bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Orientation of Liquid Crystals Inside Micropores of Metal–Organic Frameworks Having Thermoresponsivity
Authors: Anan Shizuka , Kurihara Takuya , Yamaguchi Masaki , Kikuchi Hirotsugu , Kokado Kenta
Published: January 2024

With the aim of controlling the orientation of liquid crystals (LCs) toward realizing external stimuli–responsive materials with tunable functionalities, we synthesized a composite of LCs and metal–organic frameworks (MOFs) by filling LCs into the pores of MOFs (LC@MOFs) for the first time. The included LCs interact with the MOFs through coordination bonds between the cyano groups of the LCs and the metal ions of the MOFs, enabling the orientation of the LC molecules inside the pores of the MOFs and the realization of birefringence of LC@MOFs. The three‐dimensional nanometer interstice frameworks maintained the LC orientation even at temperatures much higher than the isotropic phase transition temperature of bulk LCs. Furthermore, the orientational state changed upon heating or cooling, inducing temperature‐dependent birefringence. This study provides a new approach to the development of stimuli–responsive optical materials and stimuli–responsive MOFs.
Aerobic Asymmetric Allylic C−H Alkylation by Synergistic Chiral Primary Amine‐Palladium‐Hydroquinone Catalysis
Authors: Wang Rui , Zhang Long , Luo Sanzhong
Published: January 2024

A synergistic chiral primary amine/palladium /p‐hydroquinone catalysis was developed to facilitate oxidative asymmetric allylic C−H alkylation under aerobic conditions. The ternary synergistic catalysis enables a facile allylic C−H activation and alkylation with oxygen so that stoichiometric utilization of benzoquinone can be avoided. The identified optimal catalytic system allows for terminal addition to allyl arenes with α‐branched β‐ketocarbonyls to afford allylic adducts bearing all‐carbon quaternary centers with high regio‐ and enantioselectivity. This work provides new insights for further studies on the aerobically oxidative C−H alkylation reaction.
Bayesian Model Selection via Composite Likelihood for High‐dimensional Data Integration
Authors: Zhang Guanlin , Wu Yuehua , Gao Xin
Published: January 2024

We consider data integration problems where correlated data are collected from multiple platforms. Within each platform, there are linear relationships between the responses and a collection of predictors. We extend the linear models to include random errors coming from a much wider family of sub‐Gaussian and subexponential distributions. The goal is to select important predictors across multiple platforms, where the number of predictors and the number of observations both increase to infinity. We combine the marginal densities of the responses obtained from different platforms to form a composite likelihood and propose a model selection criterion based on Bayesian composite posterior probabilities. Under some regularity conditions, we prove that the model selection criterion is consistent to recover the union support of the predictors with divergent true model size.
Clustering spatial functional data using a geographically weighted Dirichlet process
Authors: Pan Tianyu , Shen Weining , Hu Guanyu
Published: January 2024

We propose a Bayesian nonparametric clustering approach to study the spatial heterogeneity effect for functional data observed at spatially correlated locations. We consider a geographically weighted Chinese restaurant process equipped with a conditional autoregressive prior to capture fully the spatial correlation of function curves. To sample efficiently from our model, we customize a prior called Quadratic Gamma, which ensures conjugacy. We design a Markov chain Monte Carlo algorithm to infer simultaneously the posterior distributions of the number of groups and the grouping configurations. The superior numerical performance of the proposed method over competing methods is demonstrated using simulated examples and a U.S. annual precipitation study.
Discrepancy in accelerated approvals for cancer drugs in the United States and Europe
Authors: Nierengarten Mary Beth
Published: January 2024

This news section offers Cancer readers timely information on events, public policy analysis, topical issues, and personalities. In this issue, the discrepancy in accelerated approvals for cancer drugs in the United States and Europe comes down to the two countries having different lists of which approvals have been withdrawn, resulting in patient confusion. In addition, treatment with anticancer therapies increases the risk of developing a thromboembolic event in patients with cancer and COVID‐19, and a new test for detecting cervical adenocarcinoma can find cancer that current Papanicolaou tests are less likely to pick up.
Understanding and illustrating the irreversible self‐discharge in rechargeable batteries by the Evans Diagram
Authors: Pu Xiangjun , Zheng Yingping , Qi Aiping , Lyu Linlong , Ruan Guanqiang , Cao Yuliang , Chen Zhongxue , Xu Zheng‐Long
Published: January 2024

As an intermediary between chemical and electric energy, rechargeable batteries with high conversion efficiency are indispensable to empower electric vehicles and stationary energy storage systems. Self‐discharge with adverse effects on energy output and lifespan is a long‐existing challenge and intensive endeavors have been devoted to alleviating it. Previous reports mainly focused on examining key factors influencing the rate of self‐discharge, however, its origination has rarely been revealed from the viewpoint of fundamental electrochemistry. The Evans Diagram, which is a corrosion polarization diagram based on kinetics (corrosion current density) and thermodynamics (potential), is an informative method for analyzing the corrosion process of metals. In this perspective, after an introduction to electrochemical fundamentals, as well as the identical origination of battery self‐discharging and metal corrosion, we first transferred the concept of the Evans Diagram to illustrate the origination and evolution of self‐discharge in rechargeable batteries. The corresponding Evans Diagram has been proposed for different key factors, which were eventually used as guidance to exploit thermodynamical and kinetical solutions to alleviate the parasitic reactions induced by self‐discharge. This contribution is believed to provide new insights towards understanding and regulating self‐discharge problems, and promote the establishment of feasible protocols for battery storage in practice.
Reduced Plasma Levodopa Fluctuations with More Frequent Administration of a Novel Carbidopa/Levodopa Functionally Scored Tablet
Authors: Chase Thomas N. , AL‐Sabbagh Ahmad , Koga Minako , Clarence‐Smith Kathleen
Published: January 2024

