Search

Background: Transoral robotic surgery (TORS) performed after neoadjuvant chemotherapy (NAC) is a promising treatment for advanced‐stage oropharyngeal carcinoma (OPSCC) able to reduce the adjuvant therapy administration rate. Methods: A retrospective bi‐centric study was conducted to analyze NAC + TORS versus upfront TORS patients. A 1:1 propensity score matching was used to compare the two groups. Results: Among the 300 patients with stage III‐IV OPSCC, 204 patients were matched for comparing NAC + TORS versus upfront TORS. Between the two groups, no significant difference was observed in recurrences and in survival for RFS, OS, and DSS. In the NAC + TORS p16‐positive population, adjuvant therapy could be spared in 51% versus 16% in the upfront surgery cohort (p < 0.001) due to the lower frequency of pathological risk factors after NAC. Conclusions: NAC followed by TORS for locoregionally advanced OPSCC demonstrated to achieve non‐inferior survival outcomes to upfront surgery, while in the p16‐positive population allowed to significantly spare adjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is a highly heterogeneous disease, making tailored treatment approaches challenging. Magnetic resonance imaging (MRI), notably diffusion‐weighted imaging (DWI) and the derived Apparent Diffusion Coefficient (ADC) maps, plays a crucial role in PCa characterization. In this context, radiomics is a very promising approach able to disclose insights from MRI data. However, the sensitivity of radiomic features to MRI settings, encompassing DWI protocols and multicenter variations, requires the development of robust and generalizable models. Purpose: To develop a comprehensive radiomics framework for noninvasive PCa characterization using ADC maps, focusing on identifying reliable imaging biomarkers against intra‐ and inter‐institution variations. Materials and methods: Two patient cohorts, including an internal cohort (118 PCa patients) used for both training (75%) and hold‐out testing (25%), and an external cohort (50 PCa patients) for independent testing, were employed in the study. DWI images were acquired with three different DWI protocols on two different MRI scanners: two DWI protocols acquired on a 1.5‐T scanner for the internal cohort, and one DWI protocol acquired on a 3‐T scanner for the external cohort. One hundred and seven radiomics features (i.e., shape, first order, texture) were extracted from ADC maps of the whole prostate gland. To address variations in DWI protocols and multicenter variability, a dedicated pipeline, including two‐way ANOVA, sequential‐feature‐selection (SFS), and ComBat features harmonization was implemented. Mann–Whitney U‐tests (α = 0.05) were performed to find statistically significant features dividing patients with different tumor characteristics in terms of Gleason score (GS) and T‐stage. Support‐Vector‐Machine models were then developed to predict GS and T‐stage, and the performance was assessed through the area under the curve (AUC) of receiver‐operating‐characteristic curves. Results: Downstream of ANOVA, two subsets of 38 and 41 features stable against DWI protocol were identified for GS and T‐stage, respectively. Among these, SFS revealed the most predictive features, yielding an AUC of 0.75 (GS) and 0.70 (T‐stage) in the hold‐out test. Employing ComBat harmonization improved the external‐test performance of the GS model, raising AUC from 0.72 to 0.78. Conclusion: By incorporating stable features with a harmonization procedure and validating the model on an external dataset, model robustness, and generalizability were assessed, highlighting the potential of ADC and radiomics for PCa characterization. [ABSTRACT FROM AUTHOR]

A 74‐year‐old man was admitted to our emergency department following minor trauma. Plain radiographs and standard computed tomography (CT) scans revealed no signs of fractures. Subsequently, virtual noncalcium (VNCa) images were reconstructed, showing a linear area of bone marrow edema (BME) resembling a femoral neck fracture. Magnetic resonance imaging (MRI) was performed to confirm the presence of BME and an associated intraspongious fracture. In an emergency setting, dual‐energy CT (DECT) and VNCa images can successfully identify occult femoral fractures, especially in patients with mild symptoms and minor trauma, thereby preventing misdiagnosis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cotadutide is a dual GLP‐1 and glucagon receptor agonist with balanced agonistic activity at each receptor designed to harness the advantages on promoting liver health, weight loss and glycaemic control. We characterised the effects of cotadutide on glucose, insulin, GLP‐1, GIP, and glucagon over time in a quantitative manner using our glucose dynamics systems model (4GI systems model), in combination with clinical data from a multiple ascending dose/Phase 2a (MAD/Ph2a) study in overweight and obese subjects with a history of Type 2 diabetes mellitus (NCT02548585). Experimental Approach: The cotadutide PK‐4GI systems model was calibrated to clinical data by re‐estimating only food related parameters. In vivo cotadutide efficacy was scaled based on in vitro potency. The model was used to explore the effect of weight loss on insulin sensitivity and predict the relative contribution of the GLP‐1 and glucagon receptor agonistic effects on glucose. Key Results: Cotadutide MAD/Ph2a clinical endpoints were successfully predicted. The 4GI model captured a positive effect of weight loss on insulin sensitivity and showed that the stimulating effect of glucagon on glucose production counteracts the GLP‐1 receptor‐mediated decrease in glucose, resulting in a plateau for glucose decrease around a 200‐μg cotadutide dose. Conclusion and Implications: The 4GI quantitative systems pharmacology model was able to predict the clinical effects of cotadutide on glucose, insulin, GLP‐1, glucagon and GIP given known in vitro potency. The analyses demonstrated that the quantitative systems pharmacology model, and its successive refinements, will be a valuable tool to support the clinical development of cotadutide and related compounds. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study is to conduct a systematic review of the existing literature on styloidectomy performed through transoral robotic surgery (TORS) in Eagle syndrome (ES). Design and Setting: Two independent reviewers (RC and AC) conducted a systematic review of PubMed and Embase databases, seeking articles on TORS performed for ES treatment. The search was conducted in July 2023. The review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Participants: The review included a total of 17 adult patients, comprising 12 females and 5 males, with an average age of 52.2 years, all diagnosed with ES. Main Outcome Measures: For each patient, we assessed the overall length of the styloid process, the affected side, total intervention duration, hospitalization duration, pre and postoperative Visual Analogue Scale (VAS) scores, and the presence of minor and major complications. Results: We identified 4 articles describing 17 instances of TORS as a surgical treatment for ES in the literature, totaling 18 styloidectomies. The mean age of the patients was 52.2 years, with 12 females and 5 males. The average operation time, inclusive of the docking phase, was 68.8 minutes. Sixteen patients (94.1% of the total) experienced complete symptom disappearance or near‐complete resolution after surgery. One patient (5.9%) showed improvement categorized as 'non‐meaningful.' Only one case of minor complication was reported among the 17 procedures (5.9%). [ABSTRACT FROM AUTHOR]

