Deep learning model for pleural effusion detection via active learning and pseudo-labeling: a multisite study.

BACKGROUND: The study aimed to develop and validate a deep learning-based Computer Aided Triage (CADt) algorithm for detecting pleural effusion in chest radiographs using an active learning (AL) framework. This is aimed at addressing the critical need for a clinical grade algorithm that can timely diagnose pleural effusion, which affects approximately 1.5 million people annually in the United States. METHODS: In this multisite study, 10,599 chest radiographs from 2006 to 2018 were retrospectively collected from an institution in Taiwan to train the deep learning algorithm. The AL framework utilized significantly reduced the need for expert annotations. For external validation, the algorithm was tested on a multisite dataset of 600 chest radiographs from 22 clinical sites in the United States and Taiwan, which were annotated by three U.S. board-certified radiologists. RESULTS: The CADt algorithm demonstrated high effectiveness in identifying pleural effusion, achieving a sensitivity of 0.95 (95% CI: [0.92, 0.97]) and a specificity of 0.97 (95% CI: [0.95, 0.99]). The area under the receiver operating characteristic curve (AUC) was 0.97 (95% DeLong's CI: [0.95, 0.99]). Subgroup analyses showed that the algorithm maintained robust performance across various demographics and clinical settings. CONCLUSION: This study presents a novel approach in developing clinical grade CADt solutions for the diagnosis of pleural effusion. The AL-based CADt algorithm not only achieved high accuracy in detecting pleural effusion but also significantly reduced the workload required for clinical experts in annotating medical data. This method enhances the feasibility of employing advanced technological solutions for prompt and accurate diagnosis in medical settings.

Persistent Fatigue in Patients With Hepatocellular Carcinoma Receiving Radiotherapy.

BACKGROUND: Radiation therapy has attracted much attention in the treatment of patients with hepatocellular carcinoma (HCC). However, the association between radiotherapy-related fatigue and HCC has been examined in only a few studies. PURPOSE: This study was designed to explore the change over time in fatigue in patients with HCC treated with radiotherapy and related factors. METHODS: One hundred patients were enrolled in this prospective longitudinal study using convenience sampling at a medical center in northern Taiwan. The Functional Assessment of Chronic Illness Therapy-Fatigue scale, the Brief Pain Inventory-Short Form, and the psychological subscale of Memorial Symptom Assessment Scale-Short Form were used to assess the symptoms at five time points: before radiotherapy (T0), during treatment (T1), and at 1 month (T2), 3 months (T3), and 6 months (T4) after radiotherapy. The generalized estimating equations method was used to determine the changes in fatigue and the influencing factors. RESULTS: Fatigue levels at T1, T2, T3, and T4 were significantly higher than that at T0. Higher fatigue was significantly associated with lower income and poorer functional status. Having worse pain levels and psychological symptoms were both associated with higher fatigue. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results indicate fatigue does not recover to the baseline (pretherapy) level by 6 months after radiotherapy. Thus, fatigue in patients with HCC receiving radiotherapy should be regularly and effectively assessed, and patients experiencing pain and psychological symptoms should be given greater attention from clinicians.

Synthesis of High-Molecular-Weight Poly(ether-alt-ester) by Selective Double Ring-Opening Polymerization of Spiroorthoesters.

We report the selective double ring-opening polymerization of presequenced spiroorthoester monomers to form high-molecular-weight (≈90 kDa) poly(ether-alt-ester)s with a simple cationic alkyl gallium catalyst. The selective formation of double ring-opened polymer units was confirmed by NMR and IR spectroscopies. Thermal and rheological properties of homo- and copolymers were further characterized by differential scanning calorimetry, thermogravimetric analysis, and stress-controlled rotational rheometry. Linear viscoelastic moduli show that these systems are well entangled (plateau modulus), thereby possessing nearly terminal relaxation at long time scales (low frequencies) and Rouse segmental dynamics at short time scales (high frequencies) with characteristic slopes. These are the highest-molecular-weight poly(ether-alt-ester)s reported to date.

Impact of pretreatment quality of life on tolerance and survival outcome in head and neck cancer patients undergoing definitive CCRT.

