bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined treatment of non‐small cell lung cancer using radiotherapy and immunotherapy: challenges and updates
Authors: Shang Shijie , Liu Jie , Verma Vivek , Wu Meng , Welsh James , Yu Jinming , Chen Dawei 
Published: October 2021

AbstractThe efficacy of immunotherapy for advanced non‐small cell lung cancer (NSCLC) remains unsatisfactory, as the majority of patients either do not experience an objective response or acquire secondary resistance. As a result, several methods to enhance the systemic efficacy of immunotherapy have been investigated, including a large area of active research by combining immunotherapy with radiation therapy (RT). Given the rapidly burgeoning concept of combining immunotherapy and RT for increasing therapeutic benefit, we review the progress in this field thus far and explore further avenues for enhancing this combination. This review commences with a discussion of the only two existing randomized trials (and a pooled analysis) showing that the addition of RT to immunotherapy improves the abscopal response rate, progression‐free survival, and overall survival in metastatic NSCLC patients. We then discussed factors and biomarkers that may be associated with a proportionally greater benefit to additional RT, such as low programmed cell death protein ligand 1 (PD‐L1) status, tumor mutational burden (TMB), and patient's immune function. Next, the implementation of RT to overcome immunotherapy resistance is discussed, including a mechanistic discussion and methods with which these mechanisms could be exploited. Lastly, the emerging role of low‐dose RT is discussed, which may help to overcome inhibitory signals in the tumor stroma that limit T‐cell infiltration. Taken together, given the current state of this rapidly expanding realm, these futuristic strategies may be reflected upon to further enhance the efficacy of immunotherapy for a wider group of patients.
Delay in the diagnosis and treatment of breast cancer in Vietnam
Authors: Nguyen Sang M. , Nguyen Quang T. , Nguyen Lan M. , Pham Anh T. , Luu Hung N. , Tran Huong T. T. , Tran Thuan V. , Shu Xiao‐Ou 
Published: October 2021

AbstractBackgroundDelays in diagnosis and treatment from first noticeable breast cancer symptoms are associated with poor outcomes. Understanding the reasons and barriers for patients’ delay in seeking medical care is critical to mitigating the problem.MethodsIn‐person surveys were conducted among 462 women, aged 18–79, with incident breast cancer cases, recruited from two cancer hospitals in North Vietnam. Delay, defined as the time interval between symptom recognition to the diagnosis and initiation of treatment equal to or exceeding 3 months, was categorized as follows: no delay (<3 months), moderate delay (3–8 months), and serious delay (≥9 months). Multivariable multinomial logistic regression was applied in data analyses.ResultsOver one‐quarter patients (31.5%) experienced moderate delays, and close to one‐fifth (17.5%) experienced serious delays. Adjusted odds ratios and 95% confidence intervals for moderate and serious delays were 5.60 (3.00–10.47) and 4.25 (2.05–8.85) for financial and physical barriers, respectively. Moderate delay was positively associated with psychological barriers (5.55 [1.75–17.57]) and lack of proper knowledge (3.15 [1.47–6.74]). The associations of barriers with delays in diagnosis and treatment appeared stronger among women living in rural areas. A lack of proper knowledge was significantly associated with delay among young women (<45 years old) and those with high incomes, while psychological barriers were significantly associated with delay among older women (≥45 years old).ConclusionDelays in diagnosis and treatment are common among Vietnamese breast cancer patients and are affected by several noted barriers. Proper policy needs to be developed to address this public health issue.
Interleukin‐33 as an early predictor of cetuximab treatment efficacy in patients with colorectal cancer
Authors: Zhang Xujun , Bi Kefan , Tu Xiaoxuan , Zhang Qiong , Cao Qingyi , Liang Yan , Zeng Ping , Wang Lin , Liu Tianxing , Fang Weijia , Diao Hongyan 
Published: October 2021

