Real-Time Imaging of Calcium Dynamics in Human Sperm After Precise Single-Cell Stimulation.

Calcium signaling is a critical regulator of sperm activation and function during the processes of capacitation and fertilization. Here, we describe a combined method for calcium imaging of single, live human sperm in response to stimuli administered with a precisely targeted delivery technique. This protocol is an adaptation of techniques developed for studies of murine sperm [1, 2], and enables real-time monitoring of human sperm calcium dynamics with high spatiotemporal resolution and concurrent detection of acrosome exocytosis (AE), a functional endpoint of sperm capacitation and requirement for physiological fertilization.The described imaging technique provides a valuable tool for exploration of calcium regulation in human sperm, which is essential to answer important questions and knowledge gaps regarding the link between calcium dynamics, AE, and fertilization. The versatility of this technique can be amplified through use of various indicator dyes or integration with pharmacological strategies such as pre-treating sperm with inhibitors or activators targeting specific receptors, channels, or intracellular signaling pathways of interest. Beyond fundamental inquiries into sperm physiology, this method can also be applied to assess the impact of potential contraceptive compounds on calcium signaling, AE, and membrane integrity.

Prevalência de Influenza A, vírus sincicial respiratório eSARS-CoV-2 em pacientes com síndrome respiratóriaaguda grave em Passo Fundo, Rio Grande do Sul / Prevalence of Influenza A, respiratory syncytial virus andSARS-CoV-2 in patients with severe acute respiratorysyndrome in Passo Fundo, Rio Grande do Sul

A síndrome respiratória aguda grave (SRAG) é caracterizada por sintomas de febre alta, tosse e dispneia, e, na maioria dos casos, relacionada a uma quantidade reduzida de agentes infecciosos. O objetivo foi avaliar a prevalência dos vírus respiratórios Influenza A (FluA), vírus sincicial respiratório (RSV) e do novo coronavírus (SARS-CoV-2) em pacientes com internação hospitalar por SRAG. Estudo transversal, com pacientes em internação hospitalar com SRAG entre novembro de 2021 e maio de 2022. Dados sociodemográficos e clínicos e amostras da nasofaringe foram coletados/as, as quais foram submetidas à extração de RNA e testadas quanto à positividade para Influenza A, RSV e SARS-CoV-2 por meio da técnica de PCR em tempo real pelo método SYBR Green. Foram incluídos 42 pacientes, sendo 59,5% do sexo feminino, 57,1% idosos, 54,8% com ensino fundamental. A maior parte dos pacientes reportou hábito tabagista prévio ou atual (54,8%), não etilista (73,8%) e 83,3% deles apresentavam alguma comorbidade, sendo hipertensão arterial sistêmica e diabetes mellitus tipo 2 as mais prevalentes. Um total de 10,5% dos pacientes testou positivo para FluA, nenhuma amostra positiva para RSV e 76,3% positivos para SARS-CoV-2. Na população estudada, SRAG com agravo hospitalar foi observado em maior proporção, em mulheres, idosos e pessoas com comorbidades, embora sem significância estatística, sendo o novo coronavírus o agente etiológico mais relacionado, o que evidencia a patogenicidade desse agente e suas consequências ainda são evidentes após quase 2 anos de período pandêmico.

