Prolonged Remission in Metastatic Ano-Rectal Malignant Melanoma With Single Agent Temozolomide.

Introduction: With the use of immune checkpoint inhibitors (ICIs) and targeted therapies, the clinical outcomes of metastatic melanoma have drastically improved. The current scenario has reduced the use of chemotherapy as a first-line treatment. We report an interesting case of a patient with stage IV ano-rectal canal malignant melanoma with an exceptional response to single-agent temozolomide.

Clinical utility of plasma p-tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease.

Introduction: Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance of a plasma immunoassay for tau phosphorylated at threonine 217 (p-tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based on a three-range reference, which stratified patients into low-, intermediate-, and high-risk groups for Aβ+.

Methods: Brain amyloid status (Aβ- [n = 142] vs Aβ+ [n = 73]) on amyloid PET scans was assessed along with the plasma ALZpath p-tau217 assay to derive three-range reference points for PET Aβ+ based on 90% sensitivity (lower threshold) and 90% specificity (upper threshold).

Results: Plasma p-tau217 (area under the curve [AUC] = 0.

Cognitive aging outcomes are related to both tau pathology and maintenance of cingulate cortex structure.

Introduction: Successful cognitive aging is related to both maintaining brain structure and avoiding Alzheimer's disease (AD) pathology, but how these factors interplay is unclear.

Methods: A total of 109 cognitively normal older adults (70+ years old) underwent amyloid beta (Aβ) and tau positron emission tomography (PET) imaging, structural magnetic resonance imaging (MRI), and cognitive testing. Cognitive aging was quantified using the cognitive age gap (CAG), subtracting chronological age from predicted cognitive age.

The role of CNBP in brain atrophy and its targeting in myotonic dystrophy type 2.

Myotonic Dystrophy type 2 (DM2) is a multisystem disease affecting many tissues, including skeletal muscle, heart, and brain. DM2 is caused by unstable expansion of CCTG repeats in an intron 1 of a gene coding for cellular nuclear binding protein (CNBP). The expanded CCTG repeats cause DM2 pathology due to the accumulation of RNA CCUG repeats, which affect RNA processing in patients' cells.

Inhibition of IFITM3 in cerebrovascular endothelium alleviates Alzheimer's-related phenotypes.

Introduction: Interferon-induced transmembrane protein 3 (IFITM3) modulates γ-secretase in Alzheimer's Disease (AD). Although IFITM3 knockout reduces amyloid β protein (Aβ) production, its cell-specific effect on AD remains unclear.

Methods: Single nucleus RNA sequencing (snRNA-seq) was used to assess IFITM3 expression.

HIF1α Plays a Crucial Role in the Development of TFE3-Rearranged Renal Cell Carcinoma by Orchestrating a Metabolic Shift Toward Fatty Acid Synthesis.

Tumor development often requires cellular adaptation to a unique, high metabolic state; however, the molecular mechanisms that drive such metabolic changes in TFE3-rearranged renal cell carcinoma (TFE3-RCC) remain poorly understood. TFE3-RCC, a rare subtype of RCC, is defined by the formation of chimeric proteins involving the transcription factor TFE3. In this study, we analyzed cell lines and genetically engineered mice, demonstrating that the expression of the chimeric protein PRCC-TFE3 induced a hypoxia-related signature by transcriptionally upregulating HIF1α and HIF2α.

Longitudinal Outcomes in Noonan Syndrome.

Purpose: Noonan syndrome and related disorders (NS) are multisystemic conditions affecting approximately 1:1000 individuals. Previous natural history studies were conducted prior to widespread comprehensive genetic testing. This study provides updated longitudinal natural history data in participants with molecularly confirmed NS.

Decoding brain structure to stage Alzheimer's disease pathology in Down syndrome.

Introduction: Alzheimer's disease (AD) in Down syndrome (DS) is associated with changes in brain structure. It is unknown if thickness and volumetric changes can identify AD stages and if they are similar to other genetic forms of AD.

Methods: Magnetic resonance imaging scans were collected for 178 DS adults (106 nonclinical, 45 preclinical, and 27 symptomatic).

Prospective validation study of a combined urine and plasma test for predicting high-grade prostate cancer in biopsy naïve men.

