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Lake Mattamuskeet, the largest lake in North Carolina, USA, has undergone decades‐long eutrophication causing reduced water quality and promoting cyanobacterial blooms that may produce toxins. It is therefore necessary to evaluate the cyanobacterial diversity of the lake and their toxigenic potential. We present draft genomes of Microcystis, Pelatocladus, Raphidiopsis, and Umezakia strains isolated from Lake Mattamuskeet. The whole‐genome shotgun projects for Umezakia ovalisporum BLCC‐F208, Microcystis sp. BLCC‐F209, Microcystis sp. BLCC‐F210, Pelatocladus sp. BLCC‐F211, U. ovalisporum BLCC‐F215, and Raphidiopsis BLCC‐F218 have been deposited in GenBank under accession numbers JBHFLK000000000, CP169647, JBHFLL000000000, JBHFLM000000000, JBHFLN000000000, and JBHFLO000000000, respectively. Based on the genomic analysis, several biosynthetic gene clusters (BCGs) with varying degrees of similarity to known toxic and bioactive compound gene clusters were identified across the different cyanobacterial strains. [ABSTRACT FROM AUTHOR]

Background: Perinephric fluid is commonly identified in patients with renal colic and urolithiasis, especially in cases associated with hydronephrosis. However, its clinical relevance, particularly its impact on treatment decisions and prognosis, is not well established. Methods: This retrospective, single-center study included adult patients who presented to the emergency department (ED) with suspected renal colic between January 2021 and October 2023. Patients underwent ultrasound evaluations, which were analyzed for perinephric fluid, hydronephrosis, stone size, and stone location. Data on patient demographics, laboratory results, and clinical outcomes, including the need for urological interventions, were also collected and analyzed. Multivariate logistic regression was used to assess factors associated with perinephric fluid presence. Results: Of the 509 patients included, 200 (39.3%) had perinephric fluid. Hydronephrosis was significantly associated with perinephric fluid (OR: 4.14, p = 0.007), as were stones located in the proximal (OR: 3.06, p = 0.003) and distal ureter (OR: 2.31, p = 0.018). However, sonographic perinephric fluid did not significantly affect the likelihood of urological intervention, in-hospital complications, sepsis, acute kidney injury (AKI), acute kidney disease (AKD), and prolonged hospital stay. Conclusions: Perinephric fluid is a common finding in patients with renal colic and urolithiasis, particularly in cases involving hydronephrosis and ureteral stones. However, despite its prevalence, sonographic perinephric fluid was not significantly associated with the need for urological intervention, longer hospital stays, or worse clinical outcomes. Further prospective studies are required to clarify its clinical implications fully. [ABSTRACT FROM AUTHOR]

Purpose: Iatrogenic ureteral strictures (US) after endoscopic treatment for urolithiasis represent a significant healthcare concern. However, high-quality evidence on the risk factors associated with US is currently lacking. We aimed to develop a consensus statement addressing the definition, risk factors, and follow-up management of iatrogenic US after endoscopic treatment for urolithiasis. Methods: Utilizing a modified Delphi method, a steering committee developed survey statements based on a systematic literature review. Then, a two-round online survey was submitted to 25 experts, offering voting options to assess agreement levels. A consensus panel meeting was held for unresolved statements. The predetermined consensus threshold was set at 70%. Results: The steering committee formulated 73 statements. In the initial survey, consensus was reached on 56 (77%) statements. Following in-depth discussions and refinement of 17 (23%) statements in a consensus meeting, the second survey achieved consensus on 63 (86%) statements. This process underscored agreement on pivotal factors influencing US in endoscopic urolithiasis treatments. Conclusions: This study provides a comprehensive list of categorized risk factors for US following endoscopic urolithiasis treatments. The objectives include enhancing uniformity in research, minimizing redundancy in outcome assessments, and effectively addressing risk factors associated with US. These findings are crucial for designing future clinical trials and guiding endoscopic surgeons in mitigating the risk of US. [ABSTRACT FROM AUTHOR]

We propose a model for exploring the feasibility and effectiveness of a green transition from dirty to clean technologies. It relies on an evolutionary framework for the technology selection that accounts for the environmental domain dynamics, in terms of pollution evolution. A regulator charges an environmental tax to the producers, and the agents can choose between the less profitable clean technology and the more profitable dirty one, which, however, is taxed to a greater extent with respect to the clean one. The environmental tax depends endogenously on the level of pollution, which rises because of the producers' emissions. The pollution stock also naturally decays, and can be abated by involving the resources collected from the taxation. We analytically study the resulting two-dimensional model from both statically and dynamically, to understand under what conditions the green transition can take place and results in an improvement for the environmental quality. We show that excessive over-taxation of the dirty technology may be not beneficial, as steady state pollution level can increase above a certain taxation threshold and multiple steady states can emerge. Moreover, dynamics can result in persistent endogenous oscillations that systematically lead to a significant increase in pollution levels. Finally, we discuss the economic rationale for the results also in the light of possible policy suggestions. [ABSTRACT FROM AUTHOR]

