bluuebunny/crossref_metadata_2025_split huggingface dataset:
White light emission and thermoluminescence studies of Dy3+‐activated hardystonite (Ca2ZnSi2O7) phosphor
Authors: Chandraker Siteshwari , Kaur Jagjeet , Priya Ruby , Dubey Vikas , Dubey Neha 
Published: May 2021

AbstractHere, we report the photoluminescence and thermoluminescent properties of Dy‐activated Ca2ZnSi2O7 phosphors synthesized using the solid‐state method. The synthesized phosphors showed hardystonite type structure, and had micron‐sized particles. Fourier transform infrared spectroscopy (FTIR) showed the existence of the functional groups and confirmed the formation of phosphor and photoluminescence techniques. The phosphors under excitation at 239 nm exhibited green‐yellow emission spectra in the region 481–575 nm corresponding to the 4F9/2→6H15/2 and 4F9/2→6H13/2 transitions of Dy3+ ions. The Commission Internationale de l'Eclairage (CIE) coordinates were achieved to be (0.25, 0.27), which was narrowly close to the white region. Thermoluminescence (TL) glow curve analysis of prepared Dy3+‐activated Ca2ZnSi2O7 phosphors were recorded for different ultraviolet (UV) light exposure times and found to have a linear response with dose. The TL glow curves, recorded with various UV exposure times ranging from 5 to 25 min, showed a linear response with dosage. The corresponding kinetic parameters were also calculated using a computerized glow curve deconvolution (CGCD) technique. Activation energy was observed to enhance the increase in the peak temperature and its value was substantially higher for the third peak fitted using CGCD. The obtained results indicated that the synthesized pristine phosphors could be potentially used for lighting, displays, and dosimetric applications.
Zerumbone, a ginger sesquiterpene, inhibits migration, invasion, and metastatic behavior of human malignant glioblastoma multiforme in vitro
Authors: Jalili‐Nik Mohammad , Afshari Amir R. , Sabri Hamed , Bibak Bahram , Mollazadeh Hamid , Sahebkar Amirhossein 
Published: May 2021

AbstractThe most widespread and challenging aggressive malignant tumor in the brain is glioblastoma multiforme (GBM). GBM is characterized, in particular, by significant intratumor cell variability, high growth rates, and widespread invasiveness within the surrounding normal brain parenchyma. The present study aimed to examine the impact of the natural product Zerumbone, a promising sesquiterpenoid phytochemical from Zingiber zerumbet, on U‐87 MG GBM cells and its underlying molecular mechanisms. At sub‐lethal doses, Zerumbone exerted a concentration‐ and time‐dependent suppression of cell migration ability utilizing scratch wound closure assay; it also inhibited GBM cells' invasion using Transwell invasion assay in a concentration‐dependent fashion. The enzymatic activity of matrix metalloproteinase (MMP)‐2/‐9 and their protein expression has also been reduced by administration of Zerumbone. Furthermore, Zerumbone was revealed to downregulate the mRNA expression level of IL‐1β and MCP‐1, two genes contributing to MMPs expression. We also found that Zerumbone exerted an inhibitory effect on the expression of Akt and total p44/42 MAPK (Erk1/Erk2) against U‐87 MG cells. These findings collectively provide further proof for the possible molecular signaling basis of the antimetastatic effects of Zerumbone as a promising phytochemical, indicating a therapeutic strategy for the treatment of GBM through repression of migration, invasion, and metastasis.
Can tendon reflexes be elicited by both stretch and vibration in man?
Authors: Tfelt‐Hansen Peer , Meritam Larsen Pirgit , van Deurs Ulla , Fabricius Martin 
Published: May 2021

