bluuebunny/crossref_metadata_2025 huggingface dataset:
Real‐world data for lenalidomide maintenance in responding patients of diffuse large B‐cell lymphoma
Authors: Wang Xiaoyan , Yu Lu , Jiang Xinlu , Ding Kaiyang
Published: March 2023

Background

Approximately 40% patients of diffuse large B‐cell lymphoma (DLBCL) would develop disease recurrence/progression after first‐line R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) induction therapy, with highly poor prognosis. An effective strategy to prolong the survival of this patient population is the additional single‐drug maintenance therapy. lenalidomide, an immunomodulatory drug with oral activity, has direct anti‐tumor activity and indirect effects mediated by multiple immune cells in the tumor microenvironment, such as B, T, natural killer (NK), and dendritic cells. Combining its controllable toxicity, it is promising in long‐term maintenance therapy. This study aims at evaluating the clinical effect of lenalidomide maintenance therapy in responding DLBCL patients with R‐CHOP treatment.

Methods

This retrospective study was devised in DLBCL cases who obtained complete response (CR) or partial response (PR) following 6–8 cycles of R‐CHOP treatment between January 1, 2015 and July 31, 2019. Patients (n = 141) included were respectively assigned to receive lenalidomide maintenance treatment (lenalidomide, n = 50) and drug‐free maintenance treatment (control, n = 91) after CR/PR. lenalidomide was provided orally at 25 mg/day for 10 days, with a cycle of 21 days and a treatment course of 2 years. Progression‐free survival (PFS) was taken as the primary outcome.

Results

Of the total 141 subjects, the median follow‐up time was 30.9 months (range, 5.7–68.9 months). The 2‐year PFS was 84% (95% CI: 74%–94%) in the lenalidomide group and 53% (95% CI: 43%–63%) in the control group. The median PFS of the lenalidomide group was not reached, and that of the control group was 42.9 months (HR = 0.32; 95% CI: 0.16–0.63; p = 0.001). No remarkable difference in overall survival (OS) between the two groups was indicated (HR = 0.42; 95% CI: 0.16–1.12; p = 0.08). Central nervous system (CNS) recurrence happened in 5 patients (5.5%) of the control group, while none of the patients with lenalidomide had CNS recurrence. Additionally, neutropenia and cutaneous reactions were the most common Grade 1–2 adverse reactions after lenalidomide treatment, and neutropenia was the most frequent Grade 3–4 adverse reaction.

Conclusion

Two‐year lenalidomide maintenance treatment can significantly prolong the PFS of DLBCL patients who obtained CR/PR to first‐line R‐CHOP treatment.
Starch fine molecular structures as driving factors for multiphasic starch gelatinization property in rice flour
Authors: Li Cheng , Yi Xueer , Yang Chuantian , Li Enpeng
Published: March 2023

Background and Objectives

Although the gelatinization property of isolated rice starch has been investigated in terms of its relationship to starch fine molecular structures, it remains unclear how these structures determine the gelatinization property of rice flour. The gelatinization properties of 10 rice flours with varying chain‐length distributions were thus studied.

Findings

Rice flours with larger amylose molecules, longer and higher amount of amylopectin intermediate chains showed double gelatinization peaks. The onset and peak temperatures of gelatinization for the peak having a lower gelatinization temperature showed a positive correlation with the molecular size of amylopectin. Conversely, the conclusion temperature of gelatinization for the peak with a higher gelatinization temperature exhibited a negative correlation with the molecular size of amylose and a positive correlation with the quantity of amylose and amylopectin intermediate chains. These correlations were largely different compared with those for rice flours with a single gelatinization peak.

Conclusions

These results supplied the first associations between gelatinization property of rice flour and starch fine molecular structures, which were different from those for pure rice starches.

Significance and Novelty

These results have the potential to assist the food industry in developing rice products with improved quality, depending on the molecular structure of the starch.
Eletrocarboxylation Reactions Using CO2 Both as Promoter and Carboxylative Reagent
Authors: Zhang Ke , Liu Xiao‐Fei , Ren Wei‐Min , Lu Xiao‐Bing , Zhang Wen‐Zhen
Published: March 2023

Electrocarboxylation reaction, which employs organic electrosynthesis to achieve the utilization of CO2 as a carboxylative reagent, provides a powerful and efficient tool for the preparation of organic carboxylic acid. In some electrocarboxylation reactions, CO2 also acts as a promoter to facilitate the desired reaction. This concept mainly highlights recent CO2‐promoted electrocarboxylation reactions via CO2⋅− intermediate or transiently protective carboxylation of active intermediate with CO2.
Pd−Bi Bimetallic Nanochains for Electroreduction of CO2 to Syngas in Ionic Liquid‐Based Electrolytes
Authors: Yang Han , Zhang Renjie , Yang Jie , Zhou Guangying , Jia Xiaoyan , Hua Zhixin , Yang Dexin
Published: March 2023

