bluuebunny/crossref_metadata_2025 huggingface dataset:
Exosomes in Ocular Health: Recent Insights into Pathology, Diagnostic Applications and Therapeutic Functions
Authors: Blanco-Agudín Noelia , Ye Suhui , González-Fernández Sara , Alcalde Ignacio , Merayo-Lloves Jesús , Quirós Luis M.
Published: January 2025

Exosomes are extracellular vesicles ranging from 30 to 150 nm in diameter that contain proteins, nucleic acids and other molecules. Produced by virtually all cell types, they travel throughout the body until they reach their target, where they can trigger a wide variety of effects by transferring the molecular cargo to recipient cells. In the context of ocular physiology, exosomes play a very important role in embryological development, the regulation of homeostasis and the immune system, which is crucial for normal vision. Consequently, in pathological situations, exosomes also undergo modifications in terms of quantity, composition and content, depending on the etiology of the disease. However, the mechanisms by which exosomes contribute to ocular pathology has not yet been studied in depth, and many questions remain unanswered. This review aims to summarize the most recent knowledge on the function of exosomes in the ocular system in healthy individuals and the role they play during pathological processes of a degenerative, infectious, neurodegenerative, vascular and inflammatory nature, such as keratoconus, keratitis, glaucoma, diabetic retinopathy and uveitis. Furthermore, given their unique characteristics, their potential as diagnostic biomarkers or therapeutic agents and their application in clinical ophthalmology are also explored, along with the main limitations that researchers face today in the field.
Identification of Hepatocellular Carcinoma Subtypes Based on Global Gene Expression Profiling to Predict the Prognosis and Potential Therapeutic Drugs
Authors: Zhang Cunzhen , Wang Jiyao , Jia Lin , Wen Qiang , Gao Na , Qiao Hailing
Published: January 2025

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous tumor, and distinguishing its subtypes holds significant value for diagnosis, treatment, and the prognosis. Methods: Unsupervised clustering analysis was conducted to classify HCC subtypes. Subtype signature genes were identified using LASSO, SVM, and logistic regression. Survival-related genes were identified using Cox regression, and their expression and function were validated via qPCR and gene interference. GO, KEGG, GSVA, and GSEA were used to determine enriched signaling pathways. ESTIMATE and CIBERSORT were used to calculate the stromal score, tumor purity, and immune cell infiltration. TIDE was employed to predict the patient response to immunotherapy. Finally, drug sensitivity was analyzed using the oncoPredict algorithm. Results: Two HCC subtypes with different gene expression profiles were identified, where subtype S1 exhibited a significantly shorter survival time. A subtype scoring formula and a nomogram were constructed, both of which showed an excellent predictive performance. COL11A1 and ACTL8 were identified as survival-related genes among the signature genes, and the downregulation of COL11A1 could suppress the invasion and migration of HepG2 cells. Subtype S1 was characterized by the upregulation of pathways related to collagen and the extracellular matrix, as well as downregulation associated with the xenobiotic metabolic process and fatty acid degradation. Subtype S1 showed higher stromal scores, immune scores, and ESTIMATE scores and infiltration of macrophages M0 and plasma cells, as well as lower tumor purity and infiltration of NK cells (resting/activated) and resting mast cells. Subtype S2 was more likely to benefit from immunotherapy. Subtype S1 appeared to be more sensitive to BMS-754807, JQ1, and Axitinib, while subtype S2 was more sensitive to SB505124, Pevonedistat, and Tamoxifen. Conclusions: HCC patients can be classified into two subtypes based on their gene expression profiles, which exhibit distinctions in terms of signaling pathways, the immune microenvironment, and drug sensitivity.
Venoarterial Membrane Oxygenation in Cardiogenic Shock Complicated from an Acute Myocardial Infarction: An Overview and Comprehensive Meta-Analysis
Authors: Sassani Kiarash , Syntila Styliani , Waechter Christian , Kreutz Julian , Markus Birgit , Patsalis Nikolaos , Schieffer Bernhard , Chatzis Georgios
Published: January 2025

Background: Cardiogenic shock remains a significant cause of mortality in patients with acute coronary syndrome, despite early interventions, such as coronary revascularization. Mechanical circulatory support devices, particularly venoarterial extracorporeal membrane oxygenation (VA-ECMO), are increasingly being utilized to address this issue. Limited randomized controlled trials (RCTs) exist to evaluate the efficacy of VA-ECMO in cardiogenic shock related to acute coronary syndrome. Methods: A meta-analysis was conducted to assess the effectiveness of VA-ECMO in adult patients with infarct-related cardiogenic shock. Trials were identified through database searches and selected based on specific inclusion criteria. The primary outcome was 30-day all-cause mortality, with secondary outcomes including bleeding and vascular complications. Results: A total of 24 studies met the inclusion criteria and were included in the meta-analysis, involving 4706 patients. The median age of the patients was 61.8 ± 4.1 years, with 76% of them being males. The analysis revealed that 30-day mortality rates for patients with cardiogenic shock receiving ECMO were still high, with a mortality of 63%. Vascular complications were identified as factors associated with a worse prognosis. Conclusions: The meta-analysis highlights the ongoing challenge of high mortality rates in cardiogenic shock patients despite the use of VA-ECMO. While VA-ECMO shows promise in providing circulatory support, further research is needed to explore ways to improve outcomes and reduce complications associated with the use of these devices. The complexity of patient management in cardiogenic shock cases underscores the need for a multidisciplinary approach to optimize treatment strategies and enhance patient outcomes.
Intra- and Interspecies Conjugal Transfer of Plasmids in Gram-Negative Bacteria
Authors: Savelieva Julia R. , Kondratieva Daria A. , Golikova Maria V.
Published: January 2025

