bluuebunny/crossref_metadata_2025_split huggingface dataset:
EGFR and MUC1 as dual-TAA drug targets for lung cancer and colorectal cancer
Authors: Cui Huilin , Yu Qianqian , Xu Qumiao , Lin Chen , Zhang Long , Ye Wei , Yang Yifei , Tian Sijia , Zhou Yilu , Sun Runzhe , Meng Yongsheng , Yao Ningning , Wang Haizhen , Cao Feilin , Liu Meilin , Ma Jinfeng , Liao Cheng , Sun Ruifang 
Published: November 2024

BackgroundEpidermal growth factor receptor (EGFR) is a key protein in cellular signaling that is overexpressed in many human cancers, making it a compelling therapeutic target. On-target severe skin toxicity has limited its clinical application. Dual-targeting therapy represents a novel approach to overcome the challenges of EGFR-targeted therapies.MethodsA single-cell tumor-normal RNA transcriptomic meta-atlas of lung adenocarcinoma (LUAD) and normal lung tissues was constructed from published data. Tumor associated antigens (TAAs) were screened from the genes which were expressed on cell surface and could distinguish cancer cells from normal cells. Expression of MUC1 and EGFR in tumors and normal tissues was detected by immunohistochemistry (IHC), bulk transcriptomic and single-cell transcriptomic analyses. RNA cut-off values were calculated using paired analysis of RNA sequencing and IHC in patient-derived tumor xenograft samples. They were used to estimate the abundance of EGFR- and MUC-positive subjects in The Cancer Genome Atlas Program (TCGA) database. Survival analysis of EGFR and MUC1 expression was carried out using the transcription and clinical data from TCGA.ResultsA candidate TAA target, transmembrane glycoprotein mucin 1 (MUC1), showed strong expression in cancer cells and low expression in normal cells. Single-cell analysis suggested EGFR and MUC1 together had better tumor specificity than the combination of EGFR with other drug targets. IHC data confirmed that EGFR and MUC1 were highly expressed on LUAD and colorectal cancer (CRC) clinical samples but not on various normal tissues. Notably, co-expression of EGFR and MUC1 was observed in 98.4% (n=64) of patients with LUAD and in 91.6% (n=83) of patients with CRC. It was estimated that EGFR and MUC1 were expressed in 97.5% of LUAD samples in the TCGA dataset. Besides, high expression of EGFR and MUC1 was significantly associated with poor prognosis of LUAD and CRC patients.ConclusionsSingle-cell RNA, bulk RNA and IHC data demonstrated the high expression levels and co-expression patterns of EGFR and MUC1 in tumors but not normal tissues. Therefore, it is a promising TAA combination for therapeutic targeting which could enhance on-tumor efficacy while reducing off-tumor toxicity.
Unveiling the role of TGF-β signaling pathway in breast cancer prognosis and immunotherapy
Authors: Zheng Yifan , Li Li , Cai Wenqian , Li Lin , Zhang Rongxin , Huang Wenbin , Cao Yulun 
Published: November 2024

IntroductionThe TGF-β signaling pathway (TSP) is pivotal in tumor progression. Nonetheless, the connection between genes associated with the TSP and the clinical outcomes of breast cancer, as well as their impact on the tumor microenvironment and immunotherapeutic responses, remains elusive.MethodsBreast cancer transcriptomic and single-cell sequencing data were obtained from the The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. We identified 54 genes associated with the TSP from the Molecular Signatures Database (MSigDB) and analyzed both data types to evaluate TSP activity. Using weighted gene co-expression network analysis (WGCNA), we identified modules linked to TSP activity. To assess patient risk, we used 101 machine learning algorithms to develop an optimal TGF-β pathway-related prognostic signature (TSPRS). We then examined immune activity and response to immune checkpoint inhibitors and chemotherapy in these groups. Finally, we validated ZMAT3 expression levels clinically and confirmed its relevance in breast cancer using CCK-8 and migration assays.ResultsAt the single-cell level, TSP activity was most notable in endothelial cells, with higher activity in normal tissues compared to tumors. TSPRS was developed. This signature's accuracy was confirmed through internal and external validations. A nomogram incorporating the TSPRS was created to improve prediction accuracy. Further studies showed that breast cancer patients categorized as low-risk by the TSPRS had higher immune phenotype scores and more immune cell infiltration, leading to better prognosis and enhanced immunotherapy response. Additionally, a strong link was found between the TSPRS risk score and the effectiveness of anti-tumor agents. Silencing the ZMAT3 gene in the TSPRS significantly reduced the proliferation and invasiveness of breast cancer cells.DiscussionOur study developed a TSPRS, which emerges as a potent predictive instrument for the prognosis of breast cancer, offering novel perspectives on the immunotherapeutic approach to the disease.
Estrogenized HSA induced high-affinity autoantibodies in breast cancer - Novel biomarker for early detection
Authors: Sherwani Subuhi , Khan Mohd Wajid Ali , Khan Wahid Ali , Rajendrasozhan Saravanan , Al-Motair Khalid , Khan Hamda , Ahmad Saheem 
Published: November 2024

