Clinical Use Research Articles

Synthesis and evaluation of smart drugs with integrated functions for identifying and treating oxidative microenvironments associated with cellular ferroptosis

AbstractFerroptosis is a novel form of cell death driven by oxidative damage, and is implicated in various pathological conditions, including neurodegenerative diseases, retinal damage, and ischemia‐reperfusion injury of organs. Inhibiting ferroptosis has shown great promise as a therapeutic strategy for these diseases, underscoring the urgent need to develop effective ferroptosis inhibitors. Although Ferrostatin‐1 (Fer‐1) is a potent ferroptosis inhibitor, its susceptibility to oxidation and metabolic inactivation limits its clinical utility. In this study, the accumulation of peroxides and the resulting oxidative damage in the cellular microenvironment during ferroptosis were utilized to design Ferrostatin‐1 prodrugs with reactive oxygen species‐responsive features. This approach led to the development of a series of ferroptosis inhibitors that were capable of recognizing oxidative damage in diseased areas, allowing for targeted release and improved stability. The novel compounds demonstrated significant inhibitory effects and selectivity against RSL‐3‐induced ferroptosis in HK‐2 cells, with compound a1 exhibiting an EC50 of 15.4 ± 0.7 μM, outperforming Fer‐1. These compounds effectively identify the oxidative microenvironment associated with ferroptosis, enabling the targeted release of Fer‐1, which prevents lipid peroxide accumulation and inhibits ferroptosis. This strategy holds promise for treating diseases related to ferroptosis, offering a targeted and intelligent therapeutic approach.

High-contrast Compton camera: Challenges to high-quality and broadband imaging

In the field of nuclear medicine, various radiopharmaceuticals require wideband x-ray/gamma-ray imaging devices for clinical and treatment monitoring. Compton cameras, which perform imaging using high-energy gamma rays, have the potential to significantly increase the variety of radioactive nuclides that can be imaged. However, artifacts caused by the so-called “Compton cone” have hindered their clinical use. Therefore, we propose the use of a collimator to improve the contrast of images obtained using Compton cameras. In this study, we developed a high-contrast Compton camera by attaching a tungsten collimator to its front surface. The contrast is improved by applying weighting to the signals based on the distance that the high-energy gamma rays penetrated the collimator walls. As a demonstration, we visualized 198Au plates that emit 412-keV gamma rays with and without the collimator. In addition, low-energy (<200 keV) x-ray/gamma-ray imaging, which is difficult for conventional Compton cameras, was achieved by performing single-photon emission computed tomography (SPECT) using the collimator and scatterer of the Compton camera. We demonstrated broadband gamma-ray imaging by visualizing a 133Ba standard source using 81-keV and 356-keV gamma rays based on the principles of SPECT and Compton cameras, respectively.

Socio-demographic, clinical variables and pain among Egyptian patients of opioid use disorder with and without comorbid gabapentin use

IntroductionThere is increased clinical use of gabapentin, these trends appear to chronologically align with the opioid overdose crisis and particularly with the increased restrictions on opioid prescription.ObjectivesThe study aimed to assess the clinical variables, pain quality, and severity among patients with opioid use disorder as the main substance with and without gabapentin comorbid use.MethodsThe research involved 60 patients diagnosed with substance use disorder, divided into two groups: opioid use as the main substance and opioid use with comorbid gabapentin. All participants were assessed using a semi-structured clinical addiction interview, the structured clinical interview for diagnostic and statistical manual of mental disorders, the Addiction Severity Index, urine drug test, McGill Pain Questionnaire, and Douleur Neuropathique en 4 Questionnaire, in one interview setting.ResultsThe study showed that pain relief was the main desirable effect in the gabapentin group, with 66.2% of the group experiencing it. Euphoria was the desirable effect in the opioid group, while overdose was more common in the gabapentin group. Respiratory complications were also more common in the Gabapentin group.ConclusionThe study concluded that patients with comorbid gabapentin use disorder had a higher frequency of overdose, history of pain, and significant neuropathic pain, while less abstinence.

