Comparative analysis of PDL1 and cluster of differentiation 68 marker expression in oral squamous cell carcinoma patients: Correlation with depth of invasion and immunofluorescence through immunohistochemistry.

Background: Over the past 5 years, the use of immune checkpoint inhibitors in the treatment of head-and-neck squamous cell carcinoma (HNSCC) has increased. Both programmed death-ligand 1 (PD-L1) and cluster of differentiation 68 (CD68) are overexpressed in various carcinomas. Consequently, evaluating the expression of CD68 and PD-L1 in HNSCC lesions may lead to detecting a possible marker for HNSCC. This study aimed to evaluate the expression of PDL1 and CD68 markers in a patient with oral squamous cell carcinoma (OSCC) and examine its relationship with depth of invasion (DOI) and immunofluorescence (IF) through immunohistochemistry. Materials and Methods: This cross-sectional study was conducted in the School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran, Department of Oral and Maxillofacial Pathology. Thirty-four paraffin blocks and demographic information of 15 female and 19 male OSCC patients were collected. Following sample preparations, immunohistochemical staining was performed. Subsequently, each tissue section was analyzed for tumor-infiltrating lymphocytes by CD68 marker and PD-L1 expression. Data analysis was conducted using SPSS software (version 25). Chi-square, Shapiro-Wilk, and independent t-analytical tests were employed for statistical assessments. P < 0.05 was remarked as statistically significant. Results: CD68 and PDL1 expression in the squamous cell carcinoma (SCC) group was higher than the control group (P < 0.001). There was an increasing expression of PDL1 and CD68 as the grade of the disease progressed (P < 0.001 for each), as well as an increasing expression of IF and DOI. Conclusion: The expression levels of CD68 and PDL1 were elevated in SCC tissues in comparison to the unaffected, healthy parts of the tissue section.

Correlation between clinicopathological indices and expression of cluster of differentiation 24 and cluster of differentiation 44 biomarkers in oral epithelial dysplasia and oral squamous cell carcinoma patients: A follow-up study.

Background: Oral squamous cell carcinoma (OSCC) is the most common oral cavity cancer and may occur following oral epithelial dysplasia (OED). Cancer stem cells (CSCs) can self-renew and multi-directionally differentiate to promote tumorigenesis with high expression of cluster of differentiation (CD) 24 and CD44 markers. CSCs play a pivotal role in tumor development, drug resistance, and relapse after treatment. We aimed to evaluate the correlation between both marker expressions and clinicopathological indices in OED and OSCC patients. Materials and Methods: In this follow-up study, we could access 37 patients, including 12 OEDs and 25 OSCCs (Grade I: n = 9, Grade II: n = 8, and Grade III: n = 8). Data were analyzed using SPSS software (version 26) and log-rank tests, Fisher's exact test, Chi-square, and one-way ANOVA. P < 0.05 was considered statistically significant. Results: There was no significant difference in the expression of CD24 and CD44 markers between the study groups (P > 0.05) and the expression of both markers and clinicopathological indices in the study groups (P > 0.05). The mean and standard deviation of overall survival (OS) were 54.46 ± 43.08 with a range of 6-193 months, and they were 8.24 ± 15.34 months with a range of 0-70 months for disease-free survival (DFS) in patients, respectively. The average of DFS in Grade I was significantly lower than the OED (P = 0.002) and Grade II (P = 0.039) groups. The OS average in the Grade I (P = 0.014) and Grade III (P = 0.004) groups was statistically lower than the OED group. Conclusion: Although more than half of the patients demonstrated high expression of both markers, there was no statistically significant difference between them and clinicopathological indices.

How to optimize the CAR-T Cell therapy process? A group concept mapping analysis of preconditions for a frictionless process from a German multistakeholder perspective.

