The multispecies microbial cluster of Fusobacterium, Parvimonas, Bacteroides and Faecalibacterium as a precision biomarker for colorectal cancer diagnosis.

The incidence of colorectal cancer (CRC) has increased worldwide, and early diagnosis is crucial to reduce mortality rates. Therefore, new noninvasive biomarkers for CRC are required. Recent studies have revealed an imbalance in the oral and gut microbiomes of patients with CRC, as well as impaired gut vascular barrier function. In the present study, the microbiomes of saliva, crevicular fluid, feces, and non-neoplastic and tumor intestinal tissue samples of 93 CRC patients and 30 healthy individuals without digestive disorders (non-CRC) were analyzed by 16S rRNA metabarcoding procedures. The data revealed that Parvimonas, Fusobacterium, and Bacteroides fragilis were significantly over-represented in stool samples of CRC patients, whereas Faecalibacterium and Blautia were significantly over-abundant in the non-CRC group. Moreover, the tumor samples were enriched in well-known periodontal anaerobes, including Fusobacterium, Parvimonas, Peptostreptococcus, Porphyromonas, and Prevotella. Co-occurrence patterns of these oral microorganisms were observed in the subgingival pocket and in the tumor tissues of CRC patients, where they also correlated with other gut microbes, such as Hungatella. This study provides new evidence that oral pathobionts, normally located in subgingival pockets, can migrate to the colon and probably aggregate with aerobic bacteria, forming synergistic consortia. Furthermore, we suggest that the group composed of Fusobacterium, Parvimonas, Bacteroides, and Faecalibacterium could be used to design an excellent noninvasive fecal test for the early diagnosis of CRC. The combination of these four genera would significantly improve the reliability of a discriminatory test with respect to others that use a single species as a unique CRC biomarker.

Meta-analyses of mouse and human prostate single-cell transcriptomes reveal widespread epithelial plasticity in tissue regression, regeneration, and cancer.

Recent advances in single-cell RNA-sequencing (scRNA-seq) technology have facilitated studies of cell states and plasticity in tissue maintenance and cancer, including in the prostate. Here we present meta-analyses of multiple new and published scRNA-seq datasets to establish reference cell type classifications for the normal mouse and human prostate. Our analyses demonstrate transcriptomic similarities between epithelial cell states in the normal prostate, in the regressed prostate after androgen-deprivation, and in primary prostate tumors. During regression in the mouse prostate, all epithelial cells shift their expression profiles towards a proximal periurethral (PrU) state, demonstrating an androgen-dependent plasticity that is restored to normal during androgen restoration and regeneration. In the human prostate, we find progressive rewiring of transcriptional programs across epithelial cell types in benign prostate hyperplasia and treatment-naïve prostate cancer. Notably, we detect copy number variants predominantly within Luminal Acinar cells in prostate tumors, suggesting a bias in their cell type of origin, as well as a larger field of transcriptomic alterations in non-tumor cells. Finally, we observe that Luminal Acinar tumor cells in treatment-naïve prostate cancer display heterogeneous androgen receptor (AR) signaling activity, including a split between high-AR and low-AR profiles with similarity to PrU-like states. Taken together, our analyses of cellular heterogeneity and plasticity provide important translational insights into the origin and treatment response of prostate cancer.

A novel therapy for idiopathic urethritis in children: Local steroid injection.

Idiopathic urethritis (IU) is difficult to manage and there is no standarized therapy. The technique of local steroid injection (LSI) for the treatment of IU in children and the results of the patients undergoing LSI from 2020 to 2021 in a single center are presented. Seven patients with IU underwent LSI. An internal urethrotomy was also performed in two patients with stricture. Complete resolution of symptoms and signs occurred in six patients. The remaining patient did not achieve total remission but did substantially improve symptoms. LSI seems to be an effective alternative for treatment of IU in children.

Smoother: a unified and modular framework for incorporating structural dependency in spatial omics data.

Spatial omics technologies can help identify spatially organized biological processes, but existing computational approaches often overlook structural dependencies in the data. Here, we introduce Smoother, a unified framework that integrates positional information into non-spatial models via modular priors and losses. In simulated and real datasets, Smoother enables accurate data imputation, cell-type deconvolution, and dimensionality reduction with remarkable efficiency. In colorectal cancer, Smoother-guided deconvolution reveals plasma cell and fibroblast subtype localizations linked to tumor microenvironment restructuring. Additionally, joint modeling of spatial and single-cell human prostate data with Smoother allows for spatial mapping of reference populations with significantly reduced ambiguity.

