Small extravesicular microRNA in head and neck squamous cell carcinoma and its potential as a liquid biopsy for early detection

alexandrossfakianakis shared this article with you from Inoreader Small extravesicular microRNA in head and neck squamous cell carcinoma and its potential as a liquid biopsy for early detection via Head & Neck Abstract Background The objective was to assess secretion of small extracellular vesicular microRNA (exo-miRNA) in head and neck squamous cell carcinoma (HNSCC) according to human papillomavirus (HPV) status, and determine the translational potential as a liquid biopsy for early detection. Methods This study employed a combination of cell culture and case–control study design using archival pretreatment serum. Small extracellular vesicles (sEV) were isolated from conditioned culture media and human serum samples via differential ultracentrifugation. miRNA-sequencing was performed on each sEV isolate. Results There were clear exo-miRNA profiles that distinguished HNSCC cell lines from nonpathologic oral epithelial control cells. While there was some overlap among profiles across all samples, there were apparent differences in exo-miRNA profiles according to HPV-status. Importantly, differential exo-miRNA profiles were also apparent in serum from early-stage HNSCC cases relative to cancer-free controls. Conclusions Our findings indicate that exo-miRNA are highly dysregulated in HNSCC and support the potential of exo-miRNA as biomarkers for HNSCC. View on Web

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Expression of Glial Cell‐Derived Neurotrophic Factor Receptors Within Nucleus Ambiguus During Rat Development

alexandrossfakianakis shared this article with you from Inoreader Expression of Glial Cell‐Derived Neurotrophic Factor Receptors Within Nucleus Ambiguus During Rat Development via The Laryngoscope In this paper, we show differences of Glial Cell-Derived Neurotrophic Factor (GDNF)receptors in the nucleus ambiguus during development from E14 to E20 and in the rat adulthood. We observed that there is timing of production of the different members of GDNF receptors in the motoneurons innervating the larynx and we try to establish differences between nucleus ambiguus and the other motor nuclei of the medulla oblongata such as facial and hypoglossus nuclei. These findings support the idea that GDNF may play a role during motor innervation of the rat larynx. Objective The nucleus ambiguus (NAmb) is a column of neurons in the medulla oblongata, involved in bulbar functions. Expression of Glial Cell-Derived Neurotrophic Factor (GDNF) and its receptors (GDNFR) is observed within the cell bodies during reinnervation following recurrent laryngeal nerve (RLN) injury. Little is known regarding GDNFR expression in the formation of the NAmb and the laryngeal innervation during embryogenesis. Understanding the timing and pattern of GDNFR expression in embryogenesis versus after RLN injury may provide insights into therapeutic targets for regeneration after RLN injury. Study Design Laboratory experiment. Methods Rat brainstems at E14.5/E16.5/E18.5/E20.5/adult were stained for GDNFR: GFRα-1/GFRα-2/GFRα-3/Ret. Islet1 and choline acetyltransferase were used as cell body markers. Sections were observed using fluorescent microscopy and quantified through manual cell counting. Results Expression of GFRα-1, GFRα-3, and Ret was identified within the NAmb, hypoglossal, and facial nuclei of the adult medulla. During development, GFRα-1 immunoreactivity was seen at E20.5. GFRα-2 expression was not observed at any timepoint. GFRα-3 expression began at E16.5. Ret expression within nerve fibers in the NAmb were observed beginning at E14.5, but never in the cell bodies. Conclusion Embryonic GDNFR expression in the NAmb differs from that of the adult after RLN injury. The developing brainstem experienced upregulation at discrete timepoints with signaling sustained through adulthood. In contrast, adult RLN-transected rats experienced patterns of up and down regulation. GFRα-1 may contribute to muscle targeting and neuromuscular junction maturation, GFRα-3 may contribute to both, as well as axon guidance. It is likely that GDNF is functioning via a Ret-independent pathway. Level of Evidence NA Laryngoscope, 2022 View on Web