Among 15 strains of Listeria monocytogenes tested, a synergy between amoxicillin and ceftriaxone was observed in 14 (93%) according to minimal inhibitory concentration strips and 12 (80%) per the checkerboard methods, as well as for 2 of the 3 strains tested by the time-killing curve. This association may be an alternative treatment for listeriosis in the future. [ABSTRACT FROM AUTHOR]

The Brazilian National Policy on Solid Waste assigned a key role to the Municipalities in achieving its goals, which are: to reduce waste generation, promote its integrated management, and the environmentally appropriate disposal of waste. The Municipality of Foz do Iguaçu met the main requirements of the national policy law, since it published the Municipal Plan for Integrated Solid Waste Management in 2012, closed the "dump" in 1992, and installed sanitary landfill in 2001. However, some policy instruments - such as reverse logistics and the organization of collector's associations - still need to be evaluated. The article analyzes the implementation of the public policy of solid waste in Foz do Iguaçu (PR), through a model of indicators, to prepare a diagnosis of municipal solid waste management. [ABSTRACT FROM AUTHOR]

Background/Objectives: to assess surgical, oncological, and functional outcomes of robot-assisted radical prostatectomy (RARP) performed using the novel Hugo™ RAS system. Methods: A systematic review was conducted following the PRISMA guidelines, using PubMed, Web of Science, Scopus, and Embase databases. Eligible papers included studies involving adult males undergoing RARP with the Hugo™ RAS platform, with at least ten patients analyzed. The pooled analysis was performed using a random-effect model. Results: Quantitative analysis was conducted on 12 studies including 579 patients. The pooled median docking time, console time, and operative time were 11 min (95% CI 7.95–14.50; I2 = 98.4%, ten studies), 142 min (95% CI 119.74–164.68; I2 = 96.5%, seven studies), and 176 min (95% CI 148.33–203.76; I2 = 96.3%, seven studies), respectively. The pooled median estimated blood loss was 223 mL (95% CI 166.75–280.17; I2 = 96.5%, eleven studies). The pooled median length of hospital stay and time to catheter removal were 2.8 days (95% CI 1.67–3.89; I2 = 100%, ten studies) and 8.3 days (95% CI 5.53–11.09; I2 = 100%, eight studies), respectively. The pooled rate of postoperative CD ≥ 2 complications was 4.1% (95% CI 1–8.5; I2 = 63.6%, eleven studies). The pooled rate of positive surgical margins and undetectable postoperative PSA were 20% (95% CI 12.6–28.5; I2 = 71.5%, nine studies) and 94.2% (95% CI 87.7–98.6; I2 = 48.9%, three studies), respectively. At three months, a pooled rate of social continence of 81.9% (95% CI 73.8–88.9; I2 = 66.7%, seven studies) was found. Erectile function at six months was 31% in one study. Conclusions: despite the preliminary nature of the evidence, this systematic review and pooled analysis underscores the feasibility, safety, and reproducibility of the Hugo™ RAS system in the context of RARP. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to accurately determine ureteral stricture (US) rates following urolithiasis treatments and their related risk factors. Methods: We conducted a systematic review and meta-analysis following the PRISMA guidelines using databases from inception to November 2023. Studies were deemed eligible for analysis if they included ≥ 18 years old patients with urinary lithiasis (Patients) who were subjected to endoscopic treatment (Intervention) with ureteroscopy (URS), percutaneous nephrolithotomy (PCNL), or shock wave lithotripsy (SWL) (Comparator) to assess the incidence of US (Outcome) in prospective and retrospective studies (Study design). Results: A total of 43 studies were included. The pooled US rate was 1.3% post-SWL and 2.1% post-PCNL. The pooled rate of US post-URS was 1.9% but raised to 2.7% considering the last five years’ studies and 4.9% if the stone was impacted. Moreover, the pooled US rate differed if follow-ups were under or over six months. Patients with proximal ureteral stone, preoperative hydronephrosis, intraoperative ureteral perforation, and impacted stones showed higher US risk post-endoscopic intervention with odds ratio of 1.6 (P = 0.05), 2.6 (P = 0.009), 7.1 (P < 0.001), and 7.47 (P = 0.003), respectively. Conclusions: The overall US rate ranges from 0.3 to 4.9%, with an increasing trend in the last few years. It is influenced by type of treatment, stone location and impaction, preoperative hydronephrosis and intraoperative perforation. Future standardized reporting and prospective and more extended follow-up studies might contribute to a better understanding of US risks related to calculi treatment. [ABSTRACT FROM AUTHOR]

