Unveiling Disparities: Exploring Differential Attainment in Postgraduate Training Within Clinical Oncology.

AIMS: Differential attainment (DA) in post graduate medical training is a recognised challenge and refers to unexplained variation across groups when split by several protected characteristics. The Royal College of Radiology is committed to fostering diversity, inclusivity, and equality with the goal of narrowing existing gaps and improving training outcomes. MATERIALS AND METHODS: This was a mixed methods study aiming to understand the causes of DA with view to helping the RCR develop strategies to address this. A cross-sectional survey was completed by 140 clinical oncology trainees in September 2022. Trainees and trainers (17 and 6 respectively) from across England, Scotland, Wales and Northern Ireland, took part in focus group and interviews from August to December 2022. Quantitative and qualitative data merged and interpreted. RESULT: Results showed international medical graduates and trainees from ethnic minority backgrounds were more likely to encounter challenges. The qualitative findings were used to identify three themes through which these problems could be framed. The trainee as a "space invader," the hidden curriculum of clinical oncology training and the process of navigating and tacking the training journey. CONCLUSION: Differential attainment is the product of a complex interplay between the trainee, trainer, and the training environment. Therefore, interventions must be tailored to different people and contexts. At a national level, the RCR can adopt general policies to promote this such as mentorship programmes, protected time for supervision and cultural competency training. Efficacy of proposed interventions for trial and their impact on DA should be evaluated to drive evidence-based changes.

Characterization of Responses to Lenvatinib plus Pembrolizumab in Patients with Advanced Renal Cell Carcinoma at the Final Prespecified Survival Analysis of the Phase 3 CLEAR Study.

In the phase 3 CLEAR trial, lenvatinib plus pembrolizumab (L + P) showed superior efficacy versus sunitinib in treatment-naïve patients with advanced renal cell carcinoma (aRCC). The combination treatment was associated with a robust objective response rate of 71%. Here we report tumor responses for patients in the L + P arm in CLEAR, with median follow-up of ∼4 yr at the final prespecified overall survival (OS) analysis. Tumor responses were assessed by independent review using Response Evaluation Criteria in Solid Tumors v1.1. Patients with a complete response (CR; n = 65), partial response (PR) with maximum tumor shrinkage ≥75% (near-CR; n = 59), or PR with maximum tumor shrinkage <75% (other PR; n = 129), were characterized in terms of their baseline characteristics. The median duration of response was 43.7 mo (95% confidence interval [CI] 39.2-not estimable) for the CR group, 30.5 mo (95% CI 22.4-not estimable) for the near-CR group, and 17.2 mo (95% CI 12.5-21.4) for the other PR group. The 36-mo OS rates were consistently high in the CR (97%), near-CR (86%), and other PR (62%) groups. Robust objective response rates were observed across International Metastatic RCC Database Consortium favorable-risk (69%, 95% CI 60-78%), intermediate-risk (73%, 95% CI 67-79%), and poor-risk (70%, 95% CI 54-85%) subgroups. The robust response to L + P supports this combination as a standard-of-care first-line treatment for patients with aRCC. PATIENT SUMMARY: The CLEAR trial enrolled patients with advanced kidney cancer who had not previously received any treatment for their cancer. Here we report results for tumor shrinkage observed in the group that received lenvatinib plus pembrolizumab combination treatment during the trial. Shrinkage of target tumors with this combination was long-lasting and was observed in patients irrespective of their disease severity. This trial is registered on ClinicalTrials.gov as NCT02811861.

Advancing multimodal medical image fusion: an adaptive image decomposition approach based on multilevel Guided filtering.

