bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disrupted single-subject gray matter networks are associated with cognitive decline and cortical atrophy in Alzheimer’s disease
Authors: Xiao Yaqiong , Gao Lei , Hu Yubin ,   The Alzheimer’s Disease Neuroimaging Initiative
Published: May 2024

BackgroundResearch has shown disrupted structural network measures related to cognitive decline and future cortical atrophy during the progression of Alzheimer’s disease (AD). However, evidence regarding the individual variability of gray matter network measures and the associations with concurrent cognitive decline and cortical atrophy related to AD is still sparse.ObjectiveTo investigate whether alterations in single-subject gray matter networks are related to concurrent cognitive decline and cortical gray matter atrophy during AD progression.MethodsWe analyzed structural MRI data from 185 cognitively normal (CN), 150 mild cognitive impairment (MCI), and 153 AD participants, and calculated the global network metrics of gray matter networks for each participant. We examined the alterations of single-subject gray matter networks in patients with MCI and AD, and investigated the associations of network metrics with concurrent cognitive decline and cortical gray matter atrophy.ResultsThe small-world properties including gamma, lambda, and sigma had lower values in the MCI and AD groups than the CN group. AD patients had reduced degree, clustering coefficient, and path length than the CN and MCI groups. We observed significant associations of cognitive ability with degree in the CN group, with gamma and sigma in the MCI group, and with degree, connectivity density, clustering coefficient, and path length in the AD group. There were significant correlation patterns between sigma values and cortical gray matter volume in the CN, MCI, and AD groups.ConclusionThese findings suggest the individual variability of gray matter network metrics may be valuable to track concurrent cognitive decline and cortical atrophy during AD progression. This may contribute to a better understanding of cognitive decline and brain morphological alterations related to AD.
A nomogram for predicting pathologic node negativity after neoadjuvant chemotherapy in breast cancer patients: a nationwide, multicenter retrospective cohort study (CSBrS-012)
Authors: Maimaitiaili Amina , Li Yijun , Chai Na , Liu Zhenzhen , Ling Rui , Zhao Yi , Yang Hongjian , Liu Yunjiang , Liu Ke , Zhang Jianguo , Mao Dahua , Yu Zhigang , Liu Yinhua , Fu Peifen , Wang Jiandong , Jiang Hongchuan , Zhao Zuowei , Tian Xingsong , Cao Zhongwei , Wu Kejin , Song Ailin , Jin Feng , Wu Puzhao , He Jianjun , Fan Zhimin , Zhang Huimin 
Published: May 2024

PurposeThis study aimed to investigate the factors associated with pathologic node-negativity (ypN0) in patients who received neoadjuvant chemotherapy (NAC) to develop and validate an accurate prediction nomogram.MethodsThe CSBrS-012 study (2010–2020) included female patients with primary breast cancer treated with NAC followed by breast and axillary surgery in 20 hospitals across China. In the present study, 7,711 eligible patients were included, comprising 6,428 patients in the primary cohort from 15 hospitals and 1,283 patients in the external validation cohort from five hospitals. The hospitals were randomly assigned. The primary cohort was randomized at a 3:1 ratio and divided into a training set and an internal validation set. Univariate and multivariate logistic regression analyses were performed on the training set, after which a nomogram was constructed and validated both internally and externally.ResultsIn total, 3,560 patients (46.2%) achieved ypN0, and 1,558 patients (20.3%) achieved pathologic complete response in the breast (bpCR). A nomogram was constructed based on the clinical nodal stage before NAC (cN), ER, PR, HER2, Ki67, NAC treatment cycle, and bpCR, which were independently associated with ypN0. The area under the receiver operating characteristic curve (AUC) for the training set was 0.80. The internal and external validation demonstrated good discrimination, with AUCs of 0.79 and 0.76, respectively.ConclusionWe present a real-world study based on nationwide large-sample data that can be used to effectively screen for ypN0 to provide better advice for the management of residual axillary disease in breast cancer patients undergoing NAC.
From immune equilibrium to tumor ecodynamics
Authors: Chen Xiaoping 
Published: May 2024

