerability and safety of study treatment.

Results

From April 2017 to July 2019, 28 patients (21 with hepatocellular carcinoma and 7 with intrahepatic cholangiocarcinoma) received camrelizumab plus apatinib. Two dose-limiting toxicities (both grade 3 diarrhea) were reported in the 500 mg cohort. Therefore, the 375 mg cohort was expanded. Of the 19 patients in the 375 mg cohort, dose reduction to 250 mg occurred in 8 patients within 2 months after treatment initiation. Of the 28 patients with PLC, 26 had grade ≥3 treatment-related adverse events, with hypertension being the most common (9/28). One treatment-related death occurred. The objective response rate was 10.7% (95% CI 2.3% to 28.2%). Median progression-free survival and overall survival were 3.7 months (95% CI 2.0 to 5.8) and 13.2 months (95% CI 8.9 to not reached), respectively.

Conclusion

The combination of camrelizumab with apatinib had a manageable toxicity and promising antitumor activity in patients with advanced PLC. Apatinib at a dose of 250 mg is recommended as a combination therapy for further studies of advanced PLC treatment.

Trial registration numbers

NCT03092895.
#warriors: sick children, social media and the right to an open future
Authors: Burn Elise
Published: March 2021

The phenomenon of ‘sharenting’, whereby a parent shares news and images of their child on social media, is of growing popularity in contemporary society. There is emerging research into children’s attitudes regarding sharenting and their associated concerns regarding privacy; however, this research most often involves young people who are approaching adulthood and are competent to participate. As a result, children who experience illness or disability are largely absent from current research, and as such, the moral permissibility of a parent sharing their child’s illness journey on a public social media platform is largely unexplored. In this essay, I explore this issue by using the United NationsConvention on the Rights of the Childand Joel Feinberg’s principle of the child’s right to an open future as the basis of my argument: that children with illness and disability have the same rights as healthy children to privacy, identity and an open future and that publication of their illness on a social media platform violates these rights. I conclude that parents, as surrogate decision makers for their children, have the same responsibilities in protecting their child’s privacy as they do in making medical decisions on behalf of their children. As children of the social media generation approach adulthood, it is important to consider the rights of those who cannot speak for themselves and the ethical consequences of sharenting for children with illness and disability.
Autonomy, identity and health: defining quality of life in older age
Authors: Heide Sara Kate
Published: March 2021

Defining quality of life is a difficult task as it is a subjective and personal experience. However, for the elderly, this definition is necessary for making complicated healthcare-related decisions. Commonly these decisions compare independence against safety or longevity against comfort. These choices are often not made in isolation, but with the help of a healthcare team. When the patient’s concept of quality of life is miscommunicated, there is a risk of harm to the patient whose best interests are not well understood. In order to bridge this gap in understanding and unite seniors with their caretakers as a cohesive team, we need to establish a definition of quality of life. In this paper, my personal experiences with the elderly will be analysed along with five essays on the topic of ageing. These sources provide clear evidence that quality of life for seniors is majorly determined by the ability to preserve one’s lifelong identity. When making difficult decisions in geriatric healthcare, this greater understanding of the determinants of life quality will allow treatments to best serve the elderly. Defining quality of life allows healthcare providers to shift the focus from minimising disability toward maximising ability. I believe this shift would provide seniors with better health outcomes and properly enhance the quality of their years.
Evaluation of the prognostic value of GDF-15, ABC-AF-bleeding score and ABC-AF-death score in patients with atrial fibrillation across different geographical areas
Authors: Pol Tymon , Hijazi Ziad , Lindbäck Johan , Alexander John H , Bahit M Cecilia , De Caterina Raffaele , Eikelboom JW , Ezekowitz Michael D , Gersh Bernard J , Granger Christopher B , Hylek Elaine M , Lopes Renato , Siegbahn Agneta , Wallentin Lars
Published: March 2021

Objectives

Growth differentiation factor 15 (GDF-15) is a biomarker independently associated with bleeding and death in anticoagulated patients with atrial fibrillation (AF). GDF-15 is also used as one component in the more precise biomarker-based ABC (age, biomarkers, clinical history)-AF-bleeding and ABC-AF-death risk scores. Data from large trials indicate a geographic variability in regard to overall outcomes, including bleeding and mortality risk. Our aim was to assess the consistency of the association between GDF-15, ABC-AF-bleeding score and ABC-AF-death score, with major bleeding and death, across world geographic regions.

