bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioinformatic Analysis for Exploring Target Genes and Molecular Mechanisms of Cadmium‐Induced Nonalcoholic Fatty Liver Disease and Targeted Drug Prediction
Authors: Zhang Le , Wang Rui , Xue Qian , Wang Yongjie , Xu Jiayunzhu , Wang Chaofan , Fang Xin , Gao Shidi , Zhang Haiying , Guo Li
Published: January 2025

Cadmium (Cd) is a widely available metal that has been found to have a role in causing nonalcoholic fatty liver disease (NAFLD). However, the detailed toxicological targets and mechanisms by which Cd causes NAFLD are unknown. Therefore, the present work aims to reveal the main targets of action, cellular processes, and molecular pathways by which cadmium causes NAFLD. As shown in the bioinformatics analysis, there were 74 main targets of action for cadmium‐induced NAFLD, hemopoietic cell kinase (HCK), EPH receptor A2 (EPHA2), MYC proto‐oncogene (MYC), lysyl oxidase (LOX), dipeptidyl peptidase 7 (DPP7), nuclear factor erythroid 2‐related factor 2 (NFE2L2), dual specificity phosphatase 6 (DUSP6), CD2 cytoplasmic tail binding protein 2 (CD2BP2), notch receptor 3 (NOTCH3), and phospholipase A2 group IVA (PLA2G4A) were screened as core genes. Testing these core genes in other databases, three differentially expressed genes, HCK, MYC, and DUSP6 were verified and used as targets for drug prediction in DsigDB; decitabine and retinoic acid were screened as potential therapeutic drugs for NAFLD based on the p‐value and the combined score. The results of molecular docking showed that the predicted drugs can bind well to the core targets. In conclusion, cadmium is associated with NAFLD; the identified cadmium‐toxicity targets, HCK, MYC, and DUSP6, may serve as biomarkers for the diagnosis of NAFLD and predicted drugs, decitabine and retinoic acid may have a potential role in the treatment of NAFLD.
Mechanical Analysis of Phellinus Linteus‐Induced Apoptosis of Hepatoma Cells
Authors: Huang Yuxi , Yang Fan , Liu Chuanzhi , Wang Jianfei , Wang Ying , Song Guicai , Wang Zuobin
Published: January 2025

Liver cancer is prevalent with the third highest mortality rate globally. The biomechanical properties of cancer cells play a crucial role in their proliferation and differentiation. Studying the morphological and mechanical properties of individual living cells can be helpful for early diagnosis of cancers. Herein, atomic force microscopy (AFM) was used to investigate the effects of Phellinus linteus on hepatocyte cells (HL‐7702) and hepatocellular carcinoma cells (SMCC‐7721) in terms of morphological and mechanical changes at the nanoscale. The water extract of Phellinus linteus (PLWE) resulted in increased height and surface roughness of SMCC‐7721 cells. Also, the PLWE‐treated showed that the average adhesion decreased by 1.69 nN and the average Young's modulus increased by 0.379 kPa. Additionally, the SMCC‐7721 cells treated with PLWE showed clearly reduced activity compared with HL‐7702 cells. This study suggested that Phellinus Linteus could be a potential candidate for selective anti‐cancer therapy, providing a new avenue for the treatment of hepatocellular carcinoma.
Cystathionine β‐Synthase Deficiency in the E‐HOD Registry—Part II: Dietary and Pharmacological Treatment
Authors: Morris Andrew A. M. , Sokolová Jitka , Pavlíková Markéta , Gleich Florian , Kölker Stefan , Dionisi‐Vici Carlo , Baumgartner Matthias R. , Hannibal Luciana , Blom Henk J. , Huemer Martina , Kožich Viktor ,   E‐HOD Consortium
Published: January 2025

Cystathionine β‐synthase (CBS) deficiency (classical homocystinuria) has a wide range of severity. Mildly affected patients typically present as adults with thromboembolism and respond to treatment with pyridoxine. Severely affected patients usually present during childhood with learning difficulties, ectopia lentis and skeletal abnormalities; they are pyridoxine non‐responders (NR) or partial responders (PR) and require treatment with a low‐methionine diet and/or betaine. The European network and registry for Homocystinurias and methylation Defects (E‐HOD) has published management guidelines for CBS deficiency and recommended keeping plasma total homocysteine (tHcy) concentrations below 100 μmol/L. We have now analysed data from 311 patients in the registry to see how closely treatment follows the guidelines. Pyridoxine‐responsive patients generally achieved tHcy concentrations below 50 μmol/L, but many NRs and PRs had a mean tHcy considerably above 100 μmol/L. Most NRs were managed with betaine and a special diet. This usually involved severe protein restriction and a methionine‐free amino acid mixture, but some patients had a natural protein intake substantially above the WHO safe minimum. Work is needed on the methionine content of dietary protein as estimates vary widely. Contrary to the guidelines, most NRs were on pyridoxine, sometimes at dangerously high doses. tHcy concentrations were similar in groups prescribed high or low betaine doses and natural protein intakes. High tHcy levels were probably often due to poor compliance. Comparing time‐to‐event graphs for NR patients detected by newborn screening and those ascertained clinically showed that treatment could prevent thromboembolism (risk ratio 0.073) and lens dislocation (risk ratio 0.069).
A Disposable Pipette Extraction‐UHPLC‐MS/MS Method Based on Removal of Phospholipids to Determine Anandamide, 2‐Arachidonoylglycerol, Cannabidiol, and Δ9‐Tetrahydrocannabidiol in Plasma Samples
Authors: Oliveira Igor Gustavo Carvalho , de Souza Israel Donizeti , de Crippa José Alexandre de Souza , Queiroz Maria Eugênia Costa
Published: January 2025

