UNASSIGNED: Forkhead box C2 gene (FOXC2) acts as an epithelial-mesenchymal transition (EMT) inducer while Prospero homeobox 1 gene (PROX-1) function as a regulator of lymphangiogenesis and angiogenesis in oral squamous cell carcinoma (OSCC). It is presumed that PROX-1 has both tumour-suppressive and oncogenic effects. The main aim of this study is to evaluate the role of PROX-1 and FOXC2 in the invasion and progression of OSCC cases and to correlate their expression with various histopathological parameters.
UNASSIGNED: A prospective cohort study was conducted in a total sample size of 52 OSCC tissues and histologically tumour-free margins of 20. mRNA expression and protein levels of FOXC2 and PROX-1 were evaluated using real-time PCR and sandwich enzyme-linked immunosorbent assay techniques. Chi-square analysis and correlation analysis were done. Kaplan-Meier analysis evaluated the survival rate.
UNASSIGNED: Mean Ct values of FOXC2 were 1.915 ± 0.519 and PROX-1 was 0.061 ± 0.173. There was a significant 2-fold increase in the FOXC2 expression and a 0.5-fold decrease in the PROX-1 expression in OSCC tissue. Increased levels of FOXC2 protein and decreased levels of PROX-1 with a mean difference of 1.64 ± 0.73 ng/ml and 1.27 ± 0.33 ng/ml were observed in OSCC compared to histologically tumour-free margins. A significant positive correlation was found between the FOXC2 expression and clinicopathological parameters such as staging, perineural invasion (PNI) and lymphovascular invasion (LVI) whereas PROX-1 showed a significant negative correlation with histopathological parameters such as staging, PNI, LVI and tumour staging. There was a significant positive correlation between the PROX-1 and histologically tumour-free margins in disease-free survival patients (P-value = 0.03).
UNASSIGNED: FOXC2 and PROX-1 expressions were correlated with lymphovascular invasion, OSCC tumour staging and PNI. Thus, FOXC2 and PROX-1 could be possible therapeutic targets in the treatment of OSCC that can inhibit the EMT in OSCC and thereby favouring a better prognosis.

Accurate and scalable quantification of amyloid-β (Aβ) pathology is crucial for deeper disease phenotyping and furthering research in Alzheimer Disease (AD). This multidisciplinary study addresses the current limitations on neuropathology by leveraging a machine learning (ML) pipeline to perform a granular quantification of Aβ deposits and assess their distribution in the temporal lobe. Utilizing 131 whole-slide-images from consecutive autopsied cases at the University of California Davis Alzheimer Disease Research Center, our objectives were threefold: (1) Validate an automatic workflow for Aβ deposit quantification in white matter (WM) and gray matter (GM); (2) define the distributions of different Aβ deposit types in GM and WM, and (3) investigate correlates of Aβ deposits with dementia status and the presence of mixed pathology. Our methodology highlights the robustness and efficacy of the ML pipeline, demonstrating proficiency akin to experts\' evaluations. We provide comprehensive insights into the quantification and distribution of Aβ deposits in the temporal GM and WM revealing a progressive increase in tandem with the severity of established diagnostic criteria (NIA-AA). We also present correlations of Aβ load with clinical diagnosis as well as presence/absence of mixed pathology. This study introduces a reproducible workflow, showcasing the practical use of ML approaches in the field of neuropathology, and use of the output data for correlative analyses. Acknowledging limitations, such as potential biases in the ML model and current ML classifications, we propose avenues for future research to refine and expand the methodology. We hope to contribute to the broader landscape of neuropathology advancements, ML applications, and precision medicine, paving the way for deep phenotyping of AD brain cases and establishing a foundation for further advancements in neuropathological research.

