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To further understand the barriers and facilitators to attending colonoscopy examination following a positive routinely offered stool test result, from the perspective of patients and Specialist Screening Practitioners (SSPs). Qualitative semi-structured interviews were conducted. Participants (N = 32) were patients (n = 20) who, as part of the Bowel Cancer Screening Programme (BCSP) in England, were invited to attend a colonoscopy examination, and SSPs (n = 12), who worked for the BCSP in England. Framework analysis included inductive and deductive coding. Anxiety was as a key barrier cited by patients and SSPs, arising from the moment the patient received the invitation letter. Notably, procedural-related anxieties centred upon the fear of pain and discomfort and test invasiveness. The role of family, friends and the SSP were recognised by patients and SSPs to facilitate participation. Many patients, yet not SSPs, emphasised an obligation to attend all medical test invitations. Practically orientated strategies suggested by patients and SSPs address the patient barriers identified. These include earlier information to patients on the option of sedation for pain relief, earlier notification of potential financial support for patients unable to fund their own travel costs, and fewer uses of the term cancer within written materials. [ABSTRACT FROM AUTHOR]

Unexplained B12 hypervitaminosis (HB12) in asymptomatic patients leads to a cascade of medical consultations and diagnostic tests aimed at determining its etiology. The objective of this study was to assess the efficacy of the laboratory getting involved in the detection and elimination of immune complexes with vitamin B12 in clinical practice and its economic impact. A retrospective longitudinal study was undertaken to assess the laboratory strategy of detecting B12 macrovitamin (macro-B12) in patients with HB12 >1,000 pg/mL. The clinical characteristics of patients with HB12 referred to Internal Medicine (IM) in the pre- and post-implantation period of the new strategy were compared. Additionally, the healthcare costs of one-year follow-up were estimated. The prevalences of HB12 in the pre- and post-implantation period were 3.9 % and 3 %, respectively. Macro-B12 explained 25 % of the HB12 cases initially detected. A 41 % reduction was observed in the number of patients with HB12 after the implantation of the new strategy, thereby resulting in a cost reduction of 5,000 €. The laboratory intervention for the detection of macro-B12 provides clear economic and clinical benefits in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer, including non-small-cell lung cancer (NSCLC), is one of the leading causes of cancer-related deaths worldwide. NSCLC treatment has undergone a major paradigm shift with the advent of targeted therapy and immunotherapy, which require the specific tumor and immune signatures of NSCLC to be tested to ensure careful patient selection and prediction of clinical benefits from the selected therapy. Tumor samples with large fibrotic areas and the focal nature of biomarker expression may be a source of bias in histological assays. The ex vivo analysis developed in this work allows us to rapidly explore various characteristics of cancer and tumor-infiltrating immune cells after their separation from fibrotic tissue in solid NSCLC samples and to have a better understanding of the immunological landscape and expression of different cell markers in the tumor as a whole, thereby avoiding some false negatives in the histological assay of the same tumor samples. NSCLC is a very aggressive solid tumor, with a poor prognosis due to post-surgical recurrence. Analysis of the specific tumor and immune signatures of NSCLC samples is a critical step in prognostic evaluation and management decisions for patients after surgery. Routine histological assays have some limitations. Therefore, new diagnostic tools with the capability to quickly recognize NSCLC subtypes and correctly identify various markers are needed. We developed a technique for ex vivo isolation of cancer and immune cells from surgical tumor and lung tissue samples of patients with NSCLC (adenocarcinomas and squamous cell carcinomas) and their examination on ex vivo cell preparations and, parallelly, on histological sections after Romanovsky–Giemsa and immunofluorescent/immunochemical staining for cancer-specific and immune-related markers. As a result, PD-L1 expression was detected for some patients only by ex vivo analysis. Immune cell profiling in the tumor microenvironment revealed significant differences in the immunological landscapes between the patients' tumors, with smokers' macrophages with simultaneous expression of pro- and anti-inflammatory cytokines, neutrophils, and eosinophils being the dominant populations. The proposed ex vivo analysis may be used as an additional diagnostic tool for quick examination of cancer and immune cells in whole tumor samples and to avoid false negatives in histological assays. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a significant global health issue where early detection is crucial for improving treatment outcomes and survival rates. This comprehensive review assesses the utility of stool-based tests in CRC screening, including traditional fecal occult blood tests (FOBT), both chemical (gFOBT) and immunochemical techniques (FIT), as well as multitarget stool DNA (mt-sDNA) as a novel and promising biomarker. The advancements, limitations and the impact of false positives and negatives of these methods are examined. The review analyzed various studies on current screening methods, focusing on laboratory tests and biomarkers. Findings indicate that while FIT and mt-sDNA tests offer enhanced sensitivity and specificity over traditional guaiac-based FOBT, they also come with higher costs and potential for increased false positives. FIT shows better patient adherence due to its ease to use, but incorrect usage and interpretation of FOBT can lead to significant diagnostic errors. In conclusion, despite the improvements in FOBT methods like FIT in CRC detection, careful consideration of each method's benefits and drawbacks is essential. Effective CRC screening programs should combine various methods tailored to specific population needs, aiming for early detection and reduced mortality rates. [ABSTRACT FROM AUTHOR]

Background: In Isfahan, the fecal immunochemical test (FIT) has been used since January 2016 as part of the Iran's Package of Essential Non-communicable Diseases (IraPEN) program for colorectal cancer (CRC) screening. The test is recommended for people who are 50-70 years old. Then, those with positive results would be referred for colonoscopy. This study aims to describe the uptake of the program and its outcome. Methods: A retrospective observational study was performed by collecting data from Isfahan Vice-Chancellor for Health database for this study purpose. The number of participators, the number of positive FIT, and the number of detected polyps or cancers were determined. Results: Between 2016 and 2019, the number of participants in the program reached 345 207 individuals (nearly 40% of the eligible population of 874 674). Totally, 21 264 participants (6.1%) had positive tests, of whom about 20% underwent the recommended colonoscopy with available reports, and 971 (24%) and 110 (3%) patients were diagnosed with polyps and CRC, respectively. Conclusion: Over four years of screening with FIT in Isfahan, 40% of the eligible population participated. Among those with positive FIT results, 20% underwent colonoscopy, and approximately 26% of these individuals were identified as having polyps or cancer. This study provides valuable insights into the uptake and outcomes of a population-based CRC screening program in Isfahan, Iran. The findings highlight the need for targeted interventions to increase participation rates and improve the detection of polyps and CRC cases. [ABSTRACT FROM AUTHOR]

Background: The number of adult orthodontic patients is increasing, and studies have shown that autophagy is involved in regulating orthodontic tooth movement and plays an important role in aging-related changes. Therefore, we aimed to explore the role of autophagy in aging-related changes during orthodontic tooth movement by establishing a rat orthodontic tooth movement model. Methods: Forty-five 6-week-old and sixty-five 8-month-old male Sprague–Dawley rats were selected to represent adolescents and adults and establish orthodontic tooth movement model. They were sacrificed on days 0,1,3,7 and 14. Immunohistochemistry, immunofluorescence and tartrate resistant acid phosphatase (TRAP) staining were applied to measure the expression level of osteogenesis, autophagy, aging factors and osteoclast number in periodontal membrane of left upper first molar during orthodontic tooth movement. Then, we regulated the autophagy level by injecting autophagy activator rapamycin during orthodontic tooth movement and measured these factors and tooth movement distance by micro-computed tomography. Results: Aging factor levels in the periodontal membrane were higher in adult rats than in adolescent rats and the autophagy factor levels were lower. The levels of osteogenic factors were lower on the tension side in adult rats than in adolescent rats. The peak osteoclast number on the pressure side occurred later in adult rats than in adolescent rats. The injection of rapamycin increased autophagy, accelerated orthodontic tooth movement in adult rats, and reduced the levels of aging factors. The levels of osteogenic factors were higher and reached those in adolescent rats at some time points. The number of osteoclasts increased significantly in the early stage. Conclusions: Autophagy may play a substantial role in regulating aging-related changes in orthodontic tooth movement. [ABSTRACT FROM AUTHOR]