Cannabidiol (CBD) and Δ9‐tetrahydrocannabinol (THC), the main components of Cannabis sativa plants, can interact with specific cell receptors known as cannabinoid receptors (CBs). The endogenous compounds anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG) are CB agonists, and, alongside enzymes, they constitute the endocannabinoid system (ECS) and take part in neuromodulation. Several LC‐MS/MS methods have been developed to quantify these compounds in biological matrixes, but a fast and simple method that can determine these analytes in plasma samples simultaneously is not available. Here, we propose a disposable pipette extraction technique containing a zirconia‐based sorbent (DPX(Zr)) combined with UHPLC‐MS/MS analysis to determine CBD, THC, AEA, and 2‐AG in plasma samples, simultaneously. The method combines simple protein precipitation (PPT) with a one‐step DPX procedure to remove phospholipids, one of the most common endogenous interferents in biological samples. Optimization of the combined PPT‐DPX sample preparation method reduced the matrix effect and improved the sensitivity of the analytical method. The validated DPX(Zr)‐UHPLC‐MS/MS method reported LLOQs of 0.1 ng mL−1 for AEA and 2‐AG and 1 ng mL−1 for CBD and THC. The method demonstrated intra‐ and interassay accuracy and precision of less than 20% for the LLOQ, and less than 15% for the other calibration points. Additionally, no carryover or significant matrix effect was observed. We applied this method to determine AEA, 2‐AG, and CBD in plasma samples obtained from obsessive‐compulsive disorder patients treated with CBD.
Mechanoluminescence from Lead‐Free Perovskites Cs2HfCl6: Te4+
Authors: Yan Shuangpeng , Song Hao , Liu Ya , Xu Xuhui , Peng Songcheng , Yang Xiuxia , Teng Zhaowei
Published: January 2025

Mechanoluminescence (ML) has always attracted much attention due to the broad prospects in various fields. However, the types of ML materials are still limited. Here, the traps are introduced by means of X‐ray irradiation, and finally a high brightness ML visible to the naked eye during daytime and a 20 s ML afterglow is obtained in Cs2HfCl6: Te4+ Inorganic Lead‐free halide perovskites (ILFHPs). This work will promote the further development of ML and provide a way of thinking for the exploration of new materials.
Land Misallocation and Urban Green Innovation: From the Perspective of Asymmetrical Innovation Theory
Authors: Xu Hengzhou , Sun Fenghui , Liu Shuangliang
Published: January 2025

As the conflict between economic growth and environmental pollution intensifies, green innovation is gradually recognized as a pivotal strategy for promoting sustainable urban development. The unique institution is an important asymmetric resource for innovation activities, so delving into China's land institutional context represents a significant direction for both the theoretical understanding and practical application research of innovation in China. The existing framework inadequately explores the nexus between land misallocation (LM) and urban green innovation (UGI) and fails to reveal the underlying transmission mechanism fully. To bridge this gap, this paper utilizes city‐level data from China spanning 2007 to 2020, takes an asymmetric innovation perspective, and empirically tests the impact of two types of land misallocation, industrial LM and sectoral LM, on the relationship between UGI. The results reveal that LM has a significantly direct negative impact on UGI in China. The results are still robust after changing the sample size, substituting explanatory variables, replacing regression models, and running endogeneity tests. Additionally, the negative impact of LM exhibits heterogeneity within sectors and cities of different economic levels, administrative ranks, and dominant industries. The mechanism testing results indicate that LM affects UGI through structural, scale, and agglomeration effects. These conclusions enrich the literature on the impact of institutions on urban green innovation and provide valuable insights into the sustainable development of cities.
Zero‐Hopf bifurcation of a cubic jerk system via the third order averaging method
Authors: Chen Yu‐Ming
Published: January 2025

This paper is devoted to analyze the zero‐Hopf bifurcation of a generalized three‐dimensional (3D) jerk system, the jerk function of this system has all quadratic and cubic terms. Due to the averaging method of second order, we show that at most three periodic orbits bifurcate form the zero‐Hopf equilibrium point of this jerk system, and this upper bound is sharp. Furthermore, by using the averaging method of third order, we show that three is also the maximal number of periodic orbits bifurcate from this zero‐Hopf equilibrium point. Finally, the numerical method is used to justify the theoretical analysis.
Modeling and Ulam–Hyers stability analysis of oleic acid epoxidation by using a fractional‐order kinetic model
Authors: Xu Changjin , Farman Muhammad , Shehzad Aamir , Sooppy Nisar Kottakkaran
Published: January 2025

Government initiatives, price cuts, and innovations in technology have caused a shift in the world's raw material consumption towards renewable materials. The polymer industry has shown particular interest in studies on more environmentally friendly epoxidation processes that use vegetable oils. Epoxidized vegetable oils are renewable, affordable, and eco‐friendly, which makes them a promising green material to partially replace and toughen polymers derived from petrochemicals. Using a kinetic model from the literature, this study develops a system of fractional‐order differential equations to investigate the significance of oleic acid epoxidation. With oleic acid serving as the primary raw material, the study focuses on producing epoxidized oleic acid with a high yield and a longer reaction time. We apply both qualitative and quantitative analysis to the model using fixed‐point theorems. The model's Ulam–Hyers stability is established. Investigation of the fractional operator's effect is done through computational simulations and the Laplace Adomian decomposition technique. The investigation of the effects of fractional operators on the epoxidation process reveals that temperature, molar ratios, and fractional order are significant determinants of the process.
Two‐Dimensional Jet Flows for Compressible Full Euler System With General Vorticity
Authors: Li Yan
Published: January 2025

