Therapeutic Assessment Research Articles

Animal Models in the Study of Food Allergens: Long-Term Maintenance of Allergic Reactivity in Mouse Models of Food Allergy.

Multiple mouse models have been used to characterize mechanisms of allergic sensitization and anaphylaxis and are widely used for preclinical development of novel therapeutics. However, the majority of published works with mouse models of food allergy have very short intervals between the time of sensitization and the end of the study, and the duration of maintenance of reactivity has not been widely reported. This chapter focuses on two of the most commonly used mouse models with sensitization to peanut or ovalbumin, with the focus on the long-term durability of sensitization to allow for longer therapeutic protocols and assessment of sustained unresponsiveness.

Therapeutic adherence and assessment of satisfaction patients with multiple myeloma treated with immunomodulatory drugs in a "real-world" study: Experiences of the Polish Myeloma Group.

Therapeutic adherence (TA) is one of the most important factors influencing the effectiveness of treatment. Oral anti-cancer drugs are increasingly used to treat malignancy including multiple myeloma (MM). Our study aimed to determine TA of patients with MM treated with IMiDs, to identify TA risk factors, and to determine satisfaction with medical care during the treatment with IMiDs. A cross-sectional survey-based study involving adult patients with MM treated with IMiDs. Between January 2021 and May 2021, 267 patients with MM were enrolled in the study. The dosing schedule was declared as easy by 71.8% of patients, as standard for 24.0%, and difficult for 4.2% of patients. During MM treatment, 85.0% of patients did not skip any IMiDs dose, and 87.6% did not skip the IMiDs dose in the last cycle of chemotherapy. Identified factors affecting TA included the treatment duration and education level. In addition, depending on the patient's well-being, gender, and household companionship influenced TA. Satisfaction with medical care during the treatment with IMiDs was declared by 95.5% of patients with MM. In our cohort, 95.5% of patients were satisfied with the information they received from the hematologist during treatment with IMiDs. Patients with MM treated with IMiDs are highly adherent to treatment. With time from the beginning of treatment, patients need more attention and motivation to adhere to the therapy rules.

Defining Priorities in Value-Based Cancer Care: Insights From the Alliance for Clinical Trials in Oncology National Cooperative Group Survey.

We determine how stakeholders prioritize the importance of oncologic outcomes, patient-reported outcomes (PROs), and cancer-related health care costs. A survey was distributed to the National Clinical Trials Network Alliance for Clinical Trials in Oncology cooperative group membership from May 14 to June 30, 2022. Respondents were asked to rate (5-point Likert scale) and rank (1-9) evidence-based value domains: overall survival, treatment toxicities/complications, quality of life (QOL), financial toxicity, access to care, compliance with evidence-based care, health system performance, scientific discovery and innovation, and cost to the health care system. A total of 514 members responded, including researchers (24.7%), nurses (19.5%), medical oncologists (17.9%), administrators (9.3%), surgical and radiation oncologists (9.1%), patient advocates (3.1%), and nonphysician providers (16.4%). Participants represented various practice settings including National Cancer Institute-designated cancer centers (29.8%), university-affiliated academic cancer centers (21%), hospital-owned oncology practices (21.8%), and others (27.4%). There was agreement in how respondents prioritized value domains (W = 0.39, P < .001). Respondents ranked patient QOL (mean rank: 2.6 ± 1.9) as most important above all other metrics including survival (mean rank: 3.5 ± 0.3) and access to care (mean rank: 3.5 ± 2.1; P < .001). Members engaged in direct patient care also ranked access to care of higher importance than nonclinicians (P = .026). Cost to the health care system (mean rank: 7.5 ± 2.1) and health system performance (mean rank: 7 ± 2) were ranked as least important (P < .001). Inclusion of PROs into therapeutic assessment (59.3%) was the most frequently selected priority of future cooperative group initiatives. Oncology community stakeholders deemed patient-centered value domains as most important and considered patient QOL the highest priority. Inclusion of PROs into clinical trials was endorsed as an important component of therapeutic assessment. These findings can be taken into consideration when creating a value framework for inclusion in cancer clinical trials.