Background: Persons with diabetes have 27% elevated risk of developing colorectal cancer (CRC) and are disproportionately from priority health disparities populations. Federally qualified health centers (FQHCs) struggle to implement CRC screening programs for average risk patients. Strategies to effectively prioritize and optimize CRC screening for patients with diabetes in the primary care safety-net are needed. Methods: Guided by the Exploration, Preparation, Implementation and Sustainment Framework, we conducted a stakeholder-engaged process to identify multi-level change objectives for implementing optimized CRC screening for patients with diabetes in FQHCs. To identify change objectives, an implementation planning group of stakeholders from FQHCs, safety-net screening programs, and policy implementers were assembled and met over a 7-month period. Depth interviews (n = 18–20) with key implementation actors were conducted to identify and refine the materials, methods and strategies needed to support an implementation plan across different FQHC contexts. The planning group endorsed the following multi-component implementation strategies: identifying clinic champions, development/distribution of patient educational materials, developing and implementing quality monitoring systems, and convening clinical meetings. To support clinic champions during the initial implementation phase, two learning collaboratives and bi-weekly virtual facilitation will be provided. In single group, hybrid type 2 effectiveness-implementation trial, we will implement and evaluate these strategies in a in six safety net clinics (n = 30 patients with diabetes per site). The primary clinical outcomes are: (1) clinic-level colonoscopy uptake and (2) overall CRC screening rates for patients with diabetes assessed at baseline and 12-months post-implementation. Implementation outcomes include provider and staff fidelity to the implementation plan, patient acceptability, and feasibility will be assessed at baseline and 12-months post-implementation. Discussion: Study findings are poised to inform development of evidence-based implementation strategies to be tested for scalability and sustainability in a future hybrid 2 effectiveness-implementation clinical trial. The research protocol can be adapted as a model to investigate the development of targeted cancer prevention strategies in additional chronically ill priority populations. Trial registration: This study was registered in ClinicalTrials.gov (NCT05785780) on March 27, 2023 (last updated October 21, 2023). [ABSTRACT FROM AUTHOR]

Leachate from municipal solid waste is a mixture of xenobiotics capable of contaminating bodies of water and causing damage to the health of living beings that inhabit or consume contaminated water. A previous study revealed the presence of heavy metals in Urban Solid Waste Transfer Station (USWTS) leachate above the permissible national and international limits. In the present study, we demonstrate that subchronic oral administration (5 and 25 % v/v) of leachate to male Wistar rats caused changes in the immunoreactivity of the glial markers: GFAP and Iba-1, accompanied by an increase in the expression of caspase-3, and a decrease in the expression of the NeuN protein. Results indicate that the heavy metals present in the leachate induced neuronal loss in the prefrontal cortex, suggesting that these contaminants can cause neurological problems in mammals that consume surface water with xenobiotics, since the leachate could contaminate water bodies and underground water.

Background. The objective of this study was to describe the histological and immunohistochemical aspects of vomeronasal organ in two groups of (normal and pathological) embryos and fetuses, with chromosomal morphological abnormalities. Methods. The research was based on a retrospective, descriptive analysis, carried out over a period of 5 years. The study included 46 biopsy fragments taken from aborted embryos and fetuses aged between 9 and 23 weeks. We compared the microscopic structure of the vomeronasal organ using different histologic and immunohistochemical staining procedures. Results. Our results showed that in both groups of embryos and fetuses there are three major stages of histological development of the vomeronasal organ, depending by intrauterine age. We also observed that in the group of abnormal embryos and fetuses, although the morphological and immunohistochemical characteristics of vomeronasal organ were similar to the control group, the specific structures of the vomeronasal organ persisted beyond 22 weeks. In the control group, the vomeronasal organ was no longer visible at this age. The results of the immunohistochemical study indicated that the positive surface for cytokines in the control group decreased with age, and in the group with morphological anomalies, the number of positive cells was low. On the other hand, in fetuses with chromosomal anomalies, the positivity, although a slight downward trend was recorded, it remained high. Conclusions. This study is still ongoing in order to identify the increased frequency of vomeronasal organ in fetuses. Moreover, we anticipate that our study can be a starting point for other researchers in order to identify a relationship between the behavioral pattern of the fetuses with trisomy 21 and the persistence of the VNO.

Objective: To estimate the impact on clinical outcomes and healthcare resource use from recommending that patients with 1–2 low-risk adenomas (LRAs) return to routine fecal immunochemical test (FIT) screening instead of surveillance colonoscopy, from a Canadian provincial healthcare system perspective. Methods: The OncoSim-Colorectal microsimulation model simulated average-risk individuals eligible for FIT-based colorectal cancer (CRC) screening in Alberta, Canada. We simulated two surveillance strategies that applied to individuals with 1–2 LRAs (<10 mm) removed as part of the average risk CRC screening program: (a) Surveillance colonoscopy (status quo) and (b) return to FIT screening (new strategy); both at 5 years after polypectomy. A 75 ng/mL FIT positivity threshold was used in the base case. The simulations projected average annual CRC outcomes and healthcare resource use from 2023 to 2042. We conducted alternative scenarios and sensitivity analyses on key variables. Results: Returning to FIT screening (versus surveillance colonoscopy) after polypectomy was projected to have minimal impact on long-term CRC incidence and deaths (not statistically significant). There was a projected decrease of one (4%) major bleeding event and seven (5%) perforation events per year. There was a projected increase of 4800 (1.5%) FIT screens, decrease of 3900 (5.1%) colonoscopies, and a decrease of $3.4 million (1.2%) in total healthcare costs per year, on average. The annual colonoscopies averted and healthcare cost savings increased over time. Results were similar in the alternative scenarios and sensitivity analyses. Conclusions: Returning to FIT screening would have similar clinical outcomes as surveillance colonoscopy but could reduce colonoscopy demand and healthcare costs. [ABSTRACT FROM AUTHOR]

Background: The dysregulation of gene expression is one of the key molecular features of colorectal cancer (CRC) development. This study aimed to investigate whether such dysregulation is reflected in rectal swab specimens of CRC patients and to evaluate its potential as a non-invasive approach for screening. Methods: We compared the expression level of 14 CRC-associated genes in tumor and adjacent non-tumor tissue of CRC patients and examined the correlation of their levels in tissue with paired rectal swab specimens. The level of these 14 genes in rectal swab specimens was compared among patients with CRC or polyp and control subjects, and the diagnostic potential of each dysregulated gene and the gene panel were evaluated. Results: The expression of CXCR2, SAA, COX1, PPARδ, PPARγ, Groγ, IL8, p21, c-myc, CD44 and CSF1 was significantly higher in CRC, and there was a significant correlation in the levels of most of them between the CRC and rectal swab specimens. In the training study, we showed that CD44, IL8, CXCR2 and c-myc levels were significantly higher in the rectal swab specimens of the CRC patients. Such result was confirmed in the validation study. A panel of these four genes was developed, and ROC analysis showed that this four-gene panel could identify CRC patients with an AUC value of 0.83 and identify overall polyp and precancerous adenoma patients with AUC values of 0.6522 and 0.7322, respectively. Finally, the predictive study showed that the four-gene panel demonstrated sensitivities of 63.6%, 76.9% and 88.9% in identifying overall polyp, precancerous adenoma and CRC patients, respectively, whereas the specificity for normal subjects was 72.2%. Conclusion: The expression of CRC-associated genes in rectal swab specimens reflects the dysregulation status in colorectal tissue, and the four-gene panel is a potential non-invasive biomarker for early precancerous adenoma and CRC screening. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) stands as the third most common cancer globally and the second leading cause of cancer-related deaths, imposing a substantial health burden. Recent studies highlight a concerning rise in CRC rates among individuals below 50 years old, prompting the American Cancer Society (ACS) to recommend screening starting at age 45 for average-risk individuals. Dr. Aasma Shaukat's Keynote Conference stresses the urgent need for updated screening strategies to tackle suboptimal adherence rates and effectively manage the increasing burden of CRC. Lowering the adenoma detection screening age could aid in early identification of adenomas in asymptomatic younger patients, potentially reshaping disease epidemiology. Current screening options encompass stool-based tests like multitarget stool DNA (mtDNA) tests, fecal immunochemical testing (FIT), and imaging-based tests. Moreover, blood-based tests are emerging as promising tools for early CRC detection, utilizing innovative techniques and AI algorithms. Medicare mandates specific criteria for national coverage of blood-based tests. Ongoing clinical trials, such as Freenome, Guardant, and CancerSEEK, offer hope for further advancements in blood-based CRC screening. Despite breakthroughs, accessibility and affordability challenges persist. Adapting healthcare systems to accommodate changing CRC epidemiology is imperative. Lowering the screening age and integrating blood-based tests hold the potential to alleviate the CRC-related burden amidst evolving epidemiology. Colorectal cancer (CRC) currently ranks as the third most common cancer and the second leading cause of cancer-related deaths worldwide, posing a significant global health burden to the population. Recent studies have reported the emergence of a new clinical picture of the disease, with a notable increase in CRC rates in younger populations of <50 years of age. The American Cancer Society (ACS) now recommends CRC screening starting at age 45 for average-risk individuals. Dr. Aasma Shaukat's Keynote Conference highlights the critical need for updated screening strategies, with an emphasis on addressing the suboptimal adherence rates and the effective management of the growing burden of CRC. Lowering the adenoma detection screening age can facilitate early identification of adenomas in younger asymptomatic patients, altering the epidemiologic landscape. However, its implications may not be as profound unless a drastic shift in the age distribution of CRC is observed. Currently, various screening options are available in practice, including stool-based tests like multitarget stool DNA (mtDNA) tests, fecal immunochemical testing (FIT), and imaging-based tests. In addition to existing screening methods, blood-based tests are now emerging as promising tools for early CRC detection. These tests leverage innovative techniques along with AI and machine learning algorithms, aiding in tumor detection at a significantly earlier stage, which was not possible before. Medicare mandates specific criteria for national coverage of blood-based tests, including sensitivity ≥ 74%, specificity ≥ 90%, FDA approval, and inclusion in professional society guidelines. Ongoing clinical trials, such as Freenome, Guardant, and CancerSEEK, offer hope for further advancements in blood-based CRC screening. The development of multicancer early detection tests like GRAIL demonstrates a tremendous potential for detecting various solid tumors and hematologic malignancies. Despite these breakthroughs, the question of accessibility and affordability still stands. The ever-evolving landscape of CRC screening reflects the strength of the scientific field in light of an altered disease epidemiology. Lowering screening age along with the integration of blood-based tests with existing screening methods holds great potential in reducing the CRC-related burden. At the same time, it is increasingly important to address the challenges of adaptation of the healthcare system to this change in the epidemiologic paradigm. [ABSTRACT FROM AUTHOR]