ObjectiveBreast cancer (BC) is the second most prevalent cancer worldwide. Estrogen has been increasingly recognized as a major contributor to the development of BC, playing a more critical role than previously understood. Estrogen derived nucleic acid and protein adducts have been shown to play significant roles in BC development and progression. However, the alterations in molecular mechanism(s) and immune pathways arising as a result of estrogenization still remain elusive.Patients and methods4-hydroxyestradiol (4-OHE2) was used for adduct formation with protein human serum albumin (HSA) (4-OHE2-HSA). The affinity of antibodies for 4-OHE2-HSA was evaluated in breast cancer patients. Immunoassays (direct binding ELISA, inhibition ELISA, and quantitative precipitin titration assay) were used to assess autoantibodies against estrogenized HSA in BC patients (n = 85) and healthy controls (n = 45).ResultsEstrogenization of HSA altered both its structure and function and compromised its interactions with various HSA-binding proteins. BC patients demonstrated high-affinity antibodies against 4-OHE2-HSA as compared to HSA (p &lt; 0.05). Additionally, cytokines Interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-α) were significantly elevated in BC patients as compared to the control group. Several factors, such as chemotherapy, estrogen receptors (ERs), and combination of surgery and chemotherapy, influenced the production of antibodies in cancer patients. The affinity constant for estrogenized HSA was 1.31 × 10-7 M, while for HSA and 4-OHE2, it was 1.68 × 10-6 M and 1.36 × 10-6 M, respectively.ConclusionsEstrogenized HSA is highly immunogenic, resulting in functional alterations. High affinity antibodies were detected in BC patients against 4-OHE2-HSA. Consequently, 4-OHE2-HSA may serve as a novel molecular target for potential cancer therapeutics. Furthermore, autoantibodies against 4-OHE2-HSA could serve as a potential biomarker for early detection of BC.
Lived experience of being a grandparent in one region of Spain: a qualitative study
Authors: García-Sanjuán Sofia , Gutiérrez-García Ana Isabel , Cabañero-Martínez María José , Fernández-Alcántara Manuel , Rocamora-Rodriguez Maria del Carmen , Escribano Silvia 
Published: November 2024

BackgroundThe evolution of the family model in Europe in the 21st century, and particularly in Spain, has led to grandparents playing a major role in caring for their grandchildren. Grandparents are required to take on certain functions and roles in order to provide this care. This results in changes to their daily lives, their family relationships and therefore their quality of life.ObjectiveTo explore grandparents’ lived experience of being involved in the upbringing and care of grandchildren and to determine how this affects their quality of life.MethodologyA descriptive qualitative design was used. The data collection strategy involved two focus groups in two health centres in the province of Alicante (Spain), which were attended by 19 grandparents. Thematic analysis was used to analyse the data.ResultsFour themes and their respective sub-themes emerged from the data analysis: (1) Not only caring, but also raising (implications for upbringing; dealing with their children’s rules; nutrition of grandchildren); (2) Motivation for providing care (it is what families do; financial support; barriers to caregiving that outweigh the reasons for caregiving); (3) Significance of gender (grandmothers bring up, grandfathers help out; cultural burden of caregiving for women) and (4) Implications of care (negative aspects of caregiving; positive aspects of caregiving).ConclusionThe study findings show that while grandparents recognise the value and benefits of providing regular childcare, there are important challenges that need to be addressed. It would therefore be advisable for health professionals to take into account the experience of grandparent caregivers and the process of caring for young children when developing inclusive policies for this population of caregivers.
Efficacy of extracting and preventively intervening late-stage older adults who are at high risk for spending high medical costs by using the health check-up system in Japan: a pilot study
Authors: Kazawa Kana , Kawai Madoka , Moriyama Michiko 
Published: November 2024