Long-term outcome of randomized clinical trial between polyacrylate-polyalcohol copolymer (PPC) and dextranomer-hyaluronic acid copolymer (Dx/HA) as bulking agents for endoscopic treatment of primary vesicoureteral reflux (VUR).

OBJECTIVE: The aim of our study is to compare long-term outcome of endoscopic treatment of VUR using PPC or Dx/HA. PATIENTS AND METHODS: From October 2014 to April 2017 patients with VUR grades from 3 to 5 that needed endoscopic treatment were eligible for this RCT. Patients were randomized in two groups: PPC and Dx/HA. A VCUG was performed at 6 months; if VUR > 3 was still present a second ET was performed. We included for this long-term follow-up study those patients that were successfully treated at short-term follow-up. At 36 months postoperative VCUG was performed to assess outcome. Success was considered if postoperative VUR grade was 0 at 36 months, and there was no ureteral obstruction. RESULTS: In the previous study, 60/73 ureters were successfully treated in 36/44 patients, and then we have analyzed 60 ureters in 36 patients. Three patients were lost in long-term follow-up, and then we analyzed 57 ureters in 33 patients divided. PPC group 18 patients (28 ureters); and Dx/HA group 15 patients (29 ureters). After 3 years of follow-up the VCUG showed a success rate of 26/28 of RU in PPC and 26/29 of DX/HA. Two RU in PPC group had ureteral obstruction, and then the successful rate for PPC group dropped to 24/28. The overall successful rate at long-term was 72.7% of the RU in PPC group and 70.3% in Dx/HA group. CONCLUSION: PPC and Dx/HA has similar long-term outcome in VUR resolution, but ureteral obstruction could be present at long-term follow-up in PPC group.

Parvimonas micra can translocate from the subgingival sulcus of the human oral cavity to colorectal adenocarcinoma.

Oral and intestinal samples from a cohort of 93 colorectal cancer (CRC) patients and 30 healthy controls (non-CRC) were collected for microbiome analysis. Saliva (28 non-CRC and 94 CRC), feces (30 non-CRC and 97 CRC), subgingival fluid (20 CRC), and tumor tissue samples (20 CRC) were used for 16S metabarcoding and/or RNA sequencing (RNAseq) approaches. A differential analysis of the abundance, performed with the ANCOM-BC package, adjusting the P-values by the Holm-Bonferroni method, revealed that Parvimonas was significantly over-represented in feces from CRC patients (P-value < 0.001) compared to healthy controls. A total of 11 Parvimonas micra isolates were obtained from the oral cavity and adenocarcinoma of CRC patients. Genome analysis identified a pair of isolates from the same patient that shared 99.2% identity, demonstrating that P. micra can translocate from the subgingival cavity to the gut. The data suggest that P. micra could migrate in a synergistic consortium with other periodontal bacteria. Metatranscriptomics confirmed that oral bacteria were more active in tumor than in non-neoplastic tissues. We suggest that P. micra could be considered as a CRC biomarker detected in non-invasive samples such as feces.

Inverse agonists of retinoic acid receptor/retinoid X receptor signaling as lineage-specific antitumor agents against human adenoid cystic carcinoma.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a lethal malignancy of exocrine glands, characterized by the coexistence within tumor tissues of 2 distinct populations of cancer cells, phenotypically similar to the myoepithelial and ductal lineages of normal salivary epithelia. The developmental relationship linking these 2 cell types, and their differential vulnerability to antitumor treatments, remains unknown. METHODS: Using single-cell RNA sequencing, we identified cell-surface markers (CD49f, KIT) that enabled the differential purification of myoepithelial-like (CD49fhigh/KITneg) and ductal-like (CD49flow/KIT+) cells from patient-derived xenografts (PDXs) of human ACCs. Using prospective xenotransplantation experiments, we compared the tumor-initiating capacity of the 2 cell types and tested whether one could differentiate into the other. Finally, we searched for signaling pathways with differential activation between the 2 cell types and tested their role as lineage-specific therapeutic targets. RESULTS: Myoepithelial-like cells displayed higher tumorigenicity than ductal-like cells and acted as their progenitors. Myoepithelial-like and ductal-like cells displayed differential expression of genes encoding for suppressors and activators of retinoic acid signaling, respectively. Agonists of retinoic acid receptor (RAR) or retinoid X receptor (RXR) signaling (all-trans retinoic acid, bexarotene) promoted myoepithelial-to-ductal differentiation, whereas suppression of RAR/RXR signaling with a dominant-negative RAR construct abrogated it. Inverse agonists of RAR/RXR signaling (BMS493, AGN193109) displayed selective toxicity against ductal-like cells and in vivo antitumor activity against PDX models of human ACC. CONCLUSIONS: In human ACCs, myoepithelial-like cells act as progenitors of ductal-like cells, and myoepithelial-to-ductal differentiation is promoted by RAR/RXR signaling. Suppression of RAR/RXR signaling is lethal to ductal-like cells and represents a new therapeutic approach against human ACCs.

