bluuebunny/crossref_metadata_2025 huggingface dataset:
Career services at HEI’s: what are they offering?
Authors: Khurumova Veronika , Pinto Joana Carneiro
Published: December 2024

Higher education career centers should tailor their services toward empowering students to make them employable after graduation to meet the demands of the 21st century world of work. This paper aims to reflect on career counseling services provided by Higher Education Institutions. We start by presenting a brief history of their development around the world, with particular emphasis on Portugal. Next, a study about the current situation of these services in the country is presented, starting with an analysis of their organization, the type of actions/activities/services provided, as well as their accessibility. Results indicate that the Career Services in some Portuguese Higher Education Institutions appear not to be fully developed, and where they exist, they often focus mostly (and sometimes solely) upon job placement or internship provision. More investment is needed to meet the new employability needs and demands of both students (and their families) and the labor market.
Assessment of extreme climate stress across China’s maize harvest region in CMIP6 simulations
Authors: Chen Xinmin , Shi Zexu , Xiao Dengpan , Lu Yang , Bai Huizi , Zhang Man , Ren Dandan , Qi Yongqing , Song Shikai
Published: December 2024

Climate change is expected to increase the frequency and severity of climate extremes, which will negatively impact crop production. As one of the main food and feed crops, maize is also vulnerable to extreme climate events. In order to accurately and comprehensively assess the future climate risk to maize, it is urgent to project and evaluate the stress of extreme climate related maize production under future climate scenarios. In this study, we comprehensively evaluated the spatio-temporal changes in the frequency and intensity of six extreme climate indices (ECIs) across China’s maize harvest region by using a multi-model ensemble method, and examined the capability of the Coupled Model Intercomparison Project Phase 6 (CMIP6) to capture these variations. We found that the Independence Weight Mean (IWM) ensemble results calculated by multiple Global Climate Models (GCMs) with bias correction could better reproduce each ECI. The results indicated that heat stress for maize showed consistent increase trends under four future climate scenarios in the 21st century. The intensity and frequency of the three extreme temperature indices in 2080s were significantly higher than these in 2040s, and in the high emission scenario were significantly higher than these in the low emission scenario. The three extreme precipitation indices changed slightly in the future, but the spatial changes were more significant. Therefore, with the uncertainty of climate change and the differences of climate characteristics in different regions, the optimization of specific management measures should be considered in combination with the specific conditions of future local climate change.
Depression and anxiety among pregnant women during COVID 19 pandemic in Ethiopia: a systematic review and meta-analysis
Authors: Gebeyehu Wondmeneh Temesgen , Wogris Mohhamed
Published: December 2024

Background

Coronavirus Disease-19 pandemic had an adverse impact on the mental health of the public worldwide, but the problem is worst among pregnant women due to social distancing policies and mandatory lockdown, including prenatal care services. As a result, the prevalence of depression and anxiety could increase during the pandemic, particularly among pregnant women. Thus, the purpose of this review is to determine the magnitude of depression and anxiety and contributing factors among pregnant women during the pandemic in Ethiopia.

Methods

Web of Science, Since Direct, PubMed, Google Scholar, and African Journals Online were the electronic databases searched, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed in this review. The Newcastle-Ottawa Critical Appraisal Checklist was used to assess the quality of the included studies. A predefined data extraction sheet developed in Excel was used to extract the data. The pooled prevalence of anxiety and depression was determined by a random effect model meta-analysis.

Results

4,269 and 1,672 pregnant women were involved in depression and anxiety studies, respectively. The pooled prevalence of depression and anxiety among pregnant women during the COVID-19 pandemic in Ethiopia was 24.7% (95% CI: 18.52–30.87) and 35.19% (95% CI: 26.83–43.55), respectively. Single marital status (AOR = 2.22, 95% CI: 1.07–3.37), poor social support (AOR = 2.7, 95% CI: 1.06–4.35), unplanned pregnancies (AOR = 2.17, 95% CI: 1.34–3.0), and unsatisfied marital status (AOR = 2.16, 95% CI: 1.17–3.14) were risk factors for depression. Violence against intimate partners (AOR = 2.87, 95% CI: 1.97–3.77) and poor social support (AOR = 1.98, 95% CI: 1.24–2.71) were risk factors for anxiety.

Conclusion

One-fourth and nearly one-third of pregnant women had depression and anxiety, respectively, during COVID-19 pandemic in Ethiopia. Single or unsatisfied marital status and unplanned pregnancies were risk factors for depression. Poor social support was significantly associated with depression and anxiety. Pregnant women who experienced violence against intimate partners had higher anxiety. After COVID-19 pandemic, mental health interventions are essential for reducing depression and anxiety.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=527148, PROSPERO (CRD42024527148).
Unique lymphocyte transcriptomic profiles in septic patients with chronic critical illness
Authors: Barrios Evan L. , Balzano-Nogueira Leandro , Polcz Valerie E. , Rodhouse Christine , Leary Jack R. , Darden Dijoia B. , Rincon Jaimar C. , Dirain Marvin L. , Ungaro Ricardo , Nacionales Dina C. , Larson Shawn D. , Sharma Ashish , Upchurch Gilburt , Wallet Shannon M. , Brusko Todd M. , Loftus Tyler J. , Mohr Alicia M. , Maile Robert , Bacher Rhonda , Cai Guoshuai , Kladde Michael P. , Mathews Clayton E. , Moldawer Lyle L. , Brusko Maigan A. , Efron Philip A.
Published: December 2024

Introduction

Despite continued improvement in post-sepsis survival, long term morbidity and mortality remain high. Chronic critical illness (CCI), defined as persistent inflammation and organ injury requiring prolonged intensive care, is a harbinger of poor long-term outcomes in sepsis survivors. Current dogma states that sepsis survivors are immunosuppressed, particularly in CCI. Investigation of this immune suppression in heterogeneous immune populations across distinct clinical trajectories and outcomes, along with limited sampling access, is accessible via single-cell RNA sequencing (scRNA-seq).