Methods

Data were available from 14 767 patients with AF from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and 8651 patients with AF from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial in this cohort study. GDF-15 was analysed from plasma samples obtained at randomisation. The geographical consistency of the associations between outcomes and GDF-15, ABC-AF-bleeding score and ABC-AF-death scores were assessed by Cox-regression models including interactions with predefined geographical region.

Results

GDF-15 and the ABC-AF-bleeding score were associated with major bleeding in both trials across regions (p<0.0001). Similarly, GDF-15 and the ABC-AF-death score were associated with all-cause mortality in both trials across regions (p<0.0001). Overall, the association between GDF-15, the ABC-AF-bleeding score and ABC-AF-death risk score with major bleeding and death was consistent across regions in both ARISTOTLE and the RE-LY trial cohorts. The ABC-AF-bleeding and ABC-AF-death risk scores were consistent regarding discriminative ability when comparing geographic regions in both trial cohorts. The C-indices ranged from 0.649 to 0.760 for the ABC-AF-bleeding and from 0.677 to 0.806 for the ABC-AF-death score by different geographic regions.

Conclusions

In patients with AF on anticoagulation, GDF-15 and the biomarker-based ABC-AF-bleeding and ABC-AF-death risk scores are consistently associated with respectively increased risk of major bleeding and death and have similar prognostic value across world geographic regions.

Trial registration number

ClinicalTrials.gov RegistryNCT00412984andNCT00262600.
COVID-19 in New York City as an Extreme Event: The Disruption and Resumption of the Global City
Authors: Cohen Steven
Published: March 2021

This paper discusses the need for public health infrastructure to address COVID-19 and future pandemics. It then links this need to the centrality of the global economy, and finally to the maintenance of density required for environmentally sustainable cities.
Molecular Dynamics Simulation of Diffusion and O2 Dissolution in Water Using Four Water Molecular Models
Authors: Fan Linhao , Wang Yun , Jiao Kui
Published: March 2021

This work evaluates four popular 3-site water models, TIP3P, SPC/E, SPC, and F3C, in predicting temperature-dependent O2 diffusion and dissolution and self-diffusion in liquid water for electrochemical devices, such as fuel cells, electrolyzers and metal-air batteries, using molecular dynamics simulations. We report that the TIP3P and SPC models overestimate O2 diffusivity, though qualitatively describe its temperature dependence, while the SPC/E and F3C models show a good prediction of O2 diffusivity with the former accurately predicting its activation energy. The TIP3P, SPC, and F3C models overestimate the O2 solubility with the TIP3P even incorrectly predicting its temperature dependence. The SPC/E model shows the best performance in predicting both the O2 diffusivity (<15% error) and solubility (<16% error) in the temperature range. The radial distribution functions of O atoms are present and show that lower peaks, i.e. more intermolecular space among water molecules for the random walks, leads to higher prediction of diffusivities. Comparison with literature experimental data is summarized.
Malignant Glandular Triton Tumor Arising in the Radial Nerve with Prolonged Survival: A Case Report and Review of the Literature
Authors: AlAli Batool M. , Amr Samir S.
Published: March 2021