Digital image analysis workflows for evaluation of cell behavior and tumor microenvironment to aid therapeutic assessment in high-risk neuroblastoma

Digital pathology and artificial intelligence are promising emerging tools in precision oncology as they provide more robust and reproducible analysis of histologic, morphologic and topologic characteristics of tumor cells and the surrounding microenvironment. This study aims to develop digital image analysis workflows for therapeutic assessment in preclinical in vivo models. For this purpose, we generated pipelines that enable automatic detection and quantification of vitronectin and αvβ3 in heterotopic high-risk neuroblastoma xenografts, demonstrating that digital analysis workflows can be used to provide robust detection of vitronectin secretion and αvβ3 expression by malignant neuroblasts and to evaluate the possibility of combining traditional chemotherapy (etoposide) with extracellular matrix-targeted therapies (cilengitide). Digital image analysis added evidence for the relevance of territorial vitronectin as a therapeutic target in neuroblastoma, since its expression is modified after treatment, with a mean percentage of 60.44% in combined therapy tumors vs 45.08% in control ones. In addition, the present study revealed the efficacy of cilengitide for reducing αvβ3 expression, with a mean αvβ3 positivity of 34.17% in cilengitide treated material vs 66.14% in control and with less tumor growth when combined with etoposide, with a final mean volume of 0.04 cm3 in combined therapy vs 1.45 cm3 in control. The results of this work highlight the importance of extracellular matrix-focused therapies in preclinical studies to improve therapeutic assessment for high-risk neuroblastoma patients.

Immune-related biomarkers in myocardial infarction; diagnostic/prognostic value and therapeutic potential.

The incidence of myocardial infarction (MI) is increasing worldwide on an annual basis. The incorporation of circulating biomarkers, along with electrocardiography, echocardiography, coronary angiograms, and other diagnostic techniques, is essential in the evaluation, prediction, and therapeutic efficacy assessment of patients afflicted with MI. Biomarker evaluation has been employed in the diagnosis of MI for over five decades. Further biomarker research can be carried out as newer biomarkers have been discovered in pathways such as inflammatory response, neurohormonal stimulation, or myocardial stress that initiate significantly earlier than myocyte necrosis and the diagnostic establishment of cardiac troponins. The assessment of biomarkers for MI is on the brink of a significant transformation due to advancements in comprehending the intricate pathophysiology of the condition. This has led to a pursuit of innovative biomarkers that could potentially overcome the limitations of current biomarkers. For individuals with a high-risk profile, this may facilitate tailoring of appropriate treatment. This review places emphasis on a diverse array of biomarkers that have the potential to offer diagnostic and prognostic information, as well as the latest clinical and preclinical evidence that is driving theoretical advancements in cardiovascular immunotherapy.

La tomographie par émission de positons aux ligands de l’antigène membranaire spécifique de la prostate (TEP-PSMA) dans le cancer de la prostate en France en 2023 : actualités et perspectives

Prostate-specific membrane antigen targeting positron emission tomography (PSMA-PET) has become since recent years increasingly important in the management of patients with prostate cancer. Initially limited to the use in patients with prostate cancer biochemical recurrence in France, PSMA-PET is now routinely use in various setting in prostate cancer patients, on the one hand for initial staging in patients with high-risk prostate cancer, and in the other hands to assess the eligibility for radioligand therapy using PSMA ligands. Other studies are currently assessing PSMA-PET in other settings such as the characterization of prostate disease, the guidance of biopsies or even as a tool for therapeutic assessment in patients with metastatic cancer. The objective of this review is to describe the current use of PSMA-PET in France in 2023, and the perspective of PSMA-PET imaging in the management of patients with prostate cancer in the future.

3T vs. 7T fMRI: capturing early human memory consolidation after motor task utilizing the observed higher functional specificity of 7T.