Severe acute respiratory syndrome (SARS) is characterized by symptoms of high fever, cough and dyspnea, and is in most cases related to a reduced amount of infectious agents. The objective was to assess the prevalence of respiratory viruses Influenza A (FluA), respiratory syncytial virus (RSV) and the new coronavirus (SARS-CoV-2) in patients hospitalized for SARS. Cross-sectional study, with patients hospitalized with SARS between November 2021 and May 2022. Sociodemographic and clinical data and nasopharyngeal samples were collected, which were subjected to RNA extraction and tested for positivity for Influenza A, RSV and SARS-CoV-2 using the real-time PCR technique using the SYBR Green method. 42 patients were included, 59.5% female, 57.1% elderly, 54.8% with primary education. Most patients reported previous or current smoking habits (54.8%), non-drinkers (73.8) and 83.3% of them had some comorbidity, with systemic arterial hypertension and type 2 diabetes mellitus being the most prevalent. A total of 10.5% of patients tested positive for FluA, no samples positive for RSV, and 76.3% positive for SARS-CoV-2. In the studied population, SARS with hospital injury was observed more frequently in women and the elderly, with associated comorbidities, with the new coronavirus being the most related etiological agent, which shows, although not statistically significant, that the pathogenicity of this agent and its consequences are still evident after almost 2 years of period pandemic.

Real-world data for marginal zone lymphoma patients in the French REALYSA cohort: The REALMA study.

Marginal Zone Lymphoma (MZL) comprises three subtypes: extranodal MZL (EMZL), splenic MZL (SMZL) and nodal MZL (NMZL). Since clinical trials have limited representativeness, there is a need for real-world data (RWD) evidence in MZL. Real-world data in Lymphoma and survival in Adults (REALYSA) is a prospective multicentric French cohort of newly diagnosed lymphoma patients. This study consists of the first abstraction of MZL patients prospectively included in REALYSA between 12/2018 and 01/2021 with at least 1 year of follow-up. It provides a landscape description of clinical characteristics, initial workup, quality of life and first-line therapy performed in routine practice. Among 207 included patients, 122 presented with EMZL, 51 with SMZL and 34 with NMZL. At baseline, median age was 67 years (range 28-96), and patients reported a favorable global health status (75/100 (IQR 58,83)) - which was higher in NMZL and lower in SMZL patients (p = 0.006). 18FDG-PET/CT was frequently performed at initial workup (EMZL 72%, SMZL 73%, NMZL 85%). Active surveillance was the initial management for 58 (28%) patients. The most prescribed therapies were rituximab-chlorambucil in the EMZL population (30%), rituximab monotherapy in the SMZL population (37%) and R-CHOP (24%)/bendamustine-rituximab (15%) in the NMZL population. At end of first line, overall response rate was 93% among treated patients with 75% of complete response. This French nationwide study provided for the first time prospective RWD on clinical characteristics, initial management and treatment response of MZL patients.

Selective Detection of Picric Acid by Benzodiazepine Containing Enaminone Core as Receptor and Its Application to Real Water Sample Analysis.

Nitroaromatic compounds are highly explosive and illegitimate substances. Over a decade, chemists have been affianced in extensive research on the selective and sensitive detection of these nitroaromatic explosives for homeland security and environmental protection. The benzodiazepine-based enaminone (BDE) receptor has been synthesized by aqueous extract of onion catalyzed three-component reaction between o-phenylenediamine, dimedone with an aldehyde. The BDE probe is well analyzed and applied to a sensor that selectively detects picric acid (PA). UV-Vis and fluorescence spectroscopy were used to investigate the photophysical responses of the receptor (BDE). From the observed results BDE found turn-off fluorescence with the addition of picric acid and the lowest limit of detection and limit of quantification was achieved about 24.6 nM and 73.8 nM. The fluorescence quantum yield was attained about 0.28. The BDE-PA adduct formation was confirmed by 1H NMR titration analysis. The Job's plot analysis was performed through 1H NMR titrations and established the binding stoichiometry ratio of the BDE-PA adduct as 1:1 ratio. Further, DFT calculations supported the observed photophysical responses of BDE-PA adduct to confirm the molecular level interactions. The receptor was effectively applied to approximate level of picric acid in real water sample analysis.

[Important statistical points for clinical research: from basics to applications].

