bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Aging and Nerve Growth Factor on Neuropeptide Expression and Cholinergic Innervation of the Rat Basolateral Amygdala
Authors: Pereira Pedro A. , Tavares Marta , Laires Miguel , Mota Bárbara , Madeira Maria Dulce , Paula-Barbosa Manuel M. , Cardoso Armando
Published: February 2024

The basolateral amygdala (BLA) contains interneurons that express neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), both of which are involved in the regulation of functions and behaviors that undergo deterioration with aging. There is considerable evidence that, in some brain areas, the expression of NPY and VIP might be modulated by acetylcholine. Importantly, the BLA is one of the brain regions that has one of the densest cholinergic innervations, which arise mainly from the basal forebrain cholinergic neurons. These cholinergic neurons depend on nerve growth factor (NGF) for their survival, connectivity, and function. Thus, in this study, we sought to determine if aging alters the densities of NPY- and VIP-positive neurons and cholinergic varicosities in the BLA and, in the affirmative, if those changes might rely on insufficient trophic support provided by NGF. The number of NPY-positive neurons was significantly reduced in aged rats, whereas the number of VIP-immunoreactive neurons was unaltered. The decreased NPY expression was fully reversed by the infusion of NGF in the lateral ventricle. The density of cholinergic varicosities was similar in adult and old rats. On the other hand, the density of cholinergic varicosities is significantly higher in old rats treated with NGF than in adult and old rats. Our results indicate a dissimilar resistance of different populations of BLA interneurons to aging. Furthermore, the present data also show that the BLA cholinergic innervation is particularly resistant to aging effects. Finally, our results also show that the reduced NPY expression in the BLA of aged rats can be related to changes in the NGF neurotrophic support.
Probiotics Supplementation during Pregnancy: Can They Exert Potential Beneficial Effects against Adverse Pregnancy Outcomes beyond Gestational Diabetes Mellitus?
Authors: Poulios Efthymios , Pavlidou Eleni , Papadopoulou Sousana K. , Rempetsioti Kalliopi , Migdanis Athanasios , Mentzelou Maria , Chatzidimitriou Maria , Migdanis Ioannis , Androutsos Odysseas , Giaginis Constantinos
Published: February 2024

Background: Probiotics, as supplements or food ingredients, are considered to exert promising healthy effects when administered in adequate quantity. Probiotics’ healthy effects are related with the prevention of many diseases, as well as decreasing symptom severity. Currently, the most available data concerning their potential health effects are associated with metabolic disorders, including gestational diabetes mellitus. There is also clinical evidence supporting that they may exert beneficial effects against diverse adverse pregnancy outcomes. The purpose of the current narrative study is to extensively review and analyze the current existing clinical studies concerning the probable positive impacts of probiotics supplementation during pregnancy as a protective agent against adverse pregnancy outcomes beyond gestational diabetes mellitus. Methods: a comprehensive and thorough literature search was conducted in the most precise scientific databases, such as PubMed, Scopus, and Web of Sciences, utilizing efficient, representative, and appropriate keywords. Results: in the last few years, recent research has been conducted concerning the potential beneficial effects against several adverse pregnancy outcomes such as lipid metabolism dysregulation, gestational hypertensive disorders, preterm birth, excessive gestational weight gain, caesarean risk section, vaginal microbiota impairment, mental health disturbances, and others. Conclusion: up to the present day, there is only preliminary clinical data and not conclusive results for probiotics’ healthy effects during pregnancy, and it remains questionable whether they could be used as supplementary treatment against adverse pregnancy outcomes beyond gestational diabetes mellitus.
Senescence Promotes the Recovery of Stemness among Cancer Cells via Reprograming
Authors: Wang Di , Liu Lingbo
Published: February 2024

Both the senescence of cancer cells and the maintenance of cancer stem cells seem to be mutually exclusive because senescence is considered a physiological mechanism that effectively suppresses tumor growth. Recent studies have revealed common signaling pathways between cellular senescence and the maintenance of stemness in cancer cells, thus challenging the conventional understanding of this process. Although the links between these processes have not yet been fully elucidated, emerging evidence indicates that senescent cancer cells can undergo reprograming to recover stemness. Herein, we provide a comprehensive overview of the close correlation between senescence and stemness reprograming in cancer cells, with a particular focus on the mechanisms by which senescent cancer cells recover their stemness in various tumor systems.
Hacking the Lipidome: New Ferroptosis Strategies in Cancer Therapy
Authors: Varynskyi Borys , Schick Joel A.
Published: February 2024

The concept of redirecting metabolic pathways in cancer cells for therapeutic purposes has become a prominent theme in recent research. Now, with the advent of ferroptosis, a new chink in the armor has evolved that allows for repurposing of ferroptosis-sensitive lipids in order to trigger cell death. This review presents the historical context of lipidomic and metabolic alterations in cancer cells associated with ferroptosis sensitization. The main proferroptotic genes and pathways are identified as therapeutic targets for increasing susceptibility to ferroptosis. In this review, a particular emphasis is given to pathways in cancer cells such as de novo lipogenesis, which has been described as a potential target for ferroptosis sensitization. Additionally, we propose a connection between ketolysis inhibition and sensitivity to ferroptosis as a new vulnerability in cancer cells. The main proferroptotic genes and pathways have been identified as therapeutic targets for increasing susceptibility to ferroptosis. Proferroptotic metabolic pathways and vulnerable points, along with suggested agonists or antagonists, are also discussed. Finally, general therapeutic strategies for ferroptosis sensitization based on the manipulation of the lipidome in ferroptosis-resistant cancer cell lines are proposed.
Long Intergenic Non-Coding RNAs of Human Chromosome 18: Focus on Cancers
Authors: Ershov Pavel V. , Yablokov Evgeniy O. , Mezentsev Yuri V. , Ivanov Alexis S.
Published: February 2024

