ETV5 promotes lupus pathogenesis and follicular helper T cell differentiation by inducing osteopontin expression.

Follicular helper T (TFH) cells mediate germinal center reactions to generate high affinity antibodies against specific pathogens, and their excessive production is associated with the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). ETV5, a member of the ETS transcription factor family, promotes TFH cell differentiation in mice. In this study, we examined the role of ETV5 in the pathogenesis of lupus in mice and humans. T cell-specific deletion of Etv5 alleles ameliorated TFH cell differentiation and autoimmune phenotypes in lupus mouse models. Further, we identified SPP1 as an ETV5 target that promotes TFH cell differentiation in both mice and humans. Notably, extracellular osteopontin (OPN) encoded by SPP1 enhances TFH cell differentiation by activating the CD44-AKT signaling pathway. Furthermore, ETV5 and SPP1 levels were increased in CD4+ T cells from patients with SLE and were positively correlated with disease activity. Taken together, our findings demonstrate that ETV5 is a lupus-promoting transcription factor, and secreted OPN promotes TFH cell differentiation.

Reduced-intensity conditioning with fludarabine/busulfan versus fludarabine/low-dose melphalan in patients with non-Hodgkin lymphoma undergoing allogeneic haematopoietic stem cell transplantation.

Reduced-intensity conditioning regimens are commonly used in allogeneic haematopoietic cell transplantation for non-Hodgkin lymphoma (NHL); however, the optimal regimen remains unknown. In this study, the outcomes of adult patients with NHL who received fludarabine plus reduced-dose busulfan (6.4 mg/kg; Flu/Bu2) (n = 286) and fludarabine plus low-dose melphalan (80 or 100 mg/m2; Flu/Mel80-100) (n = 283) between January 2009 and December 2020 were compared using Japanese registry data. The primary end-point was the 5-year overall survival (OS). The 5-year OS was 53.8% (95% CI, 47.6-59.6) and 42.4% (95% CI, 35.6-49.0) in the Flu/Bu2 and Flu/Mel80-100 groups respectively (p = 0.030). After inverse probability of treatment weighting adjustment, the adjusted HR of Flu/Bu2 compared with Flu/Mel80-100 group for 5-year OS was 0.77 (95% CI, 0.60-0.99, p = 0.046), 0.97 (95% CI, 0.78-1.21, p = 0.798) for 5-year progression-free survival, 0.65 (95% CI, 0.45-0.94, p = 0.022) for 5-year cumulative risk of non-relapse mortality and 1.25 (95% CI, 0.95-1.64, p = 0.115) for 5-year cumulative risk of relapse. In this study, patients with NHL who received Flu/Bu2 were associated with better OS and lower non-relapse mortality than those who received Flu/Mel80-100.

U-Shape Pillar Strip for 3D Cell-Lumped Organoid Model (3D-COM) Mimicking Lung Cancer Hypoxia Conditions in High-Throughput Screening (HTS).

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.

Scoring system for optimal cord blood unit selection for single cord blood transplantation.