A 48-year-old man with a medical history of hypertension and no family history of prostate cancer presented with abdominal distension, lower abdominal pain, and lower urinary symptoms. Physical examination revealed a palpable mass in the lower abdomen, and a digital rectal examination detected a firm mass on the anterior side of the rectum. Laboratory tests showed an elevated PSA level (7.9 ng/mL). Imaging studies indicated a solid mass connected to the prostate's posterior and rectum's anterior walls, along with bladder compression. Transperitoneal biopsy and histological analysis led to a diagnosis of a stromal tumor with uncertain potential malignancy. Considering the absence of apparent malignancy signs and the smooth outer wall of the tumor, the patient underwent, for the first time in the literature, a robot-assisted radical extraperitoneal prostatectomy for complete macroscopic resection. The surgery involved excision of the bulky pelvic mass, preservation of the urethra, and anatomical reconstruction. The postoperative course was uneventful, and we discharged the patient with no complications. The pathological examination documented the diagnosis of multilocular prostatic cystadenoma. Post-surgery follow-up examinations, including PSA levels and imaging scans, showed no signs of tumor recurrence. At the 3-, 6-, and 9-month follow-ups, the patient was asymptomatic and had fully recovered, with no urinary or sexual dysfunction reported. [ABSTRACT FROM AUTHOR]

I Corsi di Studio in Tecnico della Riabilitazione Psichiatrica ed Educazione professionale afferenti alle Scuola di medicina e chirurgia (classe Professioni sanitarie, di seguito CdL) dell'Università degli Studi di Padova) condividono una sede esterna presso un'Azienda socio-sanitaria. Ogni CdL ha un proprio piano di studi con aree comuni alle professioni sanitarie e aree specifiche per il profilo disciplinare, tutti comunque accomunati da un ambito professionalizzante strutturato attraverso tirocini clinici. In questi anni è emersa l'esigenza di poter realizzare un piano aziendale dei tirocini, tenendo conto delle diverse professionalità e finalizzato all'integrazione delle diverse figure professionali, dal momento che ciascuna di queste sarà poi coinvolta in lavori in equipe. A partire dal 2013, infatti, in Italia è avanzato il concetto degli "ospedali orientati al paziente", organizzati e strutturati con un'equipe non soltanto professionale ma multidisciplinare in termini sia diagnostici, terapeutici e riabilitativi; ed è solo attraverso il lavoro in equipe che si ricompone la frammentazione dei saperi e delle tecniche. Ma per lavorare in equipe è necessario apprendere la cultura del lavoro di gruppo, riconoscere e governare le differenze, integrare le diverse prospettive. Il lavoro in equipe non è dunque uno "stato" ma un percorso da fare insieme. Di fronte alla complessità dell'ambito sanitario, oggi più che mai, gli uomini e le donne che lavorano in questi contesti, sono chiamati ad agire in una dimensione gruppale di interdisciplinarità e transdisciplinarietà, a praticare e promuovere una cultura dello scambio e della collaborazione intesa come spazio e dinamica all'interno dei servizi socio-sanitari. Per questo è nata l'idea di poter articolare un percorso sperimentale di didattica integrata per promuovere le competenze trasversali, abituare al lavoro interdisciplinare, ad esercitare gli studenti in formazione ad un pensiero critico, argomentativo, all'agire mediante il problem solving e il cooperative learning. [ABSTRACT FROM AUTHOR]

2nd-line target therapy outperforms chemotherapy in patients with BRAFV600E-mut mCRC regardless of RNF43 status. PURPOSE: Target therapy (TT) with encorafenib plus cetuximab is a standard option in patients with BRAFV600E -mutated (mut) pretreated metastatic colorectal cancer (mCRC). Recently, mutations in RNF43 , encoding a negative regulator of the WNT pathway, were associated with longer progression-free survival (PFS) and overall survival (OS) in patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) BRAFV600E -mut mCRC treated with TT. Here, we explored the effect of RNF43 mutations on the efficacy of second-line TT versus standard chemotherapy (CT). METHODS: A retrospective cohort of patients with pMMR/MSS BRAFV600E -mut tumors, available RNF43 mutational status, and treated with second-line TT or oxaliplatin- and/or irinotecan-based CT was analyzed. RESULTS: One hundred thirty-two patients with pMMR/MSS BRAFV600E -mut mCRC were included. RNF43 was found mut in 34 (26%) cases. Among RNF43 mutants, TT was associated with longer PFS (7.7 v 3.0 months; P =.002) and higher overall response rate (ORR; 45% v 0%; P =.009) compared with CT. Conversely, among RNF43 wild-type (wt) patients, only a trend for longer PFS (4.5 v 3.7 months; P =.064) favoring TT, with no differences in ORR (P =.14), was observed. After excluding 36 patients receiving TT in third line or beyond, a longer OS (19.4 v 10.1 months; P =.022) and a numerically OS advantage (10.6 v 6.6 months; P =.068) were reported for TT both in the RNF43 -mut and in the RNF43 wt groups. However, no interaction effect was reported between RNF43 mutational status and treatment in ORR (P interaction =.96), PFS (P interaction =.13), and OS (P interaction =.44). CONCLUSION: Patients with pMMR/MSS BRAFV600E -mut mCRC achieve benefit from TT versus CT independently of RNF43 mutational status, although a higher magnitude of benefit from TT is observed in RNF43 -mut tumors. These findings deserve confirmation in concluded and ongoing randomized trials. [ABSTRACT FROM AUTHOR]