Background: Mutations in STK11 (STK11Mut) gene may present a negative impact on survival in Non-small Cell Lung Cancer (NSCLC) patients, however, its relationship with immune related genes remains unclear. This study is to unveil whether overexpressed- and mutated-STK11 impact survival in NSCLC and to explore whether immune related genes (IRGs) are involved in STK11 mutations. Methods: 188 NSCLC patients with intact formalin-fixed paraffin-embedded (FFPE) tissue available for detecting STK11 protein expression were included in the analysis. After immunohistochemical detection of STK11 protein, patients were divided into high STK11 expression group (STK11High) and low STK11 expression group (STK11Low), and then Kaplan-Meier survival analysis and COX proportional hazards model were used to compare the overall survival (OS) and progression-free survival (PFS) of the two groups of patients. In addition, the mutation data from the TCGA database was used to categorize the NSCLC population, namely STK11 Mutated (STK11Mut) and wild-type (STK11Wt) subgroups. The difference in OS between STK11Mut and STK11Wt was compared. Finally, bioinformatics analysis was used to compare the differences in IRGs expression between STK11Mut and STK11Wt populations. Results: The median follow-up time was 51.0 months (range 3.0 - 120.0 months) for real-life cohort. At the end of follow-up, 64.36% (121/188) of patients experienced recurrence or metastasis. 64.89% (122/188) of patients ended up in cancer-related death. High expression of STK11 was a significant protective factor for NSCLC patients, both in terms of PFS [HR=0.42, 95% CI= (0.29-0.61), P<0.001] and OS [HR=0.36, 95% CI= (0.25, 0.53), P<0.001], which was consistent with the finding in TCGA cohorts [HR=0.76, 95%CI= (0.65, 0.88), P<0.001 HR=0.76, 95%CI= (0.65, 0.88), P<0.001]. In TCGA cohort, STK11 mutation was a significant risk factor for NSCLC in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) histology in terms of OS [HR=6.81, 95%CI= (2.16, 21.53), P<0.001; HR=1.50, 95%CI= (1.00, 2.26), P=0.051, respectively]. Furthermore, 7 IRGs, namely CALCA, BMP6, S100P, THPO, CGA, PCSK1 and MUC5AC, were found significantly overexpressed in STK11-mutated NSCLC in both LUSC and LUAD histology. Conclusions: Low STK11 expression at protein level and presence of STK11 mutation were associated with poor prognosis in NSCLC, and mutated STK11 might probably alter the expression IRGs profiling. [ABSTRACT FROM AUTHOR]

Asymmetric transport of cargo across axonal branches is a field of active research. Mechanisms contributing to preferential cargo transport along specific branches in vivo in wild type neurons are poorly understood. We find that anterograde synaptic vesicles preferentially enter the synaptic branch or pause at the branch point in Caenorhabditis elegans Posterior Lateral Mechanosensory neurons. The synaptic vesicle anterograde kinesin motor UNC-104 /KIF1A regulates this vesicle behavior at the branch point. Reduced levels of functional UNC-104 cause vesicles to predominantly pause at the branch point and lose their preference for turning into the synaptic branch. SAM-4 /Myrlysin, which aids in recruitment/activation of UNC-104 on synaptic vesicles, regulates vesicle behavior at the branch point similar to UNC-104. Increasing the levels of UNC-104 increases the preference of vesicles to go straight toward the asynaptic end. This suggests that the neuron optimizes UNC-104 levels on the cargo surface to maximize the fraction of vesicles entering the branch and minimize the fraction going to the asynaptic end. [ABSTRACT FROM AUTHOR]

Objectives: ACE2, known as a host receptor involved with SARS‐CoV‐2 infection, binds to viral spike proteins for host cell entry. However, details regarding its induction and function in oral mucosal cells remain unknown. Materials and Methods: We examined ACE2 expression and its induction by transfected mimic nucleotides and pro‐inflammatory cytokines in oral keratinocytes (RT7) and fibroblasts (GT1). Subsequently, the effects of viral spike S1 protein via ACE2 on CXCL10 expression induced by pro‐inflammatory cytokines in both cells were examined. Results: ACE2 was constitutively expressed in RT7 and GT1. Transfected Poly(I:C) and Poly(dA:dT) increased ACE2 expression in those cells, while knockdown of RIG‐I decreased ACE2 expression induced by those transfected ds nucleotides. IFN‐γ and TNF‐α enhanced transfected ds nucleotides‐induced ACE2 expression in RT7 but not GT1. S1 protein alone did not affect CXCL10 expression in either cell type, whereas it enhanced IFN‐β‐induced CXCL10 in both, while immune responses of IFN‐γ‐ and TNF‐α‐induced CXCL10 enhanced by S1 protein were different between RT7 and GT1. Finally, knockdown of ACE2 decreased cytokines and S1 protein mediated‐CXCL10 levels in both cells. Conclusions: ACE2 in oral mucosal cells may contribute to development of infection and inflammation in cooperation with pro‐inflammatory cytokines following SARS‐CoV‐2 invasion. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the effect of mammalian‐enabled (Mena) on tongue squamous cell carcinoma (TSCC) metastasis and its mechanism. Materials and Methods: Immunochemistry was performed to investigate the Mena and tumor‐related markers expression, and its clinicopathological characteristics in 46 TSCC specimens. TSCC cell SCC9 and Cal27 untransfected or stable transfected with Mena overexpression and small interfering RNA were used to determine the role of Mena in cell proliferation, cell migration, invasion and metastasis, and EMT‐related markers in vitro, and the effect of Mena on TSCC growth and metastasis through tumor‐bearing and tumor metastasis immunodeficient mice models in vivo. Results: Immunochemistry showed that the expression of Mena was significantly correlated with lymphatic metastasis and TNM stage, E‐cadherin, Vimentin, and MMP2. Mena did not affect cell proliferation and colony formation in vitro, and tumor growth in vivo. However, it promoted cell migration and invasion in vitro, and TSCC metastasis in vivo. Conclusions: Mena expression is associated with lymphatic metastasis and tumor stage and promotes TSCC invasion and metastasis by inducing the EMT process. Thus, Mena may be a biomarker for prognosis and targeted therapy in TSCC patients. [ABSTRACT FROM AUTHOR]

Background Post-colonoscopy colorectal cancers (PCCRCs) decrease the effect of colorectal cancer (CRC) screening programs. To enable PCCRC incidence reduction in the long-term, we classified PCCRCs diagnosed after colonoscopies performed in a fecal immunochemical test (FIT)-based screening program. Methods PCCRCs diagnosed after colonoscopies performed between 2014–2016 for a positive FIT in the Dutch CRC screening program were included. PCCRCs were categorized according to the World Endoscopy Organization consensus statement into (a) interval PCCRC (diagnosed before the recommended surveillance); (b) non-interval type A (diagnosed at the recommended surveillance interval); (c) non-interval type B (diagnosed after the recommended surveillance interval); or (d) non-interval type C (diagnosed after the intended recommended surveillance interval, with surveillance not implemented owing to co-morbidity). The most probable etiology was determined by root-cause analysis. Tumor stage distributions were compared between categories. Results 116362 colonoscopies were performed after a positive FIT with 9978 screen-detected CRCs. During follow-up, 432 PCCRCs were diagnosed. The 3-year PCCRC rate was 2.7%. PCCRCs were categorized as interval (53.5%), non-interval type A (14.6%), non-interval type B (30.6%), and non-interval type C (1.4%). The most common etiology for interval PCCRCs was possible missed lesion with adequate examination (73.6%); they were more often diagnosed at an advanced stage (stage III/IV; 53.2%) compared with non-interval type A (15.9%; P <0.001) and non-interval type B (40.9%; P =0.03) PCCRCs. Conclusions The 3-year PCCRC rate was low in this FIT-based CRC screening program. Approximately half of PCCRCs were interval PCCRCs. These were mostly caused by missed lesions and were diagnosed at a more advanced stage. This emphasizes the importance of high quality colonoscopy with optimal polyp detection. [ABSTRACT FROM AUTHOR]