BACKGROUND: We conducted a retrospective study to categorize the cord blood unit (CBU)s to identify the optimal units. METHODS: A total of 8503 adults (female, n = 3592; male, n = 4911) receiving their first single cord blood transplantation (CBT) in 2000-2019 were analyzed. Factors associated with CBUs affecting overall survival (OS) and neutrophil engraftment were selected to create ranked categorization for each outcome, followed by comparison with transplantation using HLA-matched bone marrow (BMT)/peripheral blood stem cell (PBSCT) from unrelated (n = 6052) and related donors (n = 4546). RESULTS: Sex-mismatch, CD34+ cell and CFU-GM counts were selected in the OS analysis. Considering the strong interaction between sex mismatch and CD34+ cell counts, we analyzed females and males separately. For females, female CBU with CD34+ cell counts {greater than or equal to} 0.5 × 10e5/kg and CFU-GM counts {greater than or equal to} 15 × 10e3/kg offered the best OS (Group I), followed by other groups with any (Groups II-IV) or all (Group V) of the risk factors. Group I consistently showed favorable OS (Group IV: HR1.22, P = 0.027; Group V: HR1.31, P = 0.047), comparable to those of rBMT/PBSCT (OS: HR1.02, P = 0.654) and uBM/PBSCT in patients with higher rDRI (HR1.07, P = 0.353). Male patients lacked significant factors affecting OS. Categorization for neutrophil engraftment consisting of CD34+ cell and CFU-GM counts, sex-mismatch, presence of donor-specific antibodies, and the number of HLA-mismatches was effective but not predicted OS. CONCLUSION: Our ranked categorizations sufficiently predicted female OS and engraftment. The best-ranked CBUs offered preferable outcomes comparable to conventional BM/PB donors in female but not in male patients.

Percutaneous insertion of long-covered biliary stents in patients with malignant duodenobiliary stricture.

OBJECTIVE: To investigate the technical feasibility, safety, and efficacy of a long-covered biliary stent in patients with malignant duodenobiliary stricture. METHODS: This retrospective study enrolled 57 consecutive patients (34 men, 23 women; mean age, 64 years; range, 32-85 years) who presented with malignant duodenobiliary stricture between February 2019 and November 2020. All patients were treated with a long (18 or 23 cm)-covered biliary stent. RESULTS: The biliary stent deployment was technically successful in all 57 patients. The overall adverse event rate was 17.5% (10 of 57 patients). Successful internal drainage was achieved in 55 (96.5%) of 57 patients. The median patient survival and stent patency times were 99 days (95% confidence interval [CI], 58-140 days) and 73 days (95% CI, 60-86 days), respectively. Fourteen (25.5%) of the fifty-five patients presented with biliary stent dysfunction due to sludge (n = 11), tumor overgrowth (n = 1), collapse of the long biliary stent by a subsequently inserted additional duodenal stent (n = 1), or rapidly progressed duodenal cancer (n = 1). A univariate Cox proportional hazards model did not reveal any independent predictor of biliary stent patency. CONCLUSIONS: Percutaneous insertion of a subsequent biliary stent was technically feasible after duodenal stent insertion. Percutaneous insertion of a long-covered biliary stent was safe and effective in patients with malignant duodenobiliary stricture. CLINICAL RELEVANCE STATEMENT: In patients with malignant duodenobiliary stricture, percutaneous insertion of a long-covered biliary stent was safe and effective regardless of duodenal stent placement. KEY POINTS: • Percutaneous insertion of long-covered biliary stents in patients with malignant duodenobiliary stricture is a safe and effective procedure. • Biliary stent deployment was technically successful in all 57 patients and successful internal drainage was achieved in 55 (96.5%) of 57 patients. • The median patient survival and stent patency times were 99 days and 73 days, respectively, after placement of a long-covered biliary stent in patients with duodenobiliary stricture.

An indirect comparative analysis of two posterior nasal nerve ablation techniques for treating chronic rhinitis: A systemic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis evaluates and compares the effects of two treatments that ablate the posterior nasal nerves for rhinitis-related symptoms: cryotherapy and radiofrequency neurolysis. METHODS: We reviewed studies retrieved from PubMed, SCOPUS, Embase, the Web of Science and the Cochrane database up to June 2023. Papers reporting quality-of-life and rhinitis-related symptom scores before and after cryotherapy, and sham-controlled studies, were analyzed. RESULTS: In total, 738 patients enrolled in 10 studies were evaluated. Both cryotherapy and radiofrequency neurolysis significantly improved rhinitis-related symptoms including congestion, itching, rhinorrhea, and sneezing, and quality of life during 12 months of follow-up. Radiofrequency neurolysis was significantly more effective than cryotherapy in terms of reducing total nasal symptom scores at up to 12 months postoperatively. In terms of individual symptoms, itching, rhinorrhea, and congestion were significantly alleviated or tended to be reduced more by radiofrequency neurolysis than by cryotherapy. The improvements in the minimal clinically important difference in total nasal symptom scores (1.0 point) after 3 months of cryotherapy and radiofrequency therapy were 81.8 % and 92.7 %, respectively. CONCLUSIONS: Cryotherapy and radiofrequency neurolysis both improved rhinitis-symptom and quality-of-life scores. Especially, radiofrequency neurolysis showed the better effectiveness for improving the nasal symptoms related to the rhinitis than cryotherapy.

