bluuebunny/crossref_metadata_2025 huggingface dataset:
Sub‐Gaussian Matrices on Sets: Optimal Tail Dependence and Applications
Authors: Jeong Halyun , Li Xiaowei , Plan Yaniv , Yilmaz Ozgur
Published: October 2021

Random linear mappings are widely used in modern signal processing, compressed sensing, and machine learning. These mappings may be used to embed the data into a significantly lower dimension while at the same time preserving useful information. This is done by approximately preserving the distances between data points, which are assumed to belong to . Thus, the performance of these mappings is usually captured by how close they are to an isometry on the data. Gaussian linear mappings have been the object of much study, while the sub‐Gaussian settings is not yet fully understood. In the latter case, the performance depends on the sub‐Gaussian norm of the rows. In many applications, e.g., compressed sensing, this norm may be large, or even growing with dimension, and thus it is important to characterize this dependence.

We study when a sub‐Gaussian matrix can become a near isometry on a set, show that previous best‐known dependence on the sub‐Gaussian norm was suboptimal, and present the optimal dependence. Our result not only answers a remaining question posed by Liaw, Mehrabian, Plan, and Vershynin in 2017, but also generalizes their work. We also develop a new Bernstein‐type inequality for subexponential random variables, and a new Hanson‐Wright inequality for quadratic forms of sub‐Gaussian random variables, in both cases improving the bounds in the sub‐Gaussian regime under moment constraints. Finally, we illustrate popular applications such as Johnson‐Lindenstrauss embeddings, null space property for 0‐1 matrices, randomized sketches, and blind demodulation, whose theoretical guarantees can be improved by our results (in the sub‐Gaussian case). © 2021 Wiley Periodicals LLC.
Mirror‐Image Cofacial Coronene Dimers Characterized by CD and CPL Spectroscopy: A Twisted Bilayer Nanographene
Authors: Uehara Keiji , Kano Haruka , Matsuo Kyohei , Hayashi Hironobu , Fujiki Michiya , Yamada Hiroko , Aratani Naoki
Published: October 2021

The front cover artwork is provided by Naoki Aratani, Hiroko Yamada, and co‐workers at NAIST (Japan). This picture shows Mt. Fuji, the highest mountain in Japan, reflecting off the water surface in a beautiful symmetrical form. On this image, we superimposed the mirror‐image CPL spectra obtained in this study for a 1,8‐naphthylene‐linked face‐to‐face coronene dimer. Read the full text of the Communication at 10.1002/cptc.202100166.
Perennial ryegrass (Lolium perenne) culm and inflorescence density in lawns: Effects of nitrogen fertilization and scalping timing and height
Authors: Braun Ross C. , Patton Aaron J.
Published: October 2021

During late spring and early summer, perennial ryegrass (Lolium perenne L.) produces reproductive structures (i.e., culm and inflorescence), that decrease turf quality due to stemminess (i.e., culm remaining) after mowing. Research is required to understand the impact of management practices on visible culm and inflorescence presence. Field experiments were conducted to evaluate perennial ryegrass culm, inflorescence, and turf canopy responses due to various nitrogen (N) fertilization levels, scalping timings and heights. In Experiment 1, N fertilization rates ≥24 kg N ha−1 applied in early May with a slow‐release fertilizer prior to peak flowering (i.e., late May to early June) visibly decreased culms and inflorescences compared with 0 and 12 kg N ha−1. Higher N fertilizer levels, especially 98 kg N ha−1, also resulted in fewer necrotic culms remaining later in the summer along with greater overall turf quality and reduced weed cover. In Experiment 2, scalping perennial ryegrass at 3.8 or 5.1 cm on 25 May, the closest proximity prior to peak flowering, provided the lowest area under the curve (AUC) of green flowering culms. Scalping during or after peak flowering resulted in similar AUC values compared with nonscalped (7.6 cm) turf but did decrease the presence of necrotic culms later in summer to help improve turf quality. Overall, N fertility with a slow‐release fertilizer or a well‐timed scalping influences spring culm and inflorescence density and necrotic culm stemminess in perennial ryegrass turf systems. Additional research on physiological responses, such as carbohydrate partitioning, to these management practices is required.
Molecular Stabilization of Sub‐Nanometer Cu Clusters for Selective CO2 Electromethanation
Authors: Zhang Han , Yang Yu , Liang Yongxiang , Li Jun , Zhang An , Zheng Han , Geng Zhigang , Li Fengwang , Zeng Jie
Published: October 2021

Electrochemical CO2 methanation powered by renewable electricity provides a promising approach to utilizing CO2 in the form of a high‐energy‐density, clean fuel. Cu nanoclusters have been predicted by theoretical calculations to improve methane selectivity. Direct electrochemical reduction of Cu‐based metal‐organic frameworks (MOFs) results in large‐size Cu nanoparticles which favor multi‐carbon products. This study concerns an electrochemical oxidation‐reduction method to prepare Cu clusters from MOFs. The derived Cu clusters exhibit a faradaic efficiency of 51.2 % for CH4 with a partial current density of >150 mA cm−2. High‐resolution microscopy, in situ X‐ray absorption spectroscopy, in situ Raman spectroscopy, and a range of ex situ spectroscopies indicate that the distinctive CH4 selectivity is due to the sub‐nanometer size of the derived materials, as well as stabilization of the clusters by residual ligands of the pristine MOF. This work offers a new insight into steering product selectivity of Cu by an electrochemical processing method.
The Steptoean Positive Carbon Isotope Excursion (SPICE), inorganic aragonite precipitation and sea water chemistry: Insights from the Middle–Late Cambrian Port au Port Group, Newfoundland
Authors: Neilson Joyce E. , Barili Rosalia , Brasier Alexander , De Ros Luiz F. , Ledingham Sarah
Published: October 2021

