A social enterprise model for TB detection and treatment through the private sector in Pakistan.

BACKGROUND: Existing models to increase TB case notifications from the private sector in Pakistan are financially unsustainable and have achieved modest success due to limited coverage. OBJECTIVE: To evaluate the impact of a social enterprise model (SEM) intervention on TB case detection in Karachi, Pakistan, and to assess its financial sustainability. METHODS: Purpose-built centres were established within the private sector that integrated TB screening, diagnostics and treatment and operated 12 hours per day with convenient locations to improve access. TB services were offered free of cost, and revenue generation took place through user fees from other diagnostics. Private providers with a focus on the informal sector were engaged through community workers to generate screening referrals. RESULTS: Overall 171,488 people were screened and 18,683 cases were notified, including 197 individuals with drug-resistant TB. Annual TB notifications in Karachi increased from 18,105 in 2014 to a maximum of 25,840 (40% increase). The proportion of cases in Karachi notified by the centres grew to 27% in 2020. Commercial revenue reached USD288,065 and enabled operating cost recovery of 15%. Average cost per TB case notified was USD203. CONCLUSION: The SEM intervention contributed a large proportion of notifications in Karachi and achieved modest cost recovery.

CONTEXTE: Les modèles existants visant à augmenter les notifications de cas de TB par le secteur privé au Pakistan ne sont pas viables financièrement et n'ont obtenu qu'un succès modeste en raison d'une couverture limitée. OBJECTIF: Évaluer l'impact d'un modèle déntreprise sociale (SEM, pour l'anglais « social entreprise model ¼) sur la détection des cas de TB à Karachi, au Pakistan, et évaluer sa viabilité financière. MÉTHODES: Des centres spécialisés ont été créés dans le secteur privé. Ils intègrent le dépistage, le diagnostic et le traitement de la TB et fonctionnent 12 heures par jour dans des lieux adaptés afin dén faciliter l'accès. Les services de lutte contre la TB étaient gratuits et les recettes provenaient des frais d'utilisation des autres diagnostics. Des prestataires privés, axés sur le secteur informel, ont été engagés par l'intermédiaire d'agents communautaires pour orienter les patients vers les services de dépistage. RÉSULTATS: Au total, 171 488 personnes ont été dépistées et 18 683 cas ont été notifiés, dont 197 personnes atteintes de TB résistante aux médicaments. Les notifications annuelles de TB à Karachi sont passées de 18 105 en 2014 à un maximum de 25 840 (augmentation de 40%). La proportion de cas à Karachi notifiés par les centres est passée à 27% en 2020. Les recettes commerciales ont atteint 288 065 USD et ont permis un recouvrement des coûts déxploitation de 15%. Le coût moyen par cas de TB notifié était de 203 USD. CONCLUSION: L'intervention SEM a contribué à une grande proportion de notifications à Karachi et a permis un modeste recouvrement des coûts.

Identifying functional cortical plasticity after spinal tumour resection using navigated transcranial magnetic stimulation.

Our aim was to investigate the effectiveness of navigated transcranial magnetic stimulation (nTMS) brain mapping to characterise preoperative motor impairment caused by an intradural extramedullary (IDEM) tumour and postoperative cortical functional reorganisation. Preoperative and 1-year follow-up clinical, radiological and nTMS data from a case of thoracic spinal meningioma that underwent surgical resection of the lesion were collected and compared. A 67-year-old patient presented with severe progressive thoracic myelopathy (hypertonic paraparesis, clonus, insensate urinary retention) secondary to an IDEM tumour. Initial nTMS assessment showed bilateral upper limb representation with no positive responses for both lower limbs. He underwent successful surgical resection for his IDEM (meningioma WHO grade 1). At 1-year follow-up, the patient's gait was improved and his bladder function normalised. nTMS documented positive responses for both upper and lower limbs and a decrease in the area (right side: 1.01 vs 0.39cm2; left side: 1.92 vs 0.81cm2) and volume (right side: 344.2 vs 42.4uVcm2; left side: 467.1 vs 119uVcm2) of cortical activation for both upper limbs, suggesting a functional reorganisation of the motor areas after tumour resection. nTMS motor mapping and derived metrics can characterise preoperative motor deficit and cortical plasticity during follow-up after IDEM resection.

