bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced Data Encryption ​using 2D Materials
Authors: Wen Chao , Li Xuehua , Zanotti Tommaso , Puglisi Francesco Maria , Shi Yuanyuan , Saiz Fernan , Antidormi Aleandro , Roche Stephan , Zheng Wenwen , Liang Xianhu , Hu Jiaxin , Duhm Steffen , Roldan Juan B. , Wu Tianru , Chen Victoria , Pop Eric , Garrido Blas , Zhu Kaichen , Hui Fei , Lanza Mario
Published: May 2021

Advanced data encryption requires the use of true random number generators (TRNGs) to produce unpredictable sequences of bits. TRNG circuits with high degree of randomness and low power consumption may be fabricated by using the random telegraph noise (RTN) current signals produced by polarized metal/insulator/metal (MIM) devices as entropy source. However, the RTN signals produced by MIM devices made of traditional insulators, i.e., transition metal oxides like HfO2 and Al2O3, are not stable enough due to the formation and lateral expansion of defect clusters, resulting in undesired current fluctuations and the disappearance of the RTN effect. Here, the fabrication of highly stable TRNG circuits with low power consumption, high degree of randomness (even for a long string of 224 − 1 bits), and high throughput of 1 Mbit s−1 by using MIM devices made of multilayer hexagonal boron nitride (h‐BN) is shown. Their application is also demonstrated to produce one‐time passwords, which is ideal for the internet‐of‐everything. The superior stability of the h‐BN‐based TRNG is related to the presence of few‐atoms‐wide defects embedded within the layered and crystalline structure of the h‐BN stack, which produces a confinement effect that avoids their lateral expansion and results in stable operation.
Antimicrobial Surfaces for Applications on Confined Inhabited Space Stations
Authors: Wang Mengjiao , Duday David , Scolan Emmanuel , Perbal Séverine , Prato Mirko , Lasseur Christophe , Hołyńska Małgorzata
Published: May 2021

An overview of the current surface treatments/coatings that introduce antimicrobial properties to the exposed surfaces in confined space stations is provided. General aspects, such as biofilm formation and the specific requirements associated with this application, are discussed. Antimicrobial coatings used on the International Space Station (ISS) are reviewed. A selection of commercial and developed coatings targeting space applications is presented. Also, some developments that can be used in the space industry are highlighted.
Slot‐Die Coated Organic UV Indicators and Filters Processed from Green Solvents
Authors: Farahat Mahmoud E. , Welch Gregory C.
Published: May 2021

This work reports the use of the slot‐die (SD) coating solution processing method to fabricate large‐area organic thin films composed of photochromic dyes as UV indicators and UV light absorbers as UV filters on polyethylene terephthalate flexible substrates. This is the first demonstration of large‐area SD coated organic photochromic films and UV filters. Impressively, highly uniform photochromic films comprised of small molecules are formed in air, from green solvents (i.e., alcohols) and show rapid color changes upon external stimuli (i.e., light and heat). The UV filters processed under the same conditions and comprised of only small molecules show highly transparent films in the visible and near‐IR range with T% > 97%@550 nm and excellent UV blocking ability. The work highlights the utility of roll‐to‐roll compatible SD‐coating methods to make prototype organic devices in an academic laboratory setting and opens the door for additive manufacturing of simple and low‐cost UV active films for healthcare and electronic applications.
A Stretchable Scaffold with Electrochemical Sensing for 3D Culture, Mechanical Loading, and Real‐Time Monitoring of Cells
Authors: Qin Yu , Hu Xue‐Bo , Fan Wen‐Ting , Yan Jing , Cheng Shi‐Bo , Liu Yan‐Ling , Huang Wei‐Hua
Published: May 2021