Methods

scRNA-seq analysis was performed on healthy subjects (n=12), acutely septic patients at day 4 ± 1 (n=4), and those defined as rapid recovery (n=4) or CCI (n=5) at day 14-21. Differential gene expression and pathway analyses were performed on peripheral blood lymphocytes at both a population and annotated cell subset level. Cellular function was assessed via enzyme-linked immunosorbent spot (ELISpot), cytokine production analysis, and T-cell proliferation assays on an additional cohort of septic patients (19 healthy, 68 acutely septic, 27 rapid recovery and 20 classified as CCI 14-21 days after sepsis onset).

Results

Sepsis survivors that developed CCI exhibited proportional shifts within lymphoid cell populations, with expanded frequency of CD8+ and NK cells. Differential expression and pathway analyses revealed continued activation in T cells and NK cells, with generalized suppression of B-cell function. Both T and NK cell subsets displayed transcriptomic profiles of exhaustion and immunosuppression in CCI, particularly in CD8+ T effector memory (TEM) cells and NK cells. Functional validation of T-cell behavior in an independent cohort demonstrated T cells maintained proliferative responses in vitro yet exhibited a marked loss of cytokine production. IFN-γ production at the acute phase (day 4 ± 1) was significantly reduced in subjects later classified as CCI.

Discussion

Sepsis patients exhibit unique T-, B-, and NK-cell transcriptional patterns that are both time- and clinical trajectory-dependent. These transcriptomic and pathway differences in sepsis patients that develop CCI are associated with exhaustion in CD8+ TEM cells and NK cells. Understanding the specific immune system patterns of different cell subsets after sepsis at a molecular level will be key to the development of personalized immunotherapy and drug-targeting intervention.

Clinical trial registration

https://clinicaltrials.gov/, identifier NCT02276417.
A new perspective on macrophage-targeted drug research: the potential of KDELR2 in bladder cancer immunotherapy
Authors: Zhao Zhiyi , Jia Hongling , Sun Zhou , Li Yumeng , Liu Lingyun
Published: December 2024

Introduction

Bladder cancer was recognized as one of the most common malignant tumors in the urinary system, and treatment options remained largely limited to conventional surgery, radiotherapy, and chemotherapy, which limited patient benefits.

Methods

Researchers constructed an RNA transcriptome map of bladder cancer by integrating single-cell RNA sequencing and clinical data, identifying potential molecular targets for diagnosis and treatment. We also verified the antitumor activity of the target through in vitro experiment.

Results

A distinct tumor cell subpopulation characterized by elevated S100A8 expression exhibited high copy number variation, high stemness, and low differentiation. It interacted with myeloid cells via the MIF-(CD74+CD44) and MIF-(CD74+CXCR4) signaling pathways. This study underscored KDELR2’s role in promoting cell proliferation, invasion, and migration, providing new therapeutic insights. Prognostic analysis revealed that KDELR2 correlated with poor survival, higher immune scores, and increased macrophage infiltration.

Discussion

The findings suggested that patients with high KDELR2 expression might benefit from immune checkpoint therapy. KDELR2 was also shown to enhance bladder cancer cell proliferation, invasion, and migration, highlighting it as a promising target for macrophage-focused drug development.
Leveraging the synergy between anti-angiogenic therapy and immune checkpoint inhibitors to treat digestive system cancers
Authors: Xu Qinlan , Shao Dong
Published: December 2024

The response rates to immunotherapy vary widely depending on the type of cancer and the specific treatment used and can be disappointingly low for many solid tumors. Fortunately, due to their complementary mechanisms of action, immunotherapy and anti-angiogenic therapy have synergistic effects in cancer treatment. By normalizing the tumor vasculature, anti-angiogenic therapy can improve blood flow and oxygenation to facilitate better immune cell infiltration into the tumor and enhance the effectiveness of immunotherapy. It also reduces immunosuppressive factors and enhances immune activation, to create a more favorable environment for immune cells to attack the tumor. Their combination leverages the strengths of both therapies to enhance anti-tumor effects and improve patient outcomes. This review discusses the vasculature-immunity crosstalk in the tumor microenvironment and summarizes the latest advances in combining anti-angiogenic therapy and immune checkpoint inhibitors to treat digestive system tumors.
Cutaneous leishmaniasis and iron metabolism: current insights and challenges
Authors: Assouab Aicha , Kihel Ayyoub , Rouahi Myriam , Larribau Mathilde , Karim Zoubida , Akarid Khadija
Published: December 2024