Introduction: Treatment with chimeric antigen receptor T (CAR-T) cells involves a large number of interdisciplinary stakeholders and is associated with complex processes ranging from patient-specific production to follow-up care. Due to the complexity, maximum process optimization is required in order to avoid efficiency losses. This study aimed at systematically determining the preconditions for a frictionless flow of the CAR-T process by surveying the stakeholders involved. Methods: A Group Concept Mapping (GCM) analysis, a mixed-methods participatory research, was conducted. CAR-T experts from different professional backgrounds went through three steps: 1) Brainstorming relevant aspects (statements) for a frictionless process, 2) Sorting the collected statements based on their similarity, and 3) Rating the importance and feasibility of each statement. A cluster map reflecting the overarching topics was derived, and mean ratings per statement and cluster were calculated. Results: Overall, 20 CAR-T experts participated. A total of 80 statements were collected, resulting in a map of the following 10 clusters (mean importance/feasibility): Information for patients and physicians (4.16/3.77), Supportive network (4.03/3.53), Eligibility of patients (4.41/3.63), Evidence, transparency and communication (4.01/3.33), Paperwork (4.1/2.52), Interface with pharmaceutical manufacturer (4.03/2.85), Reimbursement (4.29/2.31), Quality Management (4.17/3.18), Infrastructure of CAR-T clinics (4.1/2.93), and Patient-oriented processes (4.46/3.32). Discussion: The 80 statements underlined the complex and manifold nature of the CAR-T treatment process. Our results reflect the first step in overcoming hurdles: identifying potential hurdles and required preconditions. Decision-makers and stakeholders can use the results to derive strategies and measures to further promote a frictionless process.

Subtyping of pancreatic neuroendocrine tumors by transcription factors, hormones, histology, and patient outcome.

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) show pronounced heterogeneity in terms of hormone and transcription factor (TF) expression. TFs such as ARX and PDX1 are related to alpha- and beta-cell-type features, respectively, and partly associate with patient outcome. However, detailed studies correlating hormone expression, histology, and clinical data are lacking. OBJECTIVE: The aim of this study was to identify subtypes of PanNETs that associate with histological, hormonal, and prognostic findings. METHODS: A total of 185 resected PanNETs were divided into five subtypes (types A1, A2, B, C, and D) by cluster analysis based on expression of four TFs (ARX, PDX1, ISL1, and CDX2) and correlated to the expression of hormones and DAXX/ATRX as well as ALT activation status, histology, and progression-free survival. RESULTS: Subgroup A1 (ISL1+/ARX+/PDX-/CDX2-) was most frequent (46%), followed by type B (18%; ISL1+/ARX-/PDX+/CDX2-), A2 (15%; ISL1+/ARX+/PDX+/CDX2-), C (15%; ISL1-/ARX-/PDX-/CDX2-), and D (5%; ISL1-/ARX-/PDX+/CDX2+). Subgroups A1 and A2 showed a strong association with a trabecular growth pattern and glucagon and pancreatic polypeptide (PP) expression (p < 0.001), while A2 was in addition associated with gastrin expression. Subgroup B was associated with insulin production (p < 0.001) and included all 17 insulinomas. Subgroup C was associated with solid morphology and expression of serotonin, calcitonin, and adrenocorticotropic hormone (ACTH). Subgroup D showed solid morphology, expression of ACTH, somatostatin, or serotonin and had the shortest disease-free survival (p < 0.01). ALT positivity was associated with poorer outcome in types A1 and A2 but not in other types. CONCLUSION: PanNETs can be categorized into five subgroups based on different TF signatures, which associate strongly with histology, hormone production, functionality, and patient outcome.

Thrombospondin 2 is a tumor stemness protein marker based on the cluster analysis combined with immune infiltration in gastric cancer.

Platelet reactive protein 2 (PRP2) is closely related to the characteristics of tumor stem cells. Its role in cancer development and metastasis has received increasing attention, especially its interaction with the immune microenvironment. The study used cluster analysis to extract expression data of multiple cancer types from public databases, and combined with immune infiltration analysis, to evaluate the expression level of PRP2 and its correlation with different immune cell infiltration. Bioinformatics tools were used to analyze the correlation between PRP2 and tumor stem cell markers. The results show that PRP2 is significantly upregulated in a variety of cancers and is closely related to tumor stem cell characteristics. Immunoinfiltration analysis showed that the high expression of PRP2 was associated with a significant increase in immunosuppression-related cell infiltration. Through cluster analysis, we identified the expression pattern of PRP2 in different cancer types, indicating that it may be used as a biomarker for early diagnosis and prognosis assessment, and its expression is closely related to the immune microenvironment, indicating its important role in cancer biology and potential application value in the tumor immune microenvironment.