AbstractBackgroundCetuximab is used for colorectal cancer (CRC) treatment. However, the early biomarker of treatment efficacy of cetuximab has not been identified.MethodsAfter 1 year of cetuximab treatment, patients were divided into an effective group and an ineffective group. The interleukin‐33 (IL‐33) level and the distribution of lymphatic cells in patients were investigated by analyzing the peripheral blood mononuclear cells via flow cytometry analysis and ELISA. The correlation between IL‐33 immunomodulatory effect and cetuximab treatment efficacy was determined through experiments in vivo and in vitro.ResultsThe IL‐33 level in the peripheral blood was increased at 4 weeks after cetuximab administration of effective group, meanwhile, the osteopontin (OPN) was reduced. Whereas neither IL‐33 level nor OPN level of ineffective patients changed. In the effective group, the number of natural killer (NK) and CD8+ T cells were increased. Moreover, CD137 and CD107a expression on NK cells were higher in the effective group compared to the ineffective group. In vitro cetuximab treatment also increased the number of NK and CD8+ T cells as well as CD137 and CD107a expression upon IL‐33 stimulation. Moreover, the secretion of OPN was inhibited by IL‐33 administration in cetuximab‐treated PBMCs from the effective group patients. IL‐33 upregulated the cytotoxicity of NK cells and inhibited tumor cells growth in the effective cetuximab treatment mice.ConclusionEffective cetuximab treatment induced a change of IL‐33 and OPN at the early stage and triggered the NK cells antitumor activity. Consequently, significantly increased IL‐33 level and decreased OPN level in the peripheral blood at the early treatment are proposed as potential predictors of cetuximab treatment efficacy.
Identification of novel subtypes based on ssGSEA in immune‐related prognostic signature for tongue squamous cell carcinoma
Authors: Jin Yi , Wang Zhanwang , He Dong , Zhu Yuxing , Chen Xingyu , Cao Ke 
Published: October 2021

AbstractBackgroundTongue squamous cell carcinoma (TSCC) is characterized by aggressive invasion and poor prognosis. Currently, immune checkpoint inhibitors may prolong overall survival compared with conventional treatments. However, PD1/PDL1 remain inapplicable in predicting the prognosis of TSCC; thus, it is urgent to explore the genetic characteristics of TSCC.Materials and methodsWe utilized single‐sample gene set enrichment analysis (ssGSEA) to classify TSCC patients from the TCGA database into clusters with different immune cell infiltrations. ESTIMATE (immune‐related scores) and CIBERSORT (immune cell distribution) analyses were used to evaluate the immune landscape among clusters. GO, KEGG, and GSEA analyses were performed to analyze the different underlying molecular mechanisms in the clusters. Based on the immune characteristics, we applied the LASSO Cox regression to select hub genes and construct a prognostic risk model. Finally, we established an interactive network among these hub genes by using Cytoscape, and a pan‐cancer analysis to further verify and decipher the innate function of these genes.ResultsUsing ssGSEA, we constructed three functional clusters with different overall survival and immune‐cell infiltration. ESTIMATE and CIBERSORT analyses revealed the different distributions of immune cells (T cells, B cells, and macrophages) with diverse immune‐related scores (ESTIMATE, immune, stromal, and tumor purity scores). Moreover, pathways including those of the interferon‐gamma response, hypoxia, and glycolysis of the different subtypes were investigated to elucidate their involvement in mediating the heterogeneous immune characteristics. Subsequently, after LASSO Cox regression, a signature of 15 immune‐related genes was established that is more prognostically effective than the TNM stage. Furthermore, three hub genes—PGK1, GPI, and RPE—were selected using Cytoscape evaluation and verified by immunohistochemistry. PGK1, the foremost regulator, was a comprehensively profiled pan‐cancer, and a PGK1‐based interactive network was established.ConclusionOur results suggest that immune‐related genes and clusters in TSCC have the potential to guide individualized treatments.
Essential Oils from Piper caldense C. DC. and Piper xylosteoides (Kunth) Steud.: Seasonal Variation of the Chemical Composition and Antimicrobial Activity
Authors: Maduro Carlos Eduardo P. , de Camargo Rebeca G. , Hendges Ana Paula P. K. , Ferriani Aurea P. , da Silva Allan R. , Duarte Marta Cristina T. , do Amaral Wanderlei , Sales Maia Beatriz Helena L. N. 
Published: October 2021

