Expression Score Research Articles

Suggestopedia Meets Multisensory Learning: A Synergistic Approach to Boosting Children's Creative Thinking and Expressive Language

Students must think creatively and communicate well. Students who fail to share their thoughts and discoveries may lack confidence and perform poorly in social situations. A study analyses how multisensory suggestopedia boosts student creativity and expressive language. This quantitative experiment uses non-equivalent control groups and explanations. This study featured 30 control and 30 experimental students. A sample of grade 1 elementary school students was chosen for the study. This study included questionnaires and observation checklists. A 12-item children's creative thinking questionnaire and an 8-item expressive language instrument were used in this study. This study tested normalcy and homogeneity. Data was further analysed using SPSS with independent sample t-test. Multimodal suggestopedia learning increased students' language and creative thinking, according to one study. Creative thinking and expressive language scores were high in the experimental group: 32.8 > 17.5 and 25.55 > 14.5. Additionally, each variable has a significance value of 0.000 < 0.05. The optimistic suggestions in Suggestopedia facilitate multisensory learning by engaging students' senses. Students' ability to think creatively and articulate their ideas is grown. Future students may benefit from Suggestopedia and other multisensory learning tools.

Investigating the effectiveness of transcranial direct current stimulation on the expressive language of children with autism spectrum disorder

Introduction: Autism spectrum disorder (ASD) is a neuropsychological disorder, characterized by social skill deficits, language disorders, and repetitive behaviors. Aim: The present study aimed to investigate the effects of transcranial direct current stimulation (tDCS) on the expressive language of children with ASD. Method: This semi-experimental study, with a pretest-posttest control-group design, was conducted on a statistical population of autistic children, aged 4-6 years, who were referred to the rehabilitation clinics of Yazd, Iran, during 2022. A total of 30 autistic children were randomly selected for this study. The scores of Newsha's Growth Assessment Test (2009) were compared in three intervals: before tDCS, after tDCS, and during follow-up. Data analysis was performed in SPSS Version 21, using repeated measures ANOVA. Results: The results of data analysis showed a significant difference in the mean expressive language scores of the experimental and control groups (P<0.05). The effect size of tDCS on expressive language scores was estimated at 0.421. The score of Newsha's Growth Assessment Test increased significantly in the experimental group after tDCS and during the follow-up compared to the control group (P=0.001). Conclusion: The results showed that tDCS led to the improvement of the expressive language of children with ASD. Therefore, it is recommended to use this type of treatment as one of the complementary methods in the rehabilitation of ASD patients.

Comparative analysis of GOLPH3 expression in lymph node-positive prostate cancer: immunohistochemistry staining patterns and clinical significance.

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Lymph node metastasis is a poor prognostic factor for PCa. Previous studies have found that Golgi phosphoprotein 3 (GOLPH3) is overexpressed in various cancers, including PCa. We examined GOLPH3 expression in PCa cells from primary tumor and, as the first, also in metastatic lymph nodes to assess its potential as a new risk factor for PCa progression. The study included 78 patients diagnosed with lymph node-positive PCa confirmed in the postoperative material. All the patients underwent radical prostatectomy (RP) with extended lymphadenectomy. The clinical data of the patients were retrospectively analyzed, and their histopathological specimens were selected for further analysis. Immunohistochemistry (IHC) staining was performed and the expression of GOLPH3 was assessed by an experienced uropathologist using an immunoreactive scale (IRS). A correlational analysis of the obtained data with the clinicopathological data of patients was performed. A positive IHC reaction for GOLPH3 was observed in all samples. IRS score for GOLPH3 expression was higher in the metastatic lymph nodes than in the prostate (not statistically significant; p=0.056). Several significant correlations were identified in connection with GOLPH3 expression levels in the prostate and metastatic lymph node tissues. No significant correlations were found between GOLPH3 expression and patient characteristics (e.g. BMI, EAU risk group, or preoperative PSA level), pathological features, or postoperative outcomes. However, we found that lymphovascular invasion (LVI) tended to be more common in patients with a higher percentage of GOLPH3-positive cells (p=0.02). We also found a positive association between the intensity of GOLPH3 staining in metastatic lymph nodes and the EAU classification. Finally, we found a significant negative correlation between the GOLPH3 expression and the efficacy of RP - the higher the expression of GOLPH3, the lower the efficacy of RP was (p<0.05). GOLPH3 is expressed in both prostate and metastatic lymph nodes, with higher expression in metastatic lymph nodes. High GOLPH3 expression was associated with the occurrence of LVI, higher-risk group in the EAU classification, and lower efficacy of the RP, but there was no significant correlation with other pathological features or postoperative outcomes.