Clinical usefulness of C-reactive protein-albumin-lymphocyte (CALLY) index as a prognostic biomarker in patients undergoing surgical resection of pancreatic cancer.

The C-reactive protein-albumin-lymphocyte (CALLY) index, which simultaneously evaluates the nutritional, immunological, and inflammatory statuses, is a new prognostic biomarker in patients with various cancers; however, no study has reported the clinical significance of the CALLY index in patients with pancreatic cancer. This study aimed to investigate whether the preoperative CALLY index is a prognostic biomarker in patients undergoing surgical resection of pancreatic cancer. We retrospectively enrolled 461 patients with pancreatic cancer who underwent surgical resection between January 2013 and December 2022. The overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional hazards regression models. The optimal cut-off value for the preoperative CALLY index was 1.9. In the low CALLY group, patients were older (p = 0.012), more patients underwent pancreaticoduodenectomy (p = 0.002), the median tumor size was larger (p < 0.001), more patients had pathologically confirmed metastatic lymph nodes (p = 0.015) and worse pathological stage (p = 0.015), and fewer patients received adjuvant chemotherapy (p = 0.003). A low CALLY index was associated with decreased OS (22.1 vs. 37.9months) and RFS (12.4 vs. 16.4months). Univariate and multivariate analyses showed that the preoperative CALLY index was an independent prognostic factor for OS (p < 0.001) and RFS (p = 0.045). The preoperative CALLY index is a prognostic biomarker for both OS and RFS in patients undergoing surgery for pancreatic cancer.

Magnetic Resonance Imaging - Derived Psoas Muscle Area and Survival in Patients Treated Invasively for Peripheral Arterial Disease.

Psoas muscle parameters estimated from computed tomography images, as surrogates for sarcopenia, have been found to be associated with post-interventional outcomes after a wide range of cardiovascular procedures. The pre-interventional assessment in patients undergoing invasive treatment for peripheral arterial disease is increasingly often carried out with magnetic resonance imaging (MRI), and we therefore sought to investigate the predictive potential of MRI-derived psoas muscle area in this cohort. A total of 899 patients with available sufficient quality pre-interventional MRI conducted within 6 months prior to treatment undergoing open, endovascular, or hybrid revascularization procedures for claudication and/or limb-threatening ischemia at Tampere University hospital between 2010 and 2020 were retrospectively studied in this single-center cohort study. The follow-up lasted until 17 June 2021. Psoas muscle areas were measured from the magnetic resonance images at the L4 level, and the reliability of muscle parameter measurements was tested with intraclass correlation coefficient analysis. The average psoas muscle area values (mean of left and right psoas surface areas) were z-scored and analyzed separately for men and women. The median follow-up time was 5.9 years (interquartile range (IQR) = 2.7-7.8), and the overall mortality count was 259 (28.8%) (29.5% n = 168/569 for men and 27.6% n = 91/330 for women). The intraclass correlation coefficient analysis showed excellent interrater reliability for psoas muscle measurements. The muscle surface areas were larger in men (mean = 7.58 cm2) compared to women (mean = 5.27 cm2) (p < 0.001). Higher psoas muscle area was associated with better survival in women (p = 0.003, hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.6-0.9 per 1 SD), whereas in men, an independent association of the muscle parameter with mortality was not found. MRI-derived psoas muscle area may be a prognostic factor for clinical use.

Assessment of surface hardness and impact strength of denture base resins reinforced with silver–titanium dioxide and silver–zirconium dioxide nanoparticles: In vitro study

