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.

Oral Prevotella Species and Their Connection to Events of Clinical Relevance in Gastrointestinal and Respiratory Tracts

Prevotella is recognized as one of the core anaerobic genera in the oral microbiome. In addition, members of this genus belong to microbial communities of the gastrointestinal and respiratory tracts. Several novel Prevotella species, most of them of oral origin, have been described, but limited knowledge is still available of their clinical relevance. Prevotella melaninogenica is among the anaerobic commensals on oral mucosae from early months of life onward, and other early colonizing Prevotella species in the oral cavity include Prevotella nigrescens and Prevotella pallens. Oral Prevotella species get constant access to the gastrointestinal tract via saliva swallowing and to lower airways via microaspiration. At these extra-oral sites, they play a role as commensals but also as potentially harmful agents on mucosal surfaces. The aim of this narrative review is to give an updated overview on the involvement of oral Prevotella species in gastrointestinal and respiratory health and disease.

Accuracy and Clinical Relevance of Intra-Tumoral Fusobacterium nucleatum Detection in Formalin-Fixed Paraffin-Embedded (FFPE) Tissue by Droplet Digital PCR (ddPCR) in Colorectal Cancer

The use of droplet digital PCR (ddPCR) to identify and quantify low-abundance targets is a significant advantage for accurately detecting potentially oncogenic bacteria. Fusobacterium nucleatum (Fn) is implicated in colorectal cancer (CRC) tumorigenesis and is becoming an important prognostic biomarker. We evaluated the detection accuracy and clinical relevance of Fn DNA by ddPCR in a molecularly characterized, formalin-fixed, paraffin-embedded (FFPE) CRC cohort previously analyzed by qPCR for Fn levels. Following a ddPCR assay optimization and an analytical evaluation, Fn DNA were measured in 139 CRC FFPE cases. The measures of accuracy for Fn status compared to the prior results generated by qPCR and the association with clinicopathological and molecular patients’ features were also evaluated. The ddPCR-based Fn assay was sensitive and specific to positive controls. Fn DNA were detected in 20.1% of cases and further classified as Fn-high and Fn-low/negative, according to the median amount of Fn DNA that were detected in all cases and associated with the patient’s worst prognosis. There was a low agreement between the Fn status determined by ddPCR and qPCR (Cohen’s Kappa = 0.210). Our findings show that ddPCR can detect and quantify Fn in FFPE tumor tissues and highlights its clinical relevance in Fn detection in a routine CRC setting.

Diagnostic accuracy of seven radiographic views, alone and in combination, for diagnosis of pectoral girdle fractures in wild passerines after window collisions

OBJECTIVE To determine the prevalence of pectoral girdle fractures in wild passerines found dead following presumed window collision and evaluate the diagnostic accuracy of various radiographic views for diagnosis of pectoral girdle fractures. SAMPLE Cadavers of 103 wild passerines that presumptively died as a result of window collisions. PROCEDURES Seven radiographic projections (ventrodorsal, dorsoventral, lateral, and 4 oblique views) were obtained for each cadaver. A necropsy was then performed, and each bone of the pectoral girdle (coracoid, clavicle, and scapula) was evaluated for fractures. Radiographs were evaluated in a randomized order by a blinded observer, and results were compared with results of necropsy. RESULTS Fifty-six of the 103 (54%) cadavers had ≥ 1 pectoral girdle fracture. Overall accuracy of using individual radiographic projections to diagnose pectoral girdle fractures ranged from 63.1% to 72.8%, sensitivity ranged from 21.3% to 51.1%, and specificity ranged from 85.7% to 100.0%. The sensitivity of using various combinations of radiographic projections to diagnose pectoral girdle fractures ranged from 51.1% to 66.0%; specificity ranged from 76.8% to 96.4%. CLINICAL RELEVANCE Radiography alone appeared to have limited accuracy for diagnosing fractures of the bones of the pectoral girdle in wild passerines after collision with a window. Both individual radiographic projections and combinations of projections resulted in numerous false negative but few false positive results.

Botulinum Toxins for Aesthetic Facial Injections – A scientific review to support evidence-based best practice.

Botulinum Toxins (BoNT) are complex biological products. Each licensed BoNTA has its own individual characteristics resulting into different attributes, some of them being of clinical relevance. Besides profound anatomical knowledge and understanding of aesthetic principles, the responsible injecting physician should be aware of those pharmaceutical and clinical properties. Especially against the background of new BoNTA formulations receiving approval by the authorities a critical and dedicated discussion on the individual characteristics should take place and the potential relevance on the treatment outcome should be taken into consideration.