In this paper, we consider the well‐posedness theory of two‐dimensional compressible subsonic jet flows for steady full Euler system with general vorticity. We show that the stream function formulation for such system admits a variational structure. Then the existence and uniqueness of a smooth subsonic jet flow can be established by the variational method developed by Alt, Caffarelli and Friedman. Furthermore, the far fields behavior of the flow and the existence of a critical upstream pressure are also obtained.
A New Dual‐Band Filtering Power Divider Based on a Single Multimode Modified Triangle Patch Resonator
Authors: Li Yijun , Ni Jinxuan , Gao Qiyue , Zhou Xin , Liu Zhengkang , Li Na , Zhang Gang
Published: January 2025

This letter proposes a new design of a dual‐band (DB) filtering power divider (FPD) on a single multimode‐modified triangle patch resonator. The proposed design leverages the resonant characteristics of an equilateral triangle patch resonator to exploit the TM10, TM11, TM21, and TM30 resonant modes within a single multimode‐modified triangle patch resonator, enabling the realization of an FPD with DB operation. To achieve two assumed second‐order filtering passbands, a metal via and multiple perturbed slots are introduced, providing flexible control over the resonant mode frequencies. The first passband is formed by the TM10 and TM11 modes, while the second passband is formed by the TM21 and TM30 modes. To ensure in‐band isolation for both passbands, two sets of isolation networks are developed. A prototype is designed, fabricated, and measured to validate the proposed method. The measured results demonstrate excellent agreement with the simulated ones.
Online Learning and Pricing for Multiple Products With Reference Price Effects
Authors: Ji Sheng , Yang Yi
Published: January 2025

We consider the dynamic pricing problem of a monopolist seller who sells a set of mutually substitutable products over a finite time horizon. Customer demand is sensitive to the price of each individual product and the reference price which is formed from a comparison among the prices of all products. To maximize the total expected profit, the seller needs to determine the selling price of each product and also select a reference product (to be displayed) that affects the consumer's reference price. However, the seller initially knows neither the demand function nor the optimal reference product, but can learn them from past observations on the fly. As such, the seller faces the classical trade‐off between exploration (learning the demand function and reference price) and exploitation (using what has been learned thus far to maximize revenue). We propose a rate‐optimal dynamic learning‐and‐pricing algorithm that integrates iterative least squares estimation and bandit control techniques in a seamless fashion. We show that the cumulative regret, that is, the expected revenue loss caused by not using the optimal policy over periods, is upper bounded by where hides any logarithmic factors. We also establish the regret lower bound (for any learning policies) to be . We then generalize our analysis to a more general demand model. Our algorithm performs consistently well numerically, outperforming an exploration‐exploitation benchmark. The use of price experimentation and estimation techniques could be readily applied in real retail management.
Multitopology Routing With Virtual Topologies and Segment Routing
Authors: Huin Nicolas , Martin Sébastien , Leguay Jérémie
Published: January 2025

Multitopology routing (MTR) provides an attractive alternative to segment routing (SR) for traffic engineering when network devices cannot be upgraded. However, due to a high overhead in terms of link state messages exchanged by topologies and the need to frequently update link weights to follow evolving network conditions, MTR is often limited to a small number of topologies and the satisfaction of loose QoS constraints. To overcome these limitations, we propose virtual MTR (vMTR), an MTR extension where demands are routed over virtual topologies that are silent; that is, they do not exchange LSA messages and that are continuously derived from a very limited set of real topologies, optimizing each QoS parameter. In this context, we present a polynomial and exact algorithm for vMTR and, as a benchmark, a local search algorithm for MTR. We show that vMTR helps to reduce drastically the number of real topologies and that it is more robust to QoS changes. In the case where SR can actually be rolled‐out, we also show that vMTR allows to drastically reduce SR overhead.
Preparation of Porous Novel QuEChERS Adsorbent ZIF‐67/PAA/PES Composite Microspheres and Their Application for Rapid Adsorption of Triphenylmethane Dyes in Wastewater and Fish
Authors: Wang Xiaotian , Aheyeli‐kai Yeerken , Ying Huakun , Lin Jiangli , Luo Yulu , Ma Hongying , Li Zhongyang , Su Zhen
Published: January 2025

Triphenylmethane dyes have a wide range of applications in textiles, pharmaceuticals, food, and other fields. Malachite green (MG), fuchsin acid (FA), and crystalline violet (CV) were typical representatives of triphenylmethane dyes, and they are carcinogenic and mutagenic to aquatic organisms and environment. However, they need to be separated and enriched for their accurate quantification due to their low content. Therefore, it is important to develop a rapid and accurate enrichment method to monitor these dyes in aquatic systems for human health. In this paper, a novel QuEChERS adsorbent porous ZIF67/PAA/PES composite microspheres were prepared and applied for the rapid adsorption of triphenylmethane dyes in wastewater and fish samples, which improved the adsorption capacity and the analytical sensitivity of the targets. The experimental results demonstrated that the porous ZIF‐67/PAA/PES composite microspheres exhibited excellent selective adsorption capacity of MG, FA, and CV, and after six adsorption–desorption cycles, the material adsorption amount can reach more than 90% of its original adsorption amount in wastewater. In addition, the porous ZIF67/PAA/PES composite microspheres were applied as QuEChERS adsorbents for the enrichment of MG and CV dyes in fish, and the adsorption rates of the dyes were 99.11% and 99.03%, with the RSDs of 1.58% and 1.27%, respectively. The limits of detection were 0.0093 and 0.0127 mg/L for MG and CV. Through the Langmuir adsorption isotherm models to predict the MG, FA, and CV of the maximum adsorption capacity were 5417.3622, 2119.9011, and 1654.1026 mg/g, respectively. Thus, the novel porous ZIF67/PAA/PES composite microspheres are more advantageous as QuEChERS adsorbents for sample pre‐treatment and have very important research significance.
Miscible Polymer Blend Membranes Bearing Pyrrolidone for Fractioning Sulfuric Acid and Sulfates
Authors: Yang Danni , Luo Tao , Zhang Tao , Lv Li , Zou Zongpeng , Tang Shengwei
Published: January 2025