The electroreduction of carbon dioxide (CO2) is a sustainable method for generating valuable chemicals; however, avoiding unwanted hydrogen (H2) production during the electrolysis is a major challenge. Coproduction of carbon monoxide (CO) and H2 to produce syngas is an effective strategy for solving this problem, and syngas with a desired CO/H2 ratio can be employed to produce methanol or other valuable chemicals. Herein, a series of palladium‐bismuth (Pd−Bi) bimetallic nanochains with different Pd/Bi atomic ratios were prepared and used in the electroreduction of CO2 to syngas in ionic liquid‐based electrolytes. The ratio of CO/H2 in syngas was regulated in a wide range from 1 : 7 to 9 : 1 by controlling the applied potentials, Pd/Bi atomic ratios and composition of the electrolytes. In particular, the current density reached 19.3 mA cm−2 on Pd3Bi bimetallic nanochains at an applied potential of −2.3 V versus Ag/Ag+ when the CO/H2 ratio was approximately 1 : 1. Moreover, the maximum CO Faradaic efficiency was 87.7 % for these electrocatalysts at an applied potential of −2.0 V versus Ag/Ag+. The synergistic effect of Pd and Bi in the ionic liquid‐based electrolyte was the primary reason for the distinct electrocatalytic efficiency of the Pd3Bi bimetallic nanochains. The incorporation of moderate amounts of Bi into the Pd lattice resulted in a stronger CO2 adsorption capacity, more active sites and faster electron transfer rate, which are conducive to improving the electrocatalytic activity.
Malignancy in pregnancy: Multimodality imaging and treatment
Authors: Nguyen Trinh , Bhosale Priya R. , Cassia Lorena , Surabhi Venkateswar , Javadi Sanaz , Milbourne Andrea , Faria Silvana C.
Published: March 2023

The diagnosis of cancer is increasingly made in the pregnant population, thought to be from the increasing average age of pregnancy and the use of prenatal fetal noninvasive screening techniques, leading to incidental detection of cancer in the mother. Complex challenges are associated with imaging, diagnosis, staging, and treatment of cancers in this patient population, which require highly specialized interdisciplinary management. This report discusses the use of multimodality imaging and safety considerations in pregnant patients, reviews the current guidelines for ionizing radiation imaging techniques, and presents a series of commonly and uncommonly encountered cancers in pregnancy with current diagnostic imaging guidelines. The authors also discuss the role of multidisciplinary management and treatment options and provide an overview of therapy‐related considerations in the age of novel anticancer therapies.

Plain Language Summary

The diagnosis and management of pregnant patients who have cancer are actively evolving as novel imaging techniques and anticancer therapies are being developed.

Radiologically, there are inherent difficulties in balancing the minimization of fetal ionization while acquiring diagnostic quality imaging necessary for the diagnosis, staging, and treatment of maternal disease.

Standardized imaging protocols are still being developed, with evolving imaging guidelines coupled with rapidly expanding research and development of novel anticancer therapies, which come with their side effects and complications.

Caring for this patient population is especially challenging and requires specialized multidisciplinary attention.
Solid‐Supported Membrane (SSM)‐Based Electrophysiology Assays Using Surface Electrogenic Event Reader Technology (SURFE²R) in Early Drug Discovery
Authors: Pommereau Antje , Licher Thomas , Bärenz Felix
Published: March 2023

This article presents detailed descriptions of procedures and troubleshooting tips for solid‐supported membrane (SSM)‐based electrophysiology assays (SURFE²R) to measure electrogenic solute carrier transporter proteins (SLCs) and assess the effects of compounds that modulate their activity. SURFE²R allows the use of the standard 96‐well format, making it an ideal platform for tertiary assays in a drug‐discovery campaign. The assays are performed with cell‐line‐derived membrane fractions or proteoliposomes containing the transporter of interest. Three main protocols are described for the isolation of membrane fractions from cell culture and the generation of proteoliposomes containing the transporter of interest. Additionally, detailed protocols for SURFE²R single concentration and dose‐response experiments are included to measure the potencies of test compounds in stimulating or inhibiting transporter function (EC50 or IC50 values, respectively) and kinetic functional assays to calculate apparent affinity (kM) and maximal velocity (Vmax) of substrate uptake. © 2023 Sanofi. Current Protocols published by Wiley Periodicals LLC.

This article was corrected on 23 March 2023. See the end of the full text for details.

PROTOCOL GROUP 1: Sample preparation for SSM‐based electrophysiology assays

Support Protocol 1: Production of cell batches

Support Protocol 2: Simple isolation of cell membranes

Alternate Protocol 1: Isolation of cell membranes with sucrose gradient pre‐purification

Support Protocol 3: Production and isolation of liposomes

Support Protocol 4: Preparation of sensor with isolated cell membranes

Alternate Protocol 2: Preparation of sensor with isolated proteoliposomes

PROTOCOL GROUP 2: Determination of assay parameters for SSM‐based electrophysiology assay

Support Protocol 5: Assay with stable buffer

Alternate Protocol 3: Assay with ion gradient

Support Protocol 6: Determination of membrane/liposome concentration

Support Protocol 7: Determination of substrate dependency kM

PROTOCOL GROUP 3: Determination of advanced assay parameters for SSM‐based electrophysiology assays

Support Protocol 8: Assessment of ion concentration dependency

Support Protocol 9: Assessment of pH dependency

Support Protocol 10: Assessment of DMSO dependency

Support Protocol 11: Assessment of signal stability with multiple activations

PROTOCOL GROUP 4: Compound testing through SSM‐based electrophysiology assays using SURFE²R apparatus

Support Protocol 12: Assessment of signal specificity of a published inhibitor or unknown compound(s)

Support Protocol 13: Compound wash‐out

Support Protocol 14: Statistical analysis
Effect of Ar Plasma Treatment on the Interface and Performance of CdZnTe Detectors
Authors: Cao Xiangzhi , Zhang Jijun , Wang Shulei , Xu Zheren , Wang Linjun
Published: March 2023

