bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of the Modified Thomas Test for Hip Flexor Stretching: What Are the Acute and Prolonged Effects?
Authors: Kiseljak Dalibor , Jelovica Vatroslav
Published: September 2024

Background/Objectives: The flexibility deficits of hip flexors have been identified as potential biomechanical risk factors for the lumbo–pelvic–hip complex, with postural repercussions on the trunk and lower limbs. The purpose of this study was to conduct a single gravity stretching experiment and to monitor its acute and prolonged effects. Methods: The sample comprised 14 healthy participants (8 females and 6 males). Data were collected during two-day measurement sessions. These analyzed via Kinovea software. The single intervention (i.e., gravity stretching) was performed on the first day. A modified Thomas test was used at the same time in two ways, both as a measurement and as an intervention tool. Stretching was achieved by relaxing in a position to perform the modified Thomas test where, each participant lies completely relaxed for 3 min, allowing gravity to stretch the hip flexors of the examined limb. Results: After intervention, a significant acute increase in hip extension range of motion and a decrease in knee extension range of motion were found. We did not find any significant prolonged effects; moreover, after 48 h, the hip range of motion almost returned to the initial value. Conclusions: A single 3 min stretch is very effective in terms of achieving immediate changes in the range of motion, but insufficient for long-term improvements in flexibility.
Exploring Intra-Articular Administration of Monoclonal Antibodies as a Novel Approach to Osteoarthritis Treatment: A Systematic Review
Authors: Smakaj Amarildo , Gasbarra Elena , Cardelli Tommaso , Salvati Chiara , Bonanni Roberto , Cariati Ida , Iundusi Riccardo , Tarantino Umberto
Published: September 2024

Biological drugs, including monoclonal antibodies, represent a revolutionary strategy in all fields of medicine, offering promising results even in the treatment of osteoarthritis (OA). However, their safety and efficacy have not been fully validated, highlighting the need for in-depth studies. Therefore, we provided a comprehensive systematic review of the intra-articular use of monoclonal antibodies for the treatment of OA in animal models, reflecting ongoing efforts to advance therapeutic strategies and improve patient outcomes. A systematic literature search was conducted in December 2023 following the PRISMA guidelines, using the Web of Science, Google Scholar, and PUBMED databases. Out of a total of 456, 10 articles were included in the study analyzing intra-articular antibodies and focusing on various targets, including vascular endothelial growth factor (VEGF), nerve growth factor (NGF), interleukin 4-10 (IL4-10), tumor necrosis factor α (TNF-α), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), and matrix metalloproteinase 13 (MMP-13). Most studies administered the antibodies weekly, ranging from 1 to 10 injections. Animal models varied, with mean follow-up periods of 8.9 ± 4.1 weeks. The methods of assessing outcomes, including pain and morpho-functional changes, varied. Some studies reported only morphological and immunohistochemical data, while others included a quantitative analysis of protein expression. In conclusion, monoclonal antibodies represent a promising avenue in the treatment of OA, offering targeted approaches to modulate disease pathways. Further research and clinical trials are needed to validate their safety and efficacy, with the potential to revolutionize the management of OA and reduce reliance on prosthetic interventions.
Exploring the Role of MicroRNAs in Progesterone and Estrogen Receptor Expression in Endometriosis
Authors: Hon Jing-Xian , Wahab Norhazlina Abdul , Karim Abdul Kadir Abdul , Mokhtar Norfilza Mohd , Mokhtar Mohd Helmy
Published: September 2024

Background/Objectives: Patients with endometriosis still respond poorly to progestins due to progesterone resistance associated with microRNAs (miRNAs). The aim of this study was to investigate the expression of selected miRNAs, estrogen receptor (ER)α, ERβ, progesterone receptor (PR)-A and PR-B and to determine the target genes of upregulated miRNAs in endometriosis. Methods: In this study, 18 controls, 18 eutopic and 18 ectopic samples were analysed. Profiling and validation of miRNAs associated with functions of endometriosis were performed using next-generation sequencing (NGS) and qRT-PCR. At the same time, the expression of ERα, ERβ, PR-A and PR-B was also determined using qRT-PCR. Target prediction was also performed for miR-199a-3p, miR-1-3p and miR-125b-5p using StarBase. Results: In this study, NGS identified seven significantly differentially expressed miRNAs, of which six miRNAs related to the role of endometriosis were selected for validation by qRT-PCR. The expression of miR-199a-3p, miR-1-3p, miR-146a-5p and miR-125b-5p was upregulated in the ectopic group compared to the eutopic group. Meanwhile, ERα and ERβ were significantly differentially expressed in endometriosis compared to the control group. However, the expressions of PR-A and PR-B showed no significant differences between the groups. The predicted target genes for miR-199a-3p, miR-1-3p and miR-125b-5p are SCD, TAOK1, DDIT4, LASP1, CDK6, TAGLN2, G6PD and ELOVL6. Conclusions: Our findings demonstrated that the expressions of ERα and ERβ might be regulated by miRNAs contributing to progesterone resistance, whereas the binding of miRNAs to target genes could also contribute to the pathogenesis of endometriosis. Therefore, miRNAs could be used as potential biomarkers and for targeted therapy in patients with endometriosis.
Trehalose Rescues Postmenopausal Osteoporosis Induced by Ovariectomy through Alleviating Osteoblast Pyroptosis via Promoting Autophagy
Authors: Hu Xinli , Wang Wei , Chen Xiaolong , Kong Chao , Zhao Xuan , Wang Zheng , Zhang Haojie , Lu Shibao
Published: September 2024