Malignant neoplasms are characterized by high molecular heterogeneity due to multilevel deregulation of gene expression and cellular functions. It is known that non-coding RNAs, including long intergenic non-coding RNAs (lincRNAs), can play significant roles in cancer biology. The current review focuses on a systematical analysis of genomic, transcriptomic, epigenomic, interactomic, and literature data on 65 lincRNAs of human chromosome 18 in the context of pan-cancer studies. The entire group of lincRNAs can be conditionally divided into 4 subgroups depending on experimental evidence on direct or indirect involvement in cancers and the biological associations with cancers, which we found during the data-mining process: the most studied (5 lincRNAs), moderately or poorly studied (11 lincRNAs), and understudied (31 lincRNAs). For the remaining 18 lincRNAs, data for analysis were fragmentary or missing. Among the key findings were the following: Of the lincRNAs of human chromosome 18, 40% have tissue-specific expression patterns, 22% of lincRNAs are known to have gene fusions, 40% of lincRNAs are prone to gene amplifications and/or deletions in cancers at a frequency greater than 3%, and 23% of lincRNAs are differentially expressed across cancer types, whereas 7% have subtype-specific expression patterns. LincRNAs’ interactomes consist of ‘master’ microRNAs and 47 proteins (including cancer-associated proteins and microRNAs) that can interact with 3 or more lincRNAs. Functional enrichment analysis of a set of highly co-expressed genes retrieved for 17 lincRNAs in different cancer types indicated the potential associations of these lincRNAs with cellular signaling pathways. Six lincRNAs encoded small open-reading frame (smORF) proteins with emerging roles in cancers, and microRNAs as well as proteins with known functions in molecular carcinogenesis can bind to coding regions of smORFs. We identified seven transcriptomic signatures with potential prognostic value, consisting of two to seven different lincRNAs only. Taken together, the literature, biomedical, and molecular biology data analyzed indicated that only five of all lincRNAs of human chromosome 18 are cancer-associated, while eleven other lincRNAs have the tendency to be associated with cancers.
Recent Advances in the Diagnosis and Treatment of Brain Tumors
Authors: Delaidelli Alberto , Moiraghi Alessandro
Published: February 2024

Brain tumors represent some of the most aggressive malignancies [...]
Can Brain Volume-Driven Characteristic Features Predict the Response of Alzheimer’s Patients to Repetitive Transcranial Magnetic Stimulation? A Pilot Study
Authors: Saha Chandan , Figley Chase R. , Lithgow Brian , Fitzgerald Paul B. , Koski Lisa , Mansouri Behzad , Anssari Neda , Wang Xikui , Moussavi Zahra
Published: February 2024

This study is a post-hoc examination of baseline MRI data from a clinical trial investigating the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for patients with mild–moderate Alzheimer’s disease (AD). Herein, we investigated whether the analysis of baseline MRI data could predict the response of patients to rTMS treatment. Whole-brain T1-weighted MRI scans of 75 participants collected at baseline were analyzed. The analyses were run on the gray matter (GM) and white matter (WM) of the left and right dorsolateral prefrontal cortex (DLPFC), as that was the rTMS application site. The primary outcome measure was the Alzheimer’s disease assessment scale—cognitive subscale (ADAS-Cog). The response to treatment was determined based on ADAS-Cog scores and secondary outcome measures. The analysis of covariance showed that responders to active treatment had a significantly lower baseline GM volume in the right DLPFC and a higher GM asymmetry index in the DLPFC region compared to those in non-responders. Logistic regression with a repeated five-fold cross-validated analysis using the MRI-driven features of the initial 75 participants provided a mean accuracy of 0.69 and an area under the receiver operating characteristic curve of 0.74 for separating responders and non-responders. The results suggest that GM volume or asymmetry in the target area of active rTMS treatment (DLPFC region in this study) may be a weak predictor of rTMS treatment efficacy. These results need more data to draw more robust conclusions.
Brain Swelling versus Infarct Size: A Problematizing Review
Authors: Simard J. Marc , Wilhelmy Bradley , Tsymbalyuk Natalya , Shim Bosung , Stokum Jesse A. , Evans Madison , Gaur Anandita , Tosun Cigdem , Keledjian Kaspar , Ciryam Prajwal , Serra Riccardo , Gerzanich Volodymyr
Published: February 2024

