A Phase 3, Randomized, Controlled Trial Evaluating the Efficacy and Safety of Ropeginterferon Alfa-2b in Patients with Moderate COVID-19.

INTRODUCTION: Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. This clinical study aimed to evaluate its antiviral efficacy of ropeginterferon alfa-2b against SARS-CoV-2 infection. METHODS: This is a multicenter, randomized, open-label study. Adult patients with confirmed SARS-CoV-2 infection with initial cycle threshold (Ct) value < 30 and symptom onset within 4 days were enrolled. Eligible patients were randomized in a 2:1 ratio to receive a single 250-µg dose of ropeginterferon alfa-2b subcutaneously plus standard of care (SOC) or to receive SOC alone. The primary endpoint was the proportion of patients with a negative RT-PCR result for SARS-CoV-2 or discharged from the hospital before Day 8. Change in clinical status based on the World Health Organization (WHO) clinical progression scale and pulmonary infiltrations through chest radiograph were also evaluated. RESULTS: A total of 132 patients were enrolled and treated with study medication. Higher percentages of patients who achieved Ct ≥ 30 or were discharged from the hospital were observed on Day 8 and every other time point of assessment, i.e., Days 5, 11, 15, and 22, in the ropeginterferon alfa-2b group compared to the SOC alone group. However, the difference was statistically significant on Day 11 but not on Day 8. The primary endpoint was not met. The ropeginterferon alfa-2b group showed a higher improvement rate in lung infiltration on Day 5 (27.6% vs. 0.0%, p = 0.0087) and a higher improvement rate in WHO clinical progression scores on Day 8 (69.4% vs. 35.3%, p = 0.03) than those in the SOC group. No ropeginterferon alfa-2b-related serious adverse event was observed. CONCLUSION: Our data show that ropeginterferon alfa-2b with SOC shortened the duration of SARS-CoV-2 shedding compared with SOC alone. In addition, ropeginterferon alfa-2b as an additional therapy could be beneficial by improving lung infiltration.

Positional obstructive sleep apnea and periodic limb movement during sleep: A large multi-center study.

Objectives: The relationships among positional obstructive sleep apnea (POSA), obstructive sleep apnea (OSA), and periodic limb movement during sleep (PLMS) are unclear. We analyzed these relationships according to OSA severity and explored the underlying mechanisms. Methods: We retrospectively reviewed 6,140 eligible participants who underwent full-night diagnostic polysomnography in four clinical centers over a period of 5 years with eventsynchronized analysis. The PLMS index (PLMI) and periodic limb movements with arousal index (PLMAI) were evaluated. The effects of POSA on the PLMI, PLMAI, and PLMS were analyzed according to OSA severity. Results: The mean PLMI and PLMAI, as well as PLMS prevalence, were significantly lower in those with severe OSA than in those with mild and moderate OSA. The mean PLMI was higher in mild OSA group than in control group. The mean PLMI (4.80 ± 12.71 vs. 2.59 ± 9.82 events/h, p < 0.001) and PLMAI (0.89 ± 3.66 vs. 0.53 ± 3.33 events/h, p < 0.001), and the prevalence of PLMS (11% vs. 5.3%, p < 0.001) were higher in patients with POSA than patients with non-POSA. This trend was particularly marked in severe OSA group (OR 1.55, 95%CI [1.07-2.27]) and less so in mild (OR 0.56, 95%CI [0.30-1.03]) and moderate (OR 1.82, 95%CI [0.99-3.34]) OSA groups. Conclusion: The POSA group tended to have a higher prevalence of PLMS, particularly in those with severe OSA. If PLMS is prominent, diagnosis and treatment of POSA and OSA may be considered.

Off-the-shelf CAR-T cell therapies for relapsed or refractory B-cell malignancies: latest update from ASH 2023 annual meeting.