Deep Learning-Based Four-Region Lung Segmentation in Chest Radiography for COVID-19 Diagnosis

Imaging plays an important role in assessing the severity of COVID-19 pneumonia. Recent COVID-19 research indicates that the disease progress propagates from the bottom of the lungs to the top. However, chest radiography (CXR) cannot directly provide a quantitative metric of radiographic opacities, and existing AI-assisted CXR analysis methods do not quantify the regional severity. In this paper, to assist the regional analysis, we developed a fully automated framework using deep learning-based four-region segmentation and detection models to assist the quantification of COVID-19 pneumonia. Specifically, a segmentation model is first applied to separate left and right lungs, and then a detection network of the carina and left hilum is used to separate upper and lower lungs. To improve the segmentation performance, an ensemble strategy with five models is exploited. We evaluated the clinical relevance of the proposed method compared with the radiographic assessment of the quality of lung edema (RALE) annotated by physicians. Mean intensities of segmented four regions indicate a positive correlation to the regional extent and density scores of pulmonary opacities based on the RALE. Therefore, the proposed method can accurately assist the quantification of regional pulmonary opacities of COVID-19 pneumonia patients.

Dexmedetomidine prolongs the duration of action of mepivacaine on anesthesia of the palmar digital nerves of horses

OBJECTIVE To determine whether palmar digital nerve (PDN) blockade in horses with a combination of dexmedetomidine and mepivacaine would block the response to mechanical force applied to the digit longer than would anesthetizing these nerves with mepivacaine alone or dexmedetomidine alone. ANIMALS 8 mares with no signs of lameness. PROCEDURES In a randomized, crossover, blinded, experimental study, both PDNs of the same forelimb of each horse were anesthetized by perineural injection with either 30 mg mepivacaine alone, 250 µg of dexmedetomidine alone, or 30 mg mepivacaine combined with 250 µg of dexmedetomidine. Each horse received each treatment, and treatments were administered ≥ 2 weeks apart. The mechanical nociceptive threshold was measured at a region between the heel bulbs with the use of a digital force gauge before (baseline) and at 15-minute intervals after treatment. RESULTS The mean duration of sensory blockade of the digit was 2-fold longer when a combination of mepivacaine and dexmedetomidine was administered (371 minutes), compared with when mepivacaine alone was administered (186 minutes). Treatment with dexmedetomidine alone did not change the mechanical nociceptive threshold substantially from baseline and resulted in no clinical signs of sedation. CLINICAL RELEVANCE Results indicated that relief from digital pain provided by perineural treatment with mepivacaine for PDN blockade can be extended by adding dexmedetomidine to the injectate.

Clinical, surgical, and pathological findings in client-owned rabbits with histologically confirmed appendicitis: 19 cases (2015–2019)

OBJECTIVE To report clinical, surgical, and pathological findings in client-owned rabbits with histologically confirmed appendicitis. ANIMALS 19 rabbits. PROCEDURES Medical records for client-owned rabbits that had a histologic diagnosis of appendicitis were reviewed. RESULTS Median age of the rabbits at presentation was 24.0 months (range, 4 to 84 months). Seventeen cases occurred during the summer and fall seasons. Decreased appetite (17/19 rabbits), abnormal rectal temperature (hyperthermia, 9/16 rabbits; hypothermia, 4/16 rabbits), hypocalcemia (8/11 rabbits), and hypoglycemia (7/15 rabbits) were common signs. Abdominal ultrasonography and CT findings were suggestive of appendicitis in 6 of 8 rabbits and in 1 of 2 rabbits, respectively. Of the 6 rabbits that received medical treatment, 3 died at 48 hours, 1 died at 24 hours after hospitalization, and 1 died at 10 days after presentation; 1 rabbit was alive at 1,030 days after presentation. Of the 8 rabbits that underwent appendectomy, 3 died before discharge from the hospital and 1 died 113 days after surgery; 4 rabbits were alive at 315, 334, 1,433, and 1,473 days after presentation. The remaining 5 rabbits either died or were euthanized before treatment could be instituted. In each of the 19 rabbits, the appendix had evidence of severe inflammation with mucosal ulceration, heterophilic inflammation, and necrotic debris. CLINICAL RELEVANCE For rabbits with decreased appetite and an apparently painful abdomen, hyperthermia, hypocalcemia, or hypoglycemia, appendicitis should be considered as a differential diagnosis. Further comparisons of medical and surgical treatments are required to establish treatment recommendations for rabbits with appendicitis.