Simple Sitting Baduanjin mind-body exercise: randomized controlled trial protocol for advanced cancer patients with the fatigue-sleep disturbance symptom cluster.

BACKGROUND: Advanced cancer patients commonly suffer from a fatigue-sleep disturbance symptom cluster. Baduanjin is considered a promising mind-body exercise for relieving the fatigue-sleep disturbance symptom cluster. However, few studies have investigated a tailored Baduanjin for advanced cancer patients. The proposed study will create an optimized Baduanjin exercise program to adapt to advanced cancer patients and evaluate the effect of a Simple Sitting Baduanjin (SSBDJ) mind-body exercise on the fatigue-sleep disturbance symptom cluster among advanced cancer patients. METHODS: The study will be a prospective, assessor-blinded, two-arm, randomized controlled trial, involving a 12-week intervention and 4-week follow-up. A total of 108 advanced cancer patients experiencing the fatigue-sleep disturbance symptom cluster will be recruited from two tertiary general hospitals in China. Participants will be randomized to an experimental group (n = 54) or a control group (n = 54). The experimental group will receive a 12-week SSBDJ intervention plus the usual care, and the control group will receive only the usual care. Outcomes including fatigue-sleep disturbance symptom cluster, fatigue, sleep disturbance, and quality of life will be measured before the intervention, at the 4th, 8th, and 12th weeks of the intervention, and 4 weeks after the intervention. The intention-to-treat principle and a generalized estimating equation will be used to analyze data. DISCUSSION: This study may produce a new Baduanjin exercise prescription that is user-friendly, simple to execute, more targeted, and adaptable. If proven effective, this approach may be integrated into routine cancer care to manage the fatigue-sleep disturbance symptom cluster and improve QOL in advanced cancer patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-2,300,072,331. Registered on 9 June 2023.

Unlocking Potential for Low-Carbon Hydrogen Production from U.S. Natural Gas Resources.

Hydrogen will potentially play a key role while transitioning to a net-zero economy. This study addresses resource, environmental, economic, policy, and societal issues related to low-carbon hydrogen production by steam methane reforming with carbon capture and storage in Wyoming and other natural-gas-rich states. For low-carbon hydrogen produced from natural gas and electricity supplies and which stores CO2 in saline reservoirs in Wyoming, the levelized cost of hydrogen (LCOH) ranges from $1.62-2.00/kg H2, and the life cycle emissions range from 3.85-5.74 kg CO2-eq/kg H2. If claimed, the 45Q tax credit decreases the LCOH by 19%. Although the supplies of renewable natural gas feedstock and zero- or low-carbon electricity can lower the carbon footprint to make hydrogen projects qualified for the 45V tax credit, the 45Q tax credit is still a stronger economic incentive. To reduce the supply cost, a hydrogen cluster can be developed in the state by leveraging the colocation and coavailability of multiple natural resources and transport infrastructure. Developing a hydrogen cluster can directly create several thousand construction jobs and several hundred permanent jobs in Wyoming. Low-carbon hydrogen production can also be scaled up in other states across the nation.

Symptom clusters and symptom network analysis during immunotherapy in lung cancer patients.

OBJECTIVE: This study analyzes symptoms in lung cancer patients undergoing immunotherapy to identify core symptom clusters through network analysis and lay a foundation for effective symptom management programs. METHODS: The sample comprised 240 lung cancer patients receiving immunotherapy. Participants were assessed using the Memorial Symptom Assessment Scale. Exploratory factor analysis was used to extract symptom clusters, and network analysis using JASP 0.17.3 was performed to explore the centrality indices and density of the symptom network. RESULTS: Five symptom clusters were identified, i.e., emotion-related, lung cancer-related, physical, skin, and neural symptom clusters, with a cumulative variance contribution rate of 55.819%. Network analysis revealed that sadness was the most intense symptom (rs = 2.189), dizziness was the most central symptom (rc = 1.388), and fatigue was the most significant bridging symptom (rb = 2.575). CONCLUSION: This study identified five symptom clusters and a symptom network among lung cancer patients during immunotherapy. The network analysis's centrality indices and network density results can assist healthcare professionals in devising more precise symptom management strategies.