Currently, many off-the-shelf chimeric antigen receptor (CAR)-T cell products are under investigation for the treatment of relapsed or refractory (R/R) B-cell neoplasms. Compared with autologous CAR-T cell therapy, off-the-shelf universal CAR-T cell therapies have many potential benefits, such as immediate accessibility for patients, stable quality due to industrialized manufacturing and additional infusions of CAR-T cells with different targets. However, critical challenges, including graft-versus-host disease and CAR-T cell elimination by the host immune system, still require extensive research. The most common technological approaches involve modifying healthy donor T cells via gene editing technology and altering different types of T cells. This article summarizes some of the latest data from preclinical and clinical studies of off-the-shelf CAR-T cell therapies in the treatment of R/R B-cell malignancies from the 2023 ASH Annual Meeting (ASH 2023).

Transcription Factor E3/Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Axis in Renal Cell Carcinoma Affects Tumor Microenvironment.

The role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been investigated thoroughly. Transcription factor E3 (TFE3) expression is related to a poorer prognosis and tumor microenvironment in patients with RCC. This study aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 down-regulation was achieved by transient transfection of siRNA and shRNA in UOK146 cells. TFE3 overexpression was induced by transient transfection with pcDNA3.1 encoding the constitutively active form of TFE3. The cells were treated with mammalian target of rapamycin and PI3K inhibitors. Western blot was performed to detect TFE3, programmed death-ligand 1, phospho-Akt, and Akt. Phospho-Akt expression increased significantly upon TFE3 down-regulation, and decreased significantly upon up-regulation. When RCC cells were treated with a PI3K inhibitor (LY294002), TFE3 expression increased and phospho-Akt expression decreased. TFE3 is related to the PI3K/Akt pathway in RCC, and the results of this study suggest that PI3K/Akt inhibitors potentially may aid in treatment of patients with RCC by affecting the tumor microenvironment.

Dynamics of Information Flow and Task Allocation of Social Insect Colonies: Impacts of Spatial Interactions and Task Switching.

Models of social interaction dynamics have been powerful tools for understanding the efficiency of information spread and the robustness of task allocation in social insect colonies. How workers spatially distribute within the colony, or spatial heterogeneity degree (SHD), plays a vital role in contact dynamics, influencing information spread and task allocation. We used agent-based models to explore factors affecting spatial heterogeneity and information flow, including the number of task groups, variation in spatial arrangements, and levels of task switching, to study: (1) the impact of multiple task groups on SHD, contact dynamics, and information spread, and (2) the impact of task switching on SHD and contact dynamics. Both models show a strong linear relationship between the dynamics of SHD and contact dynamics, which exists for different initial conditions. The multiple-task-group model without task switching reveals the impacts of the number and spatial arrangements of task locations on information transmission. The task-switching model allows task-switching with a probability through contact between individuals. The model indicates that the task-switching mechanism enables a dynamical state of task-related spatial fidelity at the individual level. This spatial fidelity can assist the colony in redistributing their workforce, with consequent effects on the dynamics of spatial heterogeneity degree. The spatial fidelity of a task group is the proportion of workers who perform that task and have preferential walking styles toward their task location. Our analysis shows that the task switching rate between two tasks is an exponentially decreasing function of the spatial fidelity and contact rate. Higher spatial fidelity leads to more agents aggregating to task location, reducing contact between groups, thus making task switching more difficult. Our results provide important insights into the mechanisms that generate spatial heterogeneity and deepen our understanding of how spatial heterogeneity impacts task allocation, social interaction, and information spread.

Effects of glossopharyngeal nerve block on pain control after tonsillectomy: a systemic review and meta-analysis.