Multinucleated giant cells of bladder mucosa are modified telocytes: Diagnostic and immunohistochemistry algorithm and relation to PD-L1 expression score.

Multinucleated giant cells (MGCs) in bladder carcinomas are poorly studied. To describe the function, morphogenesis, and origin of mononuclear and MGCs in urothelial carcinoma (UC) of the bladder in Bulgarian and French patients. Urothelial bladder carcinomas (n = 104) from 2016-2020 were analyzed retrospectively using immunohistochemical (IHC) and histochemical stain examination. Giant cells in the bladder stroma were found in 35.6% of cases, more often in high-grades. We confirm that MGCs in the mucosa in UC of the bladder were positive for both mesenchymal and myofibroblast markers (vimentin, smooth muscle actin, Desmin, and CD34) and the macrophage marker CD68. Furthermore, IHC studies revealed the following profile of these cells: Positive for p16; negative for epithelial (CK AE1/AE3 and GATA-3), vascular (CD31), neural (PS100 and C-KIT), cambial, blastic (CD34-blasts and C-KIT), and immune markers (IG G, immunoglobulin G4, and PD-L1); no proliferative activity, possess no specific immune function, and cannot be used to calculate the Combined Positive Score scale. In conclusion, the giant stromal cells in non-tumor and tumor bladder can be used as a characteristic and relatively constant, although nonspecific, histological marker for chronic bladder damage, reflecting the chronic irritation or inflammation. Likewise, according to the morphological and IHC of the mono- and multinucleated giant cells in the bladder, they are most likely represent telocytes capable of adapting their morphology to the pathology of the organ.

Genetic modification of inflammation- and clonal hematopoiesis-associated cardiovascular risk.

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of cardiovascular diseases (CVDs), putatively via inflammasome activation. We pursued an inflammatory gene modifier scan for CHIP-associated CVD risk among 424,651 UK Biobank participants. We identified CHIP using whole-exome sequencing data of blood DNA and modeled as a composite, considering all driver genes together, as well as separately for common drivers (DNMT3A, TET2, ASXL1, and JAK2). We developed predicted gene expression scores for 26 inflammasome-related genes and assessed how they modify CHIP-associated CVD risk. We identified IL1RAP as a potential key molecule for CHIP-associated CVD risk across genes and increased AIM2 gene expression leading to heightened JAK2- and ASXL1-associated CVD risk. We show that CRISPR-induced Asxl1-mutated murine macrophages had a particularly heightened inflammatory response to AIM2 agonism, associated with an increased DNA damage response, as well as increased IL-10 secretion, mirroring a CVD-protective effect of IL10 expression in ASXL1 CHIP. Our study supports the role of inflammasomes in CHIP-associated CVD and provides evidence to support gene-specific strategies to address CHIP-associated CVD risk.

Circulating miRNAs Detect High vs Low Visceral Adipose Tissue Inflammation in Patients Living With Obesity.

The severity of visceral adipose tissue (VAT) inflammation in individuals with obesity is thought to signify obesity subphenotype(s) associated with higher cardiometabolic risk. Yet, this tissue is not accessible for direct sampling in the nonsurgical patient. We hypothesized that circulating miRNAs (circ-miRs) could serve as biomarkers to distinguish human obesity subgroups with high or low extent of VAT inflammation. Discovery and validation cohorts of patients living with obesity undergoing bariatric surgery (n = 35 and 51, respectively) were included. VAT inflammation was classified into low/high based on an expression score derived from the messenger RNA levels of TNFA, IL6, and CCL2 (determined by reverse transcription polymerase chain reaction). Differentially expressed circ-miRs were identified, and their discriminative power to detect low/high VAT inflammation was assessed by receiver operating characteristic-area under the curve (ROC-AUC) analysis. Fifty three out of 263 circ-miRs (20%) were associated with high-VAT inflammation according to Mann-Whitney analysis in the discovery cohort. Of those, 12 (12/53 = 23%) were differentially expressed according to Deseq2, and 6 significantly discriminated between high- and low-VAT inflammation with ROC-AUC greater than 0.8. Of the resulting 5 circ-miRs that were differentially abundant in all 3 statistical approaches, 3 were unaffected by hemolysis and validated in an independent cohort. Circ-miRs 181b-5p, 1306-3p, and 3138 combined with homeostatic model assessment of insulin resistance (HOMA-IR) exhibited ROC-AUC of 0.951 (95% CI, 0.865-1) and 0.808 (95% CI, 0.654-0.963) in the discovery and validation cohorts, respectively, providing strong discriminative power between participants with low- vs high-VAT inflammation. Predicted target genes of these miRNAs are enriched in pathways of insulin and inflammatory signaling, circadian entrainment, and cellular senescence. Circ-miRs that identify patients with low- vs high-VAT inflammation constitute a putative tool to improve personalized care of patients with obesity.