The Late Cambrian Steptoean Positive Carbon Isotope Excursion marks a time of significant change in ocean chemistry and trilobite faunas. On the lead up to the carbon isotope excursion and at the excursion itself, there is global evidence from Laurentia and Gondwana of cementation by primary aragonite in shallow subtidal environments accompanied by deposition of aragonitic ooids. However, this occurred at a time widely considered to have been characterised by ‘calcite seas’ when the primary inorganic phases (marine cements and ooids) are normally presumed calcitic. This study has investigated the chemostratigraphy of the Middle–Late Cambrian Port au Port Group, Newfoundland, including the early marine cements. Here, the marine cements contain increasing concentrations of strontium towards the peak carbon isotope excursion (up to 5500 ppm at the peak excursion) before dropping off post‐peak excursion, consistent with the original cements having been aragonitic. This trend is accompanied by relict oomouldic porosity, again suggesting an aragonitic precursor. Primary inorganic mineralogy is largely controlled by the Mg/Ca ratio of sea water but estimates of the Mg/Ca ratio of Late Cambrian oceans are variable (0.8–2). At this level, other factors such as water temperature and pCO2 have been shown to affect mineralogy with warm waters and high levels of CO2 favouring aragonite. It is possible that the warm waters and anoxia that caused the carbon isotope excursion created conditions favourable for the precipitation of aragonite at the same time as major trilobite faunal turnover.
In vitro studies of hypoxia inducible factor‐prolyl hydroxylase inhibitors daprodustat, desidustat, and vadadustat for equine doping control
Authors: Philip Moses , Karakka Kal Abdul Khader , Subhahar Michael Benedict , Karatt Tajudheen K. , Mathew Binoy , Perwad Zubair
Published: October 2021

Performance‐enhancing substances and methods have become a serious problem in competitive sports. The hypoxia‐inducible factor (HIF) stabilizers can enhance the organism's capacity for molecular oxygen transport and are likely to be abused as performance‐enhancing agents in sports. This paper describes the metabolic conversion of the popular hypoxia inducible factor‐prolyl hydroxylase (HIF‐PH) inhibitors, namely, daprodustat, desidustat, and vadadustat using equine liver microsomes, determined on a QExactive high‐resolution mass spectrometer. During this study, a total of 10 metabolites for daprodustat (all are Phase I), 10 metabolites for desidustat (five each for Phase I and Phase II), and 15 metabolites for vadadustat (six for Phase I and nine for Phase II) were detected. The important findings of the current research are as follows: (1) All the three HIF‐PH inhibitor drug candidates are prone to oxidation, which results in corresponding hydroxylated metabolites; (2) in desidustat, hydrolysis and dissociation of oxime linkage also observed; (3) the glucuronic acid conjugate (except daprodustat) of the parent drugs as well as the monohydroxylated analogs were observed; (4) sulfonic acid conjugated metabolites were observed only for vadadustat.
Unraveling the complex genetics of neural tube defects: From biological models to human genomics and back
Authors: Wolujewicz Paul , Steele John W. , Kaltschmidt Julia A. , Finnell Richard H. , Ross Margaret Elizabeth
Published: October 2021

Neural tube defects (NTDs) are a classic example of preventable birth defects for which there is a proven‐effective intervention, folic acid (FA); however, further methods of prevention remain unrealized. In the decades following implementation of FA nutritional fortification programs throughout at least 87 nations, it has become apparent that not all NTDs can be prevented by FA. In the United States, FA fortification only reduced NTD rates by 28–35% (Williams et al., 2015). As such, it is imperative that further work is performed to understand the risk factors associated with NTDs and their underlying mechanisms so that alternative prevention strategies can be developed. However, this is complicated by the sheer number of genes associated with neural tube development, the heterogeneity of observable phenotypes in human cases, the rareness of the disease, and the myriad of environmental factors associated with NTD risk. Given the complex genetic architecture underlying NTD pathology and the way in which that architecture interacts dynamically with environmental factors, further prevention initiatives will undoubtedly require precision medicine strategies that utilize the power of human genomics and modern tools for assessing genetic risk factors. Herein, we review recent advances in genomic strategies for discovering genetic variants associated with these defects, and new ways in which biological models, such as mice and cell culture‐derived organoids, are leveraged to assess mechanistic functionality, the way these variants interact with other genetic or environmental factors, and their ultimate contribution to human NTD risk.
Cumulative impacts across Australia’s Great Barrier Reef: a mechanistic evaluation
Authors: Bozec Yves‐Marie , Hock Karlo , Mason Robert A. B. , Baird Mark E. , Castro‐Sanguino Carolina , Condie Scott A. , Puotinen Marji , Thompson Angus , Mumby Peter J.
Published: October 2021

