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Frontiers in Bioscience (Landmark... Jun 2024The incidence rate of oropharyngeal squamous cell carcinoma (OPSCC) worldwide is alarming. In the clinical community, there is a pressing necessity to comprehend the...
BACKGROUND
The incidence rate of oropharyngeal squamous cell carcinoma (OPSCC) worldwide is alarming. In the clinical community, there is a pressing necessity to comprehend the etiology of the OPSCC to facilitate the administration of effective treatments.
METHODS
This study confers an integrative genomics approach for identifying key oncogenic drivers involved in the OPSCC pathogenesis. The dataset contains RNA-Sequencing (RNA-Seq) samples of 46 Human papillomavirus-positive head and neck squamous cell carcinoma and 25 normal Uvulopalatopharyngoplasty cases. The differential marker selection is performed between the groups with a log2FoldChange (FC) score of 2, adjusted -value < 0.01, and screened 714 genes. The Particle Swarm Optimization (PSO) algorithm selects the candidate gene subset, reducing the size to 73. The state-of-the-art machine learning algorithms are trained with the differentially expressed genes and candidate subsets of PSO.
RESULTS
The analysis of predictive models using Shapley Additive exPlanations revealed that seven genes significantly contribute to the model's performance. These include , , and , which predominantly influence differentiating between sample groups. They were followed in importance by , , , and . The Random Forest and Bayes Net algorithms also achieved perfect validation scores when using PSO features. Furthermore, gene set enrichment analysis, protein-protein interactions, and disease ontology mining revealed a significant association between these genes and the target condition. As indicated by Shapley Additive exPlanations (SHAPs), the survival analysis of three key genes unveiled strong over-expression in the samples from "The Cancer Genome Atlas".
CONCLUSIONS
Our findings elucidate critical oncogenic drivers in OPSCC, offering vital insights for developing targeted therapies and enhancing understanding its pathogenesis.
Topics: Humans; Oropharyngeal Neoplasms; Biomarkers, Tumor; Papillomavirus Infections; Artificial Intelligence; Gene Expression Regulation, Neoplastic; Squamous Cell Carcinoma of Head and Neck; Algorithms; Sequence Analysis, RNA; Machine Learning; Papillomaviridae; Carcinoma, Squamous Cell
PubMed: 38940026
DOI: 10.31083/j.fbl2906220 -
Oral Diseases Jun 2024The COVID-19 pandemic had direct and indirect effects on oral and pharyngeal cancer (OPC) mortality due to high COVID-19 mortality risk among cancer patients, and to the...
OBJECTIVE
The COVID-19 pandemic had direct and indirect effects on oral and pharyngeal cancer (OPC) mortality due to high COVID-19 mortality risk among cancer patients, and to the COVID-19 response that caused treatment delays and reduced routine visits. This study investigated the excess OPC mortality in Europe during the early pandemic years.
METHODS
Mortality and population data were gathered from the Eurostat database. The 2011-2019 mortality rates were used to estimate the 2020-2021 expected rates through joinpoint trend analysis. The excess mortality rates (observed minus expected mortality) with 95% confidence intervals (95 CIs) were assessed.
RESULTS
Statistically significant negative excess age-standardized and crude (age strata <65 and ≥65 years) OPC mortality rates in males and females, in the European Union (EU, 27 countries) and Europe were reported. The estimated OPC missing deaths in EU were 831 (95 CI, 630-985) and 1240 (95 CI, 1039-1394) in 2020 and 2021, respectively, with differences between sexes, age strata, and countries. The OPC deaths in the EU and Europe were 3.6% and 3.5% lower than expected.
CONCLUSION
Missing OPC deaths reported in Europe in 2020-2021 could be explained by changes in death certification of OPC patients who developed COVID-19, rather than a real OPC mortality decline.
PubMed: 38938075
DOI: 10.1111/odi.15055 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Physicians are currently finding products for pediatric respiratory diseases of viral etiology to reduce the inappropriate use of antibiotic therapy. This study...
The Effectiveness of a Dietary Supplement with Honey, Propolis, Extract, and Zinc in Children Affected by Acute Tonsillopharyngitis: An Open, Randomized, and Controlled Trial.