Determinants of response to CDK4/6 inhibitors in the real-world setting

Despite widespread use and a known mechanism of action for CDK4/6 inhibitors in combination with endocrine therapy, features of disease evolution and determinants of therapeutic response in the real-world setting remain unclear. Here, a cohort of patients treated with standard-of-care combination regimens was utilized to explore features of disease and determinants of progression-free survival (PFS) and overall survival (OS). In this cohort of 280 patients, >90% of patients were treated with palbociclib in combination with either an aromatase inhibitor (AI) or fulvestrant (FUL). Most of these patients had modified Scarff–Bloom–Richardson (SBR) scores, and ER, HER2, and PR immunohistochemistry. Both the SBR score and lack of PR expression were associated with shorter PFS in patients treated with AI combinations and remained significant in multivariate analyses (HR = 3.86, p = 0.008). Gene expression analyses indicated substantial changes in cell cycle and estrogen receptor signaling during the course of treatment. Furthermore, gene expression-based subtyping indicated that predominant subtypes changed with treatment and progression. The luminal B, HER2, and basal subtypes exhibited shorter PFS in CDK4/6 inhibitor combinations when assessed in the pretreatment biopsies; however, they were not associated with OS. Using unbiased approaches, cell cycle-associated gene sets were strongly associated with shorter PFS in pretreatment biopsies irrespective of endocrine therapy. Estrogen receptor signaling gene sets were associated with longer PFS particularly in the AI-treated cohort. Together, these data suggest that there are distinct pathological and biological features of HR+/HER2− breast cancer associated with response to CDK4/6 inhibitors. Clinical trial registration number: NCT04526587.

P18.02.B RELATIONSHIP BETWEEN PROGESTERONE RECEPTOR EXPRESSION WITH HISTOPATHOLOGICAL GRADING IN MENINGIOMA

Abstract BACKGROUND Meningioma is a group of mostly benign, slow-growing neoplasms that most likely derive from meningothelial cells of the arachnoid layer of the brain and spinal medulla. Meningiomas are found in one-third of all tumors in the central nervous system. Meningioma is three times more prevalent in women than in males, it is frequently related to hormones in women, particularly progesterone, which is considered to have the utmost impact on meningioma. Objective: this study aims at discovering the relationship between progesterone receptor expression and meningioma histopathological grading in Indonesia, especially at Saiful Anwar Hospital Malang. Method: This study employed a cross-sectional analytical observational research design. The study sample was a paraffin block of meningioma cases at The Anatomical Pathology laboratory of Saiful Anwar Hospital and The Medical Faculty of Brawijaya University, obtained from 2017 to 2020. The data were collected through histopathological preparations, immunohistochemical preparations, and immunohistochemical evaluation. The data analysis was performed by using SPSS version 20. RESULTS Most meningioma cases at Dr. Saiful Anwar Malang Hospital are women between 41 and 50 years. Then, it is located in the frontal part and acquired a grade of histopathology I and has a progesterone receptor expression score of 4. The chi-square test showed no significant association between progesterone receptor expression and histopathological grading of meningioma. At the same time, partial logistic regression tests showed no significant association between sex, age, and location with meningioma histopathological grading. In addition, multinomial logistic regression tests showed that the sex, age, and location did not significantly increase or decrease the risk (odds ratio) to the grade of meningioma histopathology. CONCLUSION This study showed no significant association between progesterone receptor expression and meningioma histopathological grading and no association between the sex, age, and location of lesions with meningioma histopathological grading and no significant increased risk of histopathological grading due to gender, age, or lesion location.