Ion exchange membranes of new chemistry based on polymer blends are proposed through a convenient solution‐blending process using the hydrophobic commodity polymer polyvinyl chloride (PVC) and the hydrophilic polyvinylpyrrolidone (PVP), which are completely miscible. The pyrrolidone groups can be protonated to form oxonium ions, functioning as transient fixed positive charges for fractioning sulfuric acid and sulfates via diffusion. The influence of PVC molecular weight and the membrane composition on the physical, chemical properties, and mass transfer performance of PVC‐PVP blend membranes was systematically investigated. After equilibrium in 2.68 mol/L sulfuric acid, the sulfuric acid, and water contents in the blend membranes increase with the increase of the membrane PVP contents (20–75 wt%). The permeability coefficients of sulfuric acid and ferrous sulfate for the blend membranes also exhibit a gradual increase. Membranes of mass transfer properties comparable to commercial ones can be easily obtained by tuning the membrane PVP contents. It is proved that the larger sulfuric acid permeability over sulfates (FeSO4 as an example) is due to both larger solubility and diffusion coefficient of sulfuric acid in the membrane phase. The optimal PVC‐PVP blend membranes have shown nice performance in fractioning sulfuric acid from sulfates, when treating titania waste acid. This study provides valuable guidance for the design of high‐performance yet low‐cost ion exchange membranes with pyrrolidone chemistry from commodity polymers for resource recovery.
HPTLC‐Bioautography–MS‐Guided Strategy for the Detection of Phthalides With Antimicrobial and Antioxidant Activities From Ligusticum chuanxiong Essential Oil
Authors: Wang Zhijun , Tang Xiaomeng , Lv Lei , Qiao Sicong , Chen Mengxin , Song Hongjie
Published: January 2025

Introduction

Antimicrobial resistance and free radical‐mediated oxidative stress and inflammation involved in many pathological processes have become treatment challenges. One strategy is to search for antimicrobial and antioxidant ingredients from natural aromatic plants. This study established a rapid and high‐throughput effect‐component analysis method to screen active ingredients from Ligusticum chuanxiong essential oil (CXEO).

Objective

The study aims to screen phthalides with antimicrobial and antioxidant activities from CXEO by high‐performance thin‐layer chromatography (HPTLC)‐bioautography combined with HPLC‐TOF/MS method.

Methods

Antimicrobial activity was evaluated by disc diffusion and micro broth dilution methods. Antioxidant capacity was performed by DPPH scavenging test. Phthalides in CXEO were identified using HPLC‐TOF/MS method. HPTLC–bioautography technique was established to screen phthalides of antifungal and antioxidant activities.

Results

CXEO had significant inhibitory activity against Candida albicans, weak or undetected inhibitory activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. For tested strains of C. albicans, inhibition zone diameters ranged from 13 to 17 mm, and MICs were from 0.5 to 2 mg mL−1. CXEO also had strong antioxidant activity, IC50 value for scavenging DPPH free radicals was 1.014 ± 0.014 mg mL−1. Nine phthalides in CXEO were tentatively identified. Ligustilide and senkyunolide A were screened to have both antimicrobial activity against C. albicans and strong DPPH scavenging property.

Conclusion

HPTLC‐bioautography–MS‐guided strategy is very practical for high‐throughput screening of antifungal and antioxidant phthalides from CXEO. In vitro experiments have shown that phthalides and CXEO have good biological activities, which may be used to the treatment of C. albicans infection or oxidative stress damage caused by various diseases. The therapeutic potential should be validated in vivo in the future.
Core Concepts: Self‐Controlled Designs in Pharmacoepidemiology
Authors: Bots Sophie H. , Brown Jeremy , Wong Angel Y. S. , Martin Ivonne , Douglas Ian , Klungel Olaf H. , Schultze Anna
Published: January 2025

One of the key challenges in pharmacoepidemiological studies is that of uncontrolled confounding, which occurs when confounders are poorly measured, unmeasured or unknown. Self‐controlled designs can help address this issue, as their key comparison is not between people, but periods of time within the same person. This controls for all time‐stable confounders (genetics) and in the absence of time‐varying confounding negates the need for an external control group. However, these benefits come at the cost of strong assumptions, not all of which are verifiable. This review briefly introduces the reader to different types of self‐controlled study designs, their terminology and highlights key publications through an annotated reference list. We include a practical description of how these designs can be implemented and visualised using recent examples, and finish by discussing recent developments. We hope this review will serve as a starting point for researchers looking to apply self‐controlled designs in their own work.
Glucagon‐Like Peptide 1 Receptor Agonists and Chronic Lower Respiratory Disease Among Type 2 Diabetes Patients: Replication and Reliability Assessment Across a Research Network
Authors: Conover Mitchell M. , Albogami Yasser , Hardin Jill , Reich Christian G. , Ostropolets Anna , Ryan Patrick B. ,   Observational Health Data Sciences and Informatics (OHDSI) Research Network
Published: January 2025

Introduction

The aim of this study is to use observational methods to evaluate reliability of evidence generated by a study of the effect of glucagon‐like peptide 1 receptor agonists (GLP‐1RA) on chronic lower respiratory disease (CLRD) outcomes among Type‐2 diabetes mellitus (T2DM) patients.