Background: Osteoporosis, a prevalent bone metabolic disease, often requires long-term drug treatments that may lead to serious side effects. Trehalose, a natural disaccharide found in various organisms, has been shown to have a promoting effect on autophagy. However, whether trehalose can improve bone mass recovery in ovariectomized rats and its underlying mechanisms remains unclear. In this study, trehalose was administered to ovariectomized rats to evaluate its therapeutic potential for osteoporosis following ovariectomy. Methods: Micro-computed tomography (Micro-CT), hematoxylin and eosin (HE) and immunohistochemical staining techniques were utilized to evaluate the impact of trehalose on osteoporosis induced by ovariectomy (OVX) in mice, both in imaging and histological dimensions. Furthermore, the influence of trehalose on osteoblastogenesis and functional activity was quantified through Alizarin Red S (ARS) staining and immunoblotting assays. Results: Trehalose effectively mitigated bone loss, elevated autophagy and suppressed pyroptosis in ovariectomized rats. Furthermore, 3-methyladenine diminished the protective effects of trehalose, particularly in promoting autophagy and inhibiting pyroptosis. Conclusions: Trehalose demonstrates significant potential in treating osteoporosis by suppressing NLRP3 inflammasome-driven pyroptosis, primarily through autophagy promotion. This suggests that trehalose could be a promising, safer alternative treatment for osteoporosis.
Treatment of Refractory Mucosal Leishmaniasis Is Associated with Parasite Overexpression of HSP70 and ATPase and Reduced Host Hydrogen Peroxide Production (Brief Report)
Authors: Urdapilleta Ada Amália Ayala , Santos Alfani Adriana de Oliveira , Barroso Daniel Holanda , Vinecky Felipe , Amaral Vaz Bandeira Suzana da Glória , Andrade Alan Carvalho , Taquita Jorge Alex , Bastos Izabela Marques Dourado , Sampaio Raimunda Nonata Ribeiro
Published: September 2024

Background: Mucosal leishmaniasis (ML) is a deforming type of American Tegumentary Leishmaniasis caused by Leishmania (Viannia) braziliensis that frequently does not respond to treatment. Despite its relapsing clinical course, few parasites are usually found in mucosal lesions. Host and parasite factors may be responsible for this paradox in the pathogenesis of the disease, allowing for both a low parasite burden and the inability of the host to clear and eliminate the disease. Methods and results: In this work, we present a clinical case of relapsing ML that was treated for 25 years without success with SbV, N-methyl glucamine, sodium stibogluconate, amphotericin B deoxycholate, gabromycin, antimonial plus thalidomide, liposomal amphotericin B, Leishvacin (a vaccine made in Brazil) and miltefosine. In a comparative analysis using nanoscale liquid chromatography coupled with tandem mass spectrometry of protein extracts of L. (V.) braziliensis promastigotes isolated from the patient and from the reference strain (MHOM/BR/94/M15176), we observed increases in ATPase and HSP70 protein levels in the parasite. We also observed an impairment in the production of hydrogen peroxide by peripheral mononuclear blood monocytes (PBMCs), as assessed by the horseradish peroxidase-dependent oxidation of phenol red. Conclusions: We hypothesise that these parasite molecules may be linked to the impairment of host parasiticidal responses, resulting in Leishmania persistence in ML patients.
Serum Hepatocyte Growth Factor Concentration Correlates with Albuminuria in Individuals with Optimal Blood Pressure and Untreated Arterial Hypertension
Authors: Fistrek Prlic Margareta , Vukovic Brinar Ivana , Kos Jelena , Dika Zivka , Ivandic Ema , Fucek Mirjana , Jelakovic Bojan
Published: September 2024

Background/Objectives: Hepatocyte growth factor (HGF) is a protective factor against acute renal injury and chronic renal fibrosis. A positive correlation between HGF and blood pressure (BP) has been established. This study aimed to determine the association between serum HGF concentration and albuminuria in subjects with optimal blood pressure (OBP) and untreated arterial hypertension (UAH), as well as its association with BP levels, serum glucose levels, and inflammatory markers. Methods: Data from 563 subjects were analyzed. Albuminuria was normalized to urine creatinine and expressed as the albumin/creatinine ratio (ACR). HGF, serum glucose, C-reactive protein, and blood leucocyte counts were measured. BP was measured and subjects were divided into optimal blood pressure (BP < 120/80 mmHg, N = 295) and untreated arterial hypertension (BP > 140/90 mmHg, N = 268) groups. Results: The subjects with UAH were significantly older and had higher values of body mass index, waist circumference, serum total and LDL cholesterol levels, triglyceride levels, fasting glucose levels, and ACR (all p < 0.001). A significant positive correlation was found between serum HGF concentration and ACR in both groups. There was no difference or correlation between HGF and BP or inflammatory markers in either group. The multivariate regression analysis identified serum HGF concentration as a strong predictor of ACR increase (Beta = 0.376, p < 0.001). Conclusion: This study found that serum HGF concentration is associated with albuminuria not only in individuals with untreated arterial hypertension, but also in those with optimal blood pressure. The results suggest that serum HGF is an independent predictor of ACR increase in both groups.
Effective Boundary Correction for Deterministic Lateral Displacement Microchannels to Improve Cell Separation: A Numerical and Experimental Study
Authors: Mirhosseini Shaghayegh , Eskandarisani Mohammadmahdi , Faghih Nasiri Aryanaz , Khatami Fatemeh , Mirzaei Akram , Badieirostami Majid , Aghamir Seyed Mohammad Kazem , Kolahdouz Mohammadreza
Published: September 2024