Physicians are currently finding products for pediatric respiratory diseases of viral etiology to reduce the inappropriate use of antibiotic therapy. This study evaluated PediaFlù (Pediatrica S.r.l.), a dietary supplement already on the market composed of honey, propolis, extract, and zinc (DSHPP), in children affected by acute tonsillopharyngitis (ATR). The open-label, randomized, and controlled study compared DSHPP + standard of care (SoC) versus SoC alone for six days. Children between 3 and 10 years with an ATR ≤ 48 h, a negative rapid test for beta-hemolytic , or a culture identification of nasal and/or pharyngeal exudates were included. A tonsillitis severity score (TSS) and the number of treatment failures (using ibuprofen or high-dose paracetamol as rescue medication) were the primary endpoints. DSHPP+ SoC showed better performance than SoC alone for TSS sub-scores: throat pain and erythema on day 6 ( < 0.001 and < 0.05), swallowing ( < 0.01 on day 4), and TSS total score on days 4 and 6 ( < 0.05 and < 0.001). Only one patient (SoC group) had treatment failure for ibuprofen administration. No adverse events were reported. DSHPP is an optimal adjuvant in the treatment of URTI and could potentially be useful in the daily clinical practice of paediatricians evaluating the correct antibiotic prescription.
PubMed: 38931472
DOI: 10.3390/ph17060804 -
Medicina (Kaunas, Lithuania) May 2024Amyotrophic lateral sclerosis (ALS) is an incurable rare neurodegenerative condition, with 45% of cases showing the symptom of dysphagia; its clinical signs are atrophy,...
Amyotrophic lateral sclerosis (ALS) is an incurable rare neurodegenerative condition, with 45% of cases showing the symptom of dysphagia; its clinical signs are atrophy, weakness, and fasciculations of the facial muscles, tongue, and pharynx. Furthermore, dysphagia is the main cause of aspiration pneumonia. The traditional treatment for dysphagia varies based on the patient's difficulty of swallowing. The initial phase consists of dietary consistency adjustments, progressing to alternatives like nasogastric tubes or percutaneous endoscopic gastrostomy (PEG) in advanced stages. Osteopathic manipulative treatment (OMT) is a complementary 'hands-on' approach that has already shown positive results as an add-on therapy in various health conditions. This study is a case report of a man diagnosed with ALS with initial dysphagia, managed with a protocol that extraordinarily included OMT. The patient showed somatic dysfunctions in the mediastinal region, upper cervical region, and occipital area which are all anatomically related to the nervous system, especially the glossopharyngeal reflex. At the end of the rehabilitation protocol, there was a reduction in the swallowing problems measured with Strand Scale and swallowing tests, and the patient reported an improved psycho-physical well-being assessed with the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40). Instead, the neurological function measured with ALSFRS-S remained stable. Although the nature of this study design prevents any causal assumption, the positive results should lead to future randomized controlled trials to assess the effectiveness of OMT as an adjunctive therapeutic proposal to improve the health of ALS patients.
Topics: Humans; Amyotrophic Lateral Sclerosis; Male; Deglutition Disorders; Middle Aged; Manipulation, Osteopathic; Treatment Outcome
PubMed: 38929462
DOI: 10.3390/medicina60060845 -
International Journal of Environmental... May 2024Predictive factors associated with a decline in swallowing function after 2 years were examined in 3409 Japanese older people aged ≥ 75 years who had undergone a...
Predictive factors associated with a decline in swallowing function after 2 years were examined in 3409 Japanese older people aged ≥ 75 years who had undergone a dental checkup in Gifu Prefecture, Japan. Participants with normal swallowing function in a baseline survey in April 2018 were followed for 2 years. Swallowing function was assessed using a repetitive saliva swallowing test. In our study, 429 participants (13%) who were swallowing less than three times in 30 s based on a repetitive saliva swallowing test after 2 years were diagnosed as those with decline in swallowing function. Multivariate logistic regression analyses showed the decline in swallowing function after 2 years was associated with the male gender (odds ratio [ORs]: 0.772; 95% confidence interval [CIs]: 0.615-0.969), age ≥ 81 years (presence; ORs: 1.523; 95% CIs: 1.224-1.895), support/care-need certification (presence; ORs: 1.815; 95% CIs: 1.361-2.394), periodontal pocket depth (PPD) ≥ 4 mm (presence; ORs: 1.469; 95% CIs: 1.163-1.856), difficulty in biting hard food (yes; ORs: 1.439; 95% CIs: 1.145-1.808), choking on tea and water (yes; ORs: 2.543; 95% CIs: 2.025-3.193), and dry mouth (yes; ORs: 1.316; 95% CIs: 1.052-1.646) at baseline. Therefore, the dental checkup items associated with a decline in swallowing function after 2 years were a PPD ≥ 4 mm, difficulty in biting hard food, choking on tea and water, and dry mouth. PPD status and confirming to the self-administered questionnaire about biting, choking, and dry mouth may be useful in predicting future decline in swallowing function.