The article discusses a surgical technique called Barbed Stayed Bridge Pharyngoplasty (BSBP) as a treatment option for obstructive sleep apnea (OSA). The study conducted at Sapienza University of Rome involved ten male patients with moderate OSA who underwent BSBP surgery. The results showed improvements in sleep apnea symptoms, although statistical significance was not observed. The study suggests that BSBP is an effective and minimally invasive surgical approach for OSA treatment. [Extracted from the article]

The barbed repositioning pharyngoplasty surgical technique is becoming more widely used for patients with obstructive sleep apnea due to its safety, effectiveness, and rapidity, as evidenced by multicenter studies and Meta‐analyses. In order to achieve uniform surgical outcomes, avoid errors that could worsen outcomes, and enable adequate data comparison, a standardized procedure is required to overcome surgeon‐related variability. The aim of this paper is to provide practical tips and tricks based on our surgical practice that can make the surgeon's work easier and aid in achieving desired outcomes. [ABSTRACT FROM AUTHOR]

Synaptic homeostatic plasticity is a foundational regulatory mechanism that maintains the stability of synaptic and neural functions within the nervous system. Impairment of homeostatic regulation has been linked to synapse destabilization during the progression of Alzheimer's disease (AD). Recent epigenetic and transcriptomic characterizations of the nervous system have revealed intricate molecular details about the aging brain and the pathogenesis of neurodegenerative diseases. Yet, how abnormal epigenetic and transcriptomic alterations in different cell types in AD affect synaptic homeostatic plasticity remains to be elucidated. Various glial cell types play critical roles in modulating synaptic functions both during the aging process and in the context of AD. Here, we investigated the impact of glial dysregulation of histone acetylation and transcriptome in AD on synaptic homeostatic plasticity, using computational analysis combined with electrophysiological methods in Drosophila. By integrating snRNA‐seq and H3K9ac ChIP‐seq data from the same AD patient cohort, we pinpointed cell type‐specific signature genes that were transcriptionally altered by histone acetylation. We subsequently investigated the role of these glial genes in regulating presynaptic homeostatic potentiation in Drosophila. Remarkably, nine glial‐specific genes, which were identified through our computational method as targets of H3K9ac and transcriptional dysregulation, were found to be crucial for the regulation of synaptic homeostatic plasticity in Drosophila. Our genetic evidence connects abnormal glial transcriptomic changes in AD with the impairment of homeostatic plasticity in the nervous system. In summary, our integrative computational and genetic studies highlight specific glial genes as potential key players in the homeostatic imbalance observed in AD. [ABSTRACT FROM AUTHOR]

The pyloric sphincter receives parasympathetic vagal innervation from the dorsal motor nucleus of the vagus (DMV). However, little is known about its higher‐order neurons and the nuclei that engage the DMV neurons controlling the pylorus. The purpose of the present study was twofold. First, to identify neuroanatomical connections between higher‐order neurons and the DMV. This was carried out by using the transneuronal pseudorabies virus PRV‐152 injected into rat pylorus torus and examining the brains of these animals for PRV labeling. Second, to identify the specific sites within the DMV that functionally control the motility and tone of the pyloric sphincter. For these studies, experiments were performed to assess the effect of DMV stimulation on pylorus activity in urethane‐anesthetized male rats. A strain gauge force transducer was sutured onto the pyloric tonus to monitor tone and motility. L‐glutamate (500 pmol/30 nL) was microinjected unilaterally into the rostral and caudal areas of the DMV. Data from the first study indicated that neurons labeled with PRV occurred in the DMV, hindbrain raphe nuclei, midbrain Edinger–Westphal nucleus, ventral tegmental area, lateral habenula, and arcuate nucleus. Data from the second study indicated that microinjected L‐glutamate into the rostral DMV results in contraction of the pylorus blocked by intravenously administered atropine and ipsilateral vagotomy. L‐glutamate injected into the caudal DMV relaxed the pylorus. This response was abolished by ipsilateral vagotomy but not by intravenously administered atropine or L‐NG‐nitroarginine methyl ester (L‐NAME). These findings identify the anatomical and functional brain neurocircuitry involved in controlling the pyloric sphincter. Our results also show that site‐specific stimulation of the DMV can differentially influence the activity of the pyloric sphincter by separate vagal nerve pathways. [ABSTRACT FROM AUTHOR]

The document titled "In memoriam: Prof. Dr. Mario Stefanini November 10, 1939 – August 14, 2024" pays tribute to the life and contributions of Professor Mario Stefanini, a renowned scientist and educator in the field of andrology. Mario Stefanini's career spanned decades, during which he made significant advancements in the study of human spermatozoa and spermatogenesis. He held prestigious roles nationally and internationally, contributing to scientific committees and educational programs. Mario Stefanini's legacy extends beyond his scientific achievements, as he was also known for his passion for art, literature, and music. His passing is mourned by his family, colleagues, and students, who remember him fondly for his dedication and inspiring mentorship. [Extracted from the article]

The article "In Response to Barbed Stayed Bridge Pharyngoplasty (BSBP)" published in the Laryngoscope journal discusses the benefits of BSBP in preserving the palatopharyngeal muscle (PPM) with barbed sutures, which provides stability and stiffness. The authors emphasize the importance of increasing the number of cases studied and are conducting further short- and long-term studies to confirm their outcomes. Patient evaluations using the PPOPS questionnaire and VAS scale show minimal postoperative discomfort and quicker recovery compared to other surgical techniques. Multicentric studies are still ongoing. [Extracted from the article]