ObjectivesIn Japan, the seven diseases (femur fracture, cerebral infarction, chronic renal failure, heart failure, dementia, pneumonia, and chronic obstructive pulmonary disease) are the top causes of inpatient medical costs among the late-stage older adults aged 75 years and over. This pilot study was conducted with the following two objectives; (1) to examine the proportion of risks of onset and severity of seven diseases among the late-stage older adults, and (2) to examine the efficacy of interventions focusing on the prevention of unplanned hospitalization.MethodsParticipants were 45,233 older adults aged 75 and over living in Kure City, Japan. In addition to the government-mandated health checkup items, the Intervention group underwent additional risk screening tests included questionnaires, physical examinations, blood tests, and educational guidance by nurses. The efficacy of the intervention was examined whether there were differences in the number of hospitalizations, the use of emergency and critical care, and the incidence of hemodialysis induction between the Intervention and control groups (Usual Health Checkup group and No Health Checkup group) for the 2 years.ResultsThere were 485 participants in the Intervention group, 1,067 in the Usual Health Checkup group, and 43,712 in the No Health Checkup group. As the risks of seven diseases in the Intervention group, the largest proportion of deviations occurred for systolic blood pressure (63.3%), estimated salt intake (60.3%), and low-density lipoprotein cholesterol (51.5%). Estimated glomerular filtration rate deviated in 41.0%, N-terminal pro b-type natriuretic peptide in 37.9%. 7.5% scored &lt;2 points on the Mini-Cog©, and 9.1% performed the Timed Up and Go test in &gt;12 s. The incidence of hospitalization due to any of the seven diseases was significantly higher in the No Health Checkup group (p &lt; 0.001). There were no differences among the three groups in the use of emergency and critical care or the introduction of hemodialysis.ConclusionThis study revealed that additional health checkup tests and intervention methods could be prevented hospitalization among the adults of 75 years and older. It is necessary to make health checkups and follow-ups more accessible those are already available within the existing health system in Japan.
Does obesity create a relative sense of excess poverty?
Authors: Arbel Yuval , Arbel Yifat , Kerner Amichai , Kerner Miryam 
Published: November 2024

BackgroundThis study investigates the potential relationship between obesity and self-ranking of poverty, as a proxy for self-awareness and happiness. To the best of our knowledge, this issue has not been previously explored based on self-ranking of poverty when income is controlled.MethodOrdered Probit Regressions. We propose a new measure for the influence of western social values and norms associated with discrimination against obese women.ResultsBased on a follow-up survey after two years, findings demonstrate a drop in the projected probability of self-ranking as “not poor” with the BMI from 0.73 to 0.37 (females) – 0.48 (males) when the level of income is controlled. Similar outcomes are obtained when the independent variables are lagged and thus avoid endogeneity concerns. Finally, additional outcomes support the conclusion that the lagged BMI Granger-cause self-ranking of poverty for women, but not for men. Findings support the awareness of more obese women to lower prospects of finding a job.ConclusionSince according to twin studies, approximately 80% of obesity emanates from genetic factors, research findings stress the need to educate the public against prejudices on the grounds of obesity. In particular, our study seeks to evoke awareness among potential employers, which, in turn, might motivate avoidance of, or at least reduction in, an implicit wage penalty against obese women.
Multiple spacer sequence typing of Coxiella burnetii carried by ticks in Gansu, China
Authors: Xu Ze-Yun , Wang Fang-Ni , Jian Rui , Xue Jing , Guo Ya-Chun , Guo Wen-Ping 
Published: November 2024

BackgroundCoxiella burnetii is a zoonotic pathogen that causes Q fever and is found worldwide. Ticks serve as the primary reservoir, playing an important role in maintaining the natural cycle of C. burnetii. C. burnetii is transmitted to animals when ticks feed on their blood. However, information on C. burnetii infection in ticks remains limited, despite the widespread prevalence of the infection in humans and animals across China.MethodsIn this study, 192 engorged ticks were collected from Baiyin City of Gansu Province, China. The presence of Coxiella burnetii in ticks was specifically identified by detecting the IS1111 gene using nested polymerase chain reaction (nPCR). In addition, the 16S rRNA gene of C. burnetii was molecularly characterized using nPCR. A total of 10 spacer sequences (Cox 2, 5, 18, 20, 22, 37, 51, 56, 57, and 61) were amplified using PCR against positive specimens for MST analysis.ResultsAll collected ticks were identified as Hyalomma marginatum, and 90 of them tested positive for C. burnetii, with a positive rate of 46.9% (90/192). The 16S rRNA gene analysis showed that the novel C. burnetii variants detected in this study were closely related to other C. burnetii strains in the world. The allele codes found in the present study for loci Cox2-Cox5-Cox18-Cox20-Cox22-Cox37-Cox51-Cox56-Cox57-Cox61 were 8-4-9-5-7-5-2-3-11-6. This represents a novel combination of allele values, similar to MST28, currently designated as MST85 in the Multi Spacers Typing (MST) database.ConclusionOur results revealed the circulation of a novel MST genotype of C. burnetii in Baiyin City, Gansu Province, China. The detection of C. burnetii in ticks suggests a potential public health risk to the local human population.
Effectiveness of a Nutrition Counseling Intervention on Food Consumption, According to the Degree of Processing: A Community-Based Non-Randomized Trial of Quilombola Communities in South Brazil
Authors: Pacheco Pauline Müller , Bairros Fernanda de Souza , Neutzling Marilda Borges , Nunes Luciana Neves , Knauth Daniela Riva , dos Santos Francine Silva , Drehmer Michele 
Published: November 2024