Effectiveness of temperature-controlled radiofrequency neurolysis of the posterior nasal nerve to treat chronic rhinitis: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis evaluates the effect of TRNP on rhinitis-related symptoms. METHODS: We reviewed studies retrieved from PubMed, SCOPUS, Embase, the Web of Science, and the Cochrane database to June 2023. Studies that evaluated quality-of-life and rhinitis-related symptom scores before and after treatment were analyzed, as was one sham-treatment-controlled study. RESULTS: In total, 406 patients evaluated in five studies were analyzed. TRNP significantly improved rhinitis-related symptoms-congestion, itching, rhinorrhea, and sneezing-for up to 12 months after treatment, compared to before treatment. The most significant symptom decreases were those of rhinorrhea and nasal congestion. Rhinitis-related symptoms had improved significantly at 3 months after TRNP, compared to sham surgery. TRNP improved disease-specific quality-of-life scores on the Rhinoconjunctivitis Quality of Life Questionnaire at 6 months after treatment, compared to before treatment. The rates of clinical improvement in terms of all nasal symptoms (reduction > 30% from baseline) and in quality of life (minimal clinically important difference > 0.4) after TRNP were 79% and 84% respectively. There was no severe adverse event associated with either device use or the overall procedure. CONCLUSIONS: TRNP treatment improved subjective symptoms related to rhinitis, especially rhinorrhea and nasal congestion, and also improved disease-specific quality-of-life scores.

Empowering the Vehicular Network with RIS Technology: A State-of-the-Art Review.

Reconfigurable intelligent surfaces (RIS) are expected to bring about a revolutionary transformation in vehicular networks, thus paving the way for a future characterized by connected and automated vehicles (CAV). An RIS is a planar structure comprising many passive elements that can dynamically manipulate electromagnetic waves to enhance wireless communication by reflecting, refracting, and focusing signals in a programmable manner. RIS exhibits substantial potential for improving vehicle-to-everything (V2X) communication through various means, including coverage enhancement, interference mitigation, improving signal strength, and providing additional layers of privacy and security. This article presents a comprehensive survey that explores the emerging opportunities arising from the integration of RIS into vehicular networks. To examine the convergence of RIS and V2X communications, the survey adopted a holistic approach, thus highlighting the potential benefits and challenges of this combination. In this study, we examined several applications of RIS-aided V2X communication. Subsequently, we delve into the fundamental emerging technologies that are expected to empower vehicular networks, encompassing mobile edge computing (MEC), non-orthogonal multiple access (NOMA), millimeter-wave communication (mmWave), Artificial Intelligence (AI), and visible light communication (VLC). Finally, to stimulate further research in this domain, we emphasize noteworthy research challenges and potential avenues for future exploration.

Artificial General Intelligence for the Detection of Neurodegenerative Disorders.