2022 TB programme review in Pakistan: strengthening governance, with better patient diagnosis and treatment.

BACKGROUND: In Pakistan, 84% of healthcare is provided by the private sector. We conducted an epidemiological and programme review for TB to document progress and guide further efforts. METHODS: Surveillance and data systems were assessed before analysing epidemiological data. We reviewed the programme at federal, provincial and peripheral levels and compiled national data along with WHO estimates to describe the evolution of epidemiological and programme indicators. RESULTS: In 2021, of the estimated number of TB cases, 55% of overall cases and 18% of drug-resistant cases were diagnosed and treated respectively. The contribution of the private sector in case detection increased from 30% in 2017 to 40% by 2021. For newly diagnosed pulmonary TB cases, the overall proportion of confirmed cases was 52%. In 2021, testing for rifampicin resistance among confirmed cases was 66% for new and 84% for previously treated patients. The treatment success rate exceeded 90% for drug susceptible TB. The main challenges identified were a funding gap (60% in 2021-2023), fragmented electronic systems for data collection and suboptimal coordination among provinces. CONCLUSIONS: The main challenges prevent further progress in controlling TB. By addressing these, Pakistan could improve coverage of interventions, including diagnosis and treatment. Bacteriological confirmation using recommended diagnostics also requires further optimisation.

CONTEXTE: Au Pakistan, le secteur privé assure 84% des services de santé. Une étude épidémiologique et programmatique a été réalisée sur la TB afin de recueillir des informations sur les avancées réalisées et de guider les actions à venir. MÉTHODES: Les systèmes de surveillance et de données ont été évalués préalablement à l'analyse des données épidémiologiques. Nous avons examiné le programme aux niveaux fédéral, provincial et local et compilé les données nationales ainsi que les estimations de l'OMS afin de décrire l'évolution des indicateurs épidémiologiques et du programme. RÉSULTATS: En 2021, environ 55% de l'ensemble cas de TB et 18% des cas résistants aux médicaments ont été diagnostiqués et traités respectivement. La contribution du secteur privé dans la détection des cas est passée de 30% en 2017 à 40% en 2021. La proportion totale de cas confirmés pour les nouveaux diagnostics de TB pulmonaire s'élevait à 52%. En 2021, les tests de résistance à la rifampicine parmi les cas confirmés s'élevaient à 66% pour les nouveaux patients et de 84% pour les patients déjà traités. Le taux de réussite du traitement a dépassé 90% pour la TB sensible aux médicaments. Les défis majeurs comprennent un manque de financement (60% pour la période 2021­2023), des systèmes électroniques de collecte de données fragmentés et une coordination insuffisante entre les provinces. CONCLUSIONS: Les défis majeurs entravent les avancées dans la lutte contre la TB. En les mettant en évidence, le Pakistan pourrait améliorer la portée des interventions, y compris le diagnostic et le traitement. Il est également essentiel d'optimiser la confirmation bactériologique en utilisant les diagnostics recommandés.

SARS-CoV-2 clearance in term of Cycle Threshold (Ct) during first two waves of COVID-19 in Pakistan: a phenomenon of delayed viral clearance post-corticosteroid treatment.