Protocol for the evaluation of cyclin D1 expression in tumor tissue and surgical margins in oral squamous cell carcinoma – a retrospective study

Oral squamous cell carcinoma (OSCC) is a malignant epithelial tumor with poor prognosis. There is an increase in the proliferation of epithelial cells in OSCC which is control by cell cycle regulators like Cyclin D1. Cyclin D1 is linked to a poor prognosis for patients, including aggressive malignancies, recurrence, protracted remission, etc. To evaluate Cyclin D1 immunoexpression in different grades and surgical margins in OSCC. All tissue sections will be processed for Cyclin D1 IHC. After that light microscopic evaluation of Cyclin D1 expression was classified as weak (scoring 1-4), moderate (score 5-8), or strong based on a final expression score that was obtained by multiplying the labelling index score by the intensity score (score 9–12). The present study will find the immunohistochemical expression of Cyclin D1 in OSCC. There will be variation in the immunoexpression of Cyclin D1 among different grades of OSCC its surgical margin and normal oral mucosa. We hypothesize that: As the disease condition goes towards poor grade, intensity of cyclin D1 expression immunohistochemically may increase. Hence, the intensity can be used as a prognostic marker.

Cross-species evaluation of fibroblast activation protein alpha as potential imaging target for soft tissue sarcoma: a comparative immunohistochemical study in humans, dogs, and cats.

Complete surgical tumor resection is paramount in the management of soft tissue sarcoma (STS) in humans, dogs, and cats alike. Near-infrared targeted tracers for fluorescence-guided surgery (FGS) could facilitate intraoperative visualization of the tumor and improve resection accuracy. Target identification is complicated in STS due to the rarity and heterogeneity of the disease. This study aims to validate the expression of fibroblast activation protein alpha (FAP) in selected human, canine, and feline STS subtypes to assess the value of FAP as a target for FGS and to validate companion animals as a translational model. Formalin-fixed and paraffin-embedded tissue samples from 53 canine STSs (perivascular wall tumor (PWT), canine fibrosarcoma (cFS), and STS not further specified (NOS)), 24 feline fibrosarcomas, and 39 human STSs (myxofibrosarcoma, undifferentiated pleomorphic sarcoma, dermatofibrosarcoma protuberans, and malignant peripheral nerve sheath tumor) as well as six canine and seven feline healthy controls and 10 inflamed tissue samples were immunohistochemically stained for their FAP expression. FAP labeling in tumor, peritumoral, healthy skin, and inflamed tissue samples was quantified using a visually assessed semiquantitative expression score and digital image analysis. Target selection criteria (TASC) scoring was subsequently performed as previously described. Eighty-five percent (85%) of human (33/39), 76% of canine (40/53), and 92% of feline (22/24) STSs showed FAP positivity in over 10% of the tumor cells. A high expression was determined in 53% canine (28/53), 67% feline (16/24), and 44% human STSs (17/39). The average FAP-labeled area of canine, feline, and human STSs was 31%, 33%, and 42%, respectively (p > 0.8990). The FAP-positive tumor area was larger in STS compared to healthy and peritumoral tissue samples (p < 0.0001). TASC scores were above 18 for all feline and human STS subtypes and canine PWTs but not for canine STS NOS and cFS. This study represents the first cross-species target evaluation of FAP for STS. Our results demonstrate that FAP expression is increased in various STS subtypes compared to non-cancerous tissues across species, thereby validating dogs and cats as suitable animal models. Based on a TASC score, FAP could be considered a target for FGS.

Immunohistochemical analysis of osteoclastic and osteoblastic activity in ossifying fibroma and juvenile ossifying fibroma: A comparative study.