AbstractAim of studyWhen the biceps tendon is tapped, a contraction is elicited in the biceps muscle. This also occurs with tapping of the radial bone, and it has been suggested that vibration is a stimulus for deep tendon reflexes. We investigated whether the normal stimulus for the deep tendon reflex is a sudden stretch, a phasic vibration, or both. Furthermore, we investigated the importance of forearm position for the reflex response in controls and stroke patients.MethodsWe investigated 50 neurological outpatients without clinical signs of neurological disorders in the arms. The biceps tendon and distal radius were tapped with the forearm in the midway (90°), supinated, and pronated positions. In 10 of these patients, the two reflexes were also investigated with quantitative electromyography (EMG) measurements in the 3 positions. Another 10 patients were investigated clinically when stretch of elbow was eliminated and 17 patients were examined when prestretching of the biceps tendon was avoided. Finally, we examined 32 patients that had experienced stroke.ResultsIn 94% (47/50) of patients, after a radial tap, the biceps contraction disappeared in the supinated forearm, and the median peak‐to‐peak amplitude of the surface EMG response (n = 10) decreased from 1.1 to 0.2 mV (p < .01). Elimination of elbow stretch as well as pressure on the biceps tendon did not change the reflex response. In 84% (27/32) of stroke patients, after a radial tap, the biceps contraction persisted in supination in the arm with hyperreflexia.ConclusionThe combined clinical and EMG results are consistent with the concept that the deep tendon reflexes in man can be elicited by both stretch and phasic vibration. Clinicians should be aware that the brachioradial reflex depends on the forearm position.
Structural and functional characterization of multiple myeloma associated cytoplasmic poly(A) polymerase FAM46C
Authors: Zhang Hong , Zhang Shi‐Hui , Hu Jia‐Li , Wu Yu‐Tong , Ma Xiao‐Yan , Chen Yang , Yu Bing , Liao Shuang , Huang Huilin , Gao Song 
Published: May 2021

AbstractBackgroundMultiple myeloma (MM) is a hematologic malignancy characterized by the accumulation of aberrant plasma cells within the bone marrow. The high frequent mutation of family with sequence similarity 46, member C (FAM46C) is closely related with the occurrence and progression of MM. Recently, FAM46C has been identified as a non‐canonical poly(A) polymerase (PAP) that functions as a tumor suppressor in MM. This study aimed to elucidate the structural features of this novel non‐canonical PAP and how MM‐related mutations affect the structural and biochemical properties of FAM46C, eventually advancing our understandings towards FAM46C mutation‐related MM occurrence.MethodsWe purified and crystallized a mammalian FAM46C construct, and solved its structure. Next, we characterized the property of FAM46C as a PAP through a combination of structural analysis, site‐directed mutagenesis and biochemical assays, and by comparison with its homolog FAM46B. Finally, we structurally analyzed MM‐related FAM46C mutations and tested the enzymatic activity of corresponding mutants.ResultsWe determined the crystal structure of a mammalian FAM46C protein at 2.35 Å, and confirmed that FAM46C preferentially consumed adenosine triphosphate (ATP) and extended A‐rich RNA substrates. FAM46C showed a weaker PAP activity than its homolog FAM46B, and this difference was largely dependent on the residue variance at particular sites. Of them, residues at positions 77, 290, and 298 of mouse FAM46C were most important for the divergence in enzymatic activity. Among the MM‐associated FAM46C mutants, those residing at the catalytic site (D90G and D90H) or putative RNA‐binding site (I155L, S156F, D182Y, F184L, Y247V, and M270V) showed abolished or compromised PAP activity of FAM46C, while N72A and S248A did not severely affect the PAP activity. FAM46C mutants D90G, D90H, I155L, S156F, F184L, Y247V, and M270V had significantly lower inhibitory effect on apoptosis of RPMI‐8226 cells as compared to wild‐type FAM46C.ConclusionsFAM46C is a prokaryotic‐like PAP with preference for A‐rich RNA substrates, and showed distinct enzymatic efficiency with its homolog FAM46B. The MM‐related missense mutations of FAM46C lead to various structural and biochemical outcomes to the protein.
Counselling in football: Who is caring for the players that don’t make the cut?
Authors: Wilkinson Richard 
Published: May 2021

AbstractA high percentage of young football players enter into the world of football through academies, with the hope of one day making it to an elite professional level and representing their football club or even our national team. The reality is that <0.5% will achieve their dreams. This article explores counselling and psychotherapy support in place within football clubs, opening areas of concern that need to be highlighted by all within the game. New research offers us a greater understanding of how mental health support operates within top tier football clubs by the sports psychologist and the counsellor or psychotherapist. This article will also look at evolving infrastructures in football clubs outside the UK and how they offer mental health support to their players. This author has personal experience of deselection and is currently studying this area. He proposes that a system to support these players through counselling/psychotherapy sessions could help the football club manage players and staff with mental health issues and, above all, potentially support, protect and save the lives of some of our most vulnerable academy players following deselection.
Spatial semantic graph enhanced monocular SLAM System
Authors: Xu Zezi , Xiao Shuangjiu 
Published: May 2021