Divergent differentiation is a well-known phenomenon in malignant peripheral nerve sheath tumors (MPNST) which occurs approximately in 15% of these tumors, usually towards mesenchymal elements. Differentiation towards epithelial components, however, is quite uncommon, and even exceptionally rare is concomitant mesenchymal and glandular differentiation. To our knowledge, only 14 cases of MPNST with both mesenchymal (rhabdomyoblastic) and glandular differentiation had been reported, and only two of these tumors had frankly malignant glandular components. Herein, we report the third such case. A 26-year-old male, without any of the stigmata of NF1, presented with a 2-year history of pain in his left shoulder and an elbow swelling of six-month duration. The tumor was initially diagnosed clinically as a neurofibroma at a local hospital. The patient underwent excision of the mass there, and pathological examination at that hospital showed the tumor to be MPNST. Six months later, the patient was referred to our hospital, a tertiary care medical center, with recurrent swelling at the same location. Histopathological material from the referral hospital was reviewed, and the tumor was diagnosed as MPNST with rhabdomyoblastic differentiation or malignant triton tumor (MTT) that contained in addition foci of malignant glandular epithelium. The patient refused any surgical intervention. He received three cycles of chemotherapy followed by radiotherapy with excellent response and marked reduction in the size of the tumor. The patient had prolonged survival for 10 years following the initial resection of the tumor.
Atg16L1 as a Novel Biomarker and Autophagy Gene for Diabetic Retinopathy
Authors: Gao Xinxiao , Du Yunhui , Lau Wayne Bond , Li Yu , Zhu Siquan , Ma Xin-Liang
Published: March 2021

Objective. Accumulating evidence suggests the critical role of autophagy in the pathogenesis of diabetic retinopathy (DR). In the current study, we aim to identify autophagy genes involved in DR via microarray analyses. Methods. Gene microarrays were performed to identify differentially expressed lncRNAs/mRNAs between normal and DR retinas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of lncRNA-coexpressed mRNAs were used to determine the related pathological pathways and biological modules. Real-time polymerase chain reactions (PCR) were conducted to validate the microarray analyses. Results. A total of 2474 significantly dysregulated lncRNAs and 959 differentially expressed mRNAs were identified in the retina of DR. Based upon Signalnet analysis, Bcl2, Gabarapl2, Atg4c, and Atg16L1 participated the process of cell death in DR. Moreover, real-time PCR revealed significant upregulation of Atg16L1. Conclusion. This study indicated the importance and potential role of Atg16L1, one of the autophagy genes, as a biomarker in DR development and progression.
In Situ Stress Inversion and Distribution Characteristics of Tunnel Based on Numerical Simulation and Neural Network Technology
Authors: Zhang Pei
Published: March 2021

According to the geological conditions of the study area, the measured data of in situ stress was analyzed and the influence degree of buried depth was obtained. A numerical simulation research model with full consideration of fault structure and surface characteristics is established, and boundary condition functions with variables are used. The neural network optimized by genetic algorithm is used to establish the nonlinear relationship between the measured value and the simulated value of the variable boundary condition, and the optimal boundary condition function is obtained. Finally, the in situ stress in the study area was predicted. Through the analysis of the in situ stress field in the research target area, the stress boundary conditions are provided for the follow‐up study, and the practical basis for the division of the dangerous area of the surrounding rock of the deep and long tunnel is provided.
A Fractal Model for Predicting the Relative Permeability of Rough‐Walled Fractures
Authors: Ye Zuyang , Luo Wang , Huang Shibing , Chen Yuting , Cheng Aiping
Published: March 2021

The relative permeability and saturation relationships through fractures are fundamental for modeling multiphase flow in underground geological fractured formations. In contrast to the traditional straight capillary model from porous media, the realistic flow paths in rough‐walled fractures are tortuous. In this study, a fractal relationship between relative permeability and saturation of rough‐walled fractures is proposed associated with the fractal characteristics of tortuous parallel capillary plates, which can be generalized to several existing models. Based on the consideration that the aperture distribution of rough‐walled fracture can be represented by Gaussian and lognormal distributions, aperture‐based expressions between relative permeability and saturation are explicitly derived. The developed relationships are validated by the experimental observations on Gaussian distributed fractures and numerical results on lognormal distributed fractures, respectively.
Thermal Stability and Kinetics of Thermal Decomposition of Statistical Copolymers of N-Vinylpyrrolidone and Alkyl Methacrylates Synthesized via RAFT Polymerization
Authors: Gikarakis Theodoros , Pappas Ioannis , Arvanitaki Pothiti , Pantazi Ekaterini , Mitsoni Eleftheria , Roka Nikoletta , Pitsikalis Marinos
Published: March 2021

