bluuebunny/crossref_metadata_2025 huggingface dataset:
Core Needle Biopsy Of Periacetabular Chondrosarcoma Often Results In Undergrading But Does Not Change Management By Experienced Orthopaedic Oncologists
Authors: Harvard Hayden , Badejo Megan A. , Levine Nicole , Cantor Nicole , Visgauss Julia , Brigman Brian , Eward William C.
Published: February 2024

Background
There is discrepancy in the histologic concordance of pre-operative biopsy and post-surgical
resection grading of periacetabular chondrosarcoma. This discrepancy poses a question as to whether the treatment may differ depending on the initial assessment of the tumor grade.
Methods
This is a retrospective review of patients with periacetabular cartilaginous tumors who were treated between the years 2000 and 2022 at a single institution. All patients included in the analysis underwent surgical resection. The pre-operative biopsy and post-surgical resection histological grades were compared. Concordance and treatment implications were evaluated.
Results
Of the 23 preoperative biopsies performed, there were 19 Image Guided Core Needle Biopsies (IGCNB), three Fine Needle Aspirations (FNA), and one open biopsy. There was concordance between pre-operative and surgical resection histological grade in only 10 cases using all methods of biopsy (IGCNB, FNA, and open biopsy), giving a (10/23) 43.5% accuracy rate. When considering biopsy techniques individually there was an accuracy rate of 7/19 (36.8%) for IGCNB, 2/3 (66.7%) for FNA, and 1/1 (100%) for open biopsy. In total there were 13 cases of discrepancy between pre-operative biopsy and surgical resection regarding histological grade. In 12 cases of discrepancy, surgical resection histology revealed a higher grade than that of pre-operative biopsy histology. In one case of discrepancy, pre-operative IGCNB biopsy histology revealed a high-grade chondrosarcoma while the surgical resection histology revealed an intermediate-grade. There were no situations in which the plan made based on a preoperative biopsy resulted in an inappropriate treatment decision, even when there was not concordance between preoperative diagnosis and diagnosis after definitive resection.
Conclusions
Significant discrepancy in grading was observed with pre-operative IGCNB and FNA of periacetabular cartilaginous lesions. However, while 12 out of the 13 discordant cases (92.3%) underestimated the true grade of the tumor, there was no impact on treatment decision making.
Radiation therapy increases long-term risk of gonadotropin deficiency, hypothalamic pituitary dysfunction and brainstem necrosis in pediatric patients with brain tumor: A nationwide cohort study
Authors: Lee Feng-Chin , Chung Chi-Hsiang , Lin Sheng-Feng , Kao Wei-Fong , Hou Sen-Kuang , Chang Hsi , Hou Peter C. , Chien Wu-Chien , Chao Chun-Chieh
Published: February 2024

Background: We evaluated associations between radiation therapy (RT) and late side effects (long-term endocrine, cognitive and cerebrovascular complications) in pediatric patients with brain tumor in a nationwide population.
Methods: Data of pediatric patients with brain tumor were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. The RT cohort included 815 patients, randomly matched by age, gender, and index year with non-RT controls. Multivariable Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHR) of developing late side effects in RT patients versus non-RT controls.
Results: The risk of late side effects in RT group was 1.173-fold (aHR =1.173, 95%CI 1.063-1.430) higher than did non-RT group. RT patients exhibited 1.172-fold and 1.796-fold higher risk of long-term endocrinopathies and late-delayed complications, respectively, than did non-RT patients. For long-term endocrinopathies, patients with RT had 1.602-fold and 1.120-fold higher risk for gonadotropin deficiency and hypothalamic pituitary dysfunction, respectively, than did non-RT patients. For late-delayed complications, patients with RT had 3.208-fold higher risk for necrosis of brain stem than did non-RT patients.
Conclusion: Gonadotropin deficiency, hypothalamic pituitary dysfunction and brainstem necrosis are dominant RT-related late side effects in pediatric patients. Frequency of these deficits increases with time, warranting long-term surveillance.
Gravitational waves from dark domain walls
Authors: Christiansen Øyvind , Adamek Julian , Hassani Farbod , Mota David Fonseca
Published: February 2024

For most of cosmic history, the evolution of our Universe has been governed by the physics of a 'dark sector'1, consisting of dark matter and dark energy, whose properties are only understood in a schematic way. The influence of these constituents is mediated exclusively by the force of gravity, meaning that insight into their nature must be gleaned from gravitational phenomena. The advent of gravitational-wave astronomy2-7 has revolutionised the field of black hole astrophysics, and opens a new window of discovery for cosmological sources. Relevant examples include topological defects, such as domain walls or cosmic strings8,9, which are remnants of a phase transition. Here we present the first simulations of cosmic structure formation in which the dynamics of the dark sector introduces domain walls as a source of stochastic gravitational waves in the late Universe10,11. We study in detail how the spectrum of gravitational waves is affected by the properties of the model, and extrapolate the results to scales relevant to the recent evidence for a stochastic gravitational wave background4. Our relativistic implementation12-14 of the field dynamics paves the way for optimal use of the next generation of gravitational experiments15-18 to unravel the dark sector.
Anticancer Effect of Chestnut inner shell extract on MDA-MB-231 by Regulation of AMPK, p53, Bcl-2, and Bax Expression
Authors: Kang Min Ho , Park Ha Young , Park Jung Eun , Kim Jin Woo
Published: February 2024