BACKGROUND: We investigated the role of perioperative intraoral glossopharyngeal nerve block to minimize postoperative pain in patients undergoing tonsillectomy through a meta-analysis of the relevant literature. METHODS: We retrieved eight studies from PubMed, Scopus, Embase, Web of Science, and Cochrane databases up to August 2023. We compared perioperative glossopharyngeal nerve block with a control group, in order to examine postoperative pain, analgesic use, and other postoperative morbidities. RESULTS: Postoperative pain was significantly reduced at 1-4 h (SMD -1.26, 95% CI [-2.35; -0.17], I2 = 94.7%, P = 0.02) and 5-8 hours (SMD -1.40, 95% CI [-2.47; -0.34], I2 = 96.1%, p = 0.01) in the treatment groups compared to the control group. However, glossopharyngeal nerve block showed no efficacy in reducing pain or use of analgesic drugs after 12 h compared to the control group. The incidences of postoperative bleeding (OR 0.95, 95% CI [0.35; 2.52], I2 = 0.0%), local agent toxicity (OR 4.14, 95% CI [0.44; 38.63], I2 = 0.0%), nasal problems (OR 1.25, 95% CI [0.60; 2.61], I2 = 0.0%), postoperative nausea and vomiting (OR 1.35, 95% CI [0.78; 2.33], I2 = 0.0%), swallowing difficulty (OR 1.61, 95% CI [0.76; 3.42], I2 = 56.0%), and voice change (OR 3.11, 95% CI [0.31; 30.80], I2 = 0.0%) were not significantly different between the treatment and control groups. The treatment group showed higher prevalence of respiratory problems and dry mouth compared to control without statistical significance, but a significant increase in throat discomfort (p = 0.02). CONCLUSION: Intraoral glossopharyngeal nerve block for tonsillectomy did not significantly impact postoperative pain management and was associated with some adverse effects with increases in respiratory problems, dry mouth, and throat discomfort compared to controls.

Pyrolysis temperature and time of rice husk biochar potentially control ammonia emissions and Chinese cabbage yield from urea-fertilized soils.

Current agricultural practices are increasingly favoring the biochar application to sequester carbon, enhance crop growth, and mitigate various environmental pollutants resulting from nitrogen (N) loss. However, since biochar's characteristics can vary depending on pyrolysis conditions, it is essential to determine the optimal standard, as they can have different effects on soil health. In this study, we categorized rice husk biochars basis on their pH levels and investigated the role of each rice husk biochar in reducing ammonia (NH3) emissions and promoting the growth of Chinese cabbage in urea-fertilized fields. The findings of this study revealed that the variation in pyrolysis conditions of rice husk biochars and N rates affected both the NH3 emissions and crop growth. The neutral (pH 7.10) biochar exhibited effective NH3 volatilization reduction, attributed to its high surface area (6.49 m2 g-1), outperforming the acidic (pH 6.10) and basic (pH 11.01) biochars, particularly under high N rates (640 kg N ha-1). Chinese cabbage yield was highest, reaching 4.00 kg plant-1, with the basic biochar application with high N rates. Therefore, the neutral rice husk biochar effectively mitigate the NH3 emissions from urea-treated fields, while the agronomic performance of Chinese cabbage enhanced in all biochar amendments.

Highly Selective and Reversible Detection of Simulated Breath Hydrogen Sulfide Using Fe-Doped CuO Hollow Spheres: Enhanced Surface Redox Reaction by Multi-Valent Catalysts.

The precise and reversible detection of hydrogen sulfide (H2 S) at high humidity condition, a malodorous and harmful volatile sulfur compound, is essential for the self-assessment of oral diseases, halitosis, and asthma. However, the selective and reversible detection of trace concentrations of H2 S (≈0.1 ppm) in high humidity conditions (exhaled breath) is challenging because of irreversible H2 S adsorption/desorption at the surface of chemiresistors. The study reports the synthesis of Fe-doped CuO hollow spheres as H2 S gas-sensing materials via spray pyrolysis. 4 at.% of Fe-doped CuO hollow spheres exhibit high selectivity (response ratio ≥ 34.4) over interference gas (ethanol, 1 ppm) and reversible sensing characteristics (100% recovery) to 0.1 ppm of H2 S under high humidity (relative humidity 80%) at 175 °C. The effect of multi-valent transition metal ion doping into CuO on sensor reversibility is confirmed through the enhancement of recovery kinetics by doping 4 at.% of Ti- or Nb ions into CuO sensors. Mechanistic details of these excellent H2 S sensing characteristics are also investigated by analyzing the redox reactions and the catalytic activity change of the Fe-doped CuO sensing materials. The selective and reversible detection of H2 S using the Fe-doped CuO sensor suggested in this work opens a new possibility for halitosis self-monitoring.