The thermal stability and the kinetics of thermal decomposition of statistical copolymers of N-vinylpyrrolidone (NVP) with the alkyl methacrylates, hexyl methacrylate (HMA) and stearyl methacrylate (SMA), were studied by Thermogravimetric Analysis (TGA) and Differential Thermogravimetry (DTG). Statistical copolymers of different compositions were studied, and their thermal decomposition behavior was compared to the corresponding homopolymers. The activation energies of the thermal decomposition were calculated using the Ozawa-Flynn-Wall, the Kissinger, and the Kissinger-Akahira-Sunose methodologies. The effects of the nature of the methacrylate monomer, the copolymer composition, and the rate of heating are discussed.
Study of Inflammatory and Infection Markers in Periprosthetic Fluid: Correlation with Blood Analysis in Retrospective and Prospective Studies
Authors: Lisa Andrea , Belgiovine Cristina , Maione Luca , Rimondo Andrea , Battistini Andrea , Agnelli Benedetta , Murolo Matteo , Galtelli Leonardo , Monari Marta , Klinger Marco , Vinci Valeriano
Published: March 2021

Background. Surgical site infection represents the most severe complication in prosthetic breast reconstruction. Risk profiling represents a useful tool for both clinicians and patients. Materials and Methods. In our hospital, 534 breast reconstructions with tissue expander implants, in 500 patients, were performed. Several clinical variables were collected. In our study, we evaluated the different inflammatory markers present in the periprosthetic fluid and we compared them with the ones present in plasma. Results. The surgical site infection rate resulted to be 10.5%, and reconstruction failed in 4.5% of the cases. The hazard ratio for complications was 2.3 in women over 60 (CI: 1.3‐4.07; p = 0.004), 2.57 in patients with expander volume ≥ 500 cc (CI: 1.51‐4.38; p < 0.001), 2.14 in patients submitted to previous radiotherapy (CI: 1.05‐4.36; p < 0.037), and 1.05 in prolonged drain use (CI: 1.03‐1.07; p < 0.001). 25‐OH, PCT, and total protein were less concentrated, and ferritin and LDH were more concentrated in the periprosthetic fluid than in plasma (p < 0.001). CRP (p = 0.190) and β‐2 microglobulin (p = 0.344) did not change in the two fluids analyzed. PCT initial value is higher in patients who underwent radiotherapy, and it could be related to the higher rate of their postoperative complications. Patients with a tissue expander with a volume ≥ 500 cc show an increasing trend for CRP in time (p = 0.009). Conclusions. Several risk factors (prolonged time of drains, age older than 60 years, and radiotherapy) have been confirmed by our study. The study of markers in the periprosthetic fluid with respect to their study in plasma could point toward earlier infection detection and support early management.
Laboratory Model Test to Explore the Bearing Mechanism of Composite Foundation in the Loess Area
Authors: Xu Longfei , Xu Weijiang , Zhang Aijun , Weng Xiaolin , Zhao Gaowen , Zhu Tantan
Published: March 2021

Pile composite foundation can make good use of the bearing capacity of the soil and pile, which is widely used in the Chinese northwest loess area. However, the theory of pile composite foundation is far from sufficient, hindering its long‐term development. Aiming at this problem, a laboratory model test of pile composite foundation in the loess area was conducted to explore the common working mechanism and variations of each bearing stage. Besides, the settlement of the single pile composite foundation was calculated by using the modified tangent modulus method, and the result was compared with the experimental data. The main results of this paper are as follows: Both in the single pile and single pile composite foundation, loading‐settlement curves showed a trend of “elastic to elastoplastic to plastic,” accompanied by the appearance of plummeting point. Influenced by the pile group effect, the loading‐settlement curve of the group pile composite foundation showed a slow‐varying trend without an obvious breakdown point. Pile axis stress increased with the growth of upper load. At the beginning of loading, the pile axis stress indicated such a distribution that stress on both ends of the pile was larger than that in the middle of the pile. When reaching a certain load, the location of the biggest pile axis stress transferred to the pile top, and the pile axis stress decreased gradually as the pile became deep. The side friction resistance in the static load test of the single pile was always positive, whereas in the composite foundation of a single pile and a group of piles, negative side resistance appeared in the upper side of the neutral point. Pile‐soil stress ratio in the depth of 12 cm changed with the upper load. The outcome calculated by the modified tangent modulus method had a relatively better consistency with experimental data if the upper load was not too large.
Efficacy of Alkaloids in Alleviating Myocardial Ischemia‐Reperfusion Injury in Rats: A Meta‐Analysis of Animal Studies
Authors: Wang Shuai , Liu Han , Zhang Yang , Ren Liqun
Published: March 2021