The purpose of this study was to investigate the anticancer properties of chestnut inner shell extract (CSE) by evaluating its effect on the regulation of key apoptosis genes in human breast cancer cells (MDA-MB-231). To evaluate the anticancer effect of CSE, HEK-293 and MDA-MB-231 were treated with 1.0 mg/mL of CSE. The results showed no growth inhibition in HEK-293 cells, while the viability of MDA-MB-231 cells decreased to 82.7%, indicating an anticancer effect of CSE without suppressing the growth of normal cell (HEK-293). CSE treatment resulted in 1.8, 1.3, and 2.6 times enhancement of the expressions of AMPK-α, p53, and Bax, respectively, along with a 1.2 times decrease in Bcl-2, confirming its potential as an anticancer agent through the regulation of key apoptosis genes. The main components of CSE were analyzed using HPLC-MS/MS, and the identification of afzelin, a type of flavonoid glycoside, suggests its potential anticancer properties. Overall, CSE has been shown to effectively upregulate the expression of apoptosis genes and inhibit the growth of human breast cancer cells, making a promising natural candidate with anticancer effects in the fields of food and pharmaceuticals.
Investigation on Physicochemical Properties and Anti-nutritional content of the three sorghum Varieties Grown in Ethiopia
Authors: Bogale Getenet , Getachew Eskinder , Admassu Habtamu
Published: February 2024

The physicochemical properties of grains play very important role to determine the quality of grains. An investigation was conducted to evaluate the physicochemical properties and phytochemical content of three sorghum varieties: Tilahun, Melkam, and Argity. Results demonstrated that Melkam exhibited the highest values in bulk density (0.86 g/mL), hectoliter weight (82.67 kg/hl), and flour extraction yield (79.4%). Argity, on the other hand, displayed higher values in thousand kernel weight (45.46g), size (3.6 mm), volume (37.6 mL), and angle of repose (30.070). Additionally, Melkam presented significantly higher levels of crude protein (12.81%), crude fiber (2.74%), and crude fat (3.07%), coupled with lower moisture (12.30%) and ash content (1.27%). Furthermore, Melkam exhibited lower levels of anti-nutritional factors such as tannin (0.21 mg/100g) and phytate content (320.3 mg/100g), while Tilahun demonstrated higher levels of ash, moisture, and phytate (334.07 mg/100g). In terms of mineral content, Melkam demonstrated the highest levels of calcium (24 mg/100g), phosphorus (266.12 mg/100g), and iron (4.16 mg/100g), with Tilahun displaying lower levels of calcium (12.34 mg/100g), phosphorus (255.57 mg/100g), and iron (4.0 mg/100g). Magnesium content was found to be highest in Argity (155.77 mg/100g) and lowest in Melkam (130.89 mg/100g). Based on the physicochemical properties observed, Melkam was selected as a favorable candidate for further food product development due to its nutritional qualities.
RNF181 promotes ferroptosis by ubiquitinating HMOX1 to inhibit gastric cancer cell proliferation and chemoresistance
Authors: Cui Hongjuan , Zhou Xujun , Chen Shitong , Liu Xiyu , Song Houji , Gan Lu , Wu Zonghui , Liao Yuan , Liao Yuan , Zhong Liping
Published: February 2024

Emergence of chemotherapeutic resistance remains an important challenge in cancer treatment, especially in advanced cancers. Recent studies have shown that ferroptosis is closely associated with tumor chemoresistance, and induction of ferroptosis has been shown to reverse chemoresistance. This study focused on the important function of Ring Finger Protein 181 (RNF181) in gastric cancer and the potential mechanisms involved in chemoresistance. Here, we found that RNF181 was aberrantly activated in chemoresistant cells of gastric cancer, and high expression of RNF181 was associated with poor patient prognosis. Depletion of RNF181 inhibited the proliferation and tumorigenicity of chemoresistant cells, and increased chemotherapeutic drug sensitivity. Mechanistically, our study showed that the interaction between RNF181 and HMOX1 mediated K27-linked polyubiquitination of HMOX1 and regulated its protein stability. Upregulation of HMOX1 expression after knockdown of RNF181 resulted in excessive heme degradation and intracellular iron overload to promote ferroptosis. Generally, our study reveals the important role of RNF181 in chemoresistance in gastric cancer, and targeting RNF181 may be a rational strategy to improve the efficacy of chemotherapy in gastric cancer.
Obesity Improves Neuronal Metabolism and Functional Hyperemia in a Rat Model of Early Ad Pathology
Authors: Almanza Dustin Loren Velasco , Koletar Margaret , Lai Aaron , Lam Wilfred , Joo Lewis , Hill Mary , Stanisz Greg , McLaurin JoAnne , Stefanovic Bojana
Published: February 2024

