The Use of Magnetic Resonance Imaging in Radiation Therapy Treatment Simulation and Planning.

Ever since its introduction as a diagnostic imaging tool the potential of magnetic resonance imaging (MRI) in radiation therapy (RT) treatment simulation and planning has been recognized. Recent technical advances have addressed many of the impediments to use of this technology and as a result have resulted in rapid and growing adoption of MRI in RT. The purpose of this article is to provide a broad review of the multiple uses of MR in the RT treatment simulation and planning process, identify several of the most used clinical scenarios in which MR is integral to the simulation and planning process, highlight existing limitations and provide multiple unmet needs thereby highlighting opportunities for the diagnostic MR imaging community to contribute and collaborate with our oncology colleagues. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 5.

A video-based decision aid improved knowledge and decreased decisional conflict for asymptomatic persistent endodontic lesions.

AIM: This prospective cohort study aimed to (i) evaluate patients' treatment decisions, decisional conflict and knowledge levels before and after use of a video-based decision aid (DA) on asymptomatic persistent endodontic lesions (APEL) and to (ii) elicit important decision factors for patients in the decision-making process. METHODOLOGY: A video DA modelled after the International Patient Decision Aids Standards (IPDAS) was designed. The video was pilot-tested, revised and used on 50 patients referred to the graduate endodontic clinic and presenting with an incidental finding of APEL detected on radiographs, with informed consent (DSRB 2020/00133). Recruitment was conducted from June 2020 to November 2021. Patients' treatment decisions and decision-making process were studied. Patients also completed a questionnaire on knowledge gain, decisional conflict and confidence levels. RESULTS: Forty-three patients (48 teeth) out of 50 patients chose long-term monitoring of APEL while 7 patients (7 teeth) decided on endodontic intervention. Median knowledge scores increased from 58.3 (IQR: 41.7, 75.0) to 87.5 (IQR: 75.0, 100.0) (p < .001); median decisional conflict scale (DCS) scores decreased from 25.0 (IQR: 12.5, 34.4) to 3.1 (IQR: 0, 23.8) (p < .001), and 44 (88%) patients were confident or very confident with their treatment decisions. Statistical analyses showed that asymptomatic condition of tooth was the sole decision factor with statistical significance while socioeconomic factors (age, gender, race, education and income levels) showed no significant trend. CONCLUSIONS: The majority of patients presenting with APEL in this study chose long-term monitoring over immediate intervention. Using the video-based DA in the decision-making process significantly improved patients' knowledge and decreased their decisional conflict levels.

Retinal perfusion is linked to cognition and brain MRI biomarkers in Black Americans.

INTRODUCTION: We investigated whether retinal capillary perfusion is a biomarker of cerebral small vessel disease and impaired cognition among Black Americans, an understudied group at higher risk for dementia. METHODS: We enrolled 96 Black Americans without known cognitive impairment. Four retinal perfusion measures were derived using optical coherence tomography angiography. Neurocognitive assessment and brain magnetic resonance imaging (MRI) were performed. Multiple linear regression analyses were performed. RESULTS: Lower retinal capillary perfusion was correlated with worse Oral Symbol Digit Test (P < = 0.005) and Fluid Cognition Composite scores (P < = 0.02), but not with the Crystallized Cognition Composite score (P > = 0.41). Lower retinal perfusion was also correlated with higher free water and peak width of skeletonized mean diffusivity, and lower fractional anisotropy (all P < 0.05) on MRI (N = 35). DISCUSSION: Lower retinal capillary perfusion is associated with worse information processing, fluid cognition, and MRI biomarkers of cerebral small vessel disease, but is not related to crystallized cognition.

Knowledge of undergraduate and postgraduate dental students about managing traumatic dental injuries based on the 2020 International Association of Dental Traumatology guidelines: A online survey of 10 dental schools from 10 countries.