Background: Proper connectivity between type I spiral ganglion neurons (SGNs) and inner hair cells (IHCs) in the cochlea is necessary for conveying sound information to the brain in mammals. Previous studies have shown that type I SGNs are heterogeneous in form, function and synaptic location on IHCs, but factors controlling their patterns of connectivity are not well understood. Results: During development, cochlear supporting cells and SGNs express Semaphorin‐3A (SEMA3A), a known axon guidance factor. Mice homozygous for a point mutation that attenuates normal SEMA3A repulsive activity (Sema3aK108N) show cochleae with grossly normal patterns of IHC innervation. However, genetic sparse labeling and three‐dimensional reconstructions of individual SGNs show that cochleae from Sema3aK108N mice lacked the normal synaptic distribution of type I SGNs. Additionally, Sema3aK108N cochleae show a disrupted distribution of GLUA2 postsynaptic patches around the IHCs. The addition of SEMA3A‐Fc to postnatal cochleae led to increases in SGN branching, similar to the effects of inhibiting glutamate receptors. Ca2+ imaging studies show that SEMA3A‐Fc decreases SGN activity. Conclusions: Contrary to the canonical view of SEMA3A as a guidance ligand, our results suggest SEMA3A may regulate SGN excitability in the cochlea, which may influence the morphology and synaptic arrangement of type I SGNs. Key Findings: The cochlear components responsible for peripheral auditory transduction include hair cells and afferent spiral ganglion neurons (SGNs).Genetic sparse labeling at different development time points shows the progression of the synaptic location of type I SGNs of different fiber diameters.SEMA3A is expressed by SGNs and epithelial cells adjacent to the hair cells, whereas NRP1 (a SEMA3A receptor) is expressed by SGNs.We have found that Semaphorin‐3A (SEMA3A), a secreted factor known in axon chemo‐repulsion, regulates normal SGN‐hair cell innervation patterns, possibly by modulating SGN activity.SEMA3A is also necessary for the normal distribution of postsynaptic glutamate receptor patches found between type I SGNs and inner hair cells.The results in this report provide new knowledge regarding the maturation of type I SGNs along with an unconventional role for SEMA3A. [ABSTRACT FROM AUTHOR]

Electrospinning is the leading process allowing the fabrication of polymeric nanofibrous membranes and mats. Unfortunately, it generally requires the solubilization of the polymer in a toxic solvent causing health and environmental issues during the production. Here, it is demonstrated that polyurethane (PU) fibrous membranes can be produced by electrospinning and then, moreover, functionalized using water as the only solvent for each processing step. Waterborne polyurethane in the form of a dispersion is firstly electrospun using poly(ethylene oxide) (PEO) as template polymer. After removing PEO via a washing cycle in water, the membranes show physico‐chemical properties influenced by the initial polymeric component ratio with greater mechanical performances and hydrophobicity observed at a higher PU amount. Aqueous solutions of bio‐based tannic acid (TA) are then employed to modify the surface properties of the membranes. The high amount of galloyl units per TA molecule allows its efficient anchoring on the fiber surface through supramolecular hydrogen bonding. By varying the TA amount and the order of washing cycle, the wettability can be tuned expanding the application range of the membranes. Finally, their efficient electrospinning at high flow‐rate using a home‐made needleless emitter paves the way for industrial production via full environmentally green processing. [ABSTRACT FROM AUTHOR]

Glucagon‐like peptide‐1 (GLP‐1) receptor agonists (GLP‐1RAs) and dual GLP‐1/glucagon receptor agonists improve glycaemic control and cause significant weight loss in patients with type 2 diabetes.1 These effects are driven in part by augmenting glucose‐stimulated insulin release (incretin effect), reducing caloric intake and delayed gastric emptying. We developed and externally validated a novel integrated quantitative systems pharmacology (QSP) model to gain quantitative insight into the relative contributions and mechanisms of drugs modulating glucose regulatory pathways. This model (4GI model) incorporates known feedback mechanisms among glucose, GLP‐1, glucagon, glucose‐dependent insulinotropic peptide (GIP), and insulin after glucose provocation (i.e., food intake) and drug intervention utilizing published nonpharmacological and pharmacological (liraglutide, a GLP‐1RA) data. The resulting model accurately describes the aforementioned mechanisms and independently predicts the effects of the GLP‐1RAs (dulaglutide and semaglutide) on system dynamics. Therefore, the validated 4GI model represents a quantitative decision‐making tool to support the advancement of novel therapeutics and combination strategies modulating these pathways. [ABSTRACT FROM AUTHOR]

Mathematical models in oncology aid in the design of drugs and understanding of their mechanisms of action by simulation of drug biodistribution, drug effects, and interaction between tumor and healthy cells. The traditional approach in pharmacometrics is to develop and validate ordinary differential equation models to quantify trends at the population level. In this approach, time‐course of biological measurements is modeled continuously, assuming a homogenous population. Another approach, agent‐based models, focuses on the behavior and fate of biological entities at the individual level, which subsequently could be summarized to reflect the population level. Heterogeneous cell populations and discrete events are simulated, and spatial distribution can be incorporated. In this tutorial, an agent‐based model is presented and compared to an ordinary differential equation model for a tumor efficacy model inhibiting the pERK pathway. We highlight strengths, weaknesses, and opportunities of each approach. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is the most common sleep disorder due mainly to peripheral causes, characterized by repeated episodes of obstruction of the upper airways, associated with arousals and snoring. Sleep bruxism (SB) is a masticatory muscle activity during sleep that is characterized as rhythmic (phasic) or nonrhythmic (tonic) and is not a movement disorder or a sleep disorder in otherwise healthy individuals. Given the potentially severe consequences and complications of apnea, the concurrent high prevalence of SB in daily dental practice, getting deeper into the correlation between these phenomena is worthy of interest.. Study Objectives: The aim of this study was to investigate the correlation between SB‐related masseter muscle activity (MMA) and apnea–hypopnea events as well as to assess their temporal sequence. Methods: Thirty (N = 30) patients with sleep respiratory disorders and clinical suspicion of sleep bruxism (SB) were recruited. Ambulatory polygraphic recording was performed to detect apnea–hypopnea events (AHEs) and sleep bruxism episodes (SBEs). Pearson test was used to assess the correlation between apnea–hypopnea index (AHI) and SB index (SBI). A 5‐s time window with respect to the respiratory events was considered to describe the temporal distribution of SBEs. Furthermore, SBI was compared between groups of patients with different AHI severity (i.e., mild, moderate and severe) using ANOVA. Results: On average, AHI was 27.1 ± 21.8 and SBI 9.1 ± 7.5. No correlation was shown between AHI and SBI. Most of SBEs (66.8%) occurred without a temporal relationship with respiratory events. Considering OSA, 65.7% of SBEs occurred within 5 s after AHEs, while in the case of central apnea (CA) 83.8% of SBEs occurred before the respiratory event. The participants with severe apnea (N = 9) show a tendency to have higher bruxism indexes when compared to patients with mild (N = 11) and moderate apnea (N = 10). Conclusions: Findings suggest that: 1. At the study population level, there is no correlation between AHI and SBI, as well as any temporal relationship between SBEs and respiratory events. 2. Specific patterns of temporal relationship might be identified with future studies focusing on the different types of apnea–hypopnea events and bruxism activities. [ABSTRACT FROM AUTHOR]