Particle separation and sorting techniques based on microfluidics have found extensive applications and are increasingly gaining prominence. This research presents the design and fabrication of a microfluidic device for separating cells using deterministic lateral displacement (DLD), enabling accuracy and continuity while being size-based. Nevertheless, it remains demanding, to completely reverse the detrimental effects of the boundaries that disturb the fluidic flow in the channel and reduce particle separation efficiency. This study introduces a novel approach to enhance the boundary structure of channels. By using this design, separation efficiency is boosted, and the fluid behavior around the walls is improved. The boundary correction (BC) enhances the operation of the microchannel and is very effective in microchannels. With boundary correction, the device exhibited improved separation efficiencies, but in its absence, separation efficiencies dropped. The collected microscopic images of the isolation of prostate cancer cell lines and red blood cells revealed promising outcomes. The efficiency of circulating tumor cell (CTC) throughput in the microfluidic channel, quantified as the ratio or proportion of tumor cells exiting the channel to cells entering it, exceeds 93%. Moreover, the efficiency of CTC isolation, expressed as the proportion of tumor cells from the upper outlet of the microfluidic channel to all cells, is over 89%. Additionally, the efficiency of red blood cell isolation, evaluated as the ratio of red blood cells from the lower outlet of the microfluidic channel to all cells, surpasses 77%. While using the same DLD separator without boundary correction reduced the separation efficiency by around 5%.
A Review of Advanced Sensor Technologies for Aquatic Products Freshness Assessment in Cold Chain Logistics
Authors: Wang Baichuan , Liu Kang , Wei Guangfen , He Aixiang , Kong Weifu , Zhang Xiaoshuan
Published: September 2024

The evaluation of the upkeep and freshness of aquatic products within the cold chain is crucial due to their perishable nature, which can significantly impact both quality and safety. Conventional methods for assessing freshness in the cold chain have inherent limitations regarding specificity and accuracy, often requiring substantial time and effort. Recently, advanced sensor technologies have been developed for freshness assessment, enabling real-time and non-invasive monitoring via the detection of volatile organic compounds, biochemical markers, and physical properties. The integration of sensor technologies into cold chain logistics enhances the ability to maintain the quality and safety of aquatic products. This review examines the advancements made in multifunctional sensor devices for the freshness assessment of aquatic products in cold chain logistics, as well as the application of pattern recognition algorithms for identification and classification. It begins by outlining the categories of freshness criteria, followed by an exploration of the development of four key sensor devices: electronic noses, electronic tongues, biosensors, and flexible sensors. Furthermore, the review discusses the implementation of advanced pattern recognition algorithms in sensor devices for freshness detection and evaluation. It highlights the current status and future potential of sensor technologies for aquatic products within the cold chain, while also addressing the significant challenges that remain to be overcome.
Lack of Small-Scale Changes in Breeding Birds after a Fire: Does the Resilience of Cork Oaks Favor Rapid Recolonization in Suburban Wood Patches?
Authors: Compagnucci Silvia , Battisti Corrado , Scalici Massimiliano
Published: September 2024

Forest fires are disturbance events that can impact biological assemblages at multiple scales. In this study, the structures of breeding bird communities in cork oak patches located in an agro-mosaic suburban landscape of central Italy (Rome) were compared at the local scale with a fine-grained mapping method before (2018) and after (2023) a fire event occurred in July 2022. The analyses did not reveal any significant changes in the density of territorial pairs or in the diversity metrics, both univariate (Shannon–Wiener index, evenness, Margalef normalized richness) and bivariate (Whittaker and k-dominance plots, abundance/biomass curves) of diversity. Even when the guilds of strictly forest-related species were compared, no differences emerged before and after the fire. This counterintuitive phenomenon may be due to the characteristics of the dominant tree, the cork oak (Quercus suber), a sclerophilous tree that is very resilient to fires and able to recover foliage in the following spring season, thus allowing rapid bird recolonization. However, other small-scale phenomena (e.g., the ‘crowding effect’ and local dispersal of territorial pairs from remnant wood patches not affected by fire) may explain this lack of change in breeding bird density and diversity. Further studies should be carried out at larger spatial and temporal scales and at different levels of fire frequency and intensity to confirm these responses at the guild/community level in suburban cork oak wood patches.
Hybrid-Blockchain-Based Electronic Voting Machine System Embedded with Deepface, Sharding, and Post-Quantum Techniques
Authors: Joni Sohel Ahmed , Rahat Rabiul , Tasnin Nishat , Ghose Partho , Uddin Md. Ashraf , Ayoade John
Published: September 2024