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Abnormal Laryngopharyngeal Sensation in Adductor Laryngeal Dystonia Compared to Healthy Controls

alexandrossfakianakis shared this article with you from Inoreader Abnormal Laryngopharyngeal Sensation in Adductor Laryngeal Dystonia Compared to Healthy Controls via The Laryngoscope Laryngopharyngeal sensation is increased in adductor laryngeal dystonia compared to controls. The identification of increased laryngeal hypersensitivity in these patients may improve understanding of AdLD pathophysiology and identify future targets for intervention. Background/Objectives Laryngeal sensory abnormality has been implicated as a component of adductor laryngeal dystonia (AdLD). The study objective was to assess laryngopharyngeal sensation in AdLD utilizing a calibrated, tactile aesthesiometer to deliver differential stimuli to lateral pyriform sinus (LPS), aryepiglottic fold (AEF), and false vocal fold (FVF). Methods Patients with known Botox-responsive AdLD underwent sensory testing using a previously-validated methodology involving calibrated tactile stimuli (6–0, 5–0, 4.5–0, 4–0 nylon monofilaments). Laryngeal adductor reflex (LAR) and participant-rated perceptual strength of stimulI were evaluated. Responses were compared to normative controls (n = 33). Two-samples, Mann–Whitney and Fisher exact tests compared mean strength ratings and LAR between AdLD and control groups. Mixed-effects logistic regression and linear models assessed association of filament size, stimulus site, age, sex, and LD status on LAR and perceptual strength rating respectively. Results Thirteen AdLD patients (nine women, mean age 60+/−15 years) completed testing. Average LAR response rates were higher amongst all filament sizes in AdLD versus controls at LPS (56.3% vs. 35.7%) and AEF (96.1% vs. 70.2%) with comparable rates at FVF (90.2% vs. 91.7%). AdLD had 3.3 times the odds of observed LAR compared to controls (p = 0.005), but differences in subjective detection of stimuli, perceptual strength ratings, and cough/gag rates were insignificant on multivariate modeling (p > 0.05). Conclusions This is the first study to objectively assess laryngopharyngeal sensation in AdLD. Findings demonstrated increased laryngopharyngeal sensation in AdLD compared to controls. The identification of increased laryngeal hypersensitivity in these patients may improve understanding of AdLD pathophysiology and identify future targets for intervention. Level of Evidence 2 Laryngoscope, 2022 View on Web

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A minimally invasive method for titanium mesh fixation with resorbable sutures in guided bone regeneration: A retrospective study

alexandrossfakianakis shared this article with you from Inoreader A minimally invasive method for titanium mesh fixation with resorbable sutures in guided bone regeneration: A retrospective study via Clinical Implant Dentistry and Related Research Abstract Objectives Titanium mesh has become a mainstream choice for guided bone regeneration (GBR) owing to its excellent space maintenance. However, the traditional fixation method using titanium screws impacts surgery efficiency and increases patient trauma. We report a novel method of fixing a titanium mesh using resorbable sutures. We assessed the feasibility of resorbable sutures for fixing a titanium mesh and whether it can serve as a stable, universal, and minimally invasive fixation method for a broader application of titanium meshes. Methods Patients undergoing GBR with a digital titanium mesh fixed using titanium screws (TS group) and resorbable sutures (RS group) were observed at different time points. The stability of the fixation methods was evaluated on parameters such as titanium mesh spatial displacement, bone augmentation, and bone resorption. Results A total of 36 patients were included in this study. The exposure rate of the titanium mesh in the TS group was 16.67%, while no exposure was noted in the RS group. There was no significant difference in the parameters of titanium mesh spatial displacement, bone augmentation, and bone resorption between the two groups (p > 0.05). Conclusion The use of resorbable sutures for fixing a titanium mesh can achieve similar results to traditional fixation using titanium screws. Although this new fixation method can improve the efficiency of the surgery and reduce the risk of complications, the long-term clinical effects require further follow-up investigation. View on Web

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human monkeypox (hMPXV) re‐emergence: host immunity status and current vaccines landscape

alexandrossfakianakis shared this article with you from Inoreader human monkeypox (hMPXV) re‐emergence: host immunity status and current vaccines landscape via Journal of Medical Virology Abstract Monkeypox virus is a member of the Orthopoxvirus genus and the Poxviridae family. Orthopoxviruses are among the most intricate animal viruses. The pathogenicity of human monkeypox infection has been emphasized in response to its recent emergence in non-endemic countries and the threat of bioterrorism. It is always necessary to take appropriate precautions in exposure to emerging or re-emerging infections. Here, we focus on the current state of the human monkeypox infection outbreak, research & development of immunity responses and clinical interventions to prevent and treat human monkeypox virus and other human poxviruses. This article is protected by copyright. All rights reserved. View on Web