Background/Objectives: Plasmid-mediated resistance is a significant mechanism that contributes to the gradual decrease in the efficacy of antibiotics from various classes, including carbapenems. The aim of this study is to investigate the frequency of transfer of carbapenemase-encoding plasmids from K. pneumoniae to E. coli and P. aeruginosa. Methods: Matings were performed on agar with subsequent isolation of transconjugant, recipient, and donor colonies. The frequency of conjugation (CF) and minimum inhibitory concentrations (MICs) of meropenem were determined for the PCR-confirmed transconjugants. A pharmacodynamic study was conducted using a hollow-fiber infection model on E. coli transconjugant in order to evaluate its viability in the presence of therapeutic concentrations of meropenem. Results: CF for K. pneumoniae-K. pneumoniae was similar to that for K. pneumoniae-E. coli and was higher the higher was meropenem MIC of the K. pneumoniae donor. The meropenem MICs for K. pneumoniae and E. coli transconjugants were higher (0.25–4 μg/mL) compared to recipients (0.03–0.06 μg/mL). P. aeruginosa did not acquire plasmids from K. pneumoniae. In pharmacodynamic experiments, an E. coli transconjugant with MIC of 2 mg/L within the “susceptibility range”, failed to respond to meropenem treatment. Conclusions: The frequency of conjugation between K. pneumoniae and E. coli falls within a similar range. A higher permissiveness of K. pneumoniae for plasmids from K. pneumoniae, i.e., within the same species, was observed. Conjugation did not occur between K. pneumoniae and P. aeruginosa. The transconjugants with meropenem MICs with borderline susceptibility may pose a potential threat to the efficacy of meropenem.
Clinical Characteristics and Prognostic Factors Affecting Clinical Outcomes in Cytomegalovirus Retinitis Following Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Zeng Qiaozhu , Yao Yuou , Hou Jing , Miao Heng
Published: January 2025

Background/Objectives: This study aimed to evaluate the clinical characteristics and identify the prognostic factors affecting visual outcomes, retinal detachment, and recurrence in cytomegalovirus retinitis (CMVR) patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: A retrospective analysis of 54 CMVR patients (84 eyes) who underwent allo-HSCT between 2015 and 2024 was conducted. Ophthalmologic and systemic evaluations were performed. The visual outcomes were classified as improvement, stabilization, and deterioration. Logistic regression and LASSO regression models were used to identify the prognostic factors. Results: Improved or stabilized visual outcomes were found in 22 eyes, while 62 eyes suffered from deterioration. Larger lesion areas were independently associated with poorer visual outcomes (OR 0.989, p = 0.002). Eight (9.5%) eyes had rhegmatogenous retinal detachment and thirteen (15.5%) eyes suffered from recurrence. Retinal detachment was significantly predicted by higher baseline aqueous CMV DNA load (OR 5.087, p = 0.026). Macula involvement (OR 5.322, p = 0.032) and more intravitreal injections (IVs) (OR 1.263, p = 0.008) were independent risk factors for recurrence. No systemic factors were found to be associated with the clinical outcome of eyes with CMVR. Conclusions: Ocular characteristics, rather than systemic factors, were more useful to predict the clinical outcome of eyes with CMVR. Routine ophthalmic screening and early intervention are essential to improving outcomes in this vulnerable population.
Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft Dysfunction
Authors: Basta Giuseppina , Babboni Serena , Pezzati Daniele , Del Turco Serena , Balzano Emanuele , Catalano Gabriele , Russo Lara , Tincani Giovanni , Carrai Paola , Petruccelli Stefania , Bronzoni Jessica , Martinelli Caterina , Palladino Simona , Trizzino Arianna , Petagna Lorenzo , Romagnoli Renato , Patrono Damiano , Biancofiore Giandomenico , Peris Adriano , Lazzeri Chiara , Ghinolfi Davide
Published: January 2025

Background/Objectives: The rising use of liver grafts from donation after circulatory death (DCD) has been enabled by advances in normothermic regional perfusion (NRP) and machine perfusion (MP) technologies. We aimed to identify predictive biomarkers in DCD grafts subjected to NRP, followed by randomization to either normothermic machine perfusion (NMP) or dual hypothermic oxygenated perfusion (D-HOPE). Methods: Among 57 DCD donors, 32 liver grafts were transplanted, and recipients were monitored for one week post-transplant. Biomarkers linked with oxidative stress, hepatic injury, mitochondrial dysfunction, inflammation, regeneration, and autophagy were measured during NRP, end-ischemic MP, and one week post-transplant. Results: Arginase-1 (ARG-1) levels were consistently higher in discarded grafts and in recipients who later developed early allograft dysfunction (EAD). Specifically, ARG-1 levels at the end of MP correlated with markers of hepatic injury. Receiver operating characteristic analysis indicated that ARG-1 at the end of MP had a good predictive accuracy for EAD (AUC = 0.713; p = 0.02). Lipid peroxidation (TBARS) elevated at the start of NRP, declined over time, with higher levels in D-HOPE than in NMP, suggesting a more oxidative environment in D-HOPE. Metabolites like flavin mononucleotide (FMN) and NADH exhibited significant disparities between perfusion types, due to differences in perfusate compositions. Inflammatory biomarkers rose during NRP and NMP but normalized post-transplantation. Regenerative markers, including osteopontin and hepatocyte growth factor, increased during NRP and NMP and normalized post-transplant. Conclusions: ARG-1 demonstrates strong potential as an early biomarker for assessing liver graft viability during perfusion, supporting timely and effective decision-making in transplantation.
Electrochemical Determination of Doxorubicin in the Presence of Dacarbazine Using MWCNTs/ZnO Nanocomposite Modified Disposable Screen-Printed Electrode
Authors: Tajik Somayeh , Beitollahi Hadi , Garkani Nejad Fariba , Dourandish Zahra
Published: January 2025

