bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of NR3C2 as a functional diagnostic and prognostic biomarker and potential therapeutic target in non‐small cell lung cancer
Authors: Sun Yuan‐yuan , Gao Hai‐cheng , Guo Peng , Sun Na , Peng Chan , Cheng Zhi‐hua , Gu Jing , Liu Jin‐yi , Han Fei 
Published: May 2024

AbstractBackgroundNon‐small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor 5‐year survival rate. The identification of new powerful diagnostic biomarkers, prognostic biomarkers, and potential therapeutic targets in NSCLC is urgently required.MethodsThe UCSC Xena, UALCAN, and GEO databases were used to screen and analyze differentially expressed genes, regulatory modes, and genetic/epigenetic alterations in NSCLC. The UCSC Xena database, GEO database, tissue microarray, and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values. Gain‐of‐function assays were performed to examine the roles. The ESTIMATE, TIMER, Linked Omics, STRING, and DAVID algorithms were used to analyze potential molecular mechanisms.ResultsNR3C2 was identified as a potentially important molecule in NSCLC. NR3C2 is expressed at low levels in NSCLC, LUAD, and LUSC tissues, which is significantly related to the clinical indexes of these patients. Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC, LUAD, and especially LUSC patients. Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients. These results have been confirmed both with database analysis and real‐world clinical samples on a tissue microarray. Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD, while promoter DNA methylation is involved in its downregulation in LUSC. Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential. NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration. NR3C2 co‐expressed genes are involved in many cancer‐related signaling pathways, further supporting a potentially significant role of NR3C2 in NSCLC.ConclusionsNR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.
Comparing the clinical outcomes of initial surgery and primary definitive radiotherapy with a dosage of 6600 cGy or higher in cT1−2N0M0 oral cavity squamous cell carcinoma: A nationwide cohort study
Authors: Lin Chien‐Yu , Chen Wen‐Cheng , Wen Yu‐Wen , Fan Kang‐Hsing , Lin Jin‐Ching , Ng Shu‐Hang , Tsai Yao‐Te , Lee Shu‐Ru , Kang Chung‐Jan , Lee Li‐Yu , Chien Chih‐Yen , Hua Chun‐Hung , Wang Cheng Ping , Chen Tsung‐Ming , Terng Shyuang‐Der , Tsai Chi‐Ying , Wang Hung‐Ming , Hsieh Chia‐Hsun , Yeh Chih‐Hua , Lin Chih‐Hung , Tsao Chung‐Kan , Cheng Nai‐Ming , Fang Tuan‐Jen , Huang Shiang‐Fu , Lee Li‐Ang , Fang Ku‐Hao , Wang Yu‐Chien , Lin Wan‐Ni , Hsin Li‐Jen , Yen Tzu‐Chen , Liao Chun‐Ta 
Published: May 2024

AbstractBackgroundTo compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1−2N0M0 oral cavity squamous cell carcinoma (OCSCC).MethodsBetween 2011 and 2019, we analyzed data for 13,542 cT1−2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well‐balanced study groups (initial surgery, n = 580; definitive RT, n = 145).ResultsBefore PS matching, the 5‐year disease‐specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5‐year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5‐year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5‐year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001.ConclusionsIn Taiwanese patients with cT1−2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.
A large‐scale, multicenter characterization of BRAF G469V/A‐mutant non‐small cell lung cancer
Authors: Wu Han , Feng Jian , Lu Shun , Huang Jia 
Published: May 2024