BACKGROUND: Alzheimer\'s disease (AD) neuropathological changes present with amnestic and nonamnestic (atypical) syndromes. The contribution of comorbid neuropathology as a substratum of atypical expression of AD remains under investigated.
METHODS: We examined whether atypical AD exhibited increased comorbid neuropathology compared to typical AD and if such neuropathologies contributed to the accelerated clinical decline in atypical AD.
RESULTS: We examined 60 atypical and 101 typical AD clinicopathological cases. The number of comorbid pathologies was similar between the groups (p = 0.09). Argyrophilic grain disease was associated with atypical presentation (p = 0.008) after accounting for sex, age of onset, and disease duration. Vascular brain injury was more common in typical AD (p = 0.022). Atypical cases had a steeper Mini-Mental Status Examination (MMSE) decline over time (p = 0.033).
CONCLUSIONS: Comorbid neuropathological changes are unlikely to contribute to atypical AD presentation and the steeper cognitive decline seen in this cohort.
UNASSIGNED: Autopsy cohort of 60 atypical and 101 typical AD; does comorbid pathology explain atypical presentation?Atypical versus Typical AD: No significant differences in comorbid neuropathologies were found (p = 0.09).Argyrophilic Grain Disease Association: significantly correlates with atypical AD presentations, suggesting a unique neuropathological pattern (p = 0.008).Vascular Brain Injury Prevalence: Vascular brain injury is more common in typical AD than in atypical AD (p = 0.022).Cognitive Decline in Atypical AD: Atypical AD patients experience a steeper cognitive decline measured by MMSE than those with typical AD despite lacking more comorbid neuropathology, highlighting the severity of atypical AD pathogenesis (p = 0.033).

Introduction Primary extramammary Paget\'s disease (EMPD) is a rare neoplasm that manifests as well-defined erythematous plaques, often misdiagnosed due to its similarity with different dermatoses. It may exhibit invasive features, involving adnexal invasions. The study aims to assess and compare the clinicopathological correlation of primary EMPD with adnexal features. Materials and methodology The monocentric observational retrospective study observed 43 confirmed primary EMPD cases in patients aged 45-95, excluding those with infectious dermatoses, pseudo-tumors, secondary lesions, or survived less than a month. Demographical, clinical and pathological observations were recorded. Expert dermatopathologists, blinded to the initial diagnosis, conducted a comprehensive histopathological evaluation yielding differential pathological diagnosis. Statistical analysis involved Pearson\'s Chi-square, Mann-Whitney U, and Spearman\'s Correlations for clinicopathological concordance and adnexal features. Recurrence was evaluated using Kaplan-Meier and log-rank tests, while multivariate recurrence analyses include Cox regression. A p-value < 0.05 was deemed significant. Results There was a significant association between adnexal involvement and the site of lesion (p < 0.05). There was a significant association (p < 0.05) between involved adnexal depth and primary EMPD subtypes. Adnexal involvement has a significant association with the concordance rates derived from clinicopathological correlations (p < 0.05). Smaller lesions and non-invasive EMPD significantly predict longer recurrence onset (p < 0.01). The primary EMPD subtype was the only independent predictor for recurrence time using the Cox regression model. Conclusion Adnexal proliferation in primary EMPD is considered vital on clinicopathological correlations and recurrence predictions, suggestive of its utility on both diagnosis and prognosis.

Fewer than 26 case reports describe hypertrophic lichen planus (HLP) misdiagnosed as cutaneous squamous cell carcinoma (cSCC). It can be difficult to distinguish between HLP and cSCC, as these two conditions share many clinical and histopathological characteristics. Patients who are misdiagnosed with cSCC often undergo unnecessary medical and/or surgical interventions before receiving a diagnosis of HLP and improving on HLP-directed therapy. This case series highlights the course of three female patients, referred to a single tertiary institution between 2018 and 2022, who were initially misdiagnosed with cSCC before receiving a diagnosis of HLP. We have emphasized the clinical and histopathological distinguishing features between HLP and cSCC, the pathogenesis of HLP, and current and new HLP-directed therapy. We hope that this case series serves as a reminder to dermatologists, dermatologic surgeons, and dermatopathologists to be aware of this diagnostic challenge.