SARS-CoV-2 is recently emerged virus, which caused millions of deaths, all over the world. To tackle COVID-19 pandemic, there is an utmost need for in-depth analysis of viral replication. We aimed to examine viral load in SARS-CoV-2 patients during first two waves of COVID-19 in Pakistan. 225,615 suspected subjects from 75 different regions of Pakistan were selected in the study. SARS-CoV-2 RNAs were detected via real time PCR. During first wave (period of June-July, 2020) of COVID-19 the prevalence of SARS-CoV-2 was 20.38%. However, during second wave (period of November-December, 2020) of COVID-19, the rate of prevalence was 9.41%. During first wave of COVID-19 96.31% of participants remained PCR positive for 14 to 21 days, 3.39% of subjects showed positive results for 22 to 35 days, while delayed Ct values were observed among 0.26% of participants for 36 to 49 days. However, during second wave of COVID-19 89.31% of the subjects exhibited symptoms and showed real-time PCR positive results for 14 to 21 days, 9.42% showed positive results for 22 to 35 days, while significantly delayed Ct value results were observed among 1.026% of participants for 36 to 63 days (3.95 times higher than first wave). In contrast to first wave of COVID-19, the factors that were different in second wave were neither viral (different strains) nor host (same population). But treatment factors changed significantly. As during second wave besides azithromycin, corticosteroid dexamethasone consumption was increased consequently causing delayed Ct value negativity. This suggests that corticosteroid treatment might be linked with delayed Ct value or viral clearance. This study is crucial for re-considering effective therapeutic options against COVID-19.

Needle Biopsy of Pleura in the Aetiological Diagnosis of Pleural Effusion.

Exudative pleural effusion appears as manifestation of underlying specific disease process and pleural biopsy is usually enough to find out the underlying causative disease. The aim of the study was to find out the efficacy of needle biopsy of pleura in the aetiological diagnosis of pleural effusion. This cross-sectional study was conducted for a period of one year from January 2008 to December 2008 in the Department of Medicine, Shaheed Ziaur Rahman Medical College Hospital, Bogura, Bangladesh enrolling 50 subjects with exudative pleural effusion. The cases with transudative pleural effusion were not included. Needle biopsy was done in all the cases. Histopathological reports of pleural biopsy specimen were correlated with other data and analyzed to detect the causes of effusion. Major incidence of malignant effusion occurred between 41 to 70 years of age. No malignant effusion was found before 30 years of age. Incidence of tuberculous and malignant pleural effusion was much more common in males than in females. Sensitivity and specificity of combined pleural biopsy and pleural fluid analysis in the diagnosis of pleural effusion was 97.06% and 100.% for tuberculosis and 81.82% and 100.0% for malignancy. The present study reveals that pleural biopsy was very effective method in the diagnosis of cause of pleural effusion.

Evaluating compliance with the care standard of proactively assessing bone health in patients with diabetes: a pilot audit of practice across Asia by the Asia Pacific Consortium on Osteoporosis (APCO).

This pilot audit explored how bone health is assessed patients with diabetes in diverse centres across Asia. Only 343 of 1092 (31%) audited patients had a bone health assessment, 27% of whom were diagnosed with osteoporosis. Quality improvement strategies are needed to address gaps in patient care in this area. PURPOSE: The Asia Pacific Consortium on Osteoporosis (APCO) Framework outlines clinical standards for assessing and managing osteoporosis. A pilot audit evaluated adherence to clinical standard 4, which states that bone health should be assessed in patients with conditions associated with bone loss and/or increased fracture risk; this report summarises the audit findings in patients with diabetes. A secondary aim was to assess the practicality and real-world use of the APCO bone health audit tool kit. METHODS: Eight centres across Asia participated in the pilot audit, selecting diabetes as the target group. Participants reviewed their practice records for at least 20 consecutively treated patients with the target condition. Questions covered routine investigations, bone health assessment, osteoporosis diagnosis, and patient referral pathways. Data were summarised descriptively. RESULTS: The participants represented public hospitals, university medical centres, and private clinics from India, Malaysia, Pakistan, Singapore, Taiwan, and Vietnam that see an estimated total of 95,000 patients with diabetes per year. Overall, only 343 of 1092 audited patients (31%) had a bone health assessment. Osteoporosis was subsequently diagnosed in 92 of 343 (27%) patients. CONCLUSION: Bone health was not assessed in most patients with diabetes. The results provide insight into current practices across diverse Asian centres and demonstrate the practical value of the audit tool kit. Participant feedback has been used to improve the tool kit. Results of this pilot audit are being used in the respective centres to inform quality improvement projects needed to overcome the gap in patient care.