Levodopa/carbidopa remains the gold standard for treating Parkinson disease (PD), but chronic pulsatile administration contributes to motor complications. This Phase 1 study used a new immediate‐release (IR) formulation of carbidopa/levodopa 25/100 mg that is functionally scored for easy and precise splitting to evaluate the effects on levodopa plasma variability when smaller doses are taken more frequently. These functionally scored tablets were shown to be bioequivalent to carbidopa/levodopa 25‐/100‐mg IR generic reference tablets. Twenty‐two healthy volunteers received a whole tablet every 4 hours versus half of the tablet every 2 hours. Plasma levodopa fluctuations were significantly reduced with half‐tablets dosed every 2 hours, with a 44% reduction in peaks (P < .0001). While drug exposure did not differ, parameters that underlie motor response variations, including mean peak‐to‐trough difference and variance, were 51% and 56% less, respectively, with more frequent dosing (both P ≤ .0024). Safety and tolerability of both regimens were similar. In conclusion, more frequent administration of half‐tablets of the new functionally scored IR formulation safely provided more constant levodopa levels than whole tablets dosed less often. This tablet technology could facilitate the benefits of more physiologic dopamine replenishment in patients with PD, particularly those with reduced manual dexterity.
Effect of Tacrolimus Formulation (Prolonged‐Release vs Immediate‐Release) on Its Susceptibility to Drug‐Drug Interactions with St. John's Wort
Authors: Gümüs Katja S. , Teegelbekkers Anna , Sauter Max , Meid Andreas D. , Burhenne Jürgen , Weiss Johanna , Blank Antje , Haefeli Walter E. , Czock David
Published: January 2024

Tacrolimus is metabolized by cytochrome P450 3A (CYP3A) and is susceptible to interactions with the CYP3A and P‐glycoprotein inducer St. John's Wort (SJW). CYP3A isozymes are predominantly expressed in the small intestine and liver. Prolonged‐release tacrolimus (PR‐Tac) is largely absorbed in distal intestinal segments and is less susceptible to CYP3A inhibition. The effect of induction by SJW is unknown. In this randomized, crossover trial, 18 healthy volunteers received single oral tacrolimus doses (immediate‐release [IR]‐Tac or PR‐Tac, 5 mg each) alone and during induction by SJW. Concentrations were quantified using ultra‐high performance liquid chromatography coupled with tandem mass spectrometry and non‐compartmental pharmacokinetics were evaluated. SJW decreased IR‐Tac exposure (area under the concentration‐time curve) to 73% (95% confidence interval 60%‐88%) and maximum concentration (Cmax) to 61% (52%‐73%), and PR‐Tac exposure to 67% (55%‐81%) and Cmax to 69% (58%‐82%), with no statistical difference between the 2 formulations. The extent of interaction appeared to be less pronounced in volunteers with higher baseline CYP3A4 activity and in CYP3A5 expressors. In contrast to CYP3A inhibition, CYP3A induction by SJW showed a similar extent of interaction with both tacrolimus formulations. A higher metabolic baseline capacity appeared to attenuate the extent of induction by SJW.
Cover Crops Support Microbial Diversity: Three Case Studies
Authors: Kish Stacy
Published: January 2024

Plant diversity, including diversified rotation and cover crops, is a part of conservation agricultural practices that support soil microbial communities. Three case studies from Canada, Belgium, and the United States uphold the importance of cover crops for promoting the long‐term abundance and diversity of the soil microbiome. These results offer information on how microbial communities respond to different agricultural management practices with the goal of developing environmentally friendly, sustainable cropping systems. Earn 1 CEU in Soil & Water Management by reading this article and taking the quiz at https://web.sciencesocieties.org/Learning‐Center/Courses.
Nitrogen‐Doped Cellulose‐Derived Porous Carbon Fibers for High Mass‐Loading Aqueous Supercapacitors
Authors: Lv Ting , Wang Xiaofeng , Zhang Ying , Yang Xiaomin
Published: January 2024

Biomass‐based porous carbon with renewability and flexible structure tunability is a promising electrode material for supercapacitors. However, there is a huge gap between experimental research and practical applications. How to maintain good electrochemical performance of high mass‐loading electrodes and suppress the self‐discharge of supercapacitors is a key issue that urgently needs to be addressed. The structure regulation of electrode materials such as heteroatom doping is a promising optimization strategy for high mass‐loading electrodes. In this work, nitrogen‐doped cellulose‐derived porous carbon fibers (N‐CHPCs) were prepared by a facile bio‐template method using cotton cellulose as raw material and urea as dopant. The prepared N‐CHPCs have high specific surface area, excellent hierarchical porous structure, partial graphitization properties and suitable heteroatom content. The assembled high mass‐loading (12.8 mg cm−2; 245 μm) aqueous supercapacitor has excellent electrochemical performance, i. e., low open‐circuit voltage attenuation rate (21.39 mV h−1), high voltage retention rate (78.81 %), high specific capacitance (295.8 F g−1 at 0.1 A g−1), excellent area capacitance (3.79 F cm−2 at 0.1 A g−1), excellent cycling stability (97.28 % over 20,000 cycles at 1.0 A g−1). The excellent performance of high mass‐loading N‐CHPCs is of great significance for their practical applications in advanced aqueous supercapacitors.
Innovative flow‐through reaction system for the sustainable production of phenolic monomers from lignocellulose catalyzed by supported Mo2C.
Authors: Maisterra Maitane , Atienza‐Martínez María , Hablich Karina , Moreira Rui , Martínez‐Merino Víctor , Gandía Luis M. , Cornejo Alfonso , Bimbela Fernando
Published: January 2024