Background
While obesity has been linked to both increased and decreased rate of cognitive decline in Alzheimer’s Disease (AD) patients, the interaction between obesity and AD remains largely unknown.
Methods
In the present study, TgF344-AD rat model was used to investigate the effects of high carbohydrate, high fat (HCHF) diet on brain glucose metabolism and brain hemodynamics in the presence or absence of AD transgenes, in pre symptomatic vs. symptomatic stages of AD progression using non-invasive brain imaging.
Results
In prodromal AD, HCHF had pernicious effects: it attenuated both hippocampal glucose uptake and functional hyperemia in 6-month-old nTg and TgAD rats compared to CHOW-fed cohorts. However, HCHF was beneficial in established AD: 12-month-old HCHF-fed TgAD rats showed increased hippocampal glucose uptake and amplified functional hyperemia as well as resting perfusion that was indistinguishable from that of nTg rats; the latter effect was not due to anatomical changes in hippocampal vasculature on histopathological assays.
Conclusions
Our findings indicate that a high caloric diet in the early stages of symptomatic AD can have propitious effects on neurophysiological and cerebrovascular function, in support of our findings that the HCHF diet stabilizes executive function in this model of AD in the early symptomatic stage of the disease. Our data provide the first hitherto evidence of the disease stage-dependent effects of high caloric diet, illuminating the brain function changes underlying the obesity paradox.
Application of novel probation teaching mode in implant dentistry curriculum for Chinese undergraduate students
Authors: Liu Manqing , Li Junda , Xu Jiayun , Wang Tianlu , Xu Yuming , Wang Jinming
Published: February 2024

Background: Implant dentistry has developed rapidly due to elevated patient awareness and treatment expectations, resulting an increasing demand for educators to provide well-designed undergraduate oral implantology curriculum. However, not many studies have focused on the teaching effect of clinical probation in implant dentistry course. We conducted a retrospective study to evaluate the knowledge acquisition, attitude, and behavior of the students when exposed to three forms of oral implantology curriculum applied with different teaching modes.
Methods: We enrolled 150 fourth-year undergraduate dental students from grade 2017 to grade 2019 with 50 from each grade, respectively. Grade 2017 were exposed to conventional theoretical lectures only and selected as the Group A. Grade 2018 were provided with online probation teaching in addition to the theoretical lectures and selected as the Group B, while grade 2019 received offline probation teaching in addition to the theoretical lectures and selected as the Group C. The evaluation of the above teaching modes was conducted by final exam assessment and an online questionnaire.
Results: Overall evaluation of the course showed that probation teaching could enhance students’ satisfaction level, knowledge mastery efficiency and facilitate an appreciation of potential career options in oral implantology (P < 0.05). Further assessment regarding the comparison between online and offline mode of probation teaching demonstrated that the offline mode could effectively activate class atmosphere, increase student-teacher interaction, better foster clinical thinking ability, and meanwhile promote an early cultivation of medical humanistic spirit (P < 0.05). Assessment of final exam scores were consistent with the results of questionnaire, with Group C exhibited the best academic performance followed by Group B, then Group A (P < 0.05).
Conclusions: The utilization of the offline probation teaching mode in the undergraduate curriculum could not only improve students’ implantology knowledge and competences in a relaxing and effective manner, but also bridge the gap between theory and clinical practice.
Identification and characterization of specific motifs in effector proteins of plant parasites using MOnSTER
Authors: Bottini Silvia , calia giulia , porracciolo paola , chen yongpan , kozlowski djampa , Schuler Hannes , cestaro alessandro , quentin michael , favery bruno , Danchin Etienne
Published: February 2024

Motivation: Plant pathogens cause billions of dollars of crop loss every year and are a major threat to global food security. Identifying and characterizing pathogens effectors is crucial towards their improved control. Because of their poor sequence conservation, effector identification is challenging, and current methods generate too many candidates without indication for prioritizing experimental studies. In most phyla, effectors contain specific sequence motifs which influence their localization and targets in the plant. Therefore, there is an urgent need to develop bioinformatics tools tailored for pathogens effectors.Results To circumvent these limitations, we have developed MOnSTER a novel tool that identifies clusters of motifs of protein sequences (CLUMPs). MOnSTER can be fed with motifs identified by de novo tools or from databases such as Pfam and InterProScan. The advantage of MOnSTER is the reduction of motif redundancy by clustering them and associating a score. This score encompasses the physicochemical properties of AAs and the motif occurrences. We built up our method to identify discriminant CLUMPs in oomycetes effectors. Consequently, we applied MOnSTER on PPN and identified six CLUMPs in about 60% of the known nematode candidate parasitism proteins. Furthermore, we found co-occurrences of CLUMPs with protein domains important for invasion and pathogenicity. The potentiality of this tool goes beyond the effector characterization and can be used to easily cluster motifs and calculate the CLUMP-score on any set of protein sequences.Availability and implementation: The source python code and related data are available at: https://github.com/Plant-Net/MOnSTER_PROMOCA.git
Ingestion of Amoxicillin – Clavulanic Acid at therapeutic concentration during blood meal impacts Aedes aegypti microbiota and dengue virus transmission
Authors: Smévoorde Margot Garcia -- Van , Calvez Elodie , Quétel Isaure , Dollin Christelle , Breurec Sébastien , Vega-Rúa Anubis
Published: February 2024

Dengue virus (DENV), mainly transmitted by Aedes aegypti mosquitoes, is the most prevalent arbovirus worldwide, representing a public health problem in tropical and subtropical countries. In these areas, antibiotic consumption rises which may impact both mosquito microbiota and dengue transmission. Here, we assessed how the ingestion by Ae. aegypti of therapeutic concentrations of Amoxicillin – Clavulanic Acid association (Amox/Clav), a broad-spectrum antibiotic used to treat febrile symptoms worldwide, impacted its microbiota. We also evaluated whether simultaneous ingestion of antibiotic and DENV impacted Ae. aegyptiability to transmit this virus. We found that Amox/Clav ingestion impacted microbiota composition in Ae. aegypti and we confirmed such impact in field-collected mosquitoes. Furthermore, we observed that Amox/Clav ingestion enhanced DENV dissemination and transmission by this mosquito at late days post-DENV exposure. These findings increase our understanding of factors linked to human hosts that may influence dengue transmission dynamics in regions with mass-drug administration programs.
Potato consumption and all-cause and cardiovascular disease mortality – a long-term follow-up of a Norwegian cohort
Authors: Arnesen Erik Kristoffer , Laake Ida , Carlsen Monica H. , Veierød Marit Bragelien , Retterstøl Kjetil
Published: February 2024