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Do cone‐beam computed tomography low‐dose protocols affect the evaluation of the temporomandibular joint?

alexandrossfakianakis shared this article with you from Inoreader Do cone‐beam computed tomography low‐dose protocols affect the evaluation of the temporomandibular joint? via Journal of Oral Rehabilitation Abstract Background There is no established acquisition protocol based on scientific evidence for the acquisition of cone-beam computed tomography (CBCT) exams to evaluate the temporomandibular joint (TMJ). Objectives To evaluate the influence of acquisition protocols and jaw positioning on the diagnostic accuracy of TMJ condylar morphological alterations (CMA), dimension, position, and excursion. Methods Thirty-six TMJs on 18 dry skulls were imaged using a CBCT unit (OP300 Maxio, Instrumentarium, Tuusula, Finland) at two exposure settings (4.5 and 6.3 mA), three voxel resolutions (0.085, 0.125 and 0.280 mm), three jaw positions (concentric, anteriorized and posteriorized) and three jaw excursions (normoexcursion, hyperexcursion and hypoexcursion). The macroscopic anatomy examination and high-resolution CBCT images were used as ground truth for CMA. Twenty-five TMJs had at least one CMA with 11 healthy TMJs serving as controls. Three experienced oral and maxillofacial radiologists evaluated the parasagittal images for the presence of CMA, position, and excursion and measured dimensions. The area under the ROC curve, sensitivity, and specificity were calculated. Weighted Kappa (α=0.05) was used to determine intra- and inter-examiner reliability and comparisons between dependent variables analyzed by Analysis of Variance at an a prior level of significance of 0.05. Results The agreement of the evaluation of the position and excursion with the reference standard was high, independent of the protocol (range, 0.75-0.91). Various combinations of acquisition protocols and jaw position did not influence the CMA evaluation. Erosion was overdiagnosed in protocols with larger voxel sizes, and the detection of osteophytes greater in images with smaller voxel sizes. The anteroposterior dimension was greater in the open jaw position (p<0.05). Conclusion CBCT protocols using reduced radiation exposure from the CBCT machine evaluated in this study can be used to assess condylar morphology, dimension, position, and excursion, without compromising diagnostic performances for these parameters. View on Web

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Epigenetic upregulation of Schlafen11 renders WNT- and SHH- activated medulloblastomas sensitive to cisplatin

alexandrossfakianakis shared this article with you from Inoreader Epigenetic upregulation of Schlafen11 renders WNT- and SHH- activated medulloblastomas sensitive to cisplatin via Neuro-Oncology Advance Access Abstract Background Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma. Methods SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo. Results High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells. Conclusio ns High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin. View on Web

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The added value of skeletal surveys in the initial evaluation of children diagnosed with Langerhans cell histiocytosis in the era of staging 18F‐FDG PET/CT: A retrospective study

alexandrossfakianakis shared this article with you from Inoreader The added value of skeletal surveys in the initial evaluation of children diagnosed with Langerhans cell histiocytosis in the era of staging 18F‐FDG PET/CT: A retrospective study via Pediatric Blood & Cancer Abstract Objective Currently, there is no consensus protocol on the initial staging evaluation for Langerhans cell histiocytosis (LCH). Our institutional protocol consists of a skeletal survey and a whole-body positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography (FDG PET/CT) study. The utility of the PET/CT lies in its sensitivity in detecting osseous and extra-osseous lesions, and in determining the baseline metabolic activity of LCH lesions to assess treatment response. However, the added utility of the skeletal survey in staging LCH is unclear. Therefore, this study retrospectively assessed the added diagnostic value of skeletal surveys in patients with baseline PET/CTs for initial staging of LCH. Methods We retrospectively searched the medical records of all patients less than or equal to 18 years old at a large children's hospital (May 2013 to September 2021). The inclusion criteria were (a) biopsy-proven diagnosis of LCH and (b) initial staging PET/CT and skeletal survey performed less than or equal to 1 month apart. A blinded pediatric radiologist reviewed the skeletal surveys and another reviewed the PET/CTs in identifying LCH osseous lesions. Results Our study cohort consisted of 49 children with 86 LCH osseous lesions. In non-extremity locations, PET/CT identified 70/70 (100%) osseous lesions, while skeletal surveys detected 43/70 (61.4%) osseous lesions. In the extremities, PET/CT identified 13/16 (81.3%) osseous lesions, while skeletal surveys detected 15/16 (93.8%) osseous lesions. Conclusion Skeletal surveys increased the detection rate of osseous lesions in the extremities, but added no diagnostic value to the detection of osseous lesions in non-extremity locations. Therefore, we propose to abbreviate the skeletal survey to include only extremity radiographs. View on Web

