Neonatal acute liver failure with pulmonary yellow hyaline membrane and kernicterus

Background: Neonatal acute liver failure (NALF) is a rare and life-threatening condition. It causes bilirubin to accumulate to a dangerous level in the body, causing permanent damage to vital organs such as the brain and lungs. In many cases, the etiology of NALF remains unknown. Case presentation: We described a case of an 8-day-old baby girl who presented with poor oral intake, lethargy, and jaundice. Her clinical condition rapidly deteriorated with progression to multi-organ failure, and despite intensive resuscitation efforts, she expired. At autopsy, the most significant findings were liver necrosis, yellow hyaline membrane deposition in the lungs, and bilirubin deposition in the brain (kernicterus). Conclusions: NALF is a rare and potentially fatal condition necessitating prompt recognition and disease-specific treatment approaches. Toxic accumulation of bilirubin in the lungs can lead to hypoxia and precipitate further ischemic injury to the liver

Perception of Biostatistics by Lebanese Medical Students: A Cross-Sectional Study

Background: Inadequate use of statistics in biomedical research might not only affect science but also harm human beings if applied in medical practice. Biostatistics is fundamental to improve understanding and appraising of evidence-based medicine (EBM); yet, it is still not well understood and appreciated by medical students. Therefore, early exposure of medical students and physicians-in-training to research tools including Biostatistics is of utmostimportance.Objective: The aim of this study is to determine the perception of Biostatistics by medical students at a private medical school in Beirut, Lebanon, and to identify its best implementation time in the medical curriculum.Methods: This is a cross-sectional study based on a self-administered questionnaire distributed among medical students in their pre-clerkship years (first three years of a 6-year program) who undertook Biostatistics. The assessment of perception was based on the 5-point Likert scale anchored by Strongly disagree = 1 and Strongly agree = 5 including 36 questions distributed into four domains to assess the course value, difficulty, behavioral, and expectations.Results: 186 of 269 students responded to the questionnaire, yielding a response rate of 69.14%. Around 60% of students declared that the knowledge gained from biostatistics courses is useful to their future career, and almost 70% understood the main concepts of biostatistics. 57.7% of students perceived that lack of practicing exercises might contribute to making the course more difficult. The mean score of domains was higher in females but did not significantly differ within the three academic years. Only 35.1% of the students positively perceived the importance of biostatistics modules, mostly third-year students.Conclusion: Although the majority of medical students perceived biostatistics modules negatively, they were aware of the relevance of biostatistics to their medical career and real-life health issues

Cancer Stem Cells in Neuroblastoma: Expanding the Therapeutic Frontier

Neuroblastoma (NB) is the most common extracranial solid tumor often diagnosed in childhood. Despite intense efforts to develop a successful treatment, current available therapies are still challenged by high rates of resistance, recurrence and progression, most notably in advanced cases and highly malignant tumors. Emerging evidence proposes that this might be due to a subpopulation of cancer stem cells (CSCs) or tumor-initiating cells (TICs) found in the bulk of the tumor. Therefore, the development of more targeted therapy is highly dependent on the identification of the molecular signatures and genetic aberrations characteristic to this subpopulation of cells. This review aims at providing an overview of the key molecular players involved in NB CSCs and focuses on the experimental evidence from NB cell lines, patient-derived xenografts and primary tumors. It also provides some novel approaches of targeting multiple drivers governing the stemness of CSCs to achieve better anti-tumor effects than the currently used therapeutic agents

Genome-Wide and Phenotypic Evaluation of Stem Cell Progenitors Derived From Gprc5a-Deficient Murine Lung Adenocarcinoma With Somatic Kras Mutations

Lung adenocarcinomas (LUADs) with somatic mutations in the KRAS oncogene comprise the most common molecular subtype of lung cancer in smokers and present with overall dismal prognosis and resistance to most therapies. Our group recently demonstrated that tobacco carcinogen-exposed mice with knockout of the airway lineage G-protein coupled receptor, Gprc5a, develop LUADs with somatic mutations in Kras. Earlier work has suggested that cancer stem cells (CSCs) play crucial roles in clonal evolution of tumors and in therapy resistance. To date, our understanding of CSCs in LUADs with somatic Kras mutations remains lagging. Here we derived CSCs (as spheres in 3D cultures) with self-renewal properties from a murine Kras-mutant LUAD cell line we previously established from a tobacco carcinogen-exposed Gprc5a−/− mouse. Using syngeneic Gprc5a−/− models, we found that these CSCs, compared to their parental isoforms, exhibited increased tumorigenic potential in vivo, particularly in female animals. Using whole-transcriptome sequencing coupled with pathways analysis and confirmatory PCR, we identified gene features (n = 2,600) differentially expressed in the CSCs compared to parental cells and that were enriched with functional modules associated with an augmented malignant phenotype including stemness, tumor-promoting inflammation and anti-oxidant responses. Further, based on in silico predicted activation of GSK3β in CSCs, we found that tideglusib, an irreversible inhibitor of the kinase, exhibited marked anti-growth effects in the cultured CSCs. Our study underscores molecular cues in the pathogenesis of Kras-mutant LUAD and presents new models to study the evolution, and thus high-potential targets, of this aggressive malignancy

Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats

Traumatic brain injury (TBI) represents a critical health problem of which diagnosis, management, and treatment remain challenging. TBI is a contributing factor in approximately one-third of all injury-related deaths in the United States. The Centers for Disease Control and Prevention estimate that 1.7 million people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics-systems biology is proving to be a prominent tool in biomarker discovery for central nervous system injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI) model of experimental TBI in rat model to assess the temporal-global proteome changes after acute (1 day) and for the first time, subacute (7 days), post-injury time frame using the established cation-anion exchange chromatography-1D SDS gel electrophoresis LC-MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entity, we use

EMT Markers in Locally-Advanced Prostate Cancer: Predicting Recurrence?

Background: Prostate cancer (PCa) is the second most frequent cause of cancer-related death in men worldwide. It is a heterogeneous disease at molecular and clinical levels which makes its prognosis and treatment outcome hard to predict. The epithelial-to-mesenchymal transition (EMT) marks a key step in the invasion and malignant progression of PCa. We sought to assess the co-expression of epithelial cytokeratin 8 (CK8) and mesenchymal vimentin (Vim) in locally-advanced PCa as indicators of EMT and consequently predictors of the progression status of the disease.Methods: Co-expression of CK8 and Vim was evaluated by immunofluorescence (IF) on paraffin-embedded tissue sections of 122 patients with PCa who underwent radical prostatectomies between 1998 and 2016 at the American University of Beirut Medical Center (AUBMC). EMT score was calculated accordingly and then correlated with the patients' clinicopathological parameters and PSA failure.Results: The co-expression of CK8/Vim (EMT score), was associated with increasing Gleason group. A highly significant linear association was detected wherein higher Gleason group was associated with higher mean EMT score. In addition, the median estimated biochemical recurrence-free survival for patients with < 25% EMT score was almost double that of patients with more than 25%. The validity of this score for prediction of prognosis was further demonstrated using cox regression model. Our data also confirmed that the EMT score can predict PSA failure irrespective of Gleason group, pathological stage, or surgical margins.Conclusion: This study suggests that assessment of molecular markers of EMT, particularly CK8 and Vim, in radical prostatectomy specimens, in addition to conventional clinicopathological prognostic parameters, can aid in the development of a novel system for predicting the prognosis of locally-advanced PCa

Modeling Adipogenesis: Current and Future Perspective

Adipose tissue is contemplated as a dynamic organ that plays key roles in the human body. Adipogenesis is the process by which adipocytes develop from adipose-derived stem cells to form the adipose tissue. Adipose-derived stem cells’ differentiation serves well beyond the simple goal of producing new adipocytes. Indeed, with the current immense biotechnological advances, the most critical role of adipose-derived stem cells remains their tremendous potential in the field of regenerative medicine. This review focuses on examining the physiological importance of adipogenesis, the current approaches that are employed to model this tightly controlled phenomenon, and the crucial role of adipogenesis in elucidating the pathophysiology and potential treatment modalities of human diseases. The future of adipogenesis is centered around its crucial role in regenerative and personalized medicine

PRAME Expression in Adnexal Lesions and Common Skin Cancer-Types: Biomarker with Potential Diagnostic Utility