AbstractThe essential oils (EOs) chemical composition can be affected by several environmental factors, impacting their desired biological activities. In this sense, this work aimed to evaluate the seasonal variation of the chemical composition and antimicrobial activity of Piper caldense and Piper xylosteoides leaves EOs. Their chemical composition was determined by GC/MS and GC‐FID analyses, resulting in the identification of eighty compounds. P. caldense EOs were mainly consisted of sesquiterpene hydrocarbons, whereas in P. xylosteoides EOs, monoterpene hydrocarbons were predominant. EOs from both species strongly inhibited B. subtilis (MIC=0.25 mg mL−1), while only P. caldense EOs showed strong activity against S. aureus (MIC=0.50 mg mL−1). P. caldense spring EO showed the broadest spectrum of antimicrobial action amongst all samples. For each species, PCA seasonally differentiated EOs chemical composition. In addition, as expected, PCA of all samples showed a distinction between the two species. This study has successfully demonstrated the importance of evaluating the seasonal variation of EOs chemical composition and antimicrobial activity in obtaining a product with the desired properties.
Relationship between Maturity Stage, Triterpenoid Content and Cytotoxicity of Sorbus intermedia (EHRH.) PERS. Fruits – A Chemometric Approach
Authors: Sołtys Agnieszka , Galanty Agnieszka , Zagrodzki Paweł , Podolak Irma 
Published: October 2021

AbstractIn this study, two ursane‐type triterpenes, i. e., ursolic acid (UA) and 3‐O‐β‐acetoxyursolic acid (AUA), were isolated and quantified in Sorbus intermedia (EHRH.) PERS. fruits. UA and AUA levels differed slightly throughout fruit maturation, and both triterpenes showed similar dynamics of accumulation with the highest levels found in ripe fruits (up to 6.33±0.56 and 1.17±0.18 mg/g dw. of UA and AUA, respectively). The extracts derived from unripe fruits displayed significant cytotoxic effects against WM793, DU‐145, PC3, 8505C, Caco2 and A549 cells, but no correlation between UA and AUA levels and cytotoxicity was found. On the other hand, extracts from mature fruits were not active towards almost all of the tested cell lines. The chemometric approach showed that the extracts derived from fruits harvested earlier clustered to form a clearly distanced group from extracts prepared from more‐mature fruits. The extracts at higher concentrations formed separate groups, which indicated the concentration‐dependent effect of these extracts on the cells.
Trypanocidal Activity of Dysphania ambrosioides, Lippia alba, and Tetradenia riparia Essential Oils against Trypanosoma cruzi
Authors: Pagotti Mariana C. , Candido Ana C. B. B. , Marçal Maria G. , Vieira Tatiana M. , Groppo Milton , Silva Márcio L. A. , Ferreira Daniele S. , Esperandim Viviane R. , Crotti Antônio E. M. , Magalhães Lizandra G. 
Published: October 2021

AbstractDespite the current treatments against Chagas Disease (CD), this vector‐borne parasitic disease remains a serious public health concern. In this study, we have explored the in vitro and/or in vivo trypanocidal and cytotoxic activities of the essential oils (EOs) obtained from Dysphania ambrosioides (L.) Mosyakin & Clemants (Amaranthaceae) (DA‐EO), Lippia alba (Mill.) N.E. Brown (Verbenaceae) (LA‐EO), and Tetradenia riparia (Hochst.) Codd (Lamiaceae) (TR‐EO) grown in Brazil Southeast. DA‐EO was the most active against the trypomastigote and amastigote forms in vitro; the IC50 values were 8.7 and 12.2 μg mL−1, respectively. The EOs displayed moderate toxicity against LLCMK2 cells, but the DA‐EO showed high selectivity index (SI) for trypomastigote (SI=33.2) and amastigote (SI=11.7) forms. Treatment with 20 mg/kg DA‐EO, LA‐EO, or TR‐EO for 20 days by intraperitoneal administration reduced parasitemia by 6.36 %, 4.74 %, and 32.68 % on day 7 and by 12.04 %, 27.96 %, and 65.5 % on day 9. These results indicated that DA‐EO, LA‐EO, and TR‐EO have promising trypanocidal potential in vitro, whereas TR‐EO has also potential trypanocidal effects in vivo.
SDH‐deficient renal cell carcinoma: A case report associated with a novel germline mutation
Authors: Milionis Vassilis , Goutas Dimitrios , Vlachodimitropoulos Dimitrios , Katsoulas Nikolaos , Kyriazis Iason D. , Liatsikos Evangelos N. , Marinakis Nikolaos , Joanne Traeger‐Synodinos , Lazaris Andreas C. , Goutas Nikolaos 
Published: October 2021

AbstractThe highly syndromic nature of succinate dehydrogenase‐deficient RCCs constitutes their active surveillance and molecular profiling the alpha and omega.
COVID‐19–infected woman along with tuberculosis and psychogenic non‐epileptic seizures: A case report
Authors: Nadershahbaz Mahshid , Bidaki Reza , Azimi Saeed , Saghafi Fatemeh 
Published: October 2021

