bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence-Based Criteria Supporting Early Discharge for Pediatric Patients With Osteosarcoma Receiving High-Dose Methotrexate: A Retrospective Chart Review
Authors: Armideo, CRNP, MSN, BSN, RN, CPON Erin , Froio, BSN, RN Shannon , Johnson, CRNP, MSN, BSN, RN Meredith , Tardino-Gingrich, CRNP, MSN, BSN, RN Alison , Froh, PhD, RN Elizabeth
Published: March 2022

Purpose: The purpose of this study is to describe the outcomes following the implementation of an early discharge protocol for pediatric patients with osteosarcoma receiving high-dose methotrexate (MTX) to determine if the protocol safely decreased length of stay without increased toxicity. Methods: This was a retrospective descriptive cohort design. Participants included children, 5 to 25 years of age, diagnosed with osteosarcoma, who received methotrexate between December 2017 and July 2019. A total of 141 doses across fifteen individual patients were included in the cohort. Data were abstracted from the electronic health record and analyzed using descriptive statistics. Results: The majority of administrations (n = 94, 67%) met early discharge criteria without an increase in toxicity or hospital readmission. Conclusion: Pediatric patients receiving high-dose MTX for osteosarcoma can be safely discharged from the hospital when serum MTX level < 0.4 μmol/L with the implementation of education, hydration goals, frequent lab monitoring, and close follow-up. More than half of patients on this study were able to be discharged from the hospital sooner than prior protocol. More importantly, this retrospective chart review highlighted the ability to maintain safe administration without increasing toxicity.
Predictive Value of Chest CT Score in Assessing Disease Severity and Short-term Mortality in COVID-19 Pneumonia at a Tertiary Care Centre in Northern India: A Prospective Observational Study
Authors: Roul Pradeep Kumar , Kaushik As hish , Sherwani Poonam , Yadav Kriti , Saini Aditi , Singh O Budha Charan , Syed Anjum , Panda Prasan Kumar
Published: March 2022

Introduction: Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV-2) infection, also known as Coronavirus Disease2019 (COVID-19) is the global pandemic, first described in Wuhan city of China in December of 2019. Its diagnosis depends upon real-time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). On chest Computerised Tomography (CT), it is almost similar to other viral pneumonia with extensive parenchymal involvement. Semiquantitative scores depicting this extensiveness of involvement could correlate with disease severity, laboratory parameters, mortality, like Intensive Care Unit (ICU) admission, requirements of ventilatory support and longer hospital stay. Aim: To define role of chest CT score in determining disease severity, predicting poor prognosis and mortality of COVID-19 pneumonia in short-term follow-up. Materials and Methods: This prospective study enrolled all admitted real-time RT-PCR positive patients for COVID19 at All India Institute of Medical Sciences, Rishikesh, India between 15th April and 31st May 2021. All patients were assigned semiquantitative CT scores based on the extent of lung parenchymal involvement of 20 lung regions in chest CT. Clinical severity was matched with chest CT scoring and laboratory findings. Survival curves along with univariate and multivariate analysis were applied to define the role of CT scoring in predicting short term prognosis. Results: Total 547 subjects were included in the study, of which the chest CT score showed a significant association with clinical severities (p-value <0.001). CT score were correlating significantly with increased serum C-Reactive Protein (CRP) (p-value=0.001) and D-dimer (p-value=0.01), and decreased lymphocyte count (p-value=0.003). A CT score ≥31 was found to be associated with an increased risk of mortality in both univariate and multivariate analysis {Odd Ratio (OR)=276.8; 95% Confidence Interval (CI)= 45.21-1695.43; p-value <0.001}. Conclusion: Chest CT score can be imaging measure of disease severity and predict a higher probability of mortality in score ≥31. It can also predict other defined variables of short-term prognosis. So, it has an advantage in speedy diagnostic workflow of symptomatic cases, timely referral of patients to higher centre, and better management of critical care resources.
Understanding Suboptimal Response to Immune Checkpoint Inhibitors
Authors: Zhu Mojun , Zhang Henan , Pedersen Katrina S. , Foster Nathan R. , Jaszewski Brandy L. , Liu Xin , Hirdler Jacob B. , An Zesheng , Bekaii‐Saab Tanios S. , Halfdanarson Thorvardur R. , Boland Patrick M. , Yan Yiyi , Hubbard Joleen H. , Ma Wen Wee , Yoon Harry H. , Revzin Alexander , Fernandez‐Zapico Martin E. , Overman Michael J. , McWilliams Robert R. , Dong Haidong
Published: March 2022

Immune checkpoint inhibitors (ICIs), as a novel class of anticancer therapy, can be more efficacious and less toxic than chemotherapy, but their clinical success is confined to certain tumor types. Elucidating their targets, mechanisms and scope of action, and potential synergism with chemotherapy and/or targeted therapies are critical to widen their clinical indications. Treatment response to an ICI targeting programmed death‐1 (anti‐PD‐1) is sought to be understood here by conducting a preplanned correlative analysis of a phase II clinical trial in patients with small bowel adenocarcinoma (SBA). The cytolytic capacity of circulating immune cells in cancer patients using a novel ex vivo cytotoxicity assay is evaluated, and the utility of circulating biomarkers is investigated to predict and monitor the treatment effect of anti‐PD‐1. Baseline expression of Bim and NKG7 and upregulation of CX3CR1 in circulating T cells are associated with the clinical benefit of anti‐PD‐1 in patients with SBA. Overall, these findings suggest that the frequency and cytolytic capacity of circulating, effector immune cells may differentiate clinical response to ICIs, providing a strong rationale to support immune monitoring using patient peripheral blood.
Microstructure and Properties of Titanium Matrix Composites Synergistically Reinforced by Graphene Oxide and Alloying Elements
Authors: Yu Jiashi , Zhao Yongqing , Zhao Qinyang , Zhang Wei , Huo Wangtu , Zhang Yusheng
Published: March 2022