The integrity of democratic processes relies on secure and reliable election systems, yet achieving this reliability is challenging. This paper introduces the Post-Quantum Secured Multiparty Computed Hierarchical Authoritative Consensus Blockchain (PQMPCHAC-Bchain), a novel e-voting system designed to overcome the limitations of current Biometric Electronic Voting Machine (EVM) systems, which suffer from trust issues due to closed-source designs, cyber vulnerabilities, and regulatory concerns. Our primary objective is to develop a robust, scalable, and secure e-voting framework that enhances transparency and trust in electoral outcomes. Key contributions include integrating hierarchical authorization and access control with a novel consensus mechanism for proper electoral governance. We implement blockchain sharding techniques to improve scalability and propose a multiparty computed token generation system to prevent fraudulent voting and secure voter privacy. Post-quantum cryptography is incorporated to safeguard against potential quantum computing threats, future-proofing the system. Additionally, we enhance authentication through a deep learning-based face verification model for biometric validation. Our performance analysis indicates that the PQMPCHAC-Bchain e-voting system offers a promising solution for secure elections. By addressing critical aspects of security, scalability, and trust, our proposed system aims to advance the field of electronic voting. This research contributes to ongoing efforts to strengthen the integrity of democratic processes through technological innovation.
Breaking Down the Stigma: A Review of the Literature on the Relationships between Autism Spectrum Disorder and Criminal Behavior
Authors: Dell’Osso Liliana , Nardi Benedetta , Calvaruso Martina , Castellani Lucrezia , Pronestì Cristiana , Cremone Ivan Mirko , Pini Stefano , Carpita Barbara
Published: September 2024

Background: In recent years, there has been growing interest in the evaluation of autism spectrum disorder (ASD) and autistic traits in prison populations and offenders. Due to misleading headlines and highly publicized criminal cases, the belief that autistic individuals are more prone to commit crimes has spread among the general population, also leading to increasing research on this matter. Aims: In this context, this narrative review aimed to analyze the available scientific literature on the bi-directional link between ASD and criminal behaviors and to assess the key characteristics of eventual ASD offenders, including sociodemographic data, comorbidities, crime-related features, and interactions with the criminal justice system. Results: Our review highlighted that the available studies lack methodological rigor and present controversial results. Overall, the current state of research does not support any definitive correlation between ASD or autistic traits and the predisposition to engage in criminal conduct. Further studies are needed to confirm or reject this hypothesis.
Advancements in Pharmacological Treatment of Alzheimer’s Disease: The Advent of Disease-Modifying Therapies (DMTs)
Authors: Wang Qiong , Chen Sihui , Wang Junhui , Shang Huifang , Chen Xueping
Published: September 2024

The landscape of pharmacological treatment for Alzheimer’s disease (AD) has undergone significant transformations with the advent of disease-modifying therapies (DMTs) targeting β-Amyloid (Aβ) accumulation, one of the hallmark pathologies of AD. The approval and market introduction of monoclonal antibodies mark the dawn of a new era in AD therapeutics as well. Furthermore, considerable progress has also been made in the development of new drugs targeting non-Aβ and non-Tau protein pathways. These advancements are key in tackling the root causes of AD, offering hope for treatments that both relieve symptoms and slow disease progression, improving patient outcomes and quality of life. This review aims to provide a comprehensive update on the advances in drug development and application for AD, including those currently in clinical trials and those already approved for the market to treat patients.
Developmental Predictors of Suicidality in Schizophrenia: A Systematic Review
Authors: Benster Lindsay L. , Stapper Noah , Rodriguez Katie , Daniels Hadley , Villodas Miguel , Weissman Cory R. , Daskalakis Zafiris J. , Appelbaum Lawrence G.
Published: September 2024

Background/Objectives: Schizophrenia (SZ) is a severe psychiatric disorder characterized by a complex interplay of genetic, developmental, and environmental factors that significantly increase the risk of suicidal ideation (SI) and suicide attempts (SAs). This systematic review synthesizes current research on the developmental predictors of SI in individuals with SZ, aiming to delineate the multifactorial etiology of suicide within this population. Methods: A comprehensive search across Medline, PsycINFO, and EMBASE databases identified 23 eligible studies, emphasizing the varied methodological approaches and the global distribution of research efforts. Results: These studies demonstrate a robust association between early life adversities, particularly childhood trauma such as physical neglect, emotional abuse, and sexual abuse, and the increased prevalence of SI and SAs in SZ. This review also highlights the significant genetic factors associated with the development of suicidality in SZ, raising the possibility that polymorphisms in inflammation-related genes and neurodevelopmental abnormalities may influence susceptibility to SI. Notably, family history of psychiatric conditions may exacerbate the risk of SI through both hereditary and environmental mechanisms. Environmental factors, including socioeconomic status and social support, are also implicated, underscoring the role of broader socio-environmental conditions influencing outcomes. Conclusions: This review supports the integration of biopsychosocial models in understanding SI in SZ, advocating for interventions addressing the complex interplay of risk factors and the need for longitudinal studies to elucidate the dynamic interactions between risk factors over time. This comprehensive understanding is crucial for developing targeted preventive strategies and enhancing the clinical management of SZ, aiming to reduce suicidality in this vulnerable population.
Visual Perceptual Learning of Form–Motion Integration: Exploring the Involved Mechanisms with Transfer Effects and the Equivalent Noise Approach
Authors: Donato Rita , Contillo Adriano , Campana Gianluca , Roccato Marco , Gonçalves Óscar F. , Pavan Andrea
Published: September 2024

