Enhance Treatment Effectiveness Research Articles

Ion Mobility-Mass Spectrometry Captures the Structural Consequences of Lipid Nanoparticle Encapsulation on Ribonucleic Acid Cargo.

Ribonucleic acids (RNAs) are becoming increasingly significant in our search for improved biotherapeutics. RNA-based treatments offer high specificity, targeted delivery, and potentially lower-cost options for various debilitating human diseases. Despite these benefits, there are still relatively few FDA-approved RNA-based therapies, with the notable exceptions being the mRNA (mRNA) COVID-19 vaccines, which are delivered using lipid nanoparticle (LNP) systems. LNPs are distinctive drug delivery systems (DDSs) because of their ability to target specific cells, their biocompatibility, and their efficiency in merging with cellular membranes to enhance treatment effectiveness. While the biophysical landscapes of RNA structures in solution are relatively well understood, the impact of the LNP environment on RNA remains less clear. This study uses native ion mobility-mass spectrometry (IM-MS) and collision-induced unfolding (CIU) techniques to investigate how LNP encapsulation affects RNA structure and stability. We examine how various factors, such as ionization polarity, cofactor binding, lipid types, and lipid ratios, influence LNP-released RNA cargo. Our findings reveal that LNP DDSs induce significant changes in the structures and stabilities of their RNA cargo. However, the extent of these changes strongly depends on the type and composition of the lipids used. We conclude by discussing how IM-MS and CIU can aid in the continued development of more efficient LNP DDSs and improve DDS selection methodologies overall.

Melanocortin-4 receptor antagonist TCMCB07 alleviates chemotherapy-induced anorexia and weight loss in rats.

Cancer patients undergoing chemotherapy often experience anorexia and weight loss that substantially deteriorates overall health, reduces treatment tolerance and quality of life, and worsens oncologic outcomes. There are currently few effective therapeutic options to mitigate these side effects. The central melanocortin system, which plays a pivotal role in regulating appetite and energy homeostasis, presents a logical target for treating anorexia and weight loss. In this preclinical study, we evaluated the efficacy of TCMCB07, a synthetic antagonist of the melanocortin-4 receptor, in mitigating anorexia and weight loss in several rat models of chemotherapy: cisplatin, 5-fluorouracil, cyclophosphamide, vincristine, doxorubicin, and a combination of irinotecan and 5-fluorouracil. Our results indicate that peripheral administration of TCMCB07 improved appetite, stabilized body weight, preserved fat and heart mass, and slightly protected lean mass after multiple cycles of chemotherapy. Furthermore, combining TCMCB07 with a growth differentiation factor 15 antibody enhanced treatment effectiveness. Similar effects from TCMCB07 treatment were observed in a rat tumor model following combination chemotherapy. No notable adverse effects nor increased chemotherapy-related toxicities were observed with TCMCB07 treatment. These findings suggest that peripheral administration of TCMCB07 holds promise as a therapeutic approach for alleviating chemotherapy-induced anorexia and weight loss, potentially benefiting numerous patients undergoing chemotherapy.

Аналіз проблеми розвитку психологічної компетентності у майбутніх фахівців з фізичної реабілітації в контексті сучасних психологічних досліджень

Psychological competence is critically important for professionals in the field of physical rehabilitation, as it contributes to the emotional and psychological well-being of patients throughout the rehabilitation process. Currently, there are no systematic studies on the development of psychological competence among physical rehabilitation specialists, although such studies could be useful in enhancing the effectiveness of rehabilitation interventions. Examining the psychological readiness of physical rehabilitation professionals can help improve relationships with patients, increase patient motivation and commitment to the therapeutic process, and enhance treatment outcomes. The aim of this study is to conduct a theoretical analysis of the development of psychological competence among future physical rehabilitation specialists in the context of contemporary psychological research and to identify factors influencing its development. The object of the study is the process of forming psychological competence in future physical rehabilitation specialists, while the subject is the contemporary psychological aspects of this process. To achieve this goal, an analysis of the current state of psychological competence development in future specialists is conducted, along with the identification of key aspects and training strategies that contribute to its formation. Understanding the psychological readiness of physical rehabilitation professionals can significantly improve the quality of patient care and enhance treatment effectiveness.