Abstract Polymethyl methacrylate (PMMA) is frequently utilised for fabricating denture bases due to its perfect qualities. However, a significant issue with this resin is the occurrence of frequent fractures caused by heavy chewing power, resulting in early cracks and fractures during clinical use. This study investigates the influence of silver, titanium dioxide, and silver zirconia nanoparticles on the surface hardness and impact strength of self-cured denture base. The samples were categorised into four categories according to the incorporation of different nanoparticles. The samples were divided into three subgroups based on the nanoparticle content: 0.1, 0.3, and 0.5% of TiO2 and ZrO2. Each group had a set ratio of 0.3% Ag as an antibacterial agent. Except for the fourth group (Group D), a combination of 0.05, 0.15, and 0.25% of TiO2 and ZrO2, along with 0.3% Ag, was utilised to investigate their collective impact. The Shore D hardness and Charpy test were employed to quantify the surface hardness and impact strength, respectively. The samples were subjected to X-ray diffraction analysis and field emission-scanning electron microscopy to characterise nanoparticles and ascertain the structure of acrylic samples. All nanoparticle-modified samples showed a substantial improvement in surface hardness compared to the control group. The maximum hardness value was seen in the samples containing 0.3% Ag–0.3% TiO2 and 0.3% Ag–0.5% ZrO2. The samples treated with 0.3% Ag and 0.3% TiO2 showed the maximum impact strength. The incorporation of Ag and ZrO2 hinders the ability to withstand impact strength. The samples treated with 0.3% Ag, 0.15% TiO2, and 0.15% ZrO2 exhibited an augmentation in impact strength. Modified samples in all groups showed a colour change, which required colour modifiers.

Necessity and impact of specialization of large foundation model for medical segmentation tasks.

Large foundation models, such as the Segment Anything Model (SAM), have shown remarkable performance in image segmentation tasks. However, the optimal approach to achieve true utility of these models for domain-specific applications, such as medical image segmentation, remains an open question. Recent studies have released a medical version of the foundation model MedSAM by training on vast medical data, who promised SOTA medical segmentation. Independent community inspection and dissection is needed. Foundation models are developed for general purposes. On the other hand, stable delivery of reliable performance is key to clinical utility. This study aims at elucidating the potential advantage and limitations of landing the foundation models in clinical use by assessing the performance of off-the-shelf medical foundation model MedSAM for the segmentation of anatomical structures in pelvic MR images. We also explore the simple remedies by evaluating the dependency on prompting scheme. Finally, we demonstrate the need and performance gain of further specialized fine-tuning. MedSAM and its lightweight version LiteMedSAM were evaluated out-of-the-box on a public MR dataset consisting of 589 pelvic images split 80:20 for training and testing. An nnU-Net model was trained from scratch to serve as a benchmark and to provide bounding box prompts for MedSAM. MedSAM was evaluated using different quality bounding boxes, those derived from ground truth labels, those derived from nnU-Net, and those derived from the former two but with 5-pixel isometric expansion. Lastly, LiteMedSAM was refined on the training set and reevaluated on this task. Out-of-the-box MedSAM and LiteMedSAM both performed poorly across the structure set, especially for disjoint or non-convex structures. Varying prompt with different bounding box inputs had minimal effect. For example, the mean Dice score and mean Hausdorff distances (in mm) for obturator internus using MedSAM and LiteMedSAM were {0.251±0.110, 0.101±0.079} and {34.142±5.196, 33.688±5.306}, respectively. Fine-tuning of LiteMedSAM led to significant performance gain, improving Dice score and Hausdorff distance for the obturator internus to 0.864±0.123 and 5.022±10.684, on par with nnU-Net with no significant difference in evaluation of most structures. All segmentation structures benefited significantly from specialized refinement, at varying improvement margin. While our study alludes to the potential of deep learning models like MedSAM and LiteMedSAM for medical segmentation, it highlights the need for specialized refinement and adjudication. Off-the-shelf use of such large foundation models is highly likely to be suboptimal, and specialized fine-tuning is often necessary to achieve clinical desired accuracy and stability.