In human stroke, brain swelling is an important predictor of neurological outcome and mortality, yet treatments to reduce or prevent brain swelling are extremely limited, due in part to an inadequate understanding of mechanisms. In preclinical studies on cerebroprotection in animal models of stroke, historically, the focus has been on reducing infarct size, and in most studies, a reduction in infarct size has been associated with a corresponding reduction in brain swelling. Unfortunately, such findings on brain swelling have little translational value for treating brain swelling in patients with stroke. This is because, in humans, brain swelling usually becomes evident, either symptomatically or radiologically, days after the infarct size has stabilized, requiring that the prevention or treatment of brain swelling target mechanism(s) that are independent of a reduction in infarct size. In this problematizing review, we highlight the often-neglected concept that brain edema and brain swelling are not simply secondary, correlative phenomena of stroke but distinct pathological entities with unique molecular and cellular mechanisms that are worthy of direct targeting. We outline the advances in approaches for the study of brain swelling that are independent of a reduction in infarct size. Although straightforward, the approaches reviewed in this study have important translational relevance for identifying novel treatment targets for post-ischemic brain swelling.
The Complexity of Reading Revealed by a Study with Healthy Older Adults
Authors: Pegoraro Sara , Facchin Alessio , Luchesa Francesca , Rolandi Elena , Guaita Antonio , Arduino Lisa S. , Daini Roberta
Published: February 2024

Aging, even when healthy, involves changes in cognitive functioning that can gradually affect the everyday activities and well-being of older people. Reading, which requires the integrity of several functions and their integration, is important to maintaining high cognitive and emotional stimulation over time. Our study aimed to investigate whether reading ability declines with aging. To explore also why reading would decline, we explored the changes in the performance of visual and attention tasks. A group of 58 neurologically healthy older people aged from 65 to 75 underwent neuropsychological assessment to investigate their global cognitive functioning, reading skills, crowding, and attention components. We found a decline in reading abilities as a function of aging (β = 0.34, p < 0.05). We did not find an increase in crowding or difficulties in visual acuity. Furthermore, we found no decline with age in tasks of simple reaction times, visuospatial attention, and other single components of attention. Interestingly, we instead found a worsening with age in the Symbol Digit Modalities Test (β = −0.26, p < 0.05), involving attention, working memory, and processing speed, which explains part of the reading decline. Our results suggest that task complexity is a fundamental aspect to account for aging changes.
Research on Determinants Affecting Users’ Impulsive Purchase Intention in Live Streaming from the Perspective of Perceived Live Streamers’ Ability
Authors: Chen Jun , Luo Junying , Zhou Tian
Published: February 2024

As an innovative marketing pattern, live-streaming e-commerce supplies advantages over traditional e-commerce in stimulating impulsive purchases. This study developed a theoretical model that examines how perceived live streamers’ abilities (perceived live interaction ability and perceived linguistic persuasion ability) affect impulsive purchase intention based on interaction theory, affective distance theory, trust theory, and Aristotle’s rhetorical appeals. We conducted empirical research through a survey questionnaire to verify the effectiveness of the model. A total of 330 valid samples were gathered from live-streaming users, and partial least squares–structural equation modeling (PLS-SEM) was employed for data analysis. The results indicate that perceived live interaction ability, encompassing responsiveness, entertainment, and personalization, significantly impacts affective distance. Among the four dimensions of perceived linguistic persuasion ability, emotional contagion significantly influences affective distance, whereas expertise, logic, and morality significantly affect cognitive trust. Both affective distance and cognitive trust promote consumers’ impulsive purchases through affective trust. Our research findings provide theoretical and practical recommendations for live-streaming platforms and merchants engaged in live marketing.
Self-Concept Clarity and Loneliness among College Students: The Chain-Mediating Effect of Fear of Negative Evaluation and Self-Disclosure
Authors: Pang Tingting , Wang Haiying , Zhang Xinran , Zhang Xianbing
Published: February 2024

Self-concept clarity is considered a crucial indicator of mental health. Although several studies have examined the correlation between self-concept clarity and loneliness, few studies have investigated the underlying mechanism. Based on the evolutionary theory of loneliness and social penetration theory, this cross-sectional study focused on cognitive and behavioral factors in interpersonal communication situations, aiming to explore the relationship between self-concept clarity and loneliness as well as its internal mechanism. An online questionnaire survey comprised 1145 college students in China to assess their self-concept clarity, fear of negative evaluation, self-disclosure, and loneliness. After controlling for demographic variables, the results showed that self-concept clarity was not only able to directly and negatively predict loneliness but also indirectly predict loneliness through the independent mediating effects of fear of negative evaluation and self-disclosure, as well as the chain-mediating effect of fear of negative evaluation to self-disclosure. This study provides important implications for cognitive and behavioral intervention strategies to alleviate people’s loneliness and improve their mental health.
Defect Detection in Grouting Sleeve Grouting Material by Piezoelectric Wave Method
Authors: Qiao Qiyun , Wang Xiuyu , Liu Wenchao , Yang Hongchun
Published: February 2024