Characteristics of gene expression in epicardial adipose tissue and subcutaneous adipose tissue in patients at risk for heart failure undergoing coronary artery bypass grafting.

BACKGROUND: Epicardial adipose tissue (EAT) surrounds the heart and is hypothesised to play a role in the development of heart failure (HF). In this study, we first investigated the differences in gene expression between epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) in patients undergoing elective coronary artery bypass graft (CABG) surgery (n = 21; 95% male). Secondly, we examined the association between EAT and SAT in patients at risk for HF stage A (n = 12) and in pre-HF patients, who show signs but not symptoms of HF, stage B (n = 9). RESULTS: The study confirmed a distinct separation between EAT and SAT. In EAT 17 clusters of genes were present, of which several novel gene modules are associated with characteristics of HF. Notably, seven gene modules showed significant correlation to measures of HF, such as end diastolic left ventricular posterior wall thickness, e'mean, deceleration time and BMI. One module was particularly distinct in EAT when compared to SAT, featuring key genes such as FLT4, SEMA3A, and PTX3, which are implicated in angiogenesis, inflammation regulation, and tissue repair, suggesting a unique role in EAT linked to left ventricular dysfunction. Genetic expression was compared in EAT across all pre-HF and normal phenotypes, revealing small genetic changes in the form of 18 differentially expressed genes in ACC/AHA Stage A vs. Stage B. CONCLUSIONS: The roles of subcutaneous and epicardial fat are clearly different. We highlight the gene expression difference in search of potential modifiers of HF progress. The true implications of our findings should be corroborated in other studies since HF ACC/AHA stage B patients are common and carry a considerable risk for progression to symptomatic HF.

Two-step cluster analysis based on three-dimensional CT measurements of craniofacial structures in severe craniofacial microsomia.

BACKGROUND: The Pruzansky-Kaban and OMENS classifications do not provide additional details on temporomandibular joint deformities. The aim of this study was to classify and quantitatively define severe forms of craniofacial microsomia based on three-dimensional maxillofacial measurements, focusing on deformities in the zygomatic, temporal, and mandibular bones. METHODS: Maxillofacial computed tomography (CT) scans of children with severe types of craniofacial microsomia (CFM) from 2010 to 2020 were collected. Three-dimensional measurements of zygomatic arch length, height of mandibular ramus, height of maxilla, and occlusal cant were performed. A two-step cluster analysis was conducted based on zygomatic arch continuity, occlusal cant, and the ratio of the affected side to the unaffected side (A/U ratio) for zygomatic arch length, mandibular ramus height, and maxillary height. RESULTS: Fifty patients (32 male, 18 female) were included in the study. They were classified into 2 clusters through cluster analysis. Cluster 1 comprised subjects (44% of patients) with continuous zygomatic arches. Cluster 2 comprised subjects (39% of patients) with discontinuous zygomatic arches. The zygomatic arch A/U ratio in cluster 1 was greater than that in cluster 2, with statistical significance observed. Additionally, the maxilla height A/U ratio in cluster 1 was lower than in cluster 2, also with statistical significance. There was no statistically significant difference observed in the ramus height A/U ratio and occlusal cant between clusters 1 and 2. CONCLUSIONS: Based on craniofacial measurements, severe CFM can be categorized into two types: continuous zygomatic arch and discontinuous zygomatic arch. This cluster analysis complemented the OMENS classification and could assist in the selection and design of prosthetic joints for patients with CFM.

CISD2 counteracts the inhibition of ER-mitochondrial calcium transfer by anti-apoptotic BCL-2.