Leishmaniasis is a vector-borne parasitic infection induced by protozoa of the genus Leishmania. The disease spectrum ranges from skin lesions to visceral leishmaniasis, which is fatal if untreated. The cutaneous leishmaniasis is characterized by a clinical polymorphism of lesions with a broad range of severity ranging from a self-limited lesion to multiple disfiguring lesions stigmatizing the patient for life. Although iron is required for several process of Leishmania infection including survival, growth and virulence, the number of studies on host iron metabolism during this infection remains limited. Iron homeostasis in the body is finely regulated by hepcidin, a hyposideremic peptide highly expressed in the liver. In infectious contexts, hepcidin plays additionally an antimicrobial role, acting through various mechanisms such as retaining iron in tissues, modulating the immune response, and operating as a defensin against gram-negative bacteria. This review mainly summarizes the most important interconnections between iron metabolism, hepcidin and leishmaniasis. A deeper understanding of iron metabolism in this context could help in developing innovative treatment strategies that target the parasite while simultaneously reinforcing host defenses.
Integrating omics data and machine learning techniques for precision detection of oral squamous cell carcinoma: evaluating single biomarkers
Authors: Sun Yilan , Cheng Guozhen , Wei Dongliang , Luo Jiacheng , Liu Jiannan
Published: December 2024

Introduction

Early detection of oral squamous cell carcinoma (OSCC) is critical for improving clinical outcomes. Precision diagnostics integrating metabolomics and machine learning offer promising non-invasive solutions for identifying tumor-derived biomarkers.

Methods

We analyzed a multicenter public dataset comprising 61 OSCC patients and 61 healthy controls. Plasma metabolomics data were processed to extract 29 numerical and 47 ratio features. The Extra Trees (ET) algorithm was applied for feature selection, and the TabPFN model was used for classification and prediction.

Results

The model achieved an area under the curve (AUC) of 93% and an overall accuracy of 76.6% when using top-ranked individual biomarkers. Key metabolic features significantly differentiated OSCC patients from healthy controls, providing a detailed metabolic fingerprint of the disease.

Discussion

Our findings demonstrate the utility of integrating omics data with advanced machine learning techniques to develop accurate, non-invasive diagnostic tools for OSCC. The study highlights actionable metabolic signatures that have potential applications in personalized therapeutics and early intervention strategies.
Transcriptionally distinct B cell profiles in systemic immune tissues and peritoneal cavity of Atlantic salmon (Salmo salar) infected with salmonid alphavirus subtype 3
Authors: Jenberie Shiferaw , Sandve Simen Rød , To Thu-Hien , Kent Matthew Peter , Rimstad Espen , Jørgensen Jorunn B. , Jensen Ingvill
Published: December 2024

Teleost B cells producing neutralizing antibodies contribute to protection against salmonid alphavirus (SAV) infection, the etiological agent of pancreas disease, thereby reducing mortality and disease severity. Our previous studies show differences in B cell responses between the systemic immune tissues (head kidney (HK) and spleen) and the peritoneal cavity (PerC) after intraperitoneal SAV3 infection in Atlantic salmon (Salmo salar) where the response in PerC dominates at the late time points. By employing the same infection model, we aimed to further characterize these B cells. Immunophenotyping of teleost B cells is challenging due to limited availability of markers; however, RNA-seq opens an opportunity to explore differences in transcriptomic responses of these cells. Our analysis identified 334, 259 and 613 differentially expressed genes (DEGs) in Atlantic salmon IgM+IgD+ B cells from HK, spleen, and PerC, respectively, at 6 weeks post SAV3 infection. Of these, only 34 were common to all the three immune sites. Additionally, out of the top 100 genes with the highest fold change in expression, only four genes were common across B cells from the three sites. Functional enrichment analyses of DEGs using KEGG and GO databases demonstrated differences in enriched innate immune signaling and the cytokine-cytokine interaction pathways in B cells across the sites, with varying numbers of genes involved. Overall, these findings show the presence of transcriptionally distinct B cell subsets with innate immune functions in HK, spleen and PerC of SAV3-infected Atlantic salmon. Further, our data provide new insights into the immunoregulatory role of fish B cells through the differential expression of various cytokine ligands and receptors and will be a useful resource for further studies into B cell immune compartments.
Development and validation of a prediction model for the prognosis of renal cell carcinoma with liver metastases: a population-based cohort study
Authors: Wang Fei , Wang Pan , Wang Xihao , Lu Hengming , Han Yuchun , Wang Lianqu , Li Zhihui
Published: December 2024

Background

Current studies on the establishment of prognostic model for renal cell carcinoma (RCC) with liver metastases (LM) were scarce. This study aimed to develop nomograms to predict the prognosis of RCC with LM.

Methods

Patients diagnosed with RCC between 2010 and 2021 from the Surveillance, Epidemiology, and End Results (SEER) database were selected. The eXtreme Gradient Boosting (XGBoost) and Random Forest (RF) machine learning algorithms were used to screen for the most influential factors affecting prognosis, and the Venn diagram method was employed for further refinement. Subsequently, a nomogram related to brain metastases was constructed. The performance of the nomograms was evaluated through receiver operating characteristics (ROC) curves, calibration plots, C-index, time-dependent C-index, and decision curve analysis (DCA). Kaplan–Meier (K-M) survival curves were used to provide additional verification of the clinical efficacy of the nomogram.

