Pathology as a Basic Medical Subject: Its Relevance and Application During Clinical Practice in Jordanian MD Programs, Interns' and Residents' Perspectives.

Aim: Medical literature revealed that there is a lack of information about the opinions of medical interns and residents about curricula provided to them during their undergraduate programs, either in a group of detached subjects or an incorporated and efficacious topic (ie, pathology). Purpose: To assess and compare the interns' and residents' perspectives towards Pathology as a subject. To recognize their opinions toward the relevance and application of Pathology while practicing clinically. Methods: This study was a cross-sectional online, self-administered questionnaire targeting interns and residents. The questionnaire consisted of 30 questions, enquiring about the demographic data, subject strength, teaching duration, interest in the subject, and usefulness of Pathology as a subject in clinical practice. Results: Overall, 103 participants completed the survey. The female and male percentage was 59.2% and 40.8% respectively. 86.4% of participants were interns, while 13.6% were residents. 87% of participants agreed that applying pathology during clinical practice is a skill that should be strengthened in the early stages of preclinical education of Medicine. A modest percentage believed that a practitioner could efficiently treat the majority of patients with no need to know the specifics of the pathological mechanisms involved. Most of the participants believed that pathology courses helped them in making a differential diagnosis, analysis of normal and pathological constituents, and dissection and identification of structures. Conclusion: This study highlights the positive perceptions of Jordanian interns and residents toward pathology courses. It also demonstrates that participants prefer an active and dynamic educational model with an emphasis on better integration of pathology courses and clinical experiences that fit their needs in clinical practice. Thus, we recommend future studies to compare the competencies of interns and residents enrolled in the courses with integrated medical curricula, of pathology versus those who studied the conventional medical curricula of pathology, as well as to evaluate their perceptions of medical education.

Clinicopathological features and prognosis of IgA vasculitis nephritis with nephrotic-range proteinuria in children.

BACKGROUND: To investigate the clinical features, kidney pathology, treatment regimens, and clinical outcomes of IgA vasculitis nephritis (IgAVN) with nephrotic-range proteinuria in children. METHODS: A retrospective review of children diagnosed with IgAVN between January 2019 and December 2022 was conducted. Participants were divided into two groups based on their urine protein/creatinine (UPCR) levels. Biodata, clinical characteristics, laboratory findings, pathologic features, treatment regimens, and outcomes were abstracted from case records and analyzed. RESULTS: A total of 255 children were identified, 94 with nephrotic-range proteinuria (UPCR ≥ 200 mg/mmol) and 161 with non-nephrotic proteinuria (UPCR < 200 mg/mmol). Patients in the nephrotic-range proteinuria group were significantly younger and had worse grades of glomerular and acute tubulointerstitial injury compared to those in the non-nephrotic proteinuria group. Higher levels of blood urea nitrogen (BUN), D-dimer (DD), and fibrin degradation products (FDP), and lower levels of total protein (TP), albumin (ALB), urine creatinine (Cr), prothrombin time (PT), activated partial thromboplastin time (APTT), IgG, CD3 + cells, and CD4 + cells were found in patients in the nephrotic-range proteinuria group. Clinical outcome of patients with nephrotic-range proteinuria was significantly associated with ISKDC grading, proportion of glomerular crescents and severity of acute tubulointerstitial injury. CONCLUSIONS: Children with nephrotic-range proteinuria exhibit more severe disordered immunologic function, hypercoagulability, glomerular and tubulointerstitial pathological damage, and have worse outcomes than those with lower proteinuria levels. Clinicians should pay great attention to the kidney injury and more extensive studies are required to identify optimal treatment regimens to improve outcomes in patients.

Fluorescence confocal microscopy for evaluation of fresh surgical specimens and consecutive tumor cell isolation in rare pediatric tumors.