AbstractDuring the COVID‐19 pandemic, we should not forget about chronic, underlying and important diseases, especially diseases that cause immune system deficiency, of which TB is one and may be missed. Also, we should pay attention to the past medical history of the patients and their drug‐drug interactions during the treatment period of COVID‐19. Our main clinical message is that diseases such as TB, which weaken the immune system, may predispose a person to COVID‐19 infection and COVID‐19 may exacerbate TB and it’s mortality. On the other hand, diseases that target the lung tissue such as TB and COVID‐19, may have synergistic effects and increase mortality (for a patient whose lung capacity is reduced due to TB, superimposed COVID‐19 can worsen the situation). In addition, it may be necessary to take more serious considerations for COVID‐19 in low socio‐economy countries, such as Afghanistan, where TB is more prevalent
Rare case report of deep vein thrombosis associated with brucellosis in Iran
Authors: Ghafouri Majid , Danafar Mojtaba , Shokri Azar 
Published: October 2021

AbstractBrucellosis caused by species of Brucella is among the most prevalent zoonotic diseases that can involve any organ. Here we present a case of deep vein thrombosis due to brucellosis. We described a 62 old male farmer with a history of brucellosis and deep vein thrombosis on his right leg.
Photocatalytic Activity of Supported Metal Nanoparticles and Single Atoms
Authors: Najafi Mahnaz , Abednatanzi Sara , Yousefi Abbas , Ghaedi Mehrorang 
Published: October 2021

AbstractPhotocatalysis has been known as one of the promising technologies due to its eco‐friendly nature. However, the potential application of many photocatalysts is limited owing to their large bandgaps and inefficient use of the solar spectrum. One strategy to overcome this problem is to combine the advantages of heteroatom‐containing supports with active metal centers to accurately adjust the structural parameters. Metal nanoparticles (MNPs) and single atom catalysts (SACs) are excellent candidates due to their distinctive coordination environment which enhances photocatalytic activity. Metal‐organic frameworks (MOFs), covalent organic frameworks (COFs) and carbon nitride (g‐C3N4) have shown great potential as catalyst support for SACs and MNPs. The numerous combinations of organic linkers with various heteroatoms and metal ions provide unique structural characteristics to achieve advanced materials. This review describes the recent advancement of the modified MOFs, COFs and g‐C3N4 with SACs and NPs for enhanced photocatalytic applications with emphasis on environmental remediation.
Methane Activation by (MoO3)5O−Cluster Anions: The Importance of Orbital Orientation
Authors: Ruan Man , Zhao Yan‐Xia , Zhang Mei‐Qi , He Sheng‐Gui 
Published: October 2021

AbstractThe reactivity of the molybdenum oxide cluster anion (MoO3)5O−, bearing an unpaired electron at a bridging oxygen atom (Ob.−), towards methane under thermal collision conditions has been studied by mass spectrometry and density functional theory calculations. This reaction follows the mechanism of hydrogen atom transfer (HAT) and is facilitated by the Ob.−radical center. The reactivity of (MoO3)5O−can be traced back to the appropriate orientation of the lowest unoccupied molecular orbitals (LUMO) that is essentially the 2p orbital of the Ob.−atom. This study not only makes up the blank of thermal methane activation by the Ob.−radical on negatively charged clusters but also yields new insights into methane activation by the atomic oxygen radical anions.
Determining the Exposure Threshold for Levonorgestrel Efficacy Using an Integrated Model Based Meta‐Analysis Approach
Authors: Lingineni Karthik , Chaturvedula Ayyappa , Cicali Brian , Cristofoletti Rodrigo , Wendl Thomas , Hoechel Joachim , Brown Joshua D. , Vozmediano Valvanera , Schmidt Stephan 
Published: October 2021