Veillonella parvula, prototypical member of the oral and gut microbiota, is at times commensal yet also potentially pathogenic. The definition of the molecular basis tailoring this contrasting behavior is key for broadening our understanding of the microbiota‐driven pathogenic and/or tolerogenic mechanisms that take place within our body. In this study, we focused on the chemistry of the main constituent of the outer membrane of V. parvula, the lipopolysaccharide (LPS). LPS molecules indeed elicit pro‐inflammatory and immunomodulatory responses depending on their chemical structures. Herein we report the structural elucidation of the LPS from two strains of V. parvula and show important and unprecedented differences in both the lipid and carbohydrate moieties, including the identification of a novel galactofuranose and mannitol‐containing O‐antigen repeating unit for one of the two strains. Furthermore, by harnessing computational studies, in vitro human cell models, as well as lectin binding solid‐phase assays, we discovered that the two chemically diverse LPS immunologically behave differently and have attempted to identify the molecular determinant(s) governing this phenomenon. Whereas pro‐inflammatory potential has been evidenced for the lipid A moiety, by contrast a plausible "immune modulating" action has been proposed for the peculiar O‐antigen portion. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastomas are the most aggressive brain tumors, and affected patients still only have an extremely poor prognosis with today's therapeutic options. Further developments are still necessary, particularly in therapeutic approaches. Orlistat can act as an antitumor agent as it inhibits fatty acid synthase, decreases tumor cell proliferation, and stimulates tumor cell apoptosis. Investigations conducted on breast, pancreatic, hepatic, and colorectal tumors showed that FASN—fatty acid synthase, a protein that catalyzes the de novo synthesis of long-chain fatty acids—is strongly upregulated. Using an animal model, we tested whether the drug's effects could be demonstrated visually, quantitatively, and by texture analysis based on MR studies. Histology and immunochemistry were used as references. The key results of the present study are as follows: Firstly, a significant difference was found between orlistat-treated and untreated tumors in MRI studies based on morphology and texture analyses. Secondly, the expression of FASN was reduced in the orlistat group, which, however, did not result in a higher apoptosis rate in the treatment group. Our findings suggest that some effects of orlistat on tumor cell proliferation must have taken place during therapy. Further studies should investigate the effects of FASN inhibition when combined with targeted therapies. Background: This study aimed to investigate the effects of tetrahydrolipstatin (orlistat) on heterotopic glioblastoma in mice by applying MRI and correlating the results with histopathology and immunochemistry. Methods: Human glioblastoma cells were injected subcutaneously into the groins of immunodeficient mice. After tumor growth of >150 mm3, the animals were assigned into a treatment group (n = 6), which received daily intraperitoneal injections of orlistat, and a control group (n = 7). MRI was performed at the time of randomization and before euthanizing the animals. Tumor volumes were calculated, and signal intensities were analyzed. The internal tumor structure was evaluated visually and with texture analysis. Western blotting and protein expression analysis were performed. Results: At histology, all tumors showed high mitotic and proliferative activity (Ki67 ≥ 10%). Reduced fatty acid synthetase expression was measured in the orlistat group (p < 0.05). Based on the results of morphologic MRI-based analysis, tumor growth remained concentric in the control group and changed to eccentric in the treatment group (p < 0.05). The largest area under the receiver operating curve of the predictors derived from the texture analysis of T2w images was for wavelet transform parameters WavEnHL_s3 and WavEnLH_s4 at 0.96 and 1.00, respectively. Conclusions: Orlistat showed effects on heterotopically implanted glioblastoma multiforme in MRI studies of mice based on morphologic and texture analysis. [ABSTRACT FROM AUTHOR]

Background: The clinical application of immune checkpoint inhibitors (ICIs) is limited by their drug resistance, necessitating the development of ICI sensitizers to improve cancer immunotherapy outcomes. Huang Lian Jie Du Decoction (HLJD, Oren-gedoku-to in Japanese, Hwangryunhaedok-tang in Korean), a famous traditional Chinese medicinal prescription, has exhibited potential in the field of cancer treatment. This study aims to investigate the impact of HLJD on the efficacy of ICIs in melanoma and elucidate the underlying mechanisms. Methods: The potential synergistic effects of HLJD and ICIs were investigated on the tumor-bearing mice model of B16F10 melanoma, and the tumor infiltration of immune cells was tested by flow cytometry. The differential gene expression in tumors between HLJD and ICIs group and ICIs alone group were analyzed by RNA-seq. The effects of HLJD on oxidative stress, TLR7/8, and type I interferons (IFN-Is) signaling were further validated by immunofluorescence, PCR array, and immunochemistry in tumor tissue. Results: HLJD enhanced the anti-tumor effect of ICIs, significantly inhibited tumor growth, and prolonged the survival duration in melanoma. HLJD increased the tumor infiltration of anti-tumor immune cells, especially DCs, CD4+ T cells and CD8+T cells. Mechanically, HLJD activated the oxidative stress and TLR7/8 signaling pathway and IFN-Is-related genes in tumors. Conclusions: HLJD enhanced the therapeutic benefits of ICIs in melanoma, through increasing reactive oxygen species (ROS), promoting the TLR7/8 pathway, and activating IFN-Is signaling, which in turn activated DCs and T cells. [ABSTRACT FROM AUTHOR]

In the fruit fly Drosophila melanogaster, two cells in a cyst of 16 interconnected cells have the potential to become the oocyte, but only one of these will assume an oocyte fate as the cysts transition through regions 2a and 2b of the germarium. The mechanism of specification depends on a polarized microtubule network, a dynein dependent Egl:BicD mRNA cargo complex, a special membranous structure called the fusome and its associated proteins, and the translational regulator orb. In this work, we have investigated the role of orb and the fusome in oocyte specification. We show here that specification is a stepwise process. Initially, orb mRNAs accumulate in the two pro-oocytes in close association with the fusome. This association is accompanied by the activation of the orb autoregulatory loop, generating high levels of Orb. Subsequently, orb mRNAs become enriched in only one of the pro-oocytes, the presumptive oocyte, and this is followed, with a delay, by Orb localization to the oocyte. We find that fusome association of orb mRNAs is essential for oocyte specification in the germarium, is mediated by the orb 3′ UTR, and requires Orb protein. We also show that the microtubule minus end binding protein Patronin functions downstream of orb in oocyte specification. Finally, in contrast to a previously proposed model for oocyte selection, we find that the choice of which pro-oocyte becomes the oocyte does not seem to be predetermined by the amount of fusome material in these two cells, but instead depends upon a competition for orb gene products. [ABSTRACT FROM AUTHOR]

Primary Mucinous eccrine carcinoma (MEC) is a rare malignant neoplasm of skin believed to arise from eccrine sweat gland commonly with periocular involvement. Here we report a case of 60-year male with a recurrence of unilateral nasomaxillary mass and epiphora. Imaging suggested nasolacrimal duct as probable site of origin. Histopathology and immunochemistry confirmed the diagnosis and managed surgically. This case report emphasizes the significance of including primary MEC in the differential diagnosis of nasomaxillary mass for its recurrence nature and histological similarity with metastasis from other viscera. [ABSTRACT FROM AUTHOR]

* Context.--Breast cancer with low (1%-10%) estrogen receptor (ER) expression (ER--low positive) constitutes a small portion of invasive breast cancers, and the treatment strategy for these tumors remains debatable. Objective.--To characterize the features and outcomes of ER--low positive patients, and clarify the clinical significance of FOXC1 and SOX10 expression in ER--low positive/HER2-negative tumors. Design.--Among 9082 patients diagnosed with primary invasive breast cancer, the clinicopathologic features of those with ER--low positive breast cancer were characterized. FOXC1 and SOX10 mRNA levels were analyzed in ER--low positive/HER2-negative cases from public data sets. The expression of FOXC1 and SOX10 in ER--low positive/HER2-negative tumors was evaluated by immunohistochemistry. Results.--The clinicopathologic study of ER--low positive tumors indicated more aggressive characteristics compared with those tumors with ER .10%, while they had more overlapping features with ER-negative tumors irrespective of the HER2 status. The intrinsic molecular subtype of ER--low positive cases with high FOXC1 and SOX10 mRNA expression was more likely to be nonluminal. Among the ER--low positive/HER2-negative tumors, 56.67% (51 of 90) and 36.67% (33 of 90) were positive for FOXC1 and SOX10, respectively, which was significantly positively correlated with CK5/6 expression. In addition, the survival analysis demonstrated no significant difference between patients who received and who did not receive endocrine therapy. Conclusions.--ER--low positive breast cancers biologically overlap more with ER-negative tumors. ER--low positive/HER2-negative cases demonstrate a high rate of FOXC1 or SOX10 expression, and these cases might be better categorized as a basal-like phenotype/subtype. FOXC1 and SOX10 testing may be used for the intrinsic phenotype prediction for ER--low positive/HER2-negative patients. [ABSTRACT FROM AUTHOR]

Background: Clinical laboratories perform a wide range of tests that are used by healthcare professionals to guide medical decision making. Use of automated analyzers in the clinical laboratory can improve patient care by not only reducing the turn-around-time (TAT) of results but also improving accuracy of the reported results by reducing human error. The aim of this study was to evaluate the performance characteristics of a new automated laboratory instrument, the Atellica® CI Analyzer, Model 1900, over a 3-month period in a European laboratory setting. Methods: Analytical performance of 17 analytes (13 chemistry and four immunochemistry) was assessed by evaluating repeatability and within-laboratory precision using anonymized remnant serum samples. Method comparison studies were performed on the Atellica CI Analyzer and the Roche cobas® 6000. Results: Excellent precision was observed with coefficients of variation (CVs) less than 2 % for repeatability and less than 3 % within-laboratory imprecision for most analytes. Comparison of select assays with the cobas 6000 system resulted in correlation coefficients ranging from 0.980 to 1.000. Conclusion: This is the first reported evaluation of the Atellica CI Analyzer in a clinical laboratory setting. The strong analytical performance of the Atellica CI Analyzer demonstrates that this instrument is suitable for routine clinical use.