BACKGROUND: Health-related quality of life (HRQoL) is a predictor of treatment outcomes in cancer patients. This study aimed to evaluate the effect of pretreatment HRQoL on treatment tolerance and survival outcomes in patients with HNC planned for concurrent chemoradiotherapy (CCRT) in Taiwan. METHODS: This study included 461 patients with HNC planned for definitive CCRT at three medical centers in Taiwan between August 2017 and December 2018. HRQoL was assessed using the QLQ-HN35 one week before the initiation of CCRT. Patients were grouped based on the sum scores of QLQ-HN35 (

Targeting prostate tumor low-molecular weight tyrosine phosphatase for oxidation-sensitizing therapy.

Protein tyrosine phosphatases (PTPs) play major roles in cancer and are emerging as therapeutic targets. Recent reports suggest low-molecular weight PTP (LMPTP)-encoded by the ACP1 gene-is overexpressed in prostate tumors. We found ACP1 up-regulated in human prostate tumors and ACP1 expression inversely correlated with overall survival. Using CRISPR-Cas9-generated LMPTP knockout C4-2B and MyC-CaP cells, we identified LMPTP as a critical promoter of prostate cancer (PCa) growth and bone metastasis. Through metabolomics, we found that LMPTP promotes PCa cell glutathione synthesis by dephosphorylating glutathione synthetase on inhibitory Tyr270. PCa cells lacking LMPTP showed reduced glutathione, enhanced activation of eukaryotic initiation factor 2-mediated stress response, and enhanced reactive oxygen species after exposure to taxane drugs. LMPTP inhibition slowed primary and bone metastatic prostate tumor growth in mice. These findings reveal a role for LMPTP as a critical promoter of PCa growth and metastasis and validate LMPTP inhibition as a therapeutic strategy for treating PCa through sensitization to oxidative stress.

Dose-Escalated Radiation Therapy as Primary Treatment for Residual Bladder Cancer After Transurethral Resection.

Purpose: The aim of this study was to determine whether escalating the local radiation dose can improve the outcome of residual bladder cancer after transurethral resection of bladder tumor without increasing treatment-related toxicity. Methods and Materials: The treatment plans and medical records of patients with bladder cancer treated with curative-intent radiation therapy between 2008 and 2020 were reviewed. Those who had residual tumors in the computed tomography simulation images were included. A cumulative radiation dose higher than 6600 cGy was defined as dose escalation. The effect of dose escalation on 3-year locoregional control, progression-free survival, and overall survival was evaluated. Results: A total of 149 patients with residual tumors were identified. The median follow-up period was 27.5 months. Among them, 51 patients received an escalated radiation dose, and 98 received a standard dose in the residual tumor area. Patients in the dose-escalation group had higher 3-year locoregional control (65.6% vs 27.8%; P < .001) and progression-free survival (42.6% vs 18.2%; P < .001) than the standard-dose group. Overall survival also showed a trend favoring the dose-escalation group (54.9% vs 36.2%; P = .059). In the multivariate analyses, the differences between the dose-escalation and standard-dose groups were significant in terms of locoregional control (hazard ratio, 0.32; CI, 0.18-0.59; P = <.001) and progression-free survival (hazard ratio, 0.51; CI, 0.32-0.82; P = .005). There was no statistical difference in acute and chronic treatment-related toxicities between the 2 groups. Conclusions: The outcome of residual bladder cancer after transurethral resection of bladder tumor could be improved by dose-escalated radiation therapy.

MiR-630 Promotes Radioresistance by Induction of Anti-Apoptotic Effect via Nrf2-GPX2 Molecular Axis in Head-Neck Cancer.

Head and neck cancer (HNC) ranks among the top ten prevalent cancers worldwide. Radiotherapy stands as a pivotal treatment component for HNC; however, radioresistance in cancerous cells often leads to local recurrence, becoming a substantial factor in treatment failure. MicroRNAs (miRNAs) are compact, non-coding RNAs that regulate gene expression by targeting mRNAs to inhibit protein translation. Although several studies have indicated that the dysregulation of miRNAs is intricately linked with malignant transformation, understanding this molecular family's role in radioresistance remains limited. This study determined the role of miR-630 in regulating radiosensitivity in HNC. We discovered that miR-630 functions as an oncomiR, marked by its overexpression in HNC patients, correlating with a poorer prognosis. We further delineated the malignant function of miR-630 in HNC cells. While it had a minimal impact on cell growth, the miR-630 contributed to radioresistance in HNC cells. This result was supported by decreased cellular apoptosis and caspase enzyme activities. Moreover, miR-630 overexpression mitigated irradiation-induced DNA damage, evidenced by the reduced levels of the γ-H2AX histone protein, a marker for double-strand DNA breaks. Mechanistically, the overexpression of miR-630 decreased the cellular ROS levels and initiated Nrf2 transcriptional activity, resulting in the upregulation of the antioxidant enzyme GPX2. Thus, this study elucidates that miR-630 augments radioresistance by inducing an anti-apoptotic effect via the Nrf2-GPX2 molecular axis in HNC. The modulation of miR-630 may serve as a novel radiosensitizing target for HNC.