Cumulative impacts assessments on marine ecosystems have been hindered by the difficulty of collecting environmental data and identifying drivers of community dynamics beyond local scales. On coral reefs, an additional challenge is to disentangle the relative influence of multiple drivers that operate at different stages of coral ontogeny. We integrated coral life history, population dynamics, and spatially explicit environmental drivers to assess the relative and cumulative impacts of multiple stressors across 2,300 km of the world’s largest coral reef ecosystem, Australia’s Great Barrier Reef (GBR). Using literature data, we characterized relationships between coral life history processes (reproduction, larval dispersal, recruitment, growth, and mortality) and environmental variables. We then simulated coral demographics and stressor impacts at the organism (coral colony) level on >3,800 individual reefs linked by larval connectivity and exposed to temporally and spatially realistic regimes of acute (crown‐of‐thorns starfish outbreaks, cyclones, and mass coral bleaching) and chronic (water‐quality) stressors. Model simulations produced a credible reconstruction of recent (2008–2020) coral trajectories consistent with monitoring observations, while estimating the impacts of each stressor at reef and regional scales. Overall, simulated coral populations declined by one‐third across the GBR, from an average of ~29% to ~19% hard coral cover. By 2020, <20% of the GBR had coral cover higher than 30%, a status of reef health corroborated by scarce and sparsely distributed monitoring data. Reef‐wide annual rates of coral mortality were driven by bleaching (48%) ahead of cyclones (41%) and starfish predation (11%). Beyond the reconstructed status and trends, the model enabled the emergence of complex interactions that compound the effects of multiple stressors while promoting a mechanistic understanding of coral cover dynamics. Drivers of coral cover growth were identified; notably, water quality (suspended sediments) was estimated to delay recovery for at least 25% of inshore reefs. Standardized rates of coral loss and recovery allowed the integration of all cumulative impacts to determine the equilibrium cover for each reef. This metric, combined with maps of impacts, recovery potential, water‐quality thresholds, and reef state metrics, facilitates strategic spatial planning and resilience‐based management across the GBR.
Signal integrity analysis and Peripheral Component Interconnect Express backplane link compliance assessment
Authors: Orekhov Evgeny , Smolenskiy Anton , Popov Boris
Published: October 2021

This article presents research conducted on the backplane high‐speed Peripheral Component Interconnect Express version 4 (PCIe gen4) link between central processor root complex and the end‐point device in order to confirm its compliance. Signal integrity analysis was performed using a method that included channel segmentation, development of corner models for channel segments, full‐wave electromagnetic simulation utilizing the finite element method (FEM) and the creation of cascaded channel models, as well as determination of the worst‐case models for the channel. The results of this analysis were then used to modify the channel design in order to decrease insertion loss. Changes in the design included utilizing a very low loss dielectric for the backplane board, correcting the sizes of differential pairs and decreasing the via stubs. Frequency domain simulation of the modified channel design has shown a 25% decrease in insertion loss. The calculation of eye diagrams for the modified design has confirmed that the channel parameters meet the requirements for the PCIe gen4 standard.
Identification of Cytochrome P450 Isozymes Involved in Enantioselective Metabolism of Fipronil in Fish Liver: In Vitro Metabolic Kinetics and Molecular Modeling
Authors: Wu Siqi , Li Huizhen , You Jing
Published: October 2021

Fipronil has been frequently detected in waterways worldwide at concentrations that threaten aquatic organisms, yet the metabolic behavior of fipronil enantiomers in aquatic organisms is largely unknown, which is of significance in enantioselective toxicity evaluation. We quantitatively identified the specific cytochrome P450 (CYP) isozymes involved in metabolizing fipronil enantiomers in tilapia by combining in vitro metabolic kinetic assays and molecular docking. Inhibition studies suggested that CYP1A enzyme was the main isoform catalyzing metabolism of fipronil and that CYP3A contributed in a limited way to the metabolism in fish liver S9. Both the dissipation rate constant and the maximum metabolic velocity of R-(−)-fipronil were greater than those of S-(+)-fipronil in tilapia liver S9, suggesting that tilapia selectively metabolized R-(−)-fipronil. The CYP1A1 isozyme exhibited the highest binding capacity to R-(−)-fipronil and S-(+)-fipronil (binding energy ‒9.39 and ‒9.17 kcal/mol, respectively), followed by CYP1A2 (‒7.30 and ‒6.94 kcal/mol, respectively) and CYP3A4 (‒7.16 and ‒6.91 kcal/mol, respectively). The results of in vitro metabolic assays and molecular docking were consistent, that is, CYP1A, specifically CYP1A1, exhibited a higher metabolic capacity to fipronil than CYP3A, and fish liver S9 selectively metabolized R-(−)-fipronil. The present study provides insight into the enantioselective metabolic behavior and toxicological implications of the in vitro metabolic kinetics of fipronil in fish. Environ Toxicol Chem 2022;41:230–239. © 2021 SETAC

Abstract

Tilapia selectively metabolizes R-(-)-fipronil and CYP1A is the main isozyme involving in metabolism. CYP1A/CYP3A = cytochrome P450 1A/3A.
Preparation and characterization of Zein‐sulfated Cardamine hupingshanensis polysaccharide composite films
Authors: Zhang Zimu , Huang XiuFang , Li ShiChan , Zhang Chi , Luo Kai
Published: October 2021

Cardamine hupingshanensis polysaccharide (CHP) was modified by the sulfur trioxide–pyridine method to obtain the sulfated C. hupingshanensis polysaccharide (SCHP) with a substitution degree of 0.72. The spectral results revealed that the sulfate group was successfully introduced to CHP. In the in vitro antioxidant assay, SCHP showed the highest scavenging rate of hydroxyl radicals, ABTS, and DPPH. Different concentrations of SCHP were chosen to form a compound with Zein to prepare novel bioactive films successfully. The functional and characterization studies of the films were also conducted. The scavenging ability of the films for hydroxyl radicals, ABTS, and DPPH was improved by adding different concentrations of SCHP. Although the films showed a decrease in transparency with the addition of 4 mg/ml SCHP, there was an improvement in tensile strength compared to films without the addition of SCHP. These findings indicate that Zein‐SCHP films can be used as a functional food packaging material with antioxidant properties.
Development and validation of a predictive model for pathogenic Escherichia coli in fresh‐cut produce
Authors: Kim You Jin , Park Ju Yeon , Suh Soo Hwan , Kim Mi‐Gyeong , Kwak Hyo‐Sun , Kim Soon Han , Heo Eun Jeong
Published: October 2021