Molybdenum carbide supported on activated carbon (β‐Mo2C/AC) has been tested as catalyst in the reductive catalytic fractionation (RCF) of lignocellulosic biomass both in batch and in Flow‐Through (FT) reaction systems. High phenolic monomer yields (34 wt.%) and selectivity to monomers with reduced side alkyl chains (up to 80 wt.%) could be achieved in batch in the presence of hydrogen. FT‐RCF were made with no hydrogen feed, thus via transfer hydrogenation from ethanol. Similar selectivity could be attained in FT‐RCF using high catalyst/biomass ratios (0.6) and high molybdenum loading (35 wt.%) in the catalyst, although selectivity decreased with lower catalyst/biomass ratios or molybdenum contents. Regardless of these parameters, high delignification of the lignocellulosic biomass and similar monomer yields were observed in the FT mode (13‐15 wt.%) while preserving the holocellulose fractions in the delignified pulp. FT‐RCF system outperforms the batch reaction mode in the absence of hydrogen, both in terms of activity and selectivity to reduced monomers that is attributed to the two‐step non‐equilibrium processes and the removal of diffusional limitations that occur in the FT mode. Even though some molybdenum leaching was detected, the catalytic performance could be maintained with negligible loss of activity or selectivity for 15 consecutive runs.
Organic Chemicals from Wood: Selective Depolymerization and Dearomatization of Lignin via Aqueous Electrocatalysis
Authors: Lindenbeck Lucie M. , Barra Vanessa C. , Dahlhaus Sira , Brand Silas , Wende Luca M. , Beele Björn B. , Schebb Nils. H. , Rodrigues Bruno V. M. , Slabon Adam
Published: January 2024

Replacing crude oil as the primary industrial source of carbon‐based chemicals has become crucial for both environmental and resource sustainability reasons. In this scenario, wood arises as an excellent candidate, whilst depolymerization approaches have emerged as promising strategies to unlock the lignin potential as a resource in the production of high‐value organic chemicals. However, many drawbacks, such as toxic solvents, expensive catalysts, high energy inputs, and poor product selectivity have represented major challenges to this task. Herein, we present an unprecedented approach using electrocatalysis for the simultaneous depolymerization and dearomatization of lignin in aqueous medium under ambient conditions. By employing water/sodium carbonate as a solvent system, we demonstrated a pathway for selectively depolymerizing lignin under reductive electrochemical conditions using carbon as an electrocatalyst. After reductive electrocatalysis, the presence of aromatic compounds was no longer detected via nuclear magnetic resonance (NMR) spectroscopy. Further characterization by NMR, FTIR spectroscopy, and mass spectrometry revealed the major presences of sodium levulinate, sodium 4‐hydroxyvalerate, sodium formate, and sodium acetate as products. By achieving a complete dearomatization, valuable aliphatic intermediates with enhanced reactivity were selectively obtained, opening new avenues for further synthesis of many different organic chemicals, and contributing to a more sustainable and circular economy.
CoO supported NiFe layered double hydroxide sandwich‐like nanosheets on hierarchical carbon framework for efficient electrocatalytic oxygen evolution
Authors: Wang Changshui , Zhang Qian , Liu Zhenlu , Li Bei , Zhao Wei , Zhang Chunmei , Jiang Shaohua , Wang Jun , Liu Kunming , He Shuijian
Published: January 2024

Exploration of greatly efficient and steady non‐noble oxygen evolution reaction (OER) electrocatalysts is of great significance in improving the overall efficiency of energy density systems such as regenerative fuel cells, water electrolyzes, and metal‐air batteries. Herein, inspired by hierarchical 3D porous structures with open microchannels of natural wood, CoO@NiFe LDH sandwich‐like nanosheets were anchored on the carbonized wood (CW) via electrodeposition and calcination strategies. The strong interactions between CoO nanosheets and NiFe LDH nanosheets endow CoO@NiFe LDH/CW electrocatalyst with high catalytic properties toward the OER comparable to CoO/CW and NiFe LDH/CW. The optimized CoO@NiFe LDH/CW electrocatalyst demonstrates good OER catalytic performance with an overpotential of 230 mV at 100 mA cm−2. This work presents an innovative approach to utilize renewable resources for constructing advanced free‐standing catalysts.
Badgers remain fearless in the face of simulated wolf presence near their setts
Authors: Diserens Tom A. , Churski Marcin , Bubnicki Jakub W. , Zalewski Andrzej , Brzeziński Marcin , Kuijper Dries P. J.
Published: January 2024