ObjectivesTo evaluate the effectiveness of a nutrition counseling intervention on food consumption according to the Nova classification that reflects levels of food processing.MethodsControlled community trial was conducted in quilombola communities in the South of Brazil. Four communities were allocated to the control group (CG) and the intervention group (IG), two communities comprised each group. A total of 158 individuals (CG = 87; IG = 68) were included in the study. The intervention consisted of six theoretical and practical workshops on food and nutrition education, conducted over a 4-month period. We used a 24-hour recall at baseline and another post-intervention.ResultsThere was an increase in the consumption of traditional quilombola food as an effect of the intervention (from 14.5% to 20.7% in the IG, and from 12.7% to 16.0% in the CG, p = 0.05). There was no significant variation in the other Nova food groups according to time and intervention.ConclusionAn increase in traditional quilombola food indicates a resumption of traditional food intake and appreciation of local culture as an effect of this intervention at the community level.Clinical Trial Registration:www.clinicaltrials.gov, identifier NCT02489149.
Exogenous MnSO4 Improves Productivity of Degenerated Volvariella volvacea by Regulating Antioxidant Activity
Authors: Wang Qiaoli , Wang Wenpei , Wang Yonghui , Yun Jinmin , Zhang Yubin , Zhao Fengyun 
Published: November 2024

Manganese is one of the trace elements necessary for organisms to maintain normal biological activities and is also a cofactor for manganese superoxide dismutase (Mn-SOD) and manganese peroxidase (MnP). In order to find a simple and effective method to rejuvenate the degenerated V. volvacea strains, we explored the effect of the exogenous addition of MnSO4 on the antioxidant vigour and productivity of degenerated strains of V. volvacea. The results showed that the exogenous MnSO4 had no significant effect on the non-degenerated strain T0, but it could effectively increase the mycelial growth rate, mycelial biomass, and LBL decolouring ability of the degenerated strains T10 and T19, and reduce the production cycle and increased the biological efficiency of T10; it helped the severely degenerated T19 to regrow its fruiting body; and it also significantly increased the viability of the matrix-degrading enzymes such as EG, Lac, Xyl, etc. of T10 and T19. Meanwhile, exogenous MnSO4 significantly increased the activity of GPX, GR, CAT, SOD, and the content of GSH, polyphenols, minerals, and polysaccharides in T10 and T19 strains, which resulted in a significant decrease in the accumulation of ROS, such as O2− and H2O2 in T10 and T19. The correlation analysis showed that there was a significant correlation between antioxidant activity and the production ability of V. volvacea. This study can provide theoretical reference and technical support for the rejuvenation research of degenerated strains of V. volvacea and other edible fungi.
On the Geometry of Semi-Invariant Submanifolds in (α, p)-Golden Riemannian Manifolds
Authors: Hreţcanu Cristina Elena , Druţă-Romaniuc Simona-Luiza 
Published: November 2024

The main aim of this paper is to study some properties of submanifolds in a Riemannian manifold equipped with a new structure of golden type, called the (α, p)-golden structure, which generalizes the almost golden structure (for α=1) and the almost complex golden structure (for α=−1). We present some characterizations of isometrically immersed submanifolds in an (α, p)-golden Riemannian manifold, especially in the case of the semi-invariant submanifolds, and we find some conditions for the integrability of the distributions.
ОСОБЕННОСТИ ДВУМЕРНОЙ ПЕЧАТИ ЛЕКАРСТВЕННЫХ ФОРМ В ФАРМАЦЕВТИЧЕСКОЙ ТЕХНОЛОГИИ
Authors: К.В. Алексеев , Е.В. Блынская , С.В. Тишков , В.К. Алексеев , А.А. Иванов , С.В. Минаев , С.Э. Кондаков , Е.С. Ихалайнен 
Published: November 2024