In this work, the microstructure and mechanical properties of titanium matrix composites were tuned by introducing graphene and alloying elements. The titanium matrix composites reinforced by graphene oxide (GO) and cobalt elements (GO@ Co/TA1) are synthesized by the spark plasma sintering (SPS) technique. Results show that the precipitated Ti2Co phase is almost reticulate distributed in the tissue, while the in situ TiC particles are discontinuously distributed at the grain boundaries. The ultimate tensile strength and yield strength of GO@ Co/TA1 composites are 160% and 126% higher than those of pure TA1, respectively. In addition, composites show excellent ductility where the elongation of GO@Co/TA1 is around 10.95%. Therefore, such enhanced mechanical properties can be attributed to the synergistic strengthening effect of interfacial‐distributed TiC particles and intragranular‐distributed intermetallic compounds (Ti2Co), which would provide a new idea for the design of metal matrix composite.
Micro/Nanorobots as Active Delivery Systems for Biomedicine: From Self‐Propulsion to Controllable Navigation
Authors: Sun Zhaoli , Hou Yanglong
Published: March 2022

In recent years, micro/nanorobots have attracted intensive interests in biomedicine, which is a multidisciplinary research field involved with robotics, medicine, and nanotechnology. Different from conventional nanomaterials utilized for human being healthcare, micro/nanorobots can effectively convert diverse energy sources into movement and force, covering a broad spectrum of applications in precise drug delivery, controllable drug release, potent tissue penetration, enhanced drug retention, precise operation of minimally invasive surgery, medical sensing, and detoxification. In this review, the self‐propelled mechanisms and controllable navigation of micro/nanorobots are first summarized, then the recent progress on micro/nanorobots as active delivery systems for biomedicine are presented. Finally, the perspective and challenge are also discussed. It is expected that this review gives an insight into the active delivery systems based on micro/nanorobots for disease therapy and diagnosis, detection, and biodetoxification, aiming for more extensive research in biomedicine and the clinical transformation in the near future.
BN‐Anthracene for High‐Mobility Organic Optoelectronic Materials through Periphery Engineering
Authors: Li Wanhui , Du Cheng‐Zhuo , Chen Xing‐Yu , Fu Lin , Gao Rong‐Rong , Yao Ze‐Fan , Wang Jie‐Yu , Hu Wenping , Pei Jian , Wang Xiao‐Ye
Published: March 2022

Despite the remarkable synthetic accomplishments in creating diverse polycyclic aromatic hydrocarbons with B−N bonds (BN‐PAHs), their optoelectronic applications have been less exploited. Herein, we report the achievement of high‐mobility organic semiconductors based on existing BN‐PAHs through a “periphery engineering” strategy. Tetraphenyl‐ and diphenyl‐substituted BN‐anthracenes (TPBNA and DPBNA, respectively) are designed and synthesized. DPBNA exhibits the highest hole mobility of 1.3 cm2 V−1 s−1in organic field‐effect transistors, significantly outperforming TPBNA and all the reported BN‐PAHs. Remarkably, this is the first BN‐PAH with mobility over 1 cm2 V−1 s−1, which is a benchmark value for practical applications as compared with amorphous silicon. Furthermore, high‐performance phototransistors based on DPBNA are also demonstrated, implying the high potential of BN‐PAHs for optoelectronic applications when the “periphery engineering” strategy is implemented.
Kupfer‐katalysierte Monooxygenierung von Phenolen: Evidenz für einen mononuklearen Reaktionsmechanismus
Authors: Schneider Rebecca , Engesser Tobias A. , Näther Christian , Krossing Ingo , Tuczek Felix
Published: March 2022

Die CuI‐Salze [Cu(CH3CN)4]PF und [Cu(oDFB)2]PF mit dem sehr schwach koordinierenden Anion Al(OC(CF3)3)4− (PF), sowie [Cu(NEt3)2]PF mit dem einzigartigen, linearen Bis‐Triethylamin‐Komplex [Cu(NEt3)2]+ wurden synthetisiert und als Katalysatoren für die Umwandlung von Monophenolen zu o‐Chinonen untersucht. Die Aktivitäten dieser CuI‐Salze bei der Monooxygenierung von 2,4‐Di‐tert‐butylphenol (DTBP‐H) wurden mit denen der [Cu(CH3CN)4]X‐Salze mit “klassischen” Anionen (BF4−, OTf−, PF6−) verglichen, wobei ein Anioneneffekt auf die Aktivität des Katalysators und ein Ligandeneffekt auf die Reaktionsgeschwindigkeit festgestellt wurden. Letztere wird durch den Einsatz von CuII‐Semichinon‐Komplexen als Katalysatoren drastisch erhöht, was darauf hinweist, dass die Bildung eines CuII‐Komplexes dem eigentlichen katalytischen Zyklus vorausgeht. Diese und andere experimentelle Erkenntnisse zeigen, dass die Oxygenierung von Monophenolen mit den oben genannten Systemen nicht einem dinuklearen, sondern einem mononuklearen Weg folgt, analog zur Topachinon‐Cofaktor‐Biosynthese im Enzym Aminoxidase.
Surface‐Plasmon‐Enhanced Transmetalation between Copper and Palladium Nanoparticle Catalyst
Authors: Liu Xin , Shi Yujian , Jin Yichao , Tana Tana , Peiris Erandi , Zhang Xueming , Xu Feng , Waclawik Eric R. , Bottle Steven E. , Zhu Huaiyong , Sarina Sarina
Published: March 2022

