A transfer learning approach to identify Plasmodium in microscopic images.

Plasmodium parasites cause Malaria disease, which remains a significant threat to global health, affecting 200 million people and causing 400,000 deaths yearly. Plasmodium falciparum and Plasmodium vivax remain the two main malaria species affecting humans. Identifying the malaria disease in blood smears requires years of expertise, even for highly trained specialists. Literature studies have been coping with the automatic identification and classification of malaria. However, several points must be addressed and investigated so these automatic methods can be used clinically in a Computer-aided Diagnosis (CAD) scenario. In this work, we assess the transfer learning approach by using well-known pre-trained deep learning architectures. We considered a database with 6222 Region of Interest (ROI), of which 6002 are from the Broad Bioimage Benchmark Collection (BBBC), and 220 were acquired locally by us at Fundação Oswaldo Cruz (FIOCRUZ) in Porto Velho Velho, Rondônia-Brazil, which is part of the legal Amazon. We exhaustively cross-validated the dataset using 100 distinct partitions with 80% train and 20% test for each considering circular ROIs (rough segmentation). Our experimental results show that DenseNet201 has a potential to identify Plasmodium parasites in ROIs (infected or uninfected) of microscopic images, achieving 99.41% AUC with a fast processing time. We further validated our results, showing that DenseNet201 was significantly better (99% confidence interval) than the other networks considered in the experiment. Our results support claiming that transfer learning with texture features potentially differentiates subjects with malaria, spotting those with Plasmodium even in Leukocytes images, which is a challenge. In Future work, we intend scale our approach by adding more data and developing a friendly user interface for CAD use. We aim at aiding the worldwide population and our local natives living nearby the legal Amazon's rivers.

Individualized treatment of type A intramural hematoma-upfront surgery is not always necessary.

Background: Management of acute type A intramural hematoma (IMH) is a controversial topic, and variable treatment strategies have been reported. Upfront aortic replacement may not be necessary in all cases. The goal of our study was to evaluate clinical outcomes of patients with acute type A IMH or thrombosed false lumen (FL) treated with upfront surgery or watchful waiting. Methods: Patients admitted to our hospital with type A IMH or aortic dissection with thrombosed ascending FL from December 2012 to February 2023 were retrospectively reviewed. Results: Among the 93 patients with type A IMH, 36 (38.7%) patients underwent upfront aortic surgery (Group S), and 57 (61.3%) patients were offered watchful waiting with medical surveillance (Group W). Of the 57 patients in Group W, 32 were treated conservatively with medical therapy alone (Group C). Patients in Group S had larger ascending aortic diameter (47.8±5.3 vs. 44.4±4.2 mm: P=0.001), higher frequency of pericardial effusion (38.9% vs. 10.5%; P=0.001) and cardiac tamponade (16.7% vs. 1.8%; P=0.008). The overall mortality rate was 4.3% in the whole cohort over a median follow up of 40.5 months. Overall survival for Group S was 100% at 30 days and 1 year, and 96.2% at 5 years. Overall survival for Group W was 98.2% at 30 days, 96.3% at 1 year and 95.2% at 5 years. The difference in overall survival was not statistically significant (P=0.64). Overall survival for Group C was 100% at 30 days and 1 year, and 90.9% at 5 years. Conclusions: Survival outcomes in selected patients with type A IMH were satisfactory. An individualized approach to patients with uncomplicated type A IMH was feasible. Upfront surgery was not necessary in all cases.

[Retracted] Correlation of SOX9 and NM23 genes with the incidence and prognosis of prostate cancer.

[This retracts the article DOI: 10.3892/ol.2018.9828.].

Higher stochasticity in comammox Nitrospira community assembly in upland soils than the adjacent paddy soils at a regional scale.

Understanding the assembly mechanisms of microbial communities, particularly comammox Nitrospira, in agroecosystems is crucial for sustainable agriculture. However, the large-scale distribution and assembly processes of comammox Nitrospira in agricultural soils remain largely elusive. We investigated comammox Nitrospira abundance, community structure, and assembly processes in 16 paired upland peanuts and water-logged paddy soils in south China. Higher abundance, richness, and network complexity of comammox Nitrospira were observed in upland soils than in paddy soils, indicating a preference for upland soils over paddy soils among comammox Nitrospira taxa in agricultural environments. Clade A.2.1 and clade A.1 were the predominant comammox Nitrospira taxa in upland and paddy soils, respectively. Soil pH was the most crucial factor shaping comammox Nitrospira community structure. Stochastic processes were found to predominantly drive comammox Nitrospira community assembly in both upland and paddy soils, with deterministic processes playing a more important role in paddy soils than in upland soils. Overall, our findings demonstrate the higher stochasticity of comammox Nitrospira in upland soils than in the adjacent paddy soils, which may have implications for autotrophic nitrification in acidic agricultural soils.