Results

This research comprised 2,395 RCC patients with LM. The Venn diagram demonstrated that age, histological type, grade, AJCC T stage, AJCC N stage, surgery, chemotherapy, marital status, and lung metastasis were highly relevant variables to patients with LM. The AUC, C-index, calibration curves, and DCA curves showed excellent performance of the nomogram. Additionally, the prognostic nomogram accurately classified RCC with LM patients into low- and high-risk groups for mortality.

Conclusion

This study developed a novel nomogram to predict the prognostic factors of RCC with LM, providing a valuable reference for making accurate clinical decisions.
Case report: Malaria and hepatitis E coinfection—first experience with such imported entity in Serbia
Authors: Ranković Aleksandar , Cvetanović Maja , Miladinović Jelena , Ćosić Milica , Popović Dragonjić Lidija
Published: December 2024

Acute hepatitis E virus (HEV) and malaria are not rare infections in tropical countries; however, in the European continent, such imported entity has not been reported up to now. Herein, we report a 24-year-old male suffering from malaria and hepatitis E, who was admitted with acute hepatic failure dark colored urine, followed by coagulation and inflammation parameters increase. Blood smear analysis revealed the presence of Plasmodium falciparum, while serological tests revealed anti-HEV IgM antibodies. After the recommended antimalarial drugs and supportive therapy, the patient survived and was discharged disease-free. Conclusions: Following WHO guidelines for the treatment of severe malaria, full recovery in patient was achieved.
Probiotic effects on skin health: comprehensive visual analysis and perspectives
Authors: Deng Kexin , Fan Xiaofei , Yuan Zhigen , Li Dian
Published: December 2024

Background

Bacteria play a crucial role in maintaining the health of human skin. Research has demonstrated that probiotics present notable benefits for extraintestinal organs. Despite the extensive research on the impact of probiotics on skin health, there is a notable absence of regulatory frameworks governing their external application, with no approval from the FDA for any probiotic products for external use. The aim of this study is to offer a thorough summary of the research status in the field since 2000 and project future trends.

Method

The Web of Science Core Collection and SCI-Expanded index were selected for an extensive search of studies concerning the role of probiotics in skin health since 2000. A total of 1,306 publications were identified. Employing a double-blind method, two subsets of literature were scrutinized and subsequently combined for analysis. Using CiteSpace, this research explored key aspects such as primary countries, institutions, authors, journals, trending topics, research frontiers, and emerging patterns in research related to application of probiotic for skin health.

Result

This article included 709 research papers. The number of published papers has shown a rapid increase. The United States had the highest number of research papers (128), and Canada had the highest intermediate centrality (0.23). The University of California System emerged as the most prolific institution. Huang, Chun-Ming has published the most articles, and his research is at the forefront among those prolific authors. Twelve clusters were identified, with cluster #0 skin microbiota, #3 mechanisms, and #8 antimicrobial being the most recent. As for the hot topic, “diversity,” “health,” “skin microbiome,” “oxidative stress,” “microbiota,” and “antioxidants” have been at the forefront of the current field. The overall research trend has shifted from clinical trials to mechanistic exploration and from oral treatments to external applications, with the research level moving from general categories to specific strains.

Conclusion

This paper summarized and visualized academic achievements in the field of probiotic application for skin health using CiteSpace and VOSviewer, offering a systematic and comprehensive perspective, along with a longitudinal overview of this research field.
Functional assembly of surface microbiota of Ulva fasciata improves nutrient absorption efficiency and growth
Authors: Wang Han , Li De-hua , Wang Jing-ru , Wang Rong , Liang Chang-li , Hu Zhong , Liu Jun-he
Published: December 2024

Macroalgae growth depends on biologically available nitrogen, such as ammonium and nitrate, making nitrogen the most common growth-limiting factor for macroalgae. However, the role of surface microorganisms in promoting nitrogen transformation and improving nitrogen utilization by macroalgae remains unclear. In this study, 228 bacterial strains were isolated from the surface of U. fasciata, and high-throughput sequencing revealed significant shifts in the composition of surface bacterial communities under different nitrogen concentrations. Key bacterial families such as Rhodobacteraceae and Flavobacteriaceae were identified as essential for nitrogen cycling. Network analysis indicated that Rhodobacteraceae and Flavobacteriaceae were central nodes in microbial interactions. A synthetic microbial community (SynCom2), comprising four strains, significantly increased the biomass, nitrogen, and phosphorus acquisition of U. fasciata, with soluble sugar, protein, and Chlorophyll a level increasing by 23.9–49.2%. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis revealed that compared to untreated control plants, SynCom2 enhanced the expression of key genes associated with photosynthesis (rbcL, 1.04-fold), lipid biosynthesis (accD, 11.21-fold), and growth hormone precursor pathways (wrkY, 9.54-fold). These findings suggest that SynCom2 promotes U. fasciata growth by improving nutrient acquisition and activating growth-related genes.
Neuroimaging techniques, gene therapy, and gut microbiota: frontier advances and integrated applications in Alzheimer’s Disease research
Authors: Wang Haitao , Shi Chen , Jiang Ling , Liu Xiaozhu , Tang Rui , Tang Mingxi
Published: December 2024