Argentina is one of the five leading exporters of common bean (Phaseolus vulgaris L.) worldwide. Although common bean has been characterized as sensitive to boron toxicity, its production is often subjected to high boron concentrations. The aim of this study was to provide detailed information on the impact of increasing boron concentrations (0.5–8.0 mg L−1) on germination, growth, and root anatomy of two black bean cultivars (Leales 24 and Uirapurú) frequently produced in Argentina. Standard germination assays and pot greenhouse experiments were conducted. Radicles obtained in germination assays were used to make cross sections, which were analyzed under the microscope to identify anatomical alterations. Increasing boron concentrations had no effect on germination variables. In contrast, most of the growth variables analyzed (height, leaf area, fresh and dry weight, and water content) showed a steady decrease for boron concentrations above 1.0 mg L−1. Tissue boron concentrations showed an increase when boron concentrations increased. At the microscopic level, there seemed to be a decreasing trend in xylem vessel diameter. Our results suggest that boron concentrations above 1.0 and 2.0 mg L−1 may cause considerable growth and yield decreases in Uirapurú and Leales 24, respectively, thus affecting Argentinian bean production. Additionally, our results suggest that Leales 24 is moderately sensitive to boron toxicity and is best adapted for production in areas with higher boron concentrations. These findings highlight the importance of evaluating boron concentrations in soils and irrigation water in agricultural areas, and selecting cultivars best adapted to local conditions as tools for obtaining higher yields. [ABSTRACT FROM AUTHOR]

In this article, we present the development of a mini scanner device to characterize the full transverse spatial density of a charged particle beam using computed tomography. The profiler consists of a wire mounted on a linear translator that can rotate around the beam. Tests were performed on a millimeter electron beam with 200 eV energy and 100 nA intensity, which allowed us to control and monitor both beam focusing and deflection. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most common neoplasm in women. Although the primary tumor does not appear in a vital organ, lethality is due to the ability of tumor cells to invade and seed distant organs, causing metastases. Approaches to reduce breast cancer cell aggressiveness target hormone receptors that sustain cell growth and motility. However, other factors contribute to aberrant cell behaviors in cancer cells, and nowadays, the role of the environment surrounding cancer cells is evident. The extracellular matrix polysaccharide hyaluronan is a ubiquitous component of the tumor microenvironment that not only modulates cell growth and movement but also plays a critical role in modulating the inflammatory response. In this review, we discuss the role of hyaluronan in relation to the expression of critical hormone receptors. The expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in breast cancer cells is critical for determining tumor aggressiveness and targeting therapies. The presence of such receptors allows for the use of antagonists that effectively reduce breast cancer growth and dissemination. However, the absence of such receptors in triple-negative breast cancer (TNBC) reduces the possibility of targeted therapy, making these tumors very aggressive with a poor outcome. Cancers are not solely composed of tumor cells, but also include several types of infiltrating cells, such as fibroblasts, macrophages, and other immune cells that have critical functions in regulating cancer cell behaviors. In addition to these cells, the extracellular matrix (ECM) has become an important player in many aspects of breast cancer biology, including cell growth, motility, metabolism, and chemoresistance. Hyaluronan (HA) is a key ECM component that promotes cell proliferation and migration in several malignancies. Notably, HA accumulation in the tumor stroma is a negative prognostic factor in breast cancer. HA metabolism depends on the fine balance between HA synthesis by HA synthases and degradation yielded by hyaluronidases. All the different cell types present in the tumor can release HA in the ECM, and in this review, we will describe the role of HA and HA metabolism in different breast cancer subtypes. [ABSTRACT FROM AUTHOR]

Since December 2019, many drugs have been evaluated or advocated as potential treatments of SARS-CoV-2 induced disease (COVID-19), including many repositioned drugs and some others specifically developed for these diseases. They can be roughly classified into three categories according to their main mechanism of action (passive immunization, direct antivirals, and anti-inflammatory treatments), and their use depends on the stage of the disease. Despite often promising preclinical data, most of the treatments evaluated failed to show a significant clinical benefit. In addition, a few others have seen their effectiveness affected by the occurrence of SARS-CoV-2 variants and sub-variants. Herein, the aim of this article is to take stock of the data available as of the 14th of July 2022, concerning the specific healing options evaluated for patients suffering from COVID-19. We focus particularly on healing treatments of COVID-19 and do not deal with preventive treatments such as vaccine. Associated therapies such as venous thromboembolism prophylaxis are not detailed since they are covered in a specific chapter of this issue. Passive immunization, especially through monoclonal antibodies, showed a positive impact on the clinical evolution, whether in outpatients or inpatients without oxygen supply. However, their effectiveness strongly depends on the type of SARS-CoV-2 variant, and often decreases or even vanishes with the most recent variants. Among direct antiviral treatments, ritonavir-boosted nirmatrelvir appears to currently be the cornerstone in the management of early infections, but its use may be limited by drug interactions. Remdesivir remains as an alternative in this situation, even though it is potentially less convenient. Anti-inflammatory treatments have often been shown to be the most effective in inpatients with oxygen supply. Dexamethasone is now a cornerstone of management of these patients. Added tocilizumab seems beneficial in the case of hyper inflammation. JAK inhibitors and anakinra have also gained an interest in some studies. As a conclusion of this narrative review, the best treatment strategy has yet to be defined and is likely to evolve in the future, not only because many other drugs are still under development and evaluation, but also because of the viral epidemics and epidemiology evolution. [ABSTRACT FROM AUTHOR]