From weight loss to cancer treatment: Fasting as an adjuvant anticancer therapy

The number of studies that have been conducted on the possible benefits of different types of fasting or calorie restriction on cancer therapy, including the likelihood that these treatments lessen side effects, has been limited. However, the results are nevertheless promising. Chemotherapy’s adverse effects have led to a quest for options that reduce reliance on it. The susceptibility of tumorous cells to specific metabolites and nutrient deficiency is increasingly recognized as a key characteristic of the disease. This review delves into the data on various fasting methods and calorie restriction in rodents and humans, with a focus on biological adaptations that could potentially lower cancer risk or enhance cancer treatment results. We also emphasize recent scientific developments regarding the use of prolonged fasting and fasting-mimicking diets as a possible additional treatment for patients receiving immunotherapy or other treatments. This approach shows promise in enhancing treatment effectiveness, preventing resistance, and minimizing side effects. This study proposes that combining fasting and calorie restriction with chemotherapy, immunotherapy, or other therapies might be a potential technique to improve treatment efficacy, avoid resistance, and reduce adverse effects.

The Role of the Microbiome and of Radiotherapy-Derived Metabolites in Breast Cancer.

The gut microbiome has emerged as a crucial player in modulating cancer therapies, including radiotherapy. In the case of breast cancer, the interplay between the microbiome and radiotherapy-derived metabolites may enhance therapeutic outcomes and minimize adverse effects. In this review, we explore the bidirectional relationship between the gut microbiome and breast cancer. We explain how gut microbiome composition influences cancer progression and treatment response, and how breast cancer and its treatments influence microbiome composition. A dual role for radiotherapy-derived metabolites is explored in this article, highlighting both their therapeutic benefits and potential hazards. By integrating genomics, metabolomics, and bioinformatics tools, we present a comprehensive overview of these interactions. The study provides real-world insight through case studies and clinical trials, while therapeutic innovations such as probiotics, and dietary interventions are examined for their potential to modulate the microbiome and enhance treatment effectiveness. Moreover, ethical considerations and patient perspectives are discussed, ensuring a comprehensive understanding of the subject. Towards revolutionizing treatment strategies and improving patient outcomes, the review concludes with future research directions. It also envisions integrating microbiome and metabolite research into personalized breast cancer therapy.

Exploring the Integration of the MimicIV Database with CRRT Technology to Optimize Treatment Strategies for Critically Ill Patients

With the rapid development of medical information technology, the application of big data in medical research is increasingly widespread. The MimicIV database, as an open resource containing extensive clinical information on Intensive Care Unit (ICU) patients, provides valuable data support for researchers. Continuous Renal Replacement Therapy (CRRT), as an effective renal support technique, plays a crucial role in the treatment of critically ill patients. This paper aims to explore how to utilize the information in the MimicIV database, combined with CRRT technology, to optimize treatment strategies for critically ill patients. By analyzing clinical data from the MimicIV database, this paper proposes a series of CRRT-based treatment strategies intended to enhance treatment effectiveness, reduce complications, and improve patient outcomes.