Prognostic value of interim CT-based peritumoral and intratumoral radiomics in laryngeal and hypopharyngeal cancer patients undergoing definitive radiotherapy.

BACKGROUND AND PURPOSE: We aimed to investigate the prognostic value of peritumoral and intratumoral computed tomography (CT)-based radiomics during the course of radiotherapy (RT) in patients with laryngeal and hypopharyngeal cancer (LHC). MATERIALS AND METHODS: A total of 92 eligible patients were 1:1 randomly assigned into training and validation cohorts. Pre-RT and mid-RT radiomic features were extracted from pre-treatment and interim CT. LASSO-Cox regression was used for feature selection and model construction. Time-dependent area under the receiver operating curve (AUC) analysis was applied to evaluate the models' prognostic performances. Risk stratification ability on overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox regression. The associations between radiomics and clinical parameters as well as circulating lymphocyte counts were also evaluated. RESULTS: The mid-RT peritumoral (AUC: 0.77) and intratumoral (AUC: 0.79) radiomic models yielded better performance for predicting OS than the pre-RT intratumoral model (AUC: 0.62) in validation cohort. This was confirmed by Kaplan-Meier analysis, in which risk stratification depended on the mid-RT peritumoral (p = 0.009) and intratumoral (p = 0.003) radiomics could be improved for OS, in comparison to the pre-RT intratumoral radiomics (p = 0.199). Multivariate analysis identified mid-RT peritumoral and intratumoral radiomic models as independent prognostic factors for both OS and PFS. Mid-RT peritumoral and intratumoral radiomics were correlated with treatment-related lymphopenia. CONCLUSION: Mid-RT peritumoral and intratumoral radiomic models are promising image biomarkers that could have clinical utility for predicting OS and PFS in patients with LHC treated with RT.

Risk of temporal lobe necrosis between proton beam and volumetric modulated arc therapies in patients with different head and neck cancers.

BACKGROUND: To investigate the frequency of temporal lobe necrosis (TLN) soon after radiotherapy (RT) and identify differences among patients with various types of head and neck cancer (HNC) and between different RT methods. METHODS: We retrospectively reviewed 483 patients with HNC who had completed RT in our hospital after January, 2015. These patients were followed-up at the radio-oncology department and received contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) to identify metastases or recurrence of cancer at regular intervals. Meanwhile, the occurrence of TLN, graded according to the Common Terminology Criteria for Adverse Events V5.0, was recorded. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of TLN between the groups using Kaplan-Meier and Cox regression analyses. We further compared the cumulative occurrence of TLN between proton beam therapy (PBT) and volumetric modulated arc therapy (VMAT) in patients with any HNC, NPC, and non-NPC HNC. RESULTS: Compared with the non-NPC group, the NPC group had a higher frequency of TLN (5.6% vs. 0.4%, p < 0.01) and were more commonly associated with TLN in the Kaplan-Meier analysis (p < 0.01) and the Cox regression model after covariates were adjusted for (adjusted hazard ratio: 13.35, 95% confidence interval: 1.37-130.61) during the follow-up period. Furthermore, the frequency of TLN was similar between patients receiving PBT and those receiving VMAT (PBT vs. VMAT: 4.7% vs. 6.3%, p = 0.76). Kaplan-Meier analysis revealed that the accumulated risks of TLN were similar between PBT and VMAT in patients with any HNC (p = 0.44), NPC (p = 0.84), and non-NPC HNC (p = 0.70). CONCLUSION: Our study demonstrated that patients with NPC are susceptible to TLN during the early period after RT. In addition, PBT may be associated with an equivalent risk of TLN when compared with VMAT in patients with NPC or other HNCs.

Development and validation of a machine learning model of radiation-induced hypothyroidism with clinical and dose-volume features.