The analysis of the relief characteristics of a hydrographic basin is relevant for the study of flood danger. Its influence on hydrological and geomorphological processes and meteorological characteristics is closely related to the phenomena that manifest on its surface. The aim of the work is to analyze the parameters (average height, unevenness, slope gradient and slope orientation) that define the relief of the upper basin of the Sauce Corto stream as factors of flood hazard. Parameters and morphometric indices associated with the relief were used at two categorical levels: on the one side at the level of each sub-basin in particular and on the other side jointly according to the margin of the main course to which their waters contribute. In the southwestern and southern subbasins of the upper basin of the Sauce Corto stream (Martirio, Cerro 832, Nacimiento Oeste and Nacimiento Este) it is possible to infer sudden floods enhanced by the high slope gradients. Likewise, in the subbasins on the left bank of the main course, runoff processes are accelerated given their altitudinal and slope characteristics. This study allows us to understand the distribution and association of the relief variables that make up the hazard associated with flood events. [ABSTRACT FROM AUTHOR]

The west of Santa Catarina was occupied by indigenous groups and caboclos until the arrival of other migrants and immigrants in the 20th century. The spaces occupied by fields and forests were described as "sertões" (wilderness), as they did not have a suitable agricultural practice at the time. The object of this article is to analyze the uses and occupation process of forest areas in western Santa Catarina from 1920 to 1960, when this frontier was "closed". For this, a varied typology of sources was analyzed, in dialogue with the precepts of environmental history. The advance of colonization was responsible for the reduction of spaces dominated by the forest, which is now occupied by agriculture and animal husbandry. Both were the main elements responsible for the formation and consolidation of the agro-industrial sector in the region. [ABSTRACT FROM AUTHOR]

Resting state fMRI has been used in many studies to investigate the impact of brain tumours on functional connectivity (FC). However, these studies have so far assumed that FC is stationary, disregarding the fact that the brain fluctuates over dynamic states. Here we utilised resting state fMRI data from 33 patients with high-grade gliomas and 33 healthy controls to examine the dynamic interplay between resting-state networks and to gain insights into the impact of brain tumours on functional dynamics. By employing Hidden Markov Models, we demonstrated that functional dynamics persist even in the presence of a high-grade glioma, and that patients exhibited a global decrease of connections strength, as well as of network segregation. Furthermore, through a multivariate analysis, we demonstrated that patients' cognitive scores are highly predictive of pathological dynamics, thus supporting our hypothesis that functional dynamics could serve as valuable biomarkers for better understanding the traits of high-grade gliomas. [ABSTRACT FROM AUTHOR]

Medical diagnostics, product classification, surveillance and detection of inappropriate behavior are becoming increasingly sophisticated due to the development of methods based on image analysis using neural networks. Considering this, in this work, we evaluate state-of-the-art convolutional neural network architectures proposed in recent years to classify the driving behavior and distractions of drivers. Our main goal is to measure the performance of such architectures using only free resources (i.e., free graphic processing unit, open source) and to evaluate how much of this technological evolution is available to regular users. [ABSTRACT FROM AUTHOR]

The need to assess the competences acquired by the students of the Professional Education degree course, during their formative internship, has always appeared as extremely important and central for the institutional referents. The contribution aims to present the theoretical premises of the technical choices made during the process of construction, revision, and implementation of an apprenticeship assessment tool, resulting both from some critical issues highlighted in the previously used tool and the need to move from a selective assessment approach to a formative, transformative, and participative one. [ABSTRACT FROM AUTHOR]