The construction defects in grouting sleeves can jeopardize the safety of precast reinforced concrete structures. Thus, efficient and accurate defect detection is critical in engineering construction. In this paper, a defect detection method based on piezoelectric wave theory was proposed. Two piezoelectric ceramics were arranged within the grouting sleeve. One piezoelectric ceramic was affixed on the top of the steel bar, while the other was embedded in the grouting material, serving as the driver and sensor, respectively. The compactness defects, air cavity defects, steel anchoring defects, and water–binder ratio defects were set in the grouting sleeves, and the trends in time domain signals and signal evaluation indicators based on the wavelet packet total energy value (WPTEV) of different specimens were investigated. Based on the WPTEV, the evaluation index (EI) was proposed. In addition, the effect of the grouting material’s age on the piezoelectric wave signal was verified. Furthermore, the influence of grouting material defects on signals was simulated in ABAQUS, and the time domain signals and wavelet packet energy of sensor signals for specimens with varying defect dimensions were evaluated. The results showed that: (1) The defects in the grouting materials reduced the stress waves propagated through the grouting materials, resulting in a decrease in attenuation and an increasing trend in the signal; (2) The peak-to-peak values of piezoelectric ceramic sensors and the WPTEV of the signal increased with the degree of defects, and the WPTEV was more pronounced. For specimen M68, the WPTEV was 3.3 times that of the healthy specimen, however, the peak-to-peak value was only 2.3 times that of the healthy specimen; (3) The degree of defects was accurately determined by the defect evaluation index (EI) based on the WPTEV; (4) The signal was significantly attenuated with the increase in the age of the grouting material, especially in the first three days, and finally the signal achieved a stable value; (5) The numerical simulation indicated that the defects in the length and thickness of the air cavity in the grouting material were efficiently detected by the proposed piezoelectric arrangement in this study.
Dynamic Responses of Single-Layer Reticulated Shells under Oblique Impact Loading
Authors: Li Pengcheng , Chen Guohan , Lu Hongxin , Ke Lu , Wang Hao , Jian Bin
Published: February 2024

This paper focuses on the response of reticulated shell structures under oblique impact loads, with a departure from the traditional emphasis on vertical impact loads. These structures are typically utilised in large-span spaces such as iconic buildings and large venues. The study begins by establishing a numerical simulation method for reticulated shell structures subjected to oblique impact loads, which is then validated against existing experimental results. Building on this verified method, the research delves into the effects of varying impactor mass, velocity, and initial kinetic energy on the reticulated shell structure under oblique impacts, as well as the influence of different oblique impact angles. The study extensively examines the failure modes of the structure, node displacements in the structure, and variations in member stress under different impactor parameters. It further investigates how these parameters influence the maximum impact bearing capacity, impact duration, energy dissipation capability, and response forms of the structures, analyzing the reasons behind these effects. The findings offer valuable insights for further research and practical engineering design of reticulated shell structures.
Simulation Analysis of the Structure of an Integrated Modular House by Flat Pack Based on the Elastic–Plastic Contact Theory and Experimental Study of Its Corner Fitting Joint
Authors: Zhang Ao , Zheng Lei , Mei Yong , Zhang Jun , Chen Shengyun , Wang Xueming , Ma He , Yu Ruodan
Published: February 2024

Based on the elastic–plastic contact theory, elastic–plastic contact finite element models for the integrated modular house by flat pack are established. The structural stress and displacement distributions are obtained. An experimental test is conducted to study the performance of the corner fitting joint of the house. The finite element analysis and experimental test comprehensively demonstrated the safety and reliability of the house structure. The results show that the most unfavorable stress point of the house is located at the corner fitting joint. When the end plate connection holes of the corner column seal are designed with through holes and internal screw holes, respectively, the fastening effect of bolting between the corner fitting and corner column using the internal screw hole is better. The reliability of the repeated disassembly and assembly of the house is verified via multiple loading–unloading simulation cycle experiments of the corner fitting joint. The results of the study provide technical support and a reference basis for the optimal design and ensuring the service performance of the integrated modular house by flat pack.
The Role of Systematic Lymphadenectomy in Low-Grade Serous Ovarian Cancer: A Systematic Review and Meta-Analysis
Authors: Montero-Macías Rosa , Segura-Sampedro Juan José , Rigolet Pascal , Lecuru Fabrice , Craus-Miguel Andrea , Castillo-Tuñón Juan Manuel
Published: February 2024

Objective: To evaluate the role of systematic lymphadenectomy in low-grade serous ovarian cancer (LGSOC) and determine its impact on clinical outcomes in overall survival (OS) and disease-free survival (DFS) terms. Methods: A comprehensive, systematic computer literature search on PubMed was performed using the following Medical Subject Headings (MeSH) terms: “low grade serous ovarian cancer” AND/OR “lymphadenectomy” AND/OR “staging” AND/OR “ovarian cancer” AND/OR “cytoreduction”. Separate searches were performed with MeSH terms on MEDLINE and EMBASE to extract all the relevant literature available. We included only patients with histologically confirmed LGSOC. Results: Three studies were considered in the quantitative analysis. Systematic lymphadenectomy in LGSOC failed to provide a significant OS or PFS benefit in LGSOC when compared to no lymphadenectomy in the entire (all the stages) population (for OS: HR = 1.15, 95% CI [0.42, 3.18] I2 = 84% and for PFS: HR = 1.46, 95% CI [0.63, 3.41], I2 = 71%), nor did it in the subtype analysis regarding FIGO stages. For FIGO early-stage I-II LGSOC, the DFS data were pooled (HR = 1.48, 95% CI [0.58, 3.78], I2 = 75%). In patients with advanced-stage (FIGO II–IV), we also failed to prove survival benefit for lymphadenectomy in OS (HR = 1.74, 95% CI [0.87, 3.48], I2 = 11%) or DFS (HR = 1.48, 95% CI [0.58, 3.78], I2 = 75%) compared to no lymphadenectomy. Conclusion: More extensive prospective research is mandatory to understand the real impact of lymphadenectomy on survival in LGSOC. The existing literature does not provide strong evidence.
Melatonin and Its Role in the Epithelial-to-Mesenchymal Transition (EMT) in Cancer
Authors: Martínez-Campa Carlos , Álvarez-García Virginia , Alonso-González Carolina , González Alicia , Cos Samuel
Published: February 2024