The performance of CdZnTe detectors is not only influenced by the growth of crystal, but also by the quality of the interface layer between the crystal and the electrode. A model of CdZnTe detector with metal–semiconductor–metal structure is developed to investigate the effects of the interface on the space charge and electric field distribution. Atomic force microscopy, current–voltage (I–V) analysis, and energy spectra under 241Am irradiation are adopted to investigate the effects of argon (Ar) plasma treatment on the interface and performance of CdZnTe detectors experimentally. The simulation results show that the interface layer with low density of surface state and thin thickness can form a more uniform space charge and electric field distribution. Due to the decrease of voltage drop across the interface, the leakage current at 200 V of CdZnTe detector with Ar plasma treatment is reduced from 159 to 44 nA cm−2, and the full‐width at half‐maximum under 241Am is improved from 9.3% to 8.2%, as compared to conventional Br‐MeOH treatment.
Board gender diversity and environmental, social and governance (ESG) disclosure: Is it different for developed and developing nations?
Authors: Wasiuzzaman Shaista , Subramaniam Vasanthan
Published: March 2023

This paper examines the influence of board gender diversity on the Environmental, Social and Governance (ESG) disclosure quality of energy firms. Particularly, the study evaluates the possible differences in the influence of board gender diversity on the ESG disclosure practice of firms in developed and developing nations. Previous studies have used single country based analysis and presented diverse results, however this study uses data from 48 countries from both developed and developing nations over a period of 13 years (from year 2004 to 2016). The study finds that, in general, female directors favorably influence the quality of disclosure of ESG and its individual components (except governance). However, sub‐sample analysis of firms in developed and developing nations finds that the relationships are significant only for the sample of firms in developed nations. The results show that there are differences in the role female directors play in influencing ESG disclosure for developed and developing countries, thus this study highlights the importance of accounting standards in strengthening the contribution of female directors on corporate boards, especially in developing countries. The study also highlights the need to assess ESG components separately, in addition to the overall component, when conducting studies on ESG.
Time‐dependent charged particle stopping in quantum plasmas: testing the G1–G2 scheme for quasi‐one‐dimensional systems
Authors: Makait C. , Fajardo F. Borges , Bonitz M.
Published: March 2023

Warm dense matter—an exotic, highly compressed state on the border between solid and plasma phases is of high current interest, in particular for compact astrophysical objects, high‐pressure laboratory systems, and inertial confinement fusion. For many applications, the interaction of quantum plasmas with energetic particles is crucial. Moreover, often the system is driven far out of equilibrium. In that case, there is high interest in time‐dependent simulations to understand the physics, in particular, during thermalization. Recently a novel many‐particle technique, the G1–G2 scheme was presented with reference to the study by Schlünzen et al. (2020) which allows for first‐principle simulations of the time evolution of interacting quantum systems. Here we apply this scheme to a spatially uniform dense quantum plasma (jellium) and explore its performance. To this end, the G1–G2 scheme is transformed into momentum representation, and first results are presented for a quasi‐one‐dimensional model system.
Effect of olive oil phenols on oxidative stress biomarkers: A systematic review and dose–response meta‐analysis of randomized clinical trials
Authors: Derakhshandeh‐Rishehri Seyedeh‐Masomeh , Kazemi Asma , Shim Sung Ryul , Lotfi Mostafa , Mohabati Shabnam , Nouri Mehran , Faghih Shiva
Published: March 2023

The phenolic content of olive oil has a role in cardiovascular protection. Some clinical trial studies demonstrated that phenolic compounds of olive oil have antioxidant activity which can protect macronutrients from oxidative damages. The aim of this study was to summarize the results of clinical trials which assessed the effects of high‐ versus low‐phenol olive oil on oxidative stress biomarkers levels. We searched Scopus, PubMed, Web of Science, Google Scholar, ProQuest, and Embase up to July 2021. Eight clinical trials which evaluated the effect of the phenolic content of olive oil on oxidized‐LDL (ox‐LDL), malondialdehyde (MDA), or ferric‐reducing ability of plasma (FRAP) were included the meta analysis. A significant decrease was observed in ox‐LDL level (WMD: −0.29 U/L; 95% CI: −0.51, −0.07) and MDA (WMD: −1.82 μmoL/L; 95% CI: −3.13, −0.50). However, after subgroup analysis for MDA, the result was not significant for not serious limitation (SMD: −0.05, 95% CI: −0.35 to 0.24), but significant for serious limitation (SMD: −3.64, 95% CI: −4.29 to −2.99). Also, no significant change was found in FRAP (WMD: 0.0 mmoL/L; 95% CI: −0.03, 0.04) level. Dose–response analysis indicated a significant linear relationship between the phenolic content of olive oil and ox‐LDL. The present study showed some beneficial effects of high‐phenol compared with low‐phenol olive oil on ox‐LDL and MDA levels. According to the meta‐regression analysis along with the increasing phenolic content of olive oil, a reduction in oxidative stress biomarkers was observed.
Critical path planning for discharging older adults using a functional perspective
Authors: Salehi Vahid , Veitch Brian , Smith Doug
Published: March 2023

This study aims to introduce an innovative method to schedule and analyze the discharge planning processes under uncertain individual activity completing times. Hospital care processes ending in discharging older adults represent a major challenge, as a number of interrelated tasks or activities are involved in the processes. The functional resonance analysis method (FRAM) is used to identify activities that constitute a descriptive model of the discharge planning processes and to assign the completion time to each task or activity. Then the critical path planning technique is utilized to identify the critical path of the discharge process. To this end, the Program Evaluation and Review Technique (PERT) is employed. Published data regarding six older patients are used to examine the potential utility of the introduced method to improve the discharge process of older adults. The results show that the integration of the FRAM and PERT is able to identify the critical activities that constitute the critical path of the discharge process. It also helps analyze the completion time assigned to each task/activity and calculate the completion time of the discharge process. The probability of completing the discharge process within a target completion time is also discussed. The results add further evidence showing the applicability of the FRAM and PERT to scheduling systems for the discharge planning processes. Health care professionals could use the findings of this study in designing a scheduling system to complete the discharge process of older adults in a reasonable time.
Fanconi anemia‐isogenic head and neck cancer cell line pairs: A basic and translational science resource
Authors: Nguyen Hiep Tai , Tang Weiliang , Webster Andrew L. H. , Whiteaker Jeffrey R. , Chandler Christopher M. , Errazquin Ricardo , Roohollahi Khashayar , Fritzke Madeline , Hoskins Elizabeth E. , Jonlin Erica , Wakefield Leslie , Sullivan Lucas B. , Chen Eleanor Y. , Dorsman Josephine , Brakenhoff Ruud , Paulovich Amanda G. , Grompe Markus , Garcia‐Escudero Ramon , Wells Susanne I. , Smogorzewska Agata , Monnat Raymond J.
Published: March 2023

