Incidence of histopathological variants of oral squamous cell carcinoma: An institutional study

Squamous cell carcinoma is the most important and the most common malignant mucosal neoplasm of the head and neck accounting for over 90% of all malignancies. Conventional oral Squamous cell carcinoma is frequently present in general cancerous conditions. It is bundled up with six different variants. Histomorphologically every variant shows a unique appearance. This raises an opportunity for the different diagnostic consideration with the precise management decision.All cases of OSCC reported at our institution Dentopath Pathologies Amravati in past two months were scrutinized. Representative sections containing the full thickness of the tumor were used for histopathological grading. The structure and identification of carcinomas were done microscopically by two expert dentopathologist.In the present study, we screened 100 slides of a conventional epithelial cell carcinoma. Amonst which 30 Slides showed the verrucous carcinoma. On 5 slides adenoid squamous cell carcinoma were observed. Incidence of Papillary squamous cell carcinoma and basaloid squamous cell carcinoma was only 1 out of 100 slides each. Whereas, the spindle cell/sarcomatoid carcinoma was observed on 2 slides. Adenosquamous carcinoma is the rarest variant and hence no incidence of this carcinoma were observed in our study. The behavior of the OSCC varies amongst due to the presence of different morphological type of tumor. A few studies on OSCC malignancy grading with different clinical parameters were made. In the present study different types of variants are seen according to their histopathological appearances.Histopathological knowledge is very important for the precise diagnosis. Squamous cell carcinoma is the most common neoplasm of oral cavity. However, variants of the same show very less frequency. Hence, it became challenge for the appropriate diagnosis as many times a misdiagnosis affects the course of treatment of the patient

Molecular Characterization and Clinical Relevance of ALDH2 in Human Cancers

Background: Aldehyde dehydrogenase 2 (ALDH2) is well-known to be a key enzyme in alcohol metabolism. However, a comprehensive understanding of ALDH2 across human cancers is lacking.Methods: A systematic and comprehensive analysis of the molecular alterations and clinical relevance for ALDH2 in more than 10,000 samples from 33 cancer types was performed. qRT-PCR was performed on 60 cancer and 60 paired nontumor tissues.Results: It was observed that ALDH2 was generally downregulated in most cancers, which was mainly driven by DNA hypermethylation rather than mutations or copy number variations. Besides, ALDH2 was closely related to the inhibition and activation of tumor pathways and a variety of potential targeted agents had been discovered in our research. Last but not least, ALDH2 had the best prediction efficacy in assessing immunotherapeutic response compared with PD-L1, PD-1, CTLA4, CD8, and tumor mutation burden (TMB) in cutaneous melanoma. According to the analysis of large-scale public data and 60 pairs of clinical cancer samples, we found the downregulation of ALDH2 expression tends to suggest the malignant phenotypes and adverse prognosis, which might enhance the precise diagnosis and timely intervention of cancer patients.Conclusion: This study advanced the understanding of ALDH2 across cancers, and provided important insight into chemotherapy, immunotherapy and prognosis of patients with cancer.

A Cognitive Diagnosis Method in Adaptive Learning System Based on Preconceptions

One advantage of an adaptive learning system is the ability to personalize learning to the needs of individual users. Realizing this personalization requires first a precise diagnosis of individual users’ relevant attributes and characteristics and the provision of adaptability-enabling resources and pathways for feedback. In this paper, a preconcept system is constructed to diagnose users' cognitive status of specific learning content, including learning progress, specific preconcept viewpoint, preconcept source, and learning disability. The “Force and Movement” topic from junior high school physics is used as a case study to describe the method for constructing a preconception system. Based on the preconception system, a method and application process for diagnosing user cognition is introduced. This diagnosis method is used in three ways: firstly, as a diagnostic dimension for an adaptive learning system, improving the ability of highly-adaptive learning systems to support learning activities, such as through visualization of the cognition states of students; secondly, for an attribution analysis of preconceptions to provide a basis for adaptive learning organizations; and finally, for predicting the obstacles users may face in the learning process, in order to provide a basis for adaptive learning pathways.