Research Design and Methods

We independently reproduced a study comparing effects of GLP‐1RA versus dipeptidyl peptidase‐4 inhibitors (DPP4‐i) on CLRD outcomes among patients with T2DM and prior CLRD. We reproduced inputs and outputs using the original study data (national administrative claims) and evaluated the robustness of results in comparison to alternate design/analysis decisions. To evaluate generalizability, we applied an analysis protocol and conducted a meta‐analysis across a research network that includes a diverse array of populations and data sources. We also produced additional analyses evaluating individual drugs within the GLP‐1RA class and CLRD outcomes.

Results

We confirmed alignment of study inputs and outputs and closely reproduced effect estimates and sensitivity analyses. Adjusted effect estimates were robust to empirical calibration. Network meta‐analysis confirmed original findings but indicated weaker effects than originally published. Meta‐analysis of drugs within the GLP‐1RA class against DPP4‐i provided evidence that effects vary within the GLP‐1RA class, indicating stronger effects for exenatide and weaker effects of dulaglutide.

Conclusions

This study supports and establishes the reliability of the original study by (1) producing consistent findings in a range of alternate databases and populations, (2) demonstrating effects for multiple drugs within the GLP‐1RA class, and (3) independently confirming the reproducibility of the original study and its findings. This reliability evaluation provides the beginnings of a broader framework for using standardized tools and distributed data networks to systematically interrogate the reliability of findings generated using observational data.
Evaluation of Drug–Drug Interactions in Pharmacoepidemiologic Research
Authors: Chen Cheng , Pham Nguyen Thanh Phuong , Hughes John E. , Hennessy Sean , Leonard Charles E. , Miano Todd A. , Douros Antonios , Gagne Joshua J. , Bykov Katsiaryna
Published: January 2025

Drug–drug interactions (DDIs) represent a significant concern for clinical care and public health, but the health consequences of many DDIs remain largely underexplored. This knowledge gap underscores the critical need for pharmacoepidemiologic research to evaluate real‐world health outcomes of DDIs. In this review, we summarize the definitions commonly used in pharmacoepidemiologic DDI studies, discuss common sources of bias, and illustrate through examples how these biases can be mitigated.
Long‐Term Opioid Therapy and Risk of Opioid Overdose by Derived Clinical Indication in North Carolina, 2006–2018
Authors: DiPrete Bethany L. , Ranapurwala Shabbar I. , Pettifor Audrey E. , Powers Kimberly A. , Delamater Paul L. , Fulcher Naoko , Pence Brian W.
Published: January 2025

Purpose

Long‐term opioid therapy (LTOT) has been shown to be associated with opioid overdose, but the definition of LTOT varies widely across studies. We use a rigorous LTOT definition to examine risk of opioid overdose by duration of treatment.

Methods

Data were from a large private health insurance provider in North Carolina linked to mortality records from 2006–2018. Eligible patients were adults (18–64) newly initiating opioid therapy after a pain diagnosis or surgery. We defined LTOT as ≥ 1 opioid prescription per month totaling ≥ 60 days' supply within 90 days. We used inverse probability (IP)‐weighted cumulative incidence functions to estimate three‐year risk of opioid overdose and IP‐weighted Fine–Gray models to estimate sub‐distribution hazard ratios, comparing LTOT to short‐ to medium‐term opioid therapy (SMTOT). We also examined modification by derived indication of acute pain or surgery versus chronic pain.

Results

We identified 491 369 patients, and 1.7% were exposed to LTOT. The three‐year risk of opioid overdose was 0.3 percentage points (RDw = 0.003, 95% CI: 0.001, 0.005) higher in LTOT patients compared to patients with SMTOT. The weighted hazard of opioid overdose was 4.4 times as high (HRw 4.42, 95% CI 2.41, 8.11) among patients exposed to LTOT versus SMTOT. We did not find meaningful modification by clinical indication for opioid therapy.

Conclusions

Exposure to LTOT was associated with increased risk of opioid overdose in this population of privately insured patients using a rigorous definition of LTOT. These findings confirm the importance of guidelines to minimize duration of opioid therapy whenever possible.
p53 and ΔNp63 Transcriptional Programs in Coordination With TGF‐β1 and RAS Activation Regulate HAS2 and HAS3 in Epithelial Cells
Authors: Basu Kaustuv , Li Yanshuang , Parnigoni Arianna , Vasilaki Eleftheria , Kolliopoulos Constantinos , Heldin Paraskevi
Published: January 2025