UNASSIGNED: The haemoglobin, albumin, lymphocyte, and platelet (HALP) score, a convenient and composite laboratory biomarker, can reflect inflammation and systemic nutritional status. This study was performed to investigate the effect of the HALP score on the prognosis of patients with IgA nephropathy (IgAN).
UNASSIGNED: This is a retrospective single centre study that enrolled 895 biopsy-confirmed IgAN patients from June 2019 to June 2022 who were followed for more than 1 year. Kaplan-Meier curves and Cox regression analyses were performed to determine the relationship between HALP and adverse outcomes. The restricted cubic splines was used to identify the possible associations. The optimal cut-off value of HALP for renal poor outcome was identified by the area under the receiver operating characteristic curve (AUC).
UNASSIGNED: A total of 895 patients finally participated in the study and were divided into three groups (tertial 1-3) according to the baseline HALP score. More severe clinicopathologic features were observed in the lower HALP group, and Kaplan-Meier analysis showed patients in tertial 1 had a higher risk of kidney failure than the other groups (log-rank=11.02, P= 0.004). Multivariate Cox regression revealed that HALP score was an independent risk factor for renal prognosis in IgAN (adjusted HR: 0.967, 95% CI: 0.945-0.990, P = 0.006). The results of subgroup analysis suggested that HALP was more important in patients under the age of 50, BMI ≤ 23.9 and eGFR ≤ 90 mL/min/1.73 m2. The best cut-off HALP for renal survival was 38.83, sensitivity 72.1%, and specificity 55.9% (AUC: 0.662). Patients were further grouped according to HALP cut-off values and propensity matched. Multivariate Cox regression analysis revealed that HALP remained an independent predictor of IgAN in the matched cohort (HR 0.222, CI: 0.084-0.588, P=0.002).
UNASSIGNED: HALP is a novel and potent composite parameter to predict kidney outcome in patients with IgAN.

BACKGROUND: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by hyperphosphorylated tau (p-tau) accumulation. The clinical features associated with CTE pathology are unclear. In brain donors with autopsy-confirmed CTE, we investigated the association of CTE p-tau pathology density and location with cognitive, functional, and neuropsychiatric symptoms.
METHODS: In 364 brain donors with autopsy confirmed CTE, semi-quantitative p-tau severity (range: 0-3) was assessed in 10 cortical and subcortical regions. We summed ratings across regions to form a p-tau severity global composite (range: 0-30). Informants completed standardized scales of cognition (Cognitive Difficulties Scale, CDS; BRIEF-A Metacognition Index, MI), activities of daily living (Functional Activities Questionnaire), neurobehavioral dysregulation (BRIEF-A Behavioral Regulation Index, BRI; Barratt Impulsiveness Scale, BIS-11), aggression (Brown-Goodwin Aggression Scale), depression (Geriatric Depression Scale-15, GDS-15), and apathy (Apathy Evaluation Scale, AES). Ordinary least squares regression models examined associations between global and regional p-tau severity (separate models for each region) with each clinical scale, adjusting for age at death, racial identity, education level, and history of hypertension, obstructive sleep apnea, and substance use treatment. Ridge regression models that incorporated p-tau severity across all regions in the same model assessed which regions showed independent effects.
RESULTS: The sample was predominantly American football players (333; 91.2%); 140 (38.5%) had low CTE and 224 (61.5%) had high CTE. Global p-tau severity was associated with higher (i.e., worse) scores on the cognitive and functional scales: MI ([Formula: see text] standardized = 0.02, 95%CI = 0.01-0.04), CDS ([Formula: see text] standardized = 0.02, 95%CI = 0.01-0.04), and FAQ ([Formula: see text] standardized = 0.03, 95%CI = 0.01-0.04). After false-discovery rate correction, p-tau severity in the frontal, inferior parietal, and superior temporal cortex, and the amygdala was associated with higher CDS ([Formula: see text] sstandardized = 0.17-0.29, ps < 0.01) and FAQ ([Formula: see text] sstandardized = 0.21-0.26, ps < 0.01); frontal and inferior parietal cortex was associated with higher MI ([Formula: see text] sstandardized = 0.21-0.29, ps < 0.05); frontal cortex was associated with higher BRI ([Formula: see text] standardized = 0.21, p < 0.01). Regions with effects independent of other regions included frontal cortex (CDS, MI, FAQ, BRI), inferior parietal cortex (CDS) and amygdala (FAQ). P-tau explained 13-49% of variance in cognitive and functional scales and 6-14% of variance in neuropsychiatric scales.
CONCLUSIONS: Accumulation of p-tau aggregates, especially in the frontal cortex, are associated with cognitive, functional, and certain neurobehavioral symptoms in CTE.