Functional magnetic resonance imaging (fMRI) visualizes brain structures at increasingly higher resolution and better signal-to-noise ratio (SNR) as field strength increases. Yet, mapping the blood oxygen level dependent (BOLD) response to distinct neuronal processes continues to be challenging. Here, we investigated the characteristics of 7 T-fMRI compared to 3 T-fMRI in the human brain beyond the effect of increased SNR and verified the benefits of 7 T-fMRI in the detection of tiny, highly specific modulations of functional connectivity in the resting state following a motor task. 18 healthy volunteers underwent two resting state and a stimulus driven measurement using a finger tapping motor task at 3 and 7 T, respectively. The SNR for each field strength was adjusted by targeted voxel size variation to minimize the effect of SNR on the field strength specific outcome. Spatial and temporal characteristics of resting state ICA, network graphs, and motor task related activated areas were compared. Finally, a graph theoretical approach was used to detect resting state modulation subsequent to a simple motor task. Spatial extensions of resting state ICA and motor task related activated areas were consistent between field strengths, but temporal characteristics varied, indicating that 7 T achieved a higher functional specificity of the BOLD response than 3 T-fMRI. Following the motor task, only 7 T-fMRI enabled the detection of highly specific connectivity modulations representing an "offline replay" of previous motor activation. Modulated connections of the motor cortex were directly linked to brain regions associated with memory consolidation. These findings reveal how memory processing is initiated even after simple motor tasks, and that it begins earlier than previously shown. Thus, the superior capability of 7 T-fMRI to detect subtle functional dynamics promises to improve diagnostics and therapeutic assessment of neurological diseases.

Wide-Range SPRi Sensors Based on Aptamer/sPD-L1/anti–PD-L1 Sandwich and AuNPs Enhancement for Ultrasensitive Detection of sPD-L1

Soluble programmed death-ligand 1 (sPD-L1) levels vary widely among different stages of tumor development, so the direct quantification of sPD-L1 as a cancer biomarker is useful in cancer diagnosis, prognosis and therapeutic assessment. There is an urgent need for an sPD-L1 detection method with a broad detection range and high sensitivity for monitoring cancer progression and evaluating the effectiveness of immunotherapy in real time. Herein, we have reported an enzyme-free, label-free surface plasmon resonance imaging (SPRi) sensor based on an aptamer/sPD-L1/anti–PD-L1 sandwich structure with gold nanoparticle (AuNP) signal enhancement for the ultrasensitive quantitative measurement of sPD-L1 for the first time. The gold chip of the SPRi sensing platform was modified by DNA aptamers, sPD-L1 was specifically adsorbed on the surface of a DNA aptamer-modified gold chip and then coupled with anti–PD-L1. Thus, the detection of sPD-L1 at different concentrations was realized through the formation of an aptamer/sPD-L1/anti–PD-L1 sandwich structure. We also enhanced the SPR signal via AuNPs to further improve sensor sensitivity. The SPRi sensor is able to measure sPD-L1 within a linear range of 50 pM–10 nM and 100 fM–50 pM, and the minimum detection limit is 19 fM. The sensor is designed to be widely applicable, with better accuracy and reliability for more application scenarios. The prepared SPRi sensor shows great potential in improving the sensitivity of detecting sPD-L1. The proposed method demonstrates the excellent performance of the SPRi sensor and provides a possibility for the establishment of effective clinical assay methods in the future.

Incompleteness trends of epidemiological variables in a Brazilian high complexity cancer registry: An ecological time series study.

Hospital Cancer Registries serve as a vital source of information for clinical and epidemiological research, allowing the evaluation of patient care outcomes through therapeutic protocol analysis and patient survival assessment. This study aims to assess the trend of incompleteness in the epidemiological variables within the Hospital Cancer Registry of a renowned oncology center in a Brazilian state. An ecological time-series study was conducted using secondary data from the Hospital Santa Rita de Cássia Cancer Registry in Espírito Santo between 2000 and 2016. Data completeness was categorized as follows: excellent (<5%), good (5%-10%), fair (10%-20%), poor (20%-50%), and very poor (>50%), based on the percentage of missing information. Descriptive and bivariate statistical analyses were performed using the free software RStudio (version 2022.07.2) and R (version 4.1.0). The Mann-Kendall test was used to assess temporal trends between the evaluated years, and the Friedman test was employed to evaluate quality scores across the years. Among the variables assessed, birthplace, race/color, education, occupation, origin, marital status, history of alcohol and tobacco consumption, previous diagnosis and treatment, the most important basis for tumor diagnosis, tumor-node-metastasis staging (TNM) staging, and clinical tumor staging by group (TNM) showed the highest levels of incompleteness. Conversely, other epidemiological variables demonstrated excellent completeness, reaching 100% throughout the study period. Significant trends were observed over the years for history of alcohol consumption (P < .001), history of tobacco consumption (P < .001), TNM staging (P = .016), clinical tumor staging by group (TNM) (P = .002), first treatment received at the hospital (P = .012), disease status at the end of the first treatment at the hospital (P < .001), and family history of cancer (P < .001), and tumor laterality (P = .032). While most epidemiological variables within the Hospital Santa Rita de Cássia Cancer Registry exhibited excellent completeness, some important variables, such as TNM staging and clinical staging, showed high levels of incompleteness. Ensuring high-quality data within Cancer Registries is crucial for a comprehensive understanding of the health-disease process.