Unveiling the occurrence of COVID-19 in a diverse Bangladeshi population during the pandemic.

Introduction: COVID-19 pandemic hit Bangladesh with relatively low intensity, unlike its neighbors India and European countries and USA. Methods: The present report included data of 8,480 individuals tested for COVID-19 RT-PCR of the workers and officials from readymade garments (RMG) industry in Chandra area in Gazipur. The present data looked into the clinic-demographic factors associated with the susceptibility of the condition. Result: The data elucidated the susceptibility of the individuals to SARS-CoV-2 based on age, gender, pre-existing health conditions, and the presence of symptoms. It was observed that individuals aged over 60 had the highest rate of COVID-19 positivity, and men exhibited a higher infection rate compared to women. Regardless of age, fever and cough were the most frequently reported symptoms. Two-thirds of the individuals included in this report appeared to be asymptomatic carriers. The prevalence of comorbidities among individuals who tested positive for COVID-19 was notably higher, and this exhibited a gender-specific pattern. Discussion: Although our study provides important epidemiological insights into the initial year of the pandemic among Bangladeshi populations, it can also add value for future drug and vaccine development. However, it is essential to acknowledge the limitations like - restriction of public movement, unavailability of vehicle yielding a selection bias, due to the lockdown conditions imposed owing to the pandemic and the diverse characteristics of the participants. The report emphasizes the significance of figuring out how age, gender, and underlying health conditions impact susceptibility to and transmission of COVID-19, thereby providing valuable insights for public health strategies and future research initiatives.

The Use of Artificial Intelligence in Endodontics.

Endodontics is the dental specialty foremost concerned with diseases of the pulp and periradicular tissues. Clinicians often face patients with varying symptoms, must critically assess radiographic images in 2 and 3 dimensions, derive complex diagnoses and decision making, and deliver sophisticated treatment. Paired with low intra- and interobserver agreement for radiographic interpretation and variations in treatment outcome resulting from nonstandardized clinical techniques, there exists an unmet need for support in the form of artificial intelligence (AI), providing automated biomedical image analysis, decision support, and assistance during treatment. In the past decade, there has been a steady increase in AI studies in endodontics but limited clinical application. This review focuses on critically assessing the recent advancements in endodontic AI research for clinical applications, including the detection and diagnosis of endodontic pathologies such as periapical lesions, fractures and resorptions, as well as clinical treatment outcome predictions. It discusses the benefits of AI-assisted diagnosis, treatment planning and execution, and future directions including augmented reality and robotics. It critically reviews the limitations and challenges imposed by the nature of endodontic data sets, AI transparency and generalization, and potential ethical dilemmas. In the near future, AI will significantly affect the everyday endodontic workflow, education, and continuous learning.

Chaos and bifurcations of a two-dimensional hepatitis C virus model with hepatocyte homeostasis.

In this paper, we delve into the intricate local dynamics at equilibria within a two-dimensional model of hepatitis C virus (HCV) alongside hepatocyte homeostasis. The study investigates the existence of bifurcation sets and conducts a comprehensive bifurcation analysis to elucidate the system's behavior under varying conditions. A significant focus lies on understanding how changes in parameters can lead to bifurcations, which are pivotal points where the qualitative behavior of the system undergoes fundamental transformations. Moreover, the paper introduces and employs hybrid control feedback and Ott-Grebogi-Yorke strategies as tools to manage and mitigate chaos inherent within the HCV model. This chaos arises due to the presence of flip and Neimark-Sacker bifurcations, which can induce erratic behavior in the system. Through the implementation of these control strategies, the study aims to stabilize the system and restore it to a more manageable and predictable state. Furthermore, to validate the theoretical findings and the efficacy of the proposed control strategies, extensive numerical simulations are conducted. These simulations serve as a means of confirming the theoretical predictions and provide insight into the practical implications of the proposed control methodologies. By combining theoretical analysis with computational simulations, the paper offers a comprehensive understanding of the dynamics of the HCV model and provides valuable insights into potential strategies for controlling and managing chaos in such complex biological systems.