With the rapid development of medical imaging methods, multimodal medical image fusion techniques have caught the interest of researchers. The aim is to preserve information from diverse sensors using various models to generate a single informative image. The main challenge is to derive a trade-off between the spatial and spectral qualities of the resulting fused image and the computing efficiency. This article proposes a fast and reliable method for medical image fusion depending on multilevel Guided edge-preserving filtering (MLGEPF) decomposition rule. First, each multimodal medical image was divided into three sublayer categories using an MLGEPF decomposition scheme: small-scale component, large-scale component and background component. Secondly, two fusion strategies-pulse-coupled neural network based on the structure tensor and maximum based-are applied to combine the three types of layers, based on the layers' various properties. The three different types of fused sublayers are combined to create the fused image at the end. A total of 40 pairs of brain images from four separate categories of medical conditions were tested in experiments. The pair of images includes various case studies including magnetic resonance imaging (MRI) , TITc, single-photon emission computed tomography (SPECT) and positron emission tomography (PET). We included qualitative analysis to demonstrate that the visual contrast between the structure and the surrounding tissue is increased in our proposed method. To further enhance the visual comparison, we asked a group of observers to compare our method's outputs with other methods and score them. Overall, our proposed fusion scheme increased the visual contrast and received positive subjective review. Moreover, objective assessment indicators for each category of medical conditions are also included. Our method achieves a high evaluation outcome on feature mutual information (FMI), the sum of correlation of differences (SCD), Qabf and Qy indexes. This implies that our fusion algorithm has better performance in information preservation and efficient structural and visual transferring.

The effect of physical activity on vitamin D: A systematic review and meta-analysis of intervention studies in humans.

Objectives: Cross-sectional studies demonstrate a positive association between higher physical activity and serum 25-hydroxyvitamin D (25(OH)D) concentration. However, whether this association is causal is unclear. We conducted a systematic review to identify intervention studies that examined the effect of physical activity on serum 25(OH)D concentration in humans. Study design: Systematic review and meta-analysis. Methods: We searched PubMed, Scopus and Web of Science to identify full-text peer-reviewed articles published in English from inception until January 2023. Eligible studies were randomised controlled trials or quasi-experimental studies. We used random effects meta-analysis to calculate the weighted mean difference (WMD) in the change in 25(OH)D concentration between physical activity and control groups. We used the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) to assess the methodological quality of included studies. Results: We included 32 articles in the systematic review and 24 in the meta-analysis. The intervention varied from resistance and weight-bearing exercises (n = 13) to aerobic exercises (n = 10), moderate and moderate-to-vigorous exercises (n = 5), aquatic exercise (n = 2), and multicomponent traditional exercises (n = 2) (Tai Chi and Yijinjing). The WMD in 25(OH)D in the physical activity and control groups was 9.51 and 4.87, respectively (between-group mean difference 4.64, p = 0.002). However, the difference was only evident in studies that implemented the intervention outdoors (n = 3; between-group mean difference 17.33, p < 0.0001); when the intervention was indoors there was no significant effect of physical activity on 25(OH)D (n = 16; between-group mean difference 1.80, p = 0.113). Conclusions: This meta-analysis of physical activity interventions in humans showed that physical activity does not lead to increased 25(OH)D independently of time outdoors. However, most studies were under-powered, in many the exercise was low intensity, and vitamin D was not the primary outcome.

Early Outcome of On-pump Versus Off-pump Elective Surgical Revascularization in Patients with Prior ST-Segment Elevation Myocardial Infarction.

Coronary artery bypass graft surgery (CABG) is a proven treatment for coronary artery disease. History of a ST-elevation myocardial infarction (STEMI) is considered an independent risk factor for CABG irrespective of timing for an emergency or elective surgery. Patients with STEMI are candidates for both On-pump and Off-pump CABG procedures. This paper discusses the possible best option for elective surgical revascularization in patients with prior STEMI. This prospective clinical trial of 60 eligible patients with prior STEMI was conducted in a Tertiary Care Hospital from April 2018 to March 2019. Among them, 30 patients underwent off-pump (Group A) and 30 patients underwent on-pump (Group B) CABG procedures. Outcomes between both groups were observed from surgery to 1 month postoperatively. Data was analysed by the software statistical program for social science (SPSS 25.0 Inc). The surgery was successful in both groups of patients. Differences were observed by mean number of grafts per patient (2.77±0.43 vs. 3.10±0.71) and duration of operation (4.41±0.35 hours vs. 5.71±0.48 hours). An improvement in Left Ventricular Ejection Fraction (LVEF %) was observed in both groups postoperatively (17.98% vs. 10.98%) and the postoperative LVEF% at different time points were found statistically significant (p<0.05) over preoperative LVEF%. Multivariable stepwise logistic regression analysis correlated on-pump CABG with prolonged need for ionotropic support, need for blood transfusion, longer hospital stay and less improvement in LVEF%. The study supports the Off-pump CABG as a better surgical option over on-pump CABG in patients with prior STEMI.