In the current work, the MWCNTs/ZnO nanocomposite was successfully synthesized using simple method. Then, FE-SEM, XRD, and EDX techniques were applied for morphological and structural characterization. Afterward, a sensitive voltammetric sensor based on modification of a screen-printed carbon electrode (SPCE) using MWCNTs/ZnO nanocomposite was developed for the determination of doxorubicin in the presence of dacarbazine. To evaluate the electrochemical response of the MWCNTs/ZnO/SPCE towards doxorubicin, cyclic voltammetry (CV) was applied. The MWCNTs/ZnO nanocomposite showed a significant synergistic effect on the electrochemical response of the electrode for the redox reaction of doxorubicin. Also, the MWCNTs/ZnO/SPCE demonstrated an enhanced sensing platform for the quantification of doxorubicin, obtaining a detection limit (LOD) of 0.002 µM and a sensitivity of 0.0897 µA/µM, as determined by differential pulse voltammetry (DPV) within a linear range from 0.007 to 150.0 µM. Also, the MWCNTs/ZnO nanocomposite-modified SPCE showed high electrochemical activities towards the oxidation of doxorubicin and dacarbazine with peak-potential separation of 345 mV, which is sufficient for doxorubicin determination in the presence of dacarbazine. Also, the MWCNTs/ZnO nanocomposite-modified SPCE presented reproducible and stable responses to determine doxorubicin. Finally, the developed platform demonstrated a successful performance for doxorubicin and dacarbazine determination in real samples, with recovery in the range of 97.1% to 104.0% and relative standard deviation (RSD) from 1.8% to 3.5%.
A Novel Aggregation-Induced Emission-Based Electrochemiluminescence Aptamer Sensor Utilizing Red-Emissive Sulfur Quantum Dots for Rapid and Sensitive Malathion Detection
Authors: Wu Yajun , Ma Dongxiao , Zhu Xiaoli , Xia Fangquan
Published: January 2025

Rapid, effective, and cost-effective methods for large-scale screening of pesticide residues in the environment and agricultural products are important for assessing potential environmental risks and safeguarding human health. Here, we constructed a novel aggregation-induced emission (AIE) electrochemical aptamer (Apt) sensor based on red-emissive sulfur quantum dots (SQDs), which aimed at the rapid screening and quantitative detection of malathion. SQDs were prepared using a two-step oxidation method with good electrochemiluminescence (ECL) optical properties. These SQDs were modified onto the electrode surface to serve as ECL luminophores. Subsequently, Apt was introduced and modified to form a double-helix structure with the complementary chain (cDNA). The ECL signal was reduced because the biomolecules had poor electrical conductivity and inefficient electron transfer. When the target malathion was added, the double helix structure was unraveled, the malathion Apt fell off the electrode surface, and the ECL signal was restored. The linear range of detection was 1.0 × 10−13–1.0 × 10−8 mol·L−1, and the detection limit was 0.219 fM. The successful preparation of the sensor not only develops the ECL optical properties of SQDs but also expands the application of SQDs in ECL sensing.
Automatic Generation of Precast Concrete Component Fabrication Drawings Based on BIM and Multi-Agent Reinforcement Learning
Authors: Zhang Chao , Zhou Xuhong , Xu Chengran , Wu Zhou , Liu Jiepeng , Qi Hongtuo
Published: January 2025

Fabrication drawings are essential for design evaluation, lean manufacturing, and quality detection of precast concrete (PC) components. Due to the complicated shape of PC components, the fabrication drawing needs to be customized to determine manufacturing dimensions and relevant assembly connections. However, the traditional manual drawing method is time-consuming, labor-intensive, and error-prone. This paper presents a BIM-based framework to automatically generate the readable drawing of PC components using building information modeling (BIM) and multi-agent reinforcement learning (MARL). Firstly, an automated generation method is developed to transform BIM model to view block. Secondly, a graph-based representation method is used to create the relationship between blocks, and a reward mechanism is established according to the drawing readability criterion. Subsequently, the block layout is modeled as a layout optimization problem, and the internal spacing and position of functional category blocks are regarded as agents. Finally, the agents collaborate and interact with the environment to find the optimal layout with the guidance of a reward mechanism. Two different algorithms are utilized to validate the efficiency of the proposed method (MADQN). The proposed framework is applied to PC stairs and a double-sided shear wall to demonstrate its practicability.
Seismic Performance and Flexural Capacity Analysis of Embedded Steel Plate Composite Shear Wall Structure with Fiber-Reinforced Concrete in the Plastic Hinge Zone
Authors: Li Junlong , He Guoqiang , Tian Jianbo
Published: January 2025