AbstractBackgroundMutated BRAF is identified in 1%–5% non‐small cell lung cancer (NSCLC) patients, with non‐V600 mutations accounting for 50%–70% of these. The most common non‐V600 mutation is BRAF G469V/A. Currently, there are no targeted therapies available for non‐V600 mutated patients. A recent report provided interesting preclinical evidence revealing sensitivity of BRAF G469V to epidermal growth factor receptor (EGFR) inhibitors, raising the possibility of repurposing anti‐EGFR agents. It is therefore worthy to characterize the clinical and molecular features of BRAF G469V/A‐mutant NSCLC to provide more insights for precision therapy.MethodsWe conducted a retrospective screening of 25,694 Chinese patients with advanced or metastatic NSCLC to identify individuals with mutated BRAF. Additionally, we performed similar screenings on patients with adenocarcinoma (LUAD) from The Cancer Genome Atlas (TCGA) cohort (n = 567) and the MSKCC cohort (n = 1152). Subsequently, we characterized the clinical and molecular features of the patients carrying BRAF mutations.ResultsBRAF G469V was identified in 28 (0.1%) patients from the Chinese NSCLC cohort and 5 (0.9%) from TCGA‐LUAD. Notably, none was identified in the MSKCC cohort. G469A was found in 79 (0.3%) Chinese patients, 2 (0.4%) from TCGA‐LUAD, and 9 (0.8%) from the MSKCC cohort. Relative allele frequency analysis suggested most BRAF mutations as driven clones. Tumor mutation burden (median 4 mutations/Mb) was not significantly different between patients carrying G469V, G469A, V600E, or other BRAF mutations. Surprisingly, KRAS mutations were found in approximately 50% of patients with G469V mutation and about 8% of patients with G469A mutation, representing a prominent potential resistance mechanism against EGFR inhibitors. Structural modeling suggested BRAF G469V and G469A as binding partners of gefitinib.ConclusionOur large‐scale analysis characterized the prevalence and mutational landscape of BRAF G469V/A‐mutant NSCLC and proposed gefitinib as a potential option, providing a basis for further investigations on treating BRAF‐mutated NSCLC.
Exploring the Pharmacognostical and Phytochemical Profiles of Aqueous Extracts of Kalanchoe
Authors: Machinski Isadora , Andrade Evelyn Assis , Schaffka Vinicius Monteiro , de Almeida Valter Paes , Santos Aline , Bueno Debora , Perera Wilmer Hervet , Pereira Romaiana Picada , Manfron Jane , Miyoshi Edmar , Beltrame Flávio Luís 
Published: May 2024

AbstractThe use of plants for medicinal purposes has a long history, however it is desirable a continuous evaluation seeking for complementary scientific evidences for their safe application. Species within the Kalanchoe genus are often referred to as “miracle leaf” due to their remarkable healing properties. Traditionally, these plants have been used to treat infections, inflammation, and cancer. Despite their widespread use, the identification of their active components remains incomplete. This study aimed to differentiate K. crenata (KC), K. marmorata (KM), and K. pinnata (KP) by conducting detailed histochemical and phytochemical analyses, and to assess their antioxidant capabilities. The investigation revealed significant differences between the species, highlighting the variability in phenolic (PC) and flavonoid contents (FC) and their distinct antioxidant effects. The KM demonstrated the greatest results (PC: 59.26±1.53 mgEqGA/g; FC: 12.63±0.91 mgEqCQ/g; DPPH⋅ (IC50): 110.66 ug/mL; ABTS⋅+ (IC50): 26.81 ug/mL; ORAC: 9.65±0.75 mmolTE) when compared to KC and KP. These findings underscore a new reference for research within the Kalanchoe genus.
Comparison of thrombogenicity in different types of drug‐eluting stents during transition from DAPT to SAPT
Authors: Kawai Kenji , Sato Yu , Cornelissen Anne , Kolodgie Frank D. , Cheng Qi , Kawakami Rika , Konishi Takao , Perkins Laura E. L. , Virmani Renu , Finn Aloke V. 
Published: May 2024

AbstractBackgroundDuring the transition from dual antiplatelet therapy (DAPT) to single antiplatelet therapy (SAPT), previous studies have raised concerns about a rebound effect. We compared platelet and inflammatory cell adhesion on different types of stents in the setting of clopidogrel presence and withdrawal.MethodsIn Experiment 1, three pigs were administered with DAPT, that is, clopidogrel and acetylsalicylic acid (ASA), for 7 days. Each animal underwent an extracorporeal carotid arteriovenous shunt model implanted with fluoropolymer‐coated everolimus‐eluting stent (FP‐EES), biodegradable‐polymer sirolimus‐eluting stent (BP‐SES), and biodegradable‐polymer everolimus‐eluting stents (BP‐EES). In Experiment 2, two pigs were administered DAPT, clopidogrel was then withdrawn at day 7, and SAPT with ASA was continued for next 21 days. Then flow‐loop experiments with the drawn blood from each time point were performed for FP‐EES, BioLinx‐polymer zotarolimus‐eluting stents (BL‐ZES), and BP‐EES. The rebound effect was defined as the statistical increase of inflammation and platelet adhesion assessed with immunohistochemistry on the stent‐strut level basis from baseline to day‐14 or 28.ResultsBoth experiments showed platelet adhesion value was highest in BP‐EES, while the least in FP‐EES during DAPT therapy. There was no increase in platelet or inflammatory cell adhesion above baseline values (i.e., no therapy) due to the cessation of clopidogrel on the stent‐strut level. Monocyte adhesion was the least for FP‐EES with the same trend observed for neutrophil adhesion.ConclusionsNo evidence of rebound effect was seen after the transition from DAPT to SAPT. FP‐EES demonstrated the most favorable antithrombotic and anti‐inflammatory profile regardless of the different experimental designs.
Temporal trends with the Evolut family of self‐expanding transcatheter heart valves: A single‐center experience
Authors: Merdler Ilan , Case Brian C. , Bhogal Sukhdeep , Reddy Pavan K. , Zhang Cheng , Ali Syed , Gallino Paige E. , Jackman Caroline , Ben‐Dor Itsik , Satler Lowell F. , Cohen Jeffery E. , Rogers Toby , Waksman Ron 
Published: May 2024