Purpose. To examine the association between potato consumption and death of all-causes and cardiovascular disease (CVD) over a substantial follow-up period within a cohort predominantly consuming boiled potatoes.
Methods. Adults from three Norwegian counties were invited to three health screenings in 1974–1988 (>80% attendance). Dietary data were collected using semi-quantitative food frequency questionnaires at each screening to categorize weekly potato consumption (≤6, 7–13, or ≥14 potatoes/week) and calculate daily cumulative mean intakes (grams/day). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between potato consumption and risk of death from all-causes, CVD, ischaemic heart disease (IHD), and acute myocardial infarction (AMI).
Results. Among 78,400 subjects with a mean baseline age of 41 years, we observed 27,737 deaths, including 9,028 deaths due to CVD, over a median follow-up of 33.5 years. Subjects who consumed ≥14 potatoes/week had a lower risk of all-cause death compared to subjects consuming ≤6potatoes/week (HR=0.88; 95% CI 0.84, 0.92). Potato consumption was associated with a small, inverse risk of death due to CVD, IHD, and AMI. In continuous analyses, each 100 g/day increment was associated with 4% lower risk of death from all-causes (HR=0.96; 95% CI 0.94, 0.98) and CVD (0.96; 0.93, 0.99), along with 5% (0.95; 0.91, 1.00) and 4% lower (0.96; 0.91, 1.01) risk of IHD and AMI death, respectively.
Conclusion. In this cohort with a generally high consumption of potatoes, we found modest, inverse associations between potato consumption and death of all-causes, CVD, and IHD.
The Temporal Trajectory of the Psychedelic Mushroom Experience Mimics the Narrative Arc of the Hero’s Journey
Authors: Brouwer Ari , Brown Joshua K. , Erowid Earth , Erowid Fire , Thyssen Sylvia , Raison Charles L. , Carhart-Harris Robin L.
Published: February 2024

Psychedelic therapy has the potential to become a revolutionary and transdiagnostic mental health treatment, yielding enduring benefits that are often attributed to the experiences that coincide with peak psychedelic effects. However, there may be an underrecognized temporal structure to this process that helps explain why psychedelic and related altered states of consciousness can have a initially distressing but ultimately a distress-resolving effect. Here we present a qualitative analysis of the self-reported ‘comeup’ or onset phase, and ‘comedown’ or falling phase, of the psychedelic experience. Focusing on psilocybin or psilocybin-containing mushrooms, we show that the comeup is more often characterized by negatively valenced feeling states, while the comedown phase is more often characterized by positively valenced feeling states of the sort often observed following recovery from illness or adversity. In this way, the temporal trajectory of the psychedelic experience could be seen to mimic the narrative arc of the monomythical ‘Hero’s Journey’.
Bioinformatics analysis of the clinical value and potential mechanisms of CBS/H2S in Glioma through 1027 samples.
Authors: Si Yuanyuan , Song Ningjia , JI YONG
Published: February 2024

Background
Glioma is a highly malignant brain tumor with dismal prognosis, limiting effective treatment strategies. Thus,identifying the molecular mechanisms underlying tumor-related gene in glioma is critical. Cystathionine beta-synthase (CBS), a key kinase in the brain responsible for producing hydrogen sulfide (H2S) internally, has been implicated in the progression of malignant tumors. However, there is a paucity of studies focusing on CBS/H2S in the context of glioma.
Methods
Data analysis of mRNA-seq level was performed in a group of 325 patients with glioma from the Chinese Glioma Genome Altas (CGGA) database and 702 patients from The Cancer Genome Altas (TCGA). The TISIDB database was employed to explore the connection between CBS expression and immune cell infiltration levels.Furthermore, the variation in CBS expression across multiple cancer types were examined by GEPIA database and TISIDB database.
Results
CBS showed enrichment in low-grade gliomas and IDH-mutant gliomas. Furthermore,CBS held great promise as a biomarker for glioblastoma and an independent prognostic determinant affecting patients’ overall survival. Notably,the analysis of immune infiltration revealed inverse associations between CBS and 28 distinct types of tumor-infiltrating lymphocytes (TILs).Moreover,CBS played a pivotal role in Pan-cancer,highlighting its significance in Pan-cancer studies.
Sustainability assessment in the presence of undesirable outputs: A stochastic slack-based data envelopment analysis approach
Authors: Amirteimoori Alireza , Allahviranloo Tofigh , Khalaf Osamah Ibrahim , Algburi Sameer , Nematizadeh Maryam , Hamam Habib
Published: February 2024