Alginate is a naturally occurring polysaccharide commonly derived from brown algae cell walls which possesses unique features that make it extremely promising for several biomedical and pharmaceutical purposes. Alginate biomaterials are indeed nowadays gaining increasing interest in drug delivery and tissue engineering applications owing to their intrinsic biocompatibility, nontoxicity, versatility, low cost, and ease of functionalization. Specifically, alginate-based nanostructures show enhanced capabilities with respect to alginate bulk materials in the targeted delivery of drugs and chemotherapies, as well as in helping tissue reparation and regeneration. Hence, it is not surprising that the number of scientific reports related to this topic have rapidly grown in the last decade. With these premises, the present review aims to provide a comprehensive state-of-the-art of the most recent advances in the preparation of alginate-based nanoparticles and electrospun nanofibers for drug delivery, cancer therapy, and tissue engineering purposes. After a short introduction concerning the general properties and uses of alginate and the concept of nanotechnology, the recent literature is then critically presented to highlight the main advantages of alginate-based nanostructures. Finally, the current limitations and the future perspectives and objectives are discussed in detail. [ABSTRACT FROM AUTHOR]

Glyphosate is the active ingredient in Roundup® brand nonselective herbicides, and residue testing for food has been conducted as part of the normal regulatory processes. Additional testing has been conducted by university researchers and nongovernmental agencies. Presence of residues needs to be put into the context of safety standards. Furthermore, to appropriately interpret residue data, analytical assays must be validated for each food sample matrix. Regulatory agency surveys indicate that 99% of glyphosate residues in food are below the European maximum residue limits (MRLs) or U.S. Environmental Protection Agency tolerances. These data support the conclusion that overall residues are not elevated above MRLs/tolerances due to agricultural practices or usage on genetically modified (GM) crops. However, it is important to understand that MRLs and tolerances are limits for legal pesticide usage. MRLs only provide health information when the sum of MRLs of all foods is compared to limits established by toxicology studies, such as the acceptable daily intake (ADI). Conclusions from dietary modeling that use actual food residues, or MRLs themselves, combined with consumption data indicate that dietary exposures to glyphosate are within established safe limits. Measurements of glyphosate in urine can also be used to estimate ingested glyphosate exposure, and studies indicate that exposure is <3% of the current European ADI for glyphosate, which is 0.5 mg glyphosate/kg body weight. Conclusions of risk assessments, based on dietary modeling or urine data, are that exposures to glyphosate from food are well below the amount that can be ingested daily over a lifetime with a reasonable certainty of no harm. [ABSTRACT FROM AUTHOR]

We investigated safety and efficacy of transoral robotic surgery (TORS) for base of tongue (BOT) reduction in obstructive sleep apnea syndrome (OSAS) patients. PubMed, Cochrane Library, and Scopus were searched. A meta‐analysis was performed. Random effects models were used. Thirty‐one cohorts met our criteria (1693 patients). The analysis was based mostly on retrospective studies. The summary estimate of the reduction of Apnea–Hypoxia Index (AHI) was 24.25 abnormal events per hour (95% CI: 21.69–26.81) and reduction of Epworth Sleepiness Scale (ESS) was 7.92 (95% CI: 6.50–9.34). The summary estimate of increase in lowest O2 saturation was 6.04% (95% CI: 3.05–9.03). The success rate of TORS BOT reduction, either alone or combined with other procedures, was 69% (95% CI: 64–79). The majority of studies reported low level of evidence but suggested that TORS BOT reduction may be a safe procedure associated with improvement of AHI, ESS, and lowest O2 saturation. [ABSTRACT FROM AUTHOR]

