bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fingolimod ameliorates chronic experimental autoimmune neuritis by modulating inflammatory cytokines and Akt/mTOR/NF‐κB signaling
Authors: Feng Yuan , Feng Fang , Pan Shuyi , Zhang Jiewen , Li Wei 
Published: March 2023

AbstractObjectiveChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune‐mediated disease that targets the myelin sheaths of the peripheral nerves. Fingolimod is a sphingosine 1 phosphate (S1P) receptor antagonist with a high affinity for S1P receptors through the Akt–mTOR pathway, and prior research has suggested that it might be helpful in autoimmune illnesses.MethodsChronic experimental autoimmune neuritis (c‐EAN) was induced by immunizing Lewis rats with the S‐palm P0(180–199) peptide, and then the treatment group was intraperitoneally injected with fingolimod (1 mg/kg) daily. Hematoxylin and eosin staining was used to assess the severity of nerve injury. Immunohistochemistry staining showed that fingolimod's anti‐inflammatory effects on c‐EAN rats might be realized through the NF‐κB signaling pathway. Tumor necrosis factor‐α (TNF‐α), interferon‐γ (INF‐γ), interleukin‐1beta (IL‐1β), interleukin 6 (IL‐6), inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule‐1 (ICAM‐1) were measured to evaluate the inflammation levels, and pAkt, p‐S6, and p‐p65 were used to measure the abundance of downstream activation markers to determine whether the Akt/mTOR/NF‐κB signaling pathway was activated in the c‐EAN model.ResultsFingolimod treatment reduced the inflammatory reaction and the expression of NF‐κB in sciatic nerves. It also decreased the mRNA levels of the proinflammatory cytokines TNF‐α, IFN‐γ, IL‐1β, IL‐6, iNOS, and ICAM‐1 and pAkt, p‐S6, and p‐p65, representing the Akt/mTOR/NF‐κB signaling pathway.ConclusionOur data showed that fingolimod could improve the disease course, alleviate the decrease in inflammation, and reduce proinflammatory cytokines through the Akt/mTOR/NF‐κB axis in c‐EAN rats, which could be beneficial for the development of CIDP‐related research.
Racial disparities in opioid prescription and pain management among breast cancer survivors
Authors: Kim Sunny Jung , Retnam Reuben P. , Sutton Arnethea L. , Edmonds Megan C. , Bandyopadhyay Dipankar , Sheppard Vanessa B. 
Published: March 2023

AbstractBackgroundWe examined whether there are racial disparities in pain management, opioid medicine prescriptions, symptom severity, and quality of life constructs in breast cancer survivors.MethodsWe conducted a secondary analysis of longitudinal data from the Women's Hormonal Therapy Initiation and Persistence (WHIP) study (n = 595), a longitudinal study of hormonal receptor‐positive breast cancer survivors. Upon study enrollment, patients completed a survey assessing an array of psychological, behavioral, and treatment outcomes, including adjuvant endocrine therapy (AET)‐induced symptoms, and provided a saliva biospecimen. Opioid prescription records were extracted from the health maintenance organizations (HMOs) pharmacy database. The final analytic sample included women with complete HMO pharmacy records for 1 year.ResultsThere were 251 eligible patients, of which 169 (67.3%) were White. The average age was 61.09 years old (SD = 11.07). One hundred seventy‐two patients (68.5%) had received at least one opioid medication and 37.1% were prescribed opioids longer than 90 days (n = 93). Sixty‐four Black patients (78%) had a record of being prescribed with opioids compared to 64% of White patients (n = 108, p = 0.03). Black patients reported worse vasomotor, neuropsychological, and gastrointestinal symptoms, as well as lower quality of life and greater healthcare discrimination than White patients (p's < 0.05). Black patients were more likely to be prescribed opioids for 90 days or longer compared to White patients, when controlling for age, marital status, income, body mass index (BMI), cancer stage, and chemotherapy status (adjusted Odds Ratio = 2.72, p = 0.014).ConclusionFindings indicate that there are racial differences in opioid prescriptions supplied for pain management and symptomatic outcomes. Future research is needed to understand the causes of disparities in cancer pain management and symptomatic outcomes.
Integrated gene profiling of fine‐needle aspiration sample improves lymph node metastasis risk stratification for thyroid cancer
Authors: Zhang Weituo , Yun Xinwei , Xu Tianyu , Wang Xiaoqing , Li Qiang , Zhang Tiantian , Xie Li , Wang Suna , Li Dapeng , Wei Xi , Yu Yang , Qian Biyun 
Published: March 2023