ObjectivesThere is no theory to quantitatively describe the complex tumor ecosystem. At the same time, cancer immunotherapy is considered a revolution in oncology, but the methods used to describe tumors and the criteria used to evaluate efficacy are not keeping pace. The purpose of this study is to establish a new theory for quantitatively describing the tumor ecosystem, innovating the methods of tumor characterization, and establishing new efficacy evaluation criteria for cancer immunotherapy.MethodsBased on the mathematization of immune equilibrium theory and the establishment of immunodynamics in a previous study, the method of reverse immunodynamics was used, namely, the immune braking force was regarded as the tumor ecological force and the immune force was regarded as the tumor ecological braking force, and the concept of momentum in physics was applied to the tumor ecosystem to establish a series of tumor ecodynamic equations. These equations were used to solve the fundamental and applied problems of the complex tumor ecosystem.ResultsA series of tumor ecodynamic equations were established. The tumor ecological momentum equations and their component factors could be used to distinguish disease progression, pseudoprogression, and hyperprogression in cancer immunotherapy. On this basis, the adjusted tumor momentum equations were established to achieve the equivalence of tumor activity (including immunosuppressive activity and metabolic activity) and tumor volume, which could be used to calculate individual disease remission rate and establish new efficacy evaluation criteria (ieRECIST) for immunotherapy of solid tumor based on tumor ecodynamics. At the same time, the concept of moving cube-to-force square ratio and its expression were proposed to calculate the area under the curve of tumor ecological braking force of blood required to achieve an individual disease remission rate when the adjusted tumor ecological momentum was known.ConclusionsA new theory termed tumor ecodynamics emphasizing both tumor activity and tumor volume is established to solve a series of basic and applied problems in the complex tumor ecosystem. It can be predicted that the future will be the era of cancer immune ecotherapy that targets the entire tumor ecosystem.
Mitigating jaw osteonecrosis: bioactive glass and pericardial membrane combination in a rat model
Authors: Pellicano Alexandre Antonio , Benites Bernar M. , Paschoa Amanda F. N. , Oliveira Laura C. , Campos Ana Carolina P. , Martins Daniel O. , Real Caroline C. , de Paula Faria Daniele , Fonseca Felipe P. , Martinez Raquel R. C. , Pagano Rosana L. , Fregnani Eduardo R. 
Published: May 2024

ObjectivesBisphosphonates (BFs) show clinical effectiveness in managing osteoporosis and bone metastases but pose risks of bisphosphonate-related jaw osteonecrosis (BRONJ). With no established gold standard for BRONJ treatment, our focus is on symptom severity reduction. We aimed to assess the preventive effects of bioactive glass and/or pericardial membrane in a preclinical BRONJ model, evaluating their potential to prevent osteonecrosis and bone loss post-tooth extractions in zoledronic acid (ZA)-treated animals.MethodsRats, receiving ZA or saline biweekly for four weeks, underwent 1st and 2nd lower left molar extractions. Pericardial membrane alone or with F18 bioglass was applied post-extractions. Microarchitecture analysis and bone loss assessment utilized computerized microtomography (CT) and positron emission tomography (PET) with 18F-FDG and 18F-NaF tracers. Histological analysis evaluated bone injury.ResultsExclusive alveolar bone loss occurred post-extraction in the continuous ZA group, inducing osteonecrosis, osteolysis, osteomyelitis, and abscess formation. Concurrent pericardial membrane with F18 bioglass application prevented these outcomes. Baseline PET/CT scans showed no discernible uptake differences, but post-extraction 18F-FDG tracer imaging revealed heightened glucose metabolism at the extraction site in the ZA-treated group with membrane, contrasting the control group.ConclusionThese findings suggest pericardial membrane with F18 bioglass effectively prevents BRONJ in the preclinical model.
Activated interferon response from DNA damage in multiple myeloma cells contributes to the chemotherapeutic effects of anthracyclines
Authors: Li Jin , Jia Zhuxia , Wang Rongxuan , Xiao Bitao , Cai Yanan , Zhu Tianshu , Wang Weiya , Zhang Xinyue , Fan Shu , Fan Xiaolong , Han Wenmin , Lu Xuzhang 
Published: May 2024