Recovery of Executive Functions in Alcohol Use Disorder: role of Neuropsychological Rehabilitation

Abstract Background Alcohol Use Disorder (AUD) is a growing public health concern with high incidence of executive functions (EFs) changes, affecting disease progression and treatment effectiveness. Inconsistencies persist in studies on the role of neuropsychological rehabilitation (NR) in EF recovery within AUD interventions. Our aim is to analyse the effect of NR on EFs in AUD interventions. Methods A prospective cohort study included 65 participants of both sexes, diagnosed with AUD, free of psychiatric comorbidities or severe neurological conditions. They underwent alcohol detoxification in hospital/home from 2021 to 2023, completing three evaluation moments (M1-Baseline, M2-3 months, M3-6 months). Patients receiving usual treatment (WTG-weekly therapeutic groups) - were compared to those with additional Neuropsychological Rehabilitation (NRG) regarding Sociodemographic and Severity of Alcohol Dependence Questionnaires, Hospital Anxiety and Depression Scale, Frontal Assessment Battery (FAB), Number and Letters Subscale of Weschler Adult Intelligence Scale (WAIS). Our main outcome was FAB-general executive functioning, and secondary outcome was WAIS-working memory. Friedman test compared assessments across the three points (alpha 5%). Results Statistically significant differences were found for FAB in both groups, (p < 0.001) between M1 and both M2 and M3, indicating improved executive functioning, particularly in NRG. Working memory also improved in both groups (WTG: p = 0.036; NRG: p < 0.001), with NRG showing better M2 performance. Conclusions There is evidence that neuropsychological rehabilitation facilitates the recovery of executive functions and may play a pivotal role in relapse prevention. It is crucial that the treatment of these situations incorporates public health, preventive and damage minimization measures. KeyWords: Executive Function; Neuropsychological Rehabilitation; Alcohol Use Disorder. Key messages • Recovery of executive functions is crucial from a Public Heath perspective in AUD populations, minimizing morbidity, permanent disabilities and contributing to more effective healthcare services. • Integrating Neuropsychological Rehabilitation into standard Alcohol Use Disorder treatments can enhance treatment effectiveness, reducing disease burden.

Nanomaterial-Enhanced Microneedles: Emerging Therapies for Diabetes and Obesity.

Drug delivery systems (DDS) have improved therapeutic agent administration by enhancing efficacy and patient compliance while minimizing side effects. They enable targeted delivery, controlled release, and improved bioavailability. Transdermal drug delivery systems (TDDS) offer non-invasive medication administration and have evolved to include methods such as chemical enhancers, iontophoresis, microneedles (MN), and nanocarriers. MN technology provides innovative solutions for chronic metabolic diseases like diabetes and obesity using various MN types. For diabetes management, MNs enable continuous glucose monitoring, diabetic wound healing, and painless insulin delivery. For obesity treatment, MNs provide sustained transdermal delivery of anti-obesity drugs or nanoparticles (NPs). Hybrid systems integrating wearable sensors and smart materials enhance treatment effectiveness and patient management. Nanotechnology has advanced drug delivery by integrating nano-scaled materials like liposomes and polymeric NPs with MNs. In diabetes management, glucose-responsive NPs facilitate smart insulin delivery. At the same time, lipid nanocarriers in dissolving MNs enable extended release for obesity treatment, enhancing drug stability and absorption for improved metabolic disorder therapies. DDS for obesity and diabetes are advancing toward personalized treatments using smart MN enhanced with nanomaterials. These innovative approaches can enhance patient outcomes through precise drug administration and real-time monitoring. However, widespread implementation faces challenges in ensuring biocompatibility, improving technologies, scaling production, and obtaining regulatory approval. This review will present recent advances in developing and applying nanomaterial-enhanced MNs for diabetes and obesity management while also discussing the challenges, limitations, and future perspectives of these innovative DDS.

The crosstalk between primary MSCs and cancer cells in 2D and 3D cultures: potential therapeutic strategies and impact on drug resistance.