Impact of smoking status on clinical outcomes in patients with metastatic renal cell carcinoma treated with first-line immune checkpoint inhibitor-based regimens.

BACKGROUND: Current tobacco smoking is independently associated with decreased overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC) treated with targeted monotherapy (VEGF-TKI). Herein, we assess the influence of smoking status on the outcomes of patients with mRCC treated with the current first-line standard of care of immune checkpoint inhibitor (ICI)-based regimens. MATERIALS AND METHODS: Real-world data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were collected retrospectively. Patients with mRCC who received either dual ICI therapy or ICI with VEGF-TKI in the first-line setting were included and were categorized as current, former, or nonsmokers. The primary outcomes were OS, time to treatment failure (TTF), and objective response rate (ORR). OS and TTF were compared between groups using the log-rank test and multivariable Cox regression models. ORR was assessed between the 3 groups using a multivariable logistic regression model. RESULTS: A total of 989 eligible patients were included in the analysis, with 438 (44.3%) nonsmokers, 415 (42%) former, and 136 (13.7%) current smokers. Former smokers were older and included more males, while other baseline characteristics were comparable between groups. Median follow-up for OS was 21.2 months. In the univariate analysis, a significant difference between groups was observed for OS (P = .027) but not for TTF (P = .9), with current smokers having the worse 2-year OS rate (62.8% vs 70.8% and 73.1% in never and former smokers, respectively). After adjusting for potential confounders, no significant differences in OS or TTF were observed among the 3 groups. However, former smokers demonstrated a higher ORR compared to never smokers (OR 1.45, P = .02). CONCLUSION: Smoking status does not appear to independently influence the clinical outcomes to first-line ICI-based regimens in patients with mRCC. Nonetheless, patient counseling on tobacco cessation remains a crucial aspect of managing patients with mRCC, as it significantly reduces all-cause mortality.

Temporal and spatial patterns of Trichuris trichiura eggs: a potential threat to human health in Pakistan.

This study investigates the presence of Trichuris trichiura eggs in soil samples collected from urban areas in Lahore, Pakistan. A total of 3600 soil samples were collected over two years from Lahore's urban regions. The detection of helminth eggs in these samples was performed using sodium hypochlorite (NaOCl) as a diagnostic technique. The study reveals an overall prevalence rate of T. trichiura at 0.97 % (35 out of 3600) in the contaminated soil samples from Lahore's slum areas. When analyzing the data by geographical areas, the study found the highest prevalence of T. trichiura in Allama Iqbal Town (1.83 %, 11 out of 600), followed by Samanabad (1.16 %, 7 out of 600), Wapda Town (1.00 %, 6 out of 600), Gulberg (1.00 %, 6 out of 600), and Cantt (0.50 %, 3 out of 600). Conversely, Valencia Town had the lowest prevalence rate at 0.33 % (2 out of 600). However, these variations in prevalence rates were not statistically significant (p = 0.117). Prevalence rates of T. trichiura's eggs varied significantly across different sampling seasons (p>0.001). In autumn, a total of 900 soil samples were collected, with 19 samples (2.11 %) testing positive for T. trichiura. This rate was notably higher compared to the prevalence rates observed in winter, spring, and summer, which were 0.66 %, 0.22 %, and 0.88 %, respectively. Regarding the sampling months, the study observed a significantly higher prevalence during September (3.33 %, 10 out of 300), followed by October (2.33 %, 7 out of 300), and August (1.33 %, 4 out of 300). Prevalence rates gradually decreased in other months, ranging from 1 % to 0.33 % (3 to 1 out of 300), with no parasite detection in March (0 %, 0 out of 300) (p < 0.001). This research underscores soil contamination due to fecal waste and highlights public unawareness of parasite biology, driven by open defecation practices.

Phylogenomic reconstruction of Cryptosporidium spp. captured directly from clinical samples reveals extensive genetic diversity.