Cellular angiofibroma is a rare benign mesenchymal tumor, typically occurring in the vulvar region of middle-aged women. This report highlights the importance of histological analysis in diagnosing this uncommon condition and emphasizes its benign nature and straightforward management. We present a case of a 58-year-old North African woman who had a large, well-defined mass in the left labia majora, which had been evolving over 2 years. MRI confirmed the resectability of the tumor by delineating its boundaries. The tumor, despite its slow growth leading to delayed diagnosis, was effectively treated with wide surgical excision. Diagnosis was confirmed through histological and immunohistochemical evaluations, revealing spindle cell proliferation with thick-walled vessels. Cellular angiofibroma, although initially alarming due to its size, is generally managed successfully with surgery and prognosis is favorable with a low risk of recurrence. [ABSTRACT FROM AUTHOR]

Objective To understand the identification effect of three different markers on human lymphatic endothelial cells. Methods Human lymphatic endothelial cells were cultured. The expression of Prox1,LYVE-1,and VEGFR-3 protein and mRNA were detected by immunochemistry and PCR, respectively. Results The expression of PROX1 and LYVE1 was observed in the immunochemistry of human lymphatic endothelial cells after passage, but the expression of VEGFR-3 was not observed. Normal PCR showed that PROX1, LYVE1 and VEGFR-3 mRNA were expressed, and the expression of VEGFR-3 mRNA was significantly decreased. Conclusion Prox-1, LYVE-1 and VEGFR-3 can be used to identify suitable human lymphatic endothelial cells, and the expression of VEGFR-3 can be dynamically changed according to the literature analysis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate participation and participation patterns in a population-based screening programme for colorectal cancer (CRC) using the faecal immunochemical test (FIT). Methods: All individuals invited to three consecutive screening rounds in the population-based CRC screening between October 2015 and December 2020 in the Stockholm–Gotland Region, Sweden were included. Patterns of participation were assessed. Results: The study included 26 541 individuals which resulted in 79 623 screening events. The overall uptake rate was 71.5% and women had a significantly higher participation rate. The participation rate increased significantly between the first and third screening round for both men and women, and the increase was larger among men than women (66.1 to 70.7% vs. 73.1 to 75.4%). In total, 80.9% participated at least once. Consistent participation was the most common participation pattern (61.0%). The probability of attending all three consecutive rounds after initial participation was 87.7%. Over the three rounds, 17.4% participated after a reminder letter. Screening individuals attending after a reminder letter had a higher proportion of drop-outs in the following screening round compared to initial participants (15.4% vs 6.2%). Conclusion: A constant and high participation rate was observed in population-based FIT-screening for CRC. Initial participation was a strong predictor for continuous participation. The need for a reminder letter before participation was a risk factor for subsequent drop-out. [ABSTRACT FROM AUTHOR]

Objective: To compare interval cancer proportions (ICP) in the faecal immunochemical test (FIT)-based Scottish Bowel Screening Programme (SBoSP) with the former guaiac faecal occult blood test (gFOBT)-based SBoSP and investigate associations between interval cancer (IC) and faecal haemoglobin concentration (f-Hb) threshold, sex, age, deprivation, site, and stage. Methods: The ICP data from first year of the FIT-based SBoSP and the penultimate year of the gFOBT-based SBoSP were compared in a prospective cohort design. Results: With FIT, 801 colorectal cancers (CRCs) were screen detected (SDC), 802 were in non-participants, 548 were ICs, 39 were colonoscopy missed and 72 were diagnosed after incomplete screening; with gFOBT: 540, 904, 556, 45, and 13, respectively. FIT had a significantly higher proportion of SDC compared to IC than gFOBT. For FIT and gFOBT, ICP was significantly higher in women than men. As f-Hb threshold increased, ICP increased and, for any f-Hb threshold for men, a lower threshold was required for comparable ICP in women. In Scotland, the current threshold of ≥80 µg Hb/g faeces would have to be lowered to ≥40 µg Hb/g faeces for women to achieve sex equality for ICP. In the FIT-based SBoSP, there were four times as many stage I SDC than IC. This was reversed in advanced stages, with twice as many stage IV CRC diagnosed as IC versus SDC. Conclusions: Reducing the numbers of IC requires lowering the f-Hb threshold. Using different f-Hb thresholds for women and men could eliminate the sex disparity, but with additional colonoscopy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate interval cancer (IC) after two screening rounds of the Swedish population-based screening program of Stockholm–Gotland applying gender-specific cut-off levels in the fecal immunochemical test (FIT). Methods: All 60- to 69-year-olds invited to screening 2015–2019 were included. The cut-off level for a positive test was 40 µg/g in women and 80 µg/g in men. Screening-detected colorectal cancers (SD CRCs) and ICs were verified in the Swedish Colorectal Cancer Register, and the follow-up time was two years from invitation. The test sensitivity, the IC rate (ICs per 10,000 screening negatives) and the IC incidence (ICs per 100,000 person-years) relative to the background CRC incidence were assessed by gender and age. The FIT levels were compared in men and women for CRCs diagnosed within one year of the sample. Results: In the second screening round, 229,187 were invited, and SD CRCs and ICs were diagnosed in 193 and 144, respectively. The IC rate was 8.9 (7.4–10.3) and test sensitivity 0.61 (0.55–0.66), and was similar in men and women. For two screening rounds, the IC rate was significantly higher in men than in women, but the IC incidence/ background CRC incidence was similar in both genders. The FIT levels in female participants with CRC were significantly lower overall, and in early-staged CRCs as compared to men, and proximal localization was more common in women. In multivariable analysis, FIT levels were significantly lower in proximal CRCs. Conclusion: Over two rounds, the IC incidence relative to the background CRC incidence was similar in men and women supporting a gender-specific screening strategy. The results could be explained by lower FIT levels in women due to proximal CRC localization. [ABSTRACT FROM AUTHOR]

Simple Summary: Penile cancer is a rare but aggressive cancer. After it metastasizes, the median survival time is less than 12 months. The overall response rate to common first-line combination chemotherapy treatments is approximately 50%. There is an urgent need in advanced-penile-cancer treatment to find novel therapies that would generate better response rates than standard chemotherapy thus far and have less toxicity. Partially due to its rarity, there are few animal models and cell lines of penile cancer. We report on the generation of seven penile cancer animal models that were created by directly implanting human tumor tissue into immunocompromised mice. Metastatic penile squamous cell carcinoma (PSCC) has only a 50% response rate to first-line combination chemotherapies and there are currently no targeted-therapy approaches. Therefore, we have an urgent need in advanced-PSCC treatment to find novel therapies. Approximately half of all PSCC cases are positive for high-risk human papillomavirus (HR-HPV). Our objective was to generate HPV-positive (HPV+) and HPV-negative (HPV−) patient-derived xenograft (PDX) models and to determine the biological differences between HPV+ and HPV− disease. We generated four HPV+ and three HPV− PSCC PDX animal models by directly implanting resected patient tumor tissue into immunocompromised mice. PDX tumor tissue was found to be similar to patient tumor tissue (donor tissue) by histology and short tandem repeat fingerprinting. DNA mutations were mostly preserved in PDX tissues and similar APOBEC (apolipoprotein B mRNA editing catalytic polypeptide) mutational fractions in donor tissue and PDX tissues were noted. A higher APOBEC mutational fraction was found in HPV+ versus HPV− PDX tissues (p = 0.044), and significant transcriptomic and proteomic expression differences based on HPV status included p16 (CDKN2A), RRM2, and CDC25C. These models will allow for the direct testing of targeted therapies in PSCC and determine their response in correlation to HPV status. [ABSTRACT FROM AUTHOR]