Clinical research is conducted to investigate physicians' clinical questions and to clarify research hypotheses. When conducting clinical research, it is important to carefully consider the research design in advance. An optimal design that meets the objectives of the study and addresses practical implementation issues is desirable. Randomized comparisons during the final confirmatory phase may be the best tool for comparing treatments. However, not all clinical questions can be answered through randomized controlled trials. This article summarizes the basics of clinical study design and explains the role of randomization. It also introduces a propensity score-based method that has gained attention as a statistical method for comparing treatment groups when randomization is not feasible, and is increasingly being utilized in clinical research.

Is early-onset colorectal cancer an evolving pandemic? Real-world data from a tertiary cancer center.

BACKGROUND: Early onset Colorectal Cancer (EOCRC), defined as those diagnosed under the age of 50, has been increasing rapidly since 1970. UK data on EOCRC are currently limited and better understanding of the condition is needed. MATERIALS AND METHODS: A single-center retrospective study of patients with EOCRC treated over 9 years (2013-2021) at a large UK cancer center was performed. Clinicopathological features, risk factors, molecular drivers, treatment, and survival were analyzed. RESULTS: In total, 203 patients were included. A significant increase in cases was reported from 2018-2019 (n = 33) to 2020-2021 (n = 118). Sporadic EOCRC accounted for 70% of cases and left-sided tumors represented 70.9% (n = 144). Median duration of symptoms was 3 months, while 52.7% of the patients had de-novo metastatic disease. Progression-free survival after first-line chemotherapy was 6 months (95% CI, 4.85-7.15) and median overall survival (OS) was 38 months (95% CI, 32.86-43.14). In the advanced setting, left-sided primary tumors were associated with a median OS benefit of 14 months over right-sided primaries (28 vs 14 months, P = .009). Finally, primary tumor resection was associated with median OS benefit of 21 months compared with in situ tumors (38 vs 17 months, P < .001). CONCLUSIONS: The incidence of EOCRC is increasing, and survival outcomes remain modest. Raising public awareness and lowering the age for colorectal cancer screening are directions that could improve EOCRC clinical outcomes. There is also a need for large prospective studies to improve the understanding of the nature of EOCRC and the best therapeutic approaches.

Insight into efficient degradation of pentacyclic and hexacyclic sulfonamide antibiotics by synthetic trivalent copper: Performance and mechanism.

High valent metal species, including Mn(III), Fe(IV) and Cu(III), have been identified as key intermediates in the degradation of pollutants in many advanced oxidation processes. However, unlike Mn(III) and Fe(IV), the current exploration of the reaction activity and selective oxidation mechanism of Cu(III) towards pollutants with different structures is still quite limited. Herein, the copper(III) periodate was synthesized to investigate the reactivity towards six sulfonamide antibiotics (SAs) including typical two pentacyclic structures (sulfamethoxazole (SMX) and sulfathiazole (STZ)) and four hexacyclic structures (sulfadiazine (SDZ), sulfamerazine (SMR), sulfamonomethoxine (SMM) and sulfapyridine (SPD)). The results indicated that all SAs almost completely removed by Cu(III) system after 10 min with the molar ratio of approximately 3:1 (Cu(III):SAs) and Cu(III) direct oxidation played the most important role. SAs with 6-ring substituents were more readily degraded by Cu(III) than SAs with 5-ring substituents, and the presence of electron-rich group such as -CH3 and -S in ring substituent increased the reactivity towards Cu(III). The introduction of coexisting anions (Cl-, SO42- and HCO3-) hardly affected the degradation of SAs by Cu(III) oxidation, while the addition of HA to some extent inhibited SAs degradation. The solution pH greatly affected the degradation of SAs by Cu(III) and the removal efficiencies of SAs roughly followed the rule of neutral > acidic > alkaline. The degradation mechanism of SAs with 5-ring and 6-ring substituents in Cu(III) system mainly included amino nitration, self-coupling, hydroxylation, S-N cleavage in SAs with 5-ring substituents and SO2 extrusion in SAs with 6-ring substituents. Although the real water matrix inhibited the degradation of SAs to varying degrees, Cu(III) still played a satisfactory performance on SAs degradation especially for electron-rich structure.