The tumor microenvironment (TME) significantly influences cancer progression, and mesenchymal stem cells (MSCs) play a crucial role in interacting with tumor cells via paracrine signaling, affecting behaviors such as proliferation, migration, and epithelial-mesenchymal transition. While conventional 2D culture models have provided valuable insights, they cannot fully replicate the complexity and diversity of the TME. Therefore, developing 3D culture systems that better mimic in vivo conditions is essential. This review delves into the heterogeneous nature of the TME, spotlighting MSC-tumor cellular signaling and advancements in 3D culture technologies. Utilizing MSCs in cancer therapy presents opportunities to enhance treatment effectiveness and overcome resistance mechanisms. Understanding MSC interactions within the TME and leveraging 3D culture models can advance novel cancer therapies and improve clinical outcomes. Additionally, this review underscores the therapeutic potential of engineered MSCs, emphasizing their role in targeted anti-cancer treatments.

Machine learning in oncological pharmacogenomics: advancing personalized chemotherapy.

This review analyzes the application of machine learning (ML) in oncological pharmacogenomics, focusing on customizing chemotherapy treatments. It explores how ML can analyze extensive genomic, proteomic, and other omics datasets to identify genetic patterns associated with drug responses. This, in turn, facilitates personalized therapies that are more effective and have fewer side effects. Recent studies have emphasized ML's revolutionary role of ML in personalized oncology treatment by identifying genetic variability and understanding cancer pharmacodynamics. Integrating ML with electronic health records and clinical data shows promise in refining chemotherapy recommendations by considering the complex influencing factors. Although standard chemotherapy depends on population-based doses and treatment regimens, customized techniques use genetic information to tailor treatments for specific patients, potentially enhancing efficacy and reducing adverse effects.However, challenges, such as model interpretability, data quality, transparency, ethical issues related to data privacy, and health disparities, remain. Machine learning has been used to transform oncological pharmacogenomics by enabling personalized chemotherapy treatments. This review highlights ML's potential of ML to enhance treatment effectiveness and minimize side effects through detailed genetic analysis. It also addresses ongoing challenges including improved model interpretability, data quality, and ethical considerations. The review concludes by emphasizing the importance of rigorous clinical trials and interdisciplinary collaboration in the ethical implementation of ML-driven personalized medicine, paving the way for improved outcomes in cancer patients and marking a new frontier in cancer treatment.

Machine learning-based classification of varicocoele grading: A promising approach for diagnosis and treatment optimization.

Varicocoele is a correctable cause of male infertility. Although physical examination is still being used in diagnosis and grading, it gives conflicting results when compared to ultrasonography-based varicocoele grading. We aimed to develop a multi-class machine learning model for the grading of varicocoeles based on ultrasonographic measurements. Between January and May 2024, we enrolled unilateral varicocoele patients at an infertility clinic, assessing their varicocoele stages using the Dubin and Amelar system. We measured vascular diameter and reflux time at the testicular apex and the subinguinal region ultrasonography in both the supine and standing positions. Using these measurements, we developed four multi-class machine learning models, evaluating their performance metrics and determining which patient position and projection were most influential in varicocoele grading. We included 248 patients with unilateral varicocoele in the study, their average age was 26.61±4.95 years old. Of these, 212 had left-sided and 36 had right-sided varicocoeles. According to the Dubin and Amelar system, there were 66 grade I, 96 grade II, and 86 grade III varicocoeles. Among the models we created, the random forest (RF) model performed best, with an overall accuracy of 0.81±0.06, an F1 score of 0.79±0.02, a sensitivity of 0.69±0.02, and a specificity of 0.8±0.03. Vascular diameter measurement at the testicular apex in the supine position had the most impact on grading across all models. In support vector machine and multi-layer perceptron models, reflux time measurements from the subinguinal projection in the standing position contributed the most, while in RF and k-nearest neighbors models, measurements from the subinguinal projection in the supine position were the most influential. Machine learning methods have demonstrated superior accuracy in predicting disease compared to traditional statistical regressions and nomograms. These advancements hold promise for clinically automated prediction of varicocoele grades in patients. Tailored varicocoele grading for individuals has the potential to enhance treatment effectiveness and overall quality of life.

Exploring core and bridge symptoms in patients recovering from stroke: a network analysis.