BACKGROUND/AIM: The knowledge of dental students about managing traumatic dental injuries (TDIs) may not be uniform, depending on global location and dental education. The aim of this study was to evaluate the level of knowledge of undergraduate and postgraduate students specializing in endodontics and pediatric dentistry at 10 dental schools in 10 countries about the 2020 International Association of Dental Traumatology (IADT) guidelines regarding the management of TDIs. MATERIALS & METHODS: A previously published questionnaire was used in the current survey. It was an online survey with 12 questions regarding the management of TDIs and some additional questions regarding sociodemographic and professional profiles of the participants were added. The survey was distributed to final-year undergraduate students and postgraduate students in pediatric dentistry and endodontics from 10 dental schools. Simple frequency distributions and descriptive statistics were predominantly used to describe the data. Differences in the median percentage scores among the student categories were assessed using the Kruskal-Wallis test followed by Dwass-Steel-Critchlow-Fligner pairwise comparisons. RESULTS: A total of 347 undergraduates, 126 postgraduates in endodontics, and 72 postgraduates in pediatric dentistry from 10 dental schools participated in this survey. The postgraduates had a significantly higher percentage score for correct responses compared with the undergraduates. No significant difference was observed between the endodontic and pediatric dentistry postgraduates. CONCLUSION: The knowledge possessed by undergraduate and postgraduate students concerning the IADT-recommended management of TDIs varied across the globe and some aspects were found to be deficient. This study emphasizes the critical importance of reassessing the teaching and learning activities pertaining to the management of TDIs.

CEST MR fingerprinting (CEST-MRF) for brain tumor quantification using EPI readout and deep learning reconstruction.

PURPOSE: To develop a clinical CEST MR fingerprinting (CEST-MRF) method for brain tumor quantification using EPI acquisition and deep learning reconstruction. METHODS: A CEST-MRF pulse sequence originally designed for animal imaging was modified to conform to hardware limits on clinical scanners while keeping scan time under 2 min. Quantitative MRF reconstruction was performed using a deep reconstruction network (DRONE) to yield the water relaxation and chemical exchange parameters. The feasibility of the six parameter DRONE reconstruction was tested in simulations using a digital brain phantom. A healthy subject was scanned with the CEST-MRF sequence, conventional MRF and CEST sequences for comparison. Reproducibility was assessed via test-retest experiments and the concordance correlation coefficient calculated for white matter and gray matter. The clinical utility of CEST-MRF was demonstrated on four patients with brain metastases in comparison to standard clinical imaging sequences. Tumors were segmented into edema, solid core, and necrotic core regions and the CEST-MRF values compared to the contra-lateral side. RESULTS: DRONE reconstruction of the digital phantom yielded a normalized RMS error of ≤7% for all parameters. The CEST-MRF parameters were in good agreement with those from conventional MRF and CEST sequences and previous studies. The mean concordance correlation coefficient for all six parameters was 0.98 ± 0.01 in white matter and 0.98 ± 0.02 in gray matter. The CEST-MRF values in nearly all tumor regions were significantly different (P = 0.05) from each other and the contra-lateral side. CONCLUSION: Combination of EPI readout and deep learning reconstruction enabled fast, accurate and reproducible CEST-MRF in brain tumors.

Multi-institutional search for patient factors associated with adverse events following tracheotomy.

BACKGROUND: Tracheotomy is a common procedure for otolaryngologists. The risk of complications is difficult to predict. This study aims to identify measurable preoperative indicators associated with adverse events following tracheotomy. METHODS: The charts of adults undergoing tracheotomy for respiratory failure at one of four university-affiliated hospitals between 1/2012 and 8/2018 were reviewed. Complications were analyzed in the context of demographics, physiologic parameters, and comorbidities. RESULTS: Among 507 tracheotomies performed, the most common complications included infection, bleeding, and cardiac arrest. Mortality was 39 % in patients with pulmonary hypertension, 42 % in those with ejection fraction ≤ 40 and 32 % in those with abnormal right ventricular function, double the rates in patients without each of these findings. CONCLUSION: Many critically ill tracheotomy patients experience significant rates of adverse events. Risk factors for mortality include ejection fraction ≤ 40, pulmonary hypertension, and abnormal ventricular function. These should be considered for use in preoperative counseling.

Psycho-social perspectives of nonsurgical versus surgical endodontic interventions in persistent endodontic disease.