Influence of Statin Potency and Liposolubility on Alzheimer's disease patients: a population-based study.

Although Alzheimer's disease (AD) cause is still unknown, there are several known risk factors, such as dyslipidemia. Statins are the most prescribed lipid-modifying therapies. Recent research has suggested a relationship between statins and AD, nevertheless, their ability to prevent AD is still unclear. Therefore, this cross-sectional study aimed to examine the relationship between statin use and anti-AD drug prescription. For that purpose, a database containing information on medications prescribed to patients aged 50 years or older (n = 233183) between 2018 and 2020 was used. Defined daily doses (DDDs) were calculated according to the ATC/DDD index 2023. Statistical analyses, with logistic regression and cumulative incidence, were carried out to assess statins and anti-AD drug consumption. As a result, a total of 47852 patients aged more than 70 years who were prescribed at least one antihypertensive, antidiabetic or lipid-modifying agent were included in the study. Of these, 45345 patients were classified within the cardiovascular risk group and 2483 were classified as patients with only hyperlipidemia. Patients using low-potency or hydrophilic statins had lower odds of anti-AD usage when compared to high-potency or lipophilic statins, respectively. Similarly, rosuvastatin and pitavastatin had lower odds of anti-AD medication intake when compared to atorvastatin. Finally, pitavastatin DDDs were prone to lower the odds of anti-AD medication usage when compared to rosuvastatin. In conclusion, a potential association between statins and the intake of AD medication has been observed. Specifically, low-potency (pitavastatin) and hydrophilic (rosuvastatin) statins were associated with less use of anti-AD medication.

A scalable approach to assess the safety of recently marketed systemic treatments for atopic dermatitis in clinical practice.

Targeted systemic immune-modulating drugs (IMDs) to treat atopic dermatitis (AD) were highly efficacious in randomized trials. Trials with limited number of subjects leave questions about their safety. We describe a data and analytics structure for the production of timely, high-quality evidence on the comparative safety of recently approved IMDs in patients with AD in clinical practice. We established a series of sequential propensity score (PS)-balanced cohorts that grow in size with each annual data refresh. Nine health outcomes of interest plus conjunctivitis as a positive tracer outcome were identified. The initial treatment comparison was dupilumab, an interleukin-4/13 inhibitor, or tralokinumab, an interleukin-13 inhibitor, versus abrocitinib/upadacitinib, both JAK inhibitors. The first analysis cycle (December 2021-February 2023) compared 269 patients initiating JAK inhibitors and 2,650 initiating IL-4/IL-13 inhibitors. Patient characteristics were well balanced after PS-matching. Outpatient infections within 180 days occurred in 18% of JAK-1 inhibitor initiators versus 12% of dupilumab/ tralokinumab initiators (RR=1.50; 0.96 to 2.33) whereas acne risks were 7% vs. 3%, respectively (RR=2.29, 0.96 to 5.46). This sequential monitoring system will produce essential knowledge on the safety of IMDs to treat AD based on its growing study size of patients observed in clinical practice.

Use of transportability methods for real-world evidence generation: a review of current applications.

Aim: To evaluate how transportability methods are currently used for real-world evidence (RWE) generation to inform good practices and support adoption and acceptance of these methods in the RWE context. Methods: We conducted a targeted literature review to identify studies that transported an effect estimate of the clinical effectiveness or safety of a biomedical exposure to a target real-world population. Records were identified from PubMed-indexed articles published any time before 25 July 2023 (inclusive). Two reviewers screened abstracts/titles and reviewed the full text of candidate studies to identify the final set of articles. Data on the therapeutic area, exposure(s), outcome(s), original and target populations and details of the transportability analysis (e.g., analytic method used, estimate transported, stated assumptions) were abstracted from each article. Results: Of 458 unique records identified, six were retained in the final review. Articles were published during 2021-2023, focused on the US/Canada context, and covered a range of therapeutic areas. Four studies transported an RCT effect estimate, while two transported effect estimates derived from real-world data. Almost all articles used weighting methods to transport estimates. Two studies discussed all transportability assumptions, and one evaluated the likelihood of meeting all assumptions and the impact of potential violations. Conclusion: The use of transportability methods for RWE generation is an emerging and promising area of research to address evidence gaps in settings with limited data and infrastructure. More transparent and rigorous reporting of methods, assumptions and limitations may increase the use and acceptability of transportability for producing robust evidence on treatment effectiveness and safety.