Cemento-ossifying fibroma (COF) and juvenile ossifying fibroma (JOF) have been considered distinct entities within the category of fibro-osseous lesions. This study aimed to assess osteoblast and osteoclast activity in COF and JOF by investigating bone resorption markers, specifically receptor activator of nuclear factor-kB (RANK), RANK ligand (RANKL), and its inhibitor osteoprotegerin (OPG). A comparative analysis of these markers was performed on all lesions. Immunohistochemistry was employed to evaluate and quantify the expression of these biomarkers in a sample of 20 cases of cemento-ossifying fibroma (COF), 15 cases of psammomatoid juvenile ossifying fibroma (PsJOF), and 10 cases of trabecular juvenile ossifying fibroma (TrJOF). The expression of osteoprotegerin was significantly higher in cemento-ossifying fibroma (33.9±13.0) compared to trabecular juvenile ossifying fibroma (27.3±9.2) and psammatoid ossifying fibroma (25.2±14.9), with the COF showing the highest expression followed by the latter two (p=0.037). There was a higher percentage (80%) of stromal fibroblast cells that showed positive expression of RANKL in cemento-ossifying fibroma (COF) compared to psammomatoid juvenile ossifying fibroma (PsJOF) (33.3%) and trabecular juvenile ossifying fibroma (TrJOF) (30.0%) when considering a positive expression score of 3 (p=0.024). Cemento-ossifying fibroma demonstrated the highest expression of osteoprotegerin and RANKL-positive stromal fibroblast cells, followed by psammomatoid juvenile ossifying fibroma and trabecular juvenile ossifying fibroma. These findings provide valuable insights into the pathogenesis of these lesions.

A Pilot Study to Evaluate the Effectiveness of Parent mediated Group Intervention Program for Developmental Language Disorders

Purpose: This paper attempts to explore the significance of parent-mediated group intervention for children with developmental language disorder. The implementation of group intervention programs with the active involvement of parents creates opportunities for peer interaction in realistic settings and parents becoming more invested in the intervention process through direct observation and active participation.Methods: Eight parent child dyads participated in the group intervention. The participants were native Malayalam speakers in the age range of 3-4 years. 25 sessions were provided with intervention focused on language as well as emergent literacy skills. Vignettes are provided to demonstrate the program’s structure. Pre and post receptive expressive language scores and emergent literacy scores were assessed using Assessment of Language Disorders and Get Ready to Read.Results: The results indicated that parent mediated group intervention was effective for children with developmental language disorder. All children, with the exception of one, achieved age-appropriate language scores and improvement in emergent literacy skills. Despite the fact that all of the children’s emergent literac scores improved after intervention, none of the children’s scores exceeded the average, implying that much more focused and rigorous attention is required for training of emergent literacy skills.Conclusions: This paper calls attention to the practicality of parent mediated group intervention for children with developmental language disorders through which more children can be served in a cost and time efficient way. It emphasizes the importance of involving parents in sessions to improve speech and language skills as well as emergent literacy.

Combining bulk and single-cell RNA-sequencing data to develop an NK cell-related prognostic signature for hepatocellular carcinoma based on an integrated machine learning framework

BackgroundThe application of molecular targeting therapy and immunotherapy has notably prolonged the survival of patients with hepatocellular carcinoma (HCC). However, multidrug resistance and high molecular heterogeneity of HCC still prevent the further improvement of clinical benefits. Dysfunction of tumor-infiltrating natural killer (NK) cells was strongly related to HCC progression and survival benefits of HCC patients. Hence, an NK cell-related prognostic signature was built up to predict HCC patients’ prognosis and immunotherapeutic response.MethodsNK cell markers were selected from scRNA-Seq data obtained from GSE162616 data set. A consensus machine learning framework including a total of 77 algorithms was developed to establish the gene signature in TCGA–LIHC data set, GSE14520 data set, GSE76427 data set and ICGC–LIRI–JP data set. Moreover, the predictive efficacy on ICI response was externally validated by GSE91061 data set and PRJEB23709 data set.ResultsWith the highest C-index among 77 algorithms, a 11-gene signature was established by the combination of LASSO and CoxBoost algorithm, which classified patients into high- and low-risk group. The prognostic signature displayed a good predictive performance for overall survival rate, moderate to high predictive accuracy and was an independent risk factor for HCC patients’ prognosis in TCGA, GEO and ICGC cohorts. Compared with high-risk group, low-risk patients showed higher IPS–PD1 blocker, IPS–CTLA4 blocker, common immune checkpoints expression but lower TIDE score, which indicated low-risk patients might be prone to benefiting from ICI treatment. Moreover, a real-world cohort, PRJEB23709, also revealed better immunotherapeutic response in low-risk group.ConclusionsOverall, the present study developed a gene signature based on NK cell-related genes, which offered a novel platform for prognosis and immunotherapeutic response evaluation of HCC patients.