Background: Visual perceptual learning plays a crucial role in shaping our understanding of how the human brain integrates visual cues to construct coherent perceptual experiences. The visual system is continually challenged to integrate a multitude of visual cues, including form and motion, to create a unified representation of the surrounding visual scene. This process involves both the processing of local signals and their integration into a coherent global percept. Over the past several decades, researchers have explored the mechanisms underlying this integration, focusing on concepts such as internal noise and sampling efficiency, which pertain to local and global processing, respectively. Objectives and Methods: In this study, we investigated the influence of visual perceptual learning on non-directional motion processing using dynamic Glass patterns (GPs) and modified Random-Dot Kinematograms (mRDKs). We also explored the mechanisms of learning transfer to different stimuli and tasks. Specifically, we aimed to assess whether visual perceptual learning based on illusory directional motion, triggered by form and motion cues (dynamic GPs), transfers to stimuli that elicit comparable illusory motion, such as mRDKs. Additionally, we examined whether training on form and motion coherence thresholds improves internal noise filtering and sampling efficiency. Results: Our results revealed significant learning effects on the trained task, enhancing the perception of dynamic GPs. Furthermore, there was a substantial learning transfer to the non-trained stimulus (mRDKs) and partial transfer to a different task. The data also showed differences in coherence thresholds between dynamic GPs and mRDKs, with GPs showing lower coherence thresholds than mRDKs. Finally, an interaction between visual stimulus type and session for sampling efficiency revealed that the effect of training session on participants’ performance varied depending on the type of visual stimulus, with dynamic GPs being influenced differently than mRDKs. Conclusion: These findings highlight the complexity of perceptual learning and suggest that the transfer of learning effects may be influenced by the specific characteristics of both the training stimuli and tasks, providing valuable insights for future research in visual processing.
Unveiling the Shadow of Workplace Cyberbullying in the Digital Age: A Call for Research in Africa
Authors: Genga Cheryl Akinyi , Babalola Sunday Samson
Published: September 2024

Workplace cyberbullying, exacerbated by the growing prevalence of digital work environments, has emerged as a significant threat to employee well-being and organisational productivity. Despite increasing research attention around the world, there is a critical gap in understanding the unique context and implications of cyberbullying within African workplaces, particularly those operating in digital spaces. This bibliometric analysis, utilising Scopus and Web of Science databases, systematically examines the publications on workplace cyberbullying from 2000 to 2024 using Microsoft Excel and visualisation tools such as VOS Viewer. The findings underscore a stark disparity in research focus, with most studies originating from developed countries and neglecting African organisations’ specific challenges. Although South Africa and Ghana have made initial contributions, a comprehensive understanding of the prevalence, manifestations, and consequences of cyberbullying in diverse African cultural and organisational settings in Africa remains elusive. This study serves as a call to action for researchers and practitioners to prioritise investigations into cyberbullying in Africa, highlighting the need for culturally sensitive interventions and policies tailored to digital work environments. By addressing this research gap, organisations can promote healthier and more sustainable workplaces for employees across Africa.
Emulating the Delivery of Sawtooth Proton Arc Therapy Plans on a Cyclotron-Based Proton Beam Therapy System
Authors: Burford-Eyre Samuel , Aitkenhead Adam , Aylward Jack D. , Henthorn Nicholas T. , Ingram Samuel P. , Mackay Ranald , Manger Samuel , Merchant Michael J. , Sitch Peter , Warmenhoven John-William , Appleby Robert B.
Published: September 2024

Purpose: To evaluate and compare the deliverability of ‘sawtooth’ proton arc therapy (PAT) plans relative to static intensity modulated proton therapy (IMPT) at a cyclotron-based clinical facility. Methods: The delivery of single and dual arc Sawtooth PAT plans for an abdominal CT phantom and multiple clinical cases of brain, head and neck (H&N) and base of skull (BoS) targets was emulated under the step-and-shoot and continuous PAT delivery regimes and compared to that of a corresponding static IMPT plan. Results: Continuous PAT delivery increased the time associated with beam delivery and gantry movement in single/dual PAT plans by 4.86/7.34 min (brain), 7.51/12.40 min (BoS) and 6.59/10.57 min (H&N) on average relative to static IMPT. Step-and-shoot PAT increased this delivery time further by 4.79 min on average as the delivery was limited by gantry motion. Conclusions: The emulator can approximately model clinical sawtooth PAT delivery but requires experimental validation. No clear benefit was observed regarding beam-on time for sawtooth PAT relative to static IMPT.
Cisplatin-Containing Combinations Associate with Survival in Women from Appalachian Kentucky with Metastatic, Persistent, or Recurrent Uterine Cervix Cancer
Authors: Kunos Charles A. , Miller Rachel W. , Fabian Denise
Published: September 2024

Background: Prior preclinical studies showed promising antitumor activity and an acceptable safety profile associated with radiopharmaceuticals for patients with metastatic, persistent, or recurrent uterine cervix cancers. Whether the addition of a radiopharmaceutical to chemotherapy would significantly increase progression-free survival in such patients is untested. Our retrospective study sought to associate the line of treatment and progression-free survival as benchmarks for next-generation radiopharmaceutical development. Methods: We grouped metastatic, persistent, or recurrent uterine cervix cancer patients not amenable to curable surgery or radiotherapy between 2002 and 2023 by the line of doublet, triplet, and quadruplet chemotherapy or another intervention. After the first-line treatment, patients were monitored for radiographic progression every three months for up to three years. The primary endpoints were the first and any second or third progression-free survival intervals. Results: A total of 127 patients contributed demographic, tumor, line of treatment, and outcome data with a median follow-up of 18 months (25–75% interquartile range: 9 to 37 months). After the first-line treatment, 113 patients had local or distant progression or died from any cause, most often death from the disease (67%). Median progression-free survivals were 5.5 months (95% confidence interval: 4.8–6.0 months), 5.3 months (95% confidence interval: 4.5–6.3 months), and 3.0 months (95% confidence interval: 2.1–3.7 months) for the first-, second-, and third-line treatments, respectively. For a first-line cisplatin-containing regimen, the median progression-free survival was 6.5 months (95% confidence interval: 5.5–7.7 months). Conclusions: This study highlights the limited efficacy of current treatments for metastatic, persistent, or recurrent uterine cancer patients. A five-month progression-free survival might serve as a benchmark for the development of novel therapies in clinical efficacy trials, such as radiopharmaceuticals.
Theranostic Approaches for Gastric Cancer: An Overview of In Vitro and In Vivo Investigations
Authors: Basirinia Ghazal , Ali Muhammad , Comelli Albert , Sperandeo Alessandro , Piana Sebastiano , Alongi Pierpaolo , Longo Costanza , Di Raimondo Domenico , Tuttolomondo Antonino , Benfante Viviana
Published: September 2024