IntroductionMultiple myeloma (MM) is a malignant plasma cell disease caused by abnormal proliferation of clonal plasma cells in bone marrow. Upfront identification of tumor subgroups with specific biological markers has the potential to improve biologically-driven therapy. Previously, we established a molecular classification by stratifying multiple myeloma into two subtypes with a different prognosis based on a gene module co-expressed with MCL-1 (MCL1-M).MethodsGene Ontology (GO) analysis with differentially expressed genes was performed to identify signal pathway. Drug sensitivity was analyzed using the OncoPredict algorithm. Drug sensitivity of different myeloma cell lines was detected by CCK8 and flow cytometry. RNA-seq was performed on drug-sensitive cell lines before and after adriamycin treatment. RT-qPCR was used to further verify the sequencing results. The expression of γ-H2AX and dsDNA in sensitive and resistant cell lines was detected by immunofluorescence method.ResultsIn our study, we demonstrated that MCL1-M low MM were more sensitive to anthracyclines. We treated different myeloma cell lines with doxorubicin in vitro and discovered the association of drug sensitivity with IFN signaling. Herein, we demonstrate that the doxorubicin-sensitive myeloma cell line showed significant DNA damage and up-regulated expression of genes related to the IFN response, which was not observed in drug-insensitive cell lines.DiscussionOur results suggest that the active IFN signaling pathway may serve as a marker for predicting chemotherapy sensitivity in patients with myeloma. With our MCL1-M molecular classification system, we can screen patients with a potentially good response to the interferon signaling pathway and provide individualized treatment for MM. We propose IFN-a as adjuvant therapy for patients with myeloma sensitive to anthracyclines to further improve the therapeutic effect and prolong the survival of patients.
Outcomes and the effect of PGT-M in women with hormone-related hereditary tumor syndrome
Authors: Wang Dingran , Song Xueling , Zhu Xiaohui , Yan Liying , Zhi Xu , Yan Jie , Liang Huamao , Qiao Jie 
Published: May 2024

PurposeTo review the outcome of PGT-M in hormone-related hereditary tumor syndrome and evaluate the effect of ovarian induction on tumor growth in those patients.MethodsMedical records of PGT-M were retrospectively analyzed in patients with hormone-related heritage tumors in our reproductive center. A total of eleven women with hereditary breast and ovarian cancer (HBOC) (including BRCA1/2 mutation carriers), and Lynch syndrome (including MMR gene mutation carriers) were included. Thirteen IVF/PGT-M cycles were performed. Eleven for PGT-M and two for fertility preservation. The ovulation protocol, numbers of oocytes retrieved and two pronuclei (2PN) zygotes, PGT-M results, and clinical outcomes were analyzed. Tumor progression was also estimated by comparing transvaginal ultrasound (TVS), MR, CT, or colonoscopy according to the follow-up requirements of different tumors.ResultsEleven IVF/PGT-M cycles were performed with an antagonist protocol; Two cycles were performed with a mild stimulation protocol. The total dose of gonadotropin (Gn) was 1827 IU per patient (range from 1200 to 2625 IU). The median number of oocytes retrieved was 13 (range from 4 to 30), and the median number of 2PN zygotes was 8 (range from 2 to 16). A total of 32 embryos underwent PGT-M, and 9 (28.1%) embryos were suitable for transfer. Six transfer cycles were performed, and 5 cycles got clinical pregnancy (83%) with five newborns (83%). The follow-up examinations conducted 10-18 months after PGT-M/delivery revealed no new lesions or tumor progression.ConclusionPGT-M results can provide important information for improving the consultation of hormone-related heritage tumor patients regarding their fertility preservation and reproductive options. Ovarian induction for women with hormone-related hereditary tumor syndrome is not associated with tumor progression.
The intricate interplay between cancer stem cells and cell-of-origin of cancer: implications for therapeutic strategies
Authors: Bamodu Oluwaseun Adebayo , Chung Chen-Chih , Pisanic Thomas R. , Wu Alexander T. H. 
Published: May 2024