CISD2, a 2Fe2S cluster domain-containing protein, is implicated in Wolfram syndrome type 2, longevity and cancer. CISD2 is part of a ternary complex with IP3 receptors (IP3Rs) and anti-apoptotic BCL-2 proteins and enhances BCL-2's anti-autophagic function. Here, we examined how CISD2 impacted the function of BCL-2 in apoptosis and in controlling IP3R-mediated Ca2+ signaling. Using purified proteins, we found a direct interaction between the cytosolic region of CISD2 and BCL-2's BH4 domain with a submicromolar affinity. At the functional level, the cytosolic region of CISD2, as a purified protein, did not affect the ability of BCL-2 to inhibit BAX-pore formation. In a cellular context, loss of CISD2 did not impede the suppression of apoptosis by BCL-2. Also, in Ca2+-signaling assays, absence of CISD2 did not affect the inhibition of IP3R-mediated Ca2+ release by BCL-2. Combined, these experiments indicate that CISD2 is not essential for BCL-2 function in apoptosis and cytosolic Ca2+ signaling. Instead, CISD2 overexpression enhanced BCL-2-mediated suppression of cytosolic IP3R-mediated Ca2+ release. However, consistent with the presence of CISD2 and BCL-2 at mitochondria-associated ER membranes (MAMs), the most striking effect was observed at the level of ER-mitochondrial Ca2+ transfer. While BCL-2 overexpression inhibited ER-mitochondrial Ca2+ transfer, overexpression of CISD2 together with BCL-2 abrogated the effect of BCL-2. The underlying mechanism is linked to ER-mitochondrial contact sites, since BCL-2 reduced ER-mitochondrial contact sites while co-expression of CISD2 together with BCL-2 abolished this effect. These findings reveal a unique interplay between BCL-2 and CISD2 at Ca2+-signaling nanodomains between ER and mitochondria.

Network Analyses Applied to the Dimensions of Cancer-Related Fatigue in Women With Breast Cancer.

BACKGROUND: Understanding cancer symptom cluster through network analyses is a new approach in oncology, revealing interconnected and influential relationships among reported symptoms. We aimed to assess these relationships using network analysis in posttreatment breast cancer patients, focusing on the five dimensions of cancer-related fatigue (CRF), and on other common difficulties encountered by oncological patients (i.e., pain, anxiety, depression, sleep difficulties, cognitive impairments, and emotion regulation and mental adaptation difficulties). METHOD: This study involved a complementary analysis of data from two interventional studies. Participants completed questionnaires before and after the intervention, with baseline scores being used in this article. Partial correlation network analysis modeled the relationships between symptoms in five distinct networks, each of them including one specific dimension of CRF. The core symptom in each network was identified based on the highest centrality indices. RESULTS: Depression emerged as the core symptom in all networks, strongly associated with all fatigue dimensions (partial correlations ranging from 0.183 to 0.269) except mental fatigue. These findings indicate robust connections between symptoms, as variations in depression scores directly or indirectly influence fatigue and other symptoms within the cluster. CONCLUSION: Our results support the multidimensional aspect of CRF, and its links with other common symptoms. To effectively reduce patient CRF, interventions should address not only fatigue but also the closely related symptoms from the cluster, such as depression, given its centrality in the cluster. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03144154 and NCT04873661). Retrospectively registered on May 1, 2017 and April 29, 2021, respectively.

Predicting Outcome of Total Knee Arthroplasty by Cluster Analysis of Patient-Reported Outcome Measures.

BACKGROUND: Total knee arthroplasties (TKAs) exhibit an 8 to 30% risk of suboptimal outcomes, resulting in persistent symptoms, individual morbidity, and revision surgery, prompting a contemporary focus on risk reduction and outcome improvement. This study introduces hierarchical cluster analysis as a way of preoperatively assessing the likelihood of success/failure of TKA based on several patient-reported outcome measures, which have been analyzed both intact and with component questions as individual variables. METHODS: The study utilized data on 1,433 TKAs from The Miriam Hospital's Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) registry. Outcomes are expressed as Knee Injury and Osteoarthritis Outcome Score (KOOS) pain and function scores. Criteria for success/failure were developed with an integrative, anchor-based, minimum clinically important difference. Preoperative and postoperative patient-reported outcome measures (PROMs) were studied by cluster analysis. RESULTS: There were three sequential cluster analyses that revealed clusters of patients, based upon preoperative patient responses, that were predictive of surgical outcomes. Clusters varied most significantly in their responses to individual component questions of preoperative PROMs. Extracting and combining the clinically meaningful patient-reported component questions yielded a new, and clinically relevant, outcome measure that has the potential to preoperatively predict postoperative outcomes of total knee arthroplasty. CONCLUSION: In contrast to a single medical, psychological, or social variable, cluster analysis offers the opportunity to develop a whole-patient profile that reflects the contextual interactions of sociodemographic and clinical variables in predicting outcomes. In the context of determining clinical meaningfulness, cluster analysis has one of its major strengths.