Patients recovering from stroke experience a variety of symptoms that present as a synergistic and mutually reinforcing "symptom cluster," rather than as singular symptoms. In this study, we researched and systematic analyzed these symptom clusters, including core and bridge symptoms, to help determine the relationships between symptoms and to identify key symptom targets, providing a new approach for formulating precise symptom management interventions. Convenience sampling was applied to select 432 stroke recovery patients treated in the Seventh People's Hospital of Changzhou City from August 1, 2023 to April 14, 2024. Subsequently, a cross-sectional survey was conducted using the General Information Questionnaire and Stroke Symptom Experience Scale to extract symptom clusters via exploratory factor analysis. Finally, the "qgraph" and "bootnet" packages in the R language were used to construct a network layout to describe the relationships between symptoms and calculate the centrality index. The average age of the 432 enrolled recovering stroke patients was 68.17 ± 12.14 years, including 268 males (62.04%) and 164 females (37.96%), none of whom underwent surgical intervention. Among this cohort, the 3 symptoms with the highest incidence rates were "limb weakness" (A2, 80.56%), "fatigue" (A5, 77.78%), and "limitations of limb movement" (A1, 68.06%). A total of 5 symptom clusters were extracted: the somatic activity disorder, mood-disorder-related, cognitive-linguistic dysfunction, somatic-pain-related, and foot dysfunction symptom clusters. In the symptom network, the 2 most common symptoms in terms of intensity and expected impact were "fatigue" (A5, rs = 1.14, re = 1.00) and "pessimism about the future" (B3, rs = 1.09, re = 1.02). The symptom with the strongest bridge intensity was "limb pain" (D1, rs = 2.64). This study uses symptom network analysis to explore the symptoms of stroke patients during recovery, identifying core symptoms and bridge symptoms. Based on these findings, we can develop more targeted management plans to improve the accuracy and efficiency of interventions. Through this management approach, we can enhance treatment effectiveness, reduce unnecessary medication, lower adverse drug reactions, and optimize the allocation of medical resources.

Electrocorticography and navigated transcranial magnetic stimulation-tailored supratotal resection for epileptogenic low-grade gliomas.

Epilepsy is commonly associated with low-grade gliomas (LGGs), impacting patients' well-being. While resection is the primary treatment, seizures can persist postoperatively in 27%-55% of cases. The authors aimed to evaluate an electrocorticography (ECoG) and navigated transcranial magnetic stimulation (nTMS)-tailored supratotal resection (ETT-SpTR) for LGG in controlling seizures, preserving neurological function, and enhancing treatment effectiveness. The authors retrospectively analyzed a prospectively enrolled cohort of patients with LGG presenting with epileptic seizures with ictal/interictal activity on electroencephalography (EEG) who underwent resective surgery. The authors performed preoperative nTMS to identify functional cortical areas. ECoG was used to guide the removal of the high-risk epilepsy cortical areas (HREAs). Patients were divided into two groups: group I, the control group, underwent gross-total resection alone, whereas group II patients underwent removal of HREAs identified by ECoG (ETT-SpTR). Resection avoided functionally eloquent areas as identified on nTMS, checked with cortical mapping. Postoperative seizure outcome was assessed using the Engel classification. Fifteen patients who underwent LGG resection between January and July 2023 were included. Among 24 identified nTMS-positive points, none were included in the resection. Overall, 73.3% of patients (11/15) showed positive intraoperative ECoG, with better outcomes in group II (85.7% Engel class IA) than in group I (25% Engel class IA) at the follow-up (p = 0.02, OR 0.5 [95% CI 0.035-7.10], RR 0.19 [95% CI 0.03-1.2]). Seizure control was significantly better in group II, with no notable differences in postoperative transient neurological deficits between the two groups (p = 0.45). No permanent neurological deficits were observed during follow-up. Statistical analysis revealed significant differences between the two groups (p < 0.05). This preliminary study affirms the predictive value of TMS for postoperative neurological status and safety in epileptic patients. Intraoperative ECoG effectively identified peritumoral HREAs. ETT-SpTR significantly improved epileptic outcomes, preserving functions without permanent neurological worsening. Additional resection targets the HREAs in the temporal, frontal, and parietal lobes.