Due to its high axial bearing capacity and good ductility, the embedded steel plate composite shear wall structure has become one of the most widely used lateral force-resisting structural members in building construction. However, bending failure is prone to occur during strong earthquakes, and the single energy dissipation mechanism of the plastic hinge zone at the bottom leads to the concentration of local wall damage. To improve the embedded steel plate composite shear wall structure, the plastic hinge zone of the composite shear wall is replaced by fiber-reinforced concrete (FRC) and analyzed by ABAQUS finite element simulation analysis. Firstly, the structural model of the embedded steel plate composite shear wall structure with FRC in the plastic hinge zone is established and the accuracy of the model is verified. Secondly, the effects of steel ratio, longitudinal reinforcement ratio, and FRC strength on the bearing capacity of composite shear walls are analyzed by numerical simulation. Finally, a method for calculating the embedded steel plate composite shear wall structure with FRC in the plastic hinge zone is proposed. It is shown that the displacement and load curves and failure modes of the model are basically consistent with the experimental results, and the model has high accuracy. The axial compression ratio and FRC strength have a great influence on the bearing capacity of composite shear walls. The calculation formula of the normal section bending capacity of the embedded steel plate composite shear wall structure with FRC in the plastic hinge zone is proposed. The calculated values of the bending capacity are in good agreement with the simulated values, which can provide a reference for its engineering application.
The Patronization of Pluvial Flood Risk and Adaptation Among Tenant-Owned Housing Associations in Sweden
Authors: Hjerpe Mattias , Glaas Erik , Storbjörk Sofie
Published: January 2025

Pluvial floods are increasingly affecting urban areas worldwide. Despite growing media attention and clear owner responsibility for reducing climate-related risk for buildings in Swedish national adaptation policy, adaptation action remains slow. Understanding how different property owner categories view and act on flood risks is key for developing better incentive structures and support for accelerating adaptation action. While tenant-owned housing is a common form of housing tenure in Sweden, studies are lacking. This study enhances understanding of pluvial flood risk and adaptation views and actions by tenant-owned housing associations in two Swedish cities. It is based on assessments of 69 apartment buildings within eleven tenant-owned associations and semi-structured interviews with their eleven chairpersons. The study indicates that tenant-owned associations grossly underestimate their flood risks and responsibilities for climate adaptation, even though many buildings studied are at significant risk, and most associations have been impacted by floods, some severely and recurrently. The patronization of flood risk and responsibility for adaptation is attributed to several factors: underestimating risks and consequences, devaluing the benefit of one’s own adaptation actions, lacking knowledge about climate adaptation measures for buildings, and (overly) generous insurance terms. The findings confirm low adaptation action among housing associations, even those with recurring floods, which is concerning given the strong reliance on property-owner adaptation in national adaptation policy.
The Homeobox Transcription Factor NKX3.1 Displays an Oncogenic Role in Castration-Resistant Prostate Cancer Cells
Authors: Budreika Audris , Phoenix John T. , Kostlan Raymond J. , Deegan Carleen D. , Ferrari Marina G. , Young Kristen S. , Fanning Sean W. , Kregel Steven
Published: January 2025

Background/Objectives: Prostate cancer (PCa) is the second leading cause of cancer-related death in men. The increase in incidence rates of more advanced and aggressive forms of the disease year-to-year fuels urgency to find new therapeutic interventions and bolster already established ones. PCa is a uniquely targetable disease in that it is fueled by male hormones (androgens) that drive tumorigenesis via the androgen receptor or AR. Current standard-of-care therapies directly target AR and its aberrant signaling axis but resistance to these therapies commonly arises, and the mechanisms behind the onset of therapy-resistance are still elusive. Research has shown that even with resistant disease, AR remains the main driver of growth and survival of PCa, and AR target genes and cofactors may help mediate resistance to therapy. Here, we focused on a homeobox transcription factor that exhibits a close relationship with AR—NKX3.1. Though NKX3.1 is traditionally thought of as a tumor suppressor, it has been previously reported to promote cancer cell survival by cooperating with AR. The role of NKX3.1 as a tumor suppressor perhaps in early-stage disease also contradicts its profile as a diagnostic biomarker for advanced prostate cancer. Methods: We investigated the physical interaction between NKX3.1 and AR, a modulated NKX3.1 expression in prostate cancer cells via overexpression and knockdown and assayed subsequent viability and downstream target gene expression. Results: We find that the expression of NKX3.1 is maintained in advanced PCa, and it is often elevated because of aberrant AR activity. Transient knockdown experiments across various PCa cell line models reveal NKX3.1 expression is necessary for survival. Similarly, stable overexpression of NKX3.1 in PCa cell lines reveals an androgen insensitive phenotype, suggesting NKX3.1 is sufficient to promote growth in the absence of an AR ligand. Conclusions: Our work provides new insight into NKX3.1’s oncogenic influence on PCa and the molecular interplay of these transcription factors in models of late-stage prostate cancer.
The Clinical Utility of a Next-Generation Sequencing-Based Approach to Detecting Circulating HPV DNA in Patients with Advanced Anal Cancer
Authors: Bhamidipati Deepak , Johnson Jay R. , Lin Kangyu , Pelicano Helene , Eng Cathy , Huey Ryan , Wolff Robert A. , Halperin Daniel M. , Frumovitz Michael F. , Wistuba Ignacio I. , Duose Dzifa Y. , Mallampati Saradhi , Luthra Rajyalakshmi , Morris Van K.
Published: January 2025