Surface‐plasmon‐mediated phenylacetylide intermediate transfer from the Cu to the Pd surface affords a novel mechanism for transmetalation, enabling wavelength‐tunable cross‐coupling and homo‐coupling reaction pathway control. C−C bond forming Sonogashira coupling and Glaser coupling reactions in O2 atmosphere are efficiently driven by visible light over heterogeneous Cu and Pd nanoparticles as a mixed catalyst without base or other additives. The reaction pathway can be controlled by switching the excitation wavelength. Shorter wavelengths (400–500 nm) give the Glaser homo‐coupling diyne, whereas longer wavelength irradiation (500–940 nm) significantly increases the degree of cross‐coupling Sonogashira coupling products. The ratio of the activated intermediates of alkyne to the iodobenzene is wavelength dependent and this regulates transmetalation. This wavelength‐tunable reaction pathway is a novel way to optimize the product selectivity in important organic syntheses.
Visible‐Light‐Induced, Single‐Metal‐Catalyzed, Directed C−H Functionalization: Metal‐Substrate‐Bound Complexes as Light‐Harvesting Agents
Authors: Pei Chao , Empel Claire , Koenigs Rene M.
Published: March 2022

C−H functionalization represents one of the most rapidly advancing areas in organic synthesis and is regarded as one of the key concepts to minimize the ecological and economic footprint of organic synthesis. The ubiquity and low reactivity of C−H bonds in organic molecules, however, poses several challenges, and often necessitates harsh reaction conditions to achieve this goal, although it is highly desirable to achieve C−H functionalization reactions under mild conditions. Recently, several reports uncovered a conceptually new approach towards C−H functionalization, where a single transition‐metal complex can be used as both the photosensitizer and catalyst to promote C−H bond functionalization in the absence of an exogeneous photosensitizer. In this Minireview, we will provide an overview on recent achievements in C−H functionalization reactions, with an emphasis on the photochemical modulation of the reaction mechanism using such catalysts.
Hidden Heptacyclic Chiral N‐Acyl Iminium Ions: A New Entry to Enantioenriched Polycyclic Azepanes and Azocanes by Superacid‐Promoted Intramolecular Pictet‐Spengler Reaction
Authors: Reviriot Yasmin , Michelet Bastien , Beaud Rodolphe , Martin‐Mingot Agnès , Guégan Frédéric , Thibaudeau Sébastien , Rodriguez Jean , Bonne Damien
Published: March 2022

Enantioenriched complex fused‐tricyclic azepanes or bridged‐polycyclic azocanes were constructed via a two‐step sequence involving an enantioselective organocascade followed by superacid activation of the domino adduct. The activated oxa‐bridged azepane acts as a key hidden heptacyclic chiral N‐acyl iminium ion triggering a chemo‐ and diastereoselective intramolecular mono‐ or di‐arylation.
Nicotinic acetylcholine receptors in a songbird brain
Authors: Asogwa Norman Chinweike , Toji Noriyuki , He Ziwei , Shao Chengru , Shibata Yukino , Tatsumoto Shoji , Ishikawa Hiroe , Go Yasuhiro , Wada Kazuhiro
Published: March 2022

Nicotinic acetylcholine receptors (nAChRs) are ligand‐gated ion channels that mediate fast synaptic transmission and cell signaling, which contribute to learning, memory, and the execution of motor skills. Birdsong is a complex learned motor skill in songbirds. Although the existence of 15 nAChR subunits has been predicted in the avian genome, their expression patterns and potential contributions to song learning and production have not been comprehensively investigated. Here, we cloned all the 15 nAChR subunits (ChrnA1–10, B2–4, D, and G) from the zebra finch brain and investigated the mRNA expression patterns in the neural pathways responsible for the learning and production of birdsong during a critical period of song learning. Although there were no detectable hybridization signals for ChrnA1, A6, A9, and A10, the other 11 nAChR subunits were uniquely expressed in one or more major subdivisions in the song nuclei of the songbird brain. Of these 11 subunits, ChrnA3–5, A7, and B2 were differentially regulated in the song nuclei compared with the surrounding anatomically related regions. ChrnA5 was upregulated during the critical period of song learning in the lateral magnocellular nucleus of the anterior nidopallium. Furthermore, single‐cell RNA sequencing revealed ChrnA7 and B2 to be the major subunits expressed in neurons of the vocal motor nuclei HVC and robust nucleus of the arcopallium, indicating the potential existence of ChrnA7‐homomeric and ChrnB2‐heteromeric nAChRs in limited cell populations. These results suggest that relatively limited types of nAChR subunits provide functional contributions to song learning and production in songbirds.
Influence of the mechanical and geometrical parameters on the cellular uptake of nanoparticles: A stochastic approach
Authors: Iaquinta Sarah , Khazaie Shahram , Ishow Éléna , Blanquart Christophe , Fréour Sylvain , Jacquemin Frédéric
Published: March 2022