INTRODUCTION: Patients' experiences related to dental treatment could influence care-seeking behaviour and engender personal bias. Although endodontic retreatment and apical surgery are procedures often performed to manage previously treated teeth with persistent disease, there is lack of information regarding psycho-social perspectives of patients who undergo these treatments. Our aim was to compare experiences of patients who received these two treatment modalities using a qualitative approach. METHODS: A purposive sample of patients was taken from our previous study utilizing the Oral Health Impact Profile to compare oral health-related quality of life of 150 patients who received retreatment and apical surgery. Patients who reported impact and no impact were invited to participate in focus group discussions (FGDs). Eighteen patients from the retreatment group and 15 patients from the surgical group participated in six FGDs. Thematic analysis was conducted to identify key themes. RESULTS: Four themes emerged: (1) psycho-social disability associated with dental procedures, (2) physical disability associated with dental problems, (3) reliance on dentist's advice for treatment and (4) self-management to preserve treated teeth. Patients undergoing endodontic retreatment reported significant time loss from work and were less informed of alternative treatment options. However, they were pleased with the aesthetics of their teeth, especially if new crowns were made. Patients undergoing surgery experienced anxiety related to loss of control during surgery and apprehension on visualizing the wound post-surgery. They reported more impact on their diet, social interaction and sleep quality and some felt self-conscious due to post-treatment gingival recession. Patients in both groups placed great trust in professional advice and expressed a clear desire to maintain their natural dentition. There was low awareness regarding long-term care and future sequelae of their treated tooth. CONCLUSIONS: Patients reported different psycho-social and physical impacts following endodontic retreatment and apical surgery. Patients undergoing endodontic retreatment were more satisfied with aesthetic outcomes but experienced greater impact related to complexities and length of time taken for treatment. Patients undergoing surgery were better informed of treatment options but experienced greater physical and psycho-social disability during the recovery phase. Clinicians could consider incorporating findings from this study into the patient-dentist discussion.

A multi-institutional analysis of a general pelvis continuous Hounsfield unit synthetic CT software for radiotherapy.

PURPOSE: To validate a synthetic computed tomography (sCT) software with continuous HUs and large field-of-view (FOV) coverage for magnetic resonance imaging (MRI)-only workflow of general pelvis anatomy in radiotherapy (RT). METHODS: An sCT software for general pelvis anatomy (prostate, rectum, and female pelvis) has been developed by Philips Healthcare and includes continuous HUs assignment along with large FOV coverage. General pelvis sCTs were generated using a two-stack T1-weighted mDixon fast-field echo (FFE) sequence with a superior-inferior coverage of 36 cm. Seventy-seven prostate, 43 rectum, and 27 gynecological cases were scanned by three different institutions. mDixon image quality and sCTs were evaluated for soft tissue contrast by using a confidence level scale from 1 to 5 for bladder, prostate/rectum interface, mesorectum, and fiducial maker visibility. Dosimetric comparison was performed by recalculating the RT plans on the sCT after rigid registration. For 12 randomly selected cases, the mean absolute error (MAE) between sCT and CT was calculated to evaluate HU similarity, and the Pearson correlation coefficients (PCC) between the CT- and sCT-generated digitally reconstructed radiographs (DRRs) were obtained for quantitative comparison. To examine geometric accuracy of sCT as a reference for cone beam CT (CBCT), the difference between bone-based alignment of CBCT to CT and CBCT to sCT was obtained for 19 online-acquired CBCTs from three patients. RESULTS: Two-stack mDixon scans with large FOV did not show any image inhomogeneity or fat-water swap artifact. Fiducials, Foley catheter, and even rectal spacer were visible as dark signal on the sCT. Average visibility confidence level (average ± standard deviation) on the sCT was 5.0 ± 0.0, 4.6 ± 0.5, 3.8 ± 0.4, and 4.0 ± 1.1 for bladder, prostate/rectum interface, mesorectum and fiducial markers. Dosimetric accuracy showed on average < 1% difference with the CT-based plans for target and normal structures. The MAE of bone and soft tissue between the sCT and CT are 120.9 ± 15.4 HU, 33.4 ± 4.1 HU, respectively. Average PCC of all evaluated DRR pairs was 0.975. The average offset between CT and sCT as reference was (LR, AP, SI) = (0.19 ± 0.35, 0.14 ± 0.60, 0.44 ± 0.54) mm. CONCLUSIONS: The continuous HU sCT software-generated realistic sCTs and DRRs to enable MRI-only planning for general pelvis anatomy.

Understanding patients' and dentists' perspectives in dental trauma management: A mixed-methods study.