Comparative phylogeography reveals widespread cryptic diversity driven by ecology in Panamanian birds.

Widespread species often harbor unrecognized genetic diversity, and investigating the factors associated with such cryptic variation can help us better understand the forces driving diversification. Here, we identify potential cryptic species based on a comprehensive dataset of COI mitochondrial DNA barcodes from 2,333 individual Panamanian birds across 429 species, representing 391 (59%) of the 659 resident landbird species of the country, as well as opportunistically sampled waterbirds. We complement this dataset with additional publicly available mitochondrial loci, such as ND2 and cytochrome b, obtained from whole mitochondrial genomes from 20 taxa. Using barcode identification numbers (BINs), we find putative cryptic species in 19% of landbird species, highlighting hidden diversity in the relatively well-described avifauna of Panama. Whereas some of these mitochondrial divergence events corresponded with recognized geographic features that likely isolated populations, such as the Cordillera Central highlands, the majority (74%) of lowland splits were between eastern and western populations. The timing of these splits are not temporally coincident across taxa, suggesting that historical events, such as the formation of the Isthmus of Panama and Pleistocene climatic cycles, were not the primary drivers of cryptic diversification. Rather, we observed that forest species, understory species, insectivores, and strongly territorial species-all traits associated with lower dispersal ability-were all more likely to have multiple BINs in Panama, suggesting strong ecological associations with cryptic divergence. Additionally, hand-wing index, a proxy for dispersal capability, was significantly lower in species with multiple BINs, indicating that dispersal ability plays an important role in generating diversity in Neotropical birds. Together, these results underscore the need for evolutionary studies of tropical bird communities to consider ecological factors along with geographic explanations, and that even in areas with well-known avifauna, avian diversity may be substantially underestimated.

Especies extendidas frecuentemente tiene diversidad genética no reconocida, y investigando los factores asociados con esta variación críptica puede ayudarnos a entender las fuerzas que impulsan la diversificación. Aquí, identificamos especies crípticas potenciales basadas en un conjunto de datos de códigos de barras de ADN mitocondrial de 2,333 individuos de aves de Panama en 429 especies, representando 391 (59%) de las 659 especies de aves terrestres residentes del país, además de algunas aves acuáticas muestreada de manera oportunista. Adicionalmente, complementamos estos datos con secuencias mitocondriales disponibles públicamente de otros loci, tal como ND2 o citocroma b, obtenidos de los genomas mitocondriales completos de 20 taxones. Utilizando los números de identificación de código de barras (en ingles: BINs), un sistema taxonómico numérico que proporcina una estimación imparcial de la diversidad potencial a nivel de especie, encontramos especies crípticas putativas en 19% de las especies de aves terrestres, lo que destaca la diversidad oculta en la avifauna bien descrita de Panamá. Aunque algunos de estos eventos de divergencia conciden con características geográficas que probablemente aislaron las poblaciones, la mayoría (74%) de la divergencia en las tierras bajas se encuentra entre las poblaciones orientales y occidentales. El tiempo de esta divergencia no coincidió entre los taxones, sugiriendo que eventos históricos tales como la formación del Istmo de Panamá y los ciclos climáticos del pleistoceno, no fueron los principales impulsores de la especiación. En cambio, observamos asociaciones fuertes entre las características ecológicas y la divergencia mitocondriale: las especies del bosque, sotobosque, con una dieta insectívora, y con territorialidad fuerte mostraton múltiple BINs probables. Adicionalmente, el índice mano-ala, que está asociado a la capacidad de dispersión, fue significativamente menor en las especies con BINs multiples, sugiriendo que la capacidad de dispersión tiene un rol importamente en la generación de la diversidad de las aves neotropicales. Estos resultos demonstran la necesidad de que estudios evolutivos de las comunidades de aves tropicales consideren los factores ecológicos en conjunto con las explicaciones geográficos.