Nanoparticles (NPs) are used for drug delivery with enhanced selectivity and reduced side‐effect toxicity in cancer treatments. Based on the literature, the influence of the NPs mechanical and geometrical properties on their cellular uptake has been studied through experimental investigations. However, due to the difficulty to vary the parameters independently in such a complex system, it remains hard to efficiently conclude on the influence of each one of them on the cellular internalization of a NP. In this context, different mechanical / mathematical models for the cellular uptake of NPs have been developed. In this paper, we numerically investigate the influence of the NP's aspect ratio, the membrane tension and the cell‐NP adhesion on the uptake of the NP using the model introduced in1 coupled with a numerical stochastic scheme to measure the weight of each one of the aforementioned parameters. The results reveal that the aspect ratio of the particle is the most influential parameter on the wrapping of the particle by the cell membrane. Then the adhesion contributes twice as much as the membrane tension. Our numerical results match the previous experimental observations.
An efficient front‐to‐back depth‐buffer algorithm for real‐time rendering of partially occluded game objects in absence of GPU
Authors: Shivani Shivendra
Published: March 2022

Real‐time rendering of visual scenes is a key requirement in many emerging fields like augmented and virtual reality (AR/VR), computer graphics, and so forth. Latency in rendering the scenes due to massive shading calculations and complete rasterization of view windows is undesirable in real‐time AR/VR scenarios. Real‐time determination of occluded and visible objects is one of the significant problems the rendering process faces. The classical Z‐buffer algorithm used for this purpose requires a lot of memory to store depth values, hence maintaining a buffer. Due to scan‐line tendency, its time complexity is also too high. This article presents a new perspective on a fundamental Z‐buffer algorithm. The proposed approach is not entirely a scan‐line method. It is based on divide and conquer strategy, and it also works on the concept of the front‐to‐back concept, where rays are emitted from a viewpoint toward the objects. Based on the proposed algorithm, partially occluded game objects can also be efficiently determined. Only partial shading calculations will be done using the proposed rendering factor calculation to render those objects. It will also speed up the real‐time processing without using any GPU. This way, the proposed approach reduces the time and space complexity of the rendering process.
Timing of adoption is associated with electrophysiological brain activity and externalizing problems among children adopted internationally
Authors: Bick Johanna , Lipschutz Rebecca , Tabachnick Alexandra , Biekman Brian , Katz Danielle , Simons Robert , Dozier Mary
Published: March 2022

This study investigated middle childhood resting electroencephalography (EEG) and behavioral adjustment in 35 internationally adopted children removed from early caregiving adversity between 6 and 29 months of age. Older age of adoption was associated with more immature or atypical profiles of middle childhood cortical function, based on higher relative theta power (4–6 Hz), lower relative alpha power (7–12 Hz), lower peak alpha frequency, and lower absolute beta (13–20 Hz) and gamma (21–50 Hz) power. More immature or atypical EEG spectral power indirectly linked older age of adoption with increased risk for externalizing problems in middle childhood. The findings add to existing evidence linking duration of early adverse exposures with lasting effects on brain function and behavioral regulation even years after living in a stable adoptive family setting. Findings underscore the need to minimize and prevent children's exposures to early caregiving adversity, especially in the first years of life. They call for innovative interventions to support neurotypical development in internationally adopted children at elevated risk.
Rethinking biodiversity patterns and processes in stream ecosystems
Authors: Green Matthew D. , Anderson Kurt E. , Herbst David B. , Spasojevic Marko J.
Published: March 2022

A major goal of community ecology is understanding the processes responsible for generating biodiversity patterns along spatial and environmental gradients. In stream ecosystems, system‐specific conceptual frameworks have dominated research describing biodiversity change along longitudinal gradients of river networks. However, support for these conceptual frameworks has been mixed, mainly applicable to specific stream ecosystems and biomes, and these frameworks have placed less emphasis on general mechanisms driving biodiversity patterns. Rethinking biodiversity patterns and processes in stream ecosystems with a focus on the overarching mechanisms common across ecosystems will provide a more holistic understanding of why biodiversity patterns vary along river networks. In this study, we apply the theory of ecological communities (TEC) conceptual framework to stream ecosystems to focus explicitly on the core ecological processes structuring communities: dispersal, speciation, niche selection, and ecological drift. Using a unique case study from high‐elevation networks of connected lakes and streams, we sampled stream invertebrate communities in the Sierra Nevada, California, USA to test established stream ecology frameworks and compared them with the TEC framework. Local diversity increased and β‐diversity decreased moving downstream from the headwaters, consistent with the river continuum concept and the small but mighty framework of mountain stream biodiversity. Local diversity was also structured by distance below upstream lakes, where diversity increased with distance below upstream lakes, in support of the serial discontinuity concept. Despite some support for the biodiversity patterns predicted from the stream ecology frameworks, no single framework was fully supported, suggesting “context dependence.” By framing our results under the TEC, we found that species diversity was structured by niche selection, where local diversity was highest in environmentally favorable sites. Local diversity was also highest in sites with small community sizes, countering the predicted effects of ecological drift. Moreover, higher β‐diversity in the headwaters was influenced by dispersal and niche selection, where environmentally harsh and spatially isolated sites exhibit higher community variation. Taken together our results suggest that combining system‐specific ecological frameworks with the TEC provides a powerful approach for inferring the mechanisms driving biodiversity patterns and provides a path toward generalization of biodiversity research across ecosystems.
Liquid Contact Ion Selective Electrode Green Method for the Determination of Flavoxate HCl Main Active Metabolite in Pure Powder and Human Urine with Establishment of Urinary Excretion Pattern
Authors: Ragab Mona T. , Ramadan Nesrin K. , El‐Ragehy Nariman A. , El‐Zeany Badr A.
Published: March 2022