BACKGROUND/AIM: Patients suffering dental trauma are unprepared for the disability challenge and necessary rehabilitation, while a traumatic event places an expanded demand on the dentist who is focused on treating disease. The aim of this study was to examine the impact of traumatic dental injuries (TDI) on patients and to compare patients' and dentists' perceptions of the event. MATERIAL AND METHODS: TDI patients (aged ≥ 21 years) attending a tertiary dental hospital from 2011 to 2013, and their dentists were recruited with informed consent. An exploratory sequential mixed-methods design was adopted. The Oral Health Impact Profile (OHIP-14) quantitatively identified patients with "very often," "fairly often" or "occasionally" in at least one of the OHIP-14 questions (Phase 1) to participate in the qualitative phase of the study through focus group discussions (FGD) (Phase 2). FGD for dentists was conducted separately. RESULTS: Quantitative analysis showed 28%-55% of TDI patients had "occasional" to "very often" discomfort during eating, increased self-consciousness and embarrassment. Qualitative analysis showed patients were concerned with aesthetic disability, treatment cost and potential tooth loss but overcame their negative outlook and accepted prescribed protective measures. Dentists appreciated patients' concerns about aesthetics and functional disruptions but were less attuned to patients' sense of guilt and fear of judgement. CONCLUSIONS: TDI exert functional, psychological and social impacts on patients. Patients' and dentists' perspectives were useful for understanding the need for continuity of care, and the findings could contribute to effective TDI management.

Generation of Induced Pluripotent Stem Cell-Derived iTenocytes via Combined Scleraxis Overexpression and 2D Uniaxial Tension.

Today's challenges in tendon and ligament repair necessitate the identification of a suitable and effective candidate for cell-based therapy to promote tendon regeneration. Mesenchymal stromal cells (MSCs) have been explored as a potential tissue engineering strategy for tendon repair. While they are multipotent and have regenerative potential in vivo, they are limited in their self-renewal capacity and exhibit phenotypic heterogeneity. Induced pluripotent stem cells (iPSCs) can circumvent these limitations due to their high self-renewal capacity and unparalleled developmental plasticity. In tenocyte development, Scleraxis (Scx) is a crucial direct molecular regulator of tendon differentiation. Additionally, mechanoregulation has been shown to be a central element guiding embryonic tendon development and healing. As such, we have developed a protocol to encapsulate the synergistic effect of biological and mechanical stimulation that may be essential for generating tenocytes. iPSCs were induced to become mesenchymal stromal cells (iMSCs) and were characterized with classic mesenchymal stromal cell markers via flow cytometry. Next, using a lentiviral vector, the iMSCs were transduced to stably overexpress SCX (iMSCSCX+). These iMSCSCX+ cells can be further matured into iTenocytes via uniaxial tensile loading using a 2D bioreactor. The resulting cells were characterized by observing the upregulation of early and late tendon markers, as well as collagen deposition. This method of generating iTenocytes can be used to assist researchers in developing a potentially unlimited off-the-shelf allogeneic cell source for tendon cell therapy applications.

Prevalence of Comprehensive Eye Examination in Preschool Children With Eye Conditions.

Introduction: The purpose of this study is to assess the prevalence of comprehensive eye examinations in multiethnic preschool children, including children with visually significant eye conditions, and identify factors associated with comprehensive eye examinations. Methods: A sample of 9,197 African American, Hispanic, Asian American, and non-Hispanic White children aged 6-72 months was recruited for the Multi-Ethnic Pediatric Eye Disease Study from 2003 to 2011. Logistic regression performed in 2022 identified independent factors associated with parent-reported history of comprehensive eye examinations. The proportion of children with previous comprehensive eye examinations and the proportion with undetected amblyopia or strabismus were measured. Results: The prevalence of comprehensive eye examinations was 6.3% overall and 38.3%, 24.8%, 19.1%, 15.1%, and 9.8% among children with strabismus, amblyopia, significant anisometropia, hyperopia, and astigmatism, respectively. Children without prior comprehensive eye examinations were more likely to have undetected amblyopia or strabismus than those with comprehensive eye examination history (ps<0.001). The prevalence of comprehensive eye examinations was higher among older children. Prevalence varied by race/ethnicity, with 8.1%, 7.9%, 6.3%, and 4.9% of non-Hispanic White, Asian American, African American, and Hispanic children having had prior comprehensive eye examinations, respectively; however, the differences did not remain after adjusting for other associated factors. Older age, a primary caregiver with a college/university degree or higher, having vision insurance, gestational age <33 weeks, neurodevelopmental disorder diagnosis, strabismus, and ocular disease history were all statistically significantly associated with a relatively higher prevalence of comprehensive eye examinations in multivariable analyses. Conclusions: Comprehensive eye examinations were uncommon among preschool children, including those with treatable vision disorders. Interventions, such as parent education and vision insurance, are needed to imaprove comprehensive eye examination access and utilization for at-risk preschool children.