Background. Animal models are well established for studying the effects of alkaloids in preventing myocardial ischemia‐reperfusion injury. However, few studies have investigated the therapeutic effects of alkaloids in humans. This meta‐analysis and systematic review assessed the efficacy of alkaloids in attenuating infarct size in rats with myocardial ischemia‐reperfusion injury. Methods. An integrated literature search including the PubMed, Embase, and Cochrane Library databases was performed to identify studies that evaluated the therapeutic effects of alkaloids on myocardial ischemia‐reperfusion injury in rats. The main outcome was infarct size, and SYRCLE’s risk of bias tool was used to assess the quality of the studies. Results. 22 studies were brought into the meta‐analysis. Compared with the effects of vehicle, alkaloids significantly reduced infarct size (standardized mean difference (SMD) = −0.45; 95% confidence interval (CI) = −0.64 to − 0.26). In subgroup analyses, isoquinoline alkaloids (SMD = −0.43; 95%CI = −0.70 to − 0.16) significantly reduced infarct size versus the control. Conclusion. Isoquinoline alkaloids can potentially alleviate myocardial ischemia‐reperfusion injury. This meta‐analysis and systematic review supply a reference for research programs aiming to develop alkaloid‐based clinical drugs. This trial is registered with CRD42019135489.
Modeling NOx Emissions with an Intelligent Combinatorial Algorithm
Authors: Chen XiaoJuan , Zhang Haiyang , Xing Xiaoxue , Qin Hongwu
Published: March 2021

Coal combustion is considered to be the key source of nitrogen oxide (NOx) emissions in thermal power plants. Methods for effective reduction in these emissions are critically sought on the national and global levels. Such methods typically achieve this goal through accurate modeling and prediction. However, such modeling process is difficult because of the complexity of the NOx emission mechanisms and the influence of many factors. Furthermore, real-operation data of power plants tend to be centralized in some local areas because of working condition experiment so that no single model can deal with the complicated and changeable boiler production processes. In this paper, we address this problem and propose a model intelligent combinatorial algorithm (MICA). First, the actual production data are preprocessed by a wavelet denoising algorithm, and the model input variables are selected based on a random forest algorithm. Then, several models for NOx emission prediction are constructed by various data-driven algorithms. Finally, a C4.5 algorithm is applied to intelligently combine these models. The experimental results indicate that the proposed algorithm can construct an accurate prediction model for NOx emissions based on actual operating data. The mean absolute percentage errors are within 1%. Moreover, a correlation of 0.98 between predicted and measured values was obtained by applying the MICA model.
Positively Charged Nanoparticle Delivery of n‐Butylidenephthalide Enhances Antitumor Effect in Hepatocellular Carcinoma
Authors: Chang Kai-Fu , Huang Xiao-Fan , Lin Yu-Ling , Liao Kuang-Wen , Hsieh Ming-Chang , Chang Jinghua Tsai , Tsai Nu-Man
Published: March 2021