The main aim of this work is to develop the first liquid contact ion selective electrode potentiometric method for determination of flavoxate HCl main metabolite; 3‐methylflavone‐8‐carboxylic acid (MFC). The method can be used for studying flavoxate HCl bioavailability through tracing its active metabolite; MFC, excreted in human urine. The metabolite was determined in pure powder and in human urine with establishment of urinary excretion pattern without any sample extraction or pretreatment procedures. The suggested sensor‘s performance was assessed in accordance with IUPAC guidelines. According to the Bioanalytical Method Validation Guidance for Industry, the suggested method was validated where good results were obtained. The proposed method is an excellent green eco‐friendly analytical method.
Role of the hydrogen sulfide‐releasing donor ADT‐OH in the regulation of mammal neural precursor cells
Authors: Wei Shan‐Wen , Zou Ming‐Ming , Huan Jian , Li Di , Zhang Peng‐Fei , Lu Mei‐Hong , Xiong Jian , Ma Yan‐Xia
Published: March 2022

Neural precursor cells (NPCs) generate new neurons to supplement neuronal loss as well as to repair damaged neural circuits. Therefore, NPCs have potential applications in a variety of neurological diseases, such as spinal cord injury, traumatic brain injury, and glaucoma. Specifically, improving NPCs proliferation and manipulating their differentiated cell types can be a beneficial therapy for a variety of these diseases. ADT‐OH is a slow‐releasing organic H2S donor that produces a slow and continuous release of H2S to maintain normal brain functions. In this study, we aimed to explore the effect of ADT‐OH on NPCs. Our results demonstrated that ADT‐OH promotes self‐renewal and antiapoptosis ability of cultured NPCs. Additionally, it facilitates more NPCs to differentiate into neurons and oligodendrocytes, while inhibiting their differentiation into astrocytes. Furthermore, it enhances axonal growth. Moreover, we discovered that the mRNA and protein expression of β‐catenin, TCF7L2, c‐Myc, Ngn1, and Ngn2, which are key genes that regulate NPCs self‐renewal and differentiation, were increased in the presence of ADT‐OH. Altogether, these results indicate that ADT‐OH may be a promising drug to regulate the neurogenesis of NPCs, and needs to be studied in the future for clinical application potential.
N6‐methyladenosine modification participates in neoplastic immunoregulation and tumorigenesis
Authors: Zhao Wanzhen , Li Jianjun , Ma Qiang , Cai Jijie , Li Aixin , Wu Weijun , Lv Yuncheng , Cai Manbo
Published: March 2022

This review aims to provide insight into the role of N6‐methyladenosine (m6A) modification in neoplastic immunity and subsequent tumorigenesis. m6A modification, which is catalyzed by methyltransferases, demethylases and reader proteins, has emerged as a widespread regulatory mechanism that controls immune‐related gene expression and immune reactions during tumorigenesis. Aberrant m6A modification changes the neoplastic immune response in multiple cancers by regulating immune cell infiltration, tumor‐promoting inflammation, immunosuppression, immune surveillance, and antitumor immune responses. m6A modification affects immune cell recruitment and cancer‐promoting inflammation in hepatocellular carcinoma (HCC) to alter the progression of HCC. m6A modification has been implicated in the infiltration of immune cells and the activation of immune pathways, changing the proliferation and metastasis of gastric cancer. Immune surveillance and the antitumor immune response in breast cancer were enhanced via m6A modification, which inhibited tumor proliferation. m6A modification participates in neoplastic immunoregulation to influence tumor progression.
Association of peptidoglycan recognition protein 1 to post‐myocardial infarction and periodontal inflammation: A subgroup report from the PAROKRANK (Periodontal Disease and the Relation to Myocardial Infarction) study
Authors: Rathnayake Nilminie , Gustafsson Anders , Sorsa Timo , Norhammar Anna , Bostanci Nagihan ,   the PAROKRANK Steering Committee
Published: March 2022

Background

Peptidoglycan recognition protein 1 (PGLYRP1) is an antimicrobial and proinflammatory innate immunity protein activated during infections. We aimed to investigate whether PGYLRP1 and associated molecules of the immune response in saliva is a cumulative outcome result of both MI and periodontal inflammation.

Methods and Results

Two hundred patients with MI and another 200 matched non‐MI controls were included. A full‐mouthexamination was conducted to assess periodontal inflammation and collection of stimulated saliva was performed 6 to 10 weeks after the first MI. PGLYRP1, triggering receptor expressed on myeloid cells 1 (TREM‐1), interleukin‐1 beta (IL‐1β) were analyzed by ELISA. Matrix metalloproteinase (MMP)‐8 levels were determined by IFMA. Compared to controls, MI patients showed higher salivary PGLYRP1, but not TREM‐1 levels. The difference in PGLYRP1 levels remained after adjustment for covariates. In MI patients, the PGLYRP1 levels positively correlated with BOP and PPD 4 to 5 mm. Among non‐MI subjects, the levels of PGLYRP1 correlated positively and significantly with BOP and total PPD. Salivary PGLYRP1 concentrations also showed strong positive correlations with levels of TREM‐1, IL‐1β and MMP‐8. In multivariate linear regression analysis, in MI patients, BOP and former smokingstatus displayed an association with salivary PGLYRP1 concentration.