Monitoring complications of colonoscopies after a positive faecal immunochemical test (FIT-colonoscopies) is crucial in FIT-based colorectal cancer (CRC) screening. We investigated the occurrence of bleeding and perforation post FIT-colonoscopies (2013–2019) in Flanders and the contributing factors. A retrospective case–control study was conducted, including bleeding/perforation cases within 14 days after index colonoscopy, and controls without such events. Bleeding rates dropped from 0.9–1.1% (pre-2017) to 0.3% (2017–2018) and further to 0.05% (2019), while perforation rates remained at 0.05–0.11% (2014–2019). Male gender, polypectomy, general anaesthesia, and recent antiplatelet/antithrombotic drug use increased bleeding odds. Incomplete colonoscopy, polypectomy, general anaesthesia, and recent antiplatelet/antithrombotic drug use raised perforation odds. The endoscopists (n = 16) with highest bleeding rates (top 5%) performed only 6% of total FIT-colonoscopies, yet their patients experienced 45.5% of bleeding events. Similarly, for the top 5% of perforation rates, endoscopists conducting only 4.5% of total FIT-colonoscopy had 49.0% of perforation events occur in their patients. This study sheds light on FIT-colonoscopy-related complications in Flanders, their rates and risk factors. These findings can be incorporated into CRC screening materials and guide interventions to mitigate complications. A central colonoscopy register is currently lacking in Belgium, highlighting the need for its establishment to facilitate recurrent monitoring and evaluation. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the most common cancer diagnosed worldwide. CRC can be effectively prevented or treated if detected early, through screening. This study aimed to determine the influencing factors of CRC screening participation in 50–70-year adults in Iran. A total of 354 adults who never participated in the CRC screening from two health centers in Isfahan in September 2022 were selected randomly. A group of 329 sex and age-matched adults with a history of CRC screening was selected as a control group. Logistic regression analyses were applied to assess the cognitive differences between the two groups. According to the results, Knowledge (OR = 1.61, 95% CI:1.36–1.9), perceived susceptibility (OR = 1.17, 95% CI:1.04–1.3), response efficacy (OR = 1.24, 95% CI:1.09–1.41), and self-efficacy (OR = 1.13, 95% CI:1.06–1.2) among the control group and perceived barriers (OR = 0.88, 95% CI:0.85–0.92) in the case group, were significant factors influencing participation in the CRC screening. Results of this study suggest that an HBM education model is an advantageous approach to increase CRC screening participation in adults. Certified Health Education Specialists are key personnel in using the HBM model of care and facilitators of behavioral change that will be resulted in improved participation in CRC screening. [ABSTRACT FROM AUTHOR]

Introduction/Objectives: The fecal immunochemical test (FIT) helps triage primary care patients at risk of colorectal cancer (CRC). Improving FIT returns has received recent attention, however uncertainty exists regarding the accurate completion of samples provided for laboratory analysis. This study aims to identify the rejection rate of returned FIT samples and determine rejection causes. Methods: FIT samples from symptomatic patients within South Yorkshire, Bassetlaw, and North Derbyshire are processed at a central laboratory. Tests requests are made from 225 GP practices, which serve an estimated 2 million population. This study describes a retrospective review of FIT samples received in the central laboratory between 01/09/19 and 31/12/22. Locally held data was interrogated in March 2023 to determine the number of FIT samples received and rejected during the study period. Documented reasons for rejection were explored to identify common themes. Results: Total FIT specimens received during the study period was 126 422. Of these, 5190 (4.1%) were rejected. Monthly rejection rates fell from 17.4% in September 2019 to 1.3% in December 2022 (P <.001). Sampling errors were the most frequent cause for FIT rejection (2151/5190), with other causes including: expired specimen; no sample collection date/ time, no request form, incomplete patient information and illegible handwriting. Conclusions: This is the first study exploring FIT rejection rates in symptomatic primary care patients, which shows improvements in rejection rates over time. Targeted interventions could improve rejection rates further, thereby reducing NHS resource use and costs and diagnostic delays. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1, resulting from dominantly inherited mutations affecting neurofibromin, is among the most common human genetic syndromes associated with many neurocutaneous manifestations. Neoplasms, neurogenic and non-neurogenic, are frequent, as are the gastrointestinal manifestations. Gastrointestinal tumors and vasculopathy are well-reported in individuals with neurofibromatosis type 1. A combination of somatostatioma and gastrointestinal stromal tumor is considered pathognomonic. We here report a case of neurofibromatosis type 1 with a triad of distinct neoplasms: gastrointestinal stromal tumor, neuroendoscrine tumor, and intra-ampullary papillary-tubular neoplasm. The trilogy of these neoplasms is unique and, to our knowledge, has never been reported in the literature. The report also emphasizes the role of advanced immunochemical staining in day-to-day practice, which has improved diagnostic accuracy and yield. [ABSTRACT FROM AUTHOR]

Background: Intracranial schwannomas are benign lesions, expected to exhibit characteristic ultrastructural features and immunophenotypic profile, typically being S-100, SOX10 and collagen-IV positive, while other markers, including CD34, are not usually expressed and are employed in the diagnostic elimination process. Case presentation: A 51-year-old female presented with a rapidly deteriorating neurological status. MRI showed a heterogeneous enhancing neoplasm of the anterior fossa. Preoperative differential diagnosis predilected an esthesioneuroblastoma. A bifrontal craniotomy with total excision of the lesion was performed. Dural infiltration was present. There was no association with the olfactory system. Microscopic examination revealed a uniform population of spindled to slightly epithelioid cellular proliferation with no significant atypia, low mitotic activity, and foci of necrosis. Upon immunohistochemical investigation the tumor was consistent with cellular schwannoma. Diffuse positivity for CD34 was an unusual finding. Discussion: Cellular schwannoma should be considered in the presence of an anterior fossa tumefaction. Olfactory nerve is not directly associated with these lesions. Various theories have been proposed, with the meningeal trigeminal branches' origin being the most probable. The characteristic ultrastructural Antoni formations may be scarce or even absent in cellular schwannomas creating potential diagnostic difficulties. Unusual diffuse CD34 positivity should not be employed for excluding the diagnosis. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a disease specific to pregnancy that causes 9–10 % of maternal deaths. Early-onset PE (<34 weeks' gestation) is the most dangerous category of PE. Wnt7a and GPR124 (G protein-coupled receptor 124) are widely expressed in the human reproductive process. Especially during embryogenesis and tumorigenesis, Wnt7a plays a crucial role. However, few studies have examined the association between Wnt7a-GPR124 and early-onset PE. The aim of this study was to examine the significance of Wnt7a and GPR124 in early-onset PE as well as Wnt7a's role in trophoblast cells. Immunohistochemistry (IHC), real-time PCR, and western blotting (WB) were used to investigate Wnt7a and GPR124 expression in normal and early-onset PE placentas. Additionally, FACS, Transwell, and CCK-8 assays were used to diagnose Wnt7a involvement in migration, invasion, and proliferation. In the early-onset PE group, Wnt7a and GPR124 expression was significantly lower than in the normal group, especially in the area of syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). A negative correlation was found between Wnt7a RNA and GPR124 expression (r=−0.42, p<0.01). However, the Wnt7a RNA expression level was positive correlated with PE severity. In further cellular functional experiments, knockdown of Wnt7a inhibits HTR8/SVeno cells invasion and migration but has little effect on proliferation and apoptosis. Through the Wnt pathway, Wnt7a regulates trophoblast cell invasion and migration, and may contribute to early-onset preeclampsia pathogenesis. A molecular level study of Wnt7a will be needed to find downstream proteins and mechanisms of interaction. [ABSTRACT FROM AUTHOR]

Background. The objective of this study was to describe the histological and immunohistochemical aspects of vomeronasal organ in two groups of (normal and pathological) embryos and fetuses, with chromosomal morphological abnormalities. Methods. The research was based on a retrospective, descriptive analysis, carried out over a period of 5 years. The study included 46 biopsy fragments taken from aborted embryos and fetuses aged between 9 and 23 weeks. We compared the microscopic structure of the vomeronasal organ using different histologic and immunohistochemical staining procedures. Results. Our results showed that in both groups of embryos and fetuses there are three major stages of histological development of the vomeronasal organ, depending by intrauterine age. We also observed that in the group of abnormal embryos and fetuses, although the morphological and immunohistochemical characteristics of vomeronasal organ were similar to the control group, the specific structures of the vomeronasal organ persisted beyond 22 weeks. In the control group, the vomeronasal organ was no longer visible at this age. The results of the immunohistochemical study indicated that the positive surface for cytokines in the control group decreased with age, and in the group with morphological anomalies, the number of positive cells was low. On the other hand, in fetuses with chromosomal anomalies, the positivity, although a slight downward trend was recorded, it remained high. Conclusions. This study is still ongoing in order to identify the increased frequency of vomeronasal organ in fetuses. Moreover, we anticipate that our study can be a starting point for other researchers in order to identify a relationship between the behavioral pattern of the fetuses with trisomy 21 and the persistence of the VNO. [ABSTRACT FROM AUTHOR]