Measuring sustainability as an efficient tool to achieve sustainable development and improve economic, social, and environmental aspects is always fraught with complications. Consequently, the identification of a suitable method capable of evaluating and recognizing the strengths and weaknesses across these dimensions is paramount. Given that data in many real-world applications exist in uncertain and random forms, the primary aim of this paper is to present a model for evaluating sustainability within a stochastic environment using the technique of data envelopment analysis (DEA). The proposed model is non-radial and incorporates undesirable outputs, enabling the assessment of overall sustainability as well as each of the economic, social, and environmental dimensions simultaneously. This multi-dimensional evaluation capability is a key advantage of the proposed model. Additionally, the proposed model is based on input excesses and output shortfalls. Another notable advantage is the incorporation of the assumption of managerial disposability when dealing with undesirable outputs. To illustrate the proposed sustainability model across economic, social, and environmental dimensions, data from 59 countries spanning Africa, Europe, North America, and Asia are analyzed and evaluated within a stochastic environment.
Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma
Authors: Leek Lindsay V.M. , Notohardjo Jessica C.L. , de Joode Karlijn , Velker Eline L. , Haanen John B.A.G. , Suijkerbuijk Karijn P.M. , Aarts Maureen J.B. , de Groot Jan Willem B. , Kapiteijn Ellen , Berkmortel Franchette W.P.J. van den , Westgeest Hans M. , de Gruijl Tanja D. , Retel Valesca P. , Cuppen Edwin , Veldt Astrid A.M. van der , Labots Mariette , Voest Emile E. , de Haar Joris van , Eertwegh Alfons J.M. van den
Published: February 2024

We evaluated the prognostic value of hypoalbuminemia in context of various biomarkers at baseline, including clinical, genomic, transcriptomic, and blood-based markers, in patients with metastatic melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anti-CTLA-4 combination therapy (n=178). An independent validation cohort (n=79) was used to validate the performance of hypoalbuminemia compared to serum LDH (lactate dehydrogenase) levels. Pre-treatment hypoalbuminemia emerged as the strongest predictor of poor outcome for both OS (HR=4.01, 95% CI 2.10-7.67, Cox P=2.63e-05) and PFS (HR=3.72, 95% CI 2.06-6.73, Cox P=1.38e-05) in univariate analysis. In multivariate analysis, the association of hypoalbuminemia with PFS was independent of serum LDH, IFN-γ signature expression, TMB, ECOG PS, treatment line, treatment type (combination or monotherapy), brain and liver metastasis (HR=2.80, 95% CI 1.29-6.08, Cox P=0.00916). Our validation cohort confirmed the prognostic power of hypoalbuminemia for OS (HR=1.98, 95% CI 1.16-3.38; Cox P=0.0127) and was complementary to serum LDH in analyses for both OS (LDH-adjusted HR=2.12, 95% CI 1.2-3.72, Cox P=0.00925) and PFS (LDH-adjusted HR=1.91, 95% CI 1.08-3.38, Cox P=0.0261). In conclusion, pretreatment hypoalbuminemia was a powerful predictor of outcome in ICI in melanoma and showed remarkable complementarity to previously established biomarkers, including high LDH.
GATA2 promotes castration-resistant prostate cancer development by suppressing IFN-β axis-mediated antitumor immunity
Authors: XU MAFEI , Jin Zige , Wang Hanling , Tang Ruxian , Pan Biying , Lee Hui-ju , Liu Siqi , Wang Leiming , Qin Jun
Published: February 2024

Castration-resistant prostate cancer (CRPC) nearly inevitably develops after long-term treatment with androgen deprivation therapy (ADT), leading to significant mortality. Investigating the mechanisms driving CRPC development is imperative. Here, we determined that the pioneer transcription factor GATA2, which is frequently amplified in CRPC patients, inhibits interferon (IFN)-β-mediated antitumor immunity, thereby promoting CRPC progression. Employing a genetically engineered mouse model (GEMM), we demonstrated that GATA2 overexpression hindered castration-induced cell apoptosis and tumor shrinkage, facilitating tumor metastasis and CRPC development. Notably, GATA2 drives castration resistance predominantly via repressing castration-induced activation of IFN-β signaling and CD8 + T-cell infiltration. This finding aligns with the negative correlation between GATA2 expression and IFNB1 expression, as well as CD8 + T-cell infiltration in CRPC patients. Mechanistically, GATA2 recruited PIAS1 as corepressor, and reprogramed the cistrome of IRF3, a key transcription factor of the IFN-β axis, in an androgen-independent manner. Furthermore, we identified a novel silencer element that facilitated the function of GATA2 and PIAS1 through looping to the IFNB1 promoter. Importantly, depletion of GATA2 augmented antitumor immunity and attenuated CRPC development. Consequently, our findings elucidate a novel mechanism wherein GATA2 promotes CRPC progression by suppressing IFN-β axis-mediated antitumor immunity, underscoring GATA2 as a promising therapeutic target for CRPC.
Hazardous Effects of Heavy Metal Pollution on Histological and Gene Expression Profiles of Nile Tilapia in the Eastern Delta, Egypt Aquatic Ecosystems
Authors: Shaalan Walaa M.
Published: February 2024

Heavy metal pollution threatens the biodiversity and ecological equilibrium of the Nile River. This study investigates the impact of heavy metal pollution on aquatic animal as Nile tilapia (Oreochromis niloticus) in the Damietta branch of the River Nile and El-Rayah El-Tawfeeky, in Benha city in Egypt. Fish and water samples were subsequently analyzed using ICP-OES revealing significantly higher concentrations of Mg, Cd, Hg, Cr, Cu, Ni, Pb, and Zn in fish muscle tissues collected from Damietta branch compared to El-Rayah El-Tawfeeky samples. Histopathological examinations revealed noteworthy alterations in tilapia gill, liver, spleen, and muscle tissues, suggesting potential health risks. Gene expression analysis using RT-qPCR indicated significant changes in genes related to muscle growth (MyoD, IGF-1) and immune response (TNFa, IL6) in fish from Damietta branch relative to fish of El-Rayah El-Tawfeeky. The findings raise concerns about bioaccumulation and potential health implications for consumers. The study underscores the significance of continuous monitoring, utilizing chemical, histopathological, and molecular tools as bioindicators for environmental protection measures against aquatic pollution.
A multimodal stacked ensemble model for breast cancer prognosis prediction: a proposed CNN hyperparameter optimization using the Tug of War (TWO) algorithm
Authors: Maigari Aminu , Zainol Zurinahni , Xinying Chew
Published: February 2024