Recent Patents and Applications of Nanoemulsion and Nanoemulgel for Topical Drug Delivery

Nanocarriers like nanoemulsions and nanoemulgels have emerged as revolutionary platforms in the realm of topical drug delivery, addressing many limitations of traditional dosage forms. Conventional methods often struggle with challenges such as poor skin penetration, inconsistent drug targeting, and potential local toxicity, which can undermine therapeutic outcomes and patient adherence. Nanoemulsions, with their submicron-sized droplets, offer a promising solution by enhancing the delivery and bioavailability of therapeutic agents, especially those that are poorly soluble. Nanoemulgels further elevate this potential by providing a versatile vehicle for lipophilic drugs, overcoming the limitations of traditional formulations. These advanced formulations not only improve drug penetration through the skin but also expand the range of active compounds viable for clinical use. Their ability to target specific skin regions more effectively reduces adverse reactions and increases therapeutic efficacy. This article delves into the physicochemical properties, preparation techniques, and latest advancements in nanoemulsions and nanoemulgels. By exploring recent clinical trials and patents, the review provides valuable insights into the development and optimization of these cutting-edge topical drug delivery systems, offering a promising avenue for enhancing dermatological treatments and patient outcomes.

Development and validation of a machine learning‐based model of ischemic stroke risk in the Chinese elderly hypertensive population

AbstractMachine learning (ML) has made some significant contributions to stroke prevention, but the stability and accuracy of existing models for clinical applications are uncertain. This study develops and validates an interpretable ML model using metabolic and coagulation biomarkers to predict ischemic stroke in elderly hypertensive patients in Northwest China. The prediction model used 453 electronic medical records for the model building (80% as a training set and 20% as a test set) and 132 for external validation. The final seven key features (D‐dimer, cystatin C, homocysteine, hemoglobin A1c, prothrombin time, low‐density lipoprotein C, and triglyceride glucose‐body mass index) were selected by the advanced approach, elastic net, and classical wrapping approaches. The final model, eXtreme gradient boosting, was identified as having superior performance than the other 9 classifers (random forest, Gaussian process, multilayer perceptron, logistic regression, support vector machine, K‐nearest neighbor, decision tree, Gaussian naive bayes, and ensemble model), with area under the receiver‐operating characteristic curves of 0.97 and 0.94 for the test and external validation sets, respectively. The final model demonstrates excellent stability, accuracy, and clinical usefulness through various metrics and decision curve analysis. Additionally, an online human–machine interface application has been developed for clinical practice to help early identification and intervention for ischemic stroke in elderly hypertensive patients.

Reliability of Three Pain Assessment Tools in Children Requiring Dental Treatment: A Comparative Clinical Study

ABSTRACT Background: Accurate pain assessment in pediatric dental patients is crucial for effective pain management and treatment planning. Materials and Methods: A total of 120 children aged 6-12 years, requiring dental treatment, were enrolled in this study. Each child was assessed using the three pain scales after undergoing a standardized dental procedure. The assessments were performed by two independent evaluators to determine inter-rater reliability. The intraclass correlation coefficient (ICC) was used to evaluate the reliability of each tool. Data were analyzed using descriptive statistics and repeated measures ANOVA to compare the mean pain scores across the three scales. Results: The mean pain scores reported were 4.3 ± 1.2 for the VAS, 4.5 ± 1.4 for the FPS-R, and 4.2 ± 1.3 for the WBFPRS. The ICC values for inter-rater reliability were 0.88 for the VAS, 0.86 for the FPS-R, and 0.90 for the WBFPRS, indicating high reliability for all tools. However, the WBFPRS showed slightly higher reliability compared to the other scales. No significant differences were found in pain scores across the three tools (P = 0.72). Conclusion: All three pain assessment tools demonstrated high reliability in assessing pain in pediatric dental patients. The Wong-Baker Faces Pain Rating Scale showed the highest inter-rater reliability, suggesting it may be the most reliable tool for clinical use in this population.