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Histopathologically defined intestinal metaplasia in lesser curvature of corpus prior to Helicobacter pylori eradication is a risk factor for gastric cancer development

alexandrossfakianakis shared this article with you from Inoreader Histopathologically defined intestinal metaplasia in lesser curvature of corpus prior to Helicobacter pylori eradication is a risk factor for gastric cancer development via Helicobacter Abstract Background and Aim Helicobacter pylori eradication has been shown to reduce the risk of gastric cancer (GC), with the number of eradication therapy cases on the rise. However, GC can still occur after successful treatment, and the histological differences prior to eradication in patients with and without GC are unclear. This study investigated the pre-treatment histological risk factors for GC development following eradication therapy. Methods We retrospectively enrolled consecutive adult patients diagnosed as having H. pylori infection between April 2004 and December 2018. Atrophy and intestinal metaplasia (IM) were histologically assessed according to the updated Sydney System. The operative link on gastritis assessment and the operative link on gastric intestinal metaplasia (OLGIM) were evaluated as well. Results Of the 247 patients analyzed in this study, 11 (4.5%) experienced GC after eradication therapy. Histological IM scores in the GC group were significantly higher at all gastric biopsy sites (p < .05), and the proportion of OLGIM III/IV stage was significantly greater in GC patients (81.8% vs. 31.8%, p < .01). For GC prediction, the area under the receiver operating characteristic curve for IM score at the lesser curvature of the corpus was the highest among all biopsy sites and not inferior to OLGIM results. Conclusions Patients with histological IM prior to H. pylori eradication, especially at the lesser curvature of the corpus, may be at elevated risk for GC development after eradication therapy and require close surveillance. View on Web

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Benzene Exposure From Selected Work Tasks on Offshore Petroleum Installations

alexandrossfakianakis shared this article with you from Inoreader Benzene Exposure From Selected Work Tasks on Offshore Petroleum Installations on the Norwegian Continental Shelf, 2002–2018 via Annals of Work Exposures and Health Advance Access Abstract Objectives Work on offshore petroleum installations may cause exposure to benzene. Benzene is a carcinogenic agent, and exposure among workers should be as low as reasonably practicable. We aimed to assess short-term (less than 60 min) benzene exposure from the most frequent work tasks on offshore installations on the Norwegian continental shelf and identify determinants of exposure. In addition, we aimed to assess the time trend in task-based benzene measurements from 2002 to 2018. Methods The study included 763 task-based measurements with a sampling duration of less than 60 min, collected on 28 offshore installations from 2002 to 2018. The measurements were categorized into 10 different tasks. Multilevel mixed-effect Tobit regression models were developed for two tasks: sampling and disassembling/assembling equipment. Benzene source, season, indoors or outdoors, design of process area, year of production start, sampling meth od, and work operation were considered as potential determinants for benzene exposure in the models. Results The overall geometric mean (GM) benzene exposure was 0.02 ppm (95% confidence intervals 95%(CI: 0.01–0.04). The pipeline inspection gauge (PIG) operation task was associated with the highest exposure, with a GM of 0.33 ppm, followed by work on flotation cells, disassembling/assembling, and sampling, with GMs of 0.16, 0.04, and 0.01 ppm, respectively. Significant determinants for the disassembling/assembling task were work operation (changing or recertifying valves, changing or cleaning filters, and breaking pipes) and benzene source. For sampling, the benzene source was a significant determinant. Overall, the task-based benzene exposure declined annually by 10.2% (CI 95%: −17.4 to −2.4%) from 2002 to 2018. Conclusions The PIG operation task was associated with the highest exposure out of the ten tasks, followed by work on flotation cells and when perfo rming disassembling/assembling of equipment. The exposure was associated with the type of benzene source that was worked on. Despite the decline in task-based exposure in 2002–2018, technical measures should still be considered in order to reduce the exposure. View on Web

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