Fanconi anemia (FA) is a heritable malformation, bone marrow failure and cancer predisposition syndrome that confers an exceptionally high risk of squamous carcinomas. These carcinomas originate in epithelia lining the mouth, proximal esophagus, vulva and anus: their origins are not understood, and no effective ways have been identified to prevent or delay their appearance. Many FA‐associated carcinomas are also therapeutically challenging: they may be multi‐focal and stage‐advanced at diagnosis, and most individuals with FA cannot tolerate standard‐of‐care systemic therapies such as DNA cross‐linking drugs or ionizing radiation due to constitutional DNA damage hypersensitivity. We developed the Fanconi Anemia Cancer Cell Line Resource (FA‐CCLR) to foster new work on the origins, treatment and prevention of FA‐associated carcinomas. The FA‐CCLR consists of Fanconi‐isogenic head and neck squamous cell carcinoma (HNSCC) cell line pairs generated from five individuals with FA‐associated HNSCC, and five individuals with sporadic HNSCC. Sporadic, isogenic HNSCC cell line pairs were generated in parallel with FA patient‐derived isogenic cell line pairs to provide comparable experimental material to use to identify cell and molecular phenotypes driven by germline or somatic loss of Fanconi pathway function, and the subset of these FA‐dependent phenotypes that can be modified, complemented or suppressed. All 10 FANC‐isogenic cell line pairs are available to academic, non‐profit and industry investigators via the “Fanconi Anemia Research Materials” Resource and Repository at Oregon Health & Sciences University, Portland OR.
Prostate sarcoma
Authors: Ehat Nicholas T , Chuong Lisa , Dickman Jenna , Deng Tom , Chang George , Hwang Jonathan
Published: March 2023

Introduction

This report is intended to provide insight into the presentation, diagnosis, and treatment of prostatic sarcomas. A literature review is included to compare variables in demographics, histology, prognosis, and treatment strategies among previously reported incidences.

Case presentation

In this case, we have a 72‐year‐old man who initially presented with symptomatic nephrolithiasis that led to further workup. Magnetic resonance imaging revealed an enlarged, heterogeneous prostate with a dominant mass in the left lobe. A biopsy of the prostate revealed a high‐grade, undifferentiated sarcoma in the left lobe along with concomitant adenocarcinoma in the right lobe.

Conclusions

The patient underwent a radical prostatectomy, which according to existing literature remains the most effective treatment strategy. Staging is the most important prognostic indicator, making this cancer particularly dangerous as presenting symptoms are highly variable among patients.
Retroauricular lymph node flap: An anatomic and surgical feasibility study
Authors: Roka‐Palkovits Julia , Freystätter Christian , Tinhofer Ines E. , Keck Maike , Steinbacher Johannes , Meng Stefan , Weninger Wolfgang J. , Cheng Ming‐Huei , Tzou Chieh‐Han J.
Published: March 2023

Background

The study investigated the anatomy of the retroauricular lymph node (LN) flap and evaluate its surgical feasibility as a new donor site for a free LN flap in lymphedema surgery.

Methods

Twelve adult cadavers were examined. The course and perfusion of the anterior auricular artery (AAA) and the location and sizes of the retroauricular LNs were studied.

Results

The AAA was available in 87% and absent in 13% specimens. The AAA's origin had a mean vertical distance of 12.2 ± 6.9 mm and a mean horizontal distance of 19.1 ± 4.2 mm from the superior attachment of the ear. The mean diameter of the AAA was 0.8 ± 0.2 mm. The mean number of LN per region was 7.7 ± 2.3, with an average LN size of 4.1 ± 1.9 × 3.2 ± 1.7 mm. The LN were categorized into anterior (G1) and posterior (G2) groups, with a total of 59 and 10 LN, respectively. In a cluster analysis, three LN clusters could be detected across the anterior group (G1).

Conclusions

The retroauricular LN flap is a delicate but feasible flap with reliable anatomy, containing a mean of 7.7 LNs.
Exosomal miR‐196a‐5p enhances radioresistance in lung cancer cells by downregulating NFKBIA
Authors: Yao Fei , Shi Wei , Fang Fang , Lv Meng‐Yu , Xu Mei , Wu Shan‐Yan , Huang Chun‐Li
Published: March 2023