Clinical ocular prediction model of postoperative ametropic amblyopia in patients with congenital ectopia lentis

IntroductionDespite prompt and appropriate surgical management, a considerable proportion of patients with congenital ectopia lentis (CEL) suffer from postoperative ametropic amblyopia. To predict and identify at-risk patients early, and ensure timely amblyopia treatment, we conducted a thorough investigation into the onset and progression patterns of postoperative amblyopia in patients with CEL. Moreover, an ocular prediction model was constructed for amblyopia.MethodsIn this prospective cohort study, amblyopia analysis was conducted to reveal the prevalence of postoperative amblyopia at different time points of follow-up. Comparative analysis and logistic regression analysis were performed for the development of an amblyopia prediction model. Receiver Operating Characteristic (ROC) analysis, calibration plots, and decision curve analysis (DCA) were used to evaluate the performance of the model. A nomogram was created to determine the probability of postoperative amblyopia. Amblyopia was diagnosed according to the most recent edition of the Amblyopia Preferred Practice Pattern.ResultsA total of 889 eyes from 677 patients operated for CEL were enrolled in this study. In the pediatric cohort, the prevalence of amblyopia showed a decreasing trend with follow-up time from 1 month to 3.5 years. A prediction model based on preoperative best-corrected visual acuity (BCVA) and cardiac phenotype was established to predict postoperative amblyopia. For effective individual prediction, a nomogram was created. With great calibration, discrimination, and clinical usefulness, the prediction model demonstrated good performance.ConclusionThe findings underscore that the prevalence of ametropic amblyopia in pediatric CEL patients who underwent lens surgery exhibited a marked decline over time. The prediction model established with preoperative BCVA and cardiac phenotype can provide accurate and individualized predictions of postoperative amblyopia, and it has the potential to assist ophthalmologists in rapidly identifying high-risk patients.

Role of Vitamin C on methotrexate-induced nephrotoxicity in psoriasis context: A preclinical assessment

Methotrexate (MTX) is the most prescribed drug for systemic treatment of psoriasis. However, its clinical use is limited by its nephrotoxicity, which antioxidants can attenuate. This study evaluates the impact of vitamin C (vitC), a well-known antioxidant, on nephrotoxicity induced by high MTX doses in the context of psoriasis. To achieve this purpose, the kidney injury triggered by acute MTX exposure was established in an imiquimod-induced psoriasis-like mouse model. Mice were randomly divided into six groups: group 1 (control); group 2 (Imiquimod, IMQ), group 3 (IMQ+vitC 175 mg/kg/day); group 4 (MTX 20 mg/kg i.p); group 5 (IMQ+MTX 20 mg/kg) and group 6 (IMQ+MTX 20 mg/kg + vitC 175 mg/kg/day). The effects of these treatments were determined by considering the evolution of IMQ-induced skin lesions and serum creatinine levels. Moreover, histopathological analysis, lipid peroxidation, oxidative stress, and TNF-α production were determined in kidney tissue. Results showed that vitC attenuates renal damage in the context of IMQ-induced psoriasis. However, the opposite occurs when administered with IMQ+MTX, worsening skin psoriasis lesions and exacerbating acute renal tubular necrosis and oxidative DNA damage. These results establish new clues about the MTX-induced nephrotoxicity in the psoriasis context and the putative protective effects of vitC. It suggests that vitC supplementation could help attenuate the renal damage promoted by the psoriatic pathological environment. However, it should be avoided in psoriasis patients with renal dysfunction treated with MTX.

Chlorophyll Films for Radiation Dosimetry: A Feasibility Study

Abstract Novel Chlorophyll-PVA composite films have been prepared and tested for the dosimetry of therapeutic radiation. The radiation response has been quantified using UV-Vis spectroscopy. FTIR and XRD spectroscopies have been used to characterize the physical properties and irradiation response of the films. The films have shown response towards the therapeutic x-rays beams of 6 MV nominal energy in the tested dose range of 0.25 Gy to 32 Gy in discrete dose levels occurring in the geometric progression series of 2. The dosimeter has been found to exhibit sensitivity at a low dose of 0.25 Gy. The dose response curve of the dosimeter exhibits an exponential relationship of the absorbance and absorbed dose. A region of saturated absorbance has been observed beyond 4 Gy. The peak intensities of the FTIR spectra have been found to decrease with increasing doses as compared to the unirradiated samples, because of the changes in the bond polarities and molecular geometries. The XRD spectra indicates a change in the molecular orientation resulting in a decrease in peak intensity with increasing dose. This study indicates the feasibility of chl-PVA films in the dosimetry of therapeutic radiation. This film dosimeter can be processed locally with minimum resources and standardized against a known standard before clinical use. The chlorophyll molecules need careful handling owing to their sensitivity to light and temperature.