Simple Summary: Although the extensive use of highly active oncological treatments has led to an increased rate of secondary resections in patients with colorectal liver metastases, it has led to questions regarding the correct surgical management of disappearing liver metastases (DLM) and small residual lesions during chemotherapy. Our study aimed to evaluate the clinical outcome of DLM and small remnant liver metastases (≤10 mm) assessed by means of hepatobiliary contrast-enhanced and diffusion-weighted MR imaging (DW-MRI) in metastatic colorectal cancer patients with first-line chemotherapy treatment in order to support the clinical management and decision-making process for these liver lesions. Our results showed that DLM assessed via hepatobiliary contrast-enhanced and DW-MRI very probably indicate a complete response in patients without chemotherapy-induced sinusoidal obstruction syndrome. In these patients, a follow-up with liver MRI can be considered, and resection should be performed in the case of disease relapse. The surgical removal of small remnants of liver metastases should always be advocated whenever technically possible. We aimed to evaluate the outcome of the disappearance or small remnants of colorectal liver metastases during first-line chemotherapy assessed by hepatobiliary contrast-enhanced and diffusion-weighted MR imaging (DW-MRI). Consecutive patients with at least one disappearing liver metastasis (DLM) or small residual liver metastases (≤10 mm) assessed by hepatobiliary contrast-enhanced and DW-MRI during first-line chemotherapy were included. Liver lesions were categorized into three groups: DLM; residual tiny liver metastases (RTLM) when ≤5 mm; small residual liver metastases (SRLM) when >5mm and ≤10 mm. The outcome of resected liver metastases was assessed in terms of pathological response, whereas lesions left in situ were evaluated in terms of local relapse or progression. Fifty-two outpatients with 265 liver lesions were radiologically reviewed; 185 metastases fulfilled the inclusion criteria: 40 DLM, 82 RTLM and 60 SRLM. We observed a pCR rate of 75% (3/4) in resected DLM and 33% (12/36) of local relapse for DLM left in situ. We observed a risk of relapse of 29% and 57% for RTLM and SRLM left in situ, respectively, and a pCR rate of about 40% overall for resected lesions. DLM assessed via hepatobiliary contrast-enhanced and DW-MRI very probably indicates a complete response. The surgical removal of small remnants of liver metastases should always be advocated whenever technically possible. [ABSTRACT FROM AUTHOR]

We designed a retrospective study to assess the surgical and economic outcomes of robot-assisted laparoscopic pyeloplasty (RALP) compared with open pyeloplasty (OP), including consecutive patients suffering from ureteropelvic junction obstruction and operated on from January 2012 to January 2022 at a single center. Preoperative, intraoperative, and postoperative outcomes, including costs, were comparatively analyzed. The primary outcome was 3-month success, defined as symptom resolution and no obstruction upon diuretic renal scintigraphy. Overall, 91 patients were included (48 OP and 43 RALP). The success rate at 3 months was 93.0% and 83.3% in the RALP and OP group, respectively (p = 0.178), and the results remained stable at the last follow-up (35.4 ± 22.8 months and 56.0 ± 28.1 months, respectively). Intraoperative blood loss (p < 0.001), need for postoperative analgesics (p = 0.019) and antibiotics (p = 0.004), and early postoperative complication rate (p = 0.009) were significantly lower in the RALP group. None of the assessed variables were a predictor for failure. The mean total direct cost per surgical procedure and related hospital stay was 2373 € higher in the RALP group. RALP is an effective and safe treatment for ureteropelvic junction obstruction; however, further studies are needed to evaluate the cost-effectiveness of RALP, accounting for indirect costs and cost-saving with new surgical platforms. [ABSTRACT FROM AUTHOR]

Background: Trop-2 and Nectin-4 are transmembrane proteins overexpressed in many tumours and targets of antibody–drug conjugates (ADC). In metastatic colorectal cancer (mCRC), the role of Trop-2 and Nectin-4 has been poorly investigated. Methods: Tumour samples of patients randomised in the phase III TRIBE2 were assessed for Trop-2 and Nectin-4 expression. Results: Three hundred eighty-six tumours were assessed for Trop-2 expression. 90 (23%), 115 (30%) and 181 (47%) were Trop-2 high, medium and low, respectively. Patients with low Trop-2 tumours achieved longer PFS (12 versus 9.9 months, p = 0.047) and OS (27.3 versus 21.3 months, p = 0.015) than those with high/medium Trop-2 tumours. These findings were confirmed in multivariate analysis (p = 0.022 and p = 0.023, respectively). A greater OS benefit from treatment intensification with FOLFOXIRI/bevacizumab was observed in patients with high/medium Trop-2 tumours (p-for-interaction = 0.041). Two hundred fifty-one tumours were assessed for Nectin-4 expression. Fourteen (5%), 67 (27%) and 170 (68%) were high, medium and low, respectively. No prognostic impact was observed based on Nectin-4 expression and no interaction effect was reported between Nectin-4 expression groups and treatment arm. Conclusions: In mCRC, expression levels of Trop-2 and Nectin-4 are heterogeneous, suggesting a target-driven development of anti-Trop2 and anti-Nectin-4 ADCs. Medium/high Trop-2 expression is associated with worse prognosis and higher benefit from chemotherapy intensification. [ABSTRACT FROM AUTHOR]