This study was performed to develop and validate a predictive growth model of pathogenic Escherichia coli to ensure the safety of fresh‐cut produce. Samples were inoculated with a cocktail of seven E. coli strains of five pathotypes (EHEC, Enterohemorrhagic E. coli; ETEC, Enterotoxigenic E. coli; EPEC, Enteropathogenic E. coli; EIEC, Enteroinvasive E. coli, and EAEC, Enteroaggregative E. coli) and stored at 4, 10, 12, 15, 25, 30, and 37°C. Growth of pathogenic E. coli was observed above 12°C. The primary growth model for pathogenic E. coli in fresh‐cut produce was developed based on the Baranyi model. The secondary model was developed as a function of temperature for lag phase duration (LPD) and maximum specific growth rate (μmax) based on the polynomial second‐order model. The primary and secondary models for pathogenic E. coli were fitted with a high degree of goodness of fit (R2 ≥ 0.99). The bias factor (Bf), accuracy factor (Af), and root mean square error (RMSE) were 0.995, 1.011, and 0.084, respectively. The growth model we developed can provide useful data for assessing the quantitative microbial risk of pathogenic E. coli in fresh‐cut produce intended for human consumption. In addition, it is thought to be widely available in industries that produce, process, distribute, and sell fresh‐cut produce.
Evaluating the formative and shape‐controlled dispersive mechanisms of mud balls in a low‐energy coastal setting: New insights
Authors: Mukhopadhyay Soumik , Sen Arunava , Koley Ankan , Samanta Pradip
Published: October 2021

The study of the mud balls is one of the most common tools to unravel the flow dynamics, energy conditions, and palaeogeographies for both modern and ancient settings. The present study involves detailed analysis of the concentration, size, shape, and alignment of the long axes of the mud balls in a modern coastal setting of Chandipur, east coast of India. The study was performed throughout two consecutive years, during eight different seasonal intervals. Extensive and thorough investigation on mud balls reveals some significant insight about the multifarious mechanisms of clast formation within this low‐energy micro‐ to meso‐tidal coastal setting. The study also reveals shape‐controlled dispersion of transported mud balls under the action of wave‐generated currents. The eventual orientations of their geometric longest axes are not controlled by their mode of transportation, but by their shape and gravitational stability, fundamentally governed by the mass distribution along that axis. This shape‐controlled dispersive model contradicts a long‐standing convention that long axis orientations of the mud balls with respect to the shore line are often random and governed only by their mode of transportation and locally developed complex flow components along the coast line. In contrast, a difference in seasonal concentration of mud balls appears to be a qualitative measure of the variations in energy conditions of this intertidal setting and consequently degree of coastal erosion.
Astrocytic VEGFA: An essential mediator in blood–brain‐barrier disruption in Parkinson's disease
Authors: Lan Guoyu , Wang Pan , Chan Robin Barry , Liu Zongran , Yu Zhenwei , Liu Xiaodan , Yang Ying , Zhang Jing
Published: October 2021

The integrity of blood–brain‐barrier (BBB) is essential for normal brain functions, synaptic remodeling, and angiogenesis. BBB disruption is a common pathology during Parkinson's disease (PD), and has been hypothesized to contribute to the progression of PD. However, the molecular mechanism of BBB disruption in PD needs further investigation. Here, A53T PD mouse and a 3‐cell type in vitro BBB model were used to study the roles of α‐synuclein (α‐syn) in BBB disruption with the key results confirmed in the brains of PD patients obtained at autopsy. The A53T PD mouse studies showed that the expression of tight junction‐related proteins decreased, along with increased vascular permeability and accumulation of oligomeric α‐syn in activated astrocytes in the brain. The in vitro BBB model studies demonstrated that treatment with oligomeric α‐syn, but not monomeric or fibrillar α‐syn, resulted in significant disruption of BBB integrity. This process involved the expression and release of vascular endothelial growth factor A (VEGFA) and nitric oxide (NO) from oligomeric α‐syn treated astrocytes. Increased levels of VEGFA and iNOS were also observed in the brain of PD patients. Blocking the VEGFA signaling pathway in the in vitro BBB model effectively protected the barrier against the harmful effects of oligomeric α‐syn. Finally, the protective effects on BBB integrity associated with inhibition of VEGFA signaling pathway was also confirmed in PD mice. Taken together, our study concluded that oligomeric α‐syn is critically involved in PD‐associated BBB disruption, in a process that is mediated by astrocyte‐derived VEGFA.
The role of the arousal system in age‐related differences in cortical functional network architecture
Authors: Guardia Tiago , Geerligs Linda , Tsvetanov Kamen A. , Ye Rong , Campbell Karen L.
Published: October 2021