Cryptosporidium is a leading cause of severe diarrhea and mortality in young children and infants in Africa and southern Asia. More than twenty Cryptosporidium species infect humans, of which C. parvum and C. hominis are the major agents causing moderate to severe diarrhea. Relatively few genetic markers are typically applied to genotype and/or diagnose Cryptosporidium . Most infections produce limited oocysts making it difficult to perform whole genome sequencing (WGS) directly from stool samples. Hence, there is an immediate need to apply WGS strategies to 1) develop high-resolution genetic markers to genotype these parasites more precisely, 2) to investigate endemic regions and detect the prevalence of different genotypes, and the role of mixed infections in generating genetic diversity, and 3) to investigate zoonotic transmission and evolution. To understand Cryptosporidium global population genetic structure, we applied Capture Enrichment Sequencing (CES-Seq) using 74,973 RNA-based 120 nucleotide baits that cover ∼92% of the genome of C. parvum . CES-Seq is sensitive and successfully sequenced Cryptosporidium genomic DNA diluted up to 0.005% in human stool DNA. It also resolved mixed strain infections and captured new species of Cryptosporidium directly from clinical/field samples to promote genome-wide phylogenomic analyses and prospective GWAS studies.

WHOLE GENOME TARGETED ENRICHMENT AND SEQUENCING OF HUMAN-INFECTING CRYPTOSPORIDIUM spp.

Cryptosporidium spp. are protozoan parasites that cause severe illness in vulnerable human populations. Obtaining pure Cryptosporidium DNA from clinical and environmental samples is challenging because the oocysts shed in contaminated feces are limited in quantity, difficult to purify efficiently, may derive from multiple species, and yield limited DNA (<40 fg/oocyst). Here, we develop and validate a set of 100,000 RNA baits (CryptoCap_100k) based on six human-infecting Cryptosporidium spp. ( C. cuniculus , C. hominis , C. meleagridis , C. parvum , C. tyzzeri , and C. viatorum ) to enrich Cryptosporidium spp. DNA from a wide array of samples. We demonstrate that CryptoCap_100k increases the percentage of reads mapping to target Cryptosporidium references in a wide variety of scenarios, increasing the depth and breadth of genome coverage, facilitating increased accuracy of detecting and analyzing species within a given sample, while simultaneously decreasing costs, thereby opening new opportunities to understand the complex biology of these important pathogens.

Oleuropein, a phenolic component of Olea europaea L. ameliorates CCl4-induced liver injury in rats through the regulation of oxidative stress and inflammation.

OBJECTIVE: This study aimed to assess the hepatoprotective role of oleuropein (Olp), a phenolic compound found in olive, against carbon tetrachloride (CCl4)-induced liver damage in rats. MATERIALS AND METHODS: The research involved male albino rats, which received intraperitoneal injections of 100 mg/kg b.w. of oleuropein for 8 consecutive weeks before being subjected to carbon tetrachloride (CCl4) at a dosage of 1.0 ml/kg b.w. Changes induced by CCl4 in antioxidant and inflammatory marker levels were assessed using ELISA assay kits. Moreover, CCl4-induced liver tissue architecture alteration, fibrosis, and expression pattern of protein were evaluated by performing H&E, Sirius red, Masson trichrome, and immunohistochemistry staining. RESULTS: Increased serum transaminases and massive hepatic damage were observed by this liver toxicant. The hepatic injury was further evidenced by a significant decrease in antioxidant enzyme activity [superoxide dismutase (SOD), glutathione peroxidase (GPx), Glutathione (GSH) and Total Antioxidant Capacity (T-AOC)]. The administration of CCl4 resulted in an increased inflammatory response, which was measured by C-reactive protein, interleukin-6, as well as tumor necrosis factor-alpha. Olp as a curative regimen led to significant attenuation in the inflammatory response and oxidative/nitrosative stress. This polyphenol treatment improved the hepatic tissue architecture and decreased fibrosis. In the CCl4 treatment group, the expression pattern of IL-6 protein was high, whereas expression was decreased after Olp, as evidenced by immunohistochemistry staining. CONCLUSIONS: The study suggests that oleuropein treatment has the potential to reduce liver damage caused by CCl4 induction by inhibiting oxidative stress and inflammation and maintaining liver tissue architecture. This could make it a promising treatment option for liver pathogenesis.