Combining wireless radar sleep monitoring device with deep machine learning techniques to assess obstructive sleep apnea severity.

STUDY OBJECTIVES: The gold standard for diagnosing obstructive sleep apnea (OSA) is polysomnography (PSG). However, PSG is a time-consuming method with clinical limitations. This study aimed to create a wireless radar framework to screen the likelihood of two levels of OSA severity (i.e., moderate-to-severe and severe OSA) in accordance with clinical practice standards. METHODS: We conducted a prospective, simultaneous study using the wireless radar system and PSG in a Northern Taiwan sleep center, involving 196 patients. The wireless radar sleep monitor, incorporating hybrid models such as deep neural decision trees, estimated the respiratory disturbance index relative to the total sleep time established by PSG (RDIPSG_TST), by analyzing continuous-wave signals indicative of breathing patterns. Analyses were performed to examine the correlation and agreement between the RDIPSG_TST and apnea-hypopnea index (AHI), results obtained through PSG. Cut-off thresholds for RDIPSG_TST were determined using Youden's index, and multiclass classification was performed, after which the results were compared. RESULTS: A strong correlation (ρ = 0.91) and agreement (average difference of 0.59 events/h) between AHI and RDIPSG_TST were identified. In terms of the agreement between the two devices, the average difference between PSG-based AHI and radar-based RDIPSG_TST was 0.59 events/h, while 187 out of 196 cases (95.41%) fell within the 95% confidence interval of differences. A moderate-to-severe OSA model achieved an accuracy of 90.3% (cut-off threshold for RDIPSG_TST: 19.2 events/h). A severe OSA model achieved an accuracy of 92.4% (cut-off threshold for RDIPSG_TST: 28.86 events/h). The mean accuracy of multiclass classification performance using these cut-off thresholds was 83.7%. CONCLUSIONS: The wireless-radar-based sleep monitoring device, with cut-off thresholds, can provide rapid OSA screening with acceptable accuracy, and also alleviate the burden on PSG capacity. However, to independently apply this framework, the function of determining the radar-based total sleep time requires further optimizations and verification in future work.

Suicide warning signs that are challenging to recognize: a psychological autopsy study of Korean adolescents.

BACKGROUND: In South Korea, the leading cause of youth death has been suicide for about 20 years. In this study, we conducted a multi-method psychological autopsy to identify the psychiatric diagnosis, developmental history, personality traits, family history, school life, warning signs of suicide, and risk factors related to suicide for the first time in Korea. METHODS: This was a postmortem, retrospective, and descriptive study of 36 adolescents who died by suicide between August 2015 and July 2021 in South Korea. We obtained qualitative and quantitative data from the Korean Psychological Autopsy of Adolescent, conducted by the Suicide and School Mental Health Institute, the official student mental health policy-focused research institute of the Korean Ministry of Education. RESULTS: The adolescents comprised equal percentage of girls and boys. Approximately half of the deaths (55.6%) occurred at home and most (72.2%) involved jumping from a height. Most of the adolescents (97.2%) had one major psychiatric disorder before death, with depressive disorder being the most prevalent (75%). They were at a high risk for internet addiction before death. The most common personality trait was avoidance (28.6%), followed by submissiveness (27.3%). Half of the parents reported that the adolescents were satisfied with their school life and the teachers observed that they had no behavioral problems. One year before death, seven (19.4%) adolescents injured themselves and five (13.9%) had attempted suicide. Most of the deceased (80.6%) had expressed suicide warning signs to their families within one year before death. Adolescents had a long experience of family-related adverse events. CONCLUSIONS: Most of the adolescents had mental health disorders and expressed suicidal intentions using verbal and nonverbal signs. However, it was challenging for families to recognize the risk signs because of adolescents' personality traits or a good school life. To prevent adolescent suicide, adolescents, parents, and teachers need to be educated to recognize signs of suicide warning signs and equipped to guide adolescents to appropriate care.