Safety and Accuracy of Robot-Assisted Cervical Screw Placement: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study was to compare the accuracy and safety of robot-assisted (RA) cervical screw placement with conventional freehand (FH) technique. METHODS: Computer-based searches were conducted on various databases including PubMed, Embase, Cochrane Library, Web of Science, the China Biology Medicine, the China National Knowledge Infrastructure, and Wanfang Database. Inclusion criteria were studies reporting the use of RA techniques for cervical screw placement and providing data on safety and accuracy outcomes. Primary outcome indicators focused on the accuracy of screw placement, while secondary outcome indicators included operative time, intraoperative blood loss, length of hospital stay, complication rate, and radiation dose. Data from eligible studies were extracted and synthesized using a forest plot analysis. RESULTS: A total of 312 patients (1233 screws) from 6 studies were included, with 148 patients (47.4% with 567 screws) in the RA group. Perfect screw accuracy, as categorized by Gertzbein-Robbins grade A, was significantly superior with RA surgery compared to FH technique. RA screw implantation significantly reduced complication rates, intraoperative blood loss, length of hospitalization, and radiation dose compared to the conventional FH group. However, there was no statistically significant difference in surgery time between the RA and FH groups. CONCLUSIONS: RA surgery significantly improves the accuracy of cervical screw insertion and offers potential advantages in terms of reduced complications and blood loss, shorter hospital stays, and decreased radiation exposure. However, the impact on operative time remains uncertain. Further high-quality studies, including large-scale randomized controlled trials, are needed to strengthen the evidence base.

Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A Real-World, Retrospective Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The aim of this retrospective study was to evaluate the efficacy of adjuvant cisplatin-based chemotherapy in patients with locally advanced upper tract urothelial carcinoma (UTUC), administered following radical nephroureterectomy. @*Materials and Methods@#Patients with UTUC, arising from renal pelvis or ureter, staged pT3/T4 or N+ were treated with adjuvant chemotherapy following surgery. The chemotherapy consisted of gemcitabine 1,000 mg/m2 on days 1 and 8, cisplatin 70 mg/m2 on day 1. Treatment was repeated every 3 weeks for up to 4 cycles. Endpoints included disease-free survival (DFS), metastasis-free survival (MFS), and safety. @*Results@#Among 89 eligible patients, 85 (95.5%) completed at least 3 cycles of adjuvant chemotherapy. Chemotherapy was well tolerated, the main toxicities being mild-to-moderate gastrointestinal toxic effects and pruritus. With a median follow-up of 37 months, median DFS was 30 months (95% confidence interval, 22 to 39), and the median MFS was not reached. The 3-year DFS and MFS were 44% and 56%, respectively. Multivariate analyses revealed that the main factor associated with DFS and MFS was the lymph node involvement, whereas age, T category, grade, or the primary site of UTUC were not significantly associated with DFS or MFS. @*Conclusion@#Adjuvant cisplatin-based chemotherapy after radical surgery of pT3/T4 or N+ UTUC was feasible and may demonstrate benefits in DFS and MFS. Whether novel agents added to the chemotherapy regimen, as a concurrent combination or maintenance, impacts on survival or reduces the development of metastases remains to be studied.