Fluorescence confocal microscopy (FCM) is an optical technique that uses laser light sources of different wavelengths to generate real-time images of fresh, unfixed tissue specimens. FCM allows histological evaluation of fresh tissue samples without the associated cryo artifacts after frozen sectioning. The aim of this study was to prospectively evaluate pediatric tumor specimens and assess their suitability for fresh tumor sampling. In addition, we aimed to determine whether tumor cell isolation for stable cell culture is still feasible after FCM imaging. Pediatric tumor specimens were imaged using FCM. Tumor viability and suitability for tissue sampling were evaluated and compared with H&E staining after paraffin embedding. In addition, FCM-processed and non-FCM-processed tissue samples were sent for tumor cell isolation to evaluate possible effects after FCM processing. When comparing estimated tumor cell viability using FCM and H&E, we found good to excellent correlating estimates (intraclass correlation coefficient = 0.891, p < 0.001), as well as substantial agreement in whether the tissue appeared adequate for fresh tissue collection (κ = 0.762, p < 0.001). After FCM, seven out of eight samples yielded passable cell cultures, compared to eight out of eight for non-FCM processed samples. Our study suggests that the use of FCM in tumor sampling can increase the yield of suitable fresh tumor samples by identifying viable tumor areas and ensuring that sufficient tissue remains for diagnosis. Our study also provides first evidence that the isolation and growth of tumor cells in culture are not compromised by the FCM technique.

Liver fibrosis analysis using digital pathology.

Digital pathology has enabled the noninvasive quantification of pathological parameters. In addition, the combination of digital pathology and artificial intelligence has enabled the analysis of a vast amount of information, leading to the sharing of much information and the elimination of knowledge gaps. Fibrosis, which reflects chronic inflammation, is the most important pathological parameter in chronic liver diseases, such as viral hepatitis and metabolic dysfunction-associated steatotic liver disease. It has been reported that the quantitative evaluation of various fibrotic parameters by digital pathology can predict the prognosis of liver disease and hepatocarcinogenesis. Liver fibrosis evaluation methods include 1 fiber quantification, 2 elastin and collagen quantification, 3 s harmonic generation/two photon excitation fluorescence (SHG/TPE) microscopy, and 4 Fibronest™..　In this review, we provide an overview of role of digital pathology on the evaluation of fibrosis in liver disease and the characteristics of recent methods to assess liver fibrosis.

Benchmarking PathCLIP for Pathology Image Analysis.

Accurate image classification and retrieval are of importance for clinical diagnosis and treatment decision-making. The recent contrastive language-image pre-training (CLIP) model has shown remarkable proficiency in understanding natural images. Drawing inspiration from CLIP, pathology-dedicated CLIP (PathCLIP) has been developed, utilizing over 200,000 image and text pairs in training. While the performance the PathCLIP is impressive, its robustness under a wide range of image corruptions remains unknown. Therefore, we conduct an extensive evaluation to analyze the performance of PathCLIP on various corrupted images from the datasets of osteosarcoma and WSSS4LUAD. In our experiments, we introduce eleven corruption types including brightness, contrast, defocus, resolution, saturation, hue, markup, deformation, incompleteness, rotation, and flipping at various settings. Through experiments, we find that PathCLIP surpasses OpenAI-CLIP and the pathology language-image pre-training (PLIP) model in zero-shot classification. It is relatively robust to image corruptions including contrast, saturation, incompleteness, and orientation factors. Among the eleven corruptions, hue, markup, deformation, defocus, and resolution can cause relatively severe performance fluctuation of the PathCLIP. This indicates that ensuring the quality of images is crucial before conducting a clinical test. Additionally, we assess the robustness of PathCLIP in the task of image-to-image retrieval, revealing that PathCLIP performs less effectively than PLIP on osteosarcoma but performs better on WSSS4LUAD under diverse corruptions. Overall, PathCLIP presents impressive zero-shot classification and retrieval performance for pathology images, but appropriate care needs to be taken when using it.

Unwarranted intrusion of odontogenic cyst into the maxillary antrum.

During the early growth phase, every individual is involved in a prolonged series of developmental processes in the maxillofacial region. Formation of cysts associated with such three-dimensional growth of the maxillofacial skeleton as well as deciduous and permanent tooth development. The origin of cystic jaw lesions may be odontogenic or non-odontogenic, developmental, or inflammatory and they are epithelial-lined or non-epithelial-lined cysts in nature. These cysts are considered to be aggressive cysts when they tend to grow rapidly and can cause significant damage to the surrounding bone and tissues if left untreated. Aggressive cystic lesion of the jaw needs special attention in order to prevent recurrences or even worsen and widespread disease. The management of the maxillary sinus requires individualisation based on its clinical and histopathological characteristics. Here, we report a case of an aggressive odontogenic cyst in a 30s-aged female patient in the left maxillary sinus with the literature review.