AC-assisted microbially induced carbonate precipitation for sand reinforcement: An experimental study

Microbially induced carbonate precipitation (MICP) is a promising method for transforming natural soils into a rock-like material, enhancing soil strength and creating an environmentally friendly engineered geomaterial for load-bearing purposes. Applying alternating current (AC) for enhancing precipitation including changing the crystalline form of the calcium carbonate precipitates appeals as a possible solution to break the upper limit of the unconfined compressive strength (UCS) of bio-treated specimens. To assess the viability of AC-assisted MICP, a series of experiments were designed and conducted under various combination of conditions. The UCS, calcium carbonate content and permeability of the bio-fabricated specimens were obtained to evaluate the treatment effectiveness of AC-assisted MICP. The results demonstrate that the UCS of the sand column exhibits a linear increase with the applied voltage from 10 V to 30 V (i.e., electric field strength from 0.91 V/cm to 2.73 V/cm). The UCS value of the bio-specimen reaches 9.4 MPa after 3 treatments at a concentration of 1.00 mol/L, a voltage of 30 V, and a frequency of 100 Hz. With the assistance of an AC electric field, the adverse impacts caused by high chemical concentrations in the MICP process can be mitigated. We report that a more uniform distribution of the calcium carbonate content of the treated specimen is obtained under an optimal AC frequency of approximately 100 Hz in the current series of experiments. The induced ion vibration under the action of AC results in a change in crystalline form and an increase in the amount and uniformity of crystals precipitated on the surface of the soil grains, supported by X-ray diffraction (XRD) patterns and scanning electron microscope (SEM) images. For reference, the energy consumption and the cost for increasing the UCS of the bio-treated specimen to 5 MPa is estimated at 375.86 kWh and 676.55 HK$ per cubic meter, respectively. The findings from our experimental investigation and analysis provide compelling evidence that utilising AC electric field holds great potential for achieving an enhanced treatment effect of MICP and hence a stronger bio-soil.

Impact of Epigenetics, Diet, and Nutrition-Related Pathologies on Wound Healing.

Chronic wounds pose a significant challenge to healthcare. Stemming from impaired wound healing, the consequences can be severe, ranging from amputation to mortality. This comprehensive review explores the multifaceted impact of chronic wounds in medicine and the roles that diet and nutritional pathologies play in the wound-healing process. It has been well established that an adequate diet is crucial to proper wound healing. Nutrients such as vitamin D, zinc, and amino acids play significant roles in cellular regeneration, immune functioning, and collagen synthesis and processing. Additionally, this review discusses how patients with chronic conditions like diabetes, obesity, and nutritional deficiencies result in the formation of chronic wounds. By integrating current research findings, this review highlights the significant impact of the genetic make-up of an individual on the risk of developing chronic wounds and the necessity for adequate personalized dietary interventions. Addressing the nutritional needs of individuals, especially those with chronic conditions, is essential for improving wound outcomes and overall patient care. With new developments in the field of genomics, there are unprecedented opportunities to develop targeted interventions that can precisely address the unique metabolic needs of individuals suffering from chronic wounds, thereby enhancing treatment effectiveness and patient outcomes.