Radiation therapy is recognized as an effective modality in the treatment of lung cancer, but radioresistance resulting from prolonged treatment reduces the chances of recovery. MicroRNAs (miRNAs) play a pivotal role in radiotherapy immunity. In this study, we aimed to investigate the mechanism by which miR‐196a‐5p affects radioresistance in lung cancer. The radioresistant lung cancer cell line A549R26–1 was established by radiation treatment. Cancer‐associated fibroblasts (CAFs) and normal fibroblasts (NFs) were observed by microscopy, and the expression levels of CAF‐specific marker proteins were detected by immunofluorescence. The shape of the exosomes was observed by electron microscopy. A CCK‐8 assay was used to detect cell viability, while clone formation assays were used to detect cell proliferative capacity. Flow cytometry was performed to investigate apoptosis. The binding of miR‐196a‐5p and NFKBIA was predicted and further verified by the dual luciferase reporter experiment. qRT–PCR and western blotting were used to detect gene mRNA and protein levels. We found that exosomes secreted by CAFs could enhance lung cancer cell radioresistance. Moreover, miR‐196a‐5p potentially bound to NFKBIA, promoting malignant phenotypes in radioresistant cells. Furthermore, exosomal miR‐196a‐5p derived from CAFs increased radiotherapy immunity in lung cancer. Exosomal miR‐196a‐5p derived from CAFs enhanced radioresistance in lung cancer cells by downregulating NFKBIA, providing a new potential target for the treatment of lung cancer.
Tracking freshwater browning and coastal water darkening from boreal forests to the Arctic Ocean
Authors: Opdal Anders Frugård , Andersen Tom , Hessen Dag O. , Lindemann Christian , Aksnes Dag L.
Published: March 2023

The forest cover of Northern Europe has been steadily expanding during the last 120 years. More terrestrial vegetation and carbon fixation leads to more export to surface waters. This may cause freshwater browning, as more degraded plant‐litter ends up as chromophoric (colored) dissolved organic matter. Although most freshwater ultimately drains to coastal waters, the link between freshwater browning and coastal water darkening is poorly understood. Here, we explore this relationship through a combination of centennial records of forest cover and coastal water clarity, contemporary optical measurements in lakes and coastal waters, as well as an ocean drift model. We suggest a link between forest cover in Northern Europe and coastal water clarity in the Baltic, Kattegat, and Skagerrak Sea and show how brown‐colored freshwater from Northern European catchments can dictate coastal water clarity across thousands of kilometers, from the Baltic lakes to the Barents Sea.
Design of iterative methods with memory for solving nonlinear systems
Authors: Cordero Alicia , Garrido Neus , Torregrosa Juan R. , Triguero‐Navarro Paula
Published: March 2023

In this paper, we design two parametric classes of iterative methods without memory to solve nonlinear systems, whose convergence order is 4 and 7, respectively. From their error equations and to increase the convergence order without performing new functional evaluations, memory is introduced in these families of different forms. That allows us to increase from 4 to 6 the convergence order in the first family and from 7 to 11 in the second one. We perform some numerical experiments with big size systems for confirming the theoretical results and comparing the proposed methods along other known schemes.
Enhanced Hypoglycemic Bioactivity via RAS/Raf‐1/MEK/ERK Signaling Pathway by Combining Capsaicin and QUERCETIN from Chili Peppers
Authors: Mi Si , Zhu Wenxuan , Zhang Xiangnan , Wang Yuhang , Li Tong , Wang Xianghong
Published: March 2023

Scope

This research work is designed and conducted to explore the joint effect of capsaicin and quercetin and the potential mechanism for the regulation of hyperglycemia.

Methods and results

Insulin‐resistance HepG2 cell model and high‐fat diet combined with streptozotocin‐induced type 2 diabetes mouse model are applied for the investigation. The results illustrate that capsaicin and quercetin can exert hypoglycemic effects via reducing the concentrations of serum lipids of total cholesterol, triglyceride and low‐density lipoprotein cholesterol, decreasing hepatic enzyme activities of phosphoenolpyruvate, carboxykinase, and glucose‐6‐phosphatase, as well as improving the histopathological morphology of liver and pancreas tissues. After administration with capsaicin and quercetin, the relative protein expression abundance of Ras, Raf‐1, MEK1/2, and ERK1/2 is obviously attenuated compared to diabetic mice. Capsaicin and quercetin at a ratio of 3:1 are generally determined as the optimal combination.

Conclusion

Capsaicin and quercetin present in the chili pepper fruit can act in a synergistic way to alleviate hyperglycemia. This study provides supporting data for the discovery of novel anti‐diabetic components and for the valorization of chili pepper industry.
Study on the effect of intervention on postpartum psychological improvement and body recovery of caesarean section women based on information‐motivation‐behavioural skills model
Authors: Xu Linjun , Fang Li , Xu Qianjuan , Shen Danhong
Published: March 2023

Aim

To explore the effect of information‐motivation‐behavioural skills (IMB) model on psychological and emotional state of caesarean section (CS) women.

Design

Control‐group patients got routine nursing during the preoperative, intraoperative and postoperative periods. Observation‐group patients received routine nursing combined with the IMB model that included specific informational, motivational and behavioural interventions.

Methods

Pregnant women (n = 102) who underwent CS in Hangzhou Women's Hospital were randomly divided into Control and Observation‐groups (n = 51 each). Self‐rating anxiety scale (SAS), self‐rating depression scale (SDS) and general self‐efficacy scale (GSES) scores, complication rate, fatigue severity scale (FSS) and Edinburgh postpartum depression scale (EPDS) scores were compared.