BACKGROUND AND PURPOSE: Radiation-induced hypothyroidism (RIHT) is a common but underestimated late effect in head and neck cancers. However, no consensus exists regarding risk prediction or dose constraints in RIHT. We aimed to develop a machine learning model for the accurate risk prediction of RIHT based on clinical and dose-volume features and to evaluate its performance internally and externally. MATERIALS AND METHODS: We retrospectively searched two institutions for patients aged >20 years treated with definitive radiotherapy for nasopharyngeal or oropharyngeal cancer, and extracted their clinical information and dose-volume features. One was designated the developmental cohort, the other as the external validation cohort. We compared the performances of machine learning models with those of published normal tissue complication probability (NTCP) models. RESULTS: The developmental and external validation cohorts consisted of 378 and 49 patients, respectively. The estimated cumulative incidence rates of grade ≥1 hypothyroidism were 53.5% and 61.3% in the developmental and external validation cohorts, respectively. Machine learning models outperformed traditional NTCP models by having lower Brier scores at every time point and a lower integrated Brier score, while demonstrating a comparable calibration index and mean area under the curve. Even simplified machine learning models using only thyroid features performed better than did traditional NTCP algorithms. The machine learning models showed consistent performance between folds. The performance in a previously unseen external validation cohort was comparable to that of the cross-validation. CONCLUSIONS: Our model outperformed traditional NTCP models, with additional capabilities of predicting the RIHT risk at individual time points. A simplified model using only thyroid dose-volume features still outperforms traditional NTCP models and can be incorporated into future treatment planning systems for biological optimization.

Spectral top-down recovery of latent tree models.

Modeling the distribution of high-dimensional data by a latent tree graphical model is a prevalent approach in multiple scientific domains. A common task is to infer the underlying tree structure, given only observations of its terminal nodes. Many algorithms for tree recovery are computationally intensive, which limits their applicability to trees of moderate size. For large trees, a common approach, termed divide-and-conquer, is to recover the tree structure in two steps. First, separately recover the structure of multiple, possibly random subsets of the terminal nodes. Second, merge the resulting subtrees to form a full tree. Here, we develop spectral top-down recovery (STDR), a deterministic divide-and-conquer approach to infer large latent tree models. Unlike previous methods, STDR partitions the terminal nodes in a non random way, based on the Fiedler vector of a suitable Laplacian matrix related to the observed nodes. We prove that under certain conditions, this partitioning is consistent with the tree structure. This, in turn, leads to a significantly simpler merging procedure of the small subtrees. We prove that STDR is statistically consistent and bound the number of samples required to accurately recover the tree with high probability. Using simulated data from several common tree models in phylogenetics, we demonstrate that STDR has a significant advantage in terms of runtime, with improved or similar accuracy.

Changes in fatigue among cancer patients before, during, and after radiation therapy: A meta-analysis.

BACKGROUND: Fatigue is a common symptom in cancer patients receiving radiotherapy. However, previous studies report inconsistent patterns of fatigue change. AIM: The aim of this study was to estimate changes in fatigue among patients with cancer before, during, and after radiotherapy. METHODS: Five databases (PubMed, SDOL, CINAHL Plus with Full Text, Medline [ProQuest], and ProQuest Dissertations) were searched for studies published from January 2006 to May 2021. Three effect sizes of fatigue change (immediate, short-term, and long-term) were calculated for each primary study using standardized mean difference. A random-effect model was used to combine effect sizes across studies. Subgroup analyses and meta-regression were performed to identify potential categorical and continuous moderators, respectively. RESULTS: Sixty-five studies were included in this meta-analysis. The weighted mean effect size for immediate, short-term, and long-term effects was 0.409 (p < .001; 95% CI [0.280, 0.537]), 0.303 (p < .001; 95% CI [0.189, 0.417]), and 0.201 (p = .05; 95% CI [-0.001, 0.404]), respectively. Studies with prostate cancer patients had a significantly higher short-term (0.588) and long-term weight mean effect size (0.531) than studies with breast (0.128, -0.072) or other cancers (0.287, 0.215). Higher radiotherapy dosage was significantly associated with a higher effect size for both immediate (ß = .0002, p < .05) and short-term (ß = .0002, p < .05) effect. LINKING EVIDENCE TO ACTION: Findings from this meta-analysis indicated that radiotherapy-induced fatigue (RIF) exist for more than 3 months after the completion of treatment. Assessment of radiation-induced fatigue in cancer patients should extend long after treatment completion, especially for patients with prostate cancer and patients receiving a higher radiation dose. Interventions to reduce fatigue tailored for different treatment phases may be developed.