Hyaluronan, p53, and transforming growth factor‐β1 (TGF‐β1) play important roles in skin function. They are involved in keratinocyte growth, migration, and differentiation, although the way they interact is not well understood. Analysis of p63 genome‐wide chromatin immunoprecipitation and sequencing (ChIP‐seq) revealed that ΔNp63, a paralogue of p53, binds to the genomic loci of HAS2 and HAS3, encoding hyaluronan synthases, in human‐immortalized keratinocyte HaCaT cells which express mutant p53. Additionally, ΔNp63 binding to these loci, particularly onto the HAS2 gene, was further increased by constitutively active (ca)RAS‐ and TGF‐β1‐mediated suppression of p53. We found that p53 suppressed HAS2 and HAS3 mRNA expression, while ΔNp63 increased their expression. When mutant p53 was silenced, there was a significant increase in HAS2 and HAS3 expression in unstimulated HaCaT cells. After TGF‐β1 stimulation, HAS2 expression was further increased while HAS3 expression was suppressed. Additionally, p53 mutation and abrogation affected the levels of secreted hyaluronan. Moreover, activation of RAS played a key role in regulating TGF‐β1‐mediated expression of HAS2 and the hyaluronan receptor CD44 in a cell‐specific manner. The level of HAS3 was associated with the malignant phenotype in the MCF10A breast cancer progression model. In conclusion, we found that endogenous p53 and ΔNp63 activities are pivotal in regulating HAS2 and HAS3 mRNA expression in connection to TGF‐β1 stimulation and RAS activation.
Oxidative Destruction of p‐Chloroaniline in a Dielectric Barrier Discharge at Atmospheric Pressure in Oxygen
Authors: Gushchin Andrey , Kvitkova Elena , Ignatev Andrey , Izvekova Tatyana , Sharova Julia , Rybkin Vladimir
Published: January 2025

The paper presents the results of studies of the kinetics of decomposition of an aqueous solution of p‐chloroaniline (PCA) under the action of a dielectric barrier discharge at atmospheric pressure in an oxygen flow. The range of PCA concentrations was 10–150 mg/L, and the power density was 1.3 W/cm3. It was found that the decomposition of PCA proceeds formally according to the 1st kinetic order equation with a rate constant of (3.1–1.1) s‐1. The energy yield of decomposition (number of decomposed molecules per 100 eV of input energy) was 0.071–0.38. Data on the kinetics of the formation of degradation products (NH4+, NO2−, NO3−, Cl−, CO, CO2, carboxylic acids, aldehydes), as well as the results of biotesting of treated solutions are presented.
Microbial Ecology of Permafrost Soils: Populations, Processes, and Perspectives
Authors: Waldrop Mark P. , Ernakovich Jessica Gilman , Vishnivetskaya Tatiana A. , Schaefer Sean R. , Mackelprang Rachel , Barta Jiri , O′Brien Joy M. , Winkel Matthias , Barbato Robyn A. , Heffernan Liam , Leewis Mary‐Cathrine , Hewitt Rebecca E. , Hultman Jenni , Sun Yanchen , Biasi Christina , Bradley James A. , Liebner Susanne , Ricketts Michael P. , Muscarella Mario E. , Schütte Ursel , Abuah Fumnanya , Whalen Emily , Timling Ina , Voigt Carolina , Taş Neslihan , Lloyd Karen G. , Siljanen Henri M. P. , Rivkina Elizaveta M. , Voříšková Jana , Tao Jing , Liang Renxing , Li Zhen , Lennon Jay T. , Onstott T. C.
Published: January 2025

Permafrost microbial research has flourished in the past decades, due in part to improvements in sampling and molecular techniques, but also the increased focus on the permafrost greenhouse gas feedback to climate change and other ecological processes in high latitude and alpine permafrost soils. Permafrost microorganisms are adapted to these extreme environments and remain active at low temperatures and when resources are limited. They are also an important component of global elemental cycles as they regulate organic matter turnover and greenhouse gas production, particularly as permafrost thaws. Here we review the permafrost microbiology literature coupled with an exploration of its historical aspects, with a particular focus on a new understanding advanced by molecular biology techniques. We further identify knowledge gaps and ways forward to improve our understanding of microbial contributions to ecosystem biogeochemistry of permafrost‐affected systems.
Is there any skill in daily global precipitation forecasts over the Maritime Continent?
Authors: Mittermaier Marion P.
Published: January 2025

The presence of and spatial variation in daily precipitation forecast skill from a global deterministic Numerical Weather Prediction (NWP) model is explored over the Maritime Continent (MC). Location specificity and the variation of forecast performance with topographic height were of primary interest. The localised Fractions Skill Score (LFSS) was used alongside one well‐known derivative, the Skilful Spatial Scale (SSS). In this study a new temporal factorisation, the Lead Time Potential (LTP), is introduced and applied. It was found that whilst scores can be high, these do not necessarily imply useful skill. This is because of the impact of observed frequency of occurrence or base rate f in the 0.5 + f/2 useful skill criterion which underpins the SSS and LTP. For regions with high rainfall, such as the MC, it is not uncommon for f → 1, especially for modest thresholds, such that 0.5 + f/2 → 1. This means that even a near‐perfect score is not associated with any useful skill. Thus, if f/2 is ignored, the scales with useful skill are either considered as being smaller than they are, or worse, suggesting there is useful skill when there is none. The new LTP identifies many locations where useful skill is present up to seven days ahead. Typhoons are associated with some of the highest scores and skill, whereas persistence over land can be locally as skilful as the model forecast, though model forecasts show larger regions with better (lower) SSS and better (higher) LTP.
Enhanced Designs for the Multi‐Region Run Sum X¯${{\bar{X}}}$ Control Chart Based on the Median Run Length Metric
Authors: Teoh Wei Lin , Teoh Jing Wei , Goh Kai Le , Song Zhi , Saha Sajal
Published: January 2025