Characteristics of men and women with medically diagnosed cluster headache in a national integrated healthcare system: A Veterans Health Administration cohort study.

OBJECTIVE: Describe the epidemiology of cluster headache (CH) using Veterans Health Administration (VHA) Electronic Health Record (EHR) data. BACKGROUND: Epidemiologic studies of CH at the population level are difficult because it has a prevalence of ~0.1%. Hospital system-wide studies are an attractive alternative as they have large numbers of patients and broader populations than headache or neurology clinic-based studies. The VHA is an ideal hospital-based system in which to study CH because it is nationwide, predominantly male, has a strong focus on mood disorders and suicidality, and has accessible individual medical records. Here, we report the first headache study based on an ongoing longitudinal cohort of patients with CH using VHA EHR data. METHODS: The VHA EHR data were accessed from Fiscal Year 2008 to 2019. Patients with CH consisted of all patients with at least one outpatient visit containing a CH diagnosis code from the International Classification of Diseases (ICD)-9 or -10. We extracted data on demographic features, incidence, and prevalence, as well as pain and psychiatric comorbidities. RESULTS: Of the 1,524,960 distinct patients who presented for headache treatment in the VHA between Fiscal Year 2008-2019, 24,131 had at least one visit with a CH diagnosis. The 1-year period prevalence of a CH diagnosis in the VHA ranges from 0.08% to 0.10% for women and 0.10% to 0.18% for men. A larger proportion of women versus men received a diagnosis of unspecified CH (59.6% [1412/2368] vs. 53.6% [11,663/21,763], p < 0.001). Most patients with CH had both comorbid headache and non-headache pain diagnoses. Headache not-otherwise-specified was the most common comorbid headache disorder at 70.0% (16,885/24,131) and was more common in women (76.1%, 1801/2368) compared to men (69.3%, 15,084/21,763). Other common comorbidities included migraine, depression, tobacco use, and obstructive sleep apnea. Rates of suicidal ideation or attempt were almost 50% higher in women (5-year proportion 9.4%, 222/2368) with CH compared to men (6.6%, 1433/21,763). CONCLUSIONS: To our knowledge this is the largest hospital system study of CH to date and reinforces several previous studies. Pain, mental health, and sleep disorders comorbidities are particularly prevalent in this group and were often more common in women compared to men with CH. Future work should examine gender and race stratified prevalence estimates within the VHA and other healthcare systems.

A gene cluster for polyamine transport and modification improves salt tolerance in tomato.

Polyamines act as protective compounds directly protecting plants from stress-related damage, while also acting as signaling molecules to participate in serious abiotic stresses. However, the molecular mechanisms underlying these effects are poorly understood. Here, we utilized metabolome genome-wide association study to investigate the polyamine content of wild and cultivated tomato accessions, and we discovered a new gene cluster that drove polyamine content during tomato domestication. The gene cluster contains two polyphenol oxidases (SlPPOE and SlPPOF), two BAHD acyltransferases (SlAT4 and SlAT5), a coumaroyl-CoA ligase (Sl4CL6), and a polyamine uptake transporter (SlPUT3). SlPUT3 mediates polyamine uptake and transport, while the five other genes are involved in polyamine modification. Further salt tolerance assays demonstrated that SlPPOE, SlPPOF, and SlAT5 overexpression lines showed greater phenolamide accumulation and salt tolerance as compared with wild-type (WT). Meanwhile, the exogenous application of Spm to SlPUT3-OE lines displayed salt tolerance compared with WT, while having the opposite effect in slput3 lines, confirms that the polyamine and phenolamide can play a protective role by alleviating cell damage. SlPUT3 interacted with SlPIP2;4, a H2O2 transport protein, to maintain H2O2 homeostasis. Polyamine-derived H2O2 linked Spm to stress responses, suggesting that Spm signaling activates stress response pathways. Collectively, our finding reveals that the H2O2-polyamine-phenolamide module coordinately enhanced tomato salt stress tolerance and provide a foundation for tomato stress-resistance breeding.