Bifurcations and chaos control in a discrete Rosenzweig-Macarthur prey-predator model.

In this paper, we explore the local dynamics, chaos, and bifurcations of a discrete Rosenzweig-Macarthur prey-predator model. More specifically, we explore local dynamical characteristics at equilibrium solutions of the discrete model. The existence of bifurcations at equilibrium solutions is also studied, and that at semitrivial and trivial equilibrium solutions, the model does not undergo flip bifurcation, but at positive equilibrium solutions, it undergoes flip and Neimark-Sacker bifurcations when parameters go through certain curves. Fold bifurcation does not exist at positive equilibrium, and we have studied these bifurcations by the center manifold theorem and bifurcation theory. We also studied chaos by the feedback control method. The theoretical results are confirmed numerically.

Analytical assessment of clinical sensitivity and specificities of pharmaceutical rapid SARS-CoV-2 detection nasopharyngeal swab testing kits in Pakistan.

Despite of the global unity against COVID-19 pandemic, the threat of SARS-CoV-2 variants on the lives of human being is still not over. SARS-CoV-2 pandemic has urged the need of rapid viral detection at earliest. To cope with gradually expanding scenario of SARS-CoV-2, accurate diagnosis is extremely crucial factor which should be noticed by international health organizations. Limited research followed by sporadic marketing of SARS-CoV-2 rapid pharmaceutical detection kits raises critical questions against quality assurance and quality control measures. Herein we aimed to interrogate effectivity and specificity analysis of SARS-CoV-2 pharmaceutical rapid detection kits (nasopharyngeal swab based) using conventional gold standard triple target real-time polymerase chain reaction (USFDA approved). A cross-sectional study was conducted over 1500 suspected SARS-CoV-2 patients. 100 real time-PCR confirmed patients were evaluated for pharmaceutical RDT kits based upon nasopharyngeal swab based kits. The SARS-CoV-2 nasopharyngeal swab based rapid diagnostic kit (NSP RDTs) analysis showed 78% reactivity. Among real time PCR confirmed negative subjects, 49.3% represented false positivity. The positive predictive analysis revealed 67.82%, while negative predictive values were 64.40%. The NSP RDTs showed limited sensitivities and specificities as compared to gold standard real time PCR. Valid and authentic detection of SARS-CoV-2 is deemed necessary for accurate COVID-19 surveillance across the globe. Current study highlights the potential consequences of inadequate detection of SARS-CoV-2 and emerging novel mutants, compromising vaccine preventable diseases. Current study emphasizes need to wake higher authorities including strategic organizations for designing adequate measures to prevent future SARS-CoV-2 epidemics.

The effect of antiplatelet therapy and oral anticoagulants on the accuracy of faecal immunochemical testing.

INTRODUCTION: Faecal immunochemical testing (FIT) has been adopted to identify patients requiring further investigations on the colorectal cancer (CRC) referral pathway. We aimed to investigate the effect of antiplatelet and anticoagulant drugs on the accuracy of FIT results. METHODS: This observational study categorised patients with suspected CRC symptoms, who completed both FIT and colonic investigations, into two groups (control and exposed) based on their use of antiplatelet and anticoagulant drugs. Two-by-two tables and receiver operating characteristic (ROC) curve analysis were used to determine accuracy. RESULTS: A total of 928 patients were divided into a control (n=683) and an exposed group (n=245). A nonsignificant higher proportion of patients tested positive in the exposed group (24.1% vs 18.4%, p=0.063). For detection of CRC, improved sensitivity of 87% vs 81.2%, specificity of 84.8% vs 79.9% and negative predictive value of 99.2% vs 98.3% was calculated in the control vs exposed groups, respectively. The positive predictive value was comparable between the two groups (21.4% vs 22% in the control and exposed groups, respectively). In ROC analysis, there was no difference between the groups (AUC 90% vs 87%, p=0.56). The use of antiplatelet and anticoagulant drugs did not increase the risk of positive FIT results on multivariate logistic regression analysis. CONCLUSIONS: FIT accuracy for CRC detection remained unaffected despite more patients testing positive in the exposed group. FIT should be considered a supplementary tool for triage. Antiplatelet and anticoagulant drugs do not need to be discontinued before collection of FIT.