Hepatocellular carcinoma (HCC) is the second and sixth leading cause of cancer death in men and woman in 185 countries statistics, respectively. n‐Butylidenephthalide (BP) has shown anti‐HCC activity, but it also has an unstable structure that decreases its potential antitumor activity. The aim of this study was to investigate the cell uptake, activity protection, and antitumor mechanism of BP encapsulated in the novel liposome LPPC in HCC cells. BP/LPPC exhibited higher cell uptake and cytotoxicity than BP alone, and combined with clinical drug etoposide (VP‐16), BP/LPPC showed a synergistic effect against HCC cells. Additionally, BP/LPPC increased cell cycle regulators (p53, p‐p53, and p21) and decreased cell cycle‐related proteins (Rb, p‐Rb, CDK4, and cyclin D1), leading to cell cycle arrest at the G0/G1 phase in HCC cells. BP/LPPC induced cell apoptosis through activation of both the extrinsic (Fas‐L and Caspase‐8) and intrinsic (Bax and Caspase‐9) apoptosis pathways and activated the caspase cascade to trigger HCC cell death. In conclusion, the LPPC complex improved the antitumor activity of BP in terms of cytotoxicity, cell cycle regulation and cell apoptosis, and BP/LPPC synergistically inhibited cell growth during combination treatment with VP‐16 in HCC cells. Therefore, BP/LPPC is potentially a good candidate for clinical drug development or for use as an adjuvant for clinical drugs as a combination therapy for hepatocellular carcinoma.
Archive as a Depository of Shared Memories, History and Identity
Authors:   Institute for Migration and Ethnic Studies, Kudra Beroš Viktorija
Published: March 2021

Given their role in the preservation and protection of an authentic and credible trace of the past (documents) and, consequently, national identity, archives are considered places of choice for interpreting and representing shared memory and the past. Emphasising authenticity and credibility frames archives as seemingly neutral institutions in terms of politics and ideology. However, the trace that provides an insight into the “truth and knowledge” of our (individual and collective) past “that makes us what we are” needs to be questioned. Since the archiving procedure is based on the processes of inclusion and exclusion in all segments of everyday interpretation of material, the archive is a political and ideological institution that takes its place in the order of political power. This paper discusses the role of the archive as a place of preservation of “shared past and history” as an important part of national identity through the prism of institutional apparatuses or forms of knowledge/power (example of architecture) and technologies or manners of articulating and practising knowledge/power (example of everyday practice). The paper points to the role of archives in the (re)interpretation and (re)vision of shared memories, collective history and national identity on the examples of the Croatian State Archives and Archives of Yugoslavia, in the context of changes in the symbolic and political order (SFRY/Croatia). By constructing national memory and narratives of nationality through narratives of history and memory, and by constructing “truth” (knowledge) through exclusion and inclusion, archives (just like museums and libraries) have a role to play in “imagining” the community–nation. Or, according to the theory of performative identity (Foritier 2000), everyday practice that takes place in archives is an institutional identity practice that contributes to the unification and homogenisation of the community through a policy of interpretation by performing and producing (performative) memory (collective identity formation).
Pandemic Management Systems and Migration
Authors:   Institute for Migration and Ethnic Studies, Zagreb, Croatia, Gregurović Margareta , Gregurović Snježana ,   Institute for Migration and Ethnic Studies, Zagreb, Croatia, Kumpes Josip ,   Institute for Migration and Ethnic Studies, Zagreb, Croatia, Kuti Simona ,   Institute for Migration and Ethnic Studies, Zagreb, Croatia, Lazanin Sanja ,   Institute for Migration and Ethnic Studies, Zagreb, Croatia, Mlinarić Dubravka ,   Institute for Migration and Ethnic Studies, Zagreb, Croatia
Published: March 2021