AbstractBackgroundLymph node metastasis risk stratification is crucial for the surgical decision‐making of thyroid cancer. This study investigated whether the integrated gene profiling (combining expression, SNV, fusion) of Fine‐Needle Aspiration (FNA) samples can improve the prediction of lymph node metastasis in patients with papillary thyroid cancer.MethodsIn this retrospective cohort study, patients with papillary thyroid cancer who went through thyroidectomy and central lymph node dissection were included. Multi‐omics data of FNA samples were assessed by an integrated array. To predict lymph node metastasis, we built models using gene expressions or mutations (SNV and fusion) only and an Integrated Risk Stratification (IRS) model combining genetic and clinical information. Blinded histopathology served as the reference standard. ROC curve and decision curve analysis was applied to evaluate the predictive models.ResultsOne hundred and thirty two patients with pathologically confirmed papillary thyroid cancer were included between 2016–2017. The IRS model demonstrated greater performance [AUC = 0.87 (0.80–0.94)] than either expression classifier [AUC = 0.67 (0.61–0.74)], mutation classifier [AUC = 0.61 (0.55–0.67)] or TIRADS score [AUC = 0.68 (0.62–0.74)] with statistical significance (p < 0.001), and the IRS model had similar predictive performance in large nodule [>1 cm, AUC = 0.88 (0.79–0.97)] and small nodule [≤1 cm, AUC = 0.84 (0.74–0.93)] subgroups. The genetic risk factor showed independent predictive value (OR = 10.3, 95% CI:1.1–105.3) of lymph node metastasis in addition to the preoperative clinical information, including TIRADS grade, age, and nodule size.ConclusionThe integrated gene profiling of FNA samples and the IRS model developed by the machine‐learning method significantly improve the risk stratification of thyroid cancer, thus helping make wise decisions and reducing unnecessary extensive surgeries.
SMARCA4 and SMARCE1 in gastric cancer: Correlation with ARID1A, and microsatellite stability, and SMARCE1/ERBB2 co‐amplification
Authors: Pries Katharina , Krüger Sandra , Heckl Steffen , Behrens Hans‐Michael , Röcken Christoph 
Published: March 2023

AbstractBackgroundRecent studies have shown an association between certain subunits of the SWI/SNF complex with specific tumor characteristics in gastric cancer (GC). In an earlier study, we applied multiregional whole exome sequencing on multiple primary tumor samples and found alterations of the SWI/SNF complex in 78% of the cases. ERBB2, which encodes for Her2/neu, is a well‐known predictive biomarker used to guide the treatment of GC in the palliative setting. SMARCE1, which encodes for a subunit of the SWI/SNF complex, is localized in close genetic proximity to ERBB2.AimAs little is known about the significance of the SWI/SNF complex in GC biology and the potential relationship between ERBB2 and SMARCE1 upregulation, we examined the expression patterns of SMARCA4 and SMARCE1, two mutually exclusive catalytic ATPase subunits of the SWI/SNF complex, in a well characterized GC cohort.Materials and MethodsThe expression of SMARCA4 and SMARCE1 was studied by immunohistochemistry in connection with clinicopathological patient characteristics in a cohort of 468 GCs. Digital droplet polymerase chain reaction was performed for amplification analysis on ERBB2 and SMARCE1.ResultsImmunohistochemical staining of whole‐mount tissue sections found a diffusely “gray scale” expression of SMARCA4 in 446 (95.2%) GCs and of SMARCE1 in 463 (98.8%) GCs. The expression of SMARCA4 and SMARCE1 correlated significantly with ARID1A, p53, and microsatellite status. No correlation was found with the patient prognosis. The amplification analysis of SMARCE1 showed amplification in 4 of 34 cases. In 3 of 34 cases, SMARCE1 was co‐amplified with ERBB2. We also found a co‐expression of SMARCE1 and Her2/neu in a subset of patients.ConclusionWhile the effect of a co‐amplification is currently unknown, synergistic effects of SMARCE1 and Her2/neu overexpression should be explored in future studies, holding potential for an improved treatment of GC.
Molecular genetic characteristics of thymic epithelial tumors with distinct histological subtypes
Authors: Yang Jun , Zhang Biao , Guan Wenyan , Fan Zhiwen , Pu Xiaohong , Zhao Linyue , Jiang Wen , Cai Weijing , Quan Xueping , Miao Shuying , Nie Ling , He Lu 
Published: March 2023