Parkinson's disease and Alzheimer's disease are among the most common neurodegenerative disorders. These diseases are correlated with advancing age and are hence increasingly becoming prevalent in developed countries due to an increasingly aging demographic. Several tools are used to predict and diagnose these diseases, including pathological and genetic tests, radiological scans, and clinical examinations. Artificial intelligence is evolving to artificial general intelligence, which mimics the human learning process. Large language models can use an enormous volume of online and offline resources to gain knowledge and use it to perform different types of tasks. This work presents an understanding of two major neurodegenerative disorders, artificial general intelligence, and the efficacy of using artificial general intelligence in detecting and predicting these neurodegenerative disorders. A detailed discussion on detecting these neurodegenerative diseases using artificial general intelligence by analyzing diagnostic data is presented. An Internet of Things-based ubiquitous monitoring and treatment framework is presented. An outline for future research opportunities based on the challenges in this area is also presented.

Multi-Layered Unsupervised Learning Driven by Signal-to-Noise Ratio-Based Relaying for Vehicular Ad Hoc Network-Supported Intelligent Transport System in eHealth Monitoring.

Every year, about 1.19 million people are killed in traffic accidents; hence, the United Nations has a goal of halving the number of road traffic deaths and injuries by 2030. In line with this objective, technological innovations in telecommunication, particularly brought about by the rise of 5G networks, have contributed to the development of modern Vehicle-to-Everything (V2X) systems for communication. A New Radio V2X (NR-V2X) was introduced in the latest Third Generation Partnership Project (3GPP) releases which allows user devices to exchange information without relying on roadside infrastructures. This, together with Massive Machine Type Communication (mMTC) and Ultra-Reliable Low Latency Communication (URLLC), has led to the significantly increased reliability, coverage, and efficiency of vehicular communication networks. The use of artificial intelligence (AI), especially K-means clustering, has been very promising in terms of supporting efficient data exchange in vehicular ad hoc networks (VANETs). K-means is an unsupervised machine learning (ML) technique that groups vehicles located near each other geographically so that they can communicate with one another directly within these clusters while also allowing for inter-cluster communication via cluster heads. This paper proposes a multi-layered VANET-enabled Intelligent Transportation System (ITS) framework powered by unsupervised learning to optimize communication efficiency, scalability, and reliability. By leveraging AI in VANET solutions, the proposed framework aims to address road safety challenges and contribute to global efforts to meet the United Nations' 2030 target. Additionally, this framework's robust communication and data processing capabilities can be extended to eHealth monitoring systems, enabling real-time health data transmission and processing for continuous patient monitoring and timely medical interventions. This paper's contributions include exploring AI-driven approaches for enhanced data interaction, improved safety in VANET-based ITS environments, and potential applications in eHealth monitoring.

Development of a New Swine Model Resembling Human Empty Nose Syndrome.

Background and Objectives: Empty nose syndrome (ENS) is a debilitating condition that often results from traumatic or iatrogenic causes, such as nasal surgery. There are various conservative and surgical treatments for ENS, but their effectiveness remains uncertain. Therefore, the development of animal models that accurately mimic human ENS is essential for advancing effective treatment strategies. Materials and Methods: To investigate ENS development, turbinoplasty was performed in the nasal cavity of swine, entailing partial removal of the ventral turbinate using turbinectomy scissors followed by electrocauterization. After 56 days, samples were obtained for histological and morphological analyses. Results: A significant reduction in the volume of the ventral turbinate in the ENS model led to an expansion of the nasal cavity. Histological analysis revealed mucosal epithelial changes similar to those observed in ENS patients, including squamous cell metaplasia, goblet cell metaplasia, submucosal fibrosis, and glandular atrophy. Biomarkers related to these histopathological features were identified, and signals potentially contributing to squamous cell metaplasia were elucidated. Conclusions: The swine ENS model is anticipated to be instrumental in unraveling the pathogenesis of ENS and may also be useful for evaluating the effectiveness of various treatments for ENS.

Adverse impact of delay of platelet recovery after autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma and multiple myeloma.