A common finding in the aging literature is that of the brain's decreased within‐ and increased between‐network functional connectivity. However, it remains unclear what is causing this shift in network organization with age. Given the essential role of the ascending arousal system (ARAS) in cortical activation and previous findings of disrupted ARAS functioning with age, it is possible that age differences in ARAS functioning contribute to disrupted cortical connectivity. We test this possibility here using resting state fMRI data from over 500 individuals across the lifespan from the Cambridge Center for Aging and Neuroscience (Cam‐CAN) population‐based cohort. Our results show that ARAS‐cortical connectivity declines with age and, consistent with our expectations, significantly mediates some age‐related differences in connectivity within and between association networks (specifically, within the default mode and between the default mode and salience networks). Additionally, connectivity between the ARAS and association networks predicted cognitive performance across several tasks over and above the effects of age and connectivity within the cortical networks themselves. These findings suggest that age differences in cortical connectivity may be driven, at least in part, by altered arousal signals from the brainstem and that ARAS–cortical connectivity relates to cognitive performance with age.
Generation and validation of a PET radiomics model that predicts survival in diffuse large B cell lymphoma treated with R‐CHOP14: A SAKK 38/07 trial post‐hoc analysis
Authors: Ceriani Luca , Milan Lisa , Cascione Luciano , Gritti Giuseppe , Dalmasso Federico , Esposito Fabiana , Pirosa Maria Cristina , Schär Sämi , Bruno Andrea , Dirnhofer Stephan , Giovanella Luca , Hayoz Stefanie , Mamot Christoph , Rambaldi Alessandro , Chauvie Stephane , Zucca Emanuele
Published: October 2021

Functional parameters from positron emission tomography (PET) seem promising biomarkers in various lymphoma subtypes. This study investigated the prognostic value of PET radiomics in diffuse large B‐cell lymphoma (DLBCL) patients treated with R‐CHOP given either every 14 (testing set) or 21 days (validation set). Using the PyRadiomics Python package, 107 radiomics features were extracted from baseline PET scans of 133 patients enrolled in the Swiss Group for Clinical Cancer Research 38/07 prospective clinical trial (SAKK 38/07) [ClinicalTrial.gov identifier: NCT00544219]. The international prognostic indices, the main clinical parameters and standard PET metrics, together with 52 radiomics uncorrelated features (selected using the Spearman correlation test) were included in a least absolute shrinkage and selection operator (LASSO) Cox regression to assess their impact on progression‐free (PFS), cause‐specific (CSS), and overall survival (OS). A linear combination of the resulting parameters generated a prognostic radiomics score (RS) whose area under the curve (AUC) was calculated by receiver operating characteristic analysis. The RS efficacy was validated in an independent cohort of 107 DLBCL patients. LASSO Cox regression identified four radiomics features predicting PFS in SAKK 38/07. The derived RS showed a significant capability to foresee PFS in both testing (AUC, 0.709; p < 0.001) and validation (AUC, 0.706; p < 0.001) sets. RS was significantly associated also with CSS and OS in testing (CSS: AUC, 0.721; p < 0.001; OS: AUC, 0.740; p < 0.001) and validation (CSS: AUC, 0.763; p < 0.0001; OS: AUC, 0.703; p = 0.004) sets. The RS allowed risk classification of patients with significantly different PFS, CSS, and OS in both cohorts showing better predictive accuracy respect to clinical international indices. PET‐derived radiomics may improve the prediction of outcome in DLBCL patients.
Pre‐treatment health‐related quality of life parameters have prognostic impact in patients >65 years with newly diagnosed mantle cell lymphoma: The Nordic Lymphoma Group MCL4 (LENA‐BERIT) experience
Authors: Lindberg Åsa , Eskelund Christian Winther , Albertsson‐Lindblad Alexandra , Kolstad Arne , Laurell Anna , Räty Riikka , Grønbæk Kirsten , Geisler Christian Hartmann , Jerkeman Mats
Published: October 2021

Mantle cell lymphoma (MCL) is a rare, often aggressive type of B‐cell lymphoma with poor survival and no cure. Cancer and cancer treatment has a negative impact on health‐related quality of life (HRQOL) both during active disease and in the long term, and improvement of HRQOL is a crucial objective of cancer therapy in older patients and no curative intent. Baseline HRQOL has in other lymphoma populations been shown to be predictive of outcome. Here, we explored HRQOL, and its association with survival, by the EORTC QLQ‐C30 questionnaire, before, during and after chemotherapy in a patient cohort with MCL, treated within the NLG‐MCL4 trial, designed to evaluate the addition of lenalidomide (LEN) to rituximab‐bendamustine (R‐B) as first‐line treatment. Fifty‐one patients were enrolled, median age was 71 years (range 62–84), 37 were men (73%). Pre‐treatment HRQOL was similar to scores from the reference population with healthy individuals. During treatment, HRQOL deteriorated, but reverted to the same level as the reference population after treatment. There was a correlation between physical function (p = 0.001) and role function (p = 0.006) at baseline and WHO performance status, but not with other clinical or genetic prognostic factors. None of the baseline factors were predictive for treatment related to HRQOL in this cohort. Pre‐treatment physical (p = 0.011) and role function (p = 0.032) were independent factors associated with overall survival, and physical function (p = 0.002) was also associated with progression free survival. These findings may possibly be used to design support during treatment and improve rehabilitation. Further investigations are needed for assessment of long‐term HRQOL.
MHD mixed convection of a Cu–water nanofluid flow through a channel with an open trapezoidal cavity and an elliptical obstacle
Authors: Al‐Farhany Khaled , Alomari Mohammed A. , Al‐Saadi Ahmed , Chamkha Ali , Öztop Hakan F. , Al‐Kouz Wael
Published: October 2021