Awareness of audiology and speech-language pathology services among healthcare professionals in Saudi Arabia.

BACKGROUND:  Healthcare professionals are required to work effectively together to deliver the best healthcare services. Without awareness of other healthcare professionals' roles and responsibilities, interprofessional practice (IPP) cannot be optimally achieved. OBJECTIVES:  This study aimed to investigate healthcare professionals' awareness of audiology and speech-language pathology (SLP) services in Saudi Arabia. METHOD:  This cross-sectional descriptive study consisted of two parts. The content of a 20-item paper questionnaire was firstly validated. The full-scale study addressed the aim through distributing questionnaire items among potential participants. Descriptive statistics and chi-square test were used. RESULTS:  A total of 403 participants completed the questionnaires for the main study. Most of the participants were Saudi citizens (84.1%), aged 18 years - 40 years (84.8%) years, and lived in Riyadh region (76.2%). Allied health professionals (40.2%), physicians (22.6%), nursing (15.4%) and dentistry (11.2%) were the main group of participants working mainly at governmental hospitals (69.2%). Of the total participants, 92.6% and 95.3% reported being fully aware of the services provided by audiologists and SLPs, respectively. No statistically significant association between the specialty of participants and their familiarity with the scope of practice for SLPs and audiologists was determined. CONCLUSION:  Our study examined healthcare professionals' awareness of audiology and SLP services and revealed a high level of awareness.Contribution: The existed level of awareness is expected to facilitate IPP and enhance the quality of care. Still, awareness campaigns about audiology and SLP services are needed to address the existing lack of knowledge among some healthcare professionals.

NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation.

Emerging evidence indicates that sleep deprivation (SD) can lead to Alzheimer's disease (AD)-related pathological changes and cognitive decline. However, the underlying mechanisms remain obscure. In the present study, we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD. Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis, elevated NLRP3 inflammasome expression, GSK-3ß activation, autophagy dysfunction, and tau hyperphosphorylation in the hippocampus. Colonization with the "SD microbiota" replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice. Remarkably, both the deletion of NLRP3 in NLRP3 -/- mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux, suppressed tau hyperphosphorylation, and ameliorated cognitive deficits induced by chronic SD, while GSK-3ß activity was not regulated by the NLRP3 inflammasome in chronic SD. Notably, deletion of NLRP3 reversed NLRP3 inflammasome activation, autophagy deficits, and tau hyperphosphorylation induced by GSK-3ß activation in primary hippocampal neurons, suggesting that GSK-3ß, as a regulator of NLRP3-mediated autophagy dysfunction, plays a significant role in promoting tau hyperphosphorylation. Thus, gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction, ultimately leading to cognitive deficits. Overall, these findings highlight GSK-3ß as a regulator of NLRP3-mediated autophagy dysfunction, playing a critical role in promoting tau hyperphosphorylation.

Non-coding RNAs involved in the molecular pathology of Alzheimer's disease: a systematic review.

Alzheimer's disease (AD) is the leading cause of dementia globally, having a pathophysiology that is complex and multifactorial. Recent findings highlight the significant role of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs) in the molecular mechanisms underlying AD. These ncRNAs are involved in critical biological processes such as cell proliferation, apoptosis, oxidative stress, amyloid-beta aggregation, tau phosphorylation, neuroinflammation, and autophagy, which are pivotal in AD development and progression. This systematic review aims to consolidate current scientific knowledge on the role of ncRNAs in AD, making it the first to encompass the four types of ncRNAs associated with the disease. Our comprehensive search and analysis reveal that ncRNAs not only play crucial roles in the pathogenesis of AD but also hold potential as biomarkers for its early detection and as novel therapeutic targets. Specifically, the findings underscore the significance of miRNAs in regulating genes involved in key AD pathways such as activin receptor signaling pathway, actomyosin contractile ring organization, and advanced glycation endproducts-receptor advanced glycation endproducts (AGE-RAGE) signaling pathway. This review also highlights the potential of ncRNAs in unveiling novel diagnostic and therapeutic strategies, emphasizing the need for further research to validate their clinical utility. Our systematic exploration provides a foundation for future bioinformatic analyses and the development of ncRNA-based precision medicine approaches for AD, offering new insights into the disease's molecular pathology and paving the way for innovative treatment strategies. Systematic review registration: PROSPERO, https://www.crd.york.ac.uk/prospero/, CRD42022355307.