AbstractBackgroundThe Evolut self‐expanding valve (SEV) systems (Medtronic), were designed to accommodate varying valve sizes and reduce paravalvular leak (PVL) while maintaining a low delivery profile. These systems have evolved between product generations, alongside valve deployment techniques changing over time.Aims:This study aimed to examine whether these changes impacted clinical outcomes.MethodsEPROMPT is a prospective, investigator‐initiated, postmarketing registry of consecutive patients undergoing transfemoral transcatheter aortic valve replacement (TAVR) using the Evolut PRO/PRO+ SEV system. A total of 300 patients were divided into three consecutive cohorts of 100 patients according to implantation date (January to October 2018, November 2018 to July 2020, and August 2020 to November 2021). Procedural and clinical outcomes over these time periods were compared.ResultsValve Academic Research Consortium (VARC)−2 device implantation success improved over time (70.0% vs. 78.0% vs. 88.8%, p = 0.01), with a similar trend for VARC‐3 device success (94.7% vs. 81.7% vs. 96.8%, p < 0.001). PVL (all degrees) frequency was likewise reduced over time (31.0% vs. 17.0% vs. 19.2%, p = 0.04). Furthermore, a trend was noticed toward shorter procedure times and shorter length of stay. However, postprocedural pacemaker implantation rates did not significantly differ (15.2% vs. 21.1% vs. 14.0%, p = 0.43).ConclusionDuring a 3‐year period, we demonstrated better TAVR outcomes with newer SEV iterations, alongside changes in implantation techniques, which might result in better procedural and clinical outcomes. However, we did not see a significant change in peri‐procedural pacemaker rates for SEV.
Shedding Light on Electrocatalysts: Practical Considerations for Operando Studies with High‐Energy X‐Rays
Authors: Pittkowski Rebecca K. 
Published: May 2024

AbstractOperando studies using high‐energy X‐rays from synchrotron sources are essential for unraveling the complex material transformation that electrocatalysts undergo under operating conditions. This article explores key considerations to perform these experiments and the insights gained from such studies on nanostructured electrocatalysts. Critical factors include optimizing electrochemical performance while obtaining high‐quality X‐ray signals, which often require compromises. The electrochemical operando cell design is crucial, and several different cells are discussed here. Working electrode geometries parallel to the X‐ray beam, probed with a microfocused beam, are emerging as promising solutions for realistic electrochemical performance in operando cells. Careful attention must also be paid to the electrochemical measuring conditions, electrode loading, and beam damage to ensure reliable experiments. When carefully performed and by combining multiple characterization techniques, operando studies with high‐energy X‐rays offer the unique possibility to fully understand the structure of the active electrocatalyst.
Recent Advances in Electrochemical Cell Design for Concurrent Chemical Production and Electricity Generation
Authors: Zhao Mengting , Zeng Ye , Zhang Xiaoyi , Liang Hanfeng 
Published: May 2024

AbstractElectricity generation and chemical production are both critical cornerstone for modern society. Integrating electricity output and high value chemical production in an electrochemical system is highly attractive both environmentally and sustainably. In this review, we summarize the recent advances in the development of these multifunctional devices (electrocatalytic flow batteries) that could generate both electricity and high value chemicals through rational coupling of half‐electrode reactions, covering the basic principles, device configurations, and applications. We also discuss the current challenges and suggest potential research directions.
Detection storage time of mangoes after mild bruise based on hyperspectral imaging combined with deep learning
Authors: Yao Chi , Su Cheng‐tao , Zou Ji‐ping , Ou‐yang Shang‐tao , Wu Jian , Chen Nan , de Liu Yan , Li Bin 
Published: May 2024