Effect of prophylactic tube feeding in head and neck cancer patients with high Mallampati score undergoing definitive concurrent chemoradiotherapy.

PURPOSE: There is no consensus on the selection of appropriate prophylactic tube feeding in patients with head and neck squamous cell carcinoma (HNSCC) undergoing concurrent chemoradiotherapy (CCRT). This study aimed to evaluate the effect of prophylactic tube feeding in patients with HNSCC who presented with a high Mallampati score and underwent CCRT. METHODS: We prospectively enrolled 185 consecutive patients with stage II to IVa HNSCC and a pre-treatment Mallampati score of 3 or 4 who received CCRT between August 2017 and December 2018 with follow-up data collected retrospectively. Patients were divided to either with or without prophylactic tube feeding group for comparison of treatment tolerance, toxicities, and quality of life(QOL). Propensity score matching (PSM) was used to achieve balanced covariates across the two groups. RESULTS: Of the cohort, 52 (28.1%) and 133 (71.9%) patients were allocated to the prophylactic and non-prophylactic tube feeding groups, respectively. Before and after PSM, patients in the tube feeding group had a significantly lower incidence of incomplete radiotherapy, incompletion of chemotherapy, emergency room visits, and grade 3 or higher infection, and improved symptoms of quality of life after CCRT than those in the non-tube feeding group. CONCLUSION: Prophylactic tube feeding was associated with better treatment tolerance, safety profiles, and quality of life in patients with HNSCC and high Mallampati scores who underwent CCRT. Therefore, Mallampati score might serve as a clinical tool for proactive selection of patients receiving prophylactic tube feeding in HNSCC patients upon receiving CCRT.

Quantitative Measurement of Perineural Invasion for Prognosis Analysis of Oral Cavity Cancer Treated by Radical Surgery With or Without Adjuvant Therapy.

Objectives: Perineural invasion (PNI) was quantitatively analyzed in oral squamous cell carcinoma (OSCC) specimens obtained by radical surgery to correlate with survival outcomes. Methods: This is a retrospective study that reviewed the Cancer registry data between 2009 and 2015. Inclusion criteria were oral cavity cancer, treatment by radical surgery, presence of PNI, and available pathologic samples for S100 staining. Patients with M1 disease and those with synchronous or metachronous cancer during staging work-up were excluded. All pathologic samples were reviewed to confirm PNI status and processed by immunohistochemical staining for S100 to quantify PNI. Pathologic information and staging results were also reviewed, and clinical outcomes were analyzed. Results: The retrospective study included 92 patients; 63 had intratumoral PNI (IPNI) and 29 had extratumoral PNI (EPNI). The average number of PNI foci (APNI) was higher in the EPNI group than in the IPNI group (6.7 vs 3.8, t-test 2-tail significance = 0.021). The 3-year overall survival (OS) and time-to-recurrence (TTR) rates of all patients were 82.5% and 81.2%, respectively. Univariate analysis showed that pathological T4 or N2-3 stage correlated with poor OS, whereas APNI ≥4 correlated with poor TTR. In multivariate analysis, only the pathological N2-3 stage was significantly correlated with poor OS, whereas only APNI ≥ 4 was an independent factor of poor TTR. The 3-year TTR rates were 92.4% and 65.6% for diseases with APNI < 4 and ≥ 4, respectively (P = .008). Conclusions: In patients with OSCC with PNI, a greater amount of PNI identified by S100 staining indicated a poorer TTR regardless of stage and other prognostic factors. Quantification of PNI by S100 immunohistochemistry is a potential method for prognosis prediction.

Autoimmune rheumatic diseases in women with coronary microvascular dysfunction: a report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) project.