BACKGROUND AIMS: The prognostic impact of platelet recovery after autologous hematopoietic cell transplantation (AHCT) on clinical outcomes remains to be elucidated. We aimed to clarify the impact of platelet recovery on clinical outcomes, risk factors of delayed platelet recovery and the necessary dose of CD34+ cells for prompt platelet recovery in each patient. METHODS: Using a nationwide Japanese registry database, we retrospectively analyzed clinical outcomes of 5222 patients with aggressive non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). RESULTS: At a landmark of 28 days after AHCT, a delay of platelet recovery was observed in 1102 patients (21.1%). Prompt platelet recovery was significantly associated with superior overall survival (hazard ratio [HR] 0.32, P < 0.001), progression-free survival (HR 0.48, P < 0.001) and decreased risks of disease progression (HR 0.66, P < 0.001) and non-relapse/non-progression mortality (HR 0.19, P < 0.001). The adverse impacts of a delay of platelet recovery seemed to be more apparent in NHL. In addition to the dose of CD34+ cells/kg, disease status, performance status and the hematopoietic cell transplant-specific comorbidity index in both diseases were associated with platelet recovery. We then stratified the patients into three risk groups according to these factors. For the purpose of achieving 70% platelet recovery by 28 days in NHL, the low-, intermediate- and high-risk groups needed more than 2.0, 3.0 and 4.0 × 106 CD34+ cells/kg, respectively. In MM, the low-risk group needed approximately 1.5 × 106 CD34+ cells/kg, whereas the intermediate- and high-risk groups required 2.0 and 2.5 × 106 CD34+ cells/kg to achieve about 80% platelet recovery by 28 days. CONCLUSIONS: A delay of platelet recovery after AHCT was associated with inferior survival outcomes.

Lenalidomide treatment for recurrent adult T-cell leukemia/lymphoma after allogeneic hematopoietic cell transplantation.

Patients with recurrent adult T-cell leukemia/lymphoma (ATL) after allogeneic hematopoietic cell transplantation (allo-HCT) have a dismal prognosis. We retrospectively evaluated the safety and efficacy of lenalidomide (LEN) in 11 consecutive patients with recurrent ATL after allo-HCT. The median time from allo-HCT to ATL recurrence was 111 days (range, 20-1476), and that from allo-HCT to the initiation of LEN was 162 days (range, 43-1560). The median initial daily dose of LEN was 10 mg (range, 5-25), and the median duration of LEN treatment was 37 days (range, 3-1078). Three patients (27%) achieved complete response and two (18%) achieved partial response (PR). The rates of complete or PR according to the involved site were 57% for skin and 50% for nodal or extranodal lesions. With a median follow-up of 1033 days (range, 601-1465) among survivors, the 1-year probability of overall survival (OS) after ATL recurrence was 55%. Grade ≥3 toxicities included cytopenia (n = 4), superficial vein thrombosis (n = 1), and deep vein thrombosis (n = 1). Graft-versus-host disease (GVHD) newly developed in five patients (45%) and worsened in four patients (36%). The median duration from the initiation of LEN to GVHD onset or worsening was 5 days (range, 1-9). GVHD was manageable in all patients. Seven patients received mogamulizumab (MOG) for recurrent ATL before LEN treatment. The overall response rates to LEN were 57% in patients who had previously received MOG and 25% in those who had not. The 1-year probabilities of OS after recurrent ATL were 71% in patients who had previously received MOG and 25% in those who had not. Although cytopenia and GVHD are common among patients with recurrent ATL after allo-HCT, LEN may improve survival. Administering MOG before LEN may augment treatment efficacy in the allo-HCT population.