The International System for Reporting Serous Fluid Cytology (TIS) has been proposed by an expert working team composed of the International Academy of Cytology and the American Society of Cytopathology, following an international survey. Since its introduction, the TIS has gained worldwide acceptance, and this review aims to assess its global impact. A literature search revealed 25 studies which have presented data on the impact of the TIS. Most of them provide data, including risk of malignancy (ROM) for each diagnostic category, separately for pleural, peritoneal and pericardial effusions, while a few do not separate them. A few studies focus on specific diagnoses like mesothelioma on specific types of fluids or more specific issues like the optimal fluid volume for cytology or interobserver variability. A synopsis of the data from the literature search is presented in four tables. The ROM assessment is discussed, as well as interobserver variability and the use of ancillary diagnostic immunochemistry. In conclusion, our review of the published data suggests that the TIS is a valid classification scheme that has been widely accepted by pathologists globally, is highly reproducible and makes a valuable contribution to clinical therapeutic management. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder that currently affects as many as 50 million people worldwide. It is neurochemically characterized by an aggregation of β-amyloid plaques and tau neurofibrillary tangles that result in neuronal dysfunction, cognitive decline, and a progressive loss of brain function. TgSwDI is a well-studied transgenic mouse model of AD, but no longitudinal studies have been performed to characterize cognitive deficits or β-amyloid plaque accumulation for use as a baseline reference in future research. Thus, we use behavioral tests (T-Maze, Novel Object Recognition (NOR), Novel Object Location (NOL)) to study long-term and working memory, and immunostaining to study β-amyloid plaque deposits, as well as brain size, in hippocampal, cerebellum, and cortical slices in TgSwDI and wild-type (WT) mice at 3, 5, 8, and 12 months old. The behavioral results show that TgSwDI mice exhibit deficits in their long-term spatial memory starting at 8 months old and in long-term recognition memory at all ages, but no deficits in their working memory. Immunohistochemistry showed an exponential increase in β-amyloid plaque in the hippocampus and cortex of TgSwDI mice over time, whereas there was no significant accumulation of plaque in WT mice at any age. Staining showed a smaller hippocampus and cerebellum starting at 8 months old for the TgSwDI compared to WT mice. Our data show how TgSwDI mice differ from WT mice in their baseline levels of cognitive function and β-amyloid plaque load throughout their lives. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) screening is recommended for average‐risk adults, yet many adults are not up‐to‐date with screening. One recommended CRC screening approach is the annual completion of a fecal immunochemical test (FIT). However, usually, fewer than half of mailed FIT tests are returned. Methods: To address barriers to FIT return, a video brochure was developed providing targeted CRC screening information and step‐by‐step FIT instructions as a component in a mailed FIT program. This pilot study occurred in 2021‐2022 and partnered with a federally qualified health center in Appalachian Ohio to send a FIT to patients who were 50‐64 years old, of average risk, and not up‐to‐date on CRC screening. Patients were randomly assigned to 1 of 3 groups that differed on materials sent with the FIT: usual care (manufacturer's instructions), a video brochure (video instructions, disposable gloves, disposable stool collection device), or an audio brochure (audio instructions, disposable gloves, disposable stool collection device). Findings: Overall, 16 of 94 patients (17%) returned the FIT, and return was higher among those sent the video brochure (28%) compared to the other 2 groups (OR: 3.1; 95% CI: 1.02, 9.2; P =.046). Two patients had positive tests and were referred for colonoscopy. Patients sent the video brochure reported the content was important, relevant, and made them think about completing the FIT. Conclusions: Using a video brochure to provide understandable information in a mailed FIT kit is a promising strategy to improve CRC screening outreach programs in rural regions. [ABSTRACT FROM AUTHOR]

Introduction: Multiple Primary Malignant Tumors (MPMT) are two or more distinct primary cancers in a single patient, either occurring simultaneously (synchronous) or at different times (metachronous). MPMTs are very rare, with an incidence of 0.73% to 11.7% among cancer patients. Breast and lung cancers are the most common malignancies in women, but their coexistence as MPMT is uncommon. Case presentation: We report the case of a 51-year-old non-smoking woman who had a productive cough with bloody sputum for a week, after a two-month history of dry cough. She was diagnosed with a high-grade, poorly differentiated non-keratinizing squamous-cell carcinoma in the right lung. A PET scan also revealed a poorly defined soft tissue mass in the central sector of the right breast, which was confirmed to be a primary invasive ductal carcinoma. Discussion: The etiology and pathogenesis of MPMT are unclear, but several factors such as genetic predisposition, environmental exposure, immunodeficiency, and treatment-related effects have been proposed. The diagnosis and management of MPMT are challenging, as they require careful evaluation of each tumor and individualized treatment plans. The prognosis of MPMT depends on the stage and histology of each tumor, as well as the patient’s performance status and comorbidities. Conclusion: This case report highlights the rare occurrence of synchronous primary malignancies in the lung and breast, underreported in the medical literature. This case adds to the existing knowledge of MPMT and may stimulate further research on this topic. Clinicians should be aware of the possibility of MPMT in cancer patients and perform thorough investigations to rule out secondary or metastatic tumors.

Background & Methods: The aim of the study is to study Characterizing of Early Leprosy by routine histopathology Immunochemistry and by methods of Molecular Biological. Results: The lesions were found to be mostly in the extremities (44/50, 88%) with the upper extremities being more frequently involved. Nerve thickening was observed to be present in 26% of the cases, with cutaneous nerve involvement being seen in 5 (10%) and peripheral nerve trunk involvement in 8 (16%). The skin smear was negative for AFB in all, and the Mitsuda lepromin reaction was positive in 18/30 (60%) of the cases studied. Conclusion: The present study, 100 cases of clinically diagnosed early leprosy (Idt leprosy, early TT/BT) and, 90 cases of clinically suspect leprosy were studied from the viewpoint of histological diagnosis. Homogeneity within the two groups was achieved by selecting only untreated cases and by defining the features required to make the clinical diagnosis. Biopsies were taken from the lesion peripheries, fixed in 10% buffered formalin, and, processed for routine histopathological examination. The histological diagnosis of leprosy, using specific defined criteria was made in (36%) in the clinical category of early leprosy, and in (24.44%) in the clinical category of suspect leprosy. These findings are consistent with the low (and variable) degree of histological confirmation reported in several studies in the chosen categories of cases. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer (GC) has a poor prognosis, as it has often grown into an advanced stage when diagnosed. Genetic testing is crucial for establishing a treatment plan. In this study, next-generation sequencing (NGS) was performed to discover that LRP1B mutation was associated with a poor prognosis in GC. Through layer-by-layer research, it was found that LRP1B expression in GC was accompanied by a higher-level infiltration of CD4+ T, CD8+ T cells, and CD86/CD163. It is concluded that LRP1B expression can stimulate tumor immune cell infiltration, thus bringing clinical benefits to GC patients. Background: Recent studies have shown that low-density lipoprotein receptor-related protein 1b (LRP1B), as a potential tumor suppressor, is implicated in the response to immunotherapy. The frequency of LRP1B mutation gene is high in many cancers, but its role in gastric cancer (GC) has not been determined. Methods: The prognostic value of LRP1B mutation in a cohort containing 100 patients having received radical gastrectomy for stage II–III GC was explored. By analyzing the data of LRP1B mRNA, the risk score of differentially expressed genes (DEGs) between LRP1B mutation-type and wild-type was constructed based on the TCGA-STAD cohort. The infiltration of tumor immune cells was evaluated by the CYBERSORT algorithm and verified by immunohistochemistry. Results: LRP1B gene mutation was an independent risk factor for disease-free survival (DFS) in GC patients (HR = 2.57, 95% CI: 1.28–5.14, p = 0.008). The Kaplan–Meier curve demonstrated a shorter survival time in high-risk patients stratified according to risk score (p < 0.0001). CYBERSORT analysis showed that the DEGs were mainly concentrated in CD4+ T cells and macrophages. TIMER analysis suggested that LRP1B expression was associated with the infiltration of CD4+ T cells and macrophages. Immunohistochemistry demonstrated that LRP1B was expressed in the tumor cells (TCs) and immune cells in 16/89 and 26/89 of the cohort, respectively. LRP1B-positive TCs were associated with higher levels of CD4+ T cells, CD8+ T cells, and CD86/CD163 (p < 0.05). Multivariate analysis showed that LRP1B-positive TCs represented an independent protective factor of DFS in GC patients (HR = 0.43, 95% CI: 0.10–0.93, p = 0.042). Conclusions: LRP1B has a high prognostic value in GC. LRP1B may stimulate tumor immune cell infiltration to provide GC patients with survival benefits. [ABSTRACT FROM AUTHOR]

Simple Summary: Many cancers, especially those most common in adolescents and young adults, are initiated by a single change in the DNA sequence of a gene. The particular change creates a new gene through the fusing of the beginning of one gene to the end of a second gene. This new fusion gene will be expressed as a fusion protein that combines the functions of the two parent genes, but in new ways. Because many of the cancers that are driven by these fusion genes are rare, study of the precise function of the fusion proteins can be difficult. This article reports on the study of a particular fusion protein that drives the rare, but deadly, pediatric cancer clear cell sarcoma. The fusion protein was expressed in mice, leading to the formation of similar tumors to those it causes in humans. This permitted the study of fusion protein function in these tumors. Clear cell sarcoma (CCS) is a rare, aggressive malignancy that most frequently arises in the soft tissues of the extremities. It is defined and driven by expression of one member of a family of related translocation-generated fusion oncogenes, the most common of which is EWSR1::ATF1. The EWSR1::ATF1 fusion oncoprotein reprograms transcription. However, the binding distribution of EWSR1::ATF1 across the genome and its target genes remain unclear. Here, we interrogated the genomic distribution of V5-tagged EWSR1::ATF1 in tumors it had induced upon expression in mice that also recapitulated the transcriptome of human CCS. ChIP-sequencing of V5-EWSR1::ATF1 identified previously unreported motifs including the AP1 motif and motif comprised of TGA repeats that resemble GGAA-repeating microsatellites bound by EWSR1::FLI1 in Ewing sarcoma. ChIP-sequencing of H3K27ac identified super enhancers in the mouse model and human contexts of CCS, which showed a shared super enhancer structure that associates with activated genes. [ABSTRACT FROM AUTHOR]