Terahertz Detection by Asymmetric Dual Grating Gate Bilayer Graphene FETs with Integrated Bowtie Antenna.

An asymmetric dual-grating gate bilayer graphene-based field effect transistor (ADGG-GFET) with an integrated bowtie antenna was fabricated and its response as a Terahertz (THz) detector was experimentally investigated. The device was cooled down to 4.5 K, and excited at different frequencies (0.15, 0.3 and 0.6 THz) using a THz solid-state source. The integration of the bowtie antenna allowed to obtain a substantial increase in the photocurrent response (up to 8 nA) of the device at the three studied frequencies as compared to similar transistors lacking the integrated antenna (1 nA). The photocurrent increase was observed for all the studied values of the bias voltage applied to both the top and back gates. Besides the action of the antenna that helps the coupling of THz radiation to the transistor channel, the observed enhancement by nearly one order of magnitude of the photoresponse is also related to the modulation of the hole and electron concentration profiles inside the transistor channel by the bias voltages imposed to the top and back gates. The creation of local n and p regions leads to the formation of homojuctions (np, pn or pp+) along the channel that strongly affects the overall photoresponse of the detector. Additionally, the bias of both back and top gates could induce an opening of the gap of the bilayer graphene channel that would also contribute to the photocurrent.

Effect of COVID-19 Lockdown on Maternal and Infant Healthcare Services in an Urban Resettlement Area of East Delhi.

INTRODUCTION:  The coronavirus disease 2019 (COVID-19) pandemic has substantially disrupted essential maternal and infant healthcare services due to the diversion of resources. The imposition of lockdown was one of the critical strategies to flatten the curve in several countries, including India. This led to restricted access to pregnancy-related care, immunization services, and had an impact on home-based newborn care. We aimed to determine the effect of the COVID-19 lockdown on institutional deliveries and child healthcare services in a residential community of East Delhi. METHODS: This community-based, comparative study was conducted between January 2021 and August 2022. Seventy-seven families experiencing childbirth during the COVID-19 lockdown period (24th March 2020 to 30th November 2020) were compared with an equivalent number of families having childbirth during the corresponding period preceding the lockdown (24th March 2019 to 30th November 2019). The study involved face-to-face interviews conducted using a pretested and pre-validated interviewer-administered schedule. RESULTS: We found that non-institutional deliveries were substantially higher in the during-lockdown group (n=11, 14.3%) compared to the before-lockdown group (n=1, 1.3%) (OR=12.67 [1.59, 100.73]). Additionally, a significantly lower proportion of pregnant women received a minimum of four antenatal checkups (OR=8.26 [2.71, 25.23]), as well as iron and calcium supplementation during the lockdown. Reasons for non-institutional deliveries primarily included unavailability and denial of delivery services, as well as the fear of exposure to COVID-19 infection, as highlighted in our study. A significantly lower proportion [OR=6.07 (2.56, 14.42)] of children were found to be immunized-for-age, along with a substantial delay in vaccination among those born during the lockdown period. There was a significant decrease in home visits by community health workers during both the antenatal and postnatal periods amidst the lockdown. Moreover, the proportion of children exclusively breastfed for six months was notably lower [OR=2.32 (1.17, 4.63)], and the age until which exclusive breastfeeding was continued was lower in the during-lockdown group. Regarding healthcare-seeking behavior, services were sought by the families of 95.5% of children who fell sick during the lockdown period. Approximately 45.2% of families procured medicines from private health facilities, while about one-third acquired them from non-registered medical practitioners (NRMPs). CONCLUSION: The COVID-19 lockdown significantly affected maternal and child healthcare services, leading to adverse outcomes across various crucial aspects. Institutional deliveries, antenatal care, community health worker visits, child immunization, and healthcare-seeking behavior were all adversely affected. In times of natural disasters like pandemics, it is crucial to establish specific provisions ensuring uninterrupted maternal and child healthcare throughout the lockdown. Integrating health education into essential services becomes imperative within the pandemic preparedness plan.