Many mesocarnivores are fossorial and use burrow systems to avoid predators. But fossorial animals cannot stay safely underground forever; they must also risk emerging overground to forage and find mates. To make this trade‐off effectively and maximise their own fitness, it is imperative they assess how risk varies in space and time and adapt their denning behaviour accordingly. We used the badger in Białowieża Forest, Poland, as a model for investigating how the denning behaviour of a fossorial mesocarnivore varies in response to short‐term large carnivore risk. To this end, we experimentally simulated perceived wolf presence outside 10 badger setts using audio playbacks of wolves (their howls). We assayed two behavioural measures of fear: badger emergence time from setts on the day playbacks were broadcast and their presence in setts on the day after. We found that neither badger emergence time nor next‐day sett use varied in response to wolf playbacks. The results of the present study contrast with a previous study of ours that found badgers used setts in areas with high landscape level perceived wolf risk less often than those in lower‐risk areas. Together, these papers' findings suggest that different spatiotemporal scales of perceived risk can have differential effects on badger behaviour. We conclude that rather than take risk avoidance measures at all risky times and places, badgers likely display a diversity of reactions to large carnivore presence that depend on the context and spatiotemporal scale of the risk being perceived.
Substituent Effects on the Electronic Ground State (Singlet versus Triplet) of Indenyl Cations: DFT and CASPT2 Studies
Authors: Takano Ma‐aya , Antol Ivana , Abe Manabu
Published: January 2024

The electronic ground states of cations (singlet versus triplet) attract significant attention in the discovery of novel carbocation chemistry. Although the cyclopentadienyl cation exhibits a triplet ground state because of the antiaromaticity of the closed‐shell singlet state, the ground state of the indenyl cation, which is a benzene‐fused derivative of the cyclopentadienyl cation, is reportedly a closed‐shell singlet state rather than a triplet state. In this study, in order to establish a strategy for controlling the ground state of indenyl cations, the substituent effects at the C2 and C5 positions of their structures were computed using density functional theory and complete active space multiconfiguration second order perturbation levels of theory.
Seismic Structure‐Soil‐Structure Interaction between inelastic structures
Authors: Vicencio Felipe , Alexander Nicholas A. , Málaga‐Chuquitaype Christian
Published: January 2024

Frequently, buildings in urban areas are designed by considering their stand‐alone response, that is, as single structures with no neighboring buildings. Nevertheless, the existence of a high density of buildings in large metropolitan areas inevitably results in the likelihood of an important seismic interaction between adjacent buildings through the underlying soil. This paper explores the effects of Structure‐Soil‐Structure Interaction (SSSI) on the seismic response of two yielding structures embedded in a linear elastic soil. A simple two‐dimensional nonlinear reduced‐order parametric model is proposed, where different building parameters are considered. A nonlinear phenomenological Bouc–Wen model is assumed for the buildings. A database of 15 strong ground motion records and an additional spectrally matched seismic ground motion are considered. An extensive parametric study comprising over two million nonlinear cases is conducted. The results show important differences between nonlinear SSSI and nonlinear SSI for particular parameter configurations. Nevertheless, due to energy dissipation and increases in damping in the nonlinear case, the effects of SSSI are less relevant compared with the linear case.
Probiotic yogurt regulates gut microbiota homeostasis and alleviates hepatic steatosis and liver injury induced by high‐fat diet in golden hamsters
Authors: Zhu Linwensi , Ying Na , Hao Liuyi , Fu Ai , Ding Qinchao , Cao Feiwei , Ren Daxi , Han Qiang , Li Songtao
Published: January 2024

This study aimed to investigate the beneficial effects of probiotic yogurt on lipid metabolism and gut microbiota in metabolic‐related fatty liver disease (MAFLD) golden hamsters fed on a high‐fat diet (HFD). The results demonstrated that probiotic yogurt significantly reversed the adverse effects caused by HFD, such as body and liver weight gain, liver steatosis and damage, sterol deposition, and oxidative stress after 8 weeks of intervention. qRT‐PCR analysis showed that golden hamsters fed HFD had upregulated genes related to adipogenesis, increased free fatty acid infiltration, and downregulated genes related to lipolysis and very low‐density lipoprotein secretion. Probiotic yogurt supplements significantly inhibited HFD‐induced changes in the expression of lipid metabolism‐related genes. Furthermore, 16S rRNA gene sequencing of the intestinal content microbiota suggested that probiotic yogurt changed the diversity and composition of the gut microbiota in HFD‐fed hamsters. Probiotic yogurt decreased the ratio of the phyla Firmicutes/Bacteroidetes, the relative abundance of the LPS‐producing genus Desulfovibrio, and bacteria involved in lipid metabolism, whereas it increased the relative abundance of short‐chain fatty acids producing bacteria in HFD‐fed hamsters. Predictive functional analysis of the microbial community showed that probiotic yogurt‐modified genes involved in LPS biosynthesis and lipid metabolism. In summary, these findings support the possibility that probiotic yogurt significantly improves HFD‐induced metabolic disorders through modulating intestinal microflora and lipid metabolism and effectively regulating the occurrence and development of MAFLD. Therefore, probiotic yogurt supplementation may serve as an effective nutrition strategy for the treatment of patients with MAFLD clinically.
Impaired oligodendrogenesis in the white matter of aged mice following diffuse traumatic brain injury
Authors: Michalettos Georgios , Clausen Fredrik , Özen Ilknur , Ruscher Karsten , Marklund Niklas
Published: January 2024