Result

Interventions lowered SAS and SDS scores, significantly lower in the Observation‐group (p < 0.05), and increased GSES scores, significantly higher in the Observation‐group (p < 0.05). Observation‐group had less complications (4.08% vs. 17.39% in the Control‐group; p < 0.05), and decreased FSS and EPDS scores (p < 0.05).
Link between anisotropic electrochemistry and surface transformations at single‐crystal silicon electrodes: Implications for lithium‐ion batteries
Authors: Martín‐Yerga Daniel , Bahri Mounib , Curd Matthew E. , Xu Xiangdong , Li Weiqun , Burnett Timothy L. , Withers Philip J. , Mehdi B. Layla , Browning Nigel D. , Unwin Patrick R.
Published: March 2023

Silicon is a promising negative electrode material for high‐energy‐density Li‐ion batteries (LiBs) but suffers from significant degradation due to the mechanical stress induced by lithiation. Volume expansion and lithiation in Si are strongly anisotropic but associated early interfacial transformations linked to these phenomena and their implications for electrode performance remain poorly understood. Here we develop a novel correlative electrochemical multi‐microscopy approach to study local interfacial degradation at the early stages for three different surface orientations of Si single crystals: Si(1 0 0), Si(1 1 0) and Si(3 1 1), after Li‐ion electrochemical cycling. The experimental strategy combines scanning electrochemical cell microscopy (SECCM) measurements with subsequently recorded scanning transmission electron microscopy images of high‐quality cross sections of Si electrodes, extracted at selected SECCM regions, using a novel Xe+ plasma‐focused ion beam procedure. These studies reveal significant surface orientation–dependent nanoscale degradation mechanisms that strongly control electrode performance. Si(1 0 0) was immune to interfacial degradation showing the best lithiation reversibility, whereas local nanoscale delamination was observed in Si(1 1 0) leading to a lower Coulombic efficiency. Continuous electrochemical deactivation of Si(3 1 1) was associated with delamination across the whole interface, Li trapping and formation of thick (ca. 60 nm) SiO2 structures. These results demonstrate surface crystallography to be a critical factor when designing Si‐based battery materials and strongly suggest that promoting Si(1 0 0) facets could potentially provide longer cycling life and performance due to a higher resistance to degradation.
Analysis of tensile damage characteristics of single filled bolt hole in laminate
Authors: Zhang Fa , Zhang Huanshi , Pan Zhongxiang , Liu Meina , Liu Tierang , Wan Yumin
Published: March 2023

The strength of filled bolt holes of composites is an important parameter in developing the bearing bypass envelope curves for bolted joint structures in engineering design. This paper presents the procedures of tensile failure strengths and damage for a laminate with a filled bolt hole. Tests of two different cases, open‐hole tension (OHT) and filled‐hole tension (FHT), were performed and repeated seven times, respectively. A new type of virtual testing based on the LaRC05 criteria coupling with XFEM crack technique was developed to predict and analyze the crack initiation and early propagation around the bolt hole in the laminates. Two analytical methods were also adopted to predict the residual strength for a laminate after drilling. The results show that the thinner sample would present a higher strength with the same material system. It is also shown that the virtual test can well capture the failure modes, revealing that the 0° fiber has a natural function of crack arrest, the 90° layers that are the fracture pioneers with matrix tensile failure trigger the fiber breakage of 0° layers, and the failure of 45° layers occurs at the last. Additionally, an interesting phenomenon is observed that the initial failure around the filled hole edge does not affect the structural stiffness. Finally, a good agreement is achieved among the experimental, analytical and numerical results. It suggests that the results could provide a valuable guidance for the design of multi‐bolted joint structure.
SARS‐CoV‐2 neutralizing antibody epitopes are overlapping and highly mutated which raises the chances of escape variants and requires development of broadly reactive vaccines
Authors: Joseph Jeswin , Darpe Sukhada , Kulkarni Grishma , Raj V. Stalin
Published: March 2023

The rapid adaptation of SARS‐CoV‐2 within the host species and the increased viral transmission triggered the evolution of different SARS‐CoV‐2 variants. Though numerous monoclonal antibodies (mAbs) have been identified as prophylactic therapy for SARS‐CoV‐2, the ongoing surge in the number of SARS‐CoV‐2 infections shows the importance of understanding the mutations in the spike and developing novel vaccine strategies to target all variants. Here, we report the map of experimentally validated 74 SARS‐CoV‐2 neutralizing mAb binding epitopes of all variants. The majority (87.84%) of the potent neutralizing epitopes are localized to the receptor‐binding domain (RBD) and overlap with each other, whereas limited (12.16%) epitopes are found in the N‐terminal domain (NTD). Notably, 69 out of 74 mAb targets have at least one mutation at the epitope sites. The potent epitopes found in the RBD show higher mutations (4‐10aa) compared to lower or modest neutralizing antibodies, suggesting that these epitopes might co‐evolve with the immune pressure. The current study shows the importance of determining the critical mutations at the antibody recognition epitopes, leading to the development of broadly reactive immunogens targeting multiple SARS‐CoV‐2 variants. Further, vaccines inducing both humoral and cell‐mediated immune responses might prevent the escape of SARS‐CoV‐2 variants from neutralizing antibodies.
mRNA anti‐cancer vaccine research gains momentum
Authors: Greener Mark
Published: March 2023

Ongoing research into the use of messenger RNA (mRNA) vaccines for the treatment of cancer has been expediated by the coronavirus pandemic because similar technology was used in the development of mRNA COVID‐19 vaccines. So how close are we now to the widespread clinical use of mRNA anti‐cancer vaccines?
Anti‐synthetase syndrome associated interstitial lung disease after combination dual immune checkpoint inhibition
Authors: Bell Peter T. , Beaton Thomas , Terrill Matthew , Gillis David , Goddard John
Published: March 2023