Myosin expression and purification is important for mechanistic insights into normal function and mutation induced changes. The latter is particularly important for striated muscle myosin II where mutations cause several debilitating diseases. However, the heavy chain of this myosin is challenging to express and the standard protocol, using C2C12 cells, relies on viral infection. This is time and work intensive and associated with infrastructural demands and biological hazards, limiting widespread use and hampering fast generation of a wide range of mutations. We here develop a virus-free method to overcome these challenges. We use this system to transfect C2C12 cells with the motor domain of the human cardiac myosin heavy chain. After optimizing cell transfection, cultivation and harvesting conditions, we functionally characterized the expressed protein, co-purified with murine essential and regulatory light chains. The gliding velocity (1.5–1.7 µm/s; 25 °C) in the in vitro motility assay as well as maximum actin activated catalytic activity (kcat; 8–9 s−1) and actin concentration for half maximal activity (KATPase; 70–80 µM) were similar to those found previously using virus based infection. The results should allow new types of studies, e.g., screening of a wide range of mutations to be selected for further characterization. [ABSTRACT FROM AUTHOR]

Intracellular trafficking of AMPA receptors is a tightly regulated process which involves several adaptor proteins, and is crucial for the activity of excitatory synapses both in basal conditions and during synaptic plasticity. We found that, in rat hippocampal neurons, an intracellular pool of the tetraspanin TSPAN5 promotes exocytosis of AMPA receptors without affecting their internalisation. TSPAN5 mediates this function by interacting with the adaptor protein complex AP4 and Stargazin and possibly using recycling endosomes as a delivery route. This work highlights TSPAN5 as a new adaptor regulating AMPA receptor trafficking. [ABSTRACT FROM AUTHOR]

This paper derives equations of motion for the mean elements under an inverse-square perturbing acceleration that is a function of latitude and longitude in an inertial frame. Equations of motion for the mean elements are first derived with a perturbing acceleration described by Fourier series in true anomaly. Fourier series in true anomaly are found for spherical harmonics expansions of the perturbing acceleration in the radial, in-track, and cross-track (RIC) frame. Additionally, the rotation of a perturbing acceleration described using spherical harmonics expansions in the inertial frame into the RIC frame is provided. An analytical solution for the osculating elements is derived and used to find an analytical osculating-to-mean element conversion. Analytical and numerical characterization of the osculation magnitude about the mean elements provides important information for trajectory design and spacecraft safety. The contributions of higher-order effects not captured by first-order orbit averaging are discussed. Finally, these results are applied to a comet-orbiter with an inertially fixed attitude and shown to track well even when the dynamics used in the averaging procedure are approximate. [ABSTRACT FROM AUTHOR]

Ceftaroline fosamil (prodrug) and ceftaroline (active form; degradation product) were simultaneously determined by a new stability-indicating HPLC method. These two forms were monitored during stability investigation of drug formulation reconstituted solution following the same conditions used for clinical use (refrigeration and room temperature). In general terms, ceftaroline fosamil is stable when stored at refrigerator until 48 h, with a drug residual content of 93.99% (in saline diluent) and 97.18% (in 5% glucose diluent). At room temperature, its chemical stability is critical, being necessary attention in the time infusion. Ceftaroline free basis was formed during stability testing, and its concentration has increased along the time. A forced degradation study was also performed for evaluation of the main degradation products, which were identified by LC-MS analysis. Applying selected stress conditions, five degradation products were structurally identified, with variation on side chain and cephalosporinic ring. The opened β-lactam ring and ceftaroline free basis can be highlighted. [ABSTRACT FROM AUTHOR]

The literature is increasingly approaching the participation of households in the delivery of urban services through the lens of co-production. However, there has been no in-depth exploration of the relationship between incremental changes in the urban fabric (urban typologies and morphologies) and the forms of adaptations of co-produced water and sanitation services (WSS). The paper draws on three planned neighbourhoods in Hanoi to examine these incremental changes by considering the transformation of the neighbourhood at different scales and the consequent evolution of the sociotechnical arrangements for the delivery of water and sanitation services. By exploring forms of reconfiguration of the built environment and embedded water infrastructures, the paper outlines the possibility of an alternate reading of service co-production initiatives as incremental spatial practices, with an emphasis on the role of technology in allowing transformation processes. [ABSTRACT FROM AUTHOR]

Seth Garfield's book, "Guaraná: How Brazil Embraced the World's Most Caffeine-Rich Plant," explores the history of the guarana plant in Brazil. Garfield examines the political, environmental, and economic contexts that shaped the plant's history from the colonial period to the present. The book delves into the interests of traders, techniques of scientists, strategies of marketers, and the behaviors and tastes of consumers that contributed to the popularity of guarana. Garfield's research draws on a wide range of primary sources and fields of knowledge to provide a comprehensive understanding of the plant's significance in Brazilian history and culture. [Extracted from the article]