Background: Glial cell line‐derived neurotrophic factor (GDNF) is a soluble molecule crucial for the regulation of the spermatogonial stem cells (SSC) of the testis. The effects of GDNF on target cells have been extensively described, but mechanisms underlying GDNF regulation are currently under investigation. In the nervous system, GDNF expression is regulated by pro‐inflammatory cytokines including lipopolysaccharide (LPS), interleukin 1 beta (IL‐1β), and tumor necrosis factor alpha (TNF‐α) but the effect of these cytokines on GDNF expression in the testis is unclear. Objectives: The aim of the present study was to investigate the impact of TNF‐α on GDNF expression levels using primary murine Sertoli cells as experimental model. Material and methods: The expression of TNF‐α‐regulated genes including Gdnf in different culture conditions was determined by real‐time PCR. GDNF protein levels were determined by ELISA. The activation of the NF‐κb pathway and HES1 levels were assessed by Western Blot analysis and immunofluorescence. HES1 expression was downregulated by RNAi. Results: In primary Sertoli cells, TNF‐α downregulates GDNF levels through a nuclear factor‐κB (NF‐κB)‐dependent mechanism. Mechanistically, TNF‐α induces the transcriptional repressor HES1 by a NF‐Κb‐dependent mechanism, which in turn downregulates GDNF. Discussion: Under physiological conditions, TNF‐α is secreted by germ cells suggesting that this cytokine plays a role in the paracrine control of SSC niche by modulating GDNF levels. HES1, a well‐known target of the Notch pathway, is implicated in the regulation of GDNF expression. In Sertoli cells, TNF‐α and Notch signaling may converge at molecular level, to regulate the expression of HES1 and HES1‐ target genes, including GDNF. Conclusions: Because of the importance of GDNF for spermatogonial stem cell self‐renewal and proliferation, this data may give important insights on how cytokine signals in the testis modulate the expression of niche‐derived factors. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the clinical features of mild‐to‐moderate coronavirus disease 2019 (COVID‐19) in a sample of Italian patients and to investigate the occurrence of smell and taste disorders. Infected individuals with suspected (clinical diagnosis) or laboratory‐confirmed COVID‐19 infection were recruited. Patients completed a survey‐based questionnaire with the aim of assessing their epidemiological and clinical characteristics, general otorhinolaryngological symptoms, and smell and taste disorders. A total of 294 patients with mild‐to‐moderate COVID‐19 completed the survey (147 females). The most prevalent general symptoms included fever, myalgia, cough, and headache. A total of 70.4% and 59.2% of patients reported smell and taste disorders, respectively. A significant association between the two above‐mentioned disorders was found (rs: 0.412; P <.001). Smell disorders occurred before the other symptoms in 11.6% of patients and was not significantly associated with nasal obstruction or rhinorrhea. Interestingly, our statistical analysis did not show any significant difference, either for general symptoms or otorhinolaryngological features, between the clinical diagnosis group and the laboratory‐confirmed diagnosis (polymerase chain reaction) group. The structural equation model confirmed significant standardized paths (P <.05) between general symptoms, comorbidities, and general otorhinolaryngological complaints in the absence of a significant correlation between these elements and smell and taste alterations. The prevalence of smell and taste disorders in mild‐to‐moderate Italian COVID‐19 patients is significant both in suspected and laboratory‐confirmed cases and reveals a strong correlation between these clinical signs regardless of the presence of general or otorhinolaryngological symptoms, such as nasal obstruction or rhinorrhea. Highlights: This study evaluates the clinical features of mild‐to‐moderate COVID‐19 in a sample of adult Italian patients. The structural equation model (SEM) built to examine the clinical characteristics of the infection, confirms significant standardised paths between all the evaluated variables and underlines the absence of a significant correlation between smell and taste disorders and all the other variables. Furthermore, the study reveals a strong correlation between smell and taste alterations with a significant prevalence of these symptoms both in suspected (clinical diagnosis) and laboratory‐confirmed (pcr) cases. [ABSTRACT FROM AUTHOR]

Objective: Does nasal surgery affect multilevel surgical success outcome. Methods: Prospective eight country nonrandomized trial of 735 obstructive sleep apnea (OSA) patients, who had multilevel palate and/or tongue surgery, divided into two groups, with or without nose surgery. Results: There were 575 patients in nose group, 160 patients in no nose group. The mean age for nose group 44.6 ± 11.4, no nose group 44.2 ± 11.8. Mean preoperative BMI for nose group 27.5 ± 3.6, no nose group 27.5 ± 4.1, mean postoperative BMI nose group 26.3 ± 3.7, no nose group 27.1 ± 3.8 (P =.006). Mean preoperative AHI nose group 32.7 ± 19.4, no nose group 34.3 ± 25.0 (P =.377); and mean postoperative AHI nose group 13.5 ± 10.2, no nose group 17.1 ± 16.0 (P =.001). Mean preoperative ESS nose group was 11.3 ± 4.7, no nose group was 10.4 ± 5.4 (P =.051); and mean postoperative ESS nose group was 5.3 ± 3.2, no nose group was 6.7 ± 2.8 (P =.001). The nose group had higher percentage change (adjusted for age, gender, BMI) in AHI (33.7%, 95% CI 14% to 53.5%) compared to the no nose group (P =.001); the nose group also had more percentage change in ESS (37%, 95% CI 23.6% to 50.3%) compared to the no nose group (P <.001). Change in BMI did not affect AHI nor ESS change (Cohen effect 0.03 and 0.14, respectively). AHI change in both groups were also statistically significant in the mild OSA (P =.008) and the severe OSA (P =.01). Success rate of surgery for the nose group 68.2%, while the no nose group 55.0% (P =.002). Conclusion: Combining nose surgery in multilevel surgery improves surgical success. Level of evidence: IIC. [ABSTRACT FROM AUTHOR]

Background: Variants in TTN are frequently identified in the genetic evaluation of skeletal myopathy or cardiomyopathy. However, due to the high frequency of TTN variants in the general population, incomplete penetrance, and limited understanding of the spectrum of disease, interpretation of TTN variants is often difficult for laboratories and clinicians. Currently, cardiomyopathy is associated with heterozygous A‐band TTN variants, whereas skeletal myopathy is largely associated with homozygous or compound heterozygous TTN variants. Recent reports show pathogenic variants in TTN may result in a broader phenotypic spectrum than previously recognized. Methods: Here we report the results of a multisite study that characterized the phenotypes of probands with variants in TTN. We investigated TTN genotype‐phenotype correlations in probands with skeletal myopathy and/or cardiomyopathy. Probands with TTN truncating variants (TTNtv) or pathogenic missense variants were ascertained from two academic medical centers. Variants were identified via clinical genetic testing and reviewed according to the American College of Medical Genetics criteria. Clinical and family history data were documented via retrospective chart review. Family studies were performed for probands with atypical phenotypes. Results: Forty‐nine probands were identified with TTNtv or pathogenic missense variants. Probands were classified by clinical presentation: cardiac (n = 30), skeletal muscle (n = 12), or both (cardioskeletal, n = 7). Within the cardioskeletal group, 5/7 probands had heterozygous TTNtv predicted to affect the distal (3') end of the A‐band. All cardioskeletal probands had onset of proximal‐predominant muscle weakness before diagnosis of cardiovascular disease, five pedigrees support dominant transmission. Conclusion: Although heterozygous TTNtv in the A‐band is known to cause dilated cardiomyopathy, we present evidence that these variants may in some cases cause a novel, dominant skeletal myopathy with a limb‐girdle pattern of weakness. These findings emphasize the importance of multidisciplinary care for patients with A‐band TTNtv who may be at risk for multisystem disease. [ABSTRACT FROM AUTHOR]