The epithelial-to-mesenchymal transition (EMT) is a cell-biological program that occurs during the progression of several physiological processes and that can also take place during pathological situations such as carcinogenesis. The EMT program consists of the sequential activation of a number of intracellular signaling pathways aimed at driving epithelial cells toward the acquisition of a series of intermediate phenotypic states arrayed along the epithelial–mesenchymal axis. These phenotypic features include changes in the motility, conformation, polarity and functionality of cancer cells, ultimately leading cells to stemness, increased invasiveness, chemo- and radioresistance and the formation of cancer metastasis. Amongst the different existing types of the EMT, type 3 is directly involved in carcinogenesis. A type 3 EMT occurs in neoplastic cells that have previously acquired genetic and epigenetic alterations, specifically affecting genes involved in promoting clonal outgrowth and invasion. Markers such as E-cadherin; N-cadherin; vimentin; and transcription factors (TFs) like Twist, Snail and ZEB are considered key molecules in the transition. The EMT process is also regulated by microRNA expression. Many miRNAs have been reported to repress EMT-TFs. Thus, Snail 1 is repressed by miR-29, miR-30a and miR-34a; miR-200b downregulates Slug; and ZEB1 and ZEB2 are repressed by miR-200 and miR-205, respectively. Occasionally, some microRNA target genes act downstream of the EMT master TFs; thus, Twist1 upregulates the levels of miR-10b. Melatonin is an endogenously produced hormone released mainly by the pineal gland. It is widely accepted that melatonin exerts oncostatic actions in a large variety of tumors, inhibiting the initiation, progression and invasion phases of tumorigenesis. The molecular mechanisms underlying these inhibitory actions are complex and involve a great number of processes. In this review, we will focus our attention on the ability of melatonin to regulate some key EMT-related markers, transcription factors and micro-RNAs, summarizing the multiple ways by which this hormone can regulate the EMT. Since melatonin has no known toxic side effects and is also known to help overcome drug resistance, it is a good candidate to be considered as an adjuvant drug to conventional cancer therapies.
Promises of Protein Kinase Inhibitors in Recalcitrant Small-Cell Lung Cancer: Recent Scenario and Future Possibilities
Authors: Tiwari Aniket , Kumari Beauty , Nandagopal Srividhya , Mishra Amit , Shukla Kamla Kant , Kumar Ashok , Dutt Naveen , Ahirwar Dinesh Kumar
Published: February 2024

SCLC is refractory to conventional therapies; targeted therapies and immunological checkpoint inhibitor (ICI) molecules have prolonged survival only marginally. In addition, ICIs help only a subgroup of SCLC patients. Different types of kinases play pivotal roles in therapeutics-driven cellular functions. Therefore, there is a significant need to understand the roles of kinases in regulating therapeutic responses, acknowledge the existing knowledge gaps, and discuss future directions for improved therapeutics for recalcitrant SCLC. Here, we extensively review the effect of dysregulated kinases in SCLC. We further discuss the pharmacological inhibitors of kinases used in targeted therapies for recalcitrant SCLC. We also describe the role of kinases in the ICI-mediated activation of antitumor immune responses. Finally, we summarize the clinical trials evaluating the potential of kinase inhibitors and ICIs. This review overviews dysregulated kinases in SCLC and summarizes their potential as targeted therapeutic agents. We also discuss their clinical efficacy in enhancing anticancer responses mediated by ICIs.
Prospective Assessment of Fluorine-18-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) for Early Identification of Checkpoint-Inhibitor-Induced Pseudoprogression
Authors: Homburg Sif , Christensen Charlotte Birk , Pedersen Magnus , Sørensen Simon Grund , Donia Marco , Svane Inge Marie , Hendel Helle Westergren , Ellebaek Eva
Published: February 2024

The activity of immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma is often monitored using fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans. However, distinguishing disease progression (PD) from pseudoprogression (PsPD), where increased FDG uptake might reflect immune cell activity rather than tumor growth, remains a challenge. This prospective study compared the efficacy of dual-time point (DTP) FDG-PET/CT with modified response criteria (PERCIMT) in differentiating PsPD from PD. From July 2017–January 2021, 41 patients suspected to have PsPD on an evaluation scan were prospectively included (29 evaluable). A subsequent DTP FDG-PET/CT scan was conducted within 14 days, followed by a confirmatory FDG-PET/CT scan. Additionally, PERCIMT were applied. DTP FDG-PET/CT identified 24% with PsPD and 76% with PD. Applying PERCIMT criteria, 69% showed PsPD, while 31% had PD. On follow-up, 10 patients (34%) demonstrated confirmed PsPD, while 19 (66%) exhibited PD. The sensitivity and specificity of DTP FDG-PET/CT were 20% and 74%, respectively, and for PERCIMT this was 80% and 37%, respectively. Our findings suggest limited efficacy of DTP FDG-PET/CT in distinguishing PsPD from PD in ICI-treated patients with metastatic melanoma. The use of PERCIMT could complement clinical assessment and be incorporated in multidisciplinary team conferences for enhanced decision-making.
The Disproportionate Rise in Pancreatic Cancer in Younger Women Is Due to a Rise in Adenocarcinoma and Not Neuroendocrine Tumors: A Nationwide Time-Trend Analysis Using 2001–2018 United States Cancer Statistics Databases
Authors: Jiang Yi , Abboud Yazan , Liang Jeff , Larson Brent , Osipov Arsen , Gong Jun , Hendifar Andrew E. , Atkins Katelyn , Liu Quin , Nissen Nicholas N. , Li Debiao , Pandol Stephen J. , Lo Simon K. , Gaddam Srinivas
Published: February 2024