Fludarabine plus reduced-intensity busulfan versus fludarabine plus myeloablative busulfan in patients with non-Hodgkin lymphoma undergoing allogeneic hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (HCT) offers a possible cure for patients with relapsed and refractory non-Hodgkin lymphoma (NHL) through potentially beneficial graft versus lymphoma effects. However, allogeneic HCT is associated with high nonrelapse mortality (NRM). Fludarabine with reduced-intensity busulfan (Flu/Bu2) and myeloablative busulfan (Flu/Bu4) are commonly used in conditioning regimens for allogeneic HCT; however, data on their use in patients with NHL is limited. We investigated the effect of busulfan dose on outcomes by comparing Flu/Bu2 and Flu/Bu4 in patients with NHL who underwent allogeneic HCT. Our study included 415 adult patients with NHL who received Flu/Bu2 (315 patients) or Flu/Bu4 (100 patients) between January 2008 and December 2019. All patients were enrolled in the Transplant Registry Unified Management Program 2 of the Japanese Data Center for Hematopoietic Cell Transplantation. The primary endpoint was the 5-year overall survival (OS). To minimize potential confounding factors that may influence outcomes, we performed propensity score matching. The 5-year OS was 50.6% (95% confidence interval (CI), 39.4%-60.8%) and 32.2% (95% CI, 22.4-42.4%) in the Flu/Bu2 and Flu/Bu4 groups, respectively (p = 0.006). The hazard ratio comparing the two groups was 2.13 (95% CI, 1.30-3.50; p = 0.003). Both groups had a similar 5-year cumulative incidence of relapse (38.2% vs 41.3%; p = 0.581), and the Flu/Bu4 group had a higher cumulative incidence of 5-year NRM (15.7% vs 31.9%; p = 0.043). In this study, Flu/Bu4 was associated with worse OS compared with Flu/Bu2 because of high NRM in patients with NHL.

Comparative effectiveness of hypoglossal nerve stimulation and alternative treatments for obstructive sleep apnea: a systematic review and meta-analysis.

Continuous positive airway pressure (CPAP) is the primary therapeutic modality for obstructive sleep apnea (OSA) management. However, despite efforts to encourage patients to comply with CPAP usage, long-term adherence remains low. Consequently, surgical intervention for OSA is considered a secondary option for patients who exhibit non-compliance with CPAP. Therefore, we conducted systematic review and meta-analysis assessed the relative effectiveness of hypoglossal nerve stimulation (HNS) treatment and alternative surgical interventions for managing OSA. Five databases were searched. Studies were included if they measured polysomnography parameters and assessed sleep apnea-related quality of life (Epworth Sleepiness Scale [ESS]) both before and after HNS, and compared these outcomes with control, CPAP, or airway surgery (uvulopalatopharyngoplasty, expansion sphincter pharyngoplasty, or tongue base surgery) groups. A total of 10 studies (2209 patients) met the inclusion criteria. Compared to other airway surgeries, the rates of post-treatment apnea-hypopnea index (AHI) < 10 and < 15 events/h were significantly lower in the HNS group (odds ratio [OR] 5.33, 95% confidence interval [CI] 1.21-23.42; and 2.73, 95% CI 1.30-5.71, respectively). Additionally, postoperative AHI was significantly lower in the HNS group than in all other airway surgery groups (AHI: mean difference [MD] -8.00, 95% CI -12.03 to-3.97 events/h). However, there were no significant differences in the rate of post-treatment AHI < 5 events/h (OR 1.93, 95% CI 0.74-5.06) or postoperative ESS score (MD 0.40, 95% CI-1.52 to 2.32) between the two groups. HNS is an effective option for selected patients with moderate-to-severe OSA and CPAP intolerance.

Diagnostic Performance of Six Ultrasound Risk Stratification Systems for Thyroid Nodules: A Systematic Review and Network Meta-Analysis.