AbstractMore and more applications require accurate estimation of objects' poses. For example, Augmented Reality (AR) needs that for interactions among virtual and real objects. However, recent object‐level Simultaneous Localization and Mapping (SLAM) systems care more about trajectories than poses of objects. So, in this paper, we present SSG SLAM: a monocular SLAM system based on Spatial Semantic Graph (SSG), leveraging spatial relations to achieve good estimation of objects' poses. First, we put forward the design of SSG to organize objects and their spatial relations. Then, SSG is utilized in a monocular object SLAM and new constraints are proposed based on spatial relations. Finally, experimental evaluations performed on SSG‐Dataset show that our approach outperforms the baseline object SLAM system, as well as providing visual consistency in an AR demo.
Cytotoxic 1,2,3‐Triazoles as Potential Leads Targeting the S100A2‐p53 Complex: Synthesis and Cytotoxicity
Authors: Sun Jufeng , Baker Jennifer R. , Russell Cecilia C. , Cossar Peter J. , Ngoc Thuy Pham Hong , Sakoff Jennette A. , Scarlett Christopher J. , McCluskey Adam 
Published: May 2021

AbstractIn silico screening predicted 1 (N‐(4‐((4‐(3‐(4‐(3‐methoxyphenyl)‐1H‐1,2,3‐triazol‐1‐yl)propyl)piperazin‐1‐yl) sulfonyl)‐phenyl)acetamide) as an inhibitor of the S100A2‐p53 protein‐protein interaction. S100A2 is a validated pancreatic cancer drug target. In the MiaPaCa‐2 pancreatic cell line, 1 was a ∼50 μM growth inhibitor. Synthesis of five focused compound libraries and cytotoxicity screening revealed increased activity from the presence of electron withdrawing moieties on the sulfonamide aromatic ring, with the 3,5‐bis‐CF3 Library 3 analogues the most active, with GI50 values of 0.91 (3‐ClPh; 13 i; BxPC‐3, Pancreas) to 9.0 μM (4‐CH3; 13 d; PANC‐1, Pancreas). Activity was retained against an expanded pancreatic cancer cell line panel (MiaPaCa‐2, BxPC‐3, AsPC‐1, Capan‐2, PANC‐1 and HPAC) and the normal cell line MCF10A (breast). Bulky 4‐disposed substituents on the terminal phenyl ring enhanced broad spectrum activity with growth inhibition values spanning 1.1 to 3.1 μM (4‐C(CH3)3; 13 e; BxPC‐3 and AsPC‐1 (pancreas), respectively). Central alkyl spacer contraction from propyl to ethyl proved detrimental to activity with Library 4 and 5.5‐ to 10‐fold less cytotoxic than the propyl linked Library 2 and Library 3. The data herein was consistent with the predicted binding poses of the compounds evaluated. The highest levels of cytotoxicity were observed with those analogues best capable of adopting a near identical pose to the p53‐peptide in the S100A2‐p53 binding groove.
Coprescription of Opioids With Other Medications and Risk of Opioid Overdose
Authors: Khan Nazleen F. , Bykov Katsiaryna , Glynn Robert J. , Barnett Michael L. , Gagne Joshua J. 
Published: May 2021