Single Early Intravesical Instillation of Epirubicin for Preventing Bladder Recurrence after Nephroureterectomy in Upper Urinary Tract Urothelial Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to assess the effectiveness of early single intravesical administration of epirubicin in preventing intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. @*Materials and Methods@#Patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy between November 2018 and May 2022 were retrospectively reviewed. Intravesical epirubicin was administered within 48 hours if no evidence of leakage was observed. Epirubicin (50 mg) in 50 mL normal saline solution was introduced into the bladder via a catheter and maintained for 60 minutes. The severity of adverse events was graded using the Clavien-Dindo classification. We compared intravesical recurrence rate between the two groups. Multivariate analyses were performed to identify the independent predictors of bladder recurrence following radical nephroureterectomy. @*Results@#Epirubicin (n=55) and control (n=116) groups were included in the analysis. No grade 1 or higher bladder symptoms have been reported. A statistically significant difference in the intravesical recurrence rate was observed between the two groups (11.8% at 1 year in the epirubicin group vs. 28.4% at 1 year in the control group; log-rank p=0.039). In multivariate analysis, epirubicin instillation (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20 to 0.93; p=0.033) and adjuvant chemotherapy (HR, 0.29; 95% CI, 0.13 to 0.65; p=0.003) were independently predictive of a reduced incidence of bladder recurrence. @*Conclusion@#This retrospective review revealed that a single immediate intravesical instillation of epirubicin is safe and can reduce the incidence of intravesical recurrence after radical nephroureterectomy. However, further prospective trials are required to confirm these findings.

Neoadjuvant Cisplatin-Based Chemotherapy Followed by Selective Bladder Preservation Chemoradiotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder: Post Hoc Analysis of Two Prospective Studies / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT. @*Materials and Methods@#The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT. @*Results@#Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine and cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n=20), metastatic only (n=16), and both (n=7). In 27 patients with intravesical recurrence, transurethral resection, and Bacillus Calmette-Guerin treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% confidence interval [CI], 25.1 to 67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (hazard ratio, 0.465; 95% CI, 0.222 to 0.976). @*Conclusion@#The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.

Sextant Systematic Biopsy Versus Extended 12-Core Systematic Biopsy in Combined Biopsy for Prostate Cancer

Background@#This study assessed the comparative effectiveness of sextant and extended 12-core systematic biopsy within combined biopsy for the detection of prostate cancer. @*Methods@#Patients who underwent combined biopsy targeting lesions with a Prostate Imaging Reporting and Data System (PI-RADS) score of 3–5 were assessed. Two specialists performed all combined cognitive biopsies. Both specialists performed target biopsies with five or more cores. One performed sextant systematic biopsies, and the other performed extended 12-core systematic biopsies. A total of 550 patients were analyzed. @*Results@#Cases requiring systematic biopsy in combined biopsy exhibited a significant association with age ≥ 65 years (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.25– 4.32; P = 0.008), PI-RADS score (OR, 2.32; 95% CI, 1.25–4.32; P = 0.008), and the number of systematic biopsy cores (OR, 3.69; 95% CI, 2.11–6.44; P < 0.001). In patients with an index lesion of PI-RADS 4, an extended 12-core systematic biopsy was required (target-negative/ systematic-positive or a greater Gleason score in the systematic biopsy than in the targeted biopsy) (P < 0.001). @*Conclusion@#During combined biopsy for prostate cancer in patients with PI-RADS 3 or 5, sextant systematic biopsy should be recommended over extended 12-core systematic biopsy when an effective targeted biopsy is performed.

First-in-Human Transapical Beating-Heart Septal Myectomy in Patients With Hypertrophic Obstructive Cardiomyopathy.

BACKGROUND: To simplify surgical septal reduction therapy for hypertrophic obstructive cardiomyopathy (HOCM), we developed a novel transapical beating-heart septal myectomy (TA-BSM) procedure. OBJECTIVES: In this study, we sought to evaluate the clinical utility of TA-BSM in a first-in-human trial. METHODS: Patients with HOCM were enrolled if they presented with drug-refractory disabling symptoms. TA-BSM was performed via minithoracotomy with the use of our beating-heart myectomy device under echocardiographic guidance, without the use of cardiopulmonary bypass. Repeated resections were performed to tailor the extent of the septal myectomy for sufficient abolishment of left ventricular outflow tract (LVOT) obstruction and mitral regurgitation (MR). The primary outcome measure was procedural success, defined by resting/provoked LVOT gradient <30/50 mm Hg and residual MR grade ≤1+ (of 4+) at 3-month follow-up. RESULTS: A total of 47 patients aged 12 to 77 years were enrolled. Of the 46 patients who were followed for 3 months, 42 achieved procedural success. The maximal LVOT gradient decreased from 86 mm Hg (IQR: 67-114 mm Hg) at baseline to 19 mm Hg (IQR: 14-28 mm Hg) at 3 months. MR grade was ≤1+ in 3 patients at baseline and in 45 patients at 3 months. One patient died on postoperative day 10 owing to device-unrelated reasons. Other major adverse events included 1 delayed ventricular septal perforation and 1 intraoperative left ventricular apical tear. CONCLUSIONS: TA-BSM is a safe and efficient minimally invasive procedure for septal reduction of heterogeneous HOCM. Compared with conventional septal myectomy, TA-BSM provides real-time evaluation to guide resection while reducing surgical trauma. (Transapical Beating-Heart Septal Myectomy in Patients With Hypertrophic Obstructive Cardiomyopathy; NCT05332691).