Breast cancer (BC) is a global health challenge that affects millions of women worldwide and leads to significant mortality. Recent advancements in next-generation sequencing technology have enabled comprehensive diagnosis and prognosis determination using multiple data modalities. Deep learning methods have shown promise in utilizing these multimodal data sources, outperforming single-modal models. However, integrating these heterogeneous data sources poses significant challenges in clinical decision-making. This study proposes an optimized multimodal CNN for a stacked ensemble model (OMCNNSE) for breast cancer prognosis. Our novel method involves the integration of the Tug of War (TWO) algorithm to optimize the hyperparameters of a convolutional neural network (CNN), enhancing feature extraction from three distinct multimodal datasets: clinical profile data, copy number alteration (CNA), and gene expression data. Specifically, we employ the TWO algorithm to optimize separate CNN models for each dataset, identifying optimal values for the hyperparameters. We then trained the three baseline CNN models using the optimized values through 10-fold cross-validation. Finally, we utilize an ensemble learning approach to integrate the models' predictions and apply an SVM classifier for the final prediction. To evaluate the proposed method, we conducted experiments on the METABRIC breast cancer dataset comprising diverse patient profiles. Our results demonstrated the effectiveness of the OMCNNSE approach for predicting breast cancer prognosis. The model achieved high AUC, accuracy, sensitivity, precision, and MCC, outperforming traditional single-modal models and other state-of-the-art methods.
Determination of some quality properties of ice cream fermented with kefir culture and flavored with mint (Menthaspicata L.)
Authors: Öztürk-Yalçın Feyza , Ürkek Bayram , Şengül Mustafa
Published: February 2024

Kefir is a healthy fermented dairy product, while ice cream is one of the most consumed dairy products. In this study, the mint flavor was added in different proportions (0 (KI), 0.2% (KIM2), 0.4% (KIM4), and 0.6% (KIM6)) to ice cream fermented with kefir culture. The study investigated the microbiological, antioxidant, thermal, rheological, textural, compositional, and sensory properties of kefir ice cream samples during 45-day storage. The lactic bacilli, lactic cocci, and Leuconostoc counts of samples were around 8 log CFU/g, while the yeast counts were less than 4 log CFU/g. The addition of mint flavor did not have a negative effect on the microbiological properties of the samples. Values of IC50 and total phenolic content (except for samples KIM2 and KIM6) values did not differ significantly among samples and during storage (P<0.05). The pH and melting rate values of the samples decreased with the addition of mint flavor, while acidity values increased. Sample KI usually had the lowest values for thermal properties. The overrun, a*, WI, and hardness values of the samples decreased based on the mint flavor concentration, whereas the viscosity (at 50 rpm) and consistency coefficient values increased. Samples KI and KIM2 were scored higher than other samples for all sensory properties. As a result, 0.2% mint flavored kefir ice cream could be produced.
Vaccination Model: self-protective behavior in the face of Ransomware Attack in SMEs
Authors: Rechavi Amit , Berenblum Tamar
Published: February 2024

In today's business environment, the reliance of business processes on information technology (IT) has never been stronger, making the maintenance and security of IT systems crucial for organizations. Ransomware attacks present a significant cybersecurity risk, yet many existing solutions primarily focus on technology, overlooking the critical role of human behavior in system security. To address this gap, we experimented to assess the impact of controlled exposure to ransomware attacks on users' protection motivation and behavior. Unlike traditional security training, our approach actively engaged users in real-life scenarios and hands-on security events. The results demonstrated that controlled exposure to ransomware significantly heightened users' vigilance and improved their ability to recognize and respond to phishing campaigns. These findings indicate that hands-on exposure experiences enhance learning and boost protection motivation, sustaining positive effects on cybersecurity behavior. Our study underscores the importance of addressing the human factor in cybersecurity and introduces a promising approach to fortifying resilience against cyber threats. The vaccination model exemplifies a practical and effective strategy for improving cybersecurity readiness within authentic organizational environments by shaping users' mindsets and actions through real threat demonstrations.
Effects of NaOH Addition on Cellulose Nanocrystal Functionalization with 2,4-Dichlorophenoxyacetic Acid
Authors: Clouse Delaney E. , Collins Elise G. , Rahman Tanmay , Khodakovskaya Mariya V. , Davis Virginia A.
Published: February 2024