Filler formulations are complex systems, characterized by a high number of components with different nature, as resins, extenders, additives. One of the main properties of a two‐component epoxy filler used for yacht application is the rheology. Thus, rheological additives are studied in both components after different times from the production. Rheological analysis produces a very large amount of information so statistical methods are useful to elaborate the data. In this study, a univariate approach (ANOVA) and a multivariate data processing, namely, principal component analysis after low‐level data fusion are carried out. It is shown that the multivariate approach provides the maximum useful information on the system. No differences are highlighted in the rheological behavior for the epoxy component, by using different additives while, for the polyamide component, the best rheological additive among the tested is the one that has a polyamide nature, being a polar system as itself. [ABSTRACT FROM AUTHOR]

A 2‐day meeting was held by members of the UK Quantitative Systems Pharmacology Network () in November 2018 on the topic of Translational Challenges in Oncology. Participants from a wide range of backgrounds were invited to discuss current and emerging modeling applications in nonclinical and clinical drug development, and to identify areas for improvement. This resulting perspective explores opportunities for impactful quantitative pharmacology approaches. Four key themes arose from the presentations and discussions that were held, leading to the following recommendations: Evaluate the predictivity and reproducibility of animal cancer models through precompetitive collaboration.Apply mechanism of action (MoA) based mechanistic models derived from nonclinical data to clinical trial data.Apply MoA reflective models across trial data sets to more robustly quantify the natural history of disease and response to differing interventions.Quantify more robustly the dose and concentration dependence of adverse events through mathematical modelling techniques and modified trial design. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To investigate long-term complications of newer reconstructive palate surgery techniques.Study Design: Retrospective case-series analysis.Methods: Retrospective six-country clinical study of OSA patients who had nose and palate surgery.Results: There were 217 patients, mean age = 43.9 ± 12.5 years, mean body mass index = 25.9 ± 4.7, mean preoperative apnea-hypopnea index [AHI] = 30.5 ± 19.1, follow-up 41.3 months. A total of 217 palatal procedures were performed, including 50 expansion sphincter pharyngoplasties (ESP), 34 functional expansion pharyngoplasties (FEP), 40 barbed reposition pharyngoplasties (BRP), 64 modified uvulopalatopharyngoplasties (mUPPP), 11 uvulopalatal flap procedures (UPF), nine suspension pharyngoplasties (SP), eight relocation pharyngoplasties (RP), and one z-pharyngoplasty (ZPP). Complications included were constant and/or felt twice per week; dry throat (7.8%), throat lump feeling (11.5%), throat phlegm (10.1%), throat scar feeling (3.7%), and difficulty swallowing (0.5%). Of the 17 patients who had a dry throat complaint, two were constant (one SP, one RP), 15 were occasional (10 mUPPP, three SP, two BRP). Of the 25 patients with the throat lump feeling, four were constant (three RP, one ZPP), 21 were occasional (10 mUPPP, five SP, five UPF, one BRP). Of the 22 patients with the throat phlegm feeling, four were constant (two SP, two RP), 18 were occasional (10 mUPPP, four BRP, two FEP, two SP). Of the eight patients with throat scar feeling, eight were occasional (four SP, two mUPPP, one FEP, one RP), none were constant. One patient had difficulty swallowing (RP procedure). There was no velopharyngeal incompetence, taste disturbance, nor voice change. Highest symptom complaints were mUPPP, SP, and RP, whereas the lowest symptom complaint was ESP.Conclusions: Newer palatal techniques have shown to have less long-term complications compared to the older ablative techniques.Level Of Evidence: 4 Laryngoscope, 130:2281-2284, 2020. [ABSTRACT FROM AUTHOR]

Submandibular gland excision is generally performed through a transcervical approach, a safe procedure that, however, carries few neurological, functional and aesthetic drawbacks. Intraoral approach to the submandibular gland has been described many years ago but it has been newly proposed in recent years thanks to endoscope‐assisted and robot‐assisted surgical procedures. The main purpose of intraoral approaches is to avoid cosmetic sequelae and to reduce the risk of marginal nerve injury although the recent introduction of retroauricular, postauricular, facelift and transhairline neck incisions has overcome the need for an alternative to traditional transcervical approach. Different surgical approaches (transoral versus transcervical) to the submandibular gland as well as different type of cutaneous incisions will be illustrated and discussed in the light of advancement of endoscope‐assisted and robot‐assisted procedures. [ABSTRACT FROM AUTHOR]

SUMMARY: Linear models are generally reliable methods for analyzing tumor growth in vivo, with drug effectiveness being represented by the steepness of the regression slope. With immunotherapy, however, not all tumor growth follows a linear pattern, even after log transformation. Tumor kinetics models are mechanistic models that describe tumor proliferation and tumor killing macroscopically, through a set of differential equations. In drug combination studies, although an additional drug‐drug interaction term can be added to such models, however, the drug interactions suggested by tumor kinetics models cannot be translated directly into synergistic effects. We have developed a novel statistical approach that simultaneously models tumor growth in control, monotherapy, and combination therapy groups. This approach makes it possible to test for synergistic effects directly and to compare such effects among different studies. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To evaluate a possible regrowth of lingual tonsil lymphatic tissue in patients submitted to lingual tonsil resection with transoral robotic surgery (TORS).Study Design: Retrospective Study.Methods: Medical records of patients surgically treated by means of TORS to remove excessive lymphatic tissue of the lingual tonsil were retrospectively reviewed. Postoperative endoscopic data after long-term follow-up were analyzed to investigate possible lymphatic tissue regrowth. Preoperative and postoperative lingual tonsil lymphatic tissue were classified according to the standardized Friedman's grading scale ranging from 0 to 4.Results: Sixty-eight patients (41 male and 27 female; mean age = 51.3 years) were considered suitable for the study analysis. Clinical regrowth was observed in six (8.8%) patients: four (5.9%) and two (2.9%) patients with grade 2 and 3 lymphatic hypertrophy, respectively. No correlation between the grade of regrowth, the time interval from surgery, and the volume of lymphatic tissue removed was found.Conclusions: The lymphatic tissue regrowth after TORS resection appears to be very low.Level Of Evidence: 4 Laryngoscope, 129:2652-2657, 2019. [ABSTRACT FROM AUTHOR]