Alzheimer’s Disease (AD) is a neurodegenerative disorder marked by cognitive decline, for which effective treatments remain elusive due to complex pathogenesis. Recent advances in neuroimaging, gene therapy, and gut microbiota research offer new insights and potential intervention strategies. Neuroimaging enables early detection and staging of AD through visualization of biomarkers, aiding diagnosis and tracking of disease progression. Gene therapy presents a promising approach for modifying AD-related genetic expressions, targeting amyloid and tau pathology, and potentially repairing neuronal damage. Furthermore, emerging evidence suggests that the gut microbiota influences AD pathology through the gut-brain axis, impacting inflammation, immune response, and amyloid metabolism. However, each of these technologies faces significant challenges, including concerns about safety, efficacy, and ethical considerations. This article reviews the applications, advantages, and limitations of neuroimaging, gene therapy, and gut microbiota research in AD, with a particular focus on their combined potential for early diagnosis, mechanistic insights, and therapeutic interventions. We propose an integrated approach that leverages these tools to provide a multi-dimensional framework for advancing AD diagnosis, treatment, and prevention.
EEG-based action anticipation in human-robot interaction: a comparative pilot study
Authors: Vieira Rodrigo , Moreno Plinio , Vourvopoulos Athanasios
Published: December 2024

As robots become integral to various sectors, improving human-robot collaboration is crucial, particularly in anticipating human actions to enhance safety and efficiency. Electroencephalographic (EEG) signals offer a promising solution, as they can detect brain activity preceding movement by over a second, enabling predictive capabilities in robots. This study explores how EEG can be used for action anticipation in human-robot interaction (HRI), leveraging its high temporal resolution and modern deep learning techniques. We evaluated multiple Deep Learning classification models on a motor imagery (MI) dataset, achieving up to 80.90% accuracy. These results were further validated in a pilot experiment, where actions were accurately predicted several hundred milliseconds before execution. This research demonstrates the potential of combining EEG with deep learning to enhance real-time collaborative tasks, paving the way for safer and more efficient human-robot interactions.
MorphoGlia, an interactive method to identify and map microglia morphologies, demonstrates differences in hippocampal subregions of an Alzheimer’s disease mouse model
Authors: Maya-Arteaga Juan Pablo , Martínez-Orozco Humberto , Diaz-Cintra Sofía
Published: December 2024

Microglia are dynamic central nervous system cells crucial for maintaining homeostasis and responding to neuroinflammation, as evidenced by their varied morphologies. Existing morphology analysis often fails to detect subtle variations within the full spectrum of microglial morphologies due to their reliance on predefined categories. Here, we present MorphoGlia, an interactive, user-friendly pipeline that objectively characterizes microglial morphologies. MorphoGlia employs a machine learning ensemble to select relevant morphological features of microglia cells, perform dimensionality reduction, cluster these features, and subsequently map the clustered cells back onto the tissue, providing a spatial context for the identified microglial morphologies. We applied this pipeline to compare the responses between saline solution (SS) and scopolamine (SCOP) groups in a SCOP-induced mouse model of Alzheimer’s disease, with a specific focus on the hippocampal subregions CA1 and Hilus. Next, we assessed microglial morphologies across four groups: SS-CA1, SCOP-CA1, SS-Hilus, and SCOP-Hilus. The results demonstrated that MorphoGlia effectively differentiated between SS and SCOP-treated groups, identifying distinct clusters of microglial morphologies commonly associated with pro-inflammatory states in the SCOP groups. Additionally, MorphoGlia enabled spatial mapping of these clusters, identifying the most affected hippocampal layers. This study highlights MorphoGlia’s capability to provide unbiased analysis and clustering of microglial morphological states, making it a valuable tool for exploring microglial heterogeneity and its implications for central nervous system pathologies.
Wide-spread brain alterations early after the onset of Crohn’s disease in children in remission—a pilot study
Authors: Filip Pavel , Vojtíšek Lubomír , Jičínská Anna Marie , Valenta Zdeněk , Horák Ondřej , Hrunka Matěj , Mangia Silvia , Michaeli Shalom , Jabandžiev Petr
Published: December 2024

Background

The research on possible cerebral involvement in Crohn’s disease (CD) has been largely marginalized and failed to capitalize on recent developments in magnetic resonance imaging (MRI).

Objective

This cross-sectional pilot study searches for eventual macrostructural and microstructural brain affection in CD in remission and early after the disease onset.

Methods

14 paediatric CD patients and 14 healthy controls underwent structural, diffusion weighted imaging and quantitative relaxation metrics acquisition, both conventional free precession and adiabatic rotating frame transverse and longitudinal relaxation time constants as markers of myelination, iron content and cellular loss.

Results

While no inter-group differences in cortical thickness and relaxation metrics were found, lower mean diffusivity and higher intracellular volume fraction were detected in CD patients over vast cortical regions essential for the regulation of the autonomous nervous system, sensorimotor processing, cognition and behavior, pointing to wide-spread cytotoxic oedema in the absence of demyelination, iron deposition or atrophy.