BACKGROUND. Risk stratification systems for evaluating thyroid nodules on ultrasound use varying approaches to classify levels of suspicion for malignancy, leading to variable performance. OBJECTIVE. The purpose of this study was to perform a network meta-analysis comparing six risk stratification systems used to evaluate thyroid nodules on ultrasound in terms of their diagnostic performance for the detection of thyroid cancer. EVIDENCE ACQUISITION. Five bibliometric databases were searched for studies published through August 31, 2022, that compared at least two of six ultrasound risk stratification systems (the American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi [AACE/ACE/AME] system; American College of Radiology Thyroid Imaging Reporting and Data System [ACR TI-RADS]; the American Thyroid Association [ATA] risk stratification system; European Thyroid Association Thyroid Imaging Reporting and Data System [EU-TIRADS]; the Korean Thyroid Imaging Reporting and Data System [K-TIRADS] endorsed by the Korean Thyroid Association and the Korean Society of Thyroid Radiology; and the Thyroid Imaging Reporting and Data System developed by Kwak et al. [Kwak TIRADS]) in terms of their diagnostic performance for the detection of thyroid cancer, with cytologic or histologic evaluation used as a reference standard. The studies' risk of bias was evaluated using the Newcastle-Ottawa Scale. A meta-analysis of each system was performed to identify the risk category threshold that had the highest accuracy as well as the highest sensitivity and specificity at this threshold. Network meta-analysis was used to perform hierarchic ranking and identify the systems having the highest sensitivities and specificities at each system's most accurate threshold. EVIDENCE SYNTHESIS. The analysis included 39 studies with 49,661 patients. All studies were of fair (n = 17) or good (n = 22) quality. The most accurate risk category thresholds were class 3 (high risk) for the AACE/ACE/AME system, TR5 (highly suspicious) for ACR TI-RADS, EU-TIRADS 5 (high risk) for EU-TIRADS, 4c (moderate concern but not classic for malignancy) for Kwak TIRADS, K-TIRADS 5 (high suspicion) for K-TIRADS, and high suspicion for the ATA system. At these thresholds, the systems had sensitivity of 64-77% and specificity of 82-90%. Network meta-analysis identified the highest sensitivity and highest specificity for ACR TI-RADS, followed by K-TIRADS. CONCLUSION. Of six risk stratification systems, ACR TI-RADS had the highest diagnostic performance for the detection of thyroid nodules on ultrasound. CLINICAL IMPACT. This network meta-analysis can inform decisions regarding implementation of the risk stratification systems and can aid future system updates.

Phototoxicity-free blue light for enhancing therapeutic angiogenic efficacy of stem cells.

Low-level light therapy (LLLT) is a safe and noninvasive technique that has drawn attention as a new therapeutic method to treat various diseases. However, little is known so far about the effect of blue light for LLLT due to the generation of reactive oxygen species (ROS) that can cause cell damage. We introduced a blue organic light-emitting diode (bOLED) as a safe and effective light source that could generate a low amount of heat and luminance compared to conventional light sources (e.g., light-emitting diodes). We compared phototoxicity of bOLED light with different light fluences to human adipose-derived stem cells (hADSC). We further explored molecular mechanisms involved in the therapeutic efficacy of bOLED for enhancing angiogenic properties of hADSC, including intracellular ROS control in hADSCs. Using optimum conditions of bOLED light proposed in this study, photobiomodulation and angiogenic properties of hADSCs were enhanced. These findings might open new methods for using blue light in LLLT. Such methods can be implemented in future treatments for ischemic disease.

Relationship of estrogen synthesis capacity in the brain with obesity and self-control in men and women.

Gonadal hormones are linked to mechanisms that govern appetitive behavior and its suppression. Estrogens are synthesized from androgens by the enzyme aromatase, highly expressed in the ovaries of reproductive-aged women and in the brains of men and women of all ages. We measured aromatase availability in the amygdala using positron emission tomography (PET) with the aromatase inhibitor [11C]vorozole in a sample of 43 adult, normal-weight, overweight, or obese men and women. A subsample of 27 also completed personality measures to examine the relationship between aromatase and personality traits related to self-regulation and inhibitory control. Results indicated that aromatase availability in the amygdala was negatively associated with body mass index (BMI) (in kilograms per square meter) and positively correlated with scores of the personality trait constraint independent of sex or age. Individual variations in the brain's capacity to synthesize estrogen may influence the risk of obesity and self-control in men and women.