Tremelimumab, an anti‐cytotoxic T‐lymphocyte antigen‐4 monoclonal antibody that enhances T‐cell activation, was evaluated in a randomized, double‐blind, placebo‐controlled, phase IIb study (NCT01843374) in patients with unresectable malignant mesothelioma. The study demonstrated no clinically meaningful differences in overall survival (OS). The objective of this analysis was to evaluate the relationship of exposure with OS. A population pharmacokinetic (PK) model adequately described the PK data. Three factors (sex, C‐reactive protein, and baseline tumor size) were identified as statistically significant PK predictors (P < 0.05 on clearance). A positive association between exposure and OS was observed. However, an association between key baseline factors with OS (regardless of treatment) and imbalances in prognostic factors favoring patients with higher exposure (upper vs. lower PK quartile) was seen. Taken together, these results suggest that the exposure OS relationship observed for tremelimumab in mesothelioma is likely spurious rather than a true association of exposure with efficacy. [ABSTRACT FROM AUTHOR]

Highlights from the article: Exposure-response analyses based on pharmacokinetics (PK) and pharmacodynamics (PD) offer great promise in research and development for vaccination and immunotherapy. First, it is characterized by the delayed emergence of immune responses caused by, e.g., the slow maturation of antibodies following vaccination or the emergence of T-cell responses after immune checkpoint inhibition. For example, in therapeutic vaccination there is no "dose" that directly relates to response as the half-life of vaccines is relatively short and is not predictive of the resulting long-lived immune response. In other words, a high titer may not correspond to antibodies with the desired affinity, and higher or more frequent vaccine doses do not consistently yield an increase in the quality of the immune response.

Precision medicine aims to use patient genomic, epigenomic, specific drug dose, and other data to define disease patterns that may potentially lead to an improved treatment outcome. Personalized dosing regimens based on tumor drug penetration can play a critical role in this approach. State‐of‐the‐art techniques to measure tumor drug penetration focus on systemic exposure, tissue penetration, cellular or molecular engagement, and expression of pharmacological activity. Using in silico methods, this information can be integrated to bridge the gap between the therapeutic regimen and the pharmacological link with clinical outcome. These methodologies are described, and challenges ahead are discussed. Supported by many examples, this review shows how the combination of these techniques provides enhanced patient‐specific information on drug accessibility at the tumor tissue level, target binding, and downstream pharmacology. Our vision of how to apply tumor drug penetration measurements offers a roadmap for the clinical implementation of precision dosing. [ABSTRACT FROM AUTHOR]

Copyright of International Journal of Cosmetic Science is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Following breast conserving surgery, the standard of care has been to deliver adjuvant radiation therapy directed to the whole breast (WBI) over a period of 3‐7 weeks. Over the past decade, increasing data have supported the concept that treatment to the whole breast may not be required in selected patients, allowing for the emergence of partial breast irradiation (PBI). Multiple randomized trials with 5‐10 years of follow‐up have been published documenting the safety and efficacy associated with PBI using multiple techniques. Questions that remain to be answered include (a) what is the optimal PBI technique for each clinical scenario, (b) are there additional patients that can be effectively managed with PBI approaches, and (c) are there different techniques/dose schedules that allow for further reduction in treatment duration and/or toxicities? Partial breast irradiation represents a standard approach for appropriately selected patients. PBI provides comparable clinical outcomes to WBI while allowing for a reduction in the duration treatment and the potential for reduced toxicities. Future studies may also help to better define which patients require no radiation, PBI, hypofractionated WBI or conventional WBI, based upon patient, clinical, pathologic features as well as potentially using tumor genetics. [ABSTRACT FROM AUTHOR]

The lack of standardization in the way that quantitative and systems pharmacology (QSP) models are developed, tested, and documented hinders their reproducibility, reusability, and expansion or reduction to alternative contexts. This in turn undermines the potential impact of QSP in academic, industrial, and regulatory frameworks. This article presents a minimum set of recommendations from the UK Quantitative and Systems Pharmacology Network (UK QSP Network) to guide QSP practitioners seeking to maximize their impact, and stakeholders considering the use of QSP models in their environment. [ABSTRACT FROM AUTHOR]

We present a novel algorithm to denoise deep Monte Carlo renderings, in which pixels contain multiple colour values, each for a different range of depths. Deep images are a more expressive representation of the scene than conventional flat images. However, since each depth bin receives only a fraction of the flat pixel's samples, denoising the bins is harder due to the less accurate mean and variance estimates. Furthermore, deep images lack a regular structure in depth—the number of depth bins and their depth ranges vary across pixels. This prevents a straightforward application of patch‐based distance metrics frequently used to improve the robustness of existing denoising filters. We address these constraints by combining a flat image‐space non‐local means filter operating on pixel colours with a deep cross‐bilateral filter operating on auxiliary features (albedo, normal, etc.). Our approach significantly reduces noise in deep images while preserving their structure. To our best knowledge, our algorithm is the first to enable efficient deep‐compositing workflows with denoised Monte Carlo renderings. We demonstrate the performance of our filter on a range of scenes highlighting the challenges and advantages of denoising deep images. We present a novel algorithm to denoise deep Monte Carlo renderings, in which pixels contain multiple color values, each for a different range of depths. Our algorithm combines a flat image‐space Non‐Local Means filter operating on pixel colors with a deep cross‐bilateral filter operating on auxiliary features (albedo, normal, etc.) of individual depth bins. Our approach significantly reduces noise in deep images while preserving their structure and enables efficient deep‐compositing workflows with denoised Monte Carlo renderings. [ABSTRACT FROM AUTHOR]

Cellular senescence is considered to be a major driver of aging, yet the mechanisms explaining the accumulation of senescent cells during life time remain unclear. In this issue, Lagnado et al (2021) show that neutrophils can trigger the senescence of neighboring cells by transmitting reactive oxygen species (ROS), which they normally produce to fight pathogens. The main genomic targets of the neutrophil‐mediated ROS damage are telomeres, supporting an intimate interplay between telomere homeostasis and oxidative stress in senescence and consequently aging. [ABSTRACT FROM AUTHOR]