MicroRNA-196-5p targets Derlin-1 to induce autophagy in human osteosarcoma cells.

Osteosarcoma is a highly prevalent type of primary bone tissues in children and young adolescents. Micro-RNA (miR) dysregulation has been linked to osteosarcoma tumorigenesis. The role of miR-196-5p was investigated in modulating the growth and metastatic behaviour of human osteosarcoma cells, along with exploring its mechanism of action. As shown by RT-qPCR expression analysis, osteosarcoma cell lines exhibited prominent (P<0.05) transcriptional repression of miR-196-5p. The latter was thus transiently overexpressed in osteosarcoma cells, which resulted in the loss of cell viability and colony formation via induction of autophagy. The western blot analysis of the autophagy marker proteins revealed that the expression of Beclin 1 and LC3B II proteins was induced by miR-196-5p, whereas that of p62 and LC3BI was repressed. Moreover, osteosarcoma cells overexpressing miR-196-5p showed significantly (P<0.05) lower migration and invasion concerning the control osteosarcoma cells. According to the results of the in-silico analysis, Derlin-1 participates in the regulation of miR-196-5p in osteosarcoma, and this prediction has been validated using a dual luciferase assay. The results indicated that miR-196-5p exerted its molecular role by targeting Derlin-1 at the post-transcriptional level. Summing up, the study revealed the modulatory potential of miR-196-5p/Derlin-1 on osteosarcoma cells and provided insights into the possible implications for the treatment and prognosis of the disease.

SOX4 is a novel phenotypic regulator of endothelial cells in atherosclerosis revealed by single-cell analysis.

INTRODUCTION: Atherosclerotic complications represent the leading cause of cardiovascular mortality globally. Dysfunction of endothelial cells (ECs) often initiates the pathological events in atherosclerosis. OBJECTIVES: In this study, we sought to investigate the transcriptional profile of atherosclerotic aortae, identify novel regulator in dysfunctional ECs and hence provide mechanistic insights into atherosclerotic progression. METHODS: We applied single-cell RNA sequencing (scRNA-seq) on aortic cells from Western diet-fed apolipoprotein E-deficient (ApoE-/-) mice to explore the transcriptional landscape and heterogeneity of dysfunctional ECs. In vivo validation of SOX4 upregulation in ECs were performed in atherosclerotic tissues, including mouse aortic tissues, human coronary arteries, and human renal arteries. Single-cell analysis on human aortic aneurysmal tissue was also performed. Downstream vascular abnormalities induced by EC-specific SOX4 overexpression, and upstream modulators of SOX4 were revealed by biochemical assays, immunostaining, and wire myography. Effects of shear stress on endothelial SOX4 expression was investigated by in vitro hemodynamic study. RESULTS: Among the compendium of aortic cells, mesenchymal markers in ECs were significantly enriched. Two EC subsets were subsequently distinguished, as the 'endothelial-like' and 'mesenchymal-like' subsets. Conventional assays consistently identified SOX4 as a novel atherosclerotic marker in mouse and different human arteries, additional to a cancer marker. EC-specific SOX4 overexpression promoted atherogenesis and endothelial-to-mesenchymal transition (EndoMT). Importantly, hyperlipidemia-associated cytokines and oscillatory blood flow upregulated, whereas the anti-diabetic drug metformin pharmacologically suppressed SOX4 level in ECs. CONCLUSION: Our study unravels SOX4 as a novel phenotypic regulator during endothelial dysfunction, which exacerbates atherogenesis. Our study also pinpoints hyperlipidemia-associated cytokines and oscillatory blood flow as endogenous SOX4 inducers, providing more therapeutic insights against atherosclerotic diseases.