Background: To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA). Methods: ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4 Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types. The HPV type, copy number (CN), and integration sites were determined using a bioinformatic pipeline. Results: A total of 77 plasma samples from 28 patients with HPV-related SCCA were retrospectively analyzed. HPV ctDNA was detected in 26 cases (93%) (including uncommon subtypes). The median HPV CN was higher in metastatic versus locally recurrent/unresectable SCCA (p = 0.043). Changes in the HPV CN were concordant with the radiographic response (p = 0.027). An integration event was detected in 23 patients (82%), with presumed episomal HPV DNA present in the remaining patients. Higher HPV integration (a mean of ≥1 integration across samples) was associated with a worse overall survival from the start of immunotherapy (13.6 months versus 36.0 months; p = 0.003). Conclusions: Using HPV-informed next-generation sequencing of the ctDNA, we found changes in the HPV CN correlated with the treatment response and that HPV integration detected in the ctDNA is an unfavorable prognostic biomarker.
A Review of Neoadjuvant Therapy for Localized and Locally Advanced Renal Cell Carcinoma
Authors: Qin Qian , Tachibana Isamu , Margulis Vitaly , Cadeddu Jeffrey A. , Zhang Tian
Published: January 2025

The introduction of vascular endothelial growth factor receptor-tyrosine kinases (VEGFR-TKIs) and immune checkpoint inhibitors (IOs) have drastically altered the treatment landscape for kidney cancer, with doublet combination immunotherapy (IO/IO or IO/VEGFR-TKI) now set as the standard front-line treatment for advanced renal cell carcinoma (RCC). However, the roles of VEGFR-TKIs and IOs in the neoadjuvant setting for locoregional/locally advanced RCC remain undefined, where the goals may be primary tumor downsizing/downstaging and potentially eradicating micrometastatic disease. This review will examine VEGFR-TKI monotherapy, IO monotherapy, and VEGFR-TKI/IO combination regimens in a preoperative setting with a focus on the efficacy, toxicity, surgical, and long-term implications.
Urogenital Cancer Epidemiology in Poland (1980–2020): A Narrative Review
Authors: Wnętrzak Iwona , Didkowska Joanna , Sosnowski Roman , Czajkowski Mateusz , Sigorski Dawid , Małkiewicz Bartosz , Marczyński Piotr , Jaskulski Jarosław , Kania Piotr , Ostrowski Adam , Sieczych Artur , Kade Grzegorz , Purpurowicz Piotr , Szempliński Stanisław , Nowakowski Robert
Published: January 2025

Despite advances in prophylaxis, early diagnosis, and treatment, urogenital cancers represent a significant challenge to public health in Poland due to their relatively high prevalence and mortality rates. This narrative review aims to explore contemporary evidence on the epidemiology of urogenital cancers in Poland, such as prostate cancer, bladder cancer, kidney cancer, testicular cancer, and penile cancer, focusing on current and historical status and trends in the broader context of healthcare delivery. The literature consistently indicates that urogenital cancer continues to be a significant contributor to cancer incidence and mortality rates in Poland. Although the body of evidence is expanding, its quantity remains limited, primarily attributable to the scarcity of top-notch epidemiological investigations targeting particular forms of cancer, such as testicular and penile cancers, which are characterized by sporadic occurrences.
The Role of the Tumor Microenvironment in T-Cell Redirecting Therapies of Large B-Cell Lymphoma: Lessons Learned from CAR-T to Bispecific Antibodies
Authors: Lepik Kirill V. , Markelov Vladislav V.
Published: January 2025

T-cell redirecting therapies, which include chimeric antigen receptor T-cells (CAR-Ts) and bispecific antibodies (BSAs), have revolutionized the treatment of relapsed\refractory large B-cell lymphoma (LBCL). Expanding clinical experience with these advanced therapies shows the potential for the optimization of their use with combination or consolidation strategies, which necessitates the prognostic stratification of patients. While traditional clinical prognostic factors identified in the era of chemotherapy are characterized by limited value, the tumor microenvironment (TME) is becoming a new prognostic cluster. We examine how the heterogeneity of LBCL, characterized by variations in tumor parameters and differences in TME immune cell composition, immune checkpoint expression, and cytokine milieu, correlates with both positive responses and resistance to treatment. While classical parameters such as histological subtype, cell of origin, and target antigen expression lack proven prognostic value for T-cell redirecting therapies, the density and functional state of tumor-infiltrating lymphocytes, tumor-associated macrophages, and immune checkpoint molecules are shown to be critical determinants of therapeutic success, particularly in CAR-T therapy. We identify several gaps in the current knowledge and suggest that the insights gained from CAR-T experience could be instrumental in refining BSA applications. This report also highlights limitations in the current knowledge, as TME data derive from a limited number of registrational trials with varying methodologies, complicating cross-study comparisons and often focusing on immediate response metrics rather than long-term outcomes. By dissecting the complex interactions within the TME, this review aims to identify new prognostic factors and targets, ultimately fostering more effective and tailored treatment strategies for LBCL patients.
Unlocking the Therapeutic Potential of Algae-Derived Compounds in Hematological Malignancies
Authors: Vujović Tamara , Paradžik Tina , Babić Brčić Sanja , Piva Roberto
Published: January 2025