AbstractBackgroundDue to the low incidence and histological heterogeneity, the molecular features and underlying carcinogenic mechanisms of thymic epithelial tumors (TETs) are yet to be fully elucidated, especially for different subtypes of TETs.MethodsTumor tissue samples of 43 TETs with distinct histological subtypes were collected. We analyzed the molecular characteristics in different subtypes based on whole exome sequencing data.ResultsThe mutational profiles of the different subtypes of TETs varied. Compared with thymomas, thymic carcinomas (TCs) had a higher mutation frequency of MYO16 (33% vs. 3%, p = 0.024) and a lower frequency of ZNF729 mutations (0% vs. 35%, p = 0.044). No significant difference was observed in the median tumor mutation burden across different subtypes. The value of copy number variation burden, weighted genome instability index, and the number of amplified segments were all higher in TCs than thymomas, and they also tended to be higher in B3 thymoma than in non‐B3 thymomas, while they had no significant differences between B3 thymoma and TCs. Clustering analyses revealed that Wnt, MAPK, Hedgehog, AMPK, and cell junction assembly signaling pathways were exclusively enriched in non‐B3 thymomas, lysine degradation pathway in B3 thymoma, and extracellular matrix‐receptor (ECM‐receptor) interaction, positive regulation of cell cycle process, and activation of innate immune response pathways in TCs.ConclusionsThis study revealed distinct molecular landscapes of different subtypes of TETs, suggesting diverse pathogenesis of non‐B3 thymomas, B3 thymomas, and TCs. Our findings warrant further validation in future large‐scale studies and may provide a theoretical basis for potential personalized therapeutic strategies.
Immunophenotypic profiles and prognosis for colorectal mucinous adenocarcinomas are dependent on anatomic location
Authors: Patel Chirag , Behring Michael , Al Diffalha Sameer , Dhall Deepti , Lee Goo , Shanmugam Chandrakumar , Grizzle William E. , Manne Upender 
Published: March 2023

AbstractBackgroundThe prognostic value of mucinous adenocarcinomas (MCAs, exhibiting >50% extracellular mucin) of the colorectum, in relation to their anatomic location is not well studied.Materials and MethodsWe compared MCAs (n = 175) with non‐MCAs (NMCAs, n = 1015) and the cancer‐specific survival rates were evaluated, based on their anatomic site, by univariate Kaplan–Meier and multivariate Cox methods. Subsets of these tumors were immunostained for MUC1, MUC2, Bcl‐2, and p53.ResultsMCAs were more commonly found in the right colon, were of high‐grade, and were more prevalent in younger patients (<40 years). They exhibited strong expression of MUC2 and Bcl‐2 and showed less p53 nuclear staining. In contrast, most NMCAs were low‐grade with high expression of MUC1. MCAs of the rectum were associated with poorer outcomes relative to NMCAs (HR 1.85, CI 95% 1.15–2.97), even though the distributions of advanced‐stage tumors were similar.ConclusionLate‐stage disease and age were poor independent prognostic indicators of cancer‐specific deaths across all tumor locations. In summary, rectal MCAs have a poor prognosis.
Recent Advances in Metal Complexes for Antimicrobial Photodynamic Therapy
Authors: Rees Thomas W. , Ho Po‐Yu , Hess Jeannine 
Published: March 2023

AbstractAntimicrobial resistance (AMR) is a growing global problem with more than 1 million deaths due to AMR infection in 2019 alone. New and innovative therapeutics are required to overcome this challenge. Antimicrobial photodynamic therapy (aPDT) is a rapidly growing area of research poised to provide much needed help in the fight against AMR. aPDT works by administering a photosensitizer (PS) that is activated only when irradiated with light, allowing high spatiotemporal control and selectivity. The PS typically generates reactive oxygen species (ROS), which can damage a variety of key biological targets, potentially circumventing existing resistance mechanisms. Metal complexes are well known to display excellent optoelectronic properties, and recent focus has begun to shift towards their application in tackling microbial infections. Herein, we review the last five years of progress in the emerging field of small‐molecule metal complex PSs for aPDT.
Constraining and Modifying Peptides Using Pd‐Mediated Cysteine Allylation
Authors: Kriegesmann Julia , Schlatzer Thomas , Che Kateryna , Altdorf Claudia , Huhmann Susanne , Kählig Hanspeter , Kurzbach Dennis , Breinbauer Rolf , Becker Christian F. W. 
Published: March 2023