In previous studies, a significant increase in the incidence of pancreatic cancer among younger women compared to men in the United States was noted. However, the specific histopathologic characteristics were not delineated. This population-based study aimed to assess whether this disproportionate rise in pancreatic cancer in younger women was contributed by pancreatic ductal adenocarcinoma (PDAC) or pancreatic neuroendocrine tumors (PanNET). The United States Cancer Statistics (USCS) database was used to identify patients with pancreatic cancer between 2001 and 2018. The results showed that, in younger adults, the incidence of PDAC has increased in women [average annual percentage change (AAPC) = 0.62%], while it has remained stable in men (AAPC = −0.09%). The PDAC incidence rate among women increased at a greater rate compared to men with a statistically significant difference in AAPC (p < 0.001), with neither identical nor parallel trends. In contrast, cases of PanNET did not demonstrate a statistically significant sex-specific AAPC difference. In conclusion, this study demonstrated that the dramatic increase in the incidence rate of PDAC explains the disproportionate rise in pancreatic cancer incidence in younger women. This prompts further prospective studies to investigate the underlying reasons for these sex-specific disparities in PDAC.
Impact of Pre-Diagnostic Risk Factors on Short- and Long-Term Ovarian Cancer Survival Trajectories: A Longitudinal Observational Study
Authors: Kim Shana J. , Tworoger Shelley S. , Rosen Barry P. , McLaughlin John R. , Risch Harvey A. , Narod Steven A. , Kotsopoulos Joanne
Published: February 2024

Tumor- and treatment-related factors are established predictors of ovarian cancer survival. New studies suggest a differential impact of exposures on ovarian cancer survival trajectories (i.e., rapidly fatal to long-term disease). This study examined the impact of pre-diagnostic risk factors on short- and long-term ovarian cancer survival trajectories in the Canadian context. This population-based longitudinal observational study included women diagnosed with invasive epithelial ovarian cancer from 1995 to 2004 in Ontario. Data were obtained from medical records, interviews, and the provincial cancer registry. Extended Cox proportional hazard models estimated the association between risk factors and all-cause and ovarian cancer-specific mortality by survival time intervals (<3 years (i.e., short-term survival), 3 to <6 years, 6 to <10 years, and ≥10 years (i.e., long-term survival)). Among 1421 women, histology, stage, and residual disease were the most important predictors of all-cause mortality in all survival trajectories, particularly for short-term survival. Reproductive and lifestyle factors did not strongly impact short-term overall survival but were associated with long-term overall survival. As such, among long-term survivors, history of breastfeeding significantly decreased the risk of all-cause mortality (HR 0.65; 95% CI 0.46, 0.93; p < 0.05), whereas smoking history (HR 1.75; 95% CI 1.27, 2.40; p < 0.05) and obesity (HR 1.81; 95% CI 1.24, 2.65; p < 0.05) significantly increased the risk of all-cause mortality. The findings were consistent with ovarian cancer-specific mortality. These findings suggest that pre-diagnostic exposures differentially influence survival time following a diagnosis of ovarian cancer.
Circular STAG2 RNA Modulates Bladder Cancer Progression via miR-145-5p/TAGLN2 and Is Considered as a Biomarker for Recurrence
Authors: Du Chris , Waltzer Wayne C. , Wilusz Jeremy E. , Spaliviero Massimiliano , Darras Frank , Romanov Victor
Published: February 2024

The current study aimed to elucidate the regulatory mechanisms of the circRNA hsa_circ_0139697 (circSTAG2(16–25)) in BCa and to consider the opportunity of using circSTAG2(16–25) isolated from BCa patient urine as a marker for disease development prediction. The selection of this circRNA was determined by the special role of its parental gene STAG2 in BCa biology. The circRNA hsa_circ_0139697 was chosen from 25 STAG2 circRNAs due to its differential expression in the urine of BCa patients and healthy volunteers. Higher levels of circSTAG2(16–25) were detected in urine samples obtained from patients with recurrent tumors. A higher expression of circSTAG2(16–25) was also detected in more tumorigenic BCa cell lines. The overexpression of circSTAG2(16–25) in BCa cells induced the elevation of proliferation, motility, and invasion. To study the mechanisms of circSTAG2(16–25) activity, we confirmed that circSTAG2(16–25) can bind miR-145-5p in vitro as was predicted by bioinformatic search. miR-145-5p was shown to suppress some genes that promoted BCa progression. One of these genes, TAGLN2, encodes the protein Transgelin 2, which plays a role in BCa cell motility and invasion. Therefore, the possible mechanism of action of circSTAG2(16–25) could be sponging the tumor suppressor miR-145-5p, which results in activation of TAGLN2. In addition, circSTAG2(16–25) might be considered as a potential biomarker for recurrence prediction.
Venetoclax Initiation in Chronic Lymphocytic Leukemia: International Insights and Innovative Approaches for Optimal Patient Care
Authors: Anderson Mary Ann , Walewska Renata , Hackett Fidelma , Kater Arnon P. , Montegaard Josie , O’Brien Susan , Seymour John F. , Smith Matthew , Stilgenbauer Stephan , Whitechurch Ashley , Brown Jennifer R.
Published: February 2024