Senescence is a negative prognostic factor for outcome and recovery following traumatic brain injury (TBI). TBI‐induced white matter injury may be partially due to oligodendrocyte demise. We hypothesized that the regenerative capacity of oligodendrocyte precursor cells (OPCs) declines with age. To test this hypothesis, the regenerative capability of OPCs in young [(10 weeks ±2 (SD)] and aged [(62 weeks ±10 (SD)] mice was studied in mice subjected to central fluid percussion injury (cFPI), a TBI model causing widespread white matter injury. Proliferating OPCs were assessed by immunohistochemistry for the proliferating cell nuclear antigen (PCNA) marker and labeled by 5‐ethynyl‐2′‐deoxyuridine (EdU) administered daily through intraperitoneal injections (50 mg/kg) from day 2 to day 6 after cFPI. Proliferating OPCs were quantified in the corpus callosum and external capsule on day 2 and 7 post‐injury (dpi). The number of PCNA/Olig2‐positive and EdU/Olig2‐positive cells were increased at 2dpi (p < .01) and 7dpi (p < .01), respectively, in young mice subjected to cFPI, changes not observed in aged mice. Proliferating Olig2+/Nestin+ cells were less common (p < .05) in the white matter of brain‐injured aged mice, without difference in proliferating Olig2+/PDGFRα+ cells, indicating a diminished proliferation of progenitors with different spatial origin. Following TBI, co‐staining for EdU/CC1/Olig2 revealed a reduced number of newly generated mature oligodendrocytes in the white matter of aged mice when compared to the young, brain‐injured mice (p < .05). We observed an age‐related decline of oligodendrogenesis following experimental TBI that may contribute to the worse outcome of elderly patients following TBI.
Living well with dementia: An exploratory matched analysis of minority ethnic and white people with dementia and carers participating in the IDEAL programme
Authors: Victor Christina R. , Gamble Laura D. , Pentecost Claire , Quinn Catherine , Charlwood Catherine , Matthews Fiona E. , Clare Linda
Published: January 2024

Objectives

The increasing heterogeneity of the population of older people is reflected in an increasing number of people with dementia and carers drawn from minority ethnic groups. Data from the IDEAL study are used to compare indices of ‘living well’ among people with dementia and carers from ethnic minority groups with matched white peers.

Methods

We used an exploratory cross‐sectional case‐control design to compare ‘living well’ for people with dementia and carers from minority ethnic and white groups. Measures for both groups were quality of life, life satisfaction, wellbeing, loneliness, and social isolation and, for carers, stress, relationship quality, role captivity and caring competence.

Results

The sample of people with dementia consisted of 20 minority ethnic and 60 white participants and for carers 15 and 45 respectively. People with dementia from minority ethnic groups had poorer quality of life (−4.74, 95% CI: −7.98 to −1.50) and higher loneliness (1.72, 95% CI: 0.78–2.66) whilst minority ethnic carers had higher stress (8.17, 95% CI: 1.72–14.63) and role captivity (2.00, 95% CI: 0.43–3.57) and lower relationship quality (−9.86, 95% CI: −14.24 to −5.48) than their white peers.

Conclusion

Our exploratory study suggests that people with dementia from minority ethnic groups experience lower quality of life and carers experience higher stress and role captivity and lower relationship quality than their white peers. Confirmatory research with larger samples is required to facilitate analysis of the experiences of specific minority ethnic groups and examine the factors contributing to these disadvantages.
Possible effects of plasminogen activator inhibitor‐1 on promoting angiogenesis through matrix metalloproteinase 9 in advanced mycosis fungoides
Authors: Fujimura Taku , Ohuchi Kentaro , Ikawa Tetsuya , Kambayashi Yumi , Amagai Ryo , Furudate Sadanori , Asano Yoshihide
Published: January 2024

Mycosis fungoides (MF) progresses slowly before advancing to skin tumors followed by lymph node and visceral involvement. Among MF progression, stage IIB is an initial time point of tumor formation in MF. Since MF in tumor stage possess abundant blood vessels, it is important to evaluate the pro‐angiogenic factors before and after MF in stage IIB. In this report, we investigated pro‐angiogenic soluble factors in MF patients, as well as its pro‐angiogenetic effects on tumor cells and stroma cells. We first evaluated the serum levels of pro‐angiogenic factors in 9 MF patients without tumor formation and 8 MF patients with tumor formation. Among them, the serum MMP‐9 and plasminogen activator inhibitors 1 (PAI‐1) was significantly increased in MF with tumor formation compared in MF without tumor formation, leading to favorable formation of human dermal microvascular endothelial cells tube networks. Moreover, PAI‐1 stimulation significantly increased the mRNA expression and protein production MMP‐9 on monocytes derived M2 macrophages and HUT‐78. Furthermore, since MMP‐9 production from tumor cells as well as stromal cells is suppressed by bexarotene, we evaluate the baseline serum pro‐angiogenic factors including MMP‐9 in 16 patients with advanced cutaneous T cell lymphoma treated with bexarotene. The serum levels of MMP‐2 and MMP‐9 was significantly increased in bexarotene non‐responded patients compared to responded patients. Our present study suggested the significance of MMP‐9 and PAI‐1 for the progression of MF stage toward to the tumor stage, and could be a therapeutic target in future.
A Delphi study to determine the epidemiology and clinical management of patients treated with HDMTX who develop methotrexate (MTX) delayed elimination in France, Germany, Italy, and the UK
Authors: Bielack Stefan , Fox Christopher P. , Hoang‐Xuan Khê , Giró‐Perafita Ariadna , Rizzari Carmelo
Published: January 2024

Introduction

High‐dose methotrexate (HDMTX) is administered for the treatment of some malignancies. Serious complications after the administration of HDMTX are rare, but occasionally MTX may precipitate in the renal tubes causing a delayed elimination leading to renal, multiorgan toxicities and to life‐threatening complications. This study aims to estimate the incidence and clinical management of delayed MTX elimination in France, Germany, Italy, and the UK.