Topics: Humans; Aged; Male; Female; Japan; Aged, 80 and over; Deglutition; Deglutition Disorders; Risk Factors; East Asian People
PubMed: 38928921
DOI: 10.3390/ijerph21060674 -
Discovery Medicine Jun 2024Nasopharyngeal carcinoma (NPC) is an aggressive and highly metastatic malignant tumor. Despite recent therapeutic advances, resistance to Taxol (the generic name of...
BACKGROUND
Nasopharyngeal carcinoma (NPC) is an aggressive and highly metastatic malignant tumor. Despite recent therapeutic advances, resistance to Taxol (the generic name of paclitaxel) therapy remains a major challenge in clinical management. Therefore, it is imperative to explore the potential mechanisms of paclitaxel resistance in NPC. This study aimed to investigate the expression of aldehyde dehydrogenase 2 (ALDH2) in NPC cells and its critical role in paclitaxel resistance.
METHODS
Paclitaxel-resistant cell line CNE1/Taxol (CNE1-TR), a drug-resistant cell line, was established by exposing the CNE1 nasopharyngeal carcinoma cell line to progressively increasing concentrations of paclitaxel. Furthermore, we investigated the role of ALDH2 in paclitaxel resistance and the function of exosomes using cell culture, Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), Cell Counting Kit-8 (CCK-8), and nanoparticle tracking analysis.
RESULTS
The results showed that in the presence of paclitaxel, the CNE1-TR cells manifested higher survival rate and half-maximal inhibitory concentration (IC50) value compared to the parental cell line, indicating strong resistance to paclitaxel. CNE1-TR cells had significantly upregulated mRNA and protein levels of ALDH2. In addition, exosome analysis showed that CNE1-TR cells were able to deliver ALDH2 via exosomes, increasing paclitaxel resistance in the recipient cells. We observed that the expression levels and paclitaxel resistance in CNE1-TR cells were effectively reduced by blocking the release of exosomes.
CONCLUSION
ALDH2 is not only a key molecular marker indicative of therapeutic efficacy, but also a potential therapeutic target for developing novel anticancer strategies. By blocking the exosomal transport of ALDH2 or directly inhibiting its activity, it may be possible to overcome paclitaxel resistance, thus improving the success rate of clinical treatment.
Topics: Humans; Paclitaxel; Exosomes; Drug Resistance, Neoplasm; Aldehyde Dehydrogenase, Mitochondrial; Nasopharyngeal Carcinoma; Cell Line, Tumor; Nasopharyngeal Neoplasms; Gene Expression Regulation, Neoplastic
PubMed: 38926107
DOI: 10.24976/Discov.Med.202436185.111 -
Tierarztliche Praxis. Ausgabe K,... Jun 2024A 2-year-old Norwegian Forest cat was presented for evaluation of bilateral purulent nasal discharge and stertorous breathing. A computed tomography (CT) scan of the...
A 2-year-old Norwegian Forest cat was presented for evaluation of bilateral purulent nasal discharge and stertorous breathing. A computed tomography (CT) scan of the head revealed an intranasal mass of the left nasal cavity extending behind the tube openings and completely obstructing the nasopharynx. Rhinoscopy confirmed a pinkish, shiny mass. CT scan showed both compartments of the right middle ear filled with abnormal soft tissue attenuating material. There was no change in the bony outline of the middle ear. In the endoscopic examination, after endoscopically assisted tympanocentesis, this material in the accessible dorsolateral compartment proved to be classic polypous tissue in addition to highly viscous glue-like secretions. A secondary otitis media due to a drainage disorder was suspected.Using an endoscopic-interventional approach through the nostril, the nasopharyngeal mass was removed for histopathological examination, in order to restore the nasal airway, and to allow tube drainage. In contrast to cats with classical malignant nasal cavity masses, the cat showed several attachment points of the mass and multiple undulating elevations bilaterally in the nasopharyngeal mucosa.Cytological and histopathological examination identified the mass as a fungal granuloma in the context of a cryptococcus infection only rarely observed in Germany. Molecular genetic analysis confirmed an infection with var. .A single intranasal and nasopharyngeal endoscopic debridement resulted in a significant improvement of the clinical signs and a complete healing of the right middle ear (including the tympanic membrane) within 14 days, but not in a complete cure of the disease. The cat was therefore treated with oral itraconazole solution for several weeks.The case report shows that nasal cryptococcosis can also affect cats in Germany. Rhinoscopy reveals a nasopharyngeal mass with multiple attachment points, which is unusual for a neoplasia. In addition to the recommended removal of the mass, oral administration of systemic antimycotics is strongly advised.