In the field of three‐dimensional (3D) cell culture and tissue engineering, great advance focusing on functionalized materials and desirable culture systems has been made to mimic the natural environment of cells in vivo. Mechanical loading is one of the critical factors that affect cell/tissue behaviors and metabolic activities, but the reported models or detection methods offer little direct and real‐time information about mechanically induced cell responses. Herein, for the first time, a stretchable and multifunctional platform integrating 3D cell culture, mechanical loading, and electrochemical sensing is developed by immobilization of biomimetic peptide linked gold nanotubes on porous and elastic polydimethylsiloxane. The 3D scaffold demonstrates very good compatibility, excellent stretchability, and stable electrochemical sensing performance. This allows mimicking the articular cartilage and investigating its mechanotransduction by 3D culture, mechanical stretching of chondrocytes, and synchronously real‐time monitoring of stretch‐induced signaling molecules. The results disclose a previously unclear mechanotransduction pathway in chondrocytes that mechanical loading can rapidly activate nitric oxide signaling within seconds. This indicates the promising potential of the stretchable 3D sensing in exploring the mechanotransduction in 3D cellular systems and engineered tissues.
Periodic Stratified Porous Structures in Dynamic Polyelectrolyte Films Through Standing‐Wave Optical Crosslinking for Structural Color
Authors: Huang Wei‐Pin , Qian Hong‐Lin , Wang Jing , Ren Ke‐Feng , Ji Jian
Published: May 2021

Periodic porous structures have been introduced into functional films to meet the requirements of various applications. Though many approaches have been developed to generate desired structures in polymeric films, few of them can effectively and dynamically achieve periodic porous structures. Here, a facile way is proposed to introduce periodic stratified porous structures into polyelectrolyte films. A photo‐crosslinkable polyelectrolyte film of poly(ethylenimine) (PEI) and photoreactive poly(acrylic acid) derivative (PAA‐N3) is prepared by layer‐by‐layer (LbL) self‐assembly. Stratified crosslinking of the PEI/PAA‐N3 film is generated basing on standing‐wave optics. The periodic stratified porous structure is constructed by forming pores in noncrosslinked regions in the film. Thanks to the dynamic mobility of polyelectrolytes, this structural controlment can be repeated several times. The size of pores corresponding to the layer spacing of the film contributes to the structural colors. Furthermore, structural color patterns are fabricated in the film by selective photo‐crosslinking using photomasks. Although the large‐scale structural controlment in thick (micron‐scale and above) films needs to be explored further, this work highlights the periodic structural controlment in polymeric films and thus presents an approach for application potentials in sensor, detection, and ink‐free printing.
Uncovering LiH Triggered Thermal Runaway Mechanism of a High‐Energy LiNi0.5Co0.2Mn0.3O2/Graphite Pouch Cell
Authors: Huang Lang , Xu Gaojie , Du Xiaofan , Li Jiedong , Xie Bin , Liu Haisheng , Han Pengxian , Dong Shanmu , Cui Guanglei , Chen Liquan
Published: May 2021

The continuous energy density increase of lithium ion batteries (LIBs) inevitably accompanies with the rising of safety concerns. Here, the thermal runaway characteristics of a high‐energy 5 Ah LiNi0.5Co0.2Mn0.3O2/graphite pouch cell using a thermally stable dual‐salt electrolyte are analyzed. The existence of LiH in the graphite anode side is innovatively identified in this study, and the LiH/electrolyte exothermic reactions and H2 migration from anode to cathode side are proved to contribute on triggering the thermal runaway of the pouch cell, while the phase transformation of lithiated graphite anode and the O2‐releasing from cathode are just accelerating factors for thermal runaway. In addition, heat determination during cycling at two boundary scenarios of adiabatic and isothermal environment clearly states the necessity of designing an efficient and smart battery thermal management system for avoiding heat accumulation. These findings will shed promising lights on thermal runaway route map depiction and thermal runaway prevention, as well as formulation of electrolyte for high energy safer LIBs.
HECW2‐related disorder in four Japanese patients
Authors: Yanagishita Tomoe , Hirade Takuya , Shimojima Yamamoto Keiko , Funatsuka Makoto , Miyamoto Yusaku , Maeda Makiko , Yanagi Kumiko , Kaname Tadashi , Nagata Satoru , Nagata Miho , Ishihara Yasuki , Miyashita Yohei , Asano Yoshihiro , Sakata Yasushi , Kosaki Kenjiro , Yamamoto Toshiyuki
Published: May 2021

The HECT, C2, and WW domain containing E3 ubiquitin protein ligase 2 gene (HECW2) is involved in protein ubiquitination. Several genes associated with protein ubiquitination have been linked to neurodevelopmental disorders. HECW2‐related disorder has been established through the identification of de novo variants in HECW2 in patients with neurodevelopmental disorders with hypotonia, seizures, and absent language. Recently, we identified novel HECW2 variants in four Japanese patients with neurodevelopmental disorders. Regarding motor development, two of the patients cannot walk, whereas the other two can walk with an unsteady gait, owing to hypotonia. All HECW2 variants, including those that were previously reported, are missense, and no loss‐of‐function variants have been identified. Most of the identified variants are located around the HECT domain. These findings suggest that the dominant negative effects of missense variants around the HECT domain may be the mechanism underlying HECW2‐related disorder.
Association between social determinants of health and olfactory function: a scoping review
Authors: James Joel , Tsvik Avraham M. , Chung Sei Y. , Usseglio John , Gudis David A. , Overdevest Jonathan B.
Published: May 2021