Application of a Specific and Sensitive NQO1 Turn-On Near-Infrared Fluorescence Probe for Live Cancer Cell and Xenografted Tumor Imaging in Nude Mice.

Sensitive activity stains for enzymes selectively expressed in human cancers offer valuable tools for imaging with wide applications in experimental, diagnostic, and therapeutic settings. The scant expression of the antioxidant enzyme NQO1 in normal tissues and its great abundance in malignant counterparts due to the increased redox stress and hypoxia is one such example. Previously, we described a potent nontoxic probe that remains nonfluorescent but releases an intense fluorogenic compound after intracellular cleavage by NQO1 catalysis. This infrared probe with a 644 nm emission has excellent tissue penetrating ability and low background absorption. Described here are methods (fluorescence microscopy, flow cytometry, and in vivo animal imaging) to rapidly image NQO1 activity in hypoxic and non-hypoxic cancer cells and tumors developed in live mouse xenograft models. The specificity of the dye for NQO1 in all three procedures was verified, and the methods should be useful for both in vitro and in vivo studies.

Lenvatinib Plus Pembrolizumab Versus Sunitinib in First-Line Treatment of Advanced Renal Cell Carcinoma: Final Prespecified Overall Survival Analysis of CLEAR, a Phase III Study.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We present the final prespecified overall survival (OS) analysis of the open-label, phase III CLEAR study in treatment-naïve patients with advanced renal cell carcinoma (aRCC). With an additional follow-up of 23 months from the primary analysis, we report results from the lenvatinib plus pembrolizumab versus sunitinib comparison of CLEAR. Treatment-naïve patients with aRCC were randomly assigned to receive lenvatinib (20 mg orally once daily in 21-day cycles) plus pembrolizumab (200 mg intravenously once every 3 weeks) or sunitinib (50 mg orally once daily [4 weeks on/2 weeks off]). At this data cutoff date (July 31, 2022), the OS hazard ratio (HR) was 0.79 (95% CI, 0.63 to 0.99). The median OS (95% CI) was 53.7 months (95% CI, 48.7 to not estimable [NE]) with lenvatinib plus pembrolizumab versus 54.3 months (95% CI, 40.9 to NE) with sunitinib; 36-month OS rates (95% CI) were 66.4% (95% CI, 61.1 to 71.2) and 60.2% (95% CI, 54.6 to 65.2), respectively. The median progression-free survival (95% CI) was 23.9 months (95% CI, 20.8 to 27.7) with lenvatinib plus pembrolizumab and 9.2 months (95% CI, 6.0 to 11.0) with sunitinib (HR, 0.47 [95% CI, 0.38 to 0.57]). Objective response rate also favored the combination over sunitinib (71.3% v 36.7%; relative risk 1.94 [95% CI, 1.67 to 2.26]). Treatment-emergent adverse events occurred in >90% of patients who received either treatment. In conclusion, lenvatinib plus pembrolizumab achieved consistent, durable benefit with a manageable safety profile in treatment-naïve patients with aRCC.

Disinfection by methylthionine chloride and chitosan in combination with Photo radiation therapy on caries affected dentin nano hardness, adhesive integrity, and bond failure.