SEMES' long road to specialty status for emergency medicine in Spain. / El largo camino de SEMES hacia la especialidad de Medicina de Urgencias y Emergencias en España.

TEXT: July 2 of this year saw the publication of Spanish Royal Decree 610/2024, which establishes emergency medicine as an official specialization. This event represents the culmination of a long-running effort to improve the care of patients in the emergency and urgent care system and throughout the national health service. This article offers a brief account of some of the legal, administrative, and political steps the Spanish Society of Emergency Medicine(SEMES) took to achieve this goal over the course of nearly 40 years. The effort has involved many SEMES members, who strictly speaking had the sole obligation of knowing how to care appropriately for patients based on clinical expertise along with organizational, scientific, and other professional skills. Competences in these areas have been shown to fall short in Spain. The article provides examples of some of the bright lights and dim shadows in our rule of law. Nonetheless, the long road traveled has also shown us how skills and knowledge are developed in adverse circumstances and crises, provided there is vocation for public service.

TEXTO: La publicación del Real Decreto 610/2024, de 2 de julio, por el que se establece el título de Médica/o Especialista en Medicina de Urgencias y Emergencias, supone la culminación de una larga reclamación, orientada al logro de la mejora en la atención a los pacientes en el sistema de urgencias y emergencias y, en definitiva, del propio Sistema Sanitario español. Este artículo está orientado, de manera muy resumida, hacia algunos de los aspectos jurídicos, administrativos y políticos desempeñados por la Sociedad Española de Medicina de Urgencias y Emergencias, SEMES durante casi 40 años. Esto implica a muchos de sus miembros, profesionales que, esencialmente, solo debían saber cómo atender adecuadamente a sus pacientes, desde su conocimiento clínico, organizativo y científico, entre otros. Estos aspectos se mostraron insuficientes en España. Se ejemplifican algunas luces y sombras del Estado de Derecho español. Pero también este camino muestra las capacidades y conocimientos que se llegan a desarrollar en situaciones adversas y crisis, siempre y únicamente desde la vocación de servicio público.

A realistic approach for evaluating antimicrobial surfaces for dry surface exposure scenarios.

The severe acute respiratory syndrome coronavirus 2 pandemic has raised public awareness about the importance of hygiene, leading to an increased demand for antimicrobial surfaces to minimize microbial contamination on high-touch surfaces. This is particularly relevant in public and private transportation settings, where surfaces frequently touched by individuals pose a significant, yet preventable, risk of infection transmission. Typically, the antimicrobial activity of surfaces is tested using test methods of the International Standards Organization, American Society for Testing and Materials, or Japanese Industrial Standards, which involve complete submersion in liquid, elevated temperature (37°C), and prolonged (24 h) contact periods. However, these conditions do not accurately represent real-world scenarios where surfaces are exposed to air. In this study, we propose a modified test method designed to better reflect real-life conditions in the intended end-use setting. The modifications included using deionized water instead of nutrient broth while preparing bacterial inoculum, applying a small test inoculum to the surface and allowing it to dry, maintaining ambient temperature and relative humidity throughout the contact period, and reducing the contact period to 4 h. With this modified approach, the antimicrobial activity of 20 samples was reassessed. This screening revealed that out of 20 samples, only 2 samples were effective against all species, while 8 samples demonstrated partial effectiveness against selected species, and 10 samples showed no significant effect. These findings highlight the inadequacy of the current test standard and emphasize the urgent necessity for revised and adapted testing method to ensure a reliable and accurate evaluation.IMPORTANCEThe recent severe acute respiratory syndrome coronavirus 2 pandemic has sparked increased demand for antimicrobial surfaces to mitigate the risk of fomites-transmitted infection in both indoors and confined spaces. Commonly, the antimicrobial activity of these surfaces is assessed using test standards established by national standards bodies, which do not distinguish between different application scenarios. While these test standards are suitable for surfaces intended for submerged application, they are inappropriate for antimicrobial surfaces designed for dry surface exposure. The usage of these standards can lead to an overestimation of antimicrobial efficacy. Thus, this study introduces a modified dry exposure test method aimed at better reflecting real-life conditions in the intended end-use setting. Our results revealed the subpar antimicrobial performance of numerous samples, highlighting the necessity to revise and tailor the universal test standard to real-world scenarios in order to ensure a reliable and accurate evaluation.