Clinical Health Psychology Perspectives in Diabetes Care: A Retrospective Cohort Study Examining the Role of Depression in Adherence to Visits and Examinations in Type 2 Diabetes Management

Background: Depression in type 2 diabetes mellitus (T2DM) impacts glycemic control and complications. This study examines the influence of depression on compliance with recommended annual diabetes assessments in patients within the Local Healthcare Authority of Romagna. From a clinical health psychology perspective, understanding how depression influences patients’ engagement in managing their conditions is crucial. This insight can help improve healthcare services by ensuring they address mental health needs and thereby enhance treatment effectiveness and overall patient outcomes. Methods: This retrospective cohort study included residents of Romagna with incident T2DM from 2015 to 2017, followed from 1 January 2018 to 31 December 2022. Depression was identified via hospital discharge records or antidepressant prescriptions. Adherence to diabetes care guidelines was measured using the Guideline Composite Indicator (GCI). Results: The study included 13,285 patients, with a mean age of 61.1 years. Prevalence of post-diabetes depression increased from 3.0% in 2018 to 8.9% in 2022. Initial analyses showed higher GCI rates among patients with depression. However, propensity-score adjustment revealed that by 2021–2022, patients with pre-diabetes depression had 5% lower compliance rates (p-value ≤ 0.05). Older adults with depression had reduced adherence, while younger adults with post-diabetes depression had higher adherence rates. Conclusions: Depression significantly affects adherence to diabetes care guidelines in T2DM patients, particularly among older adults. Integrated care models addressing both diabetes and depression are crucial for improving health outcomes.

Gut Microbiota Disruption in Hematologic Cancer Therapy: Molecular Insights and Implications for Treatment Efficacy.

Hematologic malignancies (HMs), including leukemia, lymphoma, and multiple myeloma, involve the uncontrolled proliferation of abnormal blood cells, posing significant clinical challenges due to their heterogeneity and varied treatment responses. Despite recent advancements in therapies that have improved survival rates, particularly in chronic lymphocytic leukemia and acute lymphoblastic leukemia, treatments like chemotherapy and stem cell transplantation often disrupt gut microbiota, which can negatively impact treatment outcomes and increase infection risks. This review explores the complex, bidirectional interactions between gut microbiota and cancer treatments in patients with HMs. Gut microbiota can influence drug metabolism through mechanisms such as the production of enzymes like bacterial β-glucuronidases, which can alter drug efficacy and toxicity. Moreover, microbial metabolites like short-chain fatty acids can modulate the host immune response, enhancing treatment effectiveness. However, therapy often reduces the diversity of beneficial bacteria, such as Bifidobacterium and Faecalibacterium, while increasing pathogenic bacteria like Enterococcus and Escherichia coli. These findings highlight the critical need to preserve microbiota diversity during treatment. Future research should focus on personalized microbiome-based therapies, including probiotics, prebiotics, and fecal microbiota transplantation, to improve outcomes and quality of life for patients with hematologic malignancies.

Clinical advantages of incorporating predicted weekly anatomy in IMPT optimization with reduced setup error

AbstractBackgroundIn head and neck (H&amp;N) cancer treatment, a conventional setup error (SE) of 3mm is often used in robust optimization (cRO3mm). However, cRO3mm may lead to excessive radiation doses to organs at risk (OARs) and does not purposefully compensate for interfractional anatomy variations.PurposeThis study introduces a method using predicted images from an anatomical model and a reduced 1mm SE uncertainty for robust optimization (aRO1mm), aiming to decrease the dose to OARs without affecting the coverage of the clinical target volume (CTV).MethodsThis retrospective study involved 10 nasopharynx radiotherapy patients. Validation CT scans (vCT) from treatment weeks 1 to 6 were analyzed. A predictive anatomical model, designed to capture the average anatomical changes over time, provided predicted CT images for weeks 1, 3, and 5. We compared three optimization scenarios: (1) aRO1mm, using three predicted images with 1mm setup shift and 3% range uncertainty, (2) cRO3mm, with a robust 3mm setup shift and 3% range uncertainty, and (3) cRO1mm, a robust 1mm setup shift and 3% range uncertainty. The accumulated dose to CTVs and serial organs was evaluated under these uncertainties, while parallel OARs were assessed using the accumulated nominal dose (without errors).ResultsThe accumulated volume receiving 94% of the prescribed dose (V94) for CTVs in cRO3mm exceeded 98%, meeting the clinical goal. For high‐risk CTV, the minimum V94 was 96.44% in aRO1mm and 94.05% in cRO1mm. For low‐risk CTV, these values were 97.68% in aRO1mm and 97.15% in cRO1mm. When comparing aRO1mm to cRO3mm on OARs, aRO1mm reduced normal tissue complication probability (NTCP) for grade 2 xerostomia and dysphagia by averages of 3.67% and 1.54%, respectively.ConclusionaRO1mm lowers the radiation dose to OARs compared to the traditional approach, while maintaining adequate dose coverage on the target area. This method offers an improved strategy for managing uncertainties in radiation therapy planning for H&amp;N cancer, enhancing treatment effectiveness.