Immune checkpoint inhibitors (ICIs) unleash potent anti‐tumour responses but with frequent off‐target immune‐mediated adverse events (irAE). ICIs can induce a spectrum of rheumatologic manifestations including inflammatory arthritis, Sjögren's syndrome, scleroderma and systemic lupus erythematosus. Here, we describe a case of antisynthetase syndrome associated interstitial lung disease (ILD) following dual Programmed Cell Death 1 and Cytotoxic T Lymphocyte‐Associated Protein 4 checkpoint inhibition in a patient with metastatic melanoma. Initial treatment course was complicated by a number of irAEs including pneumonitis, colitis and thyroiditis. Suspicion of an underlying systemic rheumatic disease was heightened by the severe, relapsing and fibrosing nature of the interstitial pneumonitis. A diagnosis of amyopathic antisynthetase syndrome was made upon detection of circulating aminoacyl‐tRNA synthetase (anti‐EJ) autoantibodies. Intensification of induction immunosuppression followed by maintenance mycophenolate, prednisone and monthly intravenous immunoglobulin achieved long‐term disease control. Detection of de novo ICI‐induced inflammatory myositis ILD requires a high index of suspicion and carries important prognostic and treatment implications.
Dissipativity analysis for Lur'e systems with two additive time‐varying delays via some novel Lyapunov–Krasovskii functionals
Authors: Ban Jie , Guo Liang‐Dong
Published: March 2023

The problem of dissipativity analysis is discussed for Lur'e systems with two additive time‐varying delays (ATDs) in this paper. Based on the dynamic delay interval (DDI) method, some novel Lyapunov‐Krasovskii functionals (LKFs) are constructed, in which part of Lyapunov matrices are requested to be positive definite. Then strictly dissipativity criteria of Lur'e systems with ATDs are presented in terms of linear matrix inequalities (LMIs). As by‐products, the stability criteria of Lur'e systems with ATDs and the systems with ATDs are derived. Finally, several numerical examples are used to illustrate the effectiveness and superiority of these criteria.
Vanishing of the Anomaly in Lattice Chiral Gauge Theory
Authors: Mastropietro Vieri
Published: March 2023

The anomaly cancellation is a basic property of the Standard Model, crucial for its consistence. We consider a lattice chiral gauge theory of massless Wilson fermions interacting with a non-compact massive U(1) field coupled with left- and right-handed fermions in four dimensions. We prove in the infinite volume limit, for weak coupling and inverse lattice step of the order of boson mass, that the anomaly vanishes up to subleading corrections and under the same condition as in the continuum. The proof is based on a combination of exact Renormalization Group, non-perturbative decay bounds of correlations and lattice symmetries.
Methylation of histone H3 lysine 4 is required for maintenance of beta cell function in adult mice
Authors: Vanderkruk Ben , Maeshima Nina , Pasula Daniel J. , An Meilin , McDonald Cassandra L. , Suresh Priya , Luciani Dan S. , Lynn Francis C. , Hoffman Brad G.
Published: March 2023

Aims/hypothesis

Beta cells control glucose homeostasis via regulated production and secretion of insulin. This function arises from a highly specialised gene expression programme that is established during development and then sustained, with limited flexibility, in terminally differentiated cells. Dysregulation of this programme is seen in type 2 diabetes but mechanisms that preserve gene expression or underlie its dysregulation in mature cells are not well resolved. This study investigated whether methylation of histone H3 lysine 4 (H3K4), a marker of gene promoters with unresolved functional importance, is necessary for the maintenance of mature beta cell function.

Methods

Beta cell function, gene expression and chromatin modifications were analysed in conditional Dpy30 knockout mice, in which H3K4 methyltransferase activity is impaired, and in a mouse model of diabetes.

Results

H3K4 methylation maintains expression of genes that are important for insulin biosynthesis and glucose responsiveness. Deficient methylation of H3K4 leads to a less active and more repressed epigenome profile that locally correlates with gene expression deficits but does not globally reduce gene expression. Instead, developmentally regulated genes and genes in weakly active or suppressed states particularly rely on H3K4 methylation. We further show that H3K4 trimethylation (H3K4me3) is reorganised in islets from the Leprdb/db mouse model of diabetes in favour of weakly active and disallowed genes at the expense of terminal beta cell markers with broad H3K4me3 peaks.

Conclusions/interpretation

Sustained methylation of H3K4 is critical for the maintenance of beta cell function. Redistribution of H3K4me3 is linked to gene expression changes that are implicated in diabetes pathology.

Graphical abstract
Arthroscopic cystectomy and valve excision of popliteal cysts complemented with management of intra-articular pathologies: a low recurrence rate and good functional outcomes in a series of ninety seven cases
Authors: Malinowski Konrad , Mostowy Marcin , Ebisz Michał , Pękala Przemyslaw A. , Kennedy Nicholas I. , LaPrade Robert F.
Published: March 2023

Purpose

Arthroscopy in popliteal cyst surgery enables addressing all components of its pathomechanism: the cyst wall, valvular mechanism, and concomitant intra-articular pathologies. Techniques differ as to the management of the cyst wall and the valvular mechanism. This study aimed to assess the recurrence rate and functional outcomes of a cyst wall and valve excising arthroscopic technique with concurrent intra-articular pathology management. The secondary purpose was to assess cyst and valve morphology and concomitant intra-articular findings.

Methods

Between 2006 and 2012, 118 patients with symptomatic popliteal cysts refractory to at least three months of guided physiotherapy were operated on by a single surgeon using a cyst wall and valve excising arthroscopic technique with intra-articular pathology management. Patients were evaluated preoperatively and at a mean follow-up of 39 months (range 12–71) by ultrasound, Rauschning and Lindgren, Lysholm, and VAS of perceived satisfaction scales.

Results

Ninety-seven out of 118 cases were available for follow-up. Recurrence was observed on ultrasound in 12/97 cases (12.4%); however, it was symptomatic only in 2/97 cases (2.1%). Mean scores improved: Rauschning and Lindgren from 2.2 to 0.4, Lysholm from 54 to 86, and VAS of perceived satisfaction from 5.0 to 9.0. No persistent complications occurred. Arthroscopy revealed simple cyst morphology in 72/97 (74.2%) and presence of a valvular mechanism in all cases. The most prevalent intra-articular pathologies were medial meniscus (48.5%) and chondral lesions (33.0%). There were significantly more recurrences in grade III–IV chondral lesions (p = 0.03).