Intravenous versus oral tranexamic acid in elderly transforaminal lumbar interbody fusion patients: A prospective cohort study

BackgroundTranexamic acid (TXA) can effectively reduce intraoperative blood loss and transfusion rates. However, in spinal surgery, the number of surgical levels can significantly influence intraoperative and postoperative bleeding, particularly among the elderly, contributing to the persistently high rate of transfusion during the perioperative period. To verify the safety and efficacy of different application methods of TXA in elderly patients undergoing transforaminal lumbar interbody fusion (TLIF), a prospective cohort study was conducted. MethodsA total of 958 patients undergoing TLIF were randomly assigned to receive 2 g of oral TXA two hours before surgery or 15 mg/kg of intravenous TXA 30 min before surgery, or to a control group. The samples were further divided into three categories based on the number of fused segments (one-level fusion, two-level fusion, and three-level fusion). The primary outcomes were the total blood loss and transfusion rate. Secondary outcomes included intraoperative blood loss, postoperative blood loss, drainage volume, time until drain removal, perioperative transfusion volume, length of stay, thrombotic events, and other adverse events. Results336 patients received intravenous TXA and 314 patients were received oral TXA. Patient demographic factors were similar between groups. In the one-level fusion surgery cohort, comparisons across the three groups revealed no statistically significant disparities in total blood loss, transfusion rates, or drainage volumes (P > 0.05). In both two-level and three-level fusion surgeries, patients administered with TXA experienced a notably reduced perioperative bleeding compared to the control group (P < 0.01). Interestingly, a significant disparity was observed in the drainage volumes between the intravenous and oral administration groups (P = 0.026), specifically within the context of two and three-level fusion procedures. ConclusionIn elderly patients undergoing TLIF surgery, both intravenous and oral administrations of TXA are safe and effective. Oral TXA, being more economical and non-invasive compared to intravenous injection, holds promise for clinical use.

Multidisciplinary protocol to reduce surgical readmissions in Australia: American College of Surgeons National Surgical Quality Improvement Program.

Unplanned readmissions in general surgery are an important quality indicator of patient care and are associated with increased costs to healthcare services. This study aims to implement a multidisciplinary protocol in a single institution in a tertiary referral hospital to monitor and reduce unplanned readmission rates. A prospective cohort study using an institution-based protocol was conducted over an 18-month period including patients undergoing a general surgical procedure. The protocol included: (i) implementation of a surgical readmissions nurse-patient liaison; (ii) access to a surgical walk-in clinic; and (iii) early post-discharge phone contact. Data included demographic details, index procedure, hospital length of stay (LOS), and whether contact between patient/nurse occurred upon discharge. The primary outcome was the cause and rate of 30-day readmissions. Secondary outcomes were mortality, use of surgical clinic, emergency department presentations, and complications. After protocol implementation, 874 patients underwent a general surgical procedure, with 354 (49%) being male and an overall median age of 53.0 years (interquartile range: 36.0-67.0). The overall readmission rate was 5.6% (n = 49), with a median LOS after readmission of 4 days. Compared with historical pre-protocol ACS-NSQIP data, this reflects a 30% reduction compared to that of readmission rate of 7.9%, P = 0.03. The multidisciplinary protocol was efficacious in significantly reducing unplanned readmissions. Continued audits and monitoring of factors associated with readmissions are required to help design targeted projects that may lead to improved outcomes, lower costs, increased patient satisfaction, and better efficiency within our healthcare system.

Efficacy and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors for the Primary Prevention of Cardiovascular, Renal Events and Safety Outcomes in Patients with Systemic Lupus Erythematosus and Comorbid Type 2 Diabetes: A Population-based Target Trial Emulation.