AbstractOver the past decades, several strategies for inducing and stabilizing secondary structure formation in peptides have been developed to increase their proteolytic stability and their binding affinity to specific interaction partners. Here, we report how our recently introduced chemoselective Pd‐catalyzed cysteine allylation reaction can be extended to stapling and how the resulting alkene‐containing staples themselves can be further modified to introduce additional probes into such stabilized peptides. The latter is demonstrated by introducing a fluorophore as well as a PEG moiety into different stapled peptides using bioorthogonal thiol‐ene and Diels‐Alder reactions. Furthermore, we investigated structural implications of our allyl staples when used to replace conformationally relevant disulfide bridges. To this end, we chose a selective binder of integrin α3β1 (LXY3), which is only active in its cyclic disulfide form. We replaced the disulfide bridge by different stapling reagents in order to increase stability and binding affinity towards integrin α3β1.
Cost‐benefit analyses of developmental crime prevention programmes
Authors: Koegl Christopher J. , Farrington David P. , Welsh Brandon C. 
Published: March 2023

AbstractBackgroundChildren and youth who are at risk of becoming early‐onset life‐course‐persistent offenders often slip through the cracks of other systems in society (e.g., health, education, child welfare, substance use and mental health). When they do, they impose an enormous economic burden on society. Developmental crime prevention (DCP) programmes seek to reduce these costs through evidence‐based interventions that target individual child and family risk and protective factors for antisocial behaviour.AimThis study reviewed cost‐benefit analysis studies of DCP interventions to identify whether they produced monetary benefits that exceeded programme costs.MethodWe searched the literature for studies of interventions that were evaluated using high‐quality research methods (i.e., experimental or quasi‐experimental designs). Key characteristics of these evaluations are summarised and benefit‐to‐cost ratios (BCRs) are reported.ResultsEleven cost‐benefit analysis (CBA) evaluations met study criteria. The programmes varied in terms of who they targeted (e.g., pregnant mothers, at‐risk youth), the age of participants (e.g., adults, children, older youth), the intervention duration (e.g., 10 weeks to 4 years), and the follow‐up interval (e.g., 6 months to 50 years). Ten of the 11 studies produced favourable BCRs, ranging between 1.35 and 31.77, depending on the type and scope of outcomes that were monetised.ConclusionThere is strong evidence in support of DCP from a cost‐benefit perspective. However, given the small number of studies for analysis, more prospective longitudinal CBA evaluations are needed, in addition to greater consistency in the scope and methods that are used to monetise outcomes.
A novel eco‐friendly methods for simultaneous determination of aspirin, clopidogrel, and atorvastatin or rosuvastatin in their fixed‐dose combination using chemometric techniques and artificial neural networks
Authors: AlSawy Norhan S. , ElKady Ehab F. , Mostafa Eman A. 
Published: March 2023

AbstractIn this study, the simultaneous determination of aspirin, clopidogrel, and either atorvastatin or rosuvastatin in their fixed‐dose combination (FDC) formulations has been reported. As a straightforward substitute for employing distinct models for each component, UV spectrophotometry was applied with chemometric approaches and artificial neural networks to achieve this. Three chemometric techniques, including principal component regression (PCR), partial least‐squares (PLS), and classical least‐squares (CLS), were applied in addition to the radial basis function‐artificial neural network (RBF‐ANN). The validation of a set of laboratory‐prepared combinations of aspirin, clopidogrel, and atorvastatin in one ternary mixture and aspirin, clopidogrel, and rosuvastatin in a second ternary mixture was assessed, and the results from the use of these approaches were recorded and compared. The absorbance data matrix matching the concentration data matrix in CLS, PCR, and PLS was created using measurements of absorbances in the range of 250–280 nm at intervals of 0.2 nm in their zero‐order spectra. Then, in order to forecast the unknown concentrations, calibration or regression was created utilizing the concentration and absorbance data matrices. Using RBF‐ANN for the simultaneous determination of aspirin, clopidogrel, and atorvastatin or rosuvastatin in their formulations was achieved by providing the input layer with 151 neurons; there are 2 hidden layers and 3 output neurons were obtained. The green profile of the developed methods has been assessed and compared with previously reported spectrophotometric methods. The suggested techniques were effectively applied to FDC dosage forms that contained the cited medications.
Diverse Roles of ScSERF in Modifying the Fibril Growth of Amyloidogenic Proteins
Authors: Wang Chaozhe , Liu Yicong , Yu Bin , Peng Yun , Zhang Xu , Jiang Guosheng , He Lichun , Liu Maili 
Published: March 2023