Fully Integrated Biosensing System for Dynamic Monitoring of Sweat Glucose and Real-Time pH Adjustment Based on 3D Graphene MXene Aerogel.

The development of noninvasive glucose sensors capable of continuous monitoring without restricting user mobility is crucial, particularly for managing diabetes, which demands consistent and long-term observation. Traditional sensors often face challenges with accuracy and stability that curtail their practical applications. To address these issues, we have innovatively applied a three-dimensional porous aerogel composed of Ti3C2Tx MXene and reduced graphene oxide (MX-rGO) in electrochemical sensing. It significantly reduces the electron-transfer distance between the enzyme's redox center and the electrode surface while firmly anchoring the enzyme layer to effectively prevent any leakage. Another pivotal advancement in our study is the integration of the sensor with a real-time adaptive calibration mechanism tailored specifically for analyzing sweat glucose. This sensor not only measures glucose levels but also dynamically monitors and adjusts to pH fluctuations in sweat. Such capabilities ensure the precise delivery of physiological data during physical activities, providing strong support for personalized health management.

Contrast enhanced ultrasound of cystic renal lesions, from diagnosis up to treatment.

Ultrasound is the most used interdisciplinary imaging technique in clinical routine for assessment of renal pathologies. This includes the monitoring of cystic renal lesions, which can be classified as non-complicated or complicated and by means of occurrence as solitary or multifocal lesions. The Bosniak-classification (I-IV) classifies renal cysts in 5 different categories and is used for decisions of further clinical treatment. This classification was developed for computed tomography and has been adopted for magnetic resonance imaging as well as contrast-enhanced ultrasound. In the following review article, cystic kidney lesions and their differentiation using contrast-enhanced ultrasound are presented and an overview of the therapy options is given. In interventional procedures, CEUS can make a valuable contribution in histological sampling, reduce radiation exposure and, under certain circumstances, the number of interventions for the patient.

Functional disability and disease activity are affected by social determinants of health in patients with rheumatoid arthritis.

