bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractRadiation 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

AbstractThe 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.
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

ScopeThis 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 resultsInsulin‐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.ConclusionCapsaicin 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

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

AbstractSilicon 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

AbstractThe 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

AbstractThe 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.
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

AbstractImmune 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

AbstractThe 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

AbstractThe 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

Abstract
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

Abstract

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

Abstract
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

Abstract
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).