AbstractThe aggregation of amyloidogenic proteins is often related to the occurrence of neurodegenerative diseases, including fused in sarcoma protein (FUS) in frontotemporal lobar degeneration and amyotrophic lateral sclerosis diseases. Recently, the SERF protein family has been reported to have a significant regulatory effect on amyloid formation, but it is still unclear about the detailed mechanisms of SERF acting on different amyloidogenic proteins. Herein, nuclear magnetic resonance (NMR) spectroscopy and fluorescence spectroscopy were used to explore interactions of ScSERF with three amyloidogenic proteins FUS‐LC, FUS‐Core, and α‐Synuclein. NMR chemical shift perturbations reveal them sharing similar interaction sites on the N‐terminal region of ScSERF. However, the amyloid formation of α‐Synuclein protein is accelerated by ScSERF, while ScSERF inhibits fibrosis of FUS‐Core and FUS‐LC proteins. Both the primary nucleation and the total amount of fibrils produced are detained. Our results suggest a diverse role of ScSERF in regulating the fibril growth of amyloidogenic proteins.
Spin in Organic Cocrystals
Authors: Zhang Cheng , Wang Xin , Li Yang , Sun Yanqiu , Zhang Qichun 
Published: March 2023

AbstractOrganic spintronics has caused a huge revolution in creating highly efficient low‐power circuits. Spin manipulation in organic cocrystals has become a promising strategy to uncover more chemicophysical properties for diverse applications. In this Minireview, we summarize the recent advancements of spin properties in organic charge‐transfer cocrystals, and briefly describe the possible mechanisms behind them. Beside the known spin properties (spin multiplicity, mechanoresponsive spin, chiral orbit and spin‐crossover) in binary/ternary cocrystals, other spin phenomena in radical cocrystals and spin transport are also summarized and discussed. Hopefully, deep understanding of current achievements, challenges and perspectives will offer the clear direction for the introduction of spin in organic cocrystals.
Structural Complexity in the Apparently Simple Crystal Structure of Be2Ru
Authors: Agnarelli Laura , Prots Yurii , Ormeci Alim , Ramlau Reiner , Krnel Mitja , Svanidze Eteri , König Markus , Schmidt Marcus , Burkhardt Ulrich , Leithe‐Jasper Andreas , Grin Yuri 
Published: March 2023

AbstractThe structural features of the hexagonal layered crystal structure of Be2Ru (a=5.7508(3) Å,c=3.0044(2) Å, space groupP2m) were investigated by single crystal X‐ray diffraction and transmission electron microscopy (TEM). The residual electron density and high‐resolution TEM images show that the real structure can be described as an intergrowth of the main hexagonal matrix of the Fe2P type with minor orthorhombic inclusions of its stacking variants. Such atomic arrangement is stabilized by the charge transfer from Be to Ru and by a system of polar three‐ and four‐atomic bonds involving both components. The calculated electronic density of states (DOS) of Be2Ru revealed, contrarily to typical intermetallic compounds, a pseudo gap (dip) in the vicinity of the Fermi level. The temperature dependence of the electrical resistivity of Be2Ru shows metal behaviour in agreement with the non‐zero DOS at the Fermi level.
Electrolytes for Zn Batteries: Deep Eutectic Solvents in Polymer Gels
Authors: Gregorio Victor , Jankowski Piotr , Garcia Nuria , Garcia Lastra Juan Maria , Tiemblo Pilar , Chang Jin Hyun 
Published: March 2023

AbstractGel polymer electrolytes composed of deep eutectic solvent acetamide4:Zn(TFSI)2 and poly(ethylene oxide) (PEO) are prepared by using a fast, solvent‐free procedure. The effect of the PEO molecular weight and its concentration on the physicochemical and electrochemical properties of the electrolytes are studied. Gels prepared with ultrahigh molecular‐weight PEO present pseudo‐solid behavior and ionic conductivity even higher than that of the original liquid electrolyte. A decrease in the dendritic growth in soft gels with PEO contents up to 1 wt % is demonstrated. The changes in the chemical structure of the electrolyte produced by the strong interactions between ethylene oxide units and Zn2+ have also been studied. The addition of PEO takes the electrolyte out of its original eutectic composition, producing blend crystallization. However, it is possible to retain the eutectic point of the electrolyte in a gel form if the addition of PEO is accompanied by the reduction of acetamide.