Background

Social determinants of health (SDoH) include the socioeconomic, demographic, and social conditions that influence differences in health status among individuals and groups. The impact of these conditions on olfactory function remains poorly understood. In this scoping review, we systematically review the available literature to synthesize the association between SDoH and olfactory function.

Methods

In accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses extension for Scoping Review (PRISMA‐ScR) guidelines, we performed systematic search queries in PubMed, Embase, and Ovid databases and categorized articles according to themes that emerged regarding SDoH. The primary outcomes included self‐reported and objective measurements of smell.

Results

We identified 722 unique references that underwent title and abstract review by two independent reviewers, with 70 articles undergoing full‐text review and 57 relevant for data extraction. Six themes emerged in our review, under which we categorized the studies and synthesized respective associations with olfactory function. These include studies exploring socioeconomic status (n = 19, 33%), education status (n = 27, 47%), occupational exposures (n = 26, 46%), racial/ethnic disparities (n = 12, 21%), and lifestyle/behavioral factors (n = 33, 58%).

Conclusions

Within the context of this scoping review, olfactory dysfunction is significantly more prevalent in patients with lower socioeconomic status, exposure to environmental and occupational toxins, and of minority race/ethnicity, whereas the associations between olfactory dysfunction and education level and lifestyle factors such as smoking and drinking seem to be much more elusive. This review highlights the importance of accounting for SDoH in observational studies examining olfactory outcomes. Given the increased awareness of olfactory loss, special consideration should be given to understanding olfactory dysfunction in the context of these factors.
A Self‐Defocusing Effect in Series of Networks for Nano All‐Optical Switching
Authors: Xu Xiaohui , Yang Xiangbo
Published: May 2021

A theoretical design of all‐optical switches based on series of networks (SNs) is proposed. With increment of the fractal generation, the density of loops () in networks, which can efficiently produce antiresonances, increases exponentially, increasing switching efficiency to a high level. To acquire superior performance of the switching efficiency, the nonlinear material with negative nonlinear refractive index was chosen to insert into the networks, inducing self‐defocusing effect and decreasing the transmission. Further, the SNs with a defective waveguide length create ultra‐strong photonic localization and reduce the threshold energy. The switching efficiency of just the third type of SN was calculated and found to be approximately 5.25 × 1026, which is nine orders of magnitude higher than that previously reported. The threshold energy of just the third type of SN is about , which is one order of magnitude lower than that reported previously. Moreover, the switching efficiency increases monotonously, and the threshold energy decreases rapidly with increasing fractal generation.
Local Lorentz Invariance Tests for Photons and Hadrons at the Gamma Factory
Authors: Wojtsekhowski B. , Budker Dmitry
Published: May 2021

High‐precision tests of local Lorentz invariance, via monitoring of the sidereal time variation of the photon energies emitted by ultrarelativistic heavy‐ion beams and of the beam momentum, are proposed. This paper includes descriptions of the physics ideas and the concept for the detector. The experiment results will allow high‐precision tests of LLI via anisotropy of the maximum attainable speed of a photon and an ion. The projected accuracy for the asymmetries interpreted in the framework of the anisotropic relativistic mechanics corresponds to the limit on sidereal time variation of the one‐way maximum attainable speed at the levels between 10−14 and 10−17.
An Examination of Nurses’ Empowerment and Speaking Up During Postanesthesia Clinical Hand Overs
Authors: Redley Bernice , Njambi Margaret , Rawson Helen
Published: May 2021