В данном обзоре литературы рассмотрены основные технологические приемы, используемые в методе двумерной печати. Представлены разновидности технологий струйной и ротационной печати, особенности, преимущества и недостатки различных типов двумерной печати, например непрерывной струйной печати или печати по требованию. Показаны особенности производства и применения 2D-печатных лекарственных форм (оральнодиспергируемые, мукоадгезивные пленки и т.д.). Приведены примеры используемых подложек и технологии их производства с заданными характеристиками, а также требования и рецептуры используемых в печати растворов с фармацевтическими субстанциями. Изложены перспективы развития технологии 2D-печати и возможности ее применения, в частности в виде QR-кодированных лекарственных форм.
This review of the literature discusses the main technological methods used in the two-dimensional printing method. The varieties of inkjet and rotational printing technologies are presented, the features, advantages and disadvantages of various types of two-dimensional printing, for example, continuous inkjet printing or printing on demand. The features of the production and use of 2D-printed dosage forms (oral dispersible, mucoadhesive films, etc.) are shown. Examples of the substrates used and the technology of their production with given characteristics, as well as the requirements and formulations of the solutions used in printing with pharmaceutical substances are given. The prospects for the development of 2D-printing technology and the possibilities of its application, in particular in the form of QR-coded dosage forms, are set forth.
ОПРЕДЕЛЕНИЕ ЧИСТОТЫ НОВОЙ ФАРМАЦЕВТИЧЕСКОЙ СУБСТАНЦИИ 4,4’-(ПРОПАНДИАМИДО)ДИБЕНЗОАТ НАТРИЯ ХРОМАТОГРАФИЧЕСКИМИ МЕТОДАМИ
Authors: Ю.Э. Генералова , В.Ф. Апраксин , Г.М. Алексеева 
Published: November 2024

Разработаны и валидированы методики определения родственных примесей и остаточных органических растворителей для определения чистоты ранее незарегистрированной фармацевтической субстанции 4,4’-(пропандиамидо)дибензоат натрия с использованием методов высокоэффективной жидкостной хроматографии и газовой хроматографии.
For determination purity of novel active pharmaceutical ingredient in the research, procedures were developed, validated and tested for the determination of related impurities (4-aminobenzoic acid, 4-((3-oxo-3-ethoxypropanoil)amino)benzoic acid, 4-(carboxyacetyl)amino)benzoic acid and malonic ester) and residual organic solvents (o-xylene) in the new pharmaceutical substance 4,4'-(propanediamido)dibenzoate sodium using high performance liquid chromatography and gas chromatography.
ОПРЕДЕЛЕНИЕ СОДЕРЖАНИЕ ИЗОФЛАВОНОВ В СУХОМ ЭКСТРАКТЕ ТРАВЫ КЛЕВЕРА ЛУГОВОГО МЕТОДОМ ВЭЖХ
Authors: Т.Ш. Нгуен , Г.М. Алексеева , Ю.Э. Генералова , И.Е. Каухова , В.В. Сорокин 
Published: November 2024

Клевер луговой, также известный как красный клевер (Trifolium pratense L.), является природным источником фитоэстрогенных изофлавоноидов. Цель исследования-изучение качественного и количественного определения индивидуальных изофлавонов в сухом экстракте травы клевера луговогометодом ВЭЖХс целью расширения спектра лекарственных препаратов на основе данной фитосубстанции.В сухом экстракте травыклевера луговогобыли идентифицированы дайдзеин, генистеин, формононетин, прунетин и биоханинA, определено их содержание 0,360,01, 0,840,01, 3,020,05, 0,220,01 и 1,620,03 соответственно.Установленное значительное содержание в сухом экстрактеформононетинаибиоханинаAпозволяет рассматривать сухой экстракт клевера лугового как перспективную субстанцию для разработки лекарственных препаратов.
Clover meadow, also known as red clover (Trifolium pratense L.), is a natural source of phytoestrogenic isoflavonoids. The purpose of the study-to study the qualitative and quantitative content of individual isoflavones in the dried extract of red clover grass by HPLC in order to expand the range of medicines based on this phytosubstance. In the dried extract of red clover grass, daidzein, genistein, formononetin, prunetin and biochanin A were identified, their content was determined 0.360.01, 0.840.01, 3.020.05, 0.220.01 and 1.620.03 respectively. The established significant content in the dried extract of formononetin and biochanin A allows us to consider the dried extract of red clover grass as a promising substance for the development of medicines.