Fast development and transmission of disease poses a health threat for a larger population and affects the functioning of almost all social systems, both within and outside nation-state borders, thus also affecting the possibilities of free migration and movement. The main aim of this article is to discuss the principal mechanisms of disease control in relation to migration in various socio-historical contexts. It identifies and compares historical patterns and contemporary measures of preventive control systems while considering the wider social context and migrants’ specific position. This paper combines the historical insights into various administrative and political systems in Europe and Croatia that have sought adequate measures to prevent the spread of infectious diseases with the current state of the affair in the fight against the COVID-19 pandemic. As part of the regulation and management of the contemporary COVID-19 pandemic, restrictions have been introduced on cross-border movement and travel. Those restrictions and quarantine measures have abruptly halted not only international but also migration within the borders of nation-states, especially during the first wave of the pandemic in spring 2020. Emphasis has been placed on the effects of the COVID-19 pandemic on labour and forced migration, as well as on the trends in public attitudes on immigrants affected by pandemic management mechanisms.
EWS-FLI1 and Menin Converge to Regulate ATF4 Activity in Ewing Sarcoma
Authors: Jiménez Jennifer A. , Apfelbaum April A. , Hawkins Allegra G. , Svoboda Laurie K. , Kumar Abhijay , Ruiz Ramon Ocadiz , Garcia Alessandra X. , Haarer Elena , Nwosu Zeribe C. , Bradin Joshua , Purohit Trupta , Chen Dong , Cierpicki Tomasz , Grembecka Jolanta , Lyssiotis Costas A. , Lawlor Elizabeth R.
Published: March 2021

Ewing sarcomas are driven by EWS–ETS fusions, most commonly EWS-FLI1, which promotes widespread metabolic reprogramming, including activation of serine biosynthesis. We previously reported that serine biosynthesis is also activated in Ewing sarcoma by the scaffolding protein menin through as yet undefined mechanisms. Here, we investigated whether EWS-FLI1 and/or menin orchestrate serine biosynthesis via modulation of ATF4, a stress-response gene that acts as a master transcriptional regulator of serine biosynthesis in other tumors. Our results show that in Ewing sarcoma, ATF4 levels are high and that ATF4 modulates transcription of core serine synthesis pathway (SSP) genes. Inhibition of either EWS-FLI1 or menin leads to loss of ATF4, and this is associated with diminished expression of SSP transcripts and proteins. We identified and validated an EWS–FLI1 binding site at the ATF4 promoter, indicating that the fusion can directly activate ATF4 transcription. In contrast, our results suggest that menin-dependent regulation of ATF4 is mediated by transcriptional and post-transcriptional mechanisms. Importantly, our data also reveal that the downregulation of SSP genes that occurs in the context of EWS-FLI1 or menin loss is indicative of broader inhibition of ATF4-dependent transcription. Moreover, we find that menin inhibition similarly leads to loss of ATF4 and the ATF4-dependent transcriptional signature in MLL-rearranged B-cell acute lymphoblastic leukemia, extending our findings to another cancer in which menin serves an oncogenic role.

Implications:

These studies provide new insights into metabolic reprogramming in Ewing sarcoma and also uncover a previously undescribed role for menin in the regulation of ATF4.
Dasatinib Stimulates Its Own Mechanism of Resistance by Activating a CRTC3/MITF/Bcl-2 Pathway in Melanoma with Mutant or Amplified c-Kit
Authors: Sabbah Malak , Krayem Mohammad , Najem Ahmad , Sales François , Miller Wilson , del Rincon Sonia , Awada Ahmad , Ghanem Ghanem E. , Journe Fabrice
Published: March 2021

Amplification or activating mutations of c-Kit are a frequent oncogenic alteration, which occurs commonly in acral and mucosal melanoma. Among c-Kit inhibitors, dasatinib is the most active due to its ability to bind both active and inactive conformations of the receptor. However, its use as a single agent in melanoma showed limited clinical benefit. We first found that sensitivity to dasatinib is restricted to melanoma cell lines harboring c-Kit alteration but, unexpectedly, we observed lower effect at higher concentrations that can readily be found in patient blood. We then investigated relevant pathway alterations and found complete inhibition of MAPK and PI3K/AKT pathways but an increase in MITF and its downstream target Bcl-2 through CRTC3 pathway, which turn on the CREB regulated transcription of MITF. More importantly, dasatinib upregulates MITF and Bcl-2 through SIK2 inhibition revealed by CRTC3 reduced phosphorylation, CREB transcription activation of MITF, MITF transcription activation of Bcl-2 as well as pigmentation. Furthermore, overexpression of MITF renders melanoma cells resistant to all dasatinib concentrations. Selective Bcl-2 inhibition by ABT-199 or Bcl-2 knockout restores the sensitivity of melanoma cells to dasatinib, validating the involvement of MITF and Bcl-2 axis in the resistance of melanoma to dasatinib. In conclusion, we showed for the first time that dasatinib in melanoma stimulates its proper mechanism of resistance, independently of MAPK and PI3K/AKT pathways reactivation commonly associated to secondary c-Kit mutations, but through CRTC3/MITF/Bcl-2 pathway activation at clinically relevant doses which may explain the weak clinical benefit of dasatinib in patients with melanoma.