Background: While autoimmune rheumatic diseases (ARDs) have been linked with coronary microvascular dysfunction (CMD), the relationship between ARD and CMD in women with signs and symptoms of ischemia and no obstructive arteries (INOCA) are not well described. We hypothesized that among women with CMD, those with ARD history have greater angina, functional limitations, and myocardial perfusion compromise compared to those without ARD history. Methods: Women with INOCA and confirmed CMD by invasive coronary function testing were included from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) project (NCT00832702). Seattle Angina Questionnaire (SAQ), Duke Activity Status Index (DASI), and cardiac magnetic resonance myocardial perfusion reserve index (MPRI) were collected at baseline. Chart review was performed to confirm self-reported ARD diagnosis. Results: Of the 207 women with CMD, 19 (9%) had a confirmed history of ARD. Compared to those without ARD, women with ARD were younger (p = 0.04). In addition, they had lower DASI-estimated metabolic equivalents (p = 0.03) and lower MPRI (p = 0.008) but similar SAQ scores. There was a trend towards increased nocturnal angina and stress-induced angina in those with ARD (p = 0.05 for both). Invasive coronary function variables were not significantly different between groups. Conclusions: Among women with CMD, women with a history of ARD had lower functional status and worse myocardial perfusion reserve compared to women without ARD. Angina-related health status and invasive coronary function were not significantly different between groups. Further studies are warranted to understand mechanisms contributing to CMD among women with ARDs with INOCA.

Molecular Signature of Long Non-Coding RNA Associated with Areca Nut-Induced Head and Neck Cancer.

The areca nut is a high-risk carcinogen for head and neck cancer (HNC) patients in Southeast Asia. The underlying molecular mechanism of areca nut-induced HNC remains unclear, especially regarding the role of long non-coding RNA (lncRNA). This study employed a systemic strategy to identify lncRNA signatures related to areca nut-induced HNC. In total, 84 cancer-related lncRNAs were identified. Using a PCR array method, 28 lncRNAs were identified as being dysregulated in HNC cells treated with areca nut (17 upregulated and 11 downregulated). Using bioinformatics analysis of The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset, 45 lncRNAs were differentially expressed in tumor tissues from HNC patients (39 over- and 6 under-expressions). The integrated evaluation showed 10 lncRNAs dysregulated by the areca nut and altered expression in patients, suggesting that these panel molecules participate in areca nut-induced HNC. Five oncogenic (LUCAT1, MIR31HG, UCA1, HIF1A-AS2, and SUMO1P3) and tumor-suppressive (LINC00312) lncRNAs were independently validated, and three key molecules were further examined. Pathway prediction revealed that LUCAT1, UCA1, and MIR31HG modulate multiple oncogenic mechanisms, including stress response and cellular motility. Clinical assessment showed that these lncRNAs exhibited biomarker potentials in diagnosis (area under the curve = 0.815 for LUCAT1) and a worse prognosis (both p < 0.05, survival analysis). Cellular studies further demonstrated that MIR31HG facilitates areca nut-induced cancer progression, as silencing this molecule attenuated arecoline-induced invasion ability in HNC cells. This study identified lncRNA signatures that play a role in areca nut-induced HNC. These molecules may be further applied in risk assessment, diagnosis, prognosis, and therapeutics for areca nut-associated malignancies.

Standardized Behavioral Treatment Improves Chronic Cough.

OBJECTIVES: Neurogenic Laryngeal Hypersensitivity (NLH) refers to a constellation of upper airway symptoms thought to be caused by a disturbance in afferent and/or efferent neural pathways creating an exaggerated hypersensitive laryngeal response. There is evidence to support behavioral therapy as treatment for improving symptoms from laryngeal motor dysfunction to sensory disturbance. This study aims to determine if there is significant symptomatic improvement in patients with NLH who received non-pharmacologic behavioral treatment performed by trained SLPs. STUDY DESIGN: A retrospective review. METHODS: A review of all patients with NLH from 2017 to 2020 was performed at a tertiary care voice and swallowing center. Subjects with persistent symptoms despite maximal medical management were considered for inclusion. Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ) was completed by patients before and after undergoing therapy by one of three trained SLPs. Posttherapy improvement was determined by utilizing the NLHQ's minimal clinically important difference of 1.7 points. RESULTS: A total of 81 patients were included in this study. Study participants included 61 women and 20 men with an average age of 60.64±14.05 years. There was a statistically significant difference between the pre and post therapy scores amongst all patients when treated by each individual SLP and all three SLPs combined (P < 0.008). There was a clinically significant change in 66% of all patients, 76% of which presented with abnormal NLHQ scores, and 14% who presented with normal NLHQ scores. CONCLUSIONS: A standardized behavioral treatment protocol for patients with symptoms consistent with NLH is effective in improving symptoms in a large majority of patients. When following a standardized protocol SLPs can obtain similar results for their patients.