Objective: Early and accurate diagnosis of prostate cancer (PC) is crucial for effective treatment. Diagnosing  clinically insignificant cancers can lead to overdiagnosis and overtreatment, highlighting the importance of accurately selecting patients for further evaluation based on improved risk prediction tools. Novel biomarkers offer promise for enhancing this diagnostic process.

Immunohistochemical Expression of PAX8 in Central Nervous System Hemangioblastomas: A Potential Diagnostic Pitfall for Neuropathologists.

The histologic differential diagnosis between intracranial hemangioblastoma (HB) and metastatic clear cell renal cell carcinoma may be challenging, especially considering that both tumors exhibit clear cell morphology and can be associated with vHL mutation and/or Von Hippel-Lindau syndrome. As the execution of immunohistochemical analyses is often mandatory, the expression of PAX8 has been traditionally considered a reliable marker of metastatic clear cell renal cell carcinoma, being consistently negative in intracranial HB. However, as in recent years, some cases of PAX8-positive HBs have been reported in the literature; we studied the expression of this antibody on a series of 23 intracranial HB, showing that about 40% of these tumors may express PAX8 and that this immunoreactivity is often focal and weak.

Comparison of Recruitment Method on Clinical Outcomes Following Cervical Disc Arthroplasty.

Study Design: Retrospective cohort.

Objective: To compare the clinical outcomes of trial versus standard clinical practice (SCP) patients following cervical disc arthroplasty (CDA).

Background: CDA is hypothesized to reduce the shear strain and related complications resulting from fusion procedures.

Glucose Transporter 1 Deficiency Impairs Glucose Metabolism and Barrier Induction in Human Induced Pluripotent Stem Cell-Derived Astrocytes.

Glucose is a major source of energy for the brain. At the blood-brain barrier (BBB), glucose uptake is facilitated by glucose transporter 1 (GLUT1). GLUT1 Deficiency Syndrome (GLUT1DS), a haploinsufficiency affecting SLC2A1, reduces glucose brain uptake.

Increased SOX10, p16, and Cyclin D1 Immunoreactivity Differentiates MAP Kinase-activated Low-grade Gliomas From Piloid Gliosis.

Low-grade gliomas and reactive piloid gliosis can present with overlapping features on conventional histology. Given the large implications for patient treatment, there is a need for effective methods to discriminate these morphologically similar but clinically distinct entities. Using routinely available stains, we hypothesize that a limited panel including SOX10, p16, and cyclin D1 may be useful in differentiating mitogen-activated protein (MAP) kinase-activated low-grade gliomas from piloid gliosis.

Identification of IGFBP3 and LGALS1 as potential secreted biomarkers for clear cell renal cell carcinoma based on bioinformatics analysis and machine learning.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC). Due to the lack of symptoms until advanced stages, early diagnosis of ccRCC is challenging. Therefore, the identification of novel secreted biomarkers for the early detection of ccRCC is urgently needed.

Minimally Invasive vs Open Surgery for Thoracolumbar Fractures Treatment: A Meta-analysis of Randomized Controlled Trials and Prospective Studies.

Study Design: Meta-Analysis.

Objective: The purpose of this systematic review and meta-analysis was to pool the available data comparing MIS to open surgery for thoracolumbar fractures and provide a more comprehensive assessment on this topic.

Background: There remains a debate over whether minimally invasive surgery (MIS) or open fixation provides superior outcomes for patients with thoracolumbar fractures.

Deficient Mismatch Repair and BRAF Mutations in Metastatic Colorectal Cancer in the South Island of New Zealand.

Aim: Manatū Hauora, the Ministry of Health of New Zealand (NZ), published minimum standards for molecular testing of colorectal cancers (CRCs) in June 2018. These included mismatch repair (MMR) testing at diagnosis and BRAFV600E mutation analysis on newly diagnosed stage IV CRCs. This study aimed to determine the proportion of patients with CRC in the South Island of NZ with metastatic deficient mismatch repair (dMMR) CRC, the proportion of metastatic CRCs and dMMR CRCs that have a BRAFV600E mutation, and audit testing for BRAF mutations and appropriate referral to genetics services.

Determinants of Racial and Ethnic Differences in Maternal Cardiovascular Health in Early Pregnancy.