Conclusion

Although still requiring further validation in longitudinal projects enrolling larger numbers of subjects, this study provides an indication of wide-spread cortical oedema in CD patients very early after the disease onset and sets possible directions for further research.
Castleman disease variant of POEMS syndrome without M protein: a case report
Authors: Ji Min , Jin Shumin , Zang Shaolei , Li Peng , Lu Fei , Zhao Chuanli , Zhang Chunqing , Ji Chunyan , Ye Jingjing
Published: December 2024

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome is a paraneoplastic syndrome associated with an underlying plasma cell neoplasm. According to the current diagnostic criteria for POEMS syndrome, the presence of characteristic polyneuropathy and clonal plasma cell disorder are required for diagnosis. We report a case of a Castleman disease variant of POEMS syndrome without monoclonal protein (M protein) expression, which presented with polyneuropathy, organomegaly, endocrinopathy, skin lesions, and sclerotic bone lesions. The patient was treated with lenalidomide and dexamethasone (RD), after which her symptoms improved. The findings in this case suggest that the diagnostic criteria for POEMS syndrome might require reconsideration.
Expression and clinical significance of Numb and Notch-1 proteins between tissue of colon cancer and regional lymph node metastases
Authors: Ma Jingyou , Zhen Jinpeng , Yang Ningbao , Meng Changjuan , Lian Yanjun
Published: December 2024

Objective

To investigate the expression and clinical significance of Notch-1 and Numb protein in colon cancer tissues and regional lymph node metastases.

Methods

Immunohistochemical method was used to detect the expression of Notch-1 protein and Numb protein in 110 cases of colon cancer tissues, along with tumor adjacent tissues and 56 cases of MLN tissues, and to analyze its role in colon cancer and MLN tissue.

Results

Comparing colon cancer tissue or lymph node metastases with tumor adjacent tissue, the positive expression rate of Numb was significantly decreased, while the positive expression of Notch-1 was significantly increased in colon cancer tissue or lymph node metastases (both p<0.05). The expression of Notch-1 and Numb was correlated with the lymph node metastasis, TNM stage, and degree of differentiation (p<0.05). The expression between Numb and Notch-1 showed negative correlation in colon cancer tissues (r=−0.261, p<0.05). There was no relationship between the expression of Numb and Notch-1 protein in colon cancer and metastatic lymph node tissue (p>0.05).

Conclusion

Numb expression is decreased and Notch-1 expression is increased in colon cancer tissue and metastatic lymph node tissue, suggesting that the interaction between the two proteins may play a promote role in the development, invasion, and metastasis of colon cancer. There was no relationship between the expression of Numb and Notch-1 protein in colon cancer and metastatic lymph node tissue, suggesting that there is no obvious enhancement of the cancer cells; in the process of lymph node metastasis, the degree of malignant biological behavior remains relatively stable.
The role of N6-methyladenosine modification in tumor angiogenesis
Authors: Qin Lifei , Zeng Xinya , Qiu Xinze , Chen Xingmei , Liu Shiquan
Published: December 2024

Tumor angiogenesis is a characteristics of malignant cancer progression that facilitates cancer cell growth, diffusion and metastasis, and has an indispensable role in cancer development. N6-methyladenosine (m6A) is among the most prevalent internal modifications in eukaryotic RNAs, and has considerable influence on RNA metabolism, including its transcription, splicing, localization, translation, recognition, and degradation. The m6A modification is generated by m6A methyltransferases (“writers”), removed by m6A demethylases (“erasers”), and recognized by m6A-binding proteins (“readers”). There is accumulating evidence that abnormal m6A modification is involved in the pathogenesis of multiple diseases, including cancers, and promotes cancer occurrence, development, and progression through its considerable impact on oncoprotein expression. Furthermore, increasing studies have demonstrated that m6A modification can influence angiogenesis in cancers through multiple pathways to regulate malignant processes. In this review, we elaborate the role of m6A modification in tumor angiogenesis-related molecules and pathways in detail, providing insights into the interactions between m6A and tumor angiogenesis. Moreover, we describe how targeting m6A modification in combination with anti-angiogenesis drugs is expected to be a promising anti-tumor treatment strategy, with potential value for addressing the challenge of drug resistance.
Prognostic significance of CNNM4 in ovarian cancer: a comprehensive bioinformatics analysis
Authors: Wang Yiya
Published: December 2024

Background

Ovarian cancer (OV) is a common malignancy in the female reproductive system, characterized by poor prognosis and high recurrence rates. The discovery of dependable molecular markers is crucial for improving the timeliness of detection, diagnosis, and treatment, ultimately aiming to lower fatality rates. CNNM4 (cyclin and CBS domain divalent metal cation transport mediator 4), a member of the CNNM (Cyclin M) family, binds to PRL (prolactin) to regulate magnesium homeostasis and influence tumor cell proliferation. Although CNNM4 is implicated in various cancers, its role in OV remains unclear.

Methods

In vitro experiments assessed CNNM4 expression and its impact on the proliferation and migration of OV cells. Comparisons of TCGA and GTEx data were used to identify correlations between clinical features and outcomes. The role of CNNM4 in OV was further explored through comprehensive bioinformatics analyses.

Results

Elevated levels of CNNM4 expression were observed in OV cells and tissues, and were linked to a poor prognosis. CNNM4 could modulate the proliferation and migration of various OV cell lines, including IOSE-80, SKOV-3, and A2780. Through involvement in multiple signaling pathways, evidenced by GSVA and GSEA, CNNM4 was implicated in OV progression. CNNM4 positively regulated the infiltration level of Macrophages M2, T cells CD4 memory resting and NK cells resting, and had a negative regulation effect on NK cells activated and T cells gamma delta. Moreover, CNNM4 is related to drug sensitivity of OV. A prediction model based on CNNM4 expression and clinical symptoms was constructed to predict OV prognosis.