AbstractTo reduce the number of bruised mangoes at source, it is important to determine the different storage times of mangoes after mild bruise. In order to address this issue, a hyperspectral imaging combined with deep learning model was proposed. First, the average spectrum of the sample bruised area was extracted as spectral features, and then, the six eigenvalues of the most representative PC1 image were calculated as texture features based on the gray level co‐occurrence matrix. In order to find the optimal discriminative model, random forest (RF), partial least squares discriminant analysis (PLS‐DA), extreme gradient boosting (XGBoost), and convolutional neural network (CNN) models were built based on spectral features, texture features, and spectral features combined with texture features (Feature Fusion 1), respectively. The results showed that the best model discriminating model was based on CNN under Feature Fusion 1, with an overall accuracy of 90.22%. To reduce the redundant information and noise introduced by the full spectrum, uninformative variable elimination (UVE) and competitive adaptive reweighted sampling (CARS) algorithms were used to filter the spectral features. The screened spectral features were fused with texture features (Feature Fusion 2) and modeled again with RF, PLS‐DA, XGBoost, and CNN. The results showed that the optimal model for discriminating different storage times of mangoes after bruise was the CNN model based on feature fusion 2 (CARS), with an overall accuracy of 93.48%. In summary, this study shows that the spectral features combined with texture features can be used to effectively improve the model's discriminative results for different storage times of mango after mild bruise. Compared to other machine learning models, the CNN model in this paper achieves better results. It provides a theoretical basis for hyperspectral imaging combined with deep learning in discriminating different storage times of mangoes after mild bruise.
A β‐Glucosyl Sterol Probe for in situ Fluorescent Labelling in Neuronal Cells to Investigate Neurodegenerative Diseases
Authors: Borsato Giuseppe , Carnio Francesco , Lunardon Sara , Moletta Mattia , Pavan Giulio , Terrin Francesca , Scarso Alessandro , Plotegher Nicoletta , Fabris Fabrizio 
Published: May 2024

AbstractA β‐glucosyl sterol probe bearing a terminal alkyne moiety for fluorescent tagging enables the investigation of the neuronal and intracellular localization of this class of compounds involved in neurodegenerative diseases. The compound showed localization in the neuronal cells, with marked differences in the uptake and metabolism leading to enhanced persistence with respect to the un‐glycosylated sterol analogue. In addition, a different impact was observed towards lysosomes, with the simple sterol probe showing the enlargement of the lysosome structures, while the β‐glucosyl sterol was less capable to alter the morphology of this specific organelle.
High‐Pressure Synthesis and Recovery of Single Crystals of the Metastable Manganese Carbide, MnCx
Authors: Marshall Paul V. , Thiel Scott D. , Cote Elizabeth E. , Arigbede John , Whitaker Matthew L. , Walsh James P. S. 
Published: May 2024

AbstractTransition metal carbides find widespread use throughout industry due to their high strength and resilience under extreme conditions. However, they remain largely limited to compounds formed from the early d‐block elements, since the mid‐to‐late transition metals do not form thermodynamically stable carbides. We report here the high‐pressure bulk synthesis of large single crystals of a novel metastable manganese carbide compound, MnCx (P63/mmc), which adopts the anti‐NiAs‐type structure with significant substoichiometry at the carbon sites. We demonstrate how synthesis pressure modulates the carbon loading, with ~40 % occupancy being achieved at 9.9 GPa.
Collective Total Synthesis of Ecklonialactones, Eiseniachlorides and Analogs
Authors: Guy Alexandre , Delly Shanice , Galano Jean‐Marie , Durand Thierry , Oger Camille 
Published: May 2024