Immunophenotypic properties association of CLL and ALL patient cells by flow cytometry analysis.

Chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL) are blood cancers that affect lymphocytes and can be diagnosed by flow cytometry. Flow cytometry is a laboratory technique that analyzes cell properties, including cell surface markers such as cluster of differentiation 19 (CD19). Objective: The main objective of this study was to explore the correlation of the number of CD19-positive cells with other CD antigens in patients with CLL and ALL. Methods: After receiving ethical approval (Approval No. 5S/401), blood was collected from participants who had been diagnosed by a physician. Then the collected blood was prepared for flow cytometry analysis according to the protocol by staining with fluorescent antibodies. Results: The results of the current study showed that sex and different age groups had no statistical influence on the number of CD19-positive cells in the patients evaluated. The generated models did not reveal an association with the number of CD19-positive cells in patients with CLL and ALL. In patients with CLL, the number of cells expressing CD5, CD20, CD23, and CD200 was significantly and positively related with the number of CD19-positive cells. In patients with ALL, the number of cells expressing CD79 and CD99 was significantly and positively correlated with the number of CD19-positive cells. This comparison study also found that in patients with CLL, the number of CD19-positive cells was significantly higher than the number of cells expressing CD20, CD23, and CD200. In patents with ALL, there was a significantly higher number of CD19-positive cells than CD34-positive and CD79-positive cells. Conclusion: In patients with CLL, there was a strong positive correlation between the number of CD19-positive cells and the number of cells expressing CD5, CD20, CD23, and CD200. Additionally, in patients with ALL, there was a positive correlation of CD79 and CD99 with the number of CD19-positive cells.

Assessment of anti-CD69 antibody therapy alone or in combination with anti-PD-1 in murine GBM.

BACKGROUND: Glioblastoma (GBM) is an aggressive cancer with limited treatment options. Immunotherapy targeting CD69, an early activation marker on T cells, has shown promise in preclinical models of non-CNS malignancies. This study investigates anti-CD69 therapy alone or in combination with anti-PD-1 in a preclinical GBM model. RESEARCH DESIGN AND METHODS: CD69 expression in GBM patient tissues was analyzed using the TCGA database. Therapeutic efficacy of anti-CD69 was tested in a murine GBM model with different regimens. Immune cell populations in the tumor microenvironment (TME) were assessed by flow cytometry. RESULTS: Increased CD69 expression was observed in GBM patients compared to normal brain tissue and was associated with worse prognosis. Anti-CD69 treatment reduced percentages of CD69+ immune cells but did not improve survival in GBM-bearing mice. Increased PD-1 expression on NK cells was observed following anti-CD69 treatment. Anti-CD69 treatment was not improved by the addition of anti-PD-1 in vivo. CONCLUSIONS: This is the first study evaluating anti-CD69 therapy in a preclinical GBM model. Despite promising preclinical data in other cancers, anti-CD69 monotherapy or combination therapy with anti-PD-1 did not improve survival in this GBM model.

Symptom Clusters in Breast Cancer Patients Receiving Adjuvant Chemotherapy: A Systematic Review.