In the current work, numerical simulations are achieved to study the properties and the characteristics of fluid flow and heat transfer of (Cu–water) nanofluid under the magnetohydrodynamic effects in a horizontal rectangular canal with an open trapezoidal enclosure and an elliptical obstacle. The cavity lower wall is grooved and represents the heat source while the obstacle represents a stationary cold wall. On the other hand, the rest of the walls are considered adiabatic. The governing equations for this investigation are formulated, nondimensionalized, and then solved by Galerkin finite element approach. The numerical findings were examined across a wide range of Richardson number (0.1 ≤ Ri ≤ 10), Reynolds number (1 ≤ Re ≤ 125), Hartmann number (0 ≤ Ha ≤ 100), and volume fraction of nanofluid (0 ≤ φ ≤ 0.05). The current study's findings demonstrate that the flow strength increases inversely as the Reynolds number rises, which pushes the isotherms down to the lower part of the trapezoidal cavity. The Nuavg rises as the Ri rise, the maximum Nuavg = 10.345 at Ri = 10, Re = 50, ϕ = 0.05, and Ha = 0; however, it reduces with increasing Hartmann number. Also, it increase by increasing ϕ, at Ri = 10, the Nuavg increased by 8.44% when the volume fraction of nanofluid increased from (ϕ = 0–0.05).
Minimization of the entropy generation in MHD flow and heat transfer of nanofluid over a vertical cylinder under the influence of thermal radiation and slip condition
Authors: Agrawal Rashmi , Kaswan Pradeep
Published: October 2021

This investigation essentially determines the nanofluids' heat transfer performance and flow characteristics over a vertical cylinder. The influences of thermal radiation, velocity slip, and thermal slip conditions further exert effects. The mathematical model for the transport of heat and momentum is characterized by a PDE set, which is then interpreted by embracing a fourth‐order exactness program (Bvp4c). Graphical decisions reveal various parameters' values on the velocity profile, temperature profile, entropy generation, and Bejan number. A comparison of two nanofluids obtained by adding metal nanoparticles and metal oxide nanoparticles () into the base fluid () is illustrated. Heat transmission improves when the curvature parameter, mixed convection parameter, and Eckert number are raised, but it is reduced when the thermal slip parameter increases. Entropy generation is also enriched with magnetic parameter and Brinkman number, whereas it is overcome with velocity and thermal slip parameters. Furthermore, nanoparticles give a significant enhancement in the rate of heat transfer compared to nanoparticles, and entropy generation due to heat transfer is dominant for alumina nanoparticles as compared to copper nanoparticles.
Pharmacists and opioid use disorder care during COVID‐19: Call for action
Authors: Mohammad Insaf , Berri Dena , Tutag Lehr Victoria
Published: October 2021

Opioid use disorder (OUD) is a chronic relapsing condition characterized by problematic opioid use causing significant impairment in daily life. Medication for opioid use disorder using buprenorphine, methadone, and naltrexone with behavioral therapy reduces illicit opioid use and risk of overdose death. Despite evidence and decades of experience, barriers limit access to treatment and care for individuals with OUD. Barriers include a lack of treatment centers particularly in rural areas, regulations on buprenorphine prescribing, and stigma from the community and health care professionals. While many barriers are longstanding, the coronavirus disease 2019 (COVID‐19) pandemic‐forced isolation and associated stress has exacerbated challenges for individuals with mental health conditions such as OUD. Pharmacists are well‐positioned to bridge existing gaps in OUD care, particularly during the COVID‐19 pandemic. Roles for pharmacists include OUD risk identification and screening, referral of patients to treatment and support programs, ensuring medication access, expanding naloxone access, and advocacy initiatives. This review article identifies barriers to care for patients with OUD during the COVID‐19 pandemic and explores opportunities and resources for pharmacists to improve OUD care during the pandemic and beyond.
Hydroxyapatite‐hybridized double‐network hydrogel surface enhances differentiation of bone marrow‐derived mesenchymal stem cells to osteogenic cells
Authors: Kaibara Takuma , Wang Lei , Tsuda Masumi , Nonoyama Takayuki , Kurokawa Takayuki , Iwasaki Norimasa , Gong Jian Ping , Tanaka Shinya , Yasuda Kazunori
Published: October 2021

Recently, we have developed a hydroxyapatite (HAp)‐hybridized double‐network (DN) hydrogel (HAp/DN gel), which can robustly bond to the bone tissue in the living body. The purpose of this study is to clarify whether the HAp/DN gel surface can differentiate the bone marrow‐derived mesenchymal stem cells (MSCs) to osteogenic cells. We used the MSCs which were harvested from the rabbit bone marrow and cultured on the polystyrene (PS) dish using the autogenous serum‐supplemented medium. First, we confirmed the properties of MSCs by evaluating colony forming unit capacity, expression of MSC markers using flow cytometry, and multidifferential capacity. Secondly, polymerase chain reaction analysis demonstrated that the HAp/DN gel surface significantly enhanced mRNA expression of the eight osteogenic markers (TGF‐β1,BMP‐2,Runx2,Col‐1, ALP,OPN,BSP, andOCN)in the cultured MSCs at 7 days than the PS surfaces (p < 0.0001), while the DN gel and HAp surfaces provided no or only a slight effect on the expression of these markers except forRunx2. Additionally, the alkaline phosphatase activity was significantly higher in the cells cultured on the HAp/DN gel surface than in the other three material surfaces (p < 0.0001). Thirdly, when the HAp/DN gel plug was implanted into the rabbit bone marrow, MSC marker‐positive cells were recruited in the tissue generated around the plug at 3 days, and Runx2 and OCN were highly expressed in these cells. In conclusion, this study demonstrated that the HAp/DN gel surface can differentiate the MSCs into osteogenic cells.
LncRNA MIR4435‐2HG functions as a ceRNA against miR‐125a‐5p and promotes neuroglioma development by upregulating TAZ
Authors: Shen Wangzhen , Zhang Jiawei , Pan Yunfeng , Jin Yun
Published: October 2021

Background

Expression of the TAZ gene is closely related to the prognosis of glioma patients. We hoped to find long noncoding RNAs (lncRNAs) related to TAZ and a new target for glioma treatment.