AbstractEcklonialactones, Eiseniachlorides, and Egregiachlorides are synthesized in living organisms via the lipoxygenase‐mediated oxidation of polyunsaturated fatty acids. Originally isolated and identified from brown seaweed (Ecklonia stolonifera, Eisenia bicyclis, and Egregia menziesii), and later replicated on milligram scale through chemical synthesis, the full biological activities of these compounds remain to be elucidated. To bridge this gap in knowledge, we propose a unified methodology to synthesize the 14‐membered macrocyclic structures of Ecklonialactones, Eiseniachlorides and analogs using a versatile and convergent approach. This study delineates the synthesis of Ecklonialactone A, B, C, D, and Eiseniachlorides A and B, as well as ent‐Ecklonialactone B, 16‐epi‐Ecklonialactone B and 12,13‐diepi‐Ecklonialactone B.
C‐Terminal Decarboxylation of Proline‐Derived Building Blocks for Protein‐Binding Peptides
Authors: Engelhardt Pascal M. , Strippel Julian , Albat Dominik , Chiha Slim , Rojas Pión Juliana , Plein Laura , Kühne Ronald , Müller Matthias , Schmalz Hans‐Günther 
Published: May 2024

AbstractUsing a set of conformationally restricted Proline‐derived Modules (ProMs), our group has recently succeeded in developing inhibitors for the enabled/vasodilator‐stimulated phosphoprotein homology 1 (EVH1) domain, which is a key mediator of cell migration and plays an important role in tumor metastasis. While these (formally) pentapeptidic compounds show nanomolecular binding affinities towards EVH1, their drug‐like properties and cell permeability need to be further optimized before they can be clinically tested as therapeutic agents against metastasis. In this study, we sought to improve these properties by removing the C‐terminal carboxylic acid function of our peptoids, either by late‐stage decarboxylation or by direct synthesis. For late‐stage decarboxylation of ProM‐like systems, a method for reductive halo decarboxylation was optimized and applied to several proline‐derived substrates. In this way, a series of new decarboxy ProMs suitable as building blocks for decarboxy EVH1 inhibitors were obtained. In addition, we incorporated decarboxy‐ProM‐1 into the pentapeptide‐like compound Ac[2ClF][ProM‐2][Decarb‐ProM‐1], which showed similar affinity towards EVH1 as the methyl ester derivative (Ac[2Cl‐F][ProM‐2][ProM1]OMe). However, despite better calculated drug‐like properties, this compound did not inhibit chemotaxis in a cellular assay.
Internet‐Based Cognitive Behavioural Treatments for Obsessive–Compulsive Disorder: A Systematic Review and Meta‐Analysis
Authors: Polak Martin , Tanzer Norbert K. 
Published: May 2024

ABSTRACTObsessive–compulsive disorder (OCD) is a common mental health condition characterized by distressing, intrusive thoughts (obsessions) and repetitive behaviours (compulsions) aimed at reducing anxiety. Internet‐based cognitive behavioural therapy (ICBT) has emerged as an effective treatment modality for various mental health disorders. This meta‐analysis evaluates the efficacy of guided self‐help ICBT (GSH ICBT) and unguided self‐help ICBT (SH ICBT) against active and passive control conditions in adults with OCD. A comprehensive systematic literature search yielded 12 randomized controlled trials (RCTs) comprising 15 comparison arms (N = 1416) that met the inclusion criteria. Results indicate that GSH ICBT significantly reduced OCD symptomatology posttreatment compared to active controls (g = 0.378, k = 9), with no significant effects maintained at follow‐up (g = 0.153, k = 4). GSH ICBT was also found to be as effective as active CBT interventions in reducing comorbid anxiety and depression symptoms posttreatment (g = 0.278, k = 6) and at follow‐up (g = 0.124, k = 4). However, improvements in quality of life were not significant posttreatment (g = 0.115, k = 4) nor at follow‐up (g = 0.179, k = 3). Combined GSH and SH ICBT demonstrated large effects on reducing OCD symptoms (g = 0.754, k = 6), medium effects on comorbid symptoms (g = 0.547, k = 6) and small effects on quality of life (g = 0.227, k = 2) when compared to inactive controls. No significant differences were found between GSH and SH ICBT in all measured outcomes posttreatment (OCD: g = 0.098, k = 3; AD: g = 0.070, k = 3; QoL: g = −0.030, k = 1) and at follow‐up (OCD: g = 0.265, k = 2; AD: g = 0.084, k = 2; QoL: g = 0.00, k = 1). Sample size was identified as a significant moderator of treatment effects. This paper further explores clinical significance, treatment adherence, therapist time investment and moderator influences of the ICBT. The limitations of the study and recommendations for future research are thoroughly discussed.