Efficacy and safety of endoscopic septoplasty for treating nasal septal deviations compared with conventional septoplasty: A systematic review and meta-analysis.

OBJECTIVES: We assessed the effects and safety of endoscopic septoplasty in patients with nasal septal deviations (NSD), compared with those of conventional septoplasty. DESIGN AND SETTING: Systematic review and meta-analysis. PARTICIPANTS: Patients who have undergone various endoscopic septoplasty procedure, such as hemitransfixion incision, incision at the deviated site and Killian incision, and conventional septoplasty. MAIN OUTCOME MEASURES: Six databases were searched up to April 2022. We analysed studies comparing improvements in NSD-related symptoms and post-operative complications between endoscopic septoplasty and control (conventional septoplasty) groups. RESULTS: A total of 38 articles with 2733 individuals were included. There were no significant differences in operative time (-0.4354, 95% confidence interval [CI: -1.1670; 0.2962]) or intra-operative bleeding (-1.3011 [-2.8003; 0.1981]) between the two groups. In the endoscopic septoplasty group, the change in nasal obstruction symptom evaluation score (9.5143 [5.4613; 13.5674] was statistically higher and the incidence of mucosal tearing (0.2766 [0.1889; 0.4049]) was lower. The incidences of full relief from symptoms such as headache (2.1996 [1.6896; 2.8634]), hyposmia (4.4468 [2.6806; 7.3767]), nasal obstruction (5.9871 [4.3292; 8.2800]), post-nasal drip (4.7241 [3.4086; 6.5472]) and snoring (2.9980 [1.2622; 7.1211]) were significantly higher in the endoscopic septoplasty group. In terms of post-operative endoscopic findings, epistaxis (0.3043 [0.1969; 0.4703]), hematoma (0.2022 [0.0785; 0.5213]), nasal obstruction 0.3373 [0.1334; 0.8527]), residual posterior septal deviation (0.1562 [0.0921; 0.2650]), septal perforation (0.2286 [0.1069; 0.4889]), residual spur (0.1294 [0.0602; 0.2780]) and synechia (0.2537 [0.1849; 0.3483]) were significantly less common in the endoscopic septoplasty group. CONCLUSION: Endoscopic septoplasty better relieved NSD-related symptoms and reduced surgery-related complications compared to conventional septoplasty.

Are statins effective in preventing chronic rhinosinusitis? A systematic review and meta-analysis.

OBJECTIVES: To evaluate the association between statin use and chronic rhinosinusitis (CRS). DESIGN AND SETTING: Systematic review and meta-analysis. The methodological quality of studies was assessed using the Newcastle-Ottawa scale. PARTICIPANTS: Patients with CRS. MAIN OUTCOME MEASURES: Pooled odds ratios (ORs) with 95% confidence interval (CIs) in analyses of studies that compared the prevalence of CRS, nasal polyp, difference of Lund-Kennedy endoscopic score, Lund-Mackay CT score and Sino-nasal Outcome Test-22. RESULTS: The analysis included eight studies and 445 465 patients. Patients who used statins were at lower risk for CRS than those who did not (OR = 0.7457, 95% CI = 0.6629-0.8388, p < 0.0001, I2 = 0.0%). Patients with hyperlipidaemia were at higher risk for CRS than those with normal serum levels of lipid (OR = 1.3590, 95% CI = 1.2831-1.4394, p < 0.0001, I2 = 33.3%). However, there were no significant differences in the risk for nasal polyps between CRS patients using statins or not (OR = 1.0931, 95% CI = 0.7860-1.5202, p = 0.5968, I2 = 0.0%). Additionally, statin use was not related to Lund-Kennedy endoscopic scores, Lund-Mackay CT scores or sino-nasal outcome test-22 scores in CRS patients. CONCLUSION: The risk for CRS is lower in patients who use statins and those without hyperlipidaemia.