Algae are a rich source of bioactive compounds that have a wide range of beneficial effects on human health and can show significant potential in the treatment of hematological malignancies such as leukemia, lymphoma, and multiple myeloma. These diseases often pose a therapeutic challenge despite recent advances in treatment (e.g., the use of immunomodulatory drugs, proteasome inhibitors, CD38 monoclonal antibodies, stem cell transplant, and targeted therapy). A considerable number of patients experience relapses or resistance to the applied therapies. Algal compounds, alone or in combination with chemotherapy or other more advanced therapies, have exhibited antitumor and immunomodulatory effects in preclinical studies that may improve disease outcomes. These include the ability to induce apoptosis, inhibit tumor growth, and improve immune responses. However, most of these studies are conducted in vitro, often without in vivo validation or clinical trials. This paper summarizes the current evidence on the in vitro effects of algae extracts and isolated compounds on leukemia, lymphoma, and myeloma cell lines. In addition, we address the current advances in the application of algae-derived compounds as targeted drug carriers and their synergistic potential against hematologic malignancies.
Determining ED90 of Flumazenil for Selective Respiratory Distress Improvement Using Remimazolam During Endoscopic Submucosal Dissection of Gastric Neoplasms: A Prospective Study
Authors: Kim Hyun Il , Jung Da Hyun , Lee Sung Jin , Kim Namo , Kim Seung Hyun , Ji Yu Jun , Byon Hyo-Jin , Shin Sung Kwan
Published: January 2025

Background: Patients undergoing endoscopic submucosal dissection under monitored anesthesia care (MAC) with remimazolam may develop respiratory distress during the procedure. In these cases, low doses of flumazenil improved respiratory distress without completely reversing sedation, which is a novel phenomenon. This study aimed to explore the ED90 of flumazenil to selectively improve respiratory distress in patients with MAC treated with remimazolam. Methods: Flumazenil dose determination followed a biased-coin up-and-down design. Starting with a dose of 5 mcg, if respiratory distress improved, the biased-coin method was used to give the same dose in the next patient with a probability of 8/9, and a decreased dose of 5 mcg in the next patient with a probability of 1/9. Any improvement in respiratory distress within 30 s of flumazenil administration was recorded. After the procedure, patients were asked whether they had any memory recall during the procedure. Centered isotonic regression was used to determine the ED90 of flumazenil. Results: Sixty patients were included in the study. The estimated ED90 was 76.72 mcg (95% CI: 68.07–102.62). Memory recall occurred in two of thirteen patients (15%) near the ED90 dose range (75 mcg and 80 mcg). None of the patients developed major postoperative complications (bleeding, perforation, or aspiration) within the 2-day postoperative period. Conclusions: This study determined that the ED90 of flumazenil for effectively alleviating respiratory distress in patients undergoing MAC with remimazolam was 76.7 mcg, without reversing consciousness. These findings provide valuable guidance for the care of patients undergoing sedation.
Lymphangioleiomyomatosis and Pregnancy—Do We Have All the Answers for a Woman Who Desires to Conceive?—Literature Review
Authors: Constantin Ancuta-Alina , Gaburici Andreea Dumitrita , Malaescu Andreea Nicoleta , Iorga Ana-Luiza , Dragosloveanu Christiana Diana Maria , Poenaru Mircea-Octavian , Gorecki Gabriel-Petre , Amza Mihaela , Georgescu Mihai-Teodor , Dragomir Ramona-Elena , Popescu Mihai , Sima Romina-Marina
Published: January 2025

Lymphangioleiomyomatosis (LAM) is a rare, progressive, and poor-prognosis systemic disorder that primarily affects women of reproductive age, with a higher prevalence among individuals of Caucasian origin. However, there are limited reliable data on the prevalence of LAM during pregnancy. The fulminant respiratory clinical presentation that often includes progressive dyspnea on exertion, cough, or hemoptysis, frequently complicated by pneumothorax, and the increased risk of spontaneous abortion due to increased estrogen and progesterone production during gestation, are arguments that most often make the diagnosed woman avoid pregnancy. Elevated levels of vascular endothelial growth factor D (VEGF-D), decline in respiratory function, and radiological findings are sufficient arguments in favor of the diagnosis in the pregnant woman. Sirolimus, an mTOR inhibitor, has demonstrated effectiveness in slowing the decline of lung function. Although sirolimus treatment is often recommended to be discontinued before conception due to the increased risk of fetal growth restriction, maintaining a dose level of <5 pcg/mL, with serum drug levels of 3–5 pcg/L, has been considered safe. Given the potential risks, individualized decisions about pregnancy are advised for patients with LAM. For those who choose to proceed, close monitoring by a multidisciplinary team is essential to manage complications effectively. Ongoing research aims to provide clearer guidance to optimize outcomes for both mother and child.
Correction: Alaei et al. Therapeutic Potential of Targeting the Cytochrome P450 Enzymes Using Lopinavir/Ritonavir in Colorectal Cancer: A Study in Monolayers, Spheroids and In Vivo Models. Cancers 2023, 15, 3939
Authors: Alaei Maryam , Nazari Seyedeh Elnaz , Pourali Ghazaleh , Asadnia AliReza , Moetamani-Ahmadi Mehrdad , Fiuji Hamid , Tanzadehpanah Hamid , Asgharzadeh Fereshteh , Babaei Fatemeh , Khojasteh-Leylakoohi Fatemeh , Gataa Ibrahim Saeed , Kiani Mohammad Ali , Ferns Gordon A. , Lam Alfred King-yin , Hassanian Seyed Mahdi , Khazaei Majid , Giovannetti Elisa , Avan Amir
Published: January 2025