Introduction and Objective. PRAME (PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen first identified in tumor-reactive T-cell clones derived from a patient with metastatic melanoma. IHC for PRAME is useful for diagnostic purposes to support a suspected diagnosis of melanoma. Anecdotally, PRAME has been observed to stain sebaceous units in glands in background skin. We examined the expression of PRAME in adnexal lesions and common skin cancers to determine whether it is of potential diagnostic utility in distinguishing between sebaceous and non-sebaceous neoplasms. Methods. IRB approval from Mount Sinai Medical Center (MSMC) was obtained. In total, 81 patients were included: sebaceous lesions (17 cases with normal sebaceous glands, hyperplasia, heterotopia, adenoma, steatocystoma, epithelioma, carcinoma); sweat gland lesions (32 cases with hyperplasia, syringoma, hidradenoma, hidrocystoma, poroma, spiradenoma, papillary hidradenoma, and carcinoma); follicular lesions (13 cases with trichodenoma, pilomatricoma, trichilemmal cyst); basal cell carcinoma (BCC; 10 cases); squamous cell carcinoma (SCC; 9 cases). Cases from MSMC between January 01, 2012, and December 31, 2023, were included. Staining intensity was subcategorized into negative, weak, moderate, and strong, whereas expression percentage positivity into 0%, 1-25%, 26-50%, 51-75%, 76-100%. Results. We found that most sebaceous (vs. non-sebaceous) lesions exhibited positive PRAME expression (CYTOPLASMIC staining) of moderate to strong intensity in \u3e75% of cells. PRAME has a sensitivity and specificity of 100.0% and 86.7%, respectively, for sebaceous vs. non-sebaceous adnexal lesions. Also, BCCs and SCCs show weak to moderate NUCLEAR staining for PRAME (mostly in \u3e75% of cells). Of the 13 lesions of hair follicle origin, none expressed PRAME. Of the 32 lesions of sweat gland origin, 26 (81.25%) did NOT express PRAME while 6 (18.75%) expressed PRAME. Our observations demonstrated that the greater the maturation of sebaceous units (higher proportion of mature sebocytes), the stronger the PRAME staining is. Therefore, primitive sebocytes tend to lose PRAME, and PRAME stain diminishes towards the center of the sebaceous unit (strong at the periphery). Conclusions-Implications. We confirm the potential utility of PRAME for distinguishing (1) sebaceous from non-sebaceous adnexal neoplasms and (2) BCC and SCC (that may show nuclear staining) from sebaceous carcinoma (that shows cytoplasmic staining)

PRAME Expression in Adnexal Lesions and Common Skin Cancer-Types: Biomarker with Potential Diagnostic Utility

Introduction and Objective. PRAME (PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen first identified in tumor-reactive T-cell clones derived from a patient with metastatic melanoma. IHC for PRAME is useful for diagnostic purposes to support a suspected diagnosis of melanoma. Anecdotally, PRAME has been observed to stain sebaceous units in glands in background skin. We examined the expression of PRAME in adnexal lesions and common skin cancers to determine whether it is of potential diagnostic utility in distinguishing between sebaceous and non-sebaceous neoplasms. Methods. IRB approval from Mount Sinai Medical Center (MSMC) was obtained. In total, 81 patients were included: sebaceous lesions (17 cases with normal sebaceous glands, hyperplasia, heterotopia, adenoma, steatocystoma, epithelioma, carcinoma); sweat gland lesions (32 cases with hyperplasia, syringoma, hidradenoma, hidrocystoma, poroma, spiradenoma, papillary hidradenoma, and carcinoma); follicular lesions (13 cases with trichodenoma, pilomatricoma, trichilemmal cyst); basal cell carcinoma (BCC; 10 cases); squamous cell carcinoma (SCC; 9 cases). Cases from MSMC between January 01, 2012, and December 31, 2023, were included. Staining intensity was subcategorized into negative, weak, moderate, and strong, whereas expression percentage positivity into 0%, 1-25%, 26-50%, 51-75%, 76-100%. Results. We found that most sebaceous (vs. non-sebaceous) lesions exhibited positive PRAME expression (CYTOPLASMIC staining) of moderate to strong intensity in \u3e75% of cells. PRAME has a sensitivity and specificity of 100.0% and 86.7%, respectively, for sebaceous vs. non-sebaceous adnexal lesions. Also, BCCs and SCCs show weak to moderate NUCLEAR staining for PRAME (mostly in \u3e75% of cells). Of the 13 lesions of hair follicle origin, none expressed PRAME. Of the 32 lesions of sweat gland origin, 26 (81.25%) did NOT express PRAME while 6 (18.75%) expressed PRAME. Our observations demonstrated that the greater the maturation of sebaceous units (higher proportion of mature sebocytes), the stronger the PRAME staining is. Therefore, primitive sebocytes tend to lose PRAME, and PRAME stain diminishes towards the center of the sebaceous unit (strong at the periphery). Conclusions-Implications. We confirm the potential utility of PRAME for distinguishing (1) sebaceous from non-sebaceous adnexal neoplasms and (2) BCC and SCC (that may show nuclear staining) from sebaceous carcinoma (that shows cytoplasmic staining)