This article investigates the necessity of sodium hydroxide (NaOH) addition for the amine functionalization of sulfated cellulose nanocrystals (CNCs) and its effect on nanocrystal reactivity with the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). The use of CNCs as a nanocarrier of active biomolecules has grown in the past decade. Previously, CNCs were produced by laboratory sulfuric acid hydrolysis protocols that imparted sulfate half-ester groups with hydrogen counterions. Because of this, researchers cited the need to add a deprotonating base such as NaOH before amination, a common precursor reaction for further biomolecule functionalization. However, current commercially produced sulfated CNCs have a sodium counterion instead of hydrogen. This work explores whether the use of commercial sulfated CNCs negates the need for sodium hydroxide addition in amine functionalization. We investigated the effect of 10 wt% sodium hydroxide solution on the amination of 1 wt% and 2 wt% CNC dispersions. Following this step, CNCs were then further modified via EDC/NHS chemistry to attach 2,4-D. Thermogravimetric analysis coupled with infrared spectroscopy was used to qualitatively confirm attachment. Elemental analysis determined that the degree of amine substitution for all dispersions ranged from 5.4–6.7%. 2,4-D attachment to amine groups varied from 3.9–6.5% when NaOH was present to 7.1% when NaOH was not added. These results highlight how the evolution in CNC extraction methods has resulted in NaOH addition no longer being necessary for successful reactions when using commercially sourced sulfated CNCs with a sodium counterion.
Molecular Dynamics Simulation and Molecular Docking Study on the Conversion of Ginsenosides by β-Glucanase
Authors: Yao Xiangyu , Pan Hong , Hong Yinan , Wang Xiaojun , Lu Tianwen
Published: February 2024

Enzymatic conversion is an important method for producing rare ginsenosides. In order to explore the molecular mechanisms underlying the interaction of β-Glucanase during the conversion process of rare ginsenoside CK, this study employed high-performance liquid chromatography, infrared spectroscopy, ultraviolet spectroscopy, and fluorescence spectroscopy to investigate the ability of β-Glucanase to convert ginsenoside Rb1 into ginsenoside CK. Changes in the secondary structure quantity of the enzyme before and after conversion were characterized. Additionally, this study accurated binding sites of β-Glucanase with ginsenoside Rb1, as well as optimal conformations, were identified through molecular dynamics simulations and molecular docking. Spectroscopic experiments revealed a reduction in the α-helix and β-fold content of β-Glucanase in acetic acid buffer. Molecular dynamics and docking results indicated that spontaneous interactions between β-Glucanase and ginsenosides Rb1, Rd, and F2, characterized by strong binding forces and high dissociation rates. In summary, the spectroscopic experiments, molecular simulations, and docking validations collectively demonstrate structural changes in the enzyme itself and the generation of some secondary bonds between the enzyme and ginsenosides during the process of converting ginsenoside Rb1 to CK. This study provides theoretical support for the conversion of ginsenoside Rb1 by β-Glucanase, elucidating the mechanisms of enzyme immobilization and catalytic reactions of β-Glucanase, offering new insights into the interaction between proteins and small molecule ligands.
The Association between Mediterranean Diet Adherence and Behavioral Outcomes among Urban Teenagers
Authors: Julvez Jordi , Pinar Ariadna , Ruiz Marina , Ayala Nicolas , Pacual-Rubio Vicenç , Fabregat-Sanjuan Albert , Casanova-Molla Jordi , Solà-Valls Nuria , Contreras Oren , Romaguera Dora , Fernádez-Barrés Sílvia
Published: February 2024

Objective: We examined the association between Mediterranean diet and psychosocial functioning among high school students from Barcelona, Spain.
Methods: This is a sample of healthy teenagers (11 to 16 years old) recruited during 2016–2017 from 12 high schools in Barcelona. The 622 participants responded the Mediterranean Diet Quality Index for Children and Adolescents (KIDMED) and the Strengths and Difficulties Questionnaire (SDQ). Multivariable linear regression models were applied to assess the associations between KIDMED and SDQ scores and adjusting for potential confounders.
Results: KIDMED score was negatively associated with SDQ total problem score (β = -0.20 (95% CI = -0.38; -0.02)) and conduct problem score (β = -0.08 (95% CI = -0.14; -0.03)). KIDMED score was positively associated with prosocial behavior subscale score (0.08 (0.03; 0.14)).
Conclusion: Adherence to Mediterranean diet is beneficial for some domains of psychosocial functioning. Dietary patterns are important for mental health during the adolescence.
Age-related histone H3.3 accumulation associates with a repressive chromatin in mouse tibialis anterior muscle
Authors: Masuzawa Ryo , Flete Hemilce Karina Rosa , Shimizu Junya , Kawano Fuminori
Published: February 2024

Age-related alterations in epigenetic regulation are postulated to result in the disorganization of cellular functions of skeletal muscles. The accumulation of the non-canonical histone variant H3.3 increases with age in several organs and exhibits tissue-specific patterns of histone modifications. However, it is unclear how histone distribution and modifications in skeletal muscle are affected by aging. The present study aimed to investigate age-related changes in H3.3 and its role in the aging process of mouse skeletal muscles. We first analyzed age-related changes in the morphology of the tibialis anterior muscle and age-related changes in gene expression and histone distribution at target loci in the tibialis anterior muscles in mice of various ages. A significant decrease in muscle weight and the number of myonuclei was observed at 53-wk-old. H3.3 levels significantly increased with age and correlated with H3K27me3 levels. Chromatin immunoprecipitation analysis showed similar changes at both transcriptionally upregulated and downregulated loci. Next, we assessed the effect of acute exercise on gene expression and histone distribution between 8- and 53-wk-old mice. No upregulation in gene expression in response to acute exercise was noted in 53-wk-old mice. H3K27me3 levels were increased in certain loci in response to acute exercise in 8-wk-old mice. However, in 53-wk-old mice, H3.3 and H3K27me3 levels were increased at rest and were not affected by acute exercise. Furthermore, we assessed the effects of forced H3.3 expression in the skeletal muscles of 8-wk-old mice. The mice were given a viral vector expressing H3.3 under the control of a skeletal muscle-specific promoter. The latency to fall in the rotarod test significantly improved in mice with forced H3.3 expression. Downregulation of gene expression was noted in the tibialis anterior muscle of mice with forced H3.3 expression. H3.3 incorporation into the nucleosomes at these loci was promoted by forced H3.3 expression, although H3K27me3 distribution was reduced at these loci. Collectively, these results suggest that H3.3 accumulation increased with age in skeletal muscle and induced the formation of repressive chromatin in association with H3K27me3. Further, these results also suggest that H3.3 accumulation plays a positive role in muscle function if H3K27me3 is unmodified.
When Quantum Dots Meet Blue Phase Liquid Crystal Elastomers: Visualized Full-Color and Mechanically-Switchable Circularly Polarized Luminescence
Authors: Li Quan , Li Shan , Tang Yuqi , Fan Qingyan , Li Ziyuan , Zhang Xinfang , Wang Jingxia , Guo Jinbao
Published: February 2024