Epithelioid Mesothelioma Patients with Very Long Survival Display Defects in DNA Repair.

DNA repair has an important role in malignant pleural mesothelioma (MPM) tumorigenesis and progression. Prognostic/predictive biomarkers for better management of MPM patients are needed. In the present manuscript, we analyzed the expression of more than 700 genes in a cohort of MPM patients to possibly find biomarkers correlated with survival. A total of 54 MPM patients, all with epithelioid histology, whose survival follow-up and formalin-fixed paraffin-embedded tumors were available, were included in the study. Gene expression profiles were evaluated using a Nanostring platform analyzing 760 genes involved in different cellular pathways. The percentages of proliferating tumor cells positive for RAD51 and BRCA1 foci were evaluated using an immunofluorescence assay, as a readout of homologous recombination repair status. Patient median survival time was 16.9 months, and based on this value, they were classified as long and short survivors (LS/SS) with, respectively, an overall survival ≥ and <16.9 months as well as very long and very short survivors (VLS/VSS) with an overall survival ≥ than 33.8 and < than 8.45 months. A down-regulation in the DNA damage/repair expression score was observed in LS and VLS as compared to SS and VSS. These findings were validated by the lower number of both RAD51 and BRCA1-positive tumor cells in VLS as compared to VSS. The down-regulation of DNA repair signature in VLS was functionally validated by a lower % of RAD51 and BRCA1-positive tumor cells. If these data can be corroborated in a prospective trial, an easy, cost-effective test could be routinely used to better manage treatment in MPM patients.

Identification of TRPM2 as a prognostic factor correlated with immune infiltration in ovarian cancer

IntroductionOvarian cancer (OC) is one of the most common gynecologic malignant cancers with the current survival rate remaining low. TRPM2 has been reported as a survival predictor in various cancers but not in OC. The aim of this study is to explore the role and its underlying mechanism of TRPM2 in OC.MethodsThe transcriptome data and clinical data were obtained from TCGA, GTEx, and GEO (GSE17260). DriverDBv3 and PrognoScan were used to analyze survival correlations. GSEA analysis was performed to uncover the underlying mechanism. The correlations between TRPM2 and immune score, immune cell infiltration were analyzed by TIMER2.0.ResultsTRPM2 was highly expressed in OC and high TRPM2 expression was related to the poor prognosis based on the Kaplan-Meier curves, univariate and multivariate analysis. The enrichment analysis suggested that TRPM2 was involved in immune-related pathways. Positive correlations were also observed between TRPM2 expression and immune score and immune cells covering B cells, T cells, macrophage, neutrophil, and myeloid dendritic cells. We also found that TRPM2 was positively related to immune checkpoints including ICOSLG, CD40, CD86, etc. TRPM2 expression had a positive correlation with M2 macrophage, but not with M1 macrophage. Besides, TRPM2 showed a strong positive correlation with pyroptosis-related genes including NLRP3, NLRC4, NOD2, NOD1, IL1B, GSDMD.ConclusionOur study demonstrated that TRPM2 is a poor prognostic prediction factor in ovarian cancer and is correlated to the immune microenvironment and pyroptosis. TRPM2 may act as a new immunotherapy target, which promoted the survival rate of OC patients.

The generation that lived during/participated in the war and the generation that inherited it: association between veterans PTSD and adult offspring’s emotional regulation strategies and alexithymia levels