Phase-sensitive deep reconstruction method for rapid multiparametric MR fingerprinting and quantitative susceptibility mapping in the brain.

INTRODUCTION: This study explores the potential of Magnetic Resonance Fingerprinting (MRF) with a novel Phase-Sensitivity Deep Reconstruction Network (PS-DRONE) for simultaneous quantification of T1, T2, Proton Density, B1+, phase and quantitative susceptibility mapping (QSM). METHODS: Data were acquired at 3 T in vitro and in vivo using an optimized EPI-based MRF sequence. Phantom experiments were conducted using a standardized phantom for T1 and T2 maps and a custom-made agar-based gadolinium phantom for B1 and QSM maps. In vivo experiments included five healthy volunteers and one patient diagnosed with brain metastasis. PSDRONE maps were compared to reference maps obtained through standard imaging sequences. RESULTS: Total scan time was 2 min for 32 slices and a resolution of [1 mm, 1 mm, 4.5 mm]. The reconstruction of T1, T2, Proton Density, B1+ and phase maps were reconstructed within 1 s. In the phantoms, PS-DRONE analysis presented accurate and strongly correlated T1 and T2 maps (r = 0.99) compared to the reference maps. B1 maps from PS-DRONE showed slightly higher values, though still correlated (r = 0.6) with the reference. QSM values showed a small bias but were strongly correlated (r = 0.99) with reference data. In the in vivo analysis, PS-DRONE-derived T1 and T2 values for gray and white matter matched reference values in healthy volunteers. PS-DRONE B1 and QSM maps showed strong correlations with reference values. CONCLUSION: The PS-DRONE network enables concurrent acquisition of T1, T2, PD, B1+, phase and QSM maps, within 2 min of acquisition time and 1 s of reconstruction time.

Pulp Survival of Cracked Teeth with Reversible Pulpitis after Orthodontic Banding and Coronal Coverage - A Prospective Cohort Study with One Year Follow Up.

INTRODUCTION: The aim of this prospective study was to investigate the 1-year pulp survival of cracked teeth with reversible pulpitis managed with initial stabilization using orthodontic bands, followed by coronal coverage restorations. METHODS: One-hundred-and-twenty-five patients with a cracked tooth with reversible pulpitis each were recruited. Preoperative patient and tooth data were collected. After definitive pulp diagnoses were determined following an interim period of orthodontic banding, coronal coverage restorations were placed. Cox and logistic regression analyses were used to assess possible prognostic factors and to correlate initial time to pulp stabilization while in orthodontic bands with eventual outcome. Pulp survival was determined using both clinical and radiographic findings. RESULTS: One-hundred-and-six cracked teeth were followed up at 1 year. Pulp survival based on clinical and radiographic findings was found in 81 teeth (76.4%). Out of 25 failures, 11 (44%) required root canal treatment (RCT) in the orthodontic band stage and 10 (40%) required RCT during the process of or after coronal coverage restorations. Four teeth (16%) had incidental findings of periapical radiolucencies at the 1-year review without clinical symptoms. Teeth requiring RCT were found to have required longer periods in orthodontic bands prior to a definitive pulp diagnosis (P < .05). CONCLUSION: A step-by-step approach by using orthodontic banding to monitor pulp status may reduce the incidence of RCT required through definitive coronal coverage restorations for cracked teeth with reversible pulpitis.

Pancreatic neuroendocrine tumors: biology, diagnosis,and treatment.

Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are somewhat understood, but their molecular pathogenesis remains unknown. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is unpredictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally indicate a less favorable prognosis. Endocrine testing, imaging, and histological evidence are necessary to accurately diagnose PNETs. A 4-pronged aggressive treatment approach consisting of surgery, locoregional therapy, systemic therapy, and complication control has become popular in academic centers around the world. The optimal application of the multiple systemic therapeutic modalities is under development; efficacy, safety, availability, and cost should be considered when treating a specific patient. The clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including the novel Mahvash disease, are summarized.

A review of the peripheral proprioceptive apparatus in the larynx.

The larynx is an organ of the upper airway that participates in breathing, glutition, voice production, and airway protection. These complex functions depend on vocal fold (VF) movement, facilitated in turn by the action of the intrinsic laryngeal muscles (ILM). The necessary precise and near-instantaneous modulation of each ILM contraction relies on proprioceptive innervation of the larynx. Dysfunctional laryngeal proprioception likely contributes to disorders such as laryngeal dystonia, dysphagia, vocal fold paresis, and paralysis. While the proprioceptive system in skeletal muscle derived from somites is well described, the proprioceptive circuitry that governs head and neck structures such as VF has not been so well characterized. For over two centuries, researchers have investigated the question of whether canonical proprioceptive organs, muscle spindles, and Golgi tendon organs, exist in the ILM, with variable findings. The present work is a state-of-the-art review of the peripheral component of laryngeal proprioception, including current knowledge of canonical and possible alternative proprioceptive circuitry elements in the larynx.

Corrigendum: A review of the peripheral proprioceptive apparatus in the larynx.

[This corrects the article DOI: 10.3389/fnana.2023.1114817.].

4D lung MRI with high-isotropic-resolution using half-spoke (UTE) and full-spoke 3D radial acquisition and temporal compressed sensing reconstruction.

Objective. To develop a respiratory motion-resolved four-dimensional (4D) magnetic resonance imaging (MRI) technique with high-isotropic-resolution (1.1 mm) using 3D radial sampling, camera-based respiratory motion sensing, and temporal compressed sensing reconstruction for lung cancer imaging.Approach. Free-breathing half- and full-spoke 3D golden-angle radial acquisitions were performed on eight healthy volunteers and eight patients with lung tumors of varying size. A back-and-forth k-space ordering between consecutive interleaves of the 3D radial acquisition was performed to minimize eddy current-related artifacts. Data were sorted into respiratory motion states using camera-based motion navigation and 4D images were reconstructed using temporal compressed sensing to reduce scan time. Normalized sharpness indices of the diaphragm, apparent signal-to-noise ratio (aSNR) and contrast-to-noise ratio (CNR) of the lung tumor (patients only), liver, and aortic arch were compared between half- and full-spoke 4D MRI images to evaluate the impact of respiratory motion and image contrast on 4D MRI image quality. Respiration-induced changes in lung volumes and center of mass shifts were compared between half- and full-spoke 4D MRI measurements. In addition, the motion measurements from 4D MRI and the same-day 4D CT were presented in one of the lung tumor patients.Main results. Half-spoke 4D MRI provides better visualization of the lung parenchyma, while full-spoke 4D MRI presents sharper diaphragm images and higher aSNR and CNR in the lung tumor, liver, and aortic arch. Lung volume changes and center of mass shifts measured by half- and full-spoke 4D MRI were not statistically different. For the patient with 4D MRI and same-day 4D CT, lung volume changes and center of mass shifts were generally comparable.Significance. This work demonstrates the feasibility of a motion-resolved 4D MRI technique with high-isotropic-resolution using 3D radial acquisition, camera-based respiratory motion sensing, and temporal compressed sensing reconstruction for treatment planning and motion monitoring in radiotherapy of lung cancer.

Healthy Human Laryngopharyngeal Sensory Innervation Density Correlates with Age.