Patients with systemic lupus erythematosus (SLE) were excluded from sodium-glucose co-transporter 2 inhibitors (SGLT2i) clinical trials. It is unknown whether the cardiorenal benefits of SGLT2i extend to patients with SLE and comorbid type 2 diabetes (T2D). We performed an emulated clinical trial in an insurance-based cohort in the U.S., evaluating SGLT2i versus dipeptidyl peptidase 4 inhibitors (DPP4i) for primary prevention of cardiovascular, renal, and other clinical outcomes among patients with both SLE patients and comorbid T2D. SGLT2i initiators were matched to DPP4i initiators using propensity scores (PS) based on clinical and demographic factors. Hazard ratios (HR with 95% confidence intervals) were calculated using Cox models. Outcomes among 2,165 patients starting SGLT2i and 2,165 PS-matched patients starting DPP4i were compared. Over 753.1 (±479.2) mean days, SGLT2i recipients had significantly lower risks of incident acute kidney injury (HR 0.49, 95% CI 0.39-0.63), chronic kidney disease (HR 0.61, 0.50-0.76), end-stage renal disease (HR 0.40, 0.20-0.80), heart failure (HR 0.72, 0.56-0.92), and emergency department visits (HR 0.90, 0.82-0.99). Risks of all-cause mortality (HR 0.89, 0.65-1.21), lupus nephritis (HR 0.67, 0.38-1.15), myocardial infarction (HR 0.81, 0.54-1.23), stroke (HR 1.03, 0.74-1.44), and hospitalizations (HR 0.76, 0.51-1.12) did not differ. Genital infection risk (HR 1.31, 1.07-1.61) was increased, but urinary tract infection risk (HR 0.90, 0.79-1.03) did not differ. No significant difference was observed for diabetic ketoacidosis risk (HR 1.065, 0.53-2.14) and fractures (HR 0.95, 0.66-1.36). In this emulated clinical trial, SGLT2i vs. DPP4i use was associated with significantly reduced risks of several cardiorenal complications among patients with both SLE and T2D.

Enhancing Preoperative Diagnosis Accuracy of Stage III Gastric Cancer with Circulating circRNAs.

The prognosis remains poor for stage III gastric cancer, and neoadjuvant chemotherapy is increasingly used to improve outcomes. Accurate diagnosis prior to treatment is essential to develop appropriate treatment strategies for poor prognosis subgroups. This study aims to enhance the accuracy of pre-treatment gastric cancer diagnosis using a biological approach centered on circulating circular RNA (circRNA). We conducted a comprehensive analysis of circRNA expression profiles using two Gene Expression Omnibus datasets to identify circRNA candidates associated with stage III gastric cancer. Subsequently, we validated these circRNA biomarkers in two independent clinical cohorts comprising a total of 174 patients with gastric cancer and non-disease controls through real-time polymerase chain reaction (PCR). Genome-wide circRNA analysis identified a panel of four biomarkers capable of diagnosing pathologically confirmed stage III (pStage III) gastric cancer. In a training cohort (n = 83), a clinically applicable panel of four circRNAs was developed (AUC 0.81), which was successfully validated in an independent clinical cohort (n = 82; AUC 0.76). To assess clinical utility, we combined clinical imaging (cStage) with the circRNA panel. Among those initially diagnosed as cStage III but later confirmed as pStage I/II, 86% were accurately diagnosed using the molecular biological approach with circRNAs. We have developed a circRNA-based non-invasive liquid biopsy that can improve the diagnostic performance of pStage III gastric cancer before treatment. Our circRNA model could provide a sophisticated and personalized approach to assist in treatment planning for patients with advanced gastric cancer.

Evaluation of serum inhibin B and inhibin B/FSH ratio in the diagnosis of non-obstructive azoospermia and oligozoospermia.