Orofacial assessment as digital path for forensic and legal evidence record.

In forensic scenarios, such as armed conflicts or mass disasters, the oral cavity can be a valuable source of identification information relevant to legal issues. In many European Union countries, it is mandatory to register dental records for identification purposes. A pilot and quasi-experimental study was performed. The study aims to analyze two methodologies, photography and wireless intraoral (IO) laser scanner, in the scope of the orofacial record in forensic pathology, highlighting their impact on human identification. The IO scanner i700 (Medit, Lusobionic, Portugal) and Canon 5D-Full Frame equipment were used to record the individual status, living patients (n = 5), and forensic cases (n = 5). IO and extraoral anatomical structures were recorded following six parameters: time, mineralized and soft detail, communication, extra devices, and distortion. The statistical analysis was performed in accordance with a scoring system and Mann-Whitney (P < 0.05) analysis. The photography method recorded extraoral data for all samples (score range between 15 and 23). The time elapsed to complete an IO scan in forensic cases was shorter than with photography, without requiring additional sources of light or mirror devices. Living patients and corpses identified statistically significant differences. It can be concluded that laser scanners are a valuable tool in the field of forensic pathology and can be used to record and analyze anatomic-morphological data for identification purposes accurately. Key points: Human identification engages in orofacial details records.Photographic and laser scans record intraoral and extraoral anatomic structures.Forensic cases assessed by intraoral scanner technology are accurate and less time-consuming, optimizing the orofacial data for identification.

Urinary Bladder Nephrogenic Adenoma: A Histopathological Case Report.

Nephrogenic adenomas are benign lesions that develop within the urinary tract. Most often developing within the urinary bladder, these lesions have a debatable etiopathogenesis, with hamartoma, rest hyperplasia, and transplantation of renal tubular cells being the most widely accepted ones. Nephrogenic adenomas develop more often in adult males, and predisposing factors for their development are prior urinary system injury, infection, or malignancy, with a subset of cases developing in renal transplant patients. Herein, we present a case of a male patient in his seventies who initially presented to our institution with urinary disturbances and was subsequently diagnosed with low-grade, non-invasive urothelial carcinoma. After treatment, the patient remained disease-free for a period of seven calendar years. The current presentation was due to dysuria, and bladder endoscopy revealed a ureteral stricture and two small exophytic lesions neighboring the location of the previously treated urothelial carcinoma. Histology revealed complex papillary architecture and cystic spaces lined by a monolayer of monomorphous epithelial cells with foci of hobnail appearance. The papillary stroma consisted of edematous fibrous tissue with hyperemic blood vessels and focal infiltration by inflammatory cells. Based on the histological findings, the diagnosis of nephrogenic adenoma was established.

Diagnostic Potentials of Lung Ultrasound In Neonatal Care: An Updated Overview.

Recent technological strides, including high-frequency probes and lung ultrasound, have become a crucial non-invasive diagnostic tool in neonatal care, revolutionizing how respiratory conditions are assessed in the neonatal intensive care unit (NICU). High-frequency probes and portable devices significantly enhance the effectiveness of lung ultrasound in identifying respiratory distress syndrome (RDS), pneumonia, and pneumothorax, and underscore its growing significance. This comprehensive review explores the historical journey of lung ultrasonography, technological advancements, contemporary applications in neonatal care, emerging trends, and collaborative initiatives, and foresees a future where personalized healthcare optimizes outcomes for neonates.

Masked pre-training of transformers for histology image analysis.