Venetoclax, a highly selective, oral B-cell lymphoma 2 inhibitor, provides a robust targeted-therapy option for the treatment of chronic lymphocytic leukemia (CLL), including patients with high-risk del(17p)/mutated-TP53 and immunoglobulin heavy variable region unmutated CLL and those refractory to chemoimmunotherapy across all age groups. Due to the potent pro-apoptotic effect of venetoclax, treatment initiation carries a risk of tumor lysis syndrome (TLS). Prompt and appropriate management is needed to limit clinical TLS, which may entail serious adverse events and death. Venetoclax ramp-up involves gradual, stepwise increases in daily venetoclax dosing from 20 mg to 400 mg (target dose) over 5 weeks; adherence to on-label scheduling provides a tumor debulking phase, reducing the risk of TLS. The key components of safe venetoclax therapy involve assessment (radiographic evaluation and baseline blood chemistry), preparation (adequate hydration), and initiation (blood chemistry monitoring). In addition to summarizing the evidence for venetoclax’s efficacy and safety, this review uses hypothetical patient scenarios based on risk level for TLS (high, medium, low) to share the authors’ clinical experience with venetoclax initiation and present global approaches utilized in various treatment settings. These hypothetical scenarios highlight the importance of a multidisciplinary approach and shared decision-making, outlining best practices for venetoclax initiation and overall optimal treatment strategies in patients with CLL.
Exploring the Potential Link between PFAS Exposure and Endometrial Cancer: A Review of Environmental and Sociodemographic Factors
Authors: Ayodele Aderonke , Obeng-Gyasi Emmanuel
Published: February 2024

This exploratory narrative review paper delves into the intricate interplay between per- and polyfluoroalkyl substances (PFAS) exposure, sociodemographic factors, and the influence of stressors in the context of endometrial cancer. PFAS, ubiquitous environmental contaminants notorious for their persistence in the ecosystem, have garnered attention for their potential to disrupt endocrine systems and provoke immune responses. We comprehensively examine the various sources of PFAS exposure, encompassing household items, water, air, and soil, thus shedding light on the multifaceted routes through which individuals encounter these compounds. Furthermore, we explore the influence of sociodemographic factors, such as income, education, occupation, ethnicity/race, and geographical location and their relationship to endometrial cancer risk. We also investigated the role of stress on PFAS exposure and endometrial cancer risk. The results revealed a significant impact of sociodemographic factors on both PFAS levels and endometrial cancer risk. Stress emerged as a notable contributing factor influencing PFAS exposure and the development of endometrial cancer, further emphasizing the importance of stress management practices for overall well-being. By synthesizing evidence from diverse fields, this review underscores the need for interdisciplinary research and targeted interventions to comprehensively address the complex relationship between PFAS, sociodemographic factors, stressors, and endometrial cancer.
Efficacy and Safety of Ripretinib in Advanced Gastrointestinal Stromal Tumors within an Expanded Access Program: A Cohort Study
Authors: Lim Su Yin , Ferro-López Laura , Barquin Elizabeth , Lindsay Daniel , Thway Khin , Smith Myles J. , Benson Charlotte , Jones Robin L. , Napolitano Andrea
Published: February 2024

Ripretinib, a novel tyrosine kinase inhibitor used in advanced gastrointestinal stromal tumors (GIST) resistant to standard therapies, was assessed in the United Kingdom (UK) within an Expanded Access Program (EAP). A retrospective review of patients treated between January 2020 and October 2021 within the ripretinib EAP in our Institution was conducted. Clinician-documented and mRECIST 1.1 assessments were collected. The primary endpoints were progression-free survival (PFS) and time to treatment discontinuation (TTD). Treatment beyond progression (TBP), overall survival (OS), objective response rates and safety data were also analyzed. Survival curves were constructed using the Kaplan–Meier method, and univariate and multivariate Cox regression analyses were performed. All analyses were performed with R software. Overall, forty-five patients were included. After a median follow-up of 24.2 (95% CI 19.7–29.7) months, the median PFS of the group receiving 150 mg ripretinib once daily (OD) was 7.9 (95% CI 5.6–19.3) months. In the cohort of 22 patients with dose escalation upon tumor progression to 150 mg ripretinib twice daily (BD), the median PFS from BD was 5.4 (95% CI 2.8–9.3) months. Overall, median PFS and OS values for patients on ripretinib were 9.7 (95% CI 8.3–18.1) and 14.0 (95% CI 9.9–NA) months, respectively. TTD was similar to PFS. TBP was observed in about one third of all patients. Objective responses to ripretinib OD and BD treatments were observed in 16.7% and 10.0% of the patients, respectively. No new safety signals were identified. In conclusion, patients with advanced GIST receiving ripretinib in the UK within the EAP reported prolonged benefits, in line with the recent phase III clinical trials.
The Additional Value of Somatostatin Receptor Positron Emission Computed Tomography ([68Ga]Ga-DOTATOC PET/CT) Compared with Magnetic Resonance Imaging of the Head and Neck Region in Paraganglioma Patients: A Pilot Study
Authors: de Bresser Carolijn J. M. , Petri Bart-Jeroen , Braat Arthur J. A. T. , de Keizer Bart , van Treijen Mark J. C. , Dankbaar Jan Willem , Pameijer Frank A. , Kok Marius G. J. , de Ridder Mischa , van Nesselrooij Bernadette P. M. , de Bree Remco , de Borst Gert J. , Rijken Johannes A.
Published: February 2024