Hierarchical relationships can negatively affect nurses’ psychological empowerment and interprofessional hand overs. We explored nurses’ perceptions of their psychological empowerment, teamwork, and work engagement; relationships between these concepts during interprofessional clinical hand overs; and observed interactive communication behaviors during hand overs. We used surveys and observations of interprofessional clinical hand overs to collect data from 39 nurses in a postanesthesia care unit in Australia. Nurses reported high scores for psychological empowerment and work engagement. Relationships between empowerment and teamwork (r = 0.41, P = .01) and empowerment and work engagement (r = 0.65, P < .001) were positive and significant. Relationships between nurses’ observed communication behaviors and perceptions of empowerment, teamwork, and work engagement were nonsignificant. Additional research is needed to better understand how empowerment, teamwork, and work engagement affect nurses’ interactive communication behaviors during interprofessional clinical hand overs in the postanesthesia care unit.
Suture Needle Injuries During Wound Closure: Examining Sources of Distraction in the OR
Authors: DiTullio Barbara L.
Published: May 2021

Despite focus on prevention of needlestick injuries, intraoperative injuries involving suture needles have increased in the past two decades. When interruptions occur during surgery, a practitioner’s focus is disengaged, creating an “error space;” re‐engagement of the practitioner takes exponentially longer as each subsequent interruption occurs during the procedure. Human factors studies focus on the interaction between individuals and the environment in which they work (eg, processes, equipment). Researchers use a human factors approach to understand distractions during surgery. Using this methodology, wound closure is viewed as a standalone process and the effect of distractions and interruptions on suture needle injuries is examined. Competing priorities combined with interruptions present opportunities for altered situational awareness, which can lead to injury. This article redefines wound closure as a vulnerable time with great potential for error—a time during which distractions and interruptions can lead to suture needle injuries and other unexpected outcomes.
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

Here, 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

The 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

Aim of study

When 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.

Methods

We 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.

Results

In 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.

Conclusion

The 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

Background

Multiple 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.

Methods

We 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.

Results

We 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.

Conclusions

FAM46C 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

A 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

More 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

In 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

In 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

High 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

Aims

Continuous‐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 results

We 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.

Conclusions

The 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

This 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

Deep 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.
Alkaline magmatism on Neo‐Tethyan extensional domains: Evidences from the Gejiu complex in Yunnan, China
Authors: Wang Yu‐Fei , Dong Guo‐Chen , Santosh M. , Liu Chang , Chen Wei , Liang Jing‐Li , Zhang Yin‐Chu
Published: May 2021

The Gejiu alkaline complex (GAC) within the western part of the Youjiang Basin provides a window to investigate the evolution in the junction of Cathaysia, Yangtze and Indochina blocks. Here, we investigate the GAC in terms of their petrology, zircon U–Pb geochronology, whole‐rock geochemistry, and Sr–Nd isotopic data to gain insights into the origin and evolution of the alkaline magma. The GAC is lithologically composed of alkali syenites and feldspathoid syenites, in which some were altered into sericite syenites. Zircon U–Pb dating of the alkali syenites yielded an age of 85.03 ± 0.47 Ma, which is slightly older than the feldspathoid syenites. The alkali syenites and feldspathoid syenites are silica‐saturated and silica‐undersaturated, respectively, and are characterized by high alkalinity with K2O + Na2O of 11.55–17.08 wt% and Al2O3 of 18.57–22.49 wt%, low MgO of 0.11–1.39 wt%, weakly negative Eu anomalies, enrichments of LILEs such as Th and U, HFSEs like Zr and Hf but depletion of Ba, Sr, Nb, Ta, P, Ti, strongly fractionated LREEs to HREEs. Their uniform Sr–Nd isotope composition with initial 87Sr/86Sr = 0.708802–0.710571 and εNd(t) = −7.1 to −6.6 indicates that they were products of a homologous magma. They crystallized at c. 810–956°C and have a relatively high magmatic oxygen fugacity. Our geochemical and isotopic data proved that the GAC magma was derived from the low‐degree partial melting (<10%) of a phlogopite‐bearing‐enriched mantle that was metasomatized by subducting sediments and originated possibly from the spinel and garnet transition zone at a depth of 60–80 km and a pressure of about 1.8–2.4 Gpa. The primary magma experienced protracted two‐stage crystal fractionation of clinopyroxene+amphibole and biotite+K‐feldspar, forming alkali syenites and feldspathoid syenites. Crustal contamination plays a negligible role in their formation. Considering previous tectonic studies, it was therefore proposed that the GAC formed in an extensional tectonic setting related to the Neo‐Tethyan tectonic regions during the Late Cretaceous.
Conductivity characteristics of human lung tissues
Authors: Wang Yaru , Yue Shihong , Chen Jun , Li Qi
Published: May 2021