Are weight or age limits for pediatric laparoscopic pyeloplasty? Results of a multicentric study.

INTRODUCTION: Anderson-Hynes pyeloplasty is the technique of choice for the treatment of pyeloureteral junction obstruction (PUJO) with an excellent success rate. Minimally invasive surgery has become the standard of care for the management of PUJO in children. Although it has been comparable to the open approach at all levels, its diffusion or employment in younger children has not been widely adopted. Our aim is to evaluate laparoscopic pyeloplasty outcomes from international academic centers in children under 1 year of age, focusing on feasibility and outcomes including possible complications. MATERIALS AND METHODS: This is review of consecutive infants under 1 year of age who underwent laparoscopic pyeloplasty between 2009 and 2018 with more than 12 months of follow-up. Seven different training centers with different backgrounds participated in this study. Evaluation was carried out with ultrasound and renogram before and after surgery. Demographic data, perioperative characteristics, complications, and results are described and analyzed. RESULTS: Over 9 years, 124 transperitoneal laparoscopic Anderson-Hynes pyeloplasties were performed on 123 children under 1 year of age; 88 males and 35 females, with 1 case of bilateral PUJO. Of the 124 renal units, 86 were left-sided. Mean age at surgery was 6.6 months (1 week-12 months), with 56% (n = 70) done before 6 months of age. Mean weight at surgery was 6.8 kg (3-12 kg), with 59% (n = 73) weighing less than 8 kg. Mean operative time (skin-to-skin) was 150 min (75-330 min). After a mean follow-up of 46 months (12-84 months), 12 (9%) patients developed complications, with only 1 needing a redo pyeloplasty also done laparoscopically. One child, with deterioration in renal function, underwent nephrectomy. CONCLUSION: Laparoscopic pyeloplasty under 1 year of age and/or less than 12 kilos is feasible with lower complication rate. Furthermore, age younger than 6 months and weight less than 8 kg are no longer limiting factors for a successful pyeloplasty as shown by this multicentre study.

Latitudes and attitudes: A multinational study of laparoscopic pyeloplasty in children.

PURPOSE: The Anderson-Hynes technique has been the treatment of choice for primary ureteropelvic junction obstruction in children. Laparoscopic approach has shown similar outcomes to open, with advantages of shorter hospital stay and less pain. We reviewed the experience of 11 geographically diverse, tertiary pediatric urology institutions focusing on the outcomes and complications of laparoscopic pyeloplasty. MATERIALS AND METHODS: A descriptive, retrospective study was conducted evaluating patients undergoing Anderson-Hynes dismembered laparoscopic pyeloplasty. Centers from four different continents participated. Demographic data, perioperative management, results, and complications are described. RESULTS: Over a 9-year period, 744 laparoscopic pyeloplasties were performed in 743 patients. Mean follow-up was 31 months (6-120m). Mean age at surgery was 82 months (1 w-19 y). Median operative time was 177 min. An internal stent was placed in 648 patients (87%). A catheter was placed for bladder drainage in 702 patients (94%). Conversion to open pyeloplasty was necessary in seven patients. Average length of hospital stay was 2.8 days. Mean time of analgesic requirement was 3.2 days. Complications, according to Clavien-Dindo classification, were observed in 56 patients (7.5%); 10 (1%) were Clavien-Dindo IIIb. Treatment failure occurred in 35 cases with 30 requiring redo pyeloplasty (4%) and 5 cases requiring nephrectomy (0.6%). CONCLUSION: We have described the laparoscopic pyeloplasty experience of institutions with diverse cultural and economic backgrounds. They had very similar outcomes, in agreement with previously published data. Based on these findings, we conclude that laparoscopic pyeloplasty is safe and successful in diverse geographics areas of the world.

Comprehensive Generation of Historical Construction CAD Models from Data Provided by a Wearable Mobile Mapping System: A Case Study of the Church of Adanero (Ávila, Spain).

This paper presents the results of a complex three-dimensional reconstruction of the church of Nuestra Señora de la Asunción (Ávila, Spain) as an example of a successful process of verticalization from point clouds to a comprehensive computer-aided design (CAD) model. The reconstruction was carried out using the novel and advanced wearable mobile mapping system ZEB-REVO in combination with a lifting pole, in order to cover the whole geometry of the temple and, also, to model the different constructive elements. To this end, a set of good practices was followed, which allowed for passing from reality to the CAD model, such as the use of closed loops or even the use of different parametric and non-parametric strategies to capture the real geometry of the elements. As a result, this paper outlines the main guidelines for passing from point clouds to comprehensive CAD models, the former being useful for the application of smart preventive conservation processes, heritage building information models or even advanced numerical simulations.