Infertility affects approximately 15 % of couples globally, with 50 % cases of male factor infertility. Precise assessment of spermatogenesis is essential for evaluating male infertility. Recent studies suggest serum inhibin B as a promising biomarker for testicular function. This study aims to evaluate the diagnostic utility of serum inhibin B in predicting male infertility, particularly focusing on its relationship with sperm count. A cross-sectional study was conducted on 80 adult men (mean age 31.4±6.89 years) presenting with infertility at gynecology and urology outpatient departments. Semen analysis was performed following WHO (2010) guidelines, and serum inhibin B levels were quantified. The correlation between serum inhibin B levels and sperm parameters was assessed using Pearson's correlation test. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic accuracy of serum inhibin B and the inhibin B/FSH ratio for non-obstructive azoospermia (NOA) and oligozoospermia. A significant positive correlation was observed between serum inhibin B and sperm count (r=0.94, p<0.001). ROC analysis demonstrated that the inhibin B/FSH ratio had the highest diagnostic accuracy for NOA and oligozoospermia (AUC=0.986), with sensitivity of 100 % and specificity of 91.67 %. Serum inhibin B alone also showed high diagnostic value (AUC=0.965 for NOA and 0.969 for oligozoospermia). Serum inhibin B is a reliable biomarker for assessing male infertility, particularly in evaluating spermatogenic function. The inhibin B/FSH ratio provides superior diagnostic accuracy for NOA and oligozoospermia, offering valuable clinical utility in male infertility diagnosis.

MiRNA in Machine-Learning-Based Diagnostics of Oral Cancer.

MicroRNAs (miRNAs) are crucial regulators of gene expression, playing significant roles in various cellular processes, including cancer pathogenesis. Traditional cancer diagnostic methods, such as biopsies and histopathological analyses, while effective, are invasive, costly, and require specialized skills. With the rising global incidence of cancer, there is a pressing need for more accessible and less invasive diagnostic alternatives. This research investigates the potential of machine-learning (ML) models based on miRNA attributes as non-invasive diagnostic tools for oral cancer. Methods and Tools: We utilized a comprehensive methodological framework involving the generation of miRNA attributes, including sequence characteristics, target gene associations, and cancer-specific signaling pathways. The miRNAs were classified using various ML algorithms, with the BayesNet classifier demonstrating superior performance, achieving an accuracy of 95% and an area under receiver operating characteristic curve (AUC) of 0.98 during cross-validation. The model's effectiveness was further validated using independent datasets, confirming its potential clinical utility. Our findings highlight the promise of miRNA-based ML models in enhancing early cancer detection, reducing healthcare burdens, and potentially saving lives. This study paves the way for future research into miRNA biomarkers, offering a scalable and adaptable diagnostic approach for various cancers.

Clinical utility index for root canal sealers

BackgroundEffective endodontic treatment requires the use of a root canal sealer with optimal properties to ensure a hermetic seal, prevent reinfection, and promote healing. Despite the availability of various sealers, a standardized evaluation system still needs to be improved.ObjectivesTo develop a Clinical Utility Index (CUI) that systematically evaluates and ranks root canal sealers based on their sealing ability, antimicrobial efficacy, flow rate, and solubility.MethodsThe CUI was developed through a structured process involving expert identification, panel discussions, and the establishment of scoring criteria. Five sealers were evaluated (Sealers A, B, C, D, and E). Mean values for the core properties were calculated, and sealers were ranked accordingly. The total CUI for each sealer was computed based on the assigned scores for each property.ResultsSealer B achieved the highest CUI at 95%, demonstrating superior performance across all core properties. Sealer C followed with a CUI of 80%, while Sealer A ranked third with 60%. Sealers D and E showed the lowest performance, with CUIs of 30% and 35%, respectively, highlighting deficiencies in multiple properties.DiscussionThe CUI provides a comprehensive evaluation framework for root canal sealers, facilitating informed decision-making by practitioners. Sealer B's high CUI underscores the importance of balancing sealing ability, antimicrobial effect, flow rate, and solubility. The results align with existing literature emphasizing the critical role of these properties in endodontic success.ConclusionThe CUI offers a robust and balanced method for evaluating root canal sealers, aiding in selecting the most suitable sealer based on empirical data. Future research should refine the index and validate its applicability in diverse clinical scenarios to enhance endodontic treatment outcomes.