Polymer-based circularly polarized luminescence (CPL) materials with the advantage of diversified structure, easy fabrication, high thermal stability, and tunable properties have garnered considerable attention. However, adequate and precise tuning over CPL in polymer-based materials remains challenging due to the difficulty in regulating chiral structures. Herein, visualized full-color CPL is achieved by doping red, green, and blue quantum dots (QDs) into reconfigurable blue phase liquid crystal elastomers (BPLCEs). In contrast to the CPL signal observed in cholesteric liquid crystal elastomers (CLCEs), the chiral 3D cubic superstructure of BPLCEs induces an opposite CPL signal. Notably, this effect is entirely independent of photonic bandgaps (PBGs) and results in a high glum value, even without matching between PBGs and the emission bands of QDs. Meanwhile, the lattice structure of the BPLCEs can be reversibly switched via mechanical stretching force, inducing on-off switching of the CPL signals, and these variations can be further fixed using dynamic disulfide bonds in the BPLCEs. Moreover, the smart polymer-based CPL systems using the BPLCEs for anti-counterfeiting and information encryption have been demonstrated, suggesting the great potential of the BPLCEs-based CPL active materials.
Synergistic effects of anlotinib and DDP synergy in breast cancer treatment: inhibiting of cell growth and migration, and augmenting apoptosis and autophagy via modulation of the VEGF/JAK2/STAT3 axis
Authors: Zhang Hongmei , Liu Chunling , Jin Ye , Wang Zheng , Jia Zhenxian , Cui Tong , Zhang Zhi , Zhang Xuemei
Published: February 2024

Anlotinib has been shown to have good anti-tumor effects in a variety of tumors, including breast cancer (BRCA); however, the combined anti-tumor efficacy of anlotinib and DDP in BRCA, as well as the underlying mechanism, remain to fully elucidated. This study aims to explore the role of VEGFA expression in BRCA and the therapeutic efficacy of anlotinib, alone and in combination with cisplatin (DDP), in treating BRCA. BRCA cells were treated with or without anlotinib and/or DDP. The proliferation, migration and invasion capabilities of BRCA cells were evaluated using CCK-8 assays, clone formation assays, wound healing assays and transwell assays. Cell apoptosis was detected by Hoechst33342 fluorescence staining and flow cytometry technique. The potential mechanism of anlotinib in the development of BRCA was predicted through bioinformatics analysis, and the mRNA or protein levels were subsequently quantified using qPCR and western blot. The anti-breast cancer efficacy of anlotinib was evaluated in vivo using a xenograft tumor model. Our findings reveal that increased VEGFA expression in BRCA patients is associated with a poorer prognosis, underscoring the need for targeted therapeutic strategies. We demonstrate that both anlotinib and DDP independently inhibit BRCA cell growth, migration, and invasion. Their combination exhibits a synergistic effect, significantly enhancing the inhibition of these oncogenic processes. This synergy is further evident in the induction of apoptosis and autophagy within BRCA cells. Mechanistically, anlotinib's effectiveness is attributed to its inhibition of the JAK2/STAT3 pathway, a critical axis in BRCA progression. In vivo studies reinforce these findings, anlotinib markedly inhibits tumor growth in mice xenografted. This study confirms the efficacy of anlotinib or in combination with DDP and elucidates the mechanism behind anlotinib's effectiveness, highlighting its role in inhibiting the JAK2/STAT3 pathway. These findings pave the way for further clinical exploration and development of anlotinib-based therapies, offering hope for improved outcomes in breast cancer management.
Numerical approach for brain tumor growth model using higher order compact finite difference scheme
Authors: Das Hirak Jyoti , Sen Shuvam
Published: February 2024

In this article, we focus on analyzing the reaction-diffusion model applied to brain gliomas, incorporating two distinct types of growth functions. To gain a comprehensive understanding, we extend our analysis to different types of tissue environments. We explore scenarios where the diffusion coefficient remains constant, reflecting a homogeneous tissue environment. Additionally, we investigate cases where the diffusion coefficient becomes spatially variable, introducing heterogeneity into the model. This spatial variability accounts for the varying properties of different regions within the brain. Subsequently, we extend our investigation to heterogeneous tissue environments in $2$-dimensions. Our analysis of simulation results reveals differences in growth patterns based on the parameters utilized.