Mannose-Functionalized Isoniazid-Loaded Nanostructured Lipid Carriers for Pulmonary Delivery: In Vitro Prospects and In Vivo Therapeutic Efficacy Assessment.

Resistance to isoniazid (INH) is common and increases the possibility of acquiring multidrug-resistant tuberculosis. For this study, isoniazid-loaded nanostructured lipid carriers (INH-NLCs) were developed and effectively functionalized with mannose (Man) to enhance the residence time of the drug within the lungs via specific delivery and increase the therapeutic efficacy of the formulation. The mannose-functionalized isoniazid-loaded nanostructured lipid carrier (Man-INH-NLC) formulation was evaluated with respect to various formulation parameters, namely, encapsulation efficiency (EE), drug loading (DL), average particle size (PS), zeta potential (ZP), polydispersity index (PDI), in vitro drug release (DR), and release kinetics. The in vitro inhalation behavior of the developed formulation after nebulization was investigated using an Andersen cascade impactor via the estimation of the mass median aerosolized diameter (MMAD) and geometric aerodynamic diameter (GAD) and subsequently found to be suitable for effective lung delivery. An in vivo pharmacokinetic study was carried out in a guinea pig animal model, and it was demonstrated that Man-INH-NLC has a longer residence time in the lungs with improved pharmacokinetics when compared with unfunctionalized INH-NLC, indicating the enhanced therapeutic efficacy of the Man-INH-NLC formulation. Histopathological analysis led us to determine that the extent of tissue damage was more severe in the case of the pure drug solution of isoniazid compared to the Man-INH-NLC formulation after nebulization. Thus, the nebulization of Man-INH-NLC was found to be safe, forming a sound basis for enhancing the therapeutic efficacy of the drug for improved management in the treatment of pulmonary tuberculosis.

Modeling periodontal host-microbe interactions using vascularized gingival connective tissue equivalents

Gingival connective tissue and its vasculature play a crucial role in the host’s immune response against the periodontal microbiome and serve as a bridge between the oral and systemic environments. However, there is a lack of representative models that mimic the complex features of vascularized gingival connective tissue and its interaction with the periodontal microbiome, hindering our understanding of periodontal health and disease. Towards this pursuit, we present the characterization of vascularized gingival connective tissue equivalents (CTEs) as a model to study the interactions between oral biofilm colonizers and gingival tissues in healthy and diseased states. Whole-mount immunolabeling and label-free confocal reflectance microscopy of human fibrin-based matrix embedded with gingival fibroblasts and microvascular endothelial cells demonstrated the generation of bi-cellular vascularized gingival CTEs. Next, we investigated the response of the vascularized gingival CTEs to early, intermediate, and late oral biofilm colonizers. Despite colonization, the early colonizers did not elicit any significant change in the production of the cytokines and chemokines by the CTEs representative of the commensal and homeostatic state. In contrast, intermediate and late colonizers representing a transition to a diseased state exhibited connective tissue and vascular invasion, and elicited a differential immune response accompanied by increased monocyte migration. The culture supernatants produced by the vascularized gingival CTEs in response to early and intermediate colonizers polarized macrophages towards an immunomodulatory M2-like phenotype which activates and protects the host, while the late colonizers polarized towards a pro-inflammatory M1-like phenotype. Lastly, in silico analysis showed a high strength of associations between the proteins and transcripts investigated with periodontitis and vascular diseases. In conclusion, the vascularized gingival CTEs provide a biomimetic in vitro platform to study host-microbiome interactions and innate immune response in periodontal health and diseased states, which potentially paves the way toward the development and assessment of novel periodontal therapeutics.