Investigation of Interface Characteristics and Physisorption Mechanism in Quantum Dots/TiO2 Composite for Efficient and Sustainable Photoinduced Interfacial Electron Transfer.

Owing to their superior stability compared to those of conventional molecular dyes, as well as their high UV-visible absorption capacity, which can be tuned to cover the majority of the solar spectrum through size adjustment, quantum dot (QD)/TiO2 composites are being actively investigated as photosensitizing components for diverse solar energy conversion systems. However, the conversion efficiencies and durabilities of QD/TiO2-based solar cells and photocatalytic systems are still inferior to those of conventional systems that employ organic/inorganic components as photosensitizers. This is because of the poor adsorption of QDs onto the TiO2 surface, resulting in insufficient interfacial interactions between the two. The mechanism underlying QD adsorption on the TiO2 surface and its relationship to the photosensitization process remain unclear. In this study, we established that the surface characteristics of the TiO2 semiconductor and the QDs (i.e., surface defects of the metal oxide and the surface structure of the QD core) directly affect the QD adsorption capacity by TiO2 and the interfacial interactions between the QDs and TiO2, which relates to the photosensitization process from the photoexcited QDs to TiO2 (QD* → TiO2). The interfacial interaction between the QDs and TiO2 is maximized when the shape/thickness-modulated triangular QDs are composited with defect-rich anatase TiO2. Comprehensive investigations through photodynamic analyses and surface evaluation using X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and photocatalysis experiments collectively validate that tuning the surface properties of QDs and modulating the TiO2 defect concentration can synergistically amplify the interfacial interaction between the QDs and TiO2. This augmentation markedly improved the efficiency of photoinduced electron transfer from the photoexcited QDs to TiO2, resulting in significantly increased photocatalytic activity of the QD/TiO2 composite. This study provides the first in-depth characterization of the physical adhesion of QDs dispersed on a heterogeneous metal-oxide surface. Furthermore, the prepared QD/TiO2 composite exhibits exceptional adsorption stability, resisting QD detachment from the TiO2 surface over a wide pH range (pH = 2-12) in aqueous media as well as in nonaqueous solvents during two months of immersion. These findings can aid the development of practical QD-sensitized solar energy conversion systems that require the long-term stability of the photosensitizing unit.

Comparison of Liquid-Based Preparations with Conventional Smears in Thyroid Fine-Needle Aspirates: A Systematic Review and Meta-Analysis.

BACKGROUND: To compare conventional smears (CSs) and liquid-based preparations (LBPs) for diagnosing thyroid malignant or suspicious lesions. METHODS: Studies in the PubMed, SCOPUS, Embase, Web of Science, and Cochrane database published up to December 2023. We reviewed 17 studies, including 15,861 samples. RESULTS: The diagnostic odds ratio (DOR) for CS was 23.6674. The area under the summary receiver operating characteristic curve (AUC) was 0.879, with sensitivity, specificity, negative predictive value, and positive predictive value of 0.8266, 0.8668, 0.8969, and 0.7841, respectively. The rate of inadequate specimens was 0.1280. For LBP, the DOR was 25.3587, with an AUC of 0.865. The sensitivity, specificity, negative predictive value, and positive predictive value were 0.8190, 0.8833, 0.8515, and 0.8562. The rate of inadequate specimens was 0.1729. For CS plus LBP, the AUC was 0.813, with a lower DOR of 9.4557 compared to individual methods. Diagnostic accuracy did not significantly differ among CS, LBP, and CS plus LBP. Subgroup analysis was used to compare ThinPrep and SurePath. The DORs were 29.1494 and 19.7734. SurePath had a significantly higher AUC. CONCLUSIONS: There was no significant difference in diagnostic accuracy or proportion of inadequate smears between CS and LBP. SurePath demonstrated higher diagnostic accuracy than ThinPrep. Recommendations for fine-needle aspiration cytology should consider cost, feasibility, and accuracy.