Conclusion

MI patients showed higher salivary PGLYRP1 levels than healthy controls, also after adjusting for smoking, sex, age and periodontal health status. Salivary levels of PGLYRP1 may reflect the overall inflammatory burden to chronic bacterial exposure, possibly underpinning the observed associations between periodontitis and exposure with MI.
On the bias of complete‐ and shifting‐case meta‐regressions with missing covariates
Authors: Schauer Jacob M. , Lee Jihyun , Diaz Karina , Pigott Therese D.
Published: March 2022

Missing covariates is a common issue when fitting meta‐regression models. Standard practice for handling missing covariates tends to involve one of two approaches. In a complete‐case analysis, effect sizes for which relevant covariates are missing are omitted from model estimation. Alternatively, researchers have employed the so‐called "shifting units of analysis" wherein complete‐case analyses are conducted on only certain subsets of relevant covariates. In this article, we clarify conditions under which these approaches generate unbiased estimates of regression coefficients. We find that unbiased estimates are possible when the probability of observing a covariate is completely independent of effect sizes. When that does not hold, regression coefficient estimates may be biased. We study the potential magnitude of that bias assuming a log‐linear model of missingness and find that the bias can be substantial, as large as Cohen's d = 0.4–0.8 depending on the missingness mechanism.
MoS2 Decorated Silver Nanowire‐Reduced Graphene Oxide Aerogel Micro‐Particle for Thermally Conductive Polymer Composites with Enhanced Flame Retardancy
Authors: Chang Chen , Guan Xin , Lin Jingya , Nie Hui , Zhou Xingping , Xie Xiaolin , Ye Yunsheng
Published: March 2022

Multifunctional polymer composites with efficient heat dissipation and flame retardancy are highly desirable in the electronic industry. Here, by the combination of hydrothermal reaction and in situ fragmentation, molybdenum disulfide (MoS2) decorated silver nanowires (AgNWs) and 3D reduced graphene oxide (RGO) (AgNW‐RGO@MoS2) aerogel micro‐particles (AMPs) are successfully prepared. When the above AMP is introduced to epoxy (EP) resin by the simple blending method, a polymer composite with continuous thermally conductive pathways and flame barrier layers is achieved. With an AMP loading of 4.0 vol.%, the polymer composite displays superior enhancement in thermal conductivity up to 420%. Compared to neat EP, the peak heat release rate and total heat release decreases by 61.1% and 58.8%, respectively. This work provides new insights into the design and large‐scale fabrication of multifunctional polymer composites for efficient thermal management materials.
Cramér–Rao bound‐informed training of neural networks for quantitative MRI
Authors: Zhang Xiaoxia , Duchemin Quentin , Liu* Kangning , Gultekin Cem , Flassbeck Sebastian , Fernandez‐Granda Carlos , Assländer Jakob
Published: March 2022

Purpose

To improve the performance of neural networks for parameter estimation in quantitative MRI, in particular when the noise propagation varies throughout the space of biophysical parameters.

Theory and Methods

A theoretically well‐founded loss function is proposed that normalizes the squared error of each estimate with respective Cramér–Rao bound (CRB)—a theoretical lower bound for the variance of an unbiased estimator. This avoids a dominance of hard‐to‐estimate parameters and areas in parameter space, which are often of little interest. The normalization with corresponding CRB balances the large errors of fundamentally more noisy estimates and the small errors of fundamentally less noisy estimates, allowing the network to better learn to estimate the latter. Further, proposed loss function provides an absolute evaluation metric for performance: A network has an average loss of 1 if it is a maximally efficient unbiased estimator, which can be considered the ideal performance. The performance gain with proposed loss function is demonstrated at the example of an eight‐parameter magnetization transfer model that is fitted to phantom and in vivo data.

Results

Networks trained with proposed loss function perform close to optimal, that is, their loss converges to approximately 1, and their performance is superior to networks trained with the standard mean‐squared error (MSE). The proposed loss function reduces the bias of the estimates compared to the MSE loss, and improves the match of the noise variance to the CRB. This performance gain translates to in vivo maps that align better with the literature.

Conclusion

Normalizing the squared error with the CRB during the training of neural networks improves their performance in estimating biophysical parameters.
Optimization of undersampling parameters for 3D intracranial compressed sensing MR angiography at 7 T
Authors: de Buck Matthijs H. S. , Jezzard Peter , Hess Aaron T.
Published: March 2022

Purpose

3D time‐of‐flight MRA can accurately visualize the intracranial vasculature but is limited by long acquisition times. Compressed sensing reconstruction can be used to substantially accelerate acquisitions. The quality of those reconstructions depends on the undersampling patterns used. In this work, we optimize sets of undersampling parameters for various acceleration factors of Cartesian 3D time‐of‐flight MRA.

Methods

Fully sampled datasets, acquired at 7 Tesla, were retrospectively undersampled using variable‐density Poisson disk sampling with various autocalibration region sizes, polynomial orders, and acceleration factors. The accuracy of reconstructions from the different undersampled datasets was assessed using the vessel‐masked structural similarity index. Identified optimal undersampling parameters were then evaluated in additional prospectively undersampled datasets. Compressed sensing reconstruction parameters were chosen based on a preliminary reconstruction parameter optimization.

Results

For all acceleration factors, using a fully sampled calibration area of 12 12 k‐space lines and a polynomial order of 2 resulted in the highest image quality. The importance of parameter optimization of the sampling was found to increase for higher acceleration factors. The results were consistent across resolutions and regions of interest with vessels of varying sizes and tortuosity. The number of visible small vessels increased by 7.0% and 14.2% when compared to standard parameters for acceleration factors of 7.2 and 15, respectively.

Conclusion

The image quality of compressed sensing time‐of‐flight MRA can be improved by appropriate choice of undersampling parameters. The optimized sets of parameters are independent of the acceleration factor and enable a larger number of vessels to be visualized.
A propensity score‐matching analysis of angiotensin‐converting enzyme inhibitor and angiotensin receptor blocker exposure on in‐hospital mortality in patients with acute respiratory failure
Authors: Fang Yi‐Peng , Zhang Xin
Published: March 2022

Study Objective

To explore the impact of pre‐hospital ACEI and ARB exposure on the prognosis of ARF patients.