Error in Figure and Text [...]
Risk Factors for Treatment Toxicity and High Side Effect Burden Among Breast Cancer Survivors: A Retrospective Chart Review
Authors: Alkhaifi Muna , Zhang Elwyn , Peera Malika , Jerzak Katarzyna , Czarnota Gregory , Eisen Andrea , Roberts Amanda , Carmona-Gonzalez Carlos Amir , Pezo Rosanna , Gandhi Sonal
Published: January 2025

Background/Objectives: This study describes the sequelae, side effects, and toxicities experienced by Canadian breast cancer survivors at a breast cancer survivorship clinic at a tertiary academic cancer centre and identifies potential risk factors which may be associated with increased side effect burden. Methods: A retrospective chart review was performed of adult patients treated at the Sunnybrook Breast Cancer Survivorship Clinic from 6 July 2022, to 30 September 2023 (n = 435). Results: Most patients (72.6%) reported at least one side effect impacting their quality of life, and a smaller majority (55.4%) reported two or more side effects. The most common symptoms experienced were anxiety (29.4%), chronic pain (23.9%), hot flashes (21.4%), and fear of recurrence (19.8%). Older age was strongly correlated with a lower likelihood of experiencing greater side effect burden (p < 0.01). Patients who underwent chemotherapy were significantly more likely to experience higher side effect burden than patients who did not. Current smokers were more likely than nonsmokers or past smokers to have a higher burden, for both physical (p < 0.01) and psychological side effects (p < 0.01). The multivariate analysis demonstrated that younger age was strongly associated with greater side effect burden, higher likelihood of psychological and physical symptoms, and greater likelihood of requiring close follow-up. Conclusions: The results highlight the need for survivorship resources tailored to survivors under the age of 55 and the importance of referring smokers to smoking cessation programs. Additional research is required to explore the significant reluctance among patients regarding discharge. Future studies should examine the acute needs of younger breast cancer survivors and investigate the impact of smoking and treatment modalities on the side effect burden.
Predictive Value of the Loss of pRb Expression in the Malignant Transformation Risk of Oral Potentially Malignant Disorders: A Systematic Review and Meta-Analysis
Authors: López-Ansio María , Ramos-García Pablo , González-Moles Miguel Ángel
Published: January 2025

Objective: The aim of this systematic review and meta-analysis was to qualitatively and quantitatively evaluate the current evidence on the significance of the loss of early stages of oral carcinogenesis in lesions diagnosed according to clinical and/or histopathological criteria and their evolution to oral cancer. Materials and Methods: We searched MEDLINE (through PubMed), Embase, Scopus and Web of Science for primary-level studies published before November 2024, designed as prospective or retrospective longitudinal cohorts, and not restricted by language or publication date. The risk of bias was critically assessed using the QUIPS tool. Meta-analyses, heterogeneity exploration, sensitivity and small-study effect analyses were conducted. Results: The inclusion criteria were met by six primary-level studies, which recruited 330 patients with OPMDs with follow-up data. The loss of pRb expression, assessed through immunohistochemistry, was significantly associated with a higher malignant transformation risk of OPMDs (RR = 1.92, 95%CI = 1.25–2.94, p = 0.003). The leukoplakia subgroup retained this significant association (p = 0.006), being the OPMD where the loss of pRb expression showed the best predictive value for malignant transformation (RR = 2.00, 95%CI = 1.22–3.29). Regarding the immunohistochemical technique and scoring methods, better performance and results were achieved by applying a cutoff point > 10% pRb-positive cells with nuclear staining (RR = 2.10, 95%CI = 1.30–3.38, 95%CI = 0.002). Conclussion: The present systematic review and meta-analysis supports that the loss of expression of the tumor suppressor pRb, assessed through immunohistochemistry, is a predictor of the malignant transformation risk of oral leukoplakias. Future studies are needed in other OPMDs following the recommendations provided based on current evidence gaps.
Impact of Physical Exercise on Breast Cancer-Related Lymphedema and Non-Invasive Measurement Tools: A Systematic Review
Authors: Arias-Crespo Marta , García-Fernández Rubén , Calvo-Ayuso Natalia , Martín-Vázquez Cristian , de Fátima da Silva Vieira Martins Maria , Quiroga-Sánchez Enedina
Published: January 2025

Background/Objectives: Breast cancer-related lymphedema (BCRL) is a chronic disease with lasting effects, making it one of the most feared sequelae of breast cancer with significant personal and social impacts. Therapeutic exercises play a fundamental role in its treatment. This systematic review aims to provide the most up-to-date findings on the impact of physical exercise on the management of BCRL. Methods: Following the PRISMA statement guidelines, searches were conducted in the Web of Science, Scopus, and Science Direct databases. Results: Sixteen studies published between 2019 and 2024 were analyzed in detail. The combination of strength and aerobic exercises emerged as an effective strategy for both the treatment and prevention of lymphedema, also highlighting the innovative potential of virtual reality. Conclusions: It is essential to emphasize tailoring exercise programs to each patient individually. Additionally, the promising role of thermography as a non-invasive and safe tool for evaluating lymphedema progress is underscored.
Role of Thyroid Hormone in Neurodegenerative Disorders of Older People
Authors: Mooradian Arshag D. , Haas Michael J.
Published: January 2025