The cellulose-enriched tertiary cell walls present in many plant fibers have specific composition, architecture, machinery of formation, and function. To better understand the mechanisms underlying their mode of action and to reveal the peculiarities of fibers from different plant species, it is necessary to more deeply characterize the major components. Next to overwhelming cellulose, rhamnogalacturonan I (RG-I) is considered to be the key polymer of the tertiary cell wall; however, it has been isolated and biochemically characterized in very few plant species. Here, we add RG-I to the list from the phloem fibers of the Phaseolus vulgaris stem that was isolated and analyzed by nuclear magnetic resonance (NMR), dynamic light scattering, and immunolabeling, both within tissue and as an isolated polymer. Additionally, fibers with tertiary cell walls from nine species of dicotyledonous plants from the orders Malphigiales, Fabales, and Rosales were labeled with RG-I-related antibodies to check the presence of the polymer and compare the in situ presentation of its backbone and side chains. The obtained results confirm that RG-I is an obligatory polymer of the tertiary cell wall. However, there are differences in the structure of this polymer from various plant sources, and these peculiarities may be taxonomically related. [ABSTRACT FROM AUTHOR]

Background. Iron deficiency (ID) is a common micronutrient deficiency and the leading cause of anemia worldwide. ID can be caused by chronic occult blood loss from colorectal neoplasia including colorectal cancer (CRC) and advanced precancerous colorectal lesions. Current guidelines recommend colonoscopy in both men and postmenopausal women presenting with ID anemia (IDA). However, there is controversy on the investigation of patients presenting with a lower risk of CRC including younger women with ID and those with nonanemic ID (NAID). There is a need for a triaging tool to identify which ID patients may benefit from colonoscopy. The fecal immunochemical test (FIT) is sensitive for CRC screening in an asymptomatic population, but its role in ID patients is unclear. The aim of this study is to conduct a systematic review to determine the diagnostic accuracy of FIT for detecting CRC and advanced precancerous neoplasia in individuals presenting with ID with or without anemia. Methods and Analysis. This protocol conforms with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols and Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. A comprehensive search of the MEDLINE, Embase, and Web of Science databases will be undertaken for studies published after 2010 which involve patients with ID, who completed a FIT in the 6 months prior to colonoscopy, with FIT sensitivity and specificity calculated against the reference standard colonoscopy. The search will be limited to studies conducted after 2010 to reduce variability in colonoscopy quality. Risk of bias assessment will be conducted using the Quality Assessment of Diagnostic Accuracy Studies version 2. FIT sensitivity and specificity will be the primary measure of diagnostic accuracy, and data will be analysed using a random effects meta-analysis. Discussion. This review and meta-analysis will be the first to systematically explore the value of the FIT as a triaging tool for patients with ID. This trial is registered with CRD42022367162. [ABSTRACT FROM AUTHOR]

Objectives: To explore the perceptions of patients and healthcare professionals on Raman‐faecal immunochemical test (FIT) as an alternative test for colorectal cancer exclusion in primary care. Design: Semi‐structured interviews within a feasibility study. Setting: Patients presenting to primary care with colorectal symptoms and healthcare professionals working in primary and secondary care. Participants: A total of 23 patients and 12 healthcare professionals. Methods: Patient participants were asked to complete a novel combined Raman‐FIT test before being seen in secondary care. This study sought their opinions about the test. We also sought the views of healthcare professionals. Findings: Patients and healthcare professionals agreed that Raman‐FIT was a suitable test to be given in primary care. It aligned with routine practice and was a simple test for most patients to complete. Conclusions: Patients are willing and able to complete the Raman‐FIT test in primary care. Raman‐FIT may accelerate access to diagnosis with the potential to improve cancer outcomes. Patient and Public Involvement: Lay members (J. H. and I. H.) with experience and knowledge of colorectal cancer and screening contributed to developing, undertaking, and disseminating all aspects of the research. They were supported to collaborate as equal members of the research team. They were involved in developing the study as coapplicants, using personal experience to ensure that the research and its methods were relevant to the patient and public needs. Both prepared participant information sheets, coanalysed data, and contributed to study reporting and dissemination through papers, conference presentations and a lay summary. [ABSTRACT FROM AUTHOR]

The article focuses on ulcerative lymphomatoid papulosis (LyP) as a rare immune-related adverse event following immune checkpoint inhibitor (ICI) therapy and autologous stem cell transplant (autoSCT) in a patient with recurrent Hodgkin lymphoma. Topics include the rarity of LyP as an ICI-induced adverse event, the clinical presentation and histopathological features of ulcerative LyP, and the challenges in diagnosis and management of LyP in patients treated with ICIs and autoSCT.

This study aimed to explore the magnetic resonance imaging (MRI) features of dual-phenotype hepatocellular carcinoma (DPHCC) and their diagnostic value.The data of 208 patients with primary liver cancer were retrospectively analysed between January 2016 and June 2021. Based on the pathological diagnostic criteria, 27 patients were classified into the DPHCC group, 113 patients into the noncholangiocyte-phenotype hepatocellular carcinoma (NCPHCC) group, and 68 patients with intrahepatic cholangiocarcinoma (ICC) were classified into the ICC group. Two abdominal radiologists reviewed the preoperative MRI features by a double-blind method. The MRI features and key laboratory and clinical indicators were compared between the groups. The potentially valuable MRI features and key laboratory and clinical characteristics for predicting DPHCC were identified by univariate and multivariate analyses, and the odds ratios (ORs) were recorded. In multivariate analysis, tumour without capsule (P = 0.046, OR = 9.777), dynamic persistent enhancement (P = 0.006, OR = 46.941), and targetoid appearance on diffusion-weighted imaging (DWI) (P = 0.021, OR = 30.566) were independently significant factors in the detection of DPHCC compared to NCPHCC. Serum alpha-fetoprotein (AFP) > 20 µg/L (P = 0.036, OR = 67.097) and prevalence of hepatitis B virus (HBV) infection (P = 0.020, OR = 153.633) were independent significant factors in predicting DPHCC compared to ICC. The differences in other tumour marker levels and imaging features between the groups were not significant. In MR enhanced and diffusion imaging, tumour without capsule, persistent enhancement and DWI targetoid findings, combined with AFP > 20 µg/L and HBV infection-positive laboratory results, can help to diagnose DPHCC and differentiate it from NCPHCC and ICC. These results suggest that clinical, laboratory and MRI features should be integrated to construct an AI diagnostic model for DPHCC. [ABSTRACT FROM AUTHOR]

* Context.--Nonsalivary primary adenocarcinomas of the base of the tongue (PABOTs) are extremely rare and worth reporting. Objective.--To study the detailed clinicopathologic features of PABOT. Design.--Cases of PABOT diagnosed on pathology material were retrieved from the archived electronic surgical pathology records. Results.--Six cases in 4 men and 2 women (M:F ratio, 2:1), with an age range of 31 to 76 years, satisfied the criteria. The tumor epicenter was the base of the tongue in all (6 of 6; 100%), with extension to the epiglottis in 50% (3 of 6), nodal metastasis in 66.7% (4 of 6), and distant metastasis in 33.3% (2 of 6). On histology, all but one were pure adenocarcinoma. Five of 6 cases (83.3%) had a gastrointestinal (GI) phenotype, of which 2 (40%) had a colonic/lower-GI--type (small groups of cells floating in mucin, CK20+, SATB2+, and CDX2+) and 3 (60%) had an upper-GI--like adenocarcinoma (UGI-LA; malignant glands with intracellular mucin, CK7+) histology. Cystic structure suggestive of teratomatous origin was identified in 2 of 5 cases (40%), both with UGI-LA phenotype. The non--GItype case had a unique histology with squamous differentiation in addition to adenocarcinoma areas, diffuse nuclear β-catenin on immunohistochemistry, and a corresponding exon 3 CTNNB1 mutation. One patient succumbed to disease, and 4 are alive with disease (follow-up of 1-9 months after completion of therapy). Conclusions.--We suggest using the broad term primary adenocarcinomas of the base of tongue (PABOTs), which can be further subdivided into colonic-type adenocarcinoma of the tongue and oral cavity, UGI-LA, and not otherwise specified categories, and reiterate a need for recognition and distinction of PABOT from salivary gland tumors. A subset originates from teratoid/duplication cysts, necessitating extensive sampling. Multicentric studies are essential to clinically and biologically prognosticate each of these categories. [ABSTRACT FROM AUTHOR]