BACKGROUND: The relationship between social determinants of health (SDH) and disease outcomes in rheumatoid arthritis (RA) is not well documented. METHODS: Data were extracted from the Ontario Best Practices Research Initiative (OBRI) registry for patients between January 2008 and April 2022. Adjusted mixed models analysis was used to investigate the effect of baseline SDH on disease activity (Clinical Disease Activity Index (CDAI)) and functional disability (Health Assessment Questionnaire-Disability Index (HAQ-DI)) 12 months after enrollment. The analyses were completed on multiple imputed data. RESULTS: There were 2651 patients with a mean age of 58.1 years (SD 12.9). The majority (77.8%) were female. Greater improvements in physical function were seen in patients who were full-time employed (difference = - 0.20; 95% CI - 0.28, - 0.11), part-time employed (difference = - 0.10; 95% CI - 0.19, - 0.02), or retired (difference = - 0.17; 95% CI - 0.25, - 0.08), compared to unemployed, those with highest income ($75,000 or more) (difference = - 0.23; 95% CI - 0.37, - 0.09). Caucasian was also associated with a positive impact on functional ability (difference = - 0.09; 95% CI - 0.17, - 0.02). In contrast, smokers had smaller improvements in physical function (difference = 0.07; 95% CI 0.002, 0.14). Interestingly, women had greater improvement in CDAI (difference = - 2.40; 95% CI - 3.29, - 1.51), while they reported less improving in their physical function (difference = 0.33; 95% CI 0.27-0.39). Achieving CDAI low disease activity/remission state was also more common in females. CONCLUSIONS: Our findings suggest that disease activity and functional disability are affected by different SDH factors. The effects of SDH should be better understood and addressed by rheumatologists to provide equitable healthcare for all patients with RA. Key points • This study explored a comprehensive panel of social determinants of health and their relationship to clinical outcomes. • Previously unreported factors such as employment status and income were found to influence clinical outcomes. • Our findings can help physicians to identify high-risk patients who may benefit from additional attention to their social background.

Real-world clinical efficacy of tofacitinib in moderate-to-severe ulcerative colitis.

Tofacitinib is an oral small-molecule Janus kinase (JAK) inhibitor that preferentially inhibits JAK1 and JAK3. Its efficacy in inducing and maintaining remission in ulcerative colitis (UC) as well as its safety profile has been demonstrated in multicenter, randomized, double-blind, placebo-controlled trials. Additionally, real-world studies evaluating the effectiveness and adverse effects of tofacitinib have been conducted, affirming its clinical efficacy in moderate-to-severe UC.

Establishing Reference Values for Vaginal Vestibule Elastography in Healthy Postmenopausal Women.

Objective This study aims to establish normative elastography values for the vaginal vestibule in healthy postmenopausal women and assess the variability of these values with age and measurement time during the day. Methods The study included 111 women aged 40-90, excluding those with medical histories or treatments affecting vaginal health. Elastography measurements were taken twice daily, between 9-10 AM and 3-4 PM, using real-time tissue elastography technology. Statistical analysis evaluated the effects of age, body mass index (BMI), and diurnal variation on vaginal vestibule elasticity. Results A significant positive correlation between age and elastography values was found (p=8.36×10⁻7), with elastography values increasing by approximately 0.0040 units per year. The mean elastography value was 28.32% (SD=5.87%) in the morning and 28.10% (SD=5.90%) in the afternoon, with a statistically significant difference (p=0.016). BMI showed a weak negative correlation with elastography values (r=-0.2021, p=0.0334). Conclusion Establishing reference values for vaginal vestibule elastography provides a foundation for improved diagnostic accuracy and early detection of gynecological conditions. The findings support the use of elastography as a non-invasive, reliable diagnostic tool in clinical practice. Future research should validate these results across different age groups and in women with specific gynecological conditions to further solidify the clinical applicability of vaginal vestibule elastography.

Time-resolved observation of DHR123 nano-clay radio-fluorogenic gel dosimeters by photoluminescence-detected pulse radiolysis.

The importance of real-time dose evaluation has increased for recent advanced radiotherapy. However, conventional methods for real-time dosimetry using gel dosimeters face challenges owing to the delayed dose response caused by the slow completion of radiation-induced chemical reactions. In this study, a novel technique called photoluminescence-detected pulse radiolysis (PLPR) was developed, and its potential to allow real-time dose measurements using nano-clay radio-fluorogenic gel (NC-RFG) dosimeters was investigated. PLPR is a time-resolved observation method, and enables time-resolved fluorescence measurement. NC-RFG dosimeters were prepared, typically consisting of 100 µM dihydrorhodamine 123 (DHR123) and 2.0 wt.% nano-clay, along with catalytic and dissolving additives. We successfully achieved time-resolved observation of the increase in fluorescence intensity upon irradiation of the dosimeter. Dose evaluation was possible at 1 s after irradiation. The dose-rate effect was not observed for the deoxygenated dosimeter, but was observed for the aerated dosimeter. Besides the dose-rate effect, linear dose responses were obtained for both conditions. Furthermore, we made a novel observation of a decay in the fluorescence intensity over time in the early stages which named fluorescence secondary loss (FSL) and elucidated the conditions under which this phenomenon occurs.