Implications:

Dasatinib stimulates its proper mechanism of resistance through CRTC3/MITF/Bcl-2 pathway, which may explain its modest clinical efficiency in patients with melanoma.
Local Passive Heat for the Treatment of Hypertension in Autonomic Failure
Authors: Okamoto Luis E. , Celedonio Jorge E. , Smith Emily C. , Gamboa Alfredo , Shibao Cyndya A. , Diedrich André , Paranjape Sachin Y. , Black Bonnie K. , Muldowney James A. S. , Peltier Amanda C. , Habermann Ralf , Crandall Craig G. , Biaggioni Italo
Published: March 2021

Background

Supine hypertension affects a majority of patients with autonomic failure; it is associated with end‐organ damage and can worsen daytime orthostatic hypotension by inducing pressure diuresis and volume loss during the night. Because sympathetic activation prevents blood pressure (BP) from falling in healthy subjects exposed to heat, we hypothesized that passive heat had a BP‐lowering effect in patients with autonomic failure and could be used to treat their supine hypertension.

Methods and Results

In Protocol 1 (n=22), the acute effects of local heat (40–42°C applied with a heating pad placed over the abdomen for 2 hours) versus sham control were assessed in a randomized crossover fashion. Heat acutely decreased systolic BP by −19±4 mm Hg (versus 3±4 with sham,
P
<0.001) owing to decreases in stroke volume (−18±5% versus −4±4%,
P
=0.013 ) and cardiac output (−15±5% versus −2±4%,
P
=0.013). In Protocol 2 (proof‐of‐concept overnight study; n=12), we compared the effects of local heat (38°C applied with a water‐perfused heating pad placed under the torso from 10 
pm
to 6 
am
) versus placebo pill. Heat decreased nighttime systolic BP (maximal change −28±6 versus −2±6 mm Hg,
P
<0.001). BP returned to baseline by 8 
am
. The nocturnal systolic BP decrease correlated with a decrease in urinary volume (
r
=0.57,
P
=0.072) and an improvement in the morning upright systolic BP (
r
=−0.76,
P
=0.007).

Conclusions

Local heat therapy effectively lowered overnight BP in patients with autonomic failure and supine hypertension and offers a novel approach to treat this condition. Future studies are needed to assess the long‐term safety and efficacy in improving nighttime fluid loss and daytime orthostatic hypotension.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifiers: NCT02417415 and NCT03042988.
Infusing Finetuning with Semantic Dependencies
Authors: Wu Zhaofeng , Peng Hao , Smith Noah A.
Published: March 2021

For natural language processing systems, two kinds of evidence support the use of text representations from neural language models “pretrained” on large unannotated corpora: performance on application-inspired benchmarks (Peters et al., 2018, inter alia), and the emergence of syntactic abstractions in those representations (Tenney et al., 2019, inter alia). On the other hand, the lack of grounded supervision calls into question how well these representations can ever capture meaning (Bender and Koller, 2020). We apply novel probes to recent language models— specifically focusing on predicate-argument structure as operationalized by semantic dependencies (Ivanova et al., 2012)—and find that, unlike syntax, semantics is not brought to the surface by today’s pretrained models. We then use convolutional graph encoders to explicitly incorporate semantic parses into task-specific finetuning, yielding benefits to natural language understanding (NLU) tasks in the GLUE benchmark. This approach demonstrates the potential for general-purpose (rather than task-specific) linguistic supervision, above and beyond conventional pretraining and finetuning. Several diagnostics help to localize the benefits of our approach.1