Using colloidal AFM probe technique and XDLVO theory to predict the transport of nanoplastics in porous media.

The plastic concentration in terrestrial systems is orders of magnitude higher than that found in marine ecosystems, which has raised global concerns about their potential risk to agricultural sustainability. Previous research on the transport of nanoplastics in soil relied heavily on the qualitative prediction of the mean-field extended Derjaguin-Landau-Verwey-Overbeek theory (XDLVO), but direct and quantitative measurements of the interfacial forces between single nanoplastics and porous media are lacking. In this study, we conducted multiscale investigations ranging from column transport experiments to single particle measurements. The maximum effluent concentration (C/C0) of amino-modified nanoplastics (PS-NH2) was 0.94, whereas that of the carboxyl-modified nanoplastics (PS-COOH) was only 0.33, indicating PS-NH2 were more mobile than PS-COOH at different ionic strengths (1-50 mM) and pH values (5-9). This phenomenon was mainly attributed to the homogeneous aggregation of PS-COOH. In addition, the transport of PS-NH2 in the quartz sand column was inhibited with the increase of ionic strength and pH, and pH was the major factor governing their mobility. The transport of PS-COOH was inhibited with increasing ionic strength and decreasing pH. Hydrophilicity/hydrophobicity-mediated interactions and particle heterogeneity strongly interfered with interfacial forces, leading to the qualitative prediction of XDLVO, contrary to experimental observations. Through the combination of XDLVO and colloidal atomic force microscopy, accurate and quantitative interfacial forces can provide compelling insight into the fate of nanoparticles in the soil environment.

Plant Species-Driven Distribution of Individual Clades of Comammox Nitrospira in a Subtropical Estuarine Wetland.

Plant species play a crucial role in mediating the activity and community structure of soil microbiomes through differential inputs of litter and rhizosphere exudates, but we have a poor understanding of how plant species influence comammox Nitrospira, a newly discovered ammonia oxidizer with pivotal functionality. Here, we investigate the abundance, diversity, and community structure of comammox Nitrospira underneath five plant species and a bare tidal flat at three soil depths in a subtropical estuarine wetland. Plant species played a critical role in driving the distribution of individual clades of comammox Nitrospira, explaining 59.3% of the variation of community structure. Clade A.1 was widely detected in all samples, while clades A.2.1, A.2.2, A.3 and B showed plant species-dependent distribution patterns. Compared with the native species Cyperus malaccensis, the invasion of Spartina alterniflora increased the network complexity and changed the community structure of comammox Nitrospira, while the invasive effects from Kandelia obovata and Phragmites australis were relatively weak. Soil depths significantly influenced the community structure of comammox Nitrospira, but the effect was much weaker than that from plant species. Altogether, our results highlight the previously unrecognized critical role of plant species in driving the distribution of comammox Nitrospira in a subtropical estuarine wetland.

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC). @*Materials and Methods@#In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled. Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ ypT1), disease-free survival (DFS), and safety. @*Results@#Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical complete response (cCR) was achieved in 59% of intent-to-treat (ITT) population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative programmed death-ligand 1 (PD-L1) did not correlate with pCR or pathologic downstaging rates. @*Conclusion@#Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41; CRIS.nih.go.kr, KCT0003804).

2022 CMICS Expert Consensus on the Management of Isolated Tricuspid Regurgitation after Left-Sided Valve Surgery.

Tricuspid regurgitation (TR) may occur late after left-sided valve surgery (LSVS). Isolated tricuspid regurgitation after left-sided valve surgery (iTR-LSVS) refers to isolated TR without significant lesions in the mitral and/or aortic position late after mitral and/or aortic replacement or repair. Severe TR has a negative impact on long-term prognosis and requires surgical or transcatheter treatment. However, there is no clear recommendation on when and how intervention should be performed for patients with iTR-LSVS in the current guidelines for the management of valvular heart disease. The historically high operative mortality may be reduced by current minimally invasive techniques and transcatheter therapy. To further understand iTR-LSVS, standardize the treatment, improve the prognosis, and promote the collaboration, the Chinese Minimally Invasive Cardiovascular Surgery Committee (CMICS) wrote this expert consensus on the management of iTR-LSVS from the aspects of etiology, preoperative evaluation, indications for intervention, surgical treatment, transcatheter therapy, and postoperative management.