Conclusion

CNNM4 may affect the progression of OV and is associated with a poor prognosis. It has potential as a biomarker for predicting survival and as a target for therapeutic interventions in OV patients.
Enhancing cancer therapy: advanced nanovehicle delivery systems for oridonin
Authors: Su Yilin , Liu Lisha , Lin Chongyang , Deng Dashi , Li Yunfei , Huang Mou , Wang Yu , Ling Kangqiu , Wang Haobing , Chen Qiyu , Huang Guixiao
Published: December 2024

Oridonin (ORI), an ent-kaurane diterpenoid derived from Rabdosia rubescens (Hemsl.) H.Hara, serves as the primary bioactive component of this plant. It demonstrates a broad spectrum of therapeutic activities, including moderate to potent anticancer properties, alongside anti-inflammatory, antibacterial, antifibrotic, immunomodulatory, and neuromodulatory effects, thus influencing diverse biological processes. However, its clinical potential is significantly constrained by poor aqueous solubility and limited bioavailability. In alignment with the approach of developing drug candidates from natural compounds, various strategies, such as structural modification and nanocarrier systems, have been employed to address these challenges. This review provides an overview of ORI-based nano-delivery systems, emphasizing their potential to improve the clinical applicability of oridonin in oncology. Although some progress has been made in advancing ORI nano-delivery research, it remains insufficient for clinical implementation, necessitating further investigation.
Pharmacogenomic profiling of the South Korean population: Insights and implications for personalized medicine
Authors: Youn Mi Seon , Ahn Se Hwan , Kim Ju Han
Published: December 2024

Adverse drug reactions (ADRs) pose substantial public health issues, necessitating population-specific characterization due to variations in pharmacogenes. This study delineates the pharmacogenomic (PGx) landscape of the South Korean (SKR) population, focusing on 21 core pharmacogenes. Whole genome sequencing (WGS) was conducted on 396 individuals, including 99 healthy volunteers, 95 patients with chronic diseases, 81 with colon cancer, 81 with breast cancer, and 40 with gastric cancer, to identify genotype-specific drug dosing recommendations. Our detailed analysis, utilizing high-throughput genotyping (HTG) of CYP2D6 and comparative data from the 1,000 Genomes Project (1 KG) and the US National Marrow Donor Program (NMDP), revealed significant pharmacogenetic diversity in core pharmacogenes such as CYP2B6, CYP2C19, CYP4F2, NUDT15, and CYP2D6. Notably, intermediate metabolizer frequencies for CYP2B6 in SKR (3.28%) were comparable to Europeans (5.77%) and East Asians (5.36%) but significantly differed from other global populations (p < 0.01). For CYP2C19, 48.74% of SKR individuals were classified as intermediate metabolizers, with the *35 allele (2.02%) being unique to SKR, the allele not observed in other East Asian populations. Additionally, the high-risk *3 allele in CYP4F2 was significantly more frequent in SKR (34.72%) than in other East Asian populations (p < 0.01). NUDT15 poor metabolizers were found in 0.76% of SKR, aligning closely with other East Asians (1.59%), while TPMT poor metabolizers were predominantly observed in Europeans and Africans, with one case in SKR. We identified significant allele frequency differences in CYP2D6 variants rs1065852 and rs1135840. Among the 72 drugs analyzed, 93.43% (n = 370) of patients required dosage adjustments for at least one drug, with an average of 4.5 drugs per patient. Moreover, 31.31% (n = 124) required adjustments for more than five drugs. These findings reveal the substantial pharmacogenetic diversity of the SKR population within the global population, emphasizing the urgency of integrating population-specific PGx data into clinical practice to ensure safe and effective drug therapies. This comprehensive PGx profiling in SKR not only advances personalized medicine but also holds the potential to significantly improve healthcare outcomes on a broader scale.
Neuromuscular and balance adaptations following acute stretching exercise: a randomized control trial
Authors: Wang Bin , Wu Bin , Yang Yi , Cai Mengbiao , Li Shewang , Peng Hui
Published: December 2024

Purpose

This study aimed to examine the acute effects of static stretching (SS) and dynamic stretching (DS) on neuromuscular function and balance in recreationally active men.

Method

Sixty participants were randomly assigned to SS, DS, or no stretching (NS) groups. Before and after their respective stretching protocols, participants were assessed using the stork balance test (SBT), Y-balance test (YBT), T-change of direction test (CoD T-test), countermovement jump test (CMJT), squat jump test (SJT), and five-time jump test (FJT).

Results

Significant main effects of time were observed for the SBT, YBT, and CoD T-test. Significant interactions between time and group were found for the SBT, YBT, CoD T-test, and CMJT (P < 0.05). Compared to the NS group, the SS group showed significant improvement in the SBT (P < 0.05), while the DS group demonstrated significant improvements in the SBT, YBT (all directions), CoD T-test, CMJT, and SJT (P < 0.05). Post-training, the DS group showed greater improvements than the SS group in the YBT, CoD T-test, CMJT, and SJT (P < 0.05), with no significant differences in the SBT.