Advances in omics data for eosinophilic esophagitis: moving towards multi-omics analyses.

Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease of the esophagus characterized by eosinophil accumulation and has a growing global prevalence. EoE significantly impairs quality of life and poses a substantial burden on healthcare resources. Currently, only two FDA-approved medications exist for EoE, highlighting the need for broader research into its management and prevention. Recent advancements in omics technologies, such as genomics, epigenetics, transcriptomics, proteomics, and others, offer new insights into the genetic and immunologic mechanisms underlying EoE. Genomic studies have identified genetic loci and mutations associated with EoE, revealing predispositions that vary by ancestry and indicating EoE's complex genetic basis. Epigenetic studies have uncovered changes in DNA methylation and chromatin structure that affect gene expression, influencing EoE pathology. Transcriptomic analyses have revealed a distinct gene expression profile in EoE, dominated by genes involved in activated type 2 immunity and epithelial barrier function. Proteomic approaches have furthered the understanding of EoE mechanisms, identifying potential new biomarkers and therapeutic targets. However, challenges in integrating diverse omics data persist, largely due to their complexity and the need for advanced computational methods. Machine learning is emerging as a valuable tool for analyzing extensive and intricate datasets, potentially revealing new aspects of EoE pathogenesis. The integration of multi-omics data through sophisticated computational approaches promises significant advancements in our understanding of EoE, improving diagnostics, and enhancing treatment effectiveness. This review synthesizes current omics research and explores future directions for comprehensively understanding the disease mechanisms in EoE.

Effect of Mifepristone on Migration and Proliferation of Oral Cancer Cells.

Glucocorticoid receptor (GR) overexpression has been linked to increased tumour aggressiveness and treatment resistance. GR antagonists have been shown to enhance treatment effectiveness. Emerging research has investigated mifepristone, a GR antagonist, as an anticancer agent with limited research in the context of oral cancer. This study investigated the effect of mifepristone at micromolar (µM) concentrations of 1, 5, 10 and 20 on the proliferation and migration of oral cancer cells, at 24 and 48 h. Scratch and scatter assays were utilised to assess cell migration, MTT assays were used to measure cell proliferation, Western blotting was used to investigate the expression of GR and the activation of underlying Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signalling pathways, and immunofluorescence (IF) was used to determine the localisation of proteins in HaCaT (immortalised human skin keratinocytes), TYS (oral adeno squamous cell carcinoma), and SAS-H1 cells (squamous cell carcinoma of human tongue). Mifepristone resulted in a dose-dependent reduction in the proliferation of HaCaT, TYS, and SAS-H1 cells. Mifepristone at a concentration of 20 µM effectively reduced collective migration and scattering of oral cancer cells, consistent with the suppression of the PI3K-Akt and MAPK signalling pathways, and reduced expression of N-Cadherin. An elongated cell morphology was, however, observed, which may be linked to the localisation pattern of E-Cadherin in response to mifepristone. Overall, this study found that a high concentration of mifepristone was effective in the suppression of migration and proliferation of oral cancer cells via the inhibition of PI3K-Akt and MAPK signalling pathways. Further investigation is needed to define its impact on epithelial-mesenchymal transition (EMT) markers.