BACKGROUND: Breast cancer patients experience various adverse symptoms during adjuvant chemotherapy. These adverse symptoms often form symptom clusters and have a negative impact on patients. AIMS: To summarise common symptom clusters in different dimensions and their longitudinal changes among breast cancer patients receiving adjuvant chemotherapy. DESIGN: A systematic review. DATA SOURCES: Ten electronic databases were searched from 2001 to January 2024, and the search was last updated on 16 August 2024. METHODS: Two reviewers independently assessed the eligibility of each study and extracted data. The Standard Quality Assessment Criteria for Evaluating Primary Research Papers was used to evaluate the quality of included studies. The findings were synthesised narratively. This systematic review has been registered (CRD42022370210). RESULTS: Nine studies with a total of 1454 participants were included. The common symptom clusters in breast cancer patients receiving adjuvant chemotherapy were the gastrointestinal symptom cluster (nausea-lack of appetite), the fatigue-pain-sleep disturbance symptom cluster and the psychological symptom cluster (worry-sadness-nervousness-distress-feeling irritable-difficult concentrating). The severity dimension was the most frequently utilised in identifying symptom clusters, with the number and concurrence of symptom clusters showing variation over time. CONCLUSIONS: This study summarised common symptom clusters in breast cancer patients receiving adjuvant chemotherapy and revealed their changes from symptom dimensions and the chemotherapy process. These findings support further exploration of symptom cluster changes and underlying mechanisms, facilitating the design of targeted management strategies, including appropriate interventions and measurement dimensions in clinical nursing, to ultimately reduce patients' symptom burden. IMPACT: Common symptom clusters have been identified in breast cancer patients receiving adjuvant chemotherapy. Clinical nursing in oncology can prioritise these symptom clusters and provide patients with targeted management strategies. REPORTING METHODS: PRISMA guidelines and SWiM guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Smoking and cluster headache presentation and responsiveness to treatment.

BACKGROUND: Though an association between cluster headache (CH) and smoking has been postulated, data from the Middle East region is scarce. AIM OF WORK: To study the relationship between smoking and CH clinical characteristics and responsiveness to therapy in Egypt. METHODOLOGY: This was a prospective cohort hospital-based study conducted on patients with episodic and chronic CH in a tertiary headache clinic in Egypt during the period between 2019 and 2023. Patients were consecutively recruited at the time of their presentation and were followed up for two weeks after initiation of prophylactic treatment and steroids (as transitional therapy). RESULTS: Of 172 patients with CH recruited, 144 (83.7%) were smokers. Twenty-eight patients (16.3%) had chronic CH. The mean age was 42.08 ± 10.93 (20-66) years, and 131 (76.2%) were males. Smokers had a significantly higher median number of cluster bouts in the past five years (3.0 (IQR2.0-4.0) versus 2.0 (IQR 1.0-2.0)) and worse HIT-6 scores [51.0 (44.0-59.75) versus 41.0 (38.0-41.75)] than non-smokers (p < 0.001). The number of cluster bouts in the past five years was positively correlated with the smoking index (r = 0.249 (p = 0.006) and the smoking duration (in years) (r = 0.392 (p < 0.001)). HIT-6 scores were significantly correlated with the age at smoking onset (r=-0.190, = 0.023), smoking index (r = 0.519, p < 0.001), smoking duration (r = 0.611, p < 0.001), and number of cigarettes consumed per day (r = 0.392, p < 0.001). CONCLUSION: Smoking is significantly correlated with the daily frequency of CH attacks, the frequency of CH bouts in the past five years, and the HIT-6 scores among our cohort.

Profiling iNPH features through cluster analysis: an aid for clinical suspicion and diagnosis.

PURPOSE: Idiopathic Normal Pressure Hydrocephalus (iNPH) is a neurological syndrome defined by gait disturbance, cognitive impairment and urinary incontinence. However, its clinical presentation can vary widely due to overlapping syndromes and common comorbidities in older adults. This study aims to provide practical guidance to aid in the clinical suspicion and support the diagnostic and therapeutic processes for these patients. METHODS: Six quantitative variables regarding clinical, functional, and demographic aspects were considered for a large sample of patients with diagnosed iNPH. Principal component analysis (PCA) was adopted to define the main dimensions explaining the variability of the phenomenon. Then, two clusters of iNPH patients were described. RESULTS: 178 patients were included in the analysis. The PCA produced two dimensions covering 61.8% of the total variability. The first one relied mainly on both clinical (mRS, iNPHGs) and functional (TUG, Tinetti) variables, while the second one was represented mainly on the demographic pattern (age and education). Cluster analysis depicted two main groups of patients. Cluster n.1 is composed of individuals who are older, more disabled, with poor functional performances, and highly symptomatic. Cluster n.2 patients are slightly younger, more educated, fitter, and with more nuanced clinical aspects. CONCLUSIONS: Profiling iNPH patients using quantitative variables and cluster analysis can help identify distinct characteristics of these patients, aiding in the guidance of both medical and surgical interventions.