Scalable Dry Process for Fabricating a Na Superionic Conductor-Type Solid Electrolyte Sheet.

The cost reduction and mass production of oxide-based solid electrolytes are critical for the commercialization of all-solid-state batteries. In this study, an environmentally friendly, low-cost, and high-density oxide-based Na superionic conductor-type solid electrolyte sheet was fabricated via a dry process without the use of any solvent. The polytetrafluoroethylene (PTFE), used as a binder, was transformed into thin thread-like structures via shear force, resulting in a flexible solid electrolyte sheet. The solid electrolyte powder quantity was limited to 50 wt % for fabricating a uniform green sheet via the wet process. However, when the dry process was employed for green sheet fabrication, the solid electrolyte powder quantity could be increased to values exceeding 95 wt %. Therefore, the green sheets produced by using the dry process demonstrated a higher density than those fabricated by using the wet process. The binder content and particle size affected the ionic conductivity of a solid electrolyte sheet fabricated via a dry process. The sheet obtained via the blending of 3 wt % PTFE binder with a solid electrolyte powder, finely ground using a planetary ball mill, which exhibited the highest total ionic conductivity of 1.03 mS cm-1.

Surgical safety and effectiveness of bilateral axillo-breast approach robotic thyroidectomy: a systematic review and meta-analysis.

OBJECTIVES: To assess the safety and effectiveness of bilateral axillo-breast approach robotic thyroidectomy in thyroid tumor. METHODS: Bilateral axillo-breast approach robotic thyroidectomy and other approaches (open thyroidectomy, transoral robotic thyroidectomy, and bilateral axillo-breast approach endoscopic thyroidectomy) were compared in studies from 6 databases. RESULTS: Twenty-two studies (8830 individuals) were included. Bilateral axillo-breast approach robotic thyroidectomy had longer operation time, greater cosmetic satisfaction, and reduced transient hypoparathyroidism than conventional open thyroidectomy. Compared to bilateral axillo-breast approach endoscopic thyroidectomy, bilateral axillo-breast approach robotic thyroidectomy had greater amount of drainage, lower chances of transient vocal cord palsy and permanent hypothyroidism, and better surgical completeness (postopertive thyroblobulin level and lymph node removal). Bilateral axillo-breast approach robotic thyroidectomy induced greater postoperative drainage and greater patient dissatisfaction than transoral robotic thyroidectomy. CONCLUSION: Bilateral axillo-breast approach robotic thyroidectomy is inferior to transoral robotic thyroidectomy in drainage and cosmetic satisfaction but superior to bilateral axillo-breast approach endoscopic thyroidectomy in surgical performance. Its operation time is longer, but its cosmetic satisfaction is higher than open thyroidectomy.

Baseline Serum Inflammatory Proteins Predict Poor CAR T Outcomes in Diffuse Large B-cell Lymphoma.

A subset of patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 chimeric antigen receptor (CAR) T-cell therapy have poor clinical outcomes. We report serum proteins associated with severe immune-mediated toxicities and inferior clinical responses in 146 patients with DLBCL treated with axicabtagene ciloleucel. We develop a simple stratification based on pre-lymphodepletion C reactive protein (CRP) and ferritin to classify patients into low-, intermediate-, and high-risk groups. We observe that patients in the high-risk category were more likely to develop grade ≥3 toxicities and had inferior overall and progression-free survival. We sought to validate our findings with two independent international cohorts demonstrating that patients classified as low-risk have excellent efficacy and safety outcomes. Based on routine and readily available laboratory tests that can be obtained prior to lymphodepleting chemotherapy, this simple risk stratification can inform patient selection for CAR T-cell therapy. SIGNIFICANCE: CAR T-cell therapy has changed the treatment paradigm for patients with relapsed/refractory hematologic malignancies. Despite encouraging efficacy, a subset of patients have poor clinical outcomes. We show that a simple clinically applicable model using pre-lymphodepletion CRP and ferritin can identify patients at high risk of poor outcomes. This article is featured in Selected Articles from This Issue, p. 80.