Transcultural adaptation and psychometric properties of the spanish version of the therapeutic relationship Assessment Scale-Nurse

BackgroundThe nurse-patient therapeutic relationship is considered a pillar of mental health nursing, contributing to improved person-centered care and shared decision making with the patient. Given the importance of the nurse-patient therapeutic relationship, appropriate evaluation instruments are required to assess its quality. The aim of this study was to adapt and validate the Spanish version of the Therapeutic Relationship Assessment Scale-Nurse.MethodsA translation and back-translation of the scale was carried out. To analyze the psychometric properties, the scale was administered to 213 nurses working in the field of mental health care. Temporal stability or test-retest was examined by means of the intraclass correlation coefficient (ICC) in a sample of 100 nurses.ResultsConfirmatory Factor Analysis revealed a four-factor structure identical to the original version, with some poor model fit indices. The ordinal alpha values for the total scale and the four factors were 0.939, 0.654, 0.798, 0.801, and 0.866, respectively. The intraclass correlation coefficient was 0.928 (95% CI: 0.893–0.952).ConclusionsThe results show that the Spanish version of the Therapeutic Relationship Assessment Scale-Nurse is reliable for determining the quality of the therapeutic relationship that mental health nurses can establish with their patients. However, more studies are needed to analyse the model fit of the instrument’s factor structure in the Spanish population.

Study Based on the Alliance Between Serum Magnesium Levels and Preterm Labor: An Inclusive Review.

Preterm labor, regarded as the onset of labor before 37 weeks of gestation, is a highly prevalent issue in obstetrics with repercussions for neonatal health. This review article presents an in-depth analysis of the alliance between serum magnesium levels and preterm labor. The review explores the physiological roles of magnesium right through pregnancy, including its significance for energy metabolism, smooth muscle contraction, deoxyribonucleic acid (DNA), and protein synthesis. It addresses cellular transport and the homeostasis of magnesium. The pathophysiological processes encompassing inflammation, oxidative stress, calcium regulation, smooth muscle contractility, and neuroendocrine pathways are investigated. The review evaluates epidemiological studies investigating the alliance between serum magnesium levels and preterm labor. The review incorporates an assortment of study varieties, such as observational studies, case-control studies, prospective cohort studies, and meta-analyses. In the course of reviewing the prognostic relevance of serum magnesium levels in premature labor, therapeutic implications involving diagnostic precision, prognostic significance, and therapeutic response assessment have additionally been addressed. Therapeutic interventions targeting magnesium levels, such as magnesium supplementation, tocolytic therapy, and the role of magnesium in antenatal corticosteroid administration, are explored. This review provides an in-depth evaluation of the correlation between serum magnesium levels and preterm labor, stressing its therapeutic significance and repercussions for future research and treatment strategies.

Tumor targeting and therapeutic assessments of RNA nanoparticles carrying α9-nAChR aptamer and anti-miR-21 in triple-negative breast cancers