BackgroundThe long-term repercussions that war can have on both war generations and post-war generations lack in the literature. It is imperative to understand the psychological consequences of the Lebanese Civil War that took place from 1975 to 1990, on the offspring of those who took part in it. Accordingly, the objective of this study was to assess the association between paternal/veterans PTSD and adult offspring’s emotional regulation strategies and alexithymia levels, 30 years after the end of war.MethodA cross-sectional study was carried out between September 2020 and September 2021 on a sample of 75 fathers of Lebanese former veterans and paramilitary veterans and their adult offspring. For the veterans and paramilitary veterans’ population, the PTSD Checklist was used to assess post-traumatic stress disorder, and the Combat Exposure Scale (CES) was used to measure the level of combat exposure. For the offspring population, the Emotional Regulation Questionnaire (ERQ) was used to assess emotional regulation strategies and the Toronto Alexithymia Scale (TAS) was used to measure the levels of alexithymia.ResultsPaternal PTSD (Beta = 10.19) was associated with higher levels of alexithymia in the offspring population. Regarding emotional regulation strategies, results showed that paternal PTSD (Beta = -3.24) was significantly associated with a decrease in the cognitive reappraisal score in the offspring. Also, paternal PTSD (Beta = 4.57) was significantly associated with an increase in expressive suppression score. Additionally, an older father’s age (Beta = 1.11) was significantly associated with an increased alexithymia score in the offspring. Moreover, results showed that paternal combat injuries (Beta = -4.24) were significantly associated with a decrease in the alexithymia score in the offspring population and an increase in the expressive suppression score (Beta = 3.28).ConclusionThis study shows that fathers’ traumatic experience of war influences emotion regulation and alexithymia levels in their offspring. Longitudinal studies taking into account the age of the offspring at the time of onset of fathers’ symptoms may provide us with additional information to understand the influence of paternal PTSD on the emotional functioning of offspring during different phases of emotional development.

Localized Heat Treatment for Meibomian Gland Dysfunction: A Single-Center Retrospective Analysis of Efficacy over Time.

Meibomian gland dysfunction (MGD) can produce a myriad of symptoms. The effective treatment of MGD can reduce the burden of this condition. Although several studies have indicated that TearCare (Sight Sciences, Menlo Park, CA) is an effective treatment for MGD, no studies currently provide information regarding the duration of efficacy. The purpose of this analysis was to determine the duration of efficacy of symptom relief and improvement of signs (as measured by gland function) for a treatment consisting of controlled heating of the meibomian glands using SmartLids (Sight Sciences) combined with manual expression of the liquefied meibum by a physician. This study involved retrospective analysis of data gathered from a single-center ophthalmology/optometry practice. Symptoms were assessed using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, and the signs were assessed using the meibomian gland expression (MGE) scores before and at several time points (8 weeks, 6 months, 12 months, and 18 months). Further analysis evaluating the efficacy in subgroups based on age, race, and sex was performed. There were 78 patients included in this study. The mean baseline SPEED score decreased from 14 to 7.9 at 8 weeks. The mean SPEED scores at 6 and 12 months were maintained at 7.7 and 7.9, respectively, and at 18 months went to 8.9. At baseline, the mean MGE was 4.9 in the right eye and 4.8 in the left eye. In both eyes, the mean MGE increased to 9.0 in both eyes at 8 weeks. At 6 months, the mean MGE score was maintained at 8.6 in the right and 8.2 in the left and remained consistent at 12 months with 7.8 in the right and 7.8 in the left. At 18 months, the MGE score went to 6.8 in the right eye and 7.0 in the left eye. A single TearCare treatment effectively reduced both the symptoms and signs of MGD and maintained its effects for 12 months.

Intraoperative molecular imaging of colorectal lung metastases with SGM-101: a feasibility study

PurposeMetastasectomy is a common treatment option for patients with colorectal lung metastases (CLM). Challenges exist with margin assessment and identification of small nodules, especially during minimally invasive surgery. Intraoperative fluorescence imaging has the potential to overcome these challenges. The aim of this study was to assess feasibility of targeting CLM with the carcinoembryonic antigen (CEA) specific fluorescent tracer SGM-101.MethodsThis was a prospective, open-label feasibility study. The primary outcome was the number of CLM that showed a true positive fluorescence signal with SGM-101. Fluorescence positive signal was defined as a signal-to-background ratio (SBR) ≥ 1.5. A secondary endpoint was the CEA expression in the colorectal lung metastases, assessed with the immunohistochemistry, and scored by the total immunostaining score.ResultsThirteen patients were included in this study. Positive fluorescence signal with in vivo, back table, and closed-field bread loaf imaging was observed in 31%, 45%, and 94% of the tumors respectively. Median SBRs for the three imaging modalities were 1.00 (IQR: 1.00–1.53), 1.45 (IQR: 1.00–1.89), and 4.81 (IQR: 2.70–7.41). All tumor lesions had a maximum total immunostaining score for CEA expression of 12/12.ConclusionThis study demonstrated the potential of fluorescence imaging of CLM with SGM-101. CEA expression was observed in all tumors, and closed-field imaging showed excellent CEA specific targeting of the tracer to the tumor nodules. The full potential of SGM-101 for in vivo detection of the tracer can be achieved with improved minimal invasive imaging systems and optimal patient selection.Trial registrationThe study was registered in ClinicalTrial.gov under identifier NCT04737213 at February 2021.