Extensive research has focused on the multi‐region run sum control chart, a sophisticated procedure for monitoring process mean shifts, particularly utilising the average run length (ARL) metric. Nevertheless, the skewed nature of the run‐length distribution can render the ARL metric misleading, and occasionally ineffective, when assessing a control chart's performance. The employment of the ARL metric in designing the run sum chart can erode practitioners’ confidence. This might be due to its complexities and difficulties in interpreting the complicated statistical concepts involved. To address this issue, the median run length (MRL) metric is proposed in this paper, which has been endorsed by various researchers due to its robustness towards skewness in the run‐length distribution. We design two novel optimal run sum charts utilising MRL and expected MRL (EMRL) metrics, under the assumptions of deterministic and unknown shit‐size scenarios, respectively. Specifically, the performances of the 4‐region and 7‐region run sum charts in both the zero‐state and steady‐state scenarios are developed using the Markov chain approach. Our comparative studies reveal that the proposed MRL‐ and EMRL‐optimal run sum charts surpass the optimal Shewhart and exponentially weighted moving average (EWMA) charts in terms of their average detection speeds, especially for moderate to large levels of process mean shifts. Practical examples from different industries are demonstrated using the proposed optimal run sum chart.
Measuring soil carbon stocks with greater simplicity, accuracy, and repeatability
Authors: Wuest Stewart
Published: January 2025

If soil samples are collected using the traditional linear depth methods, comparisons of soil constituents are most often confounded with differences in soil bulk density. Recent interest in quantifying soil C stocks will therefore require improved soil sampling protocols. The dry mass per unit area method eliminates soil bulk density as a measurement factor and therefore allows unbiased comparisons between sampling dates, soil conditions, soil types, sampling techniques, and treatments that affect soil bulk density. This note explains how this simple change in quantifying soil depth eliminates soil bulk density as a factor and improves the quantification of soil C stocks.
Exploring the Antidiabetic Potential of Pyrimidine‐Derived Chalcones: Synthesis, Biological Evaluation, and Molecular Modeling
Authors: Fatima Miraj , Aslam Samina , Fatima Aroog , Muhammed Muhammed Tilahun , Chaudhry Faryal , Irfan Ali , Rani Sadia , Raish Mohammad , Mateev Emilio , Jardan Yousef A. Bin
Published: January 2025

In the current research work, we have prepared a series of pyrimidine moiety‐containing molecules due to their promising medicinal profile. First of all, we prepared two acetyl derivatives of pyrimidine (15, 16), and then they reacted with different aryl aldehydes to form various chalcones in a 63–84% yield. The synthesized compounds were characterized by different analytical techniques and screened for their antidiabetic activity. Almost all synthesized compounds (17–43) showed good to excellent antidiabetic activity. Among all the synthesized compounds, 17 and 30 showed remarkable antidiabetic activity with IC50 values of 5.118 µm and 5.187 µm respectively, as compared to the standard reference drug acrabose (IC50 = 37.38 µm). While compounds 18, 19, 21, 22, 23, 27, 31, 33, 38, 42, and 43 also showed excellent antidiabetic activity. Additionally, most biopotent drugs' molecular docking studies supported the distinct connections between substituent moieties and docking domains and agreed with the experimental findings. The molecular dynamics simulation study of the active compounds with the highest binding propensity to the enzyme revealed the robustness of the complexes from the docking study.
Cesium Iron (III) Pyrophosphate Prepared Using a Solid‐State Process: Structure, Mössbauer Spectroscopy, and Relaxation Dynamics
Authors: Karray Mayssa , Garoui Iheb , Nasri Saber , Znaidia Sami , Mahmoud Abdelfattah , Oueslati Abderrazek
Published: January 2025

This study aims to synthesize the cesium iron (III) pyrophosphate compound CsFeP2O7 using a conventional solid‐state reaction method. The refinement of the X‐ray diffraction pattern indicated that the sample crystallized in a monoclinic structure at room temperature. The morphology and composition of the CsFeP2O7 compound were further analyzed using scanning electron microscopy (SEM) in conjunction with energy‐dispersive X‐ray spectroscopy (EDX). The Mössbauer spectroscopy confirmed the paramagnetic behavior of the CsFeP2O7 phosphate material at room temperature. The FTIR spectrum revealed absorption peaks corresponding to the fundamental modes of P2O74− anion vibrations. The electrical and dielectric properties were characterized using impedance spectroscopy as a function of frequency and temperature. The activation energy for continuous conductivity, (σdc), was found to be 0.13 eV for the temperature range [453–533 K] and 0.44 eV for the temperature range [553–673 K]. The permittivity behavior was analyzed using the Maxwell–Wagner model of interfacial polarization. The contribution of the grains and grain boundaries to the conduction mechanism was confirmed by Nyquist plots, which were fitted with an appropriate equivalent circuit. The imaginary parts of impedance (Z″) and modulus (M″) curves indicate a dielectric relaxation in the sample.
Recent Advances in Polymorphism of Organic Solar Cells
Authors: Xin Jingming , He Zemin , Liu Zefeng , Liu Xingpeng , Zhu Huiyao , Zhang Zhe , Song Chunpeng , Yin Xipeng , Liang Qiuju , Liu Jiangang
Published: January 2025