In the treatment of lung cancer, bedside monitoring plays an important role. X‐ray computed tomography, as a mostly used technique, cannot provide medical surveillance for lung cancer patients in real‐time. In comparison, electrical impedance tomography (EIT) has the potential to solve the issue by visualizing human respiratory system; however, its spatial resolution is too low to locate the real pulmonary lesions. One feasible method is to incorporate priori information into the process of EIT imaging. This study aims to investigate the conductivity characteristics of human lung tissues as priori information. First, the impedance spectra of human lung tissues in surgical operation were measured in time in a measurement system. Then, two‐ and three‐dimensional lung models were established. Finally, the conductivity distribution models of cancerous and normal lung tissues were established. Overall, the conductivity of left lung was larger than that of right lung; the conductivity of lower lobe was larger in left lung, whereas the conductivity of upper lobe was larger in right lung. When tissues became cancerous, the conductivity increased by 33.5% on average, and by 34.8 and 31.4% in the left and right lung, respectively. The conductivity in left lung changed more obviously; and it changed more obviously in posterior basal segment of lower lobe in left lung, as well as at apex in right lung. These conclusions can lay the foundation for the further research of improving the spatial resolution of EIT for lung cancer monitoring.
Ultraviolet light accelerates the degradation of polyethylene plastics
Authors: Doğan Mustafa
Published: May 2021

Polyethylene plastics are widely used in daily life in the packaging of foodstuffs, pharmaceuticals, cosmetics, detergents, and chemicals. In this study, low‐density polyethylene (LDPE) was exposed to an ultraviolet (UV) fluorescence lamp in simulated aging and degradation experiments. Ultraviolet degradation mechanisms were investigated on the surface after sunlight and UV lamp exposure. The plastic surfaces' molecular and surface degradation results were compared with their Fourier Transform Infrared‐Attenuated Total Reflectance (FTIR‐ATR) and ultraviolet visible (UV–Vis) spectra. By growing the length of exposure time increased stages of degradation were observed. After UV lamp and sunlight exposure, changing degradation levels were also determined with spectroscopic evaluations and the results were compared. LDPE was selected since it has a simple structure and a number of branched polymer structures that facilitate easily disruption of the chemical bond. Breaks in the polymer chain were easily seen in the plastics at the end of degradation and a fragile structure was formed throughout the polymer chain after accelerating UV light aging. The FTIR spectrum clarified the changed and fractured molecular bond structures of UV‐exposed polyethylene. The change in the molecular structure of the plastic caused small changes in its color and small variations in this color change were detected by recording the Ultraviolet–Visible (UV–Vis) spectrum. The Philips UV lamp's light intensity and the wavelength spectrum range were measured. The UV lamp and sun UV light doses were calculated and compared.
Analysis of enamel/restoration interface submitted cariogenic challenge and fluoride release
Authors: Rodrigues Raquel Viana , Sampaio Camila Sobral , Girotto Aline Carvalho , Pinhatti Caroline Paiuta , Iwamoto Alexsandra Shizue , de Freitas Anderson Zanardi , Ambrosano Gláucia Maria Bovi , Puppin‐Rontani Regina Maria , Pascon Fernanda Miori
Published: May 2021

The treatment of high‐risk patients still is a challenge. The understanding and development non‐invasive, non‐destructive, and non‐ionizing techniques, can help to guide the treatment and the diagnosis of primary and recurrent caries. The present study evaluated the behavior of enamel/restoration interface after a cariogenic challenge by Fourier domain optical coherence tomography (FD‐OCT), scanning electron microscopy (SEM) examination, and the fluoride release of the different restorative materials. Cavities (1.5 × 0.5 mm) were performed in enamel surface and divided into groups (n = 8): glass ionomer cement (GIC), resin‐modified glass ionomer cement (RMGIC), and resin composite (RC). The samples were submitted to pH‐cycling, and the solutions analyzed for cumulative fluoride by ion‐analyzer. The morphology was analyzed by SEM through replicas. The optical attenuation coefficient (OAC) was calculated through exponential decay from the images generated by FD‐OCT. Data were analyzed considering α = 0.05. OAC values increased for all groups after pH‐cycling indicating demineralization (p < .05). Considering the remineralizing solution, RMGIC presented higher fluoride release rate, followed by GIC, while RC did not release any fluoride. Yet for the demineralizing solution, RMGIC and GIC released similar fluoride rates, overcoming RC (p < .05). Micrographs revealed no changes on the restorations margins, although enamel detachment was observed for RC and GIC after pH‐cycling.