OBJECTIVE: Somatosensory feedback from upper airway structures is essential for swallowing and airway defense but little is known about the identities and distributions of human upper airway neurons. Furthermore, whether sensory innervation modifies with aging is unknown. In this study, we quantify neuronal and chemosensory cell density in upper airway structures and correlate with age. METHODS: Participants underwent biopsies from base of tongue, lateral and midline pharyngeal wall, epiglottis, and arytenoids (N = 25 13 female/12 male; 20-80 years, mean 51.4 years without clinical diagnosis of dysphagia or clinical indication for biopsy). Tissue sections were labeled with antibodies for all neurons, myelinated neurons, and chemosensory cells. Densities of lamina propria innervation, epithelial innervation, solitary chemosensory cells, and taste buds were calculated and correlated with age. RESULTS: Arytenoid had the highest density of innervation and chemosensory cells across all measures compared to other sites. Taste buds were frequently observed in arytenoid and epiglottis. Base of tongue, lateral pharynx, and midline posterior pharynx had minimal innervation and few chemosensory cells. Epithelial innervation was present primarily in close proximity to chemosensory cells and taste buds. Overall innervation and myelinated fibers in the arytenoid lamina propria decline with aging. CONCLUSION: Findings establish the architecture of healthy adult sensory innervation and demonstrate the varied distribution of laryngopharyngeal innervation, necessary steps toward understanding the sensory basis for swallowing and airway defense. We also document age-related decline in arytenoid innervation density. These findings suggest that sensory afferent denervation of the upper airway may be a contributing factor to presbyphagia. LEVEL OF EVIDENCE: NA Laryngoscope, 133:773-784, 2023.

Predicting Overall Survival for Patients with Malignant Mesothelioma Following Radiotherapy via Interpretable Machine Learning.

PURPOSE/OBJECTIVES: Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer arising from the cells of the thoracic pleura with a poor prognosis. We aimed to develop a model, via interpretable machine learning (ML) methods, predicting overall survival for MPM following radiotherapy based on dosimetric metrics as well as patient characteristics. MATERIALS/METHODS: Sixty MPM (37 right, 23 left) patients treated on a Tomotherapy unit between 2013 and 2018 were retrospectively analyzed. All patients received 45 Gy (25 fractions). The multivariable Cox regression (Cox PH) model and Survival Support Vector Machine (sSVM) were applied to build predictive models of overall survival (OS) based on clinical, dosimetric, and combined variables. RESULTS: Significant differences in dosimetric endpoints for critical structures, i.e., the lung, heart, liver, kidney, and stomach, were observed according to target laterality. The OS was found to be insignificantly different (p = 0.18) between MPM patients who tested left- and right-sided, with 1-year OS of 77.3% and 75.0%, respectively. With Cox PH regression, considering dosimetric variables for right-sided patients alone, an increase in PTV_Min, Total_Lung_PTV_Mean, Contra_Lung_Volume, Contra_Lung_V20, Esophagus_Mean, and Heart_Volume had a greater hazard to all-cause death, while an increase in Total_Lung_PTV_V20, Contra_Lung_V5, and Esophagus_Max had a lower hazard to all-cause death. Considering clinical variables alone, males and increases in N stage had greater hazard to all-cause death; considering both clinical and dosimetric variables, increases in N stage, PTV_Mean, PTV_Min, and esophagus_Mean had greater hazard to all-cause death, while increases in T stage and Heart_V30 had lower hazard to all-cause-death. In terms of C-index, the Cox PH model and sSVM performed similarly and fairly well when considering clinical and dosimetric variables independently or jointly. CONCLUSIONS: Clinical and dosimetric variables may predict the overall survival of mesothelioma patients, which could guide personalized treatment planning towards a better treatment response. The identified predictors and their impact on survival offered additional value for translational application in clinical practice.

Directing iPSC differentiation into iTenocytes using combined scleraxis overexpression and cyclic loading.

Regenerative therapies for tendon are falling behind other tissues due to the lack of an appropriate and potent cell therapeutic candidate. This study aimed to induce tenogenesis using stable Scleraxis (Scx) overexpression in combination with uniaxial mechanical stretch of iPSC-derived mesenchymal stromal-like cells (iMSCs). Scx is the single direct molecular regulator of tendon differentiation known to date. Bone marrow-derived (BM-)MSCs were used as reference. Scx overexpression alone resulted in significantly higher upregulation of tenogenic markers in iMSCs compared to BM-MSCs. Mechanoregulation is known to be a central element guiding tendon development and healing. Mechanical stimulation combined with Scx overexpression resulted in morphometric and cytoskeleton-related changes, upregulation of early and late tendon markers, and increased extracellular matrix deposition and alignment, and tenomodulin perinuclear localization in iMSCs. Our findings suggest that these cells can be differentiated into tenocytes and might be a better candidate for tendon cell therapy applications than BM-MSCs.