BackgroundCancer stem cells (CSCs) have emerged as pivotal players in tumorigenesis, disease progression, and resistance to therapies.ObjectiveThis comprehensive review delves into the intricate relationship between CSCs and the cell-of-origin in diverse cancer types.DesignComprehensive review of thematically-relevant literature.MethodsWe explore the underlying molecular mechanisms that drive the conversion of normal cells into CSCs and the impact of the cell-of-origin on CSC properties, tumor initiation, and therapeutic responses. Moreover, we discuss potential therapeutic interventions targeting CSCs based on their distinct cell-of-origin characteristics.ResultsAccruing evidence suggest that the cell-of-origin, the cell type from which the tumor originates, plays a crucial role in determining the properties of CSCs and their contribution to tumor heterogeneity.ConclusionBy providing critical insights into the complex interplay between CSCs and their cellular origins, this article aims to enhance our understanding of cancer biology and pave the way for more effective and personalized cancer treatments.
Vandetanib as a prospective anti-inflammatory and anti-contractile agent in asthma
Authors: Zeng Xiaoyue , Xue Lu , Li Wei , Zhao Ping , Chen Weiwei , Wang Wenyi , Shen Jinhua 
Published: May 2024

Background: Vandetanib is a small-molecule tyrosine kinase inhibitor. It exerts its therapeutic effects primarily in a range of lung cancers by inhibiting the vascular endothelial growth factor receptor 2. However, it remains unclear whether vandetanib has therapeutic benefits in other lung diseases, particularly asthma. The present study investigated the pioneering use of vandetanib in the treatment of asthma.Methods:In vivo experiments including establishment of an asthma model, measurement of airway resistance measurement and histological analysis were used primarily to confirm the anticontractile and anti-inflammatory effects of vandetanib, while in vitro experiments, including measurement of muscle tension and whole-cell patch-clamp recording, were used to explore the underlying molecular mechanism.Results:In vivo experiments in an asthmatic mouse model showed that vandetanib could significantly alleviate systemic inflammation and a range of airway pathological changes including hypersensitivity, hypersecretion and remodeling. Subsequent in vitro experiments showed that vandetanib was able to relax the precontracted rings of the mouse trachea via calcium mobilization which was regulated by specific ion channels including VDLCC, NSCC, NCX and K+ channels.Conclusions: Taken together, our study demonstrated that vandetanib has both anticontractile and anti-inflammatory properties in the treatment of asthma, which also suggests the feasibility of using vandetanib in the treatment of asthma by reducing abnormal airway contraction and systemic inflammation.
Are Turkish pharmaceutical pricing strategies an access barrier to oncology medicines for Türkiye?
Authors: Vural Elif Hilal , Kaskati Tolga , Vural İsmail Mert , Özalp Mustafa Asım , Gümüşel Bülent 
Published: May 2024

Objectives: Cancer diagnosis is increasing day by day all over the world. Deaths due to cancer are among the most common causes of death. Access to cancer drugs is a priority of health policies. The aim of this study is to evaluate access to cancer drugs through drug box sales data by modeling population growth, cancer incidence, and Fixed Euro Exchange (FEE) rate parameters used in drug pricing in Türkiye.Methods: Access to cancer drugs was evaluated by drug box sales figures obtained from IQVIA. Box sales data were classified according to diagnosis codes (ICD-10), reference, or generic status. Consumption of cancer drugs was examined over time with panel regression analysis, taking into account variables of population growth, cancer incidence, and the FEE rate in drug pricing in Türkiye.Results: The incidence of cancer in Türkiye was 215.1 in 2010 and 223.1 (per hundred thousand) in 2017. Whereas there was a 127.02% increase in the real euro exchange rate, there was an 89.6% increase in the FEE rate. With the regression approach, there is a negative relationship between the real and fixed exchange rate difference (RFED) and reference and generic drug consumption data. Medicine access is affected depending on diagnosis codes at different levels. Colorectal cancer medicine sales had negative correlations for each variable, namely, exchange rate, population growth, and cancer incidence. On the contrary, there was a positive correlation between non-small-cell lung cancer and relevant variables. Innovative medicine groups such as monoclonal antibodies and protein kinase inhibitor consumption showed a negative correlation.Conclusion: According to our results, pricing strategy may be an access barrier for oncology medicines in Türkiye. It should be reviewing the pricing policy that is beneficial for oncology medicine access in Türkiye.
Do biobanks need pharmacists? Support of pharmacy students to biobanking of human biological material for pharmaceutical research and development
Authors: Domaradzki Jan , Majchrowska Anita , Cielecka-Piontek Judyta , Walkowiak Dariusz 
Published: May 2024