Fluorescence visualization of deep-buried hollow organs

High-definition fluorescence imaging of deep-buried organs is still challenging. Here, we develop bright fluorophores emitting to 1700 nm by enhancing electron donating ability and reducing donor-acceptor distance. In parallel, the heavy water functions as the solvent of the delicately designed fluorophores, effectively reducing the fluorescent signal loss caused by the absorption by water. The near-infrared-II (NIR-II, 900-1880 nm) emission is eventually recovered and extended beyond 1400 nm. Compared with the spectral range beyond 1500 nm, the one beyond 1400 nm gives a more accurate fluorescence visualization of the hollow organs, owing to the absorption-induced scattering suppression. In addition, the intraluminal lesions containing much water are simultaneously negatively stained, leading to a stark contrast for precise diagnosis. Eventually, the intraluminally perfused fluorescent probes are excreted from mice and thus no obvious side effects emerge. This general method can provide new avenues for future biomedical imaging of deep and highly scattering tissues.

A “Double-Locked” and Enzyme/pH-Activated Theranostic Agent for Accurate Tumor Imaging and Therapy

Theranostic agents for concurrent cancer therapy and diagnosis have begun attracting attention as a promising modality. However, accurate imaging and identification remains a great challenge for theranostic agents. Here, we designed and synthesized a novel theranostic agent H6M based on the “double-locked” strategy by introducing an electron-withdrawing nitro group into 1-position of a pH-responsive 3-amino-β-carboline and further covalently linking the hydroxamic acid group, a zinc-binding group (ZBG), to the 3-position of β-carboline to obtain histone deacetylase (HDAC) inhibitory effect for combined HDAC-targeted therapy. We found that H6M can be specifically reduced under overexpressed nitroreductase (NTR) to produce H6AQ, which emits bright fluorescence at low pH. Notably, H6M demonstrated a selective fluorescence imaging via successive reactions with NTR (first “key”) and pH (second “key”), and precisely identified tumor margins with a high S/N ratio to guide tumor resection. Finally, H6M exerted robust HDAC1/cancer cell inhibitory activities compared with a known HDAC inhibitor SAHA. Therefore, the NTR/pH-activated theranostic agent provided a novel tool for precise diagnosis and efficient tumor therapy.

Optimal encephalitis/meningitis roadmap via precise diagnosis and treatment (IMPROVE): a study protocol for a randomized controlled trial

Background Encephalitis/meningitis brings a heavy disease burden, and the origin of disease remains unknown in 30–40% of patients. It is greatly significant that combinations of nucleic acid amplification and autoimmune antibody testing improves the diagnosis and treatment of encephalitis/meningitis. Moreover, though several diagnostic methods are in clinical use, a recognized and unified diagnosis and treatment process for encephalitis management remains unclear. Methods IMPROVE is a multicenter, open label, randomized controlled clinical trial that aims to evaluate the diagnostic performance, applications, and impact on patient outcomes of a new diagnostic algorithm that combines metagenomic next-generation sequencing (mNGS), multiplex polymerase chain reaction (PCR) and autoimmune antibody testing. The enrolled patients will be grouped into two parallel groups, multiplex PCR test plus autoimmune antibody group (Group I) or the mNGS plus autoimmune antibody group (Group II) with a patient ratio of 1:1. Both groups will be followed up for 12 months. The primary outcomes include the initial time of targeted treatment and the modified Rankin scale score on the 30th day of the trial. The secondary outcomes are the cerebrospinal fluid index remission rate on the 14th day, mortality rate on the 30th day, and an evaluation of diagnostic efficacy. The two groups are predicted to comprise of 484 people in total. Discussion To optimize the roadmap of encephalitis/meningitis, precise diagnosis, and treatment are of great significance. The effect of rapid diagnosis undoubtedly depends on the progression of new diagnostic tests, such as the new multiplex PCR, mNGS, and examination of broad-spectrum autoimmune encephalitis antibodies. This randomized-controlled study could allow us to obtain an accurate atlas of the precise diagnostic ability of these tests and their effect on the treatment and prognosis of patients. Trial registration ClinicalTrial.gov, NCT04946682. Registered 29 June 2021, ‘Retrospectively registered’, https://clinicaltrials.gov/ct2/show/NCT04946682?term=NCT04946682&draw=2&rank=1