Topics: Animals; Cats; Cat Diseases; Cryptococcosis; Diagnosis, Differential; Nasopharyngeal Neoplasms; Germany; Tomography, X-Ray Computed; Nasopharyngeal Diseases
PubMed: 38925137
DOI: 10.1055/a-2324-0887 -
The New England Journal of Medicine Jun 2024Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear.
METHODS
In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients 12 to 65 years of age with symptomatic and histologically active eosinophilic esophagitis in a 1:1 ratio to receive subcutaneous benralizumab (30 mg) or placebo every 4 weeks. The two primary efficacy end points were histologic response (≤6 eosinophils per high-power field) and the change from baseline in the score on the Dysphagia Symptom Questionnaire (DSQ; range, 0 to 84, with higher scores indicating more frequent or severe dysphagia) at week 24.
RESULTS
A total of 211 patients underwent randomization: 104 were assigned to receive benralizumab, and 107 were assigned to receive placebo. At week 24, more patients had a histologic response with benralizumab than with placebo (87.4% vs. 6.5%; difference, 80.8 percentage points; 95% confidence interval [CI], 72.9 to 88.8; P<0.001). However, the change from baseline in the DSQ score did not differ significantly between the two groups (difference in least-squares means, 3.0 points; 95% CI, -1.4 to 7.4; P = 0.18). There was no substantial between-group difference in the change from baseline in the Eosinophilic Esophagitis Endoscopic Reference Score, which reflects endoscopic abnormalities. Adverse events were reported in 64.1% of the patients in the benralizumab group and in 61.7% of those in the placebo group. No patients discontinued the trial because of adverse events.
CONCLUSIONS
In this trial involving patients 12 to 65 years of age with eosinophilic esophagitis, a histologic response (≤6 eosinophils per high-power field) occurred in significantly more patients in the benralizumab group than in the placebo group. However, treatment with benralizumab did not result in fewer or less severe dysphagia symptoms than placebo. (Funded by AstraZeneca; MESSINA ClinicalTrials.gov number, NCT04543409.).
Topics: Humans; Eosinophilic Esophagitis; Antibodies, Monoclonal, Humanized; Male; Double-Blind Method; Eosinophils; Female; Adolescent; Middle Aged; Adult; Child; Young Adult; Aged; Deglutition Disorders; Leukocyte Count; Interleukin-5 Receptor alpha Subunit
PubMed: 38924732
DOI: 10.1056/NEJMoa2313318 -
Journal of Medical Virology Jun 2024
Topics: Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Chemoradiotherapy; Prognosis; Aged; Radiotherapy; Aged, 80 and over; Papillomaviridae
PubMed: 38922943
DOI: 10.1002/jmv.29535 -
CoDAS 2024To investigate the association between the number of permanent teeth and the use of removable dental prostheses with self-reported dysphagia occurrence in individuals...
PURPOSE
To investigate the association between the number of permanent teeth and the use of removable dental prostheses with self-reported dysphagia occurrence in individuals aged 60 years or older.
METHODS
A population-based cross-sectional study was conducted with 5,432 old individuals who participated in the baseline of the Brazilian Longitudinal Study of Elderly Health (ELSI-Brazil). The outcome "dysphagia" was associated with the number of permanent teeth and the use of removable dental prostheses. Sociodemographic independent variables (age, sex, and race/ethnicity) and clinical history variables (no morbidity, one morbidity, or more than two morbidities) were analyzed using Poisson Regression with robust variance and their respective 95% confidence intervals (CI).
RESULTS
The prevalence of self-reported dysphagia in non-institutionalized old individuals was 30%. The group of old individuals with 10 - 19 natural teeth showed a 52% increased risk of self-reported dysphagia complaint (PRadj 1,565 IC95% 1,34;1,826) compared to their counterparts with more teeth.
CONCLUSION
An association was found between a lower number of teeth and removable prostheses with the occurrence of dysphagia.
Topics: Humans; Brazil; Female; Male; Deglutition Disorders; Cross-Sectional Studies; Self Report; Aged; Middle Aged; Prevalence; Dental Prosthesis; Longitudinal Studies; Aged, 80 and over; Risk Factors; Socioeconomic Factors; Tooth Loss
PubMed: 38922245
DOI: 10.1590/2317-1782/20242023072pt