Triple-negative breast cancer (TNBC) is highly aggressive with a poor prognosis because of a lack of cell markers as drug targets. α9-Nicotinic acetylcholine receptor (nAChR) is expressed abundantly in TNBC; thus, it is a valuable biomarker for TNBC detection and treatment. In this study, we utilized thermodynamically stable three-way junction (3WJ) packaging RNA (pRNA) as the core to construct RNA nanoparticles with an α9-nAChR RNA aptamer as a targeting ligand and an anti-microRNA-21 (miR-21) as a therapeutic module. We compared the configuration of the two RNA nanoparticles and found that 3WJ-B-α9-nAChR-aptamer fluorescent RNA nanoparticles (3WJ-B-α9-apt-Alexa) exhibited better specificity for α9-nAChR in TNBC cells compared with 3WJ-C-α9-nAChR. Furthermore, 3WJ-B-α9-apt-Alexa bound more efficiently to TNBC patient-derived xenograft (PDX) tumors than 3WJ fluorescent RNA nanoparticles (3WJ-Alexa) with little or no accumulation in healthy organs after systemic injection in mice. Moreover, 3WJ-B-α9-nAChR-aptamer RNA nanoparticles carrying anti-miR-21 (3WJ-B-α9-apt-anti-miR-21) significantly suppressed TNBC-PDX tumor growth and induced cell apoptosis because of reduced miR-21 gene expression and upregulated the phosphatase and tensin homolog (PTEN) and programmed cell death 4 (PDCD4) proteins. In addition, no pathological changes were detected upon toxicity examination of treated mice. In conclusion, the 3WJ-B-α9-nAChR-aptamer RNA nanoparticles established in this study efficiently deliver therapeutic anti-miR-21, indicating their potential as a novel TNBC therapy.

Prevalence and Antibiotic Susceptibility Pattern of Bacterial Pathogens in Intensive Care Unit (ICU) of a Tertiary Care Facility

Aim: To determine the prevalence and antibiotic susceptibility pattern of microorganisms in the ICU patients of a tertiary care facility in Karachi, Pakistan. Method: A retrospective study was conducted on the laboratory records of 50 patients with positive culture admitted to a tertiary care facility. A structured questionnaire was used to obtain patients’ records comprising of their name, sex, age, diagnosis, sample source, isolated pathogen culture results and antibiotic susceptibility patterns. Blood, tracheal fluid, urine, sputum, pus, peritoneal fluid and catheter tips were included as specimen sources. Total 94% patients selected had clinically suspected nosocomial infections. Results: Overall, 45% of them had traumatic brain or spinal injury followed by 35% of post-operative cases, 10% respiratory disease related patients, 6% cardiac patients, 2% renal failure and 2% with miscellaneous infections. Majority of the patients admitted to the ICU were in the age range 51- 65 years. Positive microbial growth samples included blood (30%), trachea (24%), urine (26%), sputum (10%), pus (4%), peritoneal fluids (2%) and catheter tip (4%). Amongst the samples tested, Acinetobacter spp. (22%) were predominant, followed by E. coli (14%), P. aeruginosa (10%), S. aureus (10%) and Enterococcus spp. (8%). Majority of the gram negative species were resistant to amoxiclave, cefotaxime, pipercillin and teicoplanin. Conclusions: The incidence of nosocomial infections is high in ICU patients. Thus accurate antimicrobial treatment strategies together with the development of new therapeutic regimens and risk assessment in hospitals and their ICUs is significantly required to prevent antimicrobial drug resistance among microorganisms.

Prevalence and Antibiotic Susceptibility Pattern of Bacterial Pathogens in Intensive Care Unit (ICU) of a Tertiary Care Facility

Aim: To determine the prevalence and antibiotic susceptibility pattern of microorganisms in the ICU patients of a tertiary care facility in Karachi, Pakistan. Method: A retrospective study was conducted on the laboratory records of 50 patients with positive culture admitted to a tertiary care facility. A structured questionnaire was used to obtain patients’ records comprising of their name, sex, age, diagnosis, sample source, isolated pathogen culture results and antibiotic susceptibility patterns. Blood, tracheal fluid, urine, sputum, pus, peritoneal fluid and catheter tips were included as specimen sources. Total 94% patients selected had clinically suspected nosocomial infections. Results: Overall, 45% of them had traumatic brain or spinal injury followed by 35% of post-operative cases, 10% respiratory disease related patients, 6% cardiac patients, 2% renal failure and 2% with miscellaneous infections. Majority of the patients admitted to the ICU were in the age range 51- 65 years. Positive microbial growth samples included blood (30%), trachea (24%), urine (26%), sputum (10%), pus (4%), peritoneal fluids (2%) and catheter tip (4%). Amongst the samples tested, Acinetobacter spp. (22%) were predominant, followed by E. coli (14%), P. aeruginosa (10%), S. aureus (10%) and Enterococcus spp. (8%). Majority of the gram negative species were resistant to amoxiclave, cefotaxime, pipercillin and teicoplanin. Conclusions: The incidence of nosocomial infections is high in ICU patients. Thus accurate antimicrobial treatment strategies together with the development of new therapeutic regimens and risk assessment in hospitals and their ICUs is significantly required to prevent antimicrobial drug resistance among microorganisms.