Conclusion

SS acutely improves static balance, while DS has a broader impact, enhancing both neuromuscular function and balance.
Role of inducible nitric oxide (iNOS) and nitrosative stress in regulating sex differences in secondary lymphedema
Authors: Campbell Adana-Christine , Kuonqui Kevin G. , Ashokan Gopika , Rubin Jonathan , Shin Jinyeon , Pollack Bracha L. , Roberts Arielle , Sarker Ananta , Park Hyeung Ju , Kataru Raghu P. , Barrio Andrea V. , Mehrara Babak J.
Published: December 2024

Secondary lymphedema is a common complication following surgical treatment of solid tumors. Although more prevalent in women due to higher breast cancer rates, men also develop lymphedema, often with more severe manifestations. Despite these differences in clinical presentation, the cellular mechanisms underlying sex differences are poorly understood. Previous studies have shown that inducible nitric oxide synthase (iNOS) expression by inflammatory cells is an important regulator of lymphatic pumping and leakiness in lymphedema and that lymphatic endothelial cells are highly sensitive to nitrosative stress. Based on this rationale, we used a mouse tail model of lymphedema to study the role of nitric oxide in sex-related differences in disease severity. Consistent with clinical findings, we found that male mice have significantly worse tail edema and higher rates of tail necrosis compared with female mice following tail skin/lymphatic excision (p = 0.001). Our findings correlated with increased tissue infiltration of iNOS + inflammatory cells, increased iNOS protein expression, and increased nitrosative stress in male mouse lymphedematous skin tissues (p < 0.05). Importantly, transgenic male mice lacking the iNOS gene (iNOS-KO) displayed markedly reduced swelling, inflammation, and tissue necrosis rates, whereas no differences were observed between wild-type and iNOS-KO female mice. Overall, our results indicate that iNOS-mediated nitric oxide production contributes to sex-based differences in secondary lymphedema severity, emphasizing the need to consider sex as a biological variable in lymphedema research.
Tracing nitrogen use efficiency of diverse Canadian spring wheat cultivars
Authors: Congreves Kate A. , Otchere Olivia , Hucl Pierre J.
Published: December 2024

Decades of wheat breeding have provided growers with numerous high-yielding options, but it is unknown if these yield improvements are likewise characterized with improved nitrogen use efficiency (NUE). Fertilizer nitrogen (N) is an ever-increasing expense, so improving NUE by reducing the requirement for N fertilizer without risking yield and quality is necessary. The goal of our research is to identify cultivars and associated traits that may improve NUE while maintaining productivity. We compared 25 spring wheat cultivars over a three-year period (2020, 2021, 2022) at two field sites differing in background soil N level for the ability to use fertilizer-N and allocate it to the grain. To do so, we employed the 15N stable isotope technique to trace the flow of fertilizer-N and determine the 15N recovery efficiency (15NRE). The 15NRE in the grain averaged 25.0% at the higher soil N site, and 15.5% at the lower soil N site. At the higher soil N site only, dwarfing alleles (Rht-B1b) were associated with greater 15NRE. Grain 15NRE was positively associated with yield, grain N content, and the 15N harvest index (15NHI) at the high soil N environment, but never at the low soil N environment. Our findings support the notion that the genetic development of high yielding semi-dwarf cultivars also translates into an improved ability to recover fertilizer-N—but this outcome is only expressed only under rich soil N conditions. Cultivars that simultaneously produced higher 15NRE and yields, grain N, or 15NHI differed by environment; possibly suggesting different mechanisms for improving crop NUE depending on background soil N level. Ultimately, cultivar-specific 15NRE information, including that presented here, will be useful breeders to design new crosses and approaches aimed at increasing NUE for spring wheat.
Improvement of maize drought tolerance by foliar application of zinc selenide quantum dots
Authors: Kanna Venkatesan Kishanth , Djanaguiraman Maduraimuthu , Senthil Alagarswamy , Moorthy Ponnuraj Sathya , Iyanar Krishnamoorthy , Veerappan Anbazhagan
Published: December 2024

Maize (Zea mays L.) is an important cereal crop grown in arid and semiarid regions of the world. During the reproductive phase, it is more frequently exposed to drought stress, resulting in lower grain yield due to oxidative damage. Selenium and zinc oxide nanoparticles possess inherent antioxidant properties that can alleviate drought-induced oxidative stress by the catalytic scavenging of reactive oxygen species, thereby protecting maize photosynthesis and grain yield. However, the effect of zinc selenide quantum dots (ZnSe QDs) under drought stress was not been quantified. Hence, the aim of this study was to quantify the (i) toxicity potential of ZnSe QDs and (ii) drought mitigation potential of ZnSe QDs by assessing the transpiration rate, photosynthetic rate, oxidant production, antioxidant enzyme activity and seed yield of maize under limited soil moisture levels. Toxicity experiments were carried out with 0 mg L−1 to 500 mg L−1 of ZnSe QDs on earthworms and azolla. The results showed that up to 20 mg L−1, the growth rates of earthworms and azolla were not affected. The dry-down experiment was conducted with three treatments: foliar spray of (i) water, (ii) ZnSe QDs (20 mg L−1), and (iii) combined zinc sulfate (10 mg L−1) and sodium selenate (10 mg L−1). ZnSe or Se applications under drying soil reduced the transpiration rate compared to water spray by partially closing the stomata. ZnSe application at 20 mg L−1 at the tasselling stage significantly increased the photosynthetic rate (25%) by increasing catalase (98%) and peroxidase (85%) enzyme activity and decreased the hydrogen peroxide (23%) content compared to water spray, indicating that premature leaf senescence was delayed under rainfed conditions. ZnSe spray increased seed yield (26%) over water spray by increasing the number of seeds cob-1 (42%). The study concluded that foliar application of ZnSe (20 mg L−1) could decrease drought-induced effects in maize.