Design

A single‐center retrospective cohort study.

Setting

Medical Information Mart for Intensive Care‐III (MIMIC‐III) database.

Patients

The patients meeting ICD‐9 code of acute respiratory failure were enrolled.

Intervention

The primary exposure was the pre‐hospital exposure of ACEI and ARB.

Measurement and main results

The primary outcome was in‐hospital mortality. Multiple logistic regression analysis was conducted to determine the independent effect of ACEI/ARB exposure on mortality. Propensity score matching (PSM) method was adopted to reduce bias of the confounders. Subgroup analysis and sensitivity analysis were used to test the stability of the conclusion. 5335 adult ARF patients were enrolled. Mortality was significantly decreased in patients with ACEI/ARB exposure before and after PSM, and the adjusted odds ratio (OR) of ACEI/ARB exposure was 0.56 (95% CI 0.43–0.72). In the subgroup analysis, ACEI/ARB lost its protective effect in young subgroup, but no significant interaction was found between ACEI/ARB exposure and age (p = 0.082). The point estimation and lower 95% limit of E‐value was 2.97 and 2.12. In sensitivity analysis, ACEI/ARB exposure showed similar effect in ARDS cohort, but no significantly difference was found in the MIMIC‐IV database, which may be explained by small sample size of the ACEI/ARB group.

Conclusions

Among patients with acute respiratory failure, pre‐hospital ACEI/ARB exposure was associated with better outcomes and acted as an independent factor. The relationship between ACEI/ARB and prognosis of ARF is worth investigating further.
Enhancement of Arabidopsis growth by non–24 hour day–night cycles
Authors: Yamamoto Yuko , Tabata Kazufumi
Published: March 2022

Plant yield can be increased by matching the internal circadian rhythms with the external light and dark cycle (circadian resonance). The circadian resonance reported in the past was analyzed under light–dark cycles with 20‐, 24‐, or 28‐hr periods; however, the mechanism for circadian resonance is still debatable due to the experimental time schedules in previous studies being few in number and widely separated. By analyzing the yield of Arabidopsis thaliana grown under eight different external light and dark periods, we found that the yield increased when the external cycle was 22 and 26 hr instead of 24 hr. Time course RNA‐seq analysis determined that seedling circadian clock genes had a free‐running period of 22 ± 1 hr. Furthermore, a group of genes with 25‐ to 26‐hr period rhythms were also observed in the seedlings with a 22‐ ± 1‐hr period as their circadian clock. We propose that resonance that occurred by matching the expression time of a group of genes with the 25‐ to 26‐hr cycle and providing an external day–night cycle of 25 to 26 hr was one factor that caused the yield increase.
Prognostic value of protein biomarkers in liver transplantation: A systematic review
Authors: Song Wei , Xiong Xiaofu , Ge Weihong , Zhu Huaijun
Published: March 2022

Liver transplantation is currently the preferred method for the treatment of advanced liver disease and early‐stage hepatocellular carcinoma (HCC). Although advances in surgical techniques, immunosuppressive drugs and postoperative management have reduced the incidence of postoperative complications, how to effectively predict or diagnose postoperative complications earlier and reduce their incidence is still a clinical concern. We performed a comprehensive proteomics literature research to identified protein biomarkers in complications after liver transplantation. Seventeen studies met the inclusion criteria including ischemia reperfusion injury (IRI) (n = 4), acute rejection (AR) (n = 4), renal dysfunction (n = 4), HCC recurrence (n = 2), primary graft dysfunction (PGD) (n = 1), infection (n = 1), and liver fibrosis (n = 1). A total of 625 differentially expressed proteins (DEPs) have been reported between postoperative complications and controls, of which 63 have been validated by quantitative protein expression and 26 have been reported by at least two studies and showed consistently changes. The results of the bioinformation analysis show that the immune system, especially the innate immune system and cytokine signaling in immune system, is an important protein‐mediated pathway that affects the prognosis of liver transplantation.
Impact of positive surgical margin length and Gleason grade at the margin on oncologic outcomes in patients with nonorgan‐confined prostate cancer
Authors: Preisser Felix , Heinze Alexander , S. Abrams‐Pompe Raisa , Budäus Lars , Chun Felix K.‐H. , Graefen Markus , Huland Hartwig , Tilki Derya
Published: March 2022

Purpose

Positive surgical margins (PSM) represent a poor prognostic factor at radical prostatectomy (RP). To investigate the impact of PSM, its length, the focality and the Gleason grade at the PSM, on the oncologic outcomes in nonorgan‐confined RP patients.

Methods

Within a high‐volume center database, we identified patients who harbored non‐organ‐confined (pT3) prostate cancer (PCa) at RP between 2010 and 2016. Only patients without lymph node invasion were included. Kaplan–Meier analyses and multivariable Cox regression models were used to test the effect of PSM on biochemical recurrence (BCR), metastasis, and cancer‐specific death after RP in patients without adjuvant radiotherapy.