Common clinicopathological and immunological features of sarcomatoid carcinoma across organs: A histomorphology-based cross-organ study.

Sarcomatoid carcinoma (SC), which can occur in any organ, is a rare disease. To elucidate common characteristics of SC beyond organs, we evaluated clinicopathological and immunological features of SC defined by the single histological criterion beyond organs compared to randomly matched conventional carcinoma (non-SC) adjusted for the disease stage. Immunological features were assessed by multiplex immunohistochemistry, comparing immune cell density in tumor tissues and tumor programmed death-ligand 1 (PD-L1) expression. A total of 101 patients with SC or non-SC (31 lung, 19 esophagus, 22 pancreas, 15 liver, 4 bile duct, 6 kidney, 2 uterus and 2 ovary) were identified among 7197 patients who underwent surgery at our institute (1997-2020). SC was significantly associated with worse survival (HR: 1.571; 95% CI: 1.084-2.277; P = .017). The frequency of postoperative progression within 6 months was significantly higher for SC patients (54% vs 28%; P = .002). The immune profiling revealed the densities of CD8+ T cells (130 vs 72 cells/mm2 ; P = .004) and tumor-associated macrophages (566 vs 413 cells/mm2 ; P < .0001) and the tumor PD-L1 expression score (40% vs 5%; P < .0001) were significantly higher in SCs than in non-SCs. Among 73 SC patients with postoperative progression, multivariate Cox regression analysis showed that immunotherapy tended to be associated with favorable survival (HR: 0.256; 95% CI: 0.062-1.057; P = .060). Collectively, SCs shared clinicopathological and immunological features across organs. Our study can initiate to standardize the pathological definition of SC and provide a rationale for the investigation and development for this rare disease in a cross-organ manner.

BSBM-12 STAT3 EXPRESSION IN BRAIN METASTASES FROM BREAST CANCER: CORRELATIONS WITH DIFFERENT MOLECULAR SUBTYPES AND CLINICAL OUTCOME

Abstract BACKGROUND STAT3 expression in peritumoral reactive astrocytes (RA) of brain metastases (BM) from breast cancer (BC) may favor a pro-metastatic environment. MATERIAL AND METHODS 105 BM specimens from BC were identified from the biobank of Pathology Unit of University of Turin and Spanish national BrM network (RENACER). pSTAT3 expression was scored in RA of peritumoral tissue according to Priego et al. (Nat Med 2018). Clinical, molecular data, and intracranial progression (i-PFS) were retrospectively retrieved. RESULTS Median age was of 50 years (range 46–54). 31/105 patients (29.5%) had luminal BM, 35/105 (33.3%) had HER2-positive BM, and 39/105 (37.1%) had triple negative BM. Immunohistochemistry for GFAP and pSTAT3 was feasible in 88/105 (83.8%). 49/88 (55.7%) showed positive staining of pSTAT3, of which 15/88 (17%) scored with 3, 34/88 (38.6%) with 2, 28/88 (31.9%%) with 1, and 11/88 (12.6%) with 0 (negative). High pSTAT3 expression (score 2-3) was observed in 27/34 (79.4%) triple negative BM, and in 18/30 (60.0%) HER2-positive BM, while most of luminal BM (20/24 – 83.3%) had low or absent pSTAT3 expression. Median i-PFS was 16.0 months (range 7-80): low pSTAT3 BM (score 0-1) had a median i-PFS of 11 months versus 8 months for high pSTAT3 BM (score 2-3) (HR 0.4; p=0.0123). A shorter median i-PFS was observed in high pSTAT3 triple negative BM (4 months) as compared with low pSTAT3 BM (20 months). Conversely, i-PFS of high pSTAT3 BM (7 months) was similar to low pSTAT3 BM (7 months) in HER2-positive BC. CONCLUSION pSTAT3 expression in RA of triple negative BM and HER-2 positive BM is higher than in luminal BM. Of note, patients with high pSTAT3 triple negative BM progressed earlier in comparison with those with low pSTAT3, suggesting that pSTAT3 expression has an influence on the outcome.