Gastric cancer (GC) is the second most common cause of cancer-related death worldwide and a serious public health concern. This high death rate is mostly caused by late-stage diagnoses, which lead to poor treatment outcomes. Radiation immunotherapy and targeted therapies are becoming increasingly popular in GC treatment, in addition to surgery and systemic chemotherapy. In this review, we have focused on both in vitro and in vivo research, which presents a summary of recent developments in targeted therapies for gastric cancer. We explore targeted therapy approaches, including integrin receptors, HER2, Claudin 18, and glutathione-responsive systems. For instance, therapies targeting the integrin receptors such as the αvβ3 and αvβ5 integrins have shown promise in enhancing diagnostic precision and treatment efficacy. Furthermore, nanotechnology provides novel approaches to targeted drug delivery and imaging. These include glutathione-responsive nanoplatforms and cyclic RGD peptide-conjugated nanoparticles. These novel strategies seek to reduce systemic toxicity while increasing specificity and efficacy. To sum up, the review addresses the significance of personalized medicine and advancements in gastric cancer-targeted therapies. It explores potential methods for enhancing gastric cancer prognosis and treatment in the future.
p66Shc Protein—Oxidative Stress Sensor or Redox Enzyme: Its Potential Role in Mitochondrial Metabolism of Human Breast Cancer
Authors: Prill Monika , Sardão Vilma A. , Sobczak Mateusz , Nowis Dominika , Szymanski Jedrzej , Wieckowski Mariusz R.
Published: September 2024

This work presents a comprehensive evaluation of the role of p66Shc protein in mitochondrial physiology in MDA-MB-231 breast cancer cells. The use of human breast cancer cell line MDA-MB-231 and its genetically modified clones (obtained with the use of the CRISPR-Cas9 technique), expressing different levels of p66Shc protein, allowed us to demonstrate how the p66Shc protein affects mitochondrial metabolism of human breast cancer cells. Changes in the level of p66Shc (its overexpression, and overexpressing of its Serine 36-mutated version, as well as the knockout of p66Shc) exert different effects in breast cancer cells. Interestingly, knocking out p66Shc caused significant changes observed mostly in mitochondrial bioenergetic parameters. We have shown that an MDA-MB-231 (which is a strong metastatic type of breast cancer) clone lacking p66Shc protein is characterized by a significant shift in the metabolic phenotype in comparison to other MDA-MB-231 clones. Additionally, this clone is significantly more vulnerable to doxorubicin treatment. We have proved that p66Shc adaptor protein in human breast cancer cells may exert a different role than in noncancerous cells (e.g., fibroblasts).
HPV and Lung Cancer: A Systematic Review
Authors: Sequeira Telma , Pinto Rui , Cardoso Carlos , Almeida Catarina , Aragão Rita , Almodovar Teresa , Bicho Manuel , Bicho Maria Clara , Bárbara Cristina
Published: September 2024

This systematic review aims to explore the diagnostic criteria, epidemiology, etiology, and prognosis of Human Papillomavirus (HPV) infection in lung cancer. This PRISMA-guided review searched the PubMed® and EmbaseTM databases for “lung cancer AND HPV” on 10 June 2023, filtering human subject papers. A total of 97 studies encompassing 9098 patients worldwide, revealing varied HPV infection rates in lung cancer, ranging from 0% to 69%, were analyzed. While HPV16/18 was predominant in some regions, its association with lung cancer remained inconclusive due to conflicting findings. Studies from Asia reported lower HPV infection rates compared to Western populations. Some studies suggested a limited role of HPV in lung carcinogenesis, particularly in non-smokers. However, intriguing associations were noted, including HPV’s potential role in lung adenocarcinoma and squamous cell carcinoma. Discrepancies in HPV detection methods and sample sources highlight the need for further research with standardized methodologies to elucidate HPV’s role in lung carcinogenesis and its clinical implications. Overall, this systematic review offers insights into HPV’s role in lung cancer epidemiology and clinical characteristics. Despite inconclusive evidence, intriguing associations between HPV and lung adenocarcinoma and squamous cell carcinoma have emerged. Further research with standardized methodologies and larger cohorts is needed for clarity.
Liquid and Tissue Biopsies for Lung Cancer: Algorithms and Perspectives
Authors: Hofman Paul
Published: September 2024