Background: Suboptimal cardiovascular health (CVH) in pregnancy is associated with adverse maternal and offspring outcomes. To guide public health efforts to reduce disparities in maternal CVH, we determined the contribution of individual- and neighborhood-level factors to racial and ethnic differences in early pregnancy CVH.

Methods: We included nulliparous individuals with singleton pregnancies who self-identified as Hispanic, non-Hispanic Black (NHB), or non-Hispanic White (NHW) and participated in the nuMoM2b cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be).

Intratumor Heterogeneity Predicts Prognosis in Lepidic Predominant Lung Adenocarcinoma.

Objective: Among the different subtypes of invasive lung adenocarcinoma, lepidic predominant adenocarcinoma (LPA) has been recognized as the lowest-risk subtype with good prognosis. The aim of this study is to provide insight into the heterogeneity within LPA tumors and to better understand the influence of other sub-histologies on survival outcome.

Methods: Overall, 75 consecutive patients with LPA in pathologic stage I (TNM 8th edition) who underwent resection between 2010 and 2022 were included into this retrospective, single center analysis.

A co-registration method to validate optical coherence tomography in the breast surgical cavity.

Breast-conserving surgery accompanied by adjuvant radiotherapy is the standard of care for patients with early-stage breast cancer. However, re-excision is reported in 20-30 % of cases, largely because of close or involved tumor margins in the specimen. Several intraoperative tumor margin assessment techniques have been proposed to overcome this issue, however, none have been widely adopted.

Molecular dynamics model of mechanophore sensors for biological force measurement.

Cellular forces regulate an untold spectrum of living processes, such as cell migration, gene expression, and ion conduction. However, a quantitative description of mechanical control remains elusive due to the lack of general, live-cell tools to measure discrete forces between biomolecules. Here we introduce a computational pipeline for force measurement that leverages well-defined, tunable release of a mechanically activated small molecule fluorophore.

Evaluation of the Value of Fine Needle Aspiration Cytology and Cell Morphology in Determining the Histogenesis of Pancreatic Lesions With Review of Literature, Overview and Cytological Experience of 25 Years: Original Research.

Background And Aims: Benign lesions, inflammation, cysts and pseudocysts, as well as neoplasms of the exocrine and endocrine parts of the pancreas can be easily identified using cytological methods. The sensitivity and specificity can be increased with the help of additional examination methods. The sensitivity of intraoperative rapid cytology reaches about 99%.

Immunogenicity of bivalent versus monovalent mRNA booster vaccination among adult paramedics in Canada who had received three prior mRNA wild-type doses.

Comparative immunogenicity from different mRNA booster vaccines (directed at WT, BA.1 or BA.4/5 antigens) remains unclear.

Elevated Troponin T (TnT) in Non-acute Coronary Syndrome (ACS) Due to Dermatomyositis.

Troponin is a highly specific biomarker for myocardial injury. It plays a critical role in the diagnosis of acute coronary syndrome (ACS). However, elevated troponin levels are not exclusively due to cardiac ischemia and may be observed in many non-cardiac conditions, including inflammatory myopathies.

Three-Dimensional Assessment of the Condylar Position in Different Malocclusions Using Cone-Beam Computed Tomography: A Cross-Sectional Study.

Introduction The role of the condylar position in the correct functioning of the stomatognathic system has been the center of the study. Using cone-beam computed tomography (CBCT), this study looked at the three-dimensional (3D) position of the condylar bone in patients from Class I, Class II, Division 1, and Division 2. Materials and methods This cross-sectional, retrospective study was conducted using 102 CBCT records, with 34 records allocated to each category of malocclusion classification, such as dentoskeletal Class I, skeletal Class II, and dental Class II, Division 1 and 2.

Striving for excellence in a little red dot: Exploring the evolution of oral and maxillofacial surgery training and practice in Singapore.

Oral and maxillofacial surgery (OMS) is a field that straddles knowledge and clinical experience from both medical and dental specialties. In the small island nation of Singapore, the rapidly and constantly changing needs of its diverse and aging population, as well as changes in the mindsets of both students and educators have led to many developments in the local OMS program. Tied to the only dental school in the country, the curriculum of the training program has kept up with the changes in the demographics and attitudes of the local patient pool, which comprises a multicultural population with both traditional and modern mindsets.