The Dutch guideline for patients suspected of head and neck paragangliomas (HNPGLs) recommends magnetic resonance imaging (MRI) and/or computed tomography (CT) of the head and neck area. Additionally, it suggests considering additional nuclear imaging. The aim of this study was to evaluate the outcomes of [68Ga]Ga-DOTATOC PET/CT compared to MRI in patients with suspected HNPGLs and carriers of genetic variations. Methods: In this single-center pilot study, retrospective data were obtained from consecutive patients between 2016 and 2023. Both MRI and [68Ga]Ga-DOTATOC PET/CT were performed within 12 months. The primary outcome was the location of HNPGLs. Results: A total of 25 consecutive patients were included, and 7 patients (28.0%, p = 0.5) showed differences between the imaging modalities, of whom 5 patients had unexpected localizations with additional uptake by somatostatin receptors (SSTR) on the [68Ga]Ga-DOTATOC PET/CT. Conclusions: The authors recommend performing baseline imaging with [68Ga]Ga-DOTATOC PET/CT (if available) in variant carriers and using MRI/CT for follow-up according to the regional protocol, thereby shifting the gold standard for baseline imaging from MRI/CT to [68Ga]Ga-DOTATOC PET/CT.
Pushing the Operational Barriers for g-C3N4: A Comprehensive Review of Cutting-Edge Immobilization Strategies
Authors: Fdez-Sanromán Antia , Pazos Marta , Rosales Emilio , Sanromán Angeles
Published: February 2024

This comprehensive review explores recent advancements in immobilization strategies for graphitic carbon nitride (g-C3N4), a metal-free photocatalyst that has gained significant attention for its optical and physicochemical properties comparable to traditional photocatalysts like TiO2. However, a critical challenge regarding their application has emerged from the difficulty of its recovery due to its powdery nature. Therefore, several alternatives are being explored to immobilize this material, facilitating its recovery and reuse. This review systematically categorizes various physical and chemical immobilization techniques, providing an in-depth analysis of their advantages, drawbacks, and applications. Techniques such as encapsulation, electrospinning, casting, and coating, along with their adaptations for g-C3N4, are thoroughly examined. Additionally, the impact of these strategies on enhancing the photocatalytic efficiency and operational stability of g-C3N4, particularly in environmental applications, is also assessed. Thus, this review aims to provide valuable insights and guide future research in the realms of photocatalysis and environmental remediation. The review contributes to the understanding of how immobilization strategies can optimize the performance of g-C3N4, furthering its potential applications in sustainable and efficient environmental solutions.
Molecular Organization and Regulation of the Mammalian Synapse by the Post-Translational Modification SUMOylation
Authors: Chato-Astrain Isabel , Pronot Marie , Coppola Thierry , Martin Stéphane
Published: February 2024

Neurotransmission occurs within highly specialized compartments forming the active synapse where the complex organization and dynamics of the interactions are tightly orchestrated both in time and space. Post-translational modifications (PTMs) are central to these spatiotemporal regulations to ensure an efficient synaptic transmission. SUMOylation is a dynamic PTM that modulates the interactions between proteins and consequently regulates the conformation, the distribution and the trafficking of the SUMO-target proteins. SUMOylation plays a crucial role in synapse formation and stabilization, as well as in the regulation of synaptic transmission and plasticity. In this review, we summarize the molecular consequences of this protein modification in the structural organization and function of the mammalian synapse. We also outline novel activity-dependent regulation and consequences of the SUMO process and explore how this protein modification can functionally participate in the compartmentalization of both pre- and post-synaptic sites.
Unraveling Atopic Dermatitis: Insights into Pathophysiology, Therapeutic Advances, and Future Perspectives
Authors: Pareek Ashutosh , Kumari Lipika , Pareek Aaushi , Chaudhary Simran , Ratan Yashumati , Janmeda Pracheta , Chuturgoon Sanam , Chuturgoon Anil
Published: February 2024

Atopic dermatitis (AD) is an inflammatory skin condition that frequently develops before the onset of allergic rhinitis or asthma. More than 10% of children are affected by this serious skin condition, which is painful for the sufferers. Recent research has connected the environment, genetics, the skin barrier, drugs, psychological factors, and the immune system to the onset and severity of AD. The causes and consequences of AD and its cellular and molecular origins are reviewed in this paper. The exploration of interleukins and their influence on the immunological pathway in AD has been facilitated by using relevant biomarkers in clinical trials. This approach enables the identification of novel therapeutic modalities, fostering the potential for targeted translational research within the realm of personalized medicine. This review focuses on AD’s pathophysiology and the ever-changing therapeutic landscape. Beyond the plethora of biologic medications in various stages of approval or development, a range of non-biologic targeted therapies, specifically small molecules, have emerged. These include Janus kinase (JAK) inhibitors like Baricitinib, Upadacitinib, and Abrocitinib, thus expanding the spectrum of therapeutic options. This review also addresses the latest clinical efficacy data and elucidates the scientific rationale behind each targeted treatment for atopic dermatitis.