Methods

Twelve haemato‐oncology and pediatric oncology clinical experts from leading European hospitals participated in the study. A two‐round Delphi methodology was used to gather data on different variables relevant to evaluate the HDMTX induced‐toxicity impact. For quantitative data, median and interquartile ranges were calculated. Data on prevalence was calculated considering the number of patients in each hospital and the population they cover, and then, extrapolated to the country population.

Results

The total number of patients treated annually with HDMTX in France, Germany, Italy, and the UK is estimated in 7155. Of these, 16% are estimated to develop delayed MTX elimination and around 9% may develop HDMTX‐induced acute kidney injury (AKI). Leucovorin, hyperhydration and urine alkalinization are applied to prevent MTX toxicity and precipitation whilst glucarpidase, hemofiltration and hemodialysis are being used for persisting toxic MTX serum levels. Grade 3 systemic toxicities are common in these patients, hematologic and gastrointestinal being the most common ones.

Conclusions

This report provides expert clinical practice experience and opinion of the incidence and management of HDMTX‐delayed elimination in France, Germany, Italy and the UK, thereby contributing to the evidence available on this relevant medical condition which can be life‐threatening.
A systematic methodology for epicardial and epiaortic echocardiography in swine research models
Authors: Galbas Michelle C. , Meissner Florian , Asmussen Alexander , Straky Hendrik C. , Schimmel Marius , Reuter Johanna , Grundmann Sebastian , Czerny Martin , Bothe Wolfgang
Published: January 2024

Background

Perioperative echocardiography is of paramount importance during cardiac surgery. Nonetheless, in the experimental large‐animal setting, it might be challenging obtaining optimal imaging when using conventional imaging acquisition techniques, such as transthoracic and transesophageal screenings. Open‐chest surgery allows epicardial echocardiographic assessment with direct contact between probe and heart, thus providing superior quality. Standard protocols regarding the use of epicardial ultrasound in swine for research purposes are lacking.

Methods

Epicardial echocardiography was performed in 10 female German Landrace pigs undergoing cardiac surgery. A structured and comprehensive protocol for epicardial echocardiography was elaborated including apical, ventricular long and short axis, as well as epiaortic planes. All experiments were approved by the local board for animal welfare and conducted in accordance with the German animal protection law (TierSchG) and the ARRIVE guidelines.

Conclusions

Systematic protocols using epicardial echocardiography may serve as an additional tool to assess cardiac dimensions and function in experimental scenarios with swine models.
Advances in DNA walking nanomachine‐based biosensors
Authors: Shen Bo , Li Li , Guo Minghui , Li Xinyu , Fan Yunpeng , Li Xinmin , Chen Rui , Ding Shijia , Cheng Wei
Published: January 2024

The field of DNA nanotechnology has evolved beyond the realm of controllable movements and randomly shaped nanostructures, now encompassing a diverse array of nanomachines, each with unique nanostructures and biofunctional attributes. These DNA nanostructures boast exceptional characteristics such as programmability, integrability, biocompatibility, and universality. Among this variety, DNA walking nanomachines have emerged as one of the most prominent nanomotors, distinguished by their ingenious design and comprehensive functionality. In recent times, these DNA walkers have witnessed remarkable advancements in areas ranging from nanostructural designs to biological applications, including the creation of sophisticated biosensors capable of efficiently detecting tumor‐related biomarkers and bioactive substances. This review delves into the operational mechanisms of DNA walking nanomachines, which are driven by processes such as protease and DNAzyme action as well as strand displacement and photoactivated reactions. It further provides a comprehensive overview of DNA walking nanomachines with different dimensional (1D, 2D, and 3D) walking tracks. A subsequent section introduces the biosensing applications of DNA walking nanomachines including electrochemical, optical, and other biosensors. The review concludes with a forward‐looking perspective on the novel advancements and challenges in developing DNA walking nanomachine‐based biosensors.
Robust aortic media adhesion using hydrophobically modified Alaska pollock gelatin‐based adhesive for aortic dissections
Authors: Ito Temmei , Mizuta Ryo , Ito Shima , Taguchi Tetsushi
Published: January 2024

Type‐A aortic dissection is an acute injury involving the delamination of the aorta at the parts of the aortic media. Aldehyde crosslinker‐containing glues have been used to adhere to the media of the dissected aorta before joining an artificial graft. These glues effectively adhere to the aortic media; however, they show low biocompatibility due to the release of aldehyde compounds. In this study, we report innovative adhesives based on hydrophobically modified Alaska pollock gelatin (hm‐ApGltn) with different alkyl or cholesteryl (Chol) groups that adhere to the media of the dissected aorta by combining hm‐ApGltns with a biocompatible crosslinker, pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate. The modification of alkyl or Chol groups contributed to enhanced adhesion strength between porcine aortic media. The adhesion strength increased with increasing modification ratios of alkyl groups from propanoyl to dodecanoyl groups and then decreased at a modification ratio of ~20 mol %. Porcine aortic media adhered using 7.5Chol‐ApGltn adhesive showed stretchability even when expanded and shrunk vertically by 25% at least five times. Hm‐ApGltn adhesives subcutaneously injected into the backs of mice showed no severe inflammation and were degraded during the implantation period. These results indicated that hm‐ApGltn adhesives have potential applications in type‐A aortic dissection.
Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses
Authors: van de Wakker Simonides Immanuel , Bauzá‐Martinez Julia , Ríos Arceo Carla , Manjikian Herak , Snijders Blok Christian Jamie Bernard , Roefs Marieke Theodora , Willms Eduard , Maas Renee Goverdina Catharina , Pronker Matti Feije , de Jong Olivier Gerrit , Wu Wei , Görgens André , El Andaloussi Samir , Sluijter Joost Petrus Gerardus , Vader Pieter
Published: January 2024