OBJECTIVE: The aim of the study was to assess the disinfection efficacy, bond integrity, and nano hardness of caries-affected dentin (CAD) surface bonded to resin cement when disinfected with chlorhexidine (CHX), Methylene blue activated by Photodynamic therapy (MB-PDT), chitosan, silver diamine fluoride (SDF), chitosan activated by PDT, and SDF-diode laser against S. mutans. MATERIALS AND METHODS: A total of 60 human mandibular molars were extracted non-traumatically and gathered using ICDAS criteria. The dentin surface was prepared, leaving CAD to receive a disinfection procedure. After inoculation with S. mutans, the CAD samples were divided into six groups and disinfected with various disinfectants (n = 10) CHX, MB-PDT, chitosan, chitosan-PDT, SDF, and SDF+ diode laser. Survival rates of S. mutans were analyzed following the restoration of samples with resin cement via the etch and rinse method to assess SBS. Also, nano hardness was analyzed. Statistical analysis was performed by using the ANOVA and the Tukey multiple test (p<0.05). The Kruskal-Wallis test was used to evaluate the change in survival rate. RESULTS: Related to the survival rates, the SDF+ diode laser displayed the highest reduction in S. mutans levels and chitosan presented the lowest level of disinfection. The intergroup comparison revealed that CHX and chitosan-PDT displayed comparable outcomes of S. mutans survival rate to that of SDF+ diode laser (p>0.05). Likewise, MB-PDT and SDF displayed a comparable survival rate of S. mutans to Chitosan disinfection (p>0.05). Considering SBS and nano hardness, the highest SBS and NH were exhibited by the SDF+ diode laser, and the lowest SBS and NH values were exhibited by MB-PDT. The intragroup comparison revealed that CAD specimens disinfected with Chitosan-PDT showed comparable SBS and NH values to the SDF+ diode laser (p>0.05). CHX, chitosan, and SDF exhibited bond values and NH comparable to MB-PDT (p<0.05). CONCLUSIONS: Synergistic use of Silver diamine fluoride with diode laser and chitosan activated by PDT can be used as an alternative to CHX for controlling S. mutans growth, promoting enhanced bond efficacy and nano hardness for bonding resin cement to the caries-affected dentin.

Endoscopic Image Enhancement: Wavelet Transform and Guided Filter Decomposition-Based Fusion Approach.

Endoscopies are helpful for examining internal organs, including the gastrointestinal tract. The endoscope device consists of a flexible tube to which a camera and light source are attached. The diagnostic process heavily depends on the quality of the endoscopic images. That is why the visual quality of endoscopic images has a significant effect on patient care, medical decision-making, and the efficiency of endoscopic treatments. In this study, we propose an endoscopic image enhancement technique based on image fusion. Our method aims to improve the visual quality of endoscopic images by first generating multiple sub images from the single input image which are complementary to one another in terms of local and global contrast. Then, each sub layer is subjected to a novel wavelet transform and guided filter-based decomposition technique. To generate the final improved image, appropriate fusion rules are utilized at the end. A set of upper gastrointestinal tract endoscopic images were put to the test in studies to confirm the efficacy of our strategy. Both qualitative and quantitative analyses show that the proposed framework performs better than some of the state-of-the-art algorithms.

Outcomes of Patients with Brain Metastases from Renal Cell Carcinoma Receiving First-line Therapies: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Patients with brain metastases (BrM) from renal cell carcinoma and their outcomes are not well characterized owing to frequent exclusion of this population from clinical trials. We analyzed data for patients with or without BrM using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). A total of 389/4799 patients (8.1%) had BrM on initiation of systemic therapy. First-line immuno-oncology (IO)-based combination therapy was associated with longer median overall survival (OS; 32.7 mo, 95% confidence interval [CI] 22.3-not reached) versus tyrosine kinase inhibitor monotherapy (20.6 mo, 95% CI 15.7-24.5; p = 0.019), as were intensive focal therapies with stereotactic radiotherapy or neurosurgery (31.4 mo, 95% CI 22.3-37.5) versus whole-brain radiotherapy alone or no focal therapy (16.5 mo, 95% CI 10.2-21.1; p = 0.028). On multivariable analysis, IO-based regimens (HR 0.49, 95% CI 0.25-0.97; p = 0.040) and stereotactic radiotherapy or neurosurgery (HR 0.48, 95% CI 0.29-0.78; p = 0.003) were independently associated with longer OS, as was IMDC favorable or intermediate risk (HR 0.40, 95% CI 0.24-0.66; p < 0.001). Intensive systemic and focal therapies were associated with better prognosis in this population. Further studies should explore the clinical effectiveness of multimodal strategies. PATIENT SUMMARY: In a large group of patients with advanced kidney cancer, we found that 8.1% had brain metastases when starting systemic therapy. Patients with brain metastases had significantly poorer prognosis than those without brain metastases. Receipt of combination immunotherapy, stereotactic radiotherapy, or neurosurgery was associated with longer overall survival.