Methods

TAZ‐related genes were found by dual‐luciferase reporter gene assay, and the correlation of each gene was analyzed by the Pearson method. Human glioma cell lines U87 MG and U251 and glioma rats were used for cytology assays, and the related genes were transfected. We conducted immunohistochemistry, RT‐qPCR, Western blotting, CCK8 test, flow cytometry, transwell assays, clone formation analysis, and tumor weight measurements to verify the above relationship.

Results

We found that miR‐125a‐5p was closely related to the TAZ gene, and the lncRNA MIR4435‐2HG was closely related to miR‐125a‐5p. Both MIR4435‐2HG‐OE and TAZ increased the expression of the TAZ gene, activated the Wnt signaling pathway, inhibited apoptosis, and promoted migration and proliferation in glioma cells. Besides, it also increased the tumor volume of gliomas in a rat model subcutaneously inoculated with glioma cells. We also found miR‐125a‐5p could block the effect of MIR4435‐2HG‐OE and TAZ.

Conclusions

LncRNA MIR4435‐2HG obstructs the functions of miR‐125a‐5p and promotes neuroglioma development by upregulating the TAZ gene.
Differentiated service delivery for people using second‐line antiretroviral therapy: clinical outcomes from a retrospective cohort study in KwaZulu‐Natal, South Africa
Authors: Lewis Lara , Sookrajh Yukteshwar , Gate Kelly , Khubone Thokozani , Maraj Munthra , Mkhize Siyabonga , Hermans Lucas E. , Ngobese Hope , Garrett Nigel , Dorward Jienchi
Published: October 2021

Introduction

Evidence is needed to guide the inclusion of broader groups of people living with HIV (PLHIV) in differentiated service delivery (DSD) programmes. We assessed treatment outcomes among PLHIV on second‐line regimens in a community antiretroviral therapy (ART) delivery programme, compared to those who remained at clinics.

Methods

Using data from 61 public clinics, we did a retrospective cohort study among PLHIV receiving second‐line ART following rollout of the Centralized Chronic Medicines Dispensing and Distribution (CCMDD) programme in KwaZulu‐Natal, South Africa. We included PLHIV from the timepoint when they were first eligible, though not necessarily referred, for community ART within CCMDD and followed them for 18 months. We used multivariable logistic regression to compare 12‐month attrition and viraemia between clients referred for community ART and those remaining in clinic care.

Results

Among 209,744 PLHIV aged ≥ 18 years who collected ART between October 2016 and December 2018, 7511 (3.6%) received second‐line ART. Of these, 2575 (34.3%) were eligible for community ART. The median age was 39.0 years (interquartile range 34.0–45.0) and 1670 (64.9%) were women. Five hundred and eighty‐four (22.7%) were referred for community ART within 6 months of meeting eligibility criteria. Overall, 4.5% [95% confidence interval (CI) 3.0–6.6%] in community ART and 4.4% (95% CI 3.5–5.4%) in clinic care experienced attrition at 12 months post eligibility for community ART. Two thousand one hundred and thirty‐eight (83.0%) had a viral load recorded 6–18 months after becoming eligible, and of these, 10.3% (95% CI 7.7–13.3%) in community ART and 11.3% (95% CI 9.8–12.9%) in clinic care had viraemia > 200 copies/ml. In separate regressions adjusted for age, gender, district, time on second‐line ART, nucleoside reverse transcriptase inhibitor backbone and year of eligibility, no differences in the odds of attrition [adjusted odds ratio (aOR) 1.02, 95% CI 0.71–1.47] or viraemia (aOR 0.91, 95% CI 0.64–1.29) were observed between those in community ART and those remaining in clinic care.

Conclusions

We found good outcomes among PLHIV who were stable on second‐line regimens and referred for community ART. Efforts to expand DSD access among this group should be prioritized.
HIV care using differentiated service delivery during the COVID‐19 pandemic: a nationwide cohort study in the US Department of Veterans Affairs
Authors: McGinnis Kathleen A. , Skanderson Melissa , Justice Amy C. , Akgün Kathleen M. , Tate Janet P. , King Joseph T. , Rentsch Christopher T. , Marconi Vincent C. , Hsieh Evelyn , Ruser Christopher , Kidwai‐Khan Farah , Yousefzadeh Roozbeh , Erdos Joseph , Park Lesley S.
Published: October 2021

Introduction

The Department of Veterans Affairs (VA) is the largest provider of HIV care in the United States. Changes in healthcare delivery became necessary with the COVID‐19 pandemic. We compared HIV healthcare delivery during the first year of the COVID‐19 pandemic to a prior similar calendar period.

Methods

We included 27,674 people with HIV (PWH) enrolled in the Veterans Aging Cohort Study prior to 1 March 2019, with ≥1 healthcare encounter from 1 March 2019 to 29 February 2020 (2019) and/or 1 March 2020 to 28 February 2021 (2020). We counted monthly general medicine/infectious disease (GM/ID) clinic visits and HIV‐1 RNA viral load (VL) tests. We determined the percentage with ≥1 clinic visit (in‐person vs. telephone/video [virtual]) and ≥1 VL test (detectable vs. suppressed) for 2019 and 2020. Using pharmacy records, we summarized antiretroviral (ARV) medication refill length (<90 vs. ≥90 days) and monthly ARV coverage.