Cardiac progenitor cell (CPC)‐derived small extracellular vesicles (sEVs) exhibit great potential to stimulate cardiac repair. However, the multifaceted nature of sEV heterogeneity presents a challenge in understanding the distinct mechanisms underlying their regenerative abilities. Here, a dual‐step multimodal flowthrough and size‐exclusion chromatography method was applied to isolate and separate CPC‐derived sEV subpopulations to study the functional differences related to cardiac repair responses. Three distinct sEV subpopulations were identified with unique protein profiles. Functional cell assays for cardiac repair‐related processes demonstrated that the middle‐sized and smallest‐sized sEV subpopulations exhibited the highest pro‐angiogenic and anti‐fibrotic activities. Proteasome activity was uniquely seen in the smallest‐sized subpopulation. The largest‐sized subpopulation showed no effect in any of the functional assays. This research uncovers the existence of sEV subpopulations, each characterized by a distinct composition and biological function. Enhancing our understanding of sEV heterogeneity will provide valuable insights into sEV mechanisms of action, ultimately accelerating the translation of sEV therapeutics.
MRI Assessment of Cerebral White Matter Microvascular Hemodynamics Across the Adult Lifespan
Authors: Damestani Nikou L. , Jacoby John , Michel Christa B. , Rashid Barnaly , Salat David H. , Juttukonda Meher R.
Published: January 2024

Background

Changes in cerebral hemodynamics with aging are important for understanding age‐related variation in neuronal health. While many prior studies have focused on gray matter, less is known regarding white matter due in part to measurement challenges related to the lower vascular density in white matter.

Purpose

To investigate the impact of age and sex on white matter hemodynamics in a Human Connectome Project in Aging (HCP‐A) cohort using tract‐based spatial statistics (TBSS).

Study Type

Retrospective cross‐sectional.

Population

Six hundred seventy‐eight typically aging individuals (381 female), aged 36–100 years.

Field Strength/Sequence

Multi‐delay pseudo‐continuous arterial spin labeling (ASL) and diffusion‐weighted pulsed‐gradient spin‐echo echo planar imaging sequences at 3.0 T.

Assessment

A skeleton of mean fractional anisotropy (FA) was produced using TBSS. This skeleton was used to project ASL‐derived cerebral blood flow (CBF) and arterial transit time (ATT) measures onto white matter tracts.

Statistical Tests

General linear models were applied to white matter FA, CBF, and ATT maps, while covarying for age and sex. Threshold‐free cluster enhancement multiple comparisons correction was performed for the effects of age and sex, thresholded at PFWE < 0.05. CBF, ATT, and FA were compared between sex for each tract using analysis of covariance, with multiple comparisons correction for the number of tracts at PFDR < 0.05.

Results

Significantly lower white matter CBF and significantly prolonged white matter ATTs were associated with older age. These effects were widespread across tracts for ATT. Significant (PFDR < 0.05) sex differences in ATT were observed across all tracts, and significant sex differences in CBF were observed in all tracts except the bilateral uncinate fasciculus. Females demonstrated significantly higher CBF compared to males across the lifespan. Few tracts demonstrated significant sex differences in FA.

Data Conclusion

This study identified significant sex‐ and age‐associated differences in white matter hemodynamics across tracts.

Evidence Level

3

Technical Efficacy

Stage 3
Association between chronic viral infection‐related hospitalization and risk of cardiovascular disease: A population‐based cohort study
Authors: Yang Luoyao , Lu Zhen , Bian Junye , Li Feng , Zou Huachun
Published: January 2024

Chronic viral infection induces immunosenescence and systemic low‐grade inflammation, leading to worsened long‐term outcomes. We sought to explore the short‐ and long‐term effects of chronic viral infection on cardiovascular disease (CVD). Based on UK Biobank data, exposed group was identified as individuals who had chronic virus infection‐related hospitalization (IRH). Unexposed group was randomly selected, matched by 5‐year age interval, sex, and Charlson comorbidity index at a ratio up to 1:10. Restricted cubic splines were used to model time‐varying effects of IRH in nonproportional Cox models. A cut‐off value of 5 years was recorded and used in piecewise Cox proportional hazards models as we estimated short‐ and long‐term effects of IRH on CVD. A total of 2826 exposed participants and 28 212 matched unexposed participants were included. Chronic viral IRH was associated with increased risk of CVD (0–5 years: hazard ratio, 1.57 [95% confidence interval: 1.32, 1.87] and 5+ years: 1.31 [1.06, 1.61]). Elevated risk of stroke was only observed within the initial 5‐year follow‐up (0–5 years: 1.91 [1.30, 2.81]). The short‐ and long‐term associations were observed in herpes or hepatitis virus IRH with risk of CVD (all p < 0.05). Subgroup analysis revealed long‐term association between chronic viral IRH and CVD among female (5+ years: 1.68 [1.27, 2.22]) but not among male. The association between chronic viral infection and elevated CVD risk appeared to be stronger among individuals who did not take cholesterol‐lowering medication, antithrombotic medication, or certain antihypertensive medications (all p for interaction < 0.05). The risk of CVD event remained persistently higher within and over 5 years following chronic viral IRH, especially in individuals infected with herpes and hepatitis virus.
Saliva‐based Proteinase K method: A rapid and reliable diagnostic tool for the detection of SARS‐COV‐2 in children
Authors: Kim Min Jung , Park Pil‐gu , Hwang Su Jin , Bang Seung Jun , Jung Jae Hwa , Kown Eun Bin , Sul Eun Kyung , Song Kyung Chul , Choi Joon‐sik , Han Kyeo Re , Lee Hye Young , Kim Dong Hyun , Lee Jae Myun
Published: January 2024