Thyroid dysfunction is associated with a number of neuropsychiatric manifestations. Cognitive decline is a common feature of hypothyroidism and clinical or subclinical hyperthyroidism. In addition, there is a significant association between thyroid hormone (TH) levels and the degree of cognitive impairment in Parkinson’s disease (PD). The pathophysiology of TH-related neurodegeneration include changes in the blood–brain barrier, increased cellular stress, altered processing of β-amyloid precursor protein and the effect of TH on neuronal cell viability. The neurotoxicity of TH is partially mediated by the thyroid hormone responsive protein (THRP). This protein is 83% homologous to mouse c-Abl-interacting protein-2 (Abi2), a c-Abl-modulating protein with tumor suppressor activity. In cell cultures, increasing THRP expression either with TH treatment or exogenously through transfecting neuronal or PC 12 cells causes cell necrosis. The expression of exogenous THRP in other cells such as the colonic epithelial cell line Caco-2 and the glial cell line U251 has no effect on cell viability. The effect of THRP on cell viability is not modulated by c-Abl tyrosine kinase. The causal relationship between specific biochemical perturbations in cerebral tissue and thyroid dysfunction remains to be elucidated.
The Link Between Venous and Arterial Thrombosis: Is There a Role for Endothelial Dysfunction?
Authors: Donadini Marco Paolo , Calcaterra Francesca , Romualdi Erica , Ciceri Roberta , Cancellara Assunta , Lodigiani Corrado , Bacci Monica , Della Bella Silvia , Ageno Walter , Mavilio Domenico
Published: January 2025

Venous thromboembolism (VTE) and arterial thrombosis (AT) are distinct yet closely related pathological processes. While traditionally considered separate entities, accumulating evidence suggests that they share common risk factors, such as inflammation and endothelial dysfunction (ED). This review explores the parallels and differences between venous and arterial thrombosis, with particular attention to the role of unprovoked VTE and its potential links to atherosclerosis and systemic inflammation. A key focus is the role of ED, which is emerging as a critical factor in thrombogenesis across both the venous and arterial systems. We examine the current methods for clinically detecting ED, including the use of biomarkers and advanced imaging techniques. Additionally, we discuss novel research avenues, such as the potential of endothelial colony-forming cells and other innovative methodologies, to further unravel the complex mechanisms of thrombosis. Finally, we propose future clinical scenarios where targeting endothelial health could pave the way for more effective prevention and treatment strategies in thrombosis management.
Nutritional Vulnerability of Displaced Persons: A Study of Food Security and Access in Kumba Municipality, Cameroon
Authors: Metuge Kevin N. , Tambe Betrand A. , Djikeng Fabrice Tonfack , Achidi Aduni Ufuan , Chipili Given , Mbhenyane Xikombiso G.
Published: January 2025

Concerns about global food insecurity have been growing, particularly in low- and middle-income countries. This study aimed to assess the determinants of food security among internally displaced persons (IDPs)—people who have been forced to flee their homes due to conflict, natural disasters, or other crises—and their children under five, as well as the influence on their nutritional status. Using random sampling, the caregivers of IDPs and children under five in households were included in the study. The caregivers were interviewed using a validated structured questionnaire, while nutritional assessments of both children and adults were conducted through anthropometric and clinical evaluation methods. The findings revealed a high prevalence of food insecurity, with 97.6% of IDP households experiencing some degree of insecurity. Additionally, 28.3% of the surveyed households had high dietary diversity. Among the children, 50.6% were stunted, over a third were underweight, and 15.8% were wasted, indicating severe nutritional deficiencies. Among adults, 28.4% were overweight or obese, while a significant number were underweight. Multiple linear regression analysis showed that the caregivers’ monthly salary and the average amount spent on food were associated with a decrease in food insecurity. Conversely, large household sizes and coping strategies employed to mitigate food insecurity were linked to increased food insecurity. In conclusion, the study highlights a high prevalence of food insecurity among IDP households, forcing families to adopt coping strategies, mainly through dietary modifications. This, in turn, contributes to low dietary diversity and poor nutritional status, with children suffering from underweight, wasting, and stunting. These findings underscore the urgent need for comprehensive interventions, including the distribution of food vouchers, cash transfers, food banks, and support for home gardening and small-scale farming, as well as education on meal rationing, meal planning, and family planning services. Addressing the root causes of food insecurity—namely low household income and large family sizes—can improve access to nutritious food and ensure the health and well-being of IDPs. Furthermore, addressing food insecurity within this vulnerable group is critical to the broader goals of planetary health, as it highlights the intersection of human health, social equity, and environmental sustainability. By promoting sustainable food systems and supporting vulnerable populations, these interventions can contribute to the resilience of both communities and eco-systems in the face of ongoing global challenges.
Chemometric Approaches for Sustainable Pharmaceutical Analysis Using Liquid Chromatography
Authors: Aboushady Dina , Samir Liza , Masoud Alaa , Elshoura Yasmin , Mohamed Abdelgawad , Hanafi Rasha S. , El Deeb Sami
Published: January 2025

Chemometrics, which applies mathematical and statistical methods to aid in experimental design, data analysis, and process optimization, is gaining more importance. It plays an important role in enhancing the sustainability of analytical methods when integrated with green analytical chemistry. Applying chemometrics to liquid chromatographic methods can speed up the analytical method, saving time, energy, and solvent consumption. This would be reflected by a low energy footprint and environmental impact. This review discusses the application of chemometric methods like multivariant data analysis, design of experiments, retention time prediction, and peak deconvolution in green liquid chromatographic analysis of pharmaceuticals. The review highlights the impact of chemometric approaches on the global push for sustainable practices. The integration of chemometrics into sustainable chromatographic analysis will continue to revolutionize the field leading to better performance of analytical methods.