Combined oral contraceptive pills are the most commonly used hormonal contraceptives for the prevention of unintended pregnancies in United States. They consist of a progestin (e.g., levonorgestrel (LNG)) and an estrogen component, typically ethinyl estradiol (EE). In addition to adherence issues, drug‐drug interactions (DDIs) and obesity (women with body mass index (BMI) ≥ 30 kg/m2) are prime suspects for decreased LNG efficacy. Therefore, we developed an integrated physiologically‐based pharmacokinetic modeling and model‐based meta‐analysis approach to determine LNG’s efficacy threshold concentrations and to evaluate the impact of DDIs and obesity on the efficacy of LNG‐containing hormonal contraceptives (HCs). Based on this approach, co‐administration of strong CYP3A4 inducers and LNG‐containing HCs (LNG150: LNG 150 µg + EE 30 µg and LNG100: LNG 100 µg + EE 20 µg) resulted in a predicted clinically relevant decrease of LNG plasma exposure (women with BMI < 25 kg/m2: 50–65%; obese women: 70–75%). Following administration of LNG150 or LNG100 in the presence of a CYP3A4 inducer, there was an increase in mean Pearl Index of 1.2–1.30 and 1.80–2.10, respectively, in women with BMI < 25 kg/m2 (incidence rate ratios (IRRs): 1.7–2.2), whereas it ranged from 1.6–1.80 and 2.40–2.85 in obese women (IRR: 2.2–3.0), respectively. Our results suggest that the use of backup or alternate methods of contraception is not necessarily required for oral LNG + EE formulations except within circumstances of both obesity and strong CYP3A4 inducer concomitance following administration of LNG100.
Comparison of the effect of QMix and conventional root canal irrigants on push‐out bond strength of fiber post to root dentin
Authors: Afkhami Farzaneh , Sadegh Mona , Sooratgar Aidin , Amirmoezi Maryam 
Published: October 2021

AbstractObjectivesThis study aimed to assess the effect of application of QMix and common root canal irrigating solutions on the bond strength of fiber post to root dentin.Material and MethodsIn this in‐vitro study, 60 extracted incisor teeth were decoronated such that 15 mm of root length remained. The canals were prepared with ProTaper rotary system to F5 and filled with gutta‐percha and AH26 sealer. Prior to post placement, the teeth were divided into four groups based on the type of final irrigating solution namely saline, 5.25% NaOCl, 2% chlorhexidine, and QMix. The fiber posts were then cemented with Panavia F2 resin cement. The roots were sectioned perpendicular to their longitudinal axis, and four sections with 1 mm thickness were made at the middle and coronal thirds of the roots. The push‐out bond strength of fiber posts was measured by a universal testing machine in megapascals. Data were analyzed by two‐way ANOVA and Tukey's test.ResultsThe maximum and minimum bond strength values were noted in QMix and NaOCl groups in both the middle and coronal third of the root, respectively. But, there was no significant difference between the push‐out bond strength in the middle or coronal third of the root (p = 0.054). Adhesive failure was the most common mode of failure in all groups.ConclusionUse of QMix for post space irrigation does not compromise the bond strength of fiber post to root dentin, and can be used for final rinsing of the post space.
OMIP‐079: Cell cycle of CD4+ and CD8+ naïve/memory T cell subsets, and of Treg cells from mouse spleen
Authors: Natalini Ambra , Simonetti Sonia , Favaretto Gabriele , Peruzzi Giovanna , Antonangeli Fabrizio , Santoni Angela , Muñoz‐Ruiz Miguel , Hayday Adrian , Di Rosa Francesca 
Published: October 2021

AbstractA multicolor flow cytometry panel was designed and optimized to define the following nine mouse T cell subsets: Treg (CD3+ CD4+ CD8− FoxP3+), CD4+ T naïve (CD3+ CD4+ CD8−FoxP3− CD44int/low CD62L+), CD4+ T central memory (CD3+ CD4+ CD8− FoxP3− CD44high CD62L+), CD4+ T effector memory (CD3+ CD4+ CD8− FoxP3− CD44high CD62L−), CD4+ T EMRA (CD3+ CD4+ CD8− FoxP3− CD44int/low CD62L−), CD8+ T naïve (CD3+ CD8+ CD4− CD44int/low CD62L+), CD8+ T central memory (CD3+ CD8+ CD4− CD44high CD62L+), CD8+ T effector memory (CD3+ CD8+ CD4− CD44high CD62L−), and CD8+ T EMRA (CD3+ CD8+ CD4− CD44int/low CD62L−). In each T cell subset, a dual staining for Ki‐67 expression and DNA content was employed to distinguish the following cell cycle phases: G0 (Ki67−, with 2n DNA), G1 (Ki67+, with 2n DNA), and S‐G2/M (Ki67+, with 2n < DNA ≤ 4n). This panel was established for the analysis of mouse (C57BL/6J) spleen.