Synergistic Integration of Machine Learning with Microstructure/Composition-Designed SnO2 and WO3 Breath Sensors.

A high-performance semiconductor metal oxide gas sensing strategy is proposed for efficient sensor-based disease prediction by integrating a machine learning methodology with complementary sensor arrays composed of SnO2- and WO3-based sensors. The six sensors, including SnO2- and WO3-based sensors and neural network algorithms, were used to measure gas mixtures. The six constituent sensors were subjected to acetone and hydrogen environments to monitor the effect of diet and/or irritable bowel syndrome (IBS) under the interference of ethanol. The SnO2- and WO3-based sensors suffer from poor discrimination ability if sensors (a single sensor or multiple sensors) within the same group (SnO2- or WO3-based) are separately applied, even when deep learning is applied to enhance the sensing operation. However, hybrid integration is proven to be effective in discerning acetone from hydrogen even in a two-sensor configuration through the synergistic contribution of supervised learning, i.e., neural network approaches involving deep neural networks (DNNs) and convolutional neural networks (CNNs). DNN-based numeric data and CNN-based image data can be exploited for discriminating acetone and hydrogen, with the aim of predicting the status of an exercise-driven diet and IBS. The ramifications of the proposed hybrid sensor combinations and machine learning for the high-performance breath sensor domain are discussed.

Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma.

Multiple myeloma (MM) bears heterogeneous cells that poses a challenge for single-target immunotherapies. Here we constructed bispecific CS1-BCMA CAR-T cells aiming to augment BCMA targeting with CS1. Sixteen patients with relapsed or refractory (RR) MM received CS1-BCMA CAR-T infusion. Six patients (38%) had cytokine release syndrome, which was of grade 1-2 in 31%. No neurological toxicities were observed. The most common severe adverse events were hematological, including leukopenia (100%), neutropenia (94%), lymphopenia (100%) and thrombocytopenia (31%). Three patients with solitary extramedullary disease (sEMD) did not respond. At a median follow-up of 246 days, 13 patients (81%) had an overall response and attained minimal residual disease-negativity, and six (38%) reached a stringent complete response (sCR). Among the 13 responders, 1-year overall survival and progression-free survival were 72.73% and 56.26%, respectively. Four patients maintained sCR with a median duration of 17 months. Four patients experienced BCMA+ and CS1+ relapse or progression. One patient responded after anti-BCMA CAR-T treatment failure. Lenalidomide maintenance after CAR-T infusion and the resistance mechanism of sEMD were preliminarily explored in three patients. CAR-T cells persisted at a median of 406 days. Soluble BCMA could serve as an ideal biomarker for efficacy monitoring. CS1-BCMA CAR-T cells were clinically active with good safety profiles in patients with RRMM. Clinical trial registration: This study was registered on ClinicalTrials.gov, number NCT04662099.

Efficacy of HIFU for the treatment of benign thyroid nodules: a systematic review and meta-analysis.