As organic solar cells (OSCs) achieve notable advancements, a significant consensus has been highlighted that the device performance is intricately linked to the active layer morphology. With conjugated molecules being widely employed, intermolecular interactions exert substantial influence over the aggregation state and morphology formation, resulting in distinct molecular packing motifs, also known as polymorphism. This phenomenon is closely associated with processing conditions and exerts a profound impact on functional properties. Consequently, understanding the mechanisms underlying polymorphism formation and establishing a definitive correlation between polymorphism and photophysical behavior is crucial for driving high‐performance OSCs. In this review, a comprehensive synthesis of recent developments is provided and emphasizing its pivotal role in the field of OSC polymorphism. The thermodynamic and kinetic principles governing polymorphism formation are examined. Then, representative polymorphisms are classified in OSC materials, segmenting them into homopolymers, copolymers, and IDTT‐ and BTP‐based small molecules. Additionally, prevalent strategies are evaluated for manipulating polymorphism. This review culminates with an analysis of the critical effects of polymorphism on OSCs, including charge carrier characteristics, photovoltaic efficiency, and long‐term stability. By offering novel perspectives and practical insights, this work seeks to guide future efforts in the morphological optimization of high‐efficiency OSCs.
Identifying Common Properties of Coefficient Matrices Appearing in Conventional or Invariant Scheme of Method of Fundamental Solutions
Authors: Yaji Kohei
Published: January 2025

In previous studies on the method of fundamental solutions applied to Dirichlet problems, the only method for verifying the regularity of coefficient matrix has been by calculating the determinant and checking if it is non‐zero directly. These verifications were carried out in some specific cases. This paper presents an identification of common properties of coefficient matrices within the method of fundamental solutions related to regularity. It establishes sufficient conditions for coefficient matrices to be regular and diagonally dominant in the two‐dimensional plane or the three‐dimensional space. However, when dealing with both the conventional scheme and the invariant scheme, we encounter issues where achieving a good arrangement of charges while maintaining diagonal dominance is challenging. One advantage of the invariant scheme over the conventional scheme is found to be based on the solvability of the shift of the boundary data. © 2025 Institute of Electrical Engineers of Japan and Wiley Periodicals LLC.
Prostate motion in magnetic resonance imaging-guided radiotherapy and its impact on margins
Authors: Kusters Johannes , Monshouwer René , Koopmans Peter , Wendling Markus , Brunenberg Ellen , Kerkmeijer Linda , van der Bijl Erik , Kusters Martijn
Published: January 2025

Purpose

This study focused on reducing the margin for prostate cancer treatment using magnetic resonance imaging-guided radiotherapy by investigating the intrafractional motion of the prostate and different motion-mitigation strategies.

Methods

We retrospectively analyzed intrafractional prostate motion in 77 patients with low- to intermediate-risk prostate cancer treated with five fractions of 7.25 Gy on a 1.5 T magnetic resonance linear accelerator. Systematic drift motion was observed and described by an intrafractional motion model. The planning target volume (PTV) margin was calculated in a cohort of 77 patients and prospectively evaluated for geometric coverage in a separate cohort of 24 patients.

Results

The intrafractional model showed that the prostate position starts out of equilibrium for the anterior–posterior (−1.8 ± 3.1 mm) and superior–inferior (1.7 ± 2.6 mm) directions, with relaxation times of 12 and 15 min, respectively. Position verification scans are acquired at 30 min on average. At that time, the transient drift motion becomes indistinguishable from the residual random intrafractional motion. PTV margins can be reduced to 1.8 mm (left–right), 3.2 mm (anterior–posterior), and 2.9 mm (superior–inferior). Evaluation of the overlap with the clinical target volume (CTV) was performed for a total of 120 fractions of 24 patients. The overlap range between the CTV and the PTV was 93–100% and the applied 3‑mm PTV margin for the CTV had a 99.5% averaged geometric overlap for all patients.

Conclusion

A PTV margin reduction to 3 mm is feasible. A patient-specific approach could reduce the margins further.
Simultaneous integrated boost to lateral pelvic lymph nodes during chemoradiotherapy in high-risk rectal cancer
Authors: Büttner Marcel , Böke Simon , Baumeister Sabrina , Bachmann Robert , Bitzer Michael , Bösmüller Hans , Wichmann Dörte , Niyazi Maximilian , Gani Cihan
Published: January 2025

Background

Preoperative chemoradiotherapy combined with total mesorectal excision (TME) is a standard treatment for locally advanced rectal cancer (LARC). However, lateral pelvic lymph nodes (LPLNs) are often inadequately treated with standard regimens. This study examines the treatment and postoperative outcomes in LARC patients receiving a simultaneous integrated boost (SIB) for LPLNs during long-course chemoradiotherapy.

Methods

This retrospective study included high-risk LARC patients (UICC, “Union Internationale Contre le Cancer”, stage III) treated with preoperative chemoradiotherapy and SIB to LPLNs. Radiotherapy was delivered to the primary tumor and elective volumes with 50.4 Gy in 28 fractions, and an SIB with a median dose of 60.2 Gy was administered to clinically positive LPLNs. TME quality and postoperative complications were assessed using MERCURY and Clavien–Dindo, respectively. Time-to-event data were analyzed according to Kaplan–Meier.

Results

Between 2019 and 2023, 27 patients with high-risk LARC and LPLN metastases were treated with chemoradiotherapy. After a median follow-up of 19 months, 2‑year overall survival was 80%, disease-free survival 80%, and local control of dose-escalated lymph nodes 100%. Three patients were managed nonoperatively after a clinical complete response on endoscopy and imaging. Of the 22 patients who had surgery, only one had complications higher than Clavien–Dindo grade I; TME was graded as MERCURY I in 73%.

Discussion and conclusion

The SIB approach for LPLNs in LARC is feasible, does not increase postoperative morbidity, and achieves excellent local control. This study supports the consideration of dose-escalated radiotherapy for LPLNs to address high local recurrence risks.