Histology of Cardiac Sarcoidosis with Novel Considerations Arranged upon a Pathologic Basis

Sarcoidosis is a rare disease of isolated or diffuse granulomatous inflammation. Although any organs can be affected by sarcoidosis, cardiac sarcoidosis is a fatal disorder, and it is crucial to accurately diagnose it to prevent sudden death due to dysrhythmia. Although endomyocardial biopsy is invasive and has limited sensitivity for identifying granulomas, it is the only modality that yields a definitive diagnosis of cardiac sarcoidosis. It is imperative to develop novel pathological approaches for the precise diagnosis of cardiac sarcoidosis. Here, we aimed to discuss commonly used diagnostic criteria for cardiac sarcoidosis and to summarize useful and novel histopathologic criteria of cardiac sarcoidosis. While classical histologic observations including noncaseating granulomas and multinucleated giant cells (typically Langhans type) are the most important findings, others such as microgranulomas, CD68+ CD163− pro-inflammatory (M1) macrophage accumulation, CD4/CD8 T-cell ratio, Cutibacterium acnes components, lymphangiogenesis, confluent fibrosis, and fatty infiltration may help to improve the sensitivity of endomyocardial biopsy for detecting cardiac sarcoidosis. These novel histologic findings are based on the pathology of cardiac sarcoidosis. We also discussed the principal histologic differential diagnoses of cardiac sarcoidosis, such as tuberculosis myocarditis, fungal myocarditis, giant cell myocarditis, and dilated cardiomyopathy.

Molecular Mechanisms and Risk Factors for the Pathogenesis of Hydrocephalus

Hydrocephalus is a neurological condition due to the aberrant circulation and/or obstruction of cerebrospinal fluid (CSF) flow with consequent enlargement of cerebral ventricular cavities. However, it is noticed that a lot of patients may still go through symptomatic progression despite standard shunting procedures, suggesting that hydrocephalus is far more complicated than a simple CSF circulative/obstructive disorder. Growing evidence indicates that genetic factors play a fundamental role in the pathogenesis of some hydrocephalus. Although the genetic research of hydrocephalus in humans is limited, many genetic loci of hydrocephalus have been defined in animal models. In general, the molecular abnormalities involved in the pathogenesis of hydrocephalus include brain development and ependymal cell dysfunction, apoptosis, inflammation, free radical generation, blood flow, and cerebral metabolism. Moreover, recent studies have indicated that the molecular abnormalities relevant to aberrant cerebral glymphatic drainage turn into an attractive subject in the CSF circulation disorder. Furthermore, the prevalent risk factors could facilitate the development of hydrocephalus. In this review, we elicited some possible fundamental molecular mechanisms and facilitating risk factors involved in the pathogenesis of hydrocephalus, and aimed to widen the diagnosis and therapeutic strategies for hydrocephalus management. Such knowledge could be used to improve patient care in different ways, such as early precise diagnosis and effective therapeutic regimens.

Long Non-Coding RNAs in Lung Cancer: The Role in Tumor Microenvironment

The development of various therapeutic interventions, particularly immune checkpoint inhibitor therapy, have effectively induced tumor remission for patients with advanced lung cancer. However, few cancer patients can obtain significant and long-lasting therapeutic effects for the limitation of immunological nonresponse and resistance. For this case, it’s urgent to identify new biomarkers and develop therapeutic targets for future immunotherapy. Over the past decades, tumor microenvironment (TME)-related long non-coding RNAs (lncRNAs) have gradually become well known to us. A large number of existing studies have indicated that TME-related lncRNAs are one of the major factors to realize precise diagnosis and treatment of lung cancer. Herein, this paper discusses the roles of lncRNAs in TME, and the potential application of lncRNAs as biomarkers or therapeutic targets for immunotherapy in lung cancer.