Results

Overall, 3705 patients were identified. Of those, 27.2% (n = 1007) harbored PSM. At 96 months after RP, BCR‐free, metastasis‐free and cancer‐specific survival was 41.6 versus 57.5%, 82.7 versus 88.6%, and 94.7 versus 98.5% for patients with versus without PSM (all p < 0.001). BCR‐free, metastasis‐free and cancer‐specific survival rates at 96 months were 56.7 versus 26.5% (p < 0.001), 94.4 versus 67.4% (p < 0.001), and 100.0 versus 87.1% (p < 0.01) for Gleason pattern 3 versus ≥ 4 at the margin and 45.0 versus 27.8% (p < 0.01), 83.3 versus 82.3% (p = 0.2), and 95.2 versus 92.7% (p = 0.3) for <4 mm versus ≥4 mm length of margin. In multivariable Cox models PSM was an independent predictor for BCR (hazard ratio [HR]:1.53, p < 0.001) and cancer‐specific death (HR:2.75, p = 0.02). In subgroups of patients with PSM only, Gleason ≥ 4 at the margin (HR:1.60, p < 0.01) and length of PSM (HR:1.02, p < 0.05) was an independent predictor of BCR.

Conclusion

PSM represents an independent predictor for worse oncologic outcome in nonorgan‐confined PCa at RP. Gleason ≥ 4 at the margin was associated with the development of BCR, metastasis, and with cancer‐specific death after RP. Next to margin status, Gleason at the margin and its length carry important information that should be reported for the specimen.
On the applicability of urban canopy parametrization in building grey zone
Authors: Chen Song , Dipankar Anurag
Published: March 2022

With increasing interest in urban meteorology and related services, the need to appropriately represent the urban environment in climate/weather models is rising. These regional weather/climate models typically use a km‐scale horizontal grid, which is insufficient to resolve the flow around buildings. Effects of the urban environment on the atmosphere above are represented through a bulk approach using the Urban Canopy Parametrization (UCP) schemes. Existing UCPs usually use the repeating canyon–roof representation that assumes homogeneous distribution of buildings within the grid box. It is commonly accepted that the assumption of homogeneity holds at km‐scale grid resolution but whether it also holds at sub‐km scale, where the regional models are increasingly approaching, is questionable. For this reason, among others, the resolution ranges from a few hundred metres to tens of metres (i.e. building‐resolving scales) is termed the building grey zone in the existing literature. This work shows that the assumption of homogeneity indeed does not hold at the building grey zone for the city‐state Singapore. To understand the possible influences of the use of UCPs at scales from the building grey zone to the conventional mesoscale, we use an urban‐grid method that allows us to estimate the parametrized fluxes from a typical UCP at varying resolutions over the urban landcover while keeping the same atmospheric model grid. Numerical results show that different urban‐grid resolutions yield variations in the near‐surface temperature and wind to a maximum of 0.5 K and 1 m·s−1. Their impact on the boundary‐layer parameters is found to be limited. Although these near‐surface variations are small, they are comparable to the near‐surface scaling variables and are thus physically significant.
How innovating firms manage knowledge leakage: A natural experiment on the threat of worker departure
Authors: Kang Hyo , Lee Wyatt
Published: March 2022

Research Summary

Knowledge protection strategies are crucial to innovating firms facing the risk of knowledge leakage. We examine the threat of worker departure as a key mechanism through which firms choose between patents and secrecy. We exploit a 1998 California court decision that ruled out‐of‐state noncompetes were not enforceable in California, thereby creating a loophole limiting non‐California firms in their enforcement of noncompetes against their workers. When facing a higher threat of worker departure, firms strategically increased patent filings, exchanging legal protection for public disclosure of the invention. These effects were magnified for large‐sized firms and for those in complex and fast‐growing industries. Further mechanism tests on the possession of trade secrets, inventor migration, saliency of the decision, and independent inventors support our theoretical account.

Managerial Summary

Innovating firms may use patents or secrecy, among other mechanisms, to protect their knowledge from leakage. How do firms make this important strategic choice? By using a natural experiment arising from a 1998 California court decision, we show the risk of worker departure can be a key driver. The decision significantly increased the risk of workers departing non‐California firms. Our findings show that, in response to the heightened risk, affected firms increasingly relied on patents, seeking legal protection although it meant public disclosure of the invention. The effects were greater for large‐sized firms and for those in complex and fast‐growing industries. We encourage managers to consider worker mobility and, more broadly, legal environments that govern labor market conditions when formulating knowledge protection strategies.
A Water in Oil Gelled Emulsion as a Topical Release Vehicle for Curcumin
Authors: Pérez‐Salas Juan Luis , Medina‐Torres Luis , Rocha‐Guzmán Nuria Elizabeth , Calderas F. , González‐Laredo Rubén Francisco , Bernad‐Bernad María Josefa , Moreno‐Jiménez Martha Rocío , Gallegos‐Infante José Alberto
Published: March 2022

The objective of this work is to assess the influence of the concentration of polyglycerol polyricinoleate (PGPR) (at 1%, 1.5%, and 2%) on the physical properties of water in oil gelled emulsions (W/O) and evaluates their efficiency as a delivery vehicle for curcumin. Emulsions are characterized by drop size, centrifugal test, texture, and rheology during 28 days of storage. When the surfactant concentration increases, smaller droplet sizes are obtained (<5 µm), the phase separation (tested by centrifugal force) decreases from 6% to 4% with little variation of the time. The mechanical properties of emulsions show a tendency to decrease as time passed and concentration of PGPR increased. The emulsions increased viscosity as the concentration increased, but the addition of curcumin reduce the viscosity of the emulsions. About controlled release profiles, a low concentration of PGPR shows an increase in the affinity between curcumin and the emulsions, following a pseudo‐Fickian release behavior. At higher concentration of PGPR shows a decrease in the affinity between curcumin and the emulsion, displaying a Fickian release behavior. The authors were able to prepare tailor made curcumin water in oil emulsion systems for the topical release of this compound.