Objectives:This study aimed to assess the biobank awareness among Polish pharmacy students and how it affects their support for biobank research.Methods:A survey among 366 pharmacy students enrolled at two Polish medical universities: the Poznań University of Medical Sciences and Medical University of Lublin was conducted.Results:Although most pharmacy students felt positivity about biobanking and expressed the willingness to donate their biospecimens for biomedical research, their awareness on research biobanks was low. Their willingness to participate was driven by the desire to benefit society, help advance science and develop new therapies. While students supported donation for most types of research, biobanks run by medical universities were the highest trusted research institutions. The primary factors associated with student’s willingness to participate were religiosity and place of study. Notably, nonreligious students and those studying in Poznan exhibited more favourable attitudes toward donating for research and expressed greater support for the establishment of research biobanks in Poland.Conclusion:Since biobank awareness among future pharmacists is inadequate incorporating biobank competency domains into education and training of pharmacists is required.
Occupational, academic, and personal determinants of wellbeing and psychological distress in residents: results of a survey in Lyon, France
Authors: Nohales Ludivine , Fort Emmanuel , Pelloux Sophie , Coste Clio , Leblanc Pierre , De Ternay Julia , Wallon Martine , Rolland Benjamin , Fassier Jean-Baptiste ,   BASIL Study Group,   SYREL MG SAIHL SIPHL DAM
Published: May 2024

IntroductionThe mental health of residents is a growing significant concern, particularly with respect to hospital and university training conditions. Our goal was to assess the professional, academic, and psychological determinants of the mental health status of all residents of the academy of Lyon, France.Materials and methodsThe Health Barometer of Lyon Subdivision Residents (BASIL) is an initiative which consists in proposing a recurrent online survey to all residents in medicine, pharmacy, and dentistry, belonging to the Lyon subdivision. The first of these surveys was conducted from May to July 2022. Participants should complete a series of validated questionnaires, including the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS), and the Kessler Psychological Distress Scale (K6), respectively, and ad-hoc questions assessing their global health and hospital and academic working conditions. A Directed Acyclic Graph (DAG) analysis was conducted prior to multivariable analyses, to explore the determinants associated with low wellbeing (WEMWBS &lt;43) and high psychological distress (K6 ≥ 13).ResultsA total of 904 residents (response rate: 46.7%) participated in the survey. A low level of wellbeing was observed in 23% of participants, and was significantly associated to job strain (OR = 2.18; 95%CI = [1.32–3.60]), low social support (OR = 3.13; 95%CI = [2.05–4.78]) and the experience of very poor university teaching (OR = 2.51; 95%CI = [1.29–4.91]). A high level of psychological distress was identified for 13% of participants, and associated with low social support (OR = 2.41; 95%CI = [1.48–3.93]) and the experience of very poor university teaching (OR = 2.89, 95%CI = [1.16–7.21]).ConclusionHospital working conditions, social support, and the perception of teaching quality, were three major determinants of wellbeing and psychological distress among health profession residents. Demographic determinants, personal life and lifestyle habits were also associated. This supports a multilevel action in prevention programs aiming to enhance wellbeing and reduce mental distress in this specific population and local organizational specificities.