Early and accurate detection of viruses in children might help prevent transmission and severe diseases. In this study, the severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2) detection in children was evaluated using saliva specimens with a Proteinase K (PTK)‐based RNA preparation, as saliva collection is a simple and noninvasive procedure, even in young children, with fewer concerns about sample contamination. The saliva‐based PTK and the conventional paired nasopharyngeal aspiration (NPA)‐based detection methods were compared between COVID‐19‐positive and ‐negative children. In addition, the detection rate for SARS‐COV‐2 and the difference between admission and discharge by the saliva‐based PTK method was tested in COVID‐19 patients. The diagnostic accuracy of the saliva‐based PTK method was 98.8% compared to NP swab‐based reverse transcriptase polymerase chain reaction. Saliva samples showed high sensitivity (94.1%) and specificity (100%) when using the PTK method. Furthermore, the saliva‐based PTK method significantly reduced the test processing time by 2 h. Notably, Ct values at discharge increased in saliva samples compared with those at admission, which might indicate patients' clinical conditions or virus activity. In conclusion, the saliva‐based PTK implemented in this study streamlines RNA extraction, making the process faster, safer, and more cost‐effective, demonstrating that this method is a rapid and reliable diagnostic tool for SARS‐CoV‐2 detection in children.
Coinfections with additional oncoviruses in HPV+ individuals: Status, function and potential clinical implications
Authors: Dai Lu , Wilson Lillie G. , Nakagawa Mayumi , Qin Zhiqiang
Published: January 2024

Oncovirus infections account for an estimated 12%−20% of human cancers worldwide. High‐risk human papillomavirus (HPV) infection is the etiological agent of some malignancies such as cervical, oropharyngeal, anal, penile, vaginal, and vulvar cancers. However, HPV infection is not the only cause of these cancers or may not be sufficient to initiate cancer development. Actually, certain other risk factors including additional oncoviruses coinfections have been reported to increase the risk of patients exposed to HPV for developing different HPV‐related cancers. In the current review, we summarize recent findings about coinfections with different oncoviruses in HPV+ patients from both clinical and mechanistic studies. We believe such efforts may lead to an interesting direction for improving our understanding and developing new treatments for virus‐induced cancers.
Rainstorm variability is mainly influenced by the southwest monsoon in the Hanjiang River basin of China during 1985–2020
Authors: Jing Yuanyuan , Shi Peijun , Zhang Gangfeng , Sun Shao
Published: January 2024

The extreme precipitation in China is greatly influenced by the East Asian summer monsoon, which can be divided into two components: the southeast monsoon (SEM) and the southwest monsoon (SWM). The Hanjiang River basin (HJB), a representative monsoon‐influenced basin in China, is alternately influenced by the southwest monsoon and southeast monsoon throughout the year. However, the specific relationship between rainstorms and monsoons, and the relative contribution of different monsoons, remains unclear in the HJB. Using multiple datasets, this study analysed the variability of various rainstorm types in the HJB during 1985–2020, investigated their relationships with different monsoon indicators and assessed the contribution of monsoons on the rainstorm variance. The results reveal a nonsignificant increasing trend in rainstorms within the basin, the severe convective rainstorm days accounted for a high proportion of the total rainstorm days, and the spatiotemporal characteristics of different rainstorm types are different. The rainstorm indicators are significantly correlated with the monsoon within the HJB and are positively correlated with the SWM, particularly its intensity. The SEM exhibits a weak correlation with rainstorms and has limited explanation for the variance in rainstorms. The intensity of SWM within the HJB shows a significant positive correlation with all rainstorm indicators. It is also detected as the most important indicator for explaining the interannual variation in rainstorms, explaining 41.97% and 39.45% of the variance in daily rainstorm frequency and totals, which comprises more than half of the total explanatory portion. The explanation of circulation factors for the variance in daily rainstorms is higher than that for severe convective rainstorms. In addition to monsoons, the Pacific Decadal Oscillation and the Southern Oscillation Index also have a great contribution to the rainstorm variability in the HJB.
Never Ending Stories? Hebrew Writers' Creative Journey in the Second Half of Life
Authors: Aharoni Lir Shlomit , Ayalon Liat
Published: January 2024

This qualitative study explored the relationship between creativity, time, age, and the literary world among 16 award‐winning Israeli writers in the second half of their lives. Based on data collected through in‐depth interviews with the participants, the findings indicate that the writers' creativity in the second half of life was linked to Preservation, Growth, and Decline, leading to four interrelated dimensions: (a) preserving youth through creativity, (b) enhancing creativity over time, (c) navigating creativity, acclaim, and ageism, and (d) managing creativity amidst a changing world. The study found that the writers' creativity was enhanced over time, as they gained experience and developed their skills. However, some writers experienced a decline in stamina or their ability to write long novels. The study also found that the writers' experiences of acceptance from the literary world and the audience changed over time. Some writers continued to receive acclaim and attention, while others experienced ageism and a decline in the audience's interest in their work.