Polypharmacy is common among patients taking prescription opioids long‐term, and the codispensing of interacting medications may further increase opioid overdose risk. To identify nonopioid medications that may increase opioid overdose risk in this population, we conducted a case‐crossover‐based screening of electronic claims data from IBM MarketScan and Optum Clinformatics Data Mart spanning 2003 through 2019. Eligible patients were 18 years of age or older and had at least 180 days of continuous enrollment and 90 days of prescription opioid use immediately before an opioid overdose resulting in an emergency room visit or hospitalization. The main analysis quantified the odds ratio (OR) between opioid overdose and each nonopioid medication dispensed in the 90 days immediately before the opioid overdose date after adjustment for prescription opioid dosage and benzodiazepine codispensing. Additional analyses restricted to patients without cancer diagnoses and individuals who used only oxycodone for 90 days immediately before the opioid overdose date. The false discovery rate (FDR) was used to account for multiple testing. We identified 24,866 individuals who experienced opioid overdose. Baclofen (OR 1.56; FDR < 0.01; 95% confidence interval (CI), 1.29 to 1.89), lorazepam (OR 1.53; FDR < 0.01; 95% CI, 1.25 to 1.88), and gabapentin (OR 1.16; FDR = 0.09; 95% CI, 1.04 to 1.28), among other nonopioid medications, were associated with opioid overdose. Similar patterns were observed in noncancer patients and individuals who used only oxycodone. Interventions may focus on prescribing safer alternatives when a potential for interaction exists.
Assessing the Impact of US Food and Drug Administration Breakthrough Therapy Designation Timing on Trial Characteristics and Development Speed
Authors: Pregelj Lisette , Hine Damian C. , Kesselheim Aaron S. , Darrow Jonathan J. 
Published: May 2021

The US Congress created the Breakthrough Therapy designation in 2012 to expedite drug development and review through efficient clinical trial design and intensive interaction with US Food and Drug Administration (FDA) reviewers. Yet, of the 116 pivotal trials supporting Breakthrough‐designated drugs approved 2013–2018, 96 (83%) were already underway or completed when the designation was granted, limiting the potential of the designation to influence trial design. We found no difference between these trials and the 20 (17%) that had not yet begun when the designation was granted (which had greater potential to be impacted by the designation) with respect to phase, size, intervention model (single‐arm vs. multi‐arm), or use of surrogate end points under the Accelerated Approval (AA) pathway. This finding suggests that, in contrast to previous studies, observed trial characteristics were not likely attributable to the designation, and instead other factors such as disease category (e.g., oncology) may be driving both trial design and Breakthrough designation. The 20 trials in our sample that began after designation was granted were, however, over 8 months shorter than trials of nondesignated drugs. This suggests that designations granted early in clinical development may reduce trial time by influencing aspects of clinical programs other than design characteristics, such as timelines for FDA responses. Alternately, certain drugs may be more likely to both receive an early designation and have a shorter trial duration, for example, because of therapeutic category or large effect size.
Network traffic prediction method based on autoregressive integrated moving average and adaptive Volterra filter
Authors: Tian Zhongda , Li Feihong 
Published: May 2021

SummaryIn the process of controlling network congestion and network management, how to accurately predict network traffic is very important. A network traffic prediction method based on autoregressive integrated moving average (ARIMA) model and adaptive Volterra filter model is proposed in this study. Firstly, ARIMA model is utilized to capture and predict the linear features of network traffic time series. The residual sequence is generated by network traffic sequence minus ARIMA predictive value sequence. The residual sequence only contains the nonlinear characteristics of original network traffic. Then an adaptive Volterra filter is used to train and predict the nonlinear residual sequence of original network traffic. The optimal parameters of adaptive Volterra filter are obtained by improved particle swarm optimization algorithm. Add the linear value predicted by ARIMA and the nonlinear value predicted by adaptive Volterra filter to get the final predicted value. The simulation results show that the proposed prediction method has high accuracy, small prediction error, and high reliability.
High concentrations of environmental ammonia induced changes in large‐scale loach (Paramisgurnus dabryanus) immunity
Authors: Zhang Yun‐Long , Shang Ze‐Hao , Wang Guang‐Yi , You Kun , Mi Di 
Published: May 2021