Results

Most patients had ≥1 GM/ID visit in 2019 (96%) and 2020 (95%). For 2019, 27% of visits were virtual compared to 64% in 2020. In 2019, 82% had VL measured compared to 74% in 2020. Of those with VL measured, 92% and 91% had suppressed VL in 2019 and 2020. ARV refills for ≥90 days increased from 39% in 2019 to 51% in 2020. ARV coverage was similar for all months of 2019 and 2020 ranging from 76% to 80% except for March 2019 (72%). Women were less likely than men to be on ARVs or to have a VL test in both years.

Conclusions

During the COVID‐19 pandemic, the VA increased the use of virtual visits and longer ARV refills, while maintaining a high percentage of patients with suppressed VL among those with VL measured. Despite decreased in‐person services during the pandemic, access to ARVs was not disrupted. More follow‐up time is needed to determine whether overall health was impacted by the use of differentiated service delivery and to evaluate whether a long‐term shift to increased virtual healthcare could be beneficial, particularly for PWH in rural areas or with transportation barriers. Programmes to increase ARV use and VL testing for women are needed.
Faim knockout leads to gliosis and late‐onset neurodegeneration of photoreceptors in the mouse retina
Authors: Sirés Anna , Turch‐Anguera Mireia , Bogdanov Patricia , Sampedro Joel , Ramos Hugo , Ruíz Lasa Agustín , Huo Jianxin , Xu Shengli , Lam Kong‐Peng , López‐Soriano Joaquín , Pérez‐García M. Jose , Hernández Cristina , Simó Rafael , Solé Montse , Comella Joan X.
Published: October 2021

Fas Apoptotic Inhibitory Molecule protein (FAIM) is a death receptor antagonist and an apoptosis regulator. It encodes two isoforms, namely FAIM‐S (short) and FAIM‐L (long), both with significant neuronal functions. FAIM‐S, which is ubiquitously expressed, is involved in neurite outgrowth. In contrast, FAIM‐L is expressed only in neurons and it protects them from cell death. Interestingly, FAIM‐L is downregulated in patients and mouse models of Alzheimer's disease before the onset of neurodegeneration, and Faim transcript levels are decreased in mouse models of retinal degeneration. However, few studies have addressed the role of FAIM in the central nervous system, yet alone the retina. The retina is a highly specialized tissue, and its degeneration has proved to precede pathological mechanisms of neurodegenerative diseases. Here we describe that Faim depletion in mice damages the retina persistently and leads to late‐onset photoreceptor death in older mice. Immunohistochemical analyses showed that Faim knockout (Faim−/−) mice present ubiquitinated aggregates throughout the retina from early ages. Moreover, retinal cells released stress signals that can signal to Müller cells, as shown by immunofluorescence and qRT‐PCR. Müller cells monitor retinal homeostasis and trigger a gliotic response in Faim−/− mice that becomes pathogenic when sustained. In this regard, we observed pronounced vascular leakage at later ages, which may be caused by persistent inflammation. These results suggest that FAIM is an important player in the maintenance of retinal homeostasis, and they support the premise that FAIM is a plausible early marker for late photoreceptor and neuronal degeneration.
Envisioning the role of inwardly rectifying potassium (Kir) channel in epilepsy
Authors: Akyuz Enes , Koklu Betul , Uner Arda , Angelopoulou Efthalia , Paudel Yam Nath
Published: October 2021

Epilepsy is a devastating neurological disorder characterized by recurrent seizures attributed to the disruption of the dynamic excitatory and inhibitory balance in the brain. Epilepsy has emerged as a global health concern affecting about 70 million people worldwide. Despite recent advances in pre‐clinical and clinical research, its etiopathogenesis remains obscure, and there are still no treatment strategies modifying disease progression. Although the precise molecular mechanisms underlying epileptogenesis have not been clarified yet, the role of ion channels as regulators of cellular excitability has increasingly gained attention. In this regard, emerging evidence highlights the potential implication of inwardly rectifying potassium (Kir) channels in epileptogenesis. Kir channels consist of seven different subfamilies (Kir1–Kir7), and they are highly expressed in both neuronal and glial cells in the central nervous system. These channels control the cell volume and excitability. In this review, we discuss preclinical and clinical evidence on the role of the several subfamilies of Kir channels in epileptogenesis, aiming to shed more light on the pathogenesis of this disorder and pave the way for future novel therapeutic approaches.
Knowledge of chronic intestinal failure among US gastroenterologists: Cause for concern and learning opportunity
Authors: Iyer Kishore R. , Winkler Marion , Zubizarreta Nicole , Nisenholtz Marjorie , Lucero Katie , Lubarda Jovana
Published: October 2021

Background

Chronic intestinal failure (CIF) is an ultrarare disease, with an estimated national prevalence of ∼25,000 cases. There is a suspicion of widespread lack of expertise in CIF care, but no formal assessment tool or data exist. We developed and validated a knowledge test in CIF and now report our preliminary results from testing CIF knowledge in a cohort of US gastroenterologists.

Method

We developed a 20‐question knowledge test in CIF, covering four key components of IF. After internal testing, refinement, and revision, we administered the test to a convenience sample of experts and nonexperts in IF. We then deployed the validated test to a cohort of 100 US gastroenterologists.

Results

The test had a Cronbach alpha of 0.74, suggesting a reliable test, with a threshold score to discriminate experts and nonexperts of 13.4 (maximum 20) and with a sensitivity of 81.3% and specificity of 86.4%. The overall mean score of 8.2 for the 100 US gastroenterologists was at the level of nonexperts in our convenience sample.

Conclusion

The preliminary results of our validated knowledge test in IF among a broad group of US gastroenterologists demonstrate lack of knowledge in IF.