The targeted therapies and immunotherapies in thoracic oncology, particularly for NS-NSCLC, are associated with an increase in the number of predictive biomarkers to be assessed in routine clinical practice. These treatments are administered thanks to marketing authorization for use in daily practice or are evaluated during clinical trials. Since the molecular targets to be identified are more and more complex and numerous, it is now mandatory to use NGS. NGS can be developed from both tissue and fluid (mainly blood). The blood tests in oncology, so-called “liquid biopsies” (LB), are performed with plasmatic circulating free DNA (cf-DNA) and are complementary to the molecular testing performed with a TB. LB use in lung cancer is associated with international guidelines, but additional algorithms could be set up. However, even if useful for better care of patients, notably with advanced and metastatic NS-NSCLC, until now LB are not often integrated into daily practice, at least in Europe and notably in France. The purpose of this review is to describe the different opportunities and algorithms leading to the identification of the molecular signature of NS-NSCLC, using both tissue and liquid biopsies, and to introduce the principle limitations but also some perspectives in this field.
Impact of Metastatic Pattern on Survival in Patients with Posterior Uveal Melanoma: A Retrospective Cohort Study
Authors: Hindso Tine G. , Jensen Peter S. , Sjøl Mette B. , Nissen Kristoffer , Bjerrum Camilla W. , von Benzon Eric , Faber Carsten , Urbak Steen F. , Donia Marco , Svane Inge M. , Ellebaek Eva , Heegaard Steffen , Madsen Karine , Kiilgaard Jens F.
Published: September 2024

Background/Objectives: Metastatic posterior uveal melanoma (PUM) is one of the deadliest types of melanomas. Though the median survival is short, some patients with metastatic disease live for a long time. In this study, we investigated whether the anatomical location of the metastatic lesions is associated with differences in survival. Methods: One hundred and seventy-eight patients with metastatic PUM with baseline whole-body imaging were retrospectively included. The patients were divided into three groups based on the anatomical location of metastases: (1) exclusive liver metastases (hepatic pattern), (2) both hepatic and extrahepatic metastatic lesions (hepatic–extrahepatic pattern), and (3) exclusive extrahepatic lesions (extrahepatic pattern). Survival was investigated using Kaplan–Meier plots, log-rank test, and the Cox proportional hazard model. Results: In total, 95 patients (53%) presented with hepatic pattern, 66 patients (37%) presented with hepatic–extrahepatic pattern, and 17 patients (10%) presented with extrahepatic pattern. Overall survival was significantly longer in patients with extrahepatic pattern (median 17.0 months) compared to those with hepatic pattern (median 11.0 months) and hepatic–extrahepatic pattern (median 7.0 months) (p < 0.001, log-rank test). Multivariate Cox regression analysis showed increased hazard ratios (HR) for hepatic pattern (HR 2.37, 95% CI 1.08–5.17, p = 0.031) and hepatic–extrahepatic pattern (3.25, 95% CI 1.42–7.41, p = 0.005) compared to extrahepatic pattern. Most patients with hepatic (95%) and hepatic–extrahepatic patterns (82%) were diagnosed with metastases by liver ultrasonography screening, whereas 81% of patients with extrahepatic pattern developed symptoms that led to the diagnosis. Conclusions: Extrahepatic pattern was associated with prolonged survival in patients with metastatic PUM, despite there being a larger proportion of symptomatic patients. It is therefore important to consider the anatomical location of the metastatic lesions when stratifying patients into clinical trials.
Risk of Colorectal Cancer among Patients with One or Multiple Metabolic Syndrome Components
Authors: Sundaram Shanmuga , Lamichhane Rajan , Cecchetti Alfred , Murughiyan Usha , Sundaram Uma
Published: September 2024

Background/Objectives: Dysfunctions of metabolic syndrome (MetS) have been identified as a significant risk factor for colorectal cancer (CRC). However, current colon cancer guidelines do not classify patients with MetS as high risk, thereby leaving these individuals vulnerable. Consequently, we explored the relationship between MetS, its individual components, and the development of CRC in a cohort of patients with MetS to assess the necessity for CRC screening in these individuals. Methods: This study included patients ages 18 and older that received a service from the Marshall-Health (MH) practice plan, Cabell-Huntington Hospital (CHH), MU/JCESOM’s Edwards Comprehensive Cancer Center (ECCC), or the University of Kentucky HealthCare (UKHC) system between 2010 and 2018. We implemented log-binomial regression models to assess the individual and collective effects of MetS components after adjusting other CRC risk factors. Results: Given that CRC prevalence increases in the older population (aged 65 years and above), and that multiple components of MetS are observed within the same population, we analyzed the concurrent impact of all MetS components on CRC. Log-binomial regression models were implemented to assess the risk of CRC due to MetS components after adjusting other risk factors. Conclusions: We identified specific components that markedly increased CRC risk, suggesting that individuals with these components should be prioritized for early screening. These findings could significantly influence early CRC screening protocols, with the ultimate aim to reduce mortality associated with the disease.
Tumor Immune Microenvironment Biomarkers for Recurrence Prediction in Locally Advanced Rectal Cancer Patients after Neoadjuvant Chemoradiotherapy
Authors: Hwang Jun-Eul , Kim Sung-Sun , Bang Hyun-Jin , Kim Hyeon-Jong , Shim Hyun-Jeong , Bae Woo-Kyun , Chung Ik-Joo , Sun Eun-Gene , Lee Taebum , Ock Chan-Young , Nam Jeong-Seok , Cho Sang-Hee
Published: September 2024