Advances in the application of computational pathology in diagnosis, immunomicroenvironment recognition, and immunotherapy evaluation of breast cancer: a narrative review.

Breast cancer (BC) is a prevalent and highly lethal malignancy affecting women worldwide. Immunotherapy has emerged as a promising therapeutic strategy for BC, offering potential improvements in patient survival. Neoadjuvant therapy (NAT) has also gained significant clinical traction. With the advancement of computer technology, Artificial Intelligence (AI) has been increasingly applied in pathology research, expanding and redefining the scope of the field. This narrative review aims to provide a comprehensive overview of the current literature on the application of computational pathology in BC, specifically focusing on diagnosis, immune microenvironment recognition, and the evaluation of immunotherapy and NAT response. A thorough examination of relevant literature was conducted, focusing on studies investigating the role of computational pathology in BC diagnosis, immune microenvironment recognition, and immunotherapy and NAT assessment. The application of computational pathology has shown significant potential in BC management. AI-based techniques enable improved diagnosis and classification of BC subtypes, enhance the identification and characterization of the immune microenvironment, and facilitate the evaluation of immunotherapy and NAT response. However, challenges related to data quality, standardization, and algorithm development still need to be addressed. The integration of computational pathology and AI has transformative implications for BC patient care. By leveraging AI-based technologies, clinicians can make more informed decisions in diagnosis, treatment planning, and therapeutic response assessment. Future research should focus on refining AI algorithms, addressing technical challenges, and conducting large-scale clinical validation studies to facilitate the translation of computational pathology into routine clinical practice for BC patients.

Integrating Motor Variability Evaluation Into Movement System Assessment.

This Perspective contends that traditional therapeutic assessments do not adequately evaluate the ability of individuals to adapt their movements to the challenges faced when negotiating the dynamic environments encountered during daily life. Assessment of motor variability derived during movement execution can address this issue and provide better insight into a patient's movement stability and maneuverability in the real world. Creating such a shift in motor system assessment would advance understanding of rehabilitative approaches to motor system recovery and intervention.

A Call for Discovery and Therapeutic Development for Cutaneous Neurofibromas

A Call for Discovery and Therapeutic Development for Cutaneous Neurofibromas

Rheumatologist's Perspective on Non-Infectious Uveitis: Patterns from Tertiary Referral Rheumatologic Clinics in Italy.

Non-infectious uveitis (NIU) can be an early or even the first extra-articular manifestation of systemic rheumatic diseases, or the first one; thus, rheumatologists are often involved in the diagnostic and therapeutic assessment of NIU. We evaluated 130 patients with a diagnosis of NIU who were admitted to two Italian rheumatologic clinics (Tor Vergata University Hospital in Rome, and Federico II University in Naples) from January 2018 to December 2021. Anterior uveitis (AU) occurred in 75.4% of patients, followed by posterior uveitis (PU, 21.5%); acute (54.6%) and recurrent (35.4%) NIU were more documented than chronic NIU (10%), and a bilateral involvement was observed in 38.7% of cases. Half of NIU cases were associated with spondyloarthritis (SpA); the remaining were affected by Behçet disease (BD)-related uveitis (13.9%) and idiopathic NIU (9.2%). HLA-B27+ patients (34.8%) had a higher prevalence of anterior and unilateral NIU (p = 0.005) with acute course (p = 0.04) than HLA-B27- patients. On the contrary, HLA-B51+ patients (19.6%) had mostly PU and bilateral NIU (p < 0.0001) and recurrent course (p = 0.04) than HLA-B51- patients. At the first rheumatologic referral, 117 patients (90%) received systemic treatments. Findings from this study demonstrate that rheumatologic referral has a pivotal role in the diagnostic work-up of NIU and may dramatically influence NIU-treatment strategies.