OBJECTIVE: Thyroid nodules are common and sometimes associated with cosmetic issues. Surgical treatment has several disadvantages, including visible scarring. High-intensity focused ultrasound (HIFU) is a recent noninvasive treatment for thyroid nodules. The present study aims to evaluate the effectiveness and safety of HIFU for the treatment of benign thyroid nodules. METHODS: We searched PubMed, Embase, and Cochrane Library for studies evaluating the outcomes of HIFU for patients with benign thyroid nodules. We conducted a meta-analysis by using a random effects model and evaluated the volume reduction ratio, treatment success rate, and incidence of treatment-related complications. RESULTS: Thirty-two studies were included in the systematic review. Only 14 studies were used in the meta-analysis because the other 18 involved data collected during overlapping periods. The average volume reduction ratios at 3, 6, and 12 months after treatment were 39.02% (95% CI: 27.57 to 50.47%, I2: 97.9%), 48.55% (95% CI: 35.53 to 61.57%, I2: 98.2%), and 55.02% (95% CI: 41.55 to 68.48%, I2: 99%), respectively. Regarding complications, the incidences of vocal cord paresis and Horner's syndrome after HIFU were 2.1% (95% CI: 0.2 to 4.1%, I2: 14.6%) and 0.7% (95% CI: 0 to 1.9%, I2: 0%), respectively. CONCLUSIONS: HIFU is an effective and safe treatment option for patients with benign thyroid nodules. However, the effects of HIFU on nodules of large sizes and with different properties require further investigation. Additional studies, particularly randomized controlled trials involving long-term follow-up, are warranted. CLINICAL RELEVANCE STATEMENT: Surgical treatment for thyroid nodules often results in permanent visible scars and is associated with a risk of bleeding, nerve injury, and hypothyroidism. High-intensity focused ultrasound may be an alternative for patients with benign thyroid nodules. KEY POINTS: • The success rate of HIFU treatment for thyroid nodules is 75.8% at 6 months. Average volume reduction ratios are 48.55% and 55.02% at 6 and 12 months. • The incidence of complications such as vocal fold paresis, Horner's syndrome, recurrent laryngeal nerve palsy, hypothyroidism, and skin redness is low. • HIFU is both effective and safe as a treatment for benign thyroid nodules.

Synthesis of Iron Sulfide Nanocrystals Encapsulated in Highly Porous Carbon-Coated CNT Microsphere as Anode Materials for Sodium-Ion Batteries.

Highly porous carbon materials with a rationally designed pore structure can be utilized as reservoirs for metal or nonmetal components. The use of small-sized metal or metal compound nanoparticles, completely encapsulated by carbon materials, has attracted significant attention as an effective approach to enhancing sodium ion storage properties. These materials have the ability to mitigate structural collapse caused by volume expansion during the charging process, enable short ion transport length, and prevent polysulfide elution. In this study, a concept of highly porous carbon-coated carbon nanotube (CNT) porous microspheres, which serve as excellent reservoir materials is suggested and a porous microsphere is developed by encapsulating iron sulfide nanocrystals within the highly porous carbon-coated CNTs using a sulfidation process. Furthermore, various sulfidation processes to determine the optimal method for achieving complete encapsulation are investigated by comparing the morphologies of diverse iron sulfide-carbon composites. The fully encapsulated structure, combined with the porous carbon, provides ample space to accommodate the significant volume changes during cycling. As a result, the porous iron sulfide-carbon-CNT composite microspheres exhibited outstanding cycling stability (293 mA h g-1 over 600 cycles at 1 A g-1 ) and remarkable rate capability (100 mA h g-1 at 5 A g-1 ).

Effectiveness of Radiofrequency Device Treatment for Nasal Valve Collapse in Patients With Nasal Obstruction.

OBJECTIVE: Internal nasal valve dysfunction is a prevalent cause of nasal obstruction. This systematic review, along with a Meta-analysis, evaluated the efficacy of temperature-controlled radiofrequency device (RFD) treatment in alleviating nasal obstruction by rectifying nasal valve collapse. DATA SOURCES: A comprehensive review of studies retrieved from PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases (up to December 2022) was conducted. REVIEW METHODS: We included studies that evaluated the quality of life and nasal obstruction scores before and after RFD treatment. In addition, sham-controlled studies were analyzed. RESULTS: In total, 451 patients across 8 studies were included in the analysis. Patients who underwent RFD treatment reported a significantly enhanced quality of life 24 months after treatment compared to pretreatment scores. The rates of clinically improved states and positive responses regarding quality of life after treatment were 82% and 91%, respectively. Moreover, the disease-specific quality of life, as assessed by the Nasal Obstruction Symptom Evaluation score, significantly improved. CONCLUSION: RFD may help improve nasal obstruction symptoms. Further randomized clinical studies on larger cohorts are essential to substantiate its efficacy in enhancing nasal valve function.