Machine learning and deep learning predictive models for type 2 diabetes: a systematic review.

Diabetes Mellitus is a severe, chronic disease that occurs when blood glucose levels rise above certain limits. Over the last years, machine and deep learning techniques have been used to predict diabetes and its complications. However, researchers and developers still face two main challenges when building type 2 diabetes predictive models. First, there is considerable heterogeneity in previous studies regarding techniques used, making it challenging to identify the optimal one. Second, there is a lack of transparency about the features used in the models, which reduces their interpretability. This systematic review aimed at providing answers to the above challenges. The review followed the PRISMA methodology primarily, enriched with the one proposed by Keele and Durham Universities. Ninety studies were included, and the type of model, complementary techniques, dataset, and performance parameters reported were extracted. Eighteen different types of models were compared, with tree-based algorithms showing top performances. Deep Neural Networks proved suboptimal, despite their ability to deal with big and dirty data. Balancing data and feature selection techniques proved helpful to increase the model's efficiency. Models trained on tidy datasets achieved almost perfect models.

Cuerpo extraño intravesical / Intravesical foreign body

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Imposibilidad para el sondaje vesical: siringocele de Cowper / Impossibility for bladder catheterization: Cowper's syringocele

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Optimization of Ultrasound-Assisted Extraction of Bioactive Compounds from Pelvetia canaliculata to Sunflower Oil.

In this study, Pelvetia canaliculata L. macroalga, collected from the Atlantic Portuguese coast, was used as a source of bioactive compounds, mostly antioxidants, to incorporate them in sunflower oil with the aim of increasing its biological value and oxidative stability. The lyophilized alga was added to the oil, and ultrasound-assisted extraction (UAE) was performed. Algae concentration and UAE time varied following a central composite rotatable design (CCRD) to optimize extraction conditions. The following parameters were analyzed in the oils: oxidation products, acidity, color, chlorophyll pigments, carotenoids, flavonoids, total phenolic content, antioxidant activity by DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) assays, and sensory analysis. Extraction conditions did not affect the acidity and the amount of oxidation products in the oil. Chlorophylls and carotenoid contents increased with algae concentration, while flavonoid extraction did not depend on algae content or UAE time. Total phenolics in the oil were highly related only to FRAP antioxidant activity. Storage experiments of supplemented oil (12.5% algae; 20 min UAE) were carried out under accelerated oxidation conditions at 60 °C/12 days. Antioxidant activity (FRAP) of supplemented oil was 6-fold higher than the value of non-supplemented oil. Final samples retained 40% of their initial antioxidant activity. The presence of algae extracts contributed to the increased oxidative stability of sunflower oil.

Design consideration of an x-ray imaging crystal spectrometer for China Fusion Engineering Test Reactor.

The x-ray imaging crystal spectrometer (XICS) is proposed as the principal method of diagnostics for plasma ion temperature and rotation for the China Fusion Engineering Test Reactor (CFETR) for its simplicity in implementation and no reliance on neutral beams. For D-T experiments with the electron temperature as high as 35-40 keV at the core region, highly charged high-Z ions can serve as the diagnostic ions for the XICS. For the CFETR, Xe44+, Xe51+, and W64+ are selected as the impurity ions. Appropriate crystal parameters are selected, as well as the preliminary layout for the spectrometer. We estimated the general performance of the spectrometer, including the emissivity of the impurities, the spatial resolution of the x-ray detector, and the expected count rate of line emissions. For the application in the fusion reactor environment, the effect of neutron irradiation on the crystal is briefly discussed.

Compression and Strain Predictive Models in Non-Structural Recycled Concretes Made from Construction and Demolition Wastes.

This work aims to investigate different predictive models for estimating the unconfined compressive strength and the maximum peak strain of non-structural recycled concretes made up by ceramic and concrete wastes. The extensive experimental campaign carried out during this research includes granulometric analysis, physical and chemical analysis, and compression tests along with the use of the 3D digital image correlation as a method to estimate the maximum peak strain. The results obtained show that it is possible to accurately estimate the unconfined compressive strength for both types of concretes, as well as the maximum peak strain of concretes made up by ceramic waste. The peak strain for mixtures with concrete waste shows lower correlation values.