Background: APOE4 has broad effects, one of which is worsened cognitive outcomes in cancer survivors following chemotherapy treatment compared to APOE3. Method: 1‐2 month old female APOE3 and APOE4‐Targeted Replacement (TR) mice were used for whole cell patch‐clamp experiments in the entorhinal cortex. Chemotherapy was introduced via a single injection of doxorubicin (10 mg/kg) or saline (control) and treated APOE‐TR mice were euthanized 1 week post‐injection. 0.5% biocytin internal solution was used to visualize cell morphology post hoc under a confocal microscope. Results: Pyramidal cells in the entorhinal cortex of APOE4‐TR mice (4 mice, n = 26 cells) exhibit significantly decreased spontaneous excitatory and inhibitory postsynaptic current frequencies, thereby contributing to an elevated excitatory‐inhibitory balance compared to APOE3‐TR mice (4 mice, n = 23 cells). Doxorubicin‐treated APOE3‐TR mice (4 mice, n = 33 cells) show a significant increase in spontaneous excitatory and inhibitory postsynaptic current amplitudes compared to controls (2 mice, n = 16 cells), while doxorubicin‐treated APOE4‐TR mice (5 mice, n = 20 cells) display no such synaptic changes compared to controls (4 mice, n = 19 cells). Conclusion: APOE4 has baseline effects on entorhinal cortex circuit inhibition and the lack of response to chemotherapy may reflect reduced resilience to stressors. [ABSTRACT FROM AUTHOR]

Amyloidosis is to be considered in the differential diagnosis of postoperative edema of tongue base after its ablation. It might be triggered by surgical trauma. After establishment of diagnosis, cause of secondary amyloidosis should be excluded. [ABSTRACT FROM AUTHOR]

Background: The first edition of the European position paper (EPP) on drug‐induced sleep endoscopy (DISE) was published in 2014 with the aim to standardise the procedure, to provide an in‐depth insight into the main aspects of this technique and to have a basis for future research. Since 2014, new studies have been published concerning new sedative agents or new insights into the pattern/levels of the obstruction depending on the depth of sedation. Therefore, an enlarged group of European experts in the field of sleep breathing disorders (SBD), including the most of the first DISE EPP main authors, has decided to publish an update of the European position paper on DISE, in order to include new evidence and to find a common language useful for reporting the findings of this endoscopic evaluation in adult population affected by SBD. Methods: The authors have evaluated all the available evidence reported in the literature and have compared experience among various departments in leading European centres in order to provide an update regarding the standardisation of the DISE procedure and an in‐depth insight into the main aspects of this technique. Results: After the first European Position Consensus Meeting on DISE and its update, consensus was confirmed for indications, required preliminary examinations, where to perform DISE, technical equipment required, staffing, local anaesthesia, nasal decongestion, other medications, patient positioning, basics and special diagnostic manoeuvres, drugs and observation windows. So far, no consensus could be reached on a scoring and classification system. However, regarding this aim, the idea of an essential classification, such as VOTE with the possibility of its graded implementation of information and descriptions, seems to be the best way to reach a universal consensus on DISE classification at this stage. A common DISE language is mandatory, and attempts to come to a generally accepted system should be pursued. [ABSTRACT FROM AUTHOR]

Abstract: We evaluated the proportion of patients eligible for alternatives to standard whole breast irradiation (WBI) following breast‐conserving surgery using the National Cancer Database (NCDB). Using the 2016 dataset, Stage I‐III patients were identified. Eligibility for hypofractionated WBI (HFRT), accelerated partial breast irradiation (APBI) and endocrine therapy (ET‐alone) was defined using eligibility from large clinical trials as well as consensus guidelines. For patients with pN0 breast cancer, 20.6% and 37.0% were eligible for ET‐alone based on the CALGB 9343/PRIME‐II trials, respectively. In terms of HFRT, 72.5% and 50.4% were eligible based on IMPORT LOW/ASTRO HFRT guidelines, respectively. Based on IMPORT LOW/GEC‐ESTRO trial/ASTRO guidelines/ABS guidelines/GEC‐ESTRO guidelines, 72.5%, 86.1%, 39.0%, 72.5%, 45.7%, respectively, were eligible for APBI. Of those who qualify for HFRT per ASTRO guidelines, approximately 90% were eligible for APBI and 50% for ET‐alone. This analysis shows that a large proportion of patients with node‐negative breast cancer are eligible for HFRT, APBI and/or ET‐alone after breast‐conserving surgery. [ABSTRACT FROM AUTHOR]

Abstract: Granular cell tumor is a rare condition that occasionally affects breast parenchyma: approximately, 5%‐15% of all granular cell tumors represent 1:1000 of breast tumors. In this study, we reported a consecutive series of 12 patients with primary granular cell tumor of the breast observed at our institute, focusing attention on preoperative management, surgical approach, and long‐term follow‐up. Eight cases (8/12; 66.78%) presented with left‐breast tumors; in the majority of patients (11/12; 91.7%), the lesion was identified in one of the upper quadrants. Specifically, upper intern quadrants (10 cases) were more affected. Surgical excision was performed in all patients. Mean diameter at pathologic section was 11.4 mm (range: 5‐22). Tumor relapse was reported only in one case (8.3%). Mean follow‐up was 98.1 months (range: 1‐192). We proposed a model to explain the molecular mechanism of granular cell tumorigenesis associating to the high level of S100 protein. Management of primary granular cell tumor of the breast requires a correct initial diagnosis using breast imaging associated with core biopsy. Surgical procedure with wide resection or quadrantectomy requires a careful evaluation of breast margins. [ABSTRACT FROM AUTHOR]

ABSTRACT: The methodology to create alginate and alginate/hyaluronic acid membranes, which involves wet conditions electrospinning, is presented in this paper. The wet conditions allow simultaneously to work in water solutions avoiding the toxic solvents and to obtain crosslinked alginate. An accurate rheological characterization of all solutions examined is performed. By optimizing the electrospinning parameters, it is possible to obtain alginate membranes with homogeneous nanofibers and a narrow diameter distribution (i.e., around 100 nm) as well as alginate/hyaluronic acid membranes characterized by a network of bimodal distribution of the dimensions, namely nanofibers with a diameter comparable to the ones of the alginate membrane, in which are blocked microfibers with a ribbon like appearance, as observed in the SEM images. In order to facilitate the electrospinning process, poly(ethylene oxide) is added to the solutions and then removed after membranes preparation, as demonstrated by the differential scanning calorimetry results, obtaining membranes made up only biopolymers. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46390. [ABSTRACT FROM AUTHOR]