Conclusions

Arthroscopic popliteal cyst treatment had a low recurrence rate and good functional outcomes. Severe chondral lesions increase the risk of cyst recurrence.
Predictive Factors for Adverse Event Outcomes After Transarterial Radioembolization with Yttrium-90 Resin Microspheres in Europe: Results from the Prospective Observational CIRT Study
Authors: Maleux Geert , Albrecht Thomas , Arnold Dirk , Bargellini Irene , Cianni Roberto , Helmberger Thomas , Kolligs Frank , Munneke Graham , Peynircioglu Bora , Sangro Bruno , Schaefer Niklaus , Pereira Helena , Zeka Bleranda , de Jong Niels , Bilbao José I. ,   the CIRT Principal Investigators, Albrecht Thomas , D’Archambeau Olivier , Balli Tugsan , Bilgic Sadik , Bloom Allan , Cioni Roberto , Fischbach Roman , Flamen Patrick , Gerard Laurent , Golfieri Rita , Grözinger Gerd , Katoh Marcus , Koehler Michael , Kröger Jan Robert , Kuhl Christiane , Orsi Franco , Özgün Murat , Reimer Peter , Ronot Maxime , Schmid Axel , Vit Alessandro , Maleux Geert , Sangro Bruno , Pech Maciej , Helmberger Thomas , Cianni Roberto , Pfammatter Thomas
Published: March 2023

Background

Using data collected in the prospective observational study CIRSE Registry for SIR-Spheres Therapy, the present study aimed at identifying predictors of adverse events (AEs) following transarterial radioembolization (TARE) with Yttrium-90 resin microspheres for liver tumours.

Methods

We analysed 1027 patients enrolled between January 2015 and December 2017 and followed up for 24 months. Four hundred and twenty-two patients with hepatocellular carcinoma (HCC), 120 with intrahepatic carcinoma (ICC), 237 with colorectal liver metastases and 248 with liver metastases from other primaries were included. Prognostic factors were calculated with a univariable analysis by using the overall AEs burden score (AEBS).

Results

All-cause AEs were reported in 401/1027 (39.1%) patients, with AEs associated with TARE, such as abdominal pain (16.6%), fatigue (17%), and nausea (11.7%) reported most frequently. Grade 3 or higher AEs were reported in 92/1027 (9%) patients. Reports on grade ≥ 3 gastrointestinal ulcerations (0.4%), gastritis (0.3%), radiation cholecystitis (0.2%) or radioembolization-induced liver disease (0.5%) were uncommon. Univariable analysis showed that in HCC, AEBS increased for Eastern Cooperative Oncology Group (ECOG) 0 (p = 0.0045), 1 tumour nodule (0.0081),  > 1 TARE treatment (p = 0.0224), no prophylactic embolization (p = 0.0211), partition model dosimetry (p = 0.0007) and unilobar treatment target (0.0032). For ICC,  > 1 TARE treatment was associated with an increase in AEBS (p = 0.0224), and for colorectal liver metastases, ECOG 0 (p = 0.0188), > 2 prior systemic treatments (p = 0.0127), and 1 tumour nodule (p = 0.0155) were associated with an increased AEBS.

Conclusion

Our study confirms that TARE is a safe treatment with low toxicity and a minimal impact on quality of life.
Safety and pharmacokinetics of GB1211, an oral galectin-3 inhibitor: a single- and multiple-dose first-in-human study in healthy participants
Authors: Aslanis Vassilios , Slack Robert J. , MacKinnon Alison C. , McClinton Catherine , Tantawi Susan , Gravelle Lise , Nilsson Ulf J. , Leffler Hakon , Brooks Ashley , Khindri Sanjeev K. , Marshall Richard P. , Pedersen Anders , Schambye Hans , Zetterberg Fredrik
Published: March 2023

Purpose

Galectin-3, a β-galactoside-binding lectin, plays a key role in several cellular pathways involved in chronic inflammation, heart disease and cancer. GB1211 is an orally bioavailable galectin-3 inhibitor, developed to be systemically active. We report safety and pharmacokinetics (PK) of GB1211 in healthy participants.

Methods

This phase 1, double-blind, placebo-controlled, first-in-human study (NCT03809052) included a single ascending-dose phase (with a food-effect cohort) where participants across seven sequential cohorts were randomized 3:1 to receive oral GB1211 (5, 20, 50, 100, 200 or 400 mg) or placebo. In the multiple ascending-dose phase, participants received 50 or 100 mg GB1211 or placebo twice daily for 10 days. All doses were administered in the fasted state except in the food-effect cohort where doses were given 30 min after a high-fat meal.

Results

All 78 participants received at least one GB1211 dose (n = 58) or placebo (n = 20) and completed the study. No safety concerns were identified. Following single and multiple oral doses under fasted conditions, maximum GB1211 plasma concentrations were reached at 1.75–4 h (median) post-dose; mean half-life was 11–16 h. There was a ~ twofold GB1211 accumulation in plasma with multiple dosing, with steady-state reached within 3 days; 30% of the administered dose was excreted in urine as unchanged drug. Absorption in the fed state was delayed by 2 h but systemic exposure was unaffected.

Conclusion

GB1211 was well tolerated, rapidly absorbed, and displayed favorable PK, indicating a potential to treat multiple disease types. These findings support further clinical development of GB1211.

Clinical trial registration

The study was registered with ClinicalTrials.gov (identifier: NCT03809052).