In digital pathology, whole-slide images (WSIs) are widely used for applications such as cancer diagnosis and prognosis prediction. Vision transformer (ViT) models have recently emerged as a promising method for encoding large regions of WSIs while preserving spatial relationships among patches. However, due to the large number of model parameters and limited labeled data, applying transformer models to WSIs remains challenging. In this study, we propose a pretext task to train the transformer model in a self-supervised manner. Our model, MaskHIT, uses the transformer output to reconstruct masked patches, measured by contrastive loss. We pre-trained MaskHIT model using over 7000 WSIs from TCGA and extensively evaluated its performance in multiple experiments, covering survival prediction, cancer subtype classification, and grade prediction tasks. Our experiments demonstrate that the pre-training procedure enables context-aware understanding of WSIs, facilitates the learning of representative histological features based on patch positions and visual patterns, and is essential for the ViT model to achieve optimal results on WSI-level tasks. The pre-trained MaskHIT surpasses various multiple instance learning approaches by 3% and 2% on survival prediction and cancer subtype classification tasks, and also outperforms recent state-of-the-art transformer-based methods. Finally, a comparison between the attention maps generated by the MaskHIT model with pathologist's annotations indicates that the model can accurately identify clinically relevant histological structures on the whole slide for each task.

A Case Report of an Unusually Large Heterotopic Pancreas.

Heterotopic pancreas (HP) is the presence of pancreatic tissue outside of its normal anatomical position without vascular continuity from the main pancreas. HP is most commonly found within the gastrointestinal tract, particularly the stomach through the jejunum. This report shares the case of a 57-year-old man who presented with persistent vomiting despite medical therapy. Given the nonspecific and broad differential diagnosis, a histopathological examination was warranted for a definitive diagnosis that showed a uniquely large and well-differentiated type I HP in the lesser curvature of the stomach. Resection was completed which was followed with resolution of symptoms.

Letter to the Editor on "Radiologic serosal invasion sign as a new criterion of T4a gastric cancer on computed tomography: diagnostic performance and prognostic significance in patients with advanced gastric cancer".

We provide commentary on the paper by You et al., which proposed the 'serosal invasion sign' as a new criterion for T4a gastric cancer on CT. We clarify the anatomical relationship between the perigastric vessels and the serosa, correcting for an anatomical oversight in the original figures. We affirm the significance of this diagnostic sign in the T-staging of gastric cancer. Our insights aim to enhance the understanding and clinical application of this criterion in staging advanced gastric cancer.

The expression and clinical significance of CFAP65 in colon cancer.

BACKGROUND: CFAP65 (cilia and flagella associated protein 65) is a fundamental protein in the development and formation of ciliated flagella, but few studies have focused on its role in cancer. This study aimed to investigate the prognostic significance of CFAP65 in colon cancer. METHODS: The functionally enriched genes related to CFAP65 were analyzed through the Gene Ontology (GO) database. Subsequently, CFAP65 expression levels in colon cancer were evaluated by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) and immunoblotting in 20 pairs of frozen samples, including tumors and their matched paratumor tissue. Furthermore, protein expression of CFAP65 in 189 colon cancer patients were assessed via immunohistochemical staining. The correlations between CFAP65 expression and clinical features as well as long-term survival were statistically analyzed. RESULTS: CFAP65-related genes are significantly enriched on cellular processes of cell motility, ion channels, and GTPase-associated signaling. The expression of CFAP65 was significantly higher in colon cancer tissue compared to paratumor tissue. The proportion of high expression and low expression of CFAP65 in the clinical samples of colon cancer were 61.9% and 38.1%, respectively, and its expression level was not associated with the clinical parameters including gender, age, tumor location, histological differentiation, tumor stage, vascular invasion and mismatch repair deficiency. The five-year disease-free survival rate of the patients with CFAP65 low expression tumors was significantly lower than that those with high expression tumors (56.9% vs. 72.6%, P = 0.03), but the overall survival rate has no significant difference (69% vs. 78.6%, P = 0.171). The cox hazard regression analysis model showed that CFAP65 expression, tumor stage and tumor location were independent prognostic factors. CONCLUSIONS: In conclusion, we demonstrate CFAP65 is a potential predictive marker for tumor progression in colon cancer.