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UNASSIGNED: Lupus nephritis (LN) is the assemblage of glomerular, tubulointerstitial and vascular changes. Despite the fact that glomerular changes are overemphasized in pathological classification and scoring system, but the existence of vascular damage negatively impact the clinical course.
UNASSIGNED: This study was conducted to determine the clinicopathological spectrum of renal vascular lesions in lupus nephritis.
UNASSIGNED: Renal microvascular lesions in biopsy proven lupus nephritis were classified into 5 major categories-thrombotic microangiopathy, true vasculitis; lupus vasculopathy, uncomplicated vascular immune deposits, and arterial. Clinical details, laboratory parameters and histopathological variables were compared among all groups. Summary of chronic changes was also assessed.
UNASSIGNED: Biopsies from 56 patients revealed thrombotic microangiopathy (2), lupus vasculopathy (3), uncomplicated vascular immune deposit (6), PAN type vasculitis (1) and arterial sclerosis (13). No renal vascular lesions were found in 35.18% of patients. At the time of biopsy, arterial sclerosis or lupus vasculopathy patients were older Nephritis subtype. Activity indices were higher in lupus vasculopathy group whereas patients with arteriosclerosis showed highest chronicity index.
UNASSIGNED: Renal vascular lesions are common in systemic lupus erythematosus patients with nephritis and may be associated with aggressive clinical course.

BACKGROUND: microRNA(miRNA)-196a and miRNA-196b expression has been found to be dysregulated and involved in tumorigenesis and tumor progression in array of cancers through different targets. The role of these miRNAs together in clinical application is not always consistent and, its prognostic value in oral squamous cell carcinoma (OSCC) is still elusive. This study was performed to investigate the correlation of these miRNAs expression with histological grades of OSCC according to Bryne\'s histological grading system, to predict prognosis and to evaluate their relationship with clinico-pathological data.
METHODS: Real-time quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) was done to evaluate the expression levels of miRNA-196a and miRNA-196b in 75 pairs of OSCC tissue matched with adjacent normal mucosa, used as a control.
RESULTS: miRNA-196a and 196b expression in OSCC was significantly higher than that in corresponding adjacent normal tissues (p > 0.001). Also, a significant differential correlation was found in between the expression levels of these two miRNAs (Pearson correlation test r = 0.676, p-value<0.0001). The increased expression of these miRNAs was more frequently observed in OSCC tissues with advanced clinical and pathological TNM stages (IVa and IVb, pIVb respectively, p-value<0.0001). Significant correlation was found between miRNA-196a upregulation and moderate prognostic score (p-value<0.0001) in comparison with good and poor prognostic score of histological grades of OSCC. Sensitivity and specificity for miRNA-196a were 95 % and 85 %, respectively (AUC = 1, 95 % CI = 0.617-0.850; p 0.001), while for miRNA-196b were 94 % and 86 %, respectively (AUC = 0.808, 95 % CI = 0.701-0.916; p0.0001).
CONCLUSIONS: These findings suggest that the increased expression of miRNA-196a and 196b may play an important role in tumor progression in OSCC. miRNA-196a might be a useful marker for predicting the clinical outcome of OSCC, especially for advanced stages. In conclusion, our data demonstrate for the first time that these miRNAs may serve as a potent prognostic marker for tumor progression. We further highlight miRNA-196a and miRNA-196b as a promising predictor of prognostic assessment in OSCC.