Recurrence plot embeddings as short segment nonlinear features for multimodal speaker identification using air, bone and throat microphones.

Speech is produced by a nonlinear, dynamical Vocal Tract (VT) system, and is transmitted through multiple (air, bone and skin conduction) modes, as captured by the air, bone and throat microphones respectively. Speaker specific characteristics that capture this nonlinearity are rarely used as stand-alone features for speaker modeling, and at best have been used in tandem with well known linear spectral features to produce tangible results. This paper proposes Recurrent Plot (RP) embeddings as stand-alone, non-linear speaker-discriminating features. Two datasets, the continuous multimodal TIMIT speech corpus and the consonant-vowel unimodal syllable dataset, are used in this study for conducting closed-set speaker identification experiments. Experiments with unimodal speaker recognition systems show that RP embeddings capture the nonlinear dynamics of the VT system which are unique to every speaker, in all the modes of speech. The Air (A), Bone (B) and Throat (T) microphone systems, trained purely on RP embeddings perform with an accuracy of 95.81%, 98.18% and 99.74%, respectively. Experiments using the joint feature space of combined RP embeddings for bimodal (A-T, A-B, B-T) and trimodal (A-B-T) systems show that the best trimodal system (99.84% accuracy) performs on par with trimodal systems using spectrogram (99.45%) and MFCC (99.98%). The 98.84% performance of the B-T bimodal system shows the efficacy of a speaker recognition system based entirely on alternate (bone and throat) speech, in the absence of the standard (air) speech. The results underscore the significance of the RP embedding, as a nonlinear feature representation of the dynamical VT system that can act independently for speaker recognition. It is envisaged that speech recognition too will benefit from this nonlinear feature.

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.

Leveraging single-cell sequencing to classify and characterize tumor subgroups in bulk RNA-sequencing data.

PURPOSE: Accurate classification of cancer subgroups is essential for precision medicine, tailoring treatments to individual patients based on their cancer subtypes. In recent years, advances in high-throughput sequencing technologies have enabled the generation of large-scale transcriptomic data from cancer samples. These data have provided opportunities for developing computational methods that can improve cancer subtyping and enable better personalized treatment strategies. METHODS: Here in this study, we evaluated different feature selection schemes in the context of meningioma classification. To integrate interpretable features from the bulk (n = 77 samples) and single-cell profiling (∼ 10 K cells), we developed an algorithm named CLIPPR which combines the top-performing single-cell models, RNA-inferred copy number variation (CNV) signals, and the initial bulk model to create a meta-model. RESULTS: While the scheme relying solely on bulk transcriptomic data showed good classification accuracy, it exhibited confusion between malignant and benign molecular classes in approximately ∼ 8% of meningioma samples. In contrast, models trained on features learned from meningioma single-cell data accurately resolved the sub-groups confused by bulk-transcriptomic data but showed limited overall accuracy. CLIPPR showed superior overall accuracy and resolved benign-malignant confusion as validated on n = 789 bulk meningioma samples gathered from multiple institutions. Finally, we showed the generalizability of our algorithm using our in-house single-cell (∼ 200 K cells) and bulk TCGA glioma data (n = 711 samples). CONCLUSION: Overall, our algorithm CLIPPR synergizes the resolution of single-cell data with the depth of bulk sequencing and enables improved cancer sub-group diagnoses and insights into their biology.

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.

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.

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.

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.