Background/Objectives: The tumor microenvironment (TME) has emerged as a significant prognostic factor. This study aimed to identify prognostic factors by combining clinicopathologic parameters and the TME biomarkers in patients who underwent surgery following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC). Methods: CD8+ T cells, CXCR3, CXCL10, and α-smooth muscle actin (α-SMA) were analyzed via immunohistochemical staining. We also incorporated AI-powered digital pathology to assess the spatial TME. The associations between these biomarkers, clinicopathologic parameters, and survival outcomes were evaluated. Results: CD8+ T cell expression, CXCR3 expression in tumor-infiltrating lymphocytes (TILs), and immune phenotypes were correlated. LARC patients with a high expression of CD8+ T cells, CXCR3 in TILs, and an inflamed phenotype had a significantly better prognosis than their counterparts did. In the multivariate analysis, the expression of CD8+ T cells and the inflamed/immune-excluded phenotype were significant tumor immune microenvironment (TiME) biomarkers for recurrence-free survival (RFS) but not for overall survival (OS). Notably, patients with the immune-desert phenotype had a poor prognosis regardless of pathologic stage, even if postoperative chemotherapy was administered (p < 0.001). Conclusions: CD8+ T cells and AI-powered immune phenotypes, alongside clinical factors, can guide personalized treatment in LARC patients receiving nCRT. A therapeutic strategy to modify the TiME after nCRT could help reduce recurrence after surgery.
Comprehensive Axillary Management of Clinically Node-Positive (cN+) Breast Cancer Patients: A Narrative Review on Neoadjuvant Chemotherapy
Authors: Cipolla Calogero , Gebbia Vittorio , D’Agati Eleonora , Greco Martina , Mesi Chiara , Scandurra Giuseppa , Valerio Maria Rosaria
Published: September 2024

Background. In breast cancer (BC) patients, axillary management has undergone major improvements over the last few years, and efforts to identify the optimal strategy for the management of axillary surgery are still ongoing. Methods. In current clinical practice, women with clinically node-positive (cN+) BC usually receive neoadjuvant chemotherapy (NACT) with the aim of reducing the extent of primary disease and, thus, allowing for axillary-conservative surgery. Remarkably, after NACT, up to one out of three patients achieves an axillary pathologic complete response, which, in turn, is associated with a more favorable prognosis than residual axillary disease. However, NACT is not without drawbacks, as NACT-associated inflammation can damage lymphatic vessels. Furthermore, varying degrees of response may occur in the axillary lymph nodes, increasing the false negative rate for sentinel biopsy. Results. At present, there is no consensus on the optimal approach in patients with cN+ BC undergoing NACT, although multidisciplinary management seems to be recommended. Conclusions. This narrative review provides a comprehensive overview of axillary management in cN+ BC patients undergoing NACT. It uses a multidisciplinary approach that encompasses the oncological management perspectives, as well as surgical and chemotherapeutic viewpoints.
Implications of CD154 and Its Receptors in the Pathogenesis and Treatment of Systemic Lupus Erythematosus
Authors: Allard Catherine Cornet , Salti Suzanne , Mourad Walid , Hassan Ghada S.
Published: September 2024

CD154, also known as CD40 ligand, is a costimulatory molecule involved in humoral and adaptive immune responses upon pairing with its classical receptor, CD40. The CD154/CD40 dyad is a key participant in the pathogenesis of many autoimmune diseases, including systemic lupus erythematosus (SLE). In SLE, the major cells at play, T and B lymphocytes, are shown to overexpress CD154 and CD40, respectively. Subsequently, these cells and other CD40-positive cells engage in numerous effector functions contributing to SLE development. With the recent identification of additional receptors for CD154, all belonging to the integrin family, the role of CD154 in SLE is more complex and calls for deeper investigation into its biological significance. Many therapeutic strategies directed against the CD154/CD40 couple have been deployed for the treatment of SLE and proved efficient in animal models and human studies. However, the incidence of thromboembolic complications in patients treated with these anti-CD154/CD40 antibodies halted their further clinical assessments and called for another class of therapies targeting these molecules. Second-generation antibodies directed against CD154 or CD40 are showing promising results in the advanced stages of clinical testing. Our review presents a thorough description of CD154 and its receptors, CD40 and the integrin family members in SLE pathogenesis. All these elements of the CD154 system represent important therapeutic targets for the treatment of SLE.
The Role of CENPK Splice Variant in Abiraterone Response in Metastatic Castration-Resistant Prostate Cancer
Authors: Huang Minhong , Qin Sisi , Gao Huanyao , Kim Wootae , Xie Fang , Yin Ping , John August , Weinshilboum Richard M. , Wang Liewei
Published: September 2024

Most patients with metastatic prostate cancer eventually develop resistance to primary androgen deprivation therapy. To identify predictive biomarker for Abiraterone acetate/prednisone resistance, we screened alternative splice variants between responders and non-responders from the PROMOTE clinical study and pinned down the most significant variant, CENPK–delta8. Through preclinical patient-derived mouse xenograft (PDX) and 3D organoids obtained from responders and non-responders, as well as in vitro models, aberrant CENPK–delta8 expression was determined to link to drug resistance via enhanced migration and proliferation. The FLNA and FLOT1 were observed to specifically bind to CENK–delta8 rather than wild-type CENPK, underscoring the role of CENPK–delta8 in cytoskeleton organization and cell migration. Our study, leveraging data from the PROMOTE study, TCGA, and TCGA SpliceReq databases, highlights the important function of alternative splice variants in drug response and their potential to be prognostic biomarkers for improving individual therapeutic outcomes in precision medicine.