AbstractHigh concentrations of environmental ammonia can cause reduced immunity and death in fish, causing enormous economic losses. Air‐breathing fish usually have a high ammonia tolerance and are very suitable for high‐density fish farming. However, research on the effects of environmental ammonia on air‐breathing fish immunity is lacking. Therefore, this study investigated the effects of environmental ammonia on the immunity of large‐scale loach (Paramisgurnus dabryanus) by exposing fish to 30 mmol/L NH4Cl solution and subsequently analyzing the changes in serum and liver immune indicators, including total protein, albumin, globulin, immunoglobulin (Ig) M, lysozyme, complement component (C) 3 and C4, heat shock protein (HSP) 70, HSP90, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, and IL‐12. Results revealed that ammonia exposure significantly affected the total protein, albumin, globulin, IgM, complement C3 and C4, HSP70, HSP90, and inflammatory cytokine contents in the body, indicating that ammonia exposure induced a significant immune response and lowered bodily immunity. However, most of the immune indicators significantly decreased in the later stages of the experiment, suggesting a weakened immune response, which may be due to the species‐specific ammonia detoxification ability of large‐scale loach that reduces ammonia toxicity in the body.
Cost‐effectiveness of left ventricular assist devices as destination therapy in the United Kingdom
Authors: Schueler Stephan , Silvestry Scott C. , Cotts William G. , Slaughter Mark S. , Levy Wayne C. , Cheng Richard K. , Beckman Jennifer A. , Villinger Jonas , Ismyrloglou Eleni , Tsintzos Stelios I. , Mahr Claudius 
Published: May 2021

AbstractAimsContinuous‐flow left ventricular assist devices (LVADs) as destination therapy (DT) are a recommended treatment by National Institute for Health and Care Excellence England for end‐stage heart failure patients ineligible for cardiac transplantation. Despite the fact that DT is frequently used as an LVAD indication across other major European countries and the United States, with consistent improvements in quality‐of‐life and longevity, National Health Service (NHS) England does not currently fund DT, mainly due to concerns over cost‐effectiveness. On the basis of the recently published ENDURANCE Supplemental Trial studying DT patients, we assessed for the first time the cost‐effectiveness of DT LVADs compared with medical management (MM) in the NHS England.Methods and resultsWe developed a Markov multiple‐state economic model using NHS cost data. LVAD survival and adverse event rates were derived from the ENDURANCE Supplemental Trial. MM survival was based on Seattle Heart Failure Model estimates in the absence of contemporary clinical trials for this population. Incremental cost‐effectiveness ratios (ICERs) were calculated over a lifetime horizon. A discount rate of 3.5% per year was applied to costs and benefits. Deterministic ICER was £46 207 per quality‐adjusted life year (QALY). Costs and utilities were £204 022 and 3.27 QALYs for the LVAD arm vs. £77 790 and 0.54 QALYs for the MM arm. Sensitivity analyses confirmed robustness of the primary analysis.ConclusionsThe implantation of the HeartWare™ HVAD™ System in patients ineligible for cardiac transplantation as DT is a cost‐effective therapy in the NHS England healthcare system under the end‐of‐life willingness‐to‐pay threshold of £50 000/QALY, which applies for VAD patients.
Moving beyond Volatility Index (VIX): HARnessing the term structure of implied volatility
Authors: Clements Adam , Liao Yin , Tang Yusui 
Published: May 2021

AbstractThis paper considers how information from the implied volatility (IV) term structure can be harnessed to improve stock return volatility forecasting within the state‐of‐the‐art HAR model. Factors are extracted from the IV term structure and included as exogenous variables in the HAR framework. We found that including slope and curvature factors leads to significant forecast improvements over the HAR benchmark at a range of forecast horizons, compared with the standard HAR model and HAR model with VIX as IV information set.
An introduction to deep generative modeling
Authors: Ruthotto Lars , Haber Eldad 
Published: May 2021

AbstractDeep generative models (DGM) are neural networks with many hidden layers trained to approximate complicated, high‐dimensional probability distributions using samples. When trained successfully, we can use the DGM to estimate the likelihood of each observation and to create new samples from the underlying distribution. Developing DGMs has become one of the most hotly researched fields in artificial intelligence in recent years. The literature on DGMs has become vast and is growing rapidly. Some advances have even reached the public sphere, for example, the recent successes in generating realistic‐looking images, voices, or movies; so‐called deep fakes. Despite these successes, several mathematical and practical issues limit the broader use of DGMs: given a specific dataset, it remains challenging to design and train a DGM and even more challenging to find out why a particular model is or is not effective. To help advance the theoretical understanding of DGMs, we introduce DGMs and provide a concise mathematical framework for modeling the three most popular approaches: normalizing flows, variational autoencoders, and generative adversarial networks. We illustrate the advantages and disadvantages of these basic approaches using numerical experiments. Our goal is to enable and motivate the reader to contribute to this proliferating research area. Our presentation also emphasizes relations between generative modeling and optimal transport.