Identification and characterization of select oxysterols as ligands for GPR17.

BACKGROUND AND PURPOSE: G-protein coupled receptor 17 (GPR17) is an orphan receptor involved in the process of myelination, due to its ability to inhibit the maturation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Despite multiple claims that the biological ligand has been identified, it remains an orphan receptor. EXPERIMENTAL APPROACH: Seventy-seven oxysterols were screened in a cell-free [35 S]GTPγS binding assay using membranes from cells expressing GPR17. The positive hits were characterized using adenosine 3',5' cyclic monophosphate (cAMP), inositol monophosphate (IP1) and calcium mobilization assays, with results confirmed in rat primary oligodendrocytes. Rat and pig brain extracts were separated by high-performance liquid chromatography (HPLC) and endogenous activator(s) were identified in receptor activation assays. Gene expression studies of GPR17, and CYP46A1 (cytochrome P450 family 46 subfamily A member 1) enzymes responsible for the conversion of cholesterol into specific oxysterols, were performed using quantitative real-time PCR. KEY RESULTS: Five oxysterols were able to stimulate GPR17 activity, including the brain cholesterol, 24(S)-hydroxycholesterol (24S-HC). A specific brain fraction from rat and pig extracts containing 24S-HC activates GPR17 in vitro. Expression of Gpr17 during mouse brain development correlates with the expression of Cyp46a1 and the levels of 24S-HC itself. Other active oxysterols have low brain concentrations below effective ranges. CONCLUSIONS AND IMPLICATIONS: Oxysterols, including but not limited to 24S-HC, could be physiological activators for GPR17 and thus potentially regulate OPC differentiation and myelination through activation of the receptor.

Modeling local coronavirus outbreaks.

This article presents an overview of methods developed for the modeling and control of local coronavirus outbreaks. The article reviews early transmission dynamics featuring exponential growth in infections, and links this to a renewal epidemic model where the current incidence of infection depends upon the expected value of incidence randomly lagged into the past. This leads directly to simple formulas for the fraction of the population infected in an unmitigated outbreak, and reveals herd immunity as the solution to an optimization problem. The model also leads to direct and easy-to-understand formulas for aligning observable epidemic indicators such as cases, hospitalizations and deaths with the unobservable incidence of infection, and as a byproduct leads to a simple first-order approach for estimating the effective reproduction number R t . The model also leads naturally to direct assessments of the effectiveness of isolation in preventing the spread of infection. This is illustrated with application to repeat asymptomatic screening programs of the sort utilized by universities, sports teams and businesses to prevent the spread of infection.

1-Year Results of Combined Modified Wendler Glottoplasty with Voice Therapy in Transgender Women.

BACKGROUND: To date, 1-year evaluation of pitch elevation in patients undergoing modified Wendler glottoplasty (WG) in combination with VT has not been assessed. OBJECTIVES: To determine whether 1-year pitch elevation is sustained in patients who undergo modified WG in combination with VT for voice feminization. METHODS: A retrospective review of patients who underwent WG in combination with voice therapy (VT) was performed from 2016 to 2020. Charts were reviewed for sustained vowel fundamental frequency (F0/a/), speaking fundamental frequency (SF0), and Trans Woman Voice Questionnaire (TWVQ) at preoperative, initial postoperative (3-6 months after surgery), and 12-month postoperative visits. RESULTS: Change in average F0/a/, SF0 and TWVQ was 50.25 Hz, 32.96 Hz, and 32.6 at 12-months postoperatively compared to preoperative values. Initial and 12-month postoperative SF0 were significantly higher than preoperative SF0 (Mann-Whitney U test p = 0.0042, p = 0.0010). There was no difference in initial postoperative and 12-month postoperative SF0 (p = 0.50). TWVQ at 12 months was significantly lower than preoperative TWVQ (ANOVA p < 0.001, Tukey honestly significant difference HSD p < 0.05). CONCLUSIONS: Pitch elevation remains sustained at one year in patients undergoing modified WG in combination with VT. Modified Wendler glottoplasty combined with VT results in relatively long-term improvements in voice-related quality of life and is possibly a beneficial addition in the long-term management of patients who desire voice feminization. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:615-620, 2023.