Revolutionizing tomato disease detection in complex environments.

In the current agricultural landscape, a significant portion of tomato plants suffer from leaf diseases, posing a major challenge to manual detection due to the task's extensive scope. Existing detection algorithms struggle to balance speed with accuracy, especially when identifying small-scale leaf diseases across diverse settings. Addressing this need, this study presents FCHF-DETR (Faster-Cascaded-attention-High-feature-fusion-Focaler Detection-Transformer), an innovative, high-precision, and lightweight detection algorithm based on RT-DETR-R18 (Real-Time-Detection-Transformer-ResNet18). The algorithm was developed using a carefully curated dataset of 3147 RGB images, showcasing tomato leaf diseases across a range of scenes and resolutions. FasterNet replaces ResNet18 in the algorithm's backbone network, aimed at reducing the model's size and improving memory efficiency. Additionally, replacing the conventional AIFI (Attention-based Intra-scale Feature Interaction) module with Cascaded Group Attention and the original CCFM (CNN-based Cross-scale Feature-fusion Module) module with HSFPN (High-Level Screening-feature Fusion Pyramid Networks) in the Efficient Hybrid Encoder significantly enhanced detection accuracy without greatly affecting efficiency. To tackle the challenge of identifying challenging samples, the Focaler-CIoU loss function was incorporated, refining the model's performance throughout the dataset. Empirical results show that FCHF-DETR achieved 96.4% Precision, 96.7% Recall, 89.1% mAP (Mean Average Precision) 50-95 and 97.2% mAP50 on the test set, with a reduction of 9.2G in FLOPs (floating point of operations) and 3.6M in parameters. These findings clearly demonstrate that the proposed method improves detection accuracy and reduces computational complexity, addressing the dual challenges of precision and efficiency in tomato leaf disease detection.

Long-term treatment results of pembrolizumab monotherapy: reconsideration of immune checkpoint inhibitor monotherapy.

Objective: The extended outcomes of the KEYNOTE-024 study demonstrated a favorable 5-year overall survival (OS) rate of 31.9%. The present study investigated the outcomes of pembrolizumab monotherapy for advanced or recurrent non-small cell lung cancer (NSCLC) at our institution. Patient: The long-term outcomes of 102 patients with advanced or recurrent NSCLC treated with pembrolizumab monotherapy between March 2017 and December 2022 were retrospectively assessed. Results: This study included a total of 102 patients [mean age: 72 ± 9.6 years (range: 41-91 years), male/female=77/25; performance status (PS; 0, 1, 2, 3, 4)=49/38/15/0/0; smokers=91 (89%), non-squamous cell carcinoma/squamous cell carcinoma=66/36, PD-L1 tumor proportion score (TPS) ≥50%/1-49%=80/22, positive for EGFR mutation=5, advanced/postoperative recurrence=51/51, treatment line: first/second or later=81/21, treatment courses: median 8 (range: 1-39), objective response rate/disease control rate=44%/55%, immune-related adverse events (irAEs): 47, 5-year OS=34%]. On univariate analysis, PS, PD-L1 TPS, and irAEs were significant prognostic factors. On multivariate analysis, histology, PD-L1 TPS, and irAEs were significant prognostic factors. Conclusion: Pembrolizumab monotherapy demonstrated promising treatment outcomes for advanced or recurrent NSCLC, as evidenced by the significant association of PD-L1 TPS with irAEs and prognosis, suggesting its potential as a beneficial therapeutic option.