Background: Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0. Methods: The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet ± bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples. Results: A significant interaction effect between primary sidedness and treatment intensity was reported in terms of both PFS (p = 0.010) and OS (p = 0.003), with a beneficial effect of the triplet in the right-sided group and a possible detrimental effect in the left-sided. No interaction effect was observed between ECOG-PS and chemo-backbone. In the MSS/pMMR population, a consistent trend for a side-related subgroup effect was observed when FOLFOXIRI ± bevacizumab was compared to oxaliplatin-based doublets±bevacizumab (p = 0.097 and 0.16 for PFS and OS, respectively). Among MSS/pMMR tumours, the BM1 subtype was more prevalent in the right-sided group (p = 0.0019, q = 0.0139). No significant differences were observed according to sidedness in the MSI-H/dMMR population. Conclusions: Real-life data support the use of FOLFOXIRI ± bevacizumab only in BRAFV600E-mutated mCRC patients with right-sided tumours. [ABSTRACT FROM AUTHOR]

Cerebral vasculitides, both isolated or in systemic disorders, could be triggered by infections, and few cases have been associated to coronavirus disease 2019 (COVID-19). This study searched for publications in Pubmed, EMBASE, and Cochrane library databases for case reports and series of isolated central nervous system (CNS) vasculitides triggered by severe acute respiratory syndrome coronavirus-2. We included 12 studies (published from June 2020 to July 2022) and collected 39 adult patients (5/39 pathologically or radiologically proven, 34/39 suggestive for primary CNS vasculitis or PCNSV). All cases had a positive real-time polymerase chain reaction on a nasopharyngeal swab or a respiratory tract specimen. About the 85% of the included cases were males, and disease onset occurred later than 50 years old in all but three subjects. In total, 33/39 patients presented severe COVID-19 pneumonia, frequently requiring intensive care unit care. The most common neurological features were headache, obnubilation, and coma. PCNSV was suspected mainly on radiological findings, whereas the cerebrospinal fluid analysis was minimally altered. Magnetic resonance imaging showed vessel wall enhancement in 32/39 cases, generally with the concomitant presence of microbleeds, subarachnoid haemorrhages, and/or multiple ischemic lesions. Despite the severe respiratory and neurological disease course, most cases (93%) improved spontaneously or after a course of high-dose intravenous steroids with no need for immunosuppression. In conclusion, PCNSV could rarely relate to COVID-19 and independently from pulmonary disease severity. Adults with COVID-19-related PCNSV could have a favourable prognosis. [ABSTRACT FROM AUTHOR]

Background: Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0.Methods: The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet ± bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples.Results: A significant interaction effect between primary sidedness and treatment intensity was reported in terms of both PFS (p = 0.010) and OS (p = 0.003), with a beneficial effect of the triplet in the right-sided group and a possible detrimental effect in the left-sided. No interaction effect was observed between ECOG-PS and chemo-backbone. In the MSS/pMMR population, a consistent trend for a side-related subgroup effect was observed when FOLFOXIRI ± bevacizumab was compared to oxaliplatin-based doublets±bevacizumab (p = 0.097 and 0.16 for PFS and OS, respectively). Among MSS/pMMR tumours, the BM1 subtype was more prevalent in the right-sided group (p = 0.0019, q = 0.0139). No significant differences were observed according to sidedness in the MSI-H/dMMR population.Conclusions: Real-life data support the use of FOLFOXIRI ± bevacizumab only in BRAFV600E-mutated mCRC patients with right-sided tumours. [ABSTRACT FROM AUTHOR]

Silica fillers are used in various nanocomposites in combination with silanes as a reinforcing filler. In tire technology, silica is generally functionalized before (pre-treated) or during mixing (in-situ silanization or post-treated). In both cases, a soft base catalyst (e.g., triethylamine or diphenyl guanidine, DPG) is typically used to accelerate and increase the yield of the silane/silica coupling reaction. In this study, we investigated how pre-treatments of silica particles with either strong amine or hydride bases impact the silanization of silica prior to or during SBR mixing for silica-rubber nanocomposite fabrication. Our findings are supported by molecular characterization (solid state 29Si NMR, 1H NMR and TGA), and scanning electron microscopy. In addition, the impact of these silica pre-treatments on a nanocomposite's mechanical properties was evaluated using dynamic mechanical analysis (DMA). [ABSTRACT FROM AUTHOR]

Background: Cyanobacteria blooms have become a major environmental problem and concern because of secondary metabolites produced by cyanobacteria released into the water. Cyanobacteria produce volatile organic compounds (VOCs), such as the compounds β-cyclocitral and β-ionone, which comprise odors, off-flavors, defense compounds, as well as growth regulators. Therefore, the general objective of this work was to evaluate the VOCs produced by two strains of Microcystis aeruginosa, differing in their ability to produce microcystins (LTPNA 01—non-producing and LTPNA 08—toxin-producing). The analysis of VOC production was carried out in (1) normal culture conditions, (2) under different light intensities (LI), and (3) after the external application of β-ionone in both cultures. Results: The results showed that β-cyclocitral and β-ionone are produced in all growth phases of LTPNA 01 and LTPNA 08. Both strains were producers of β-cyclocitral and β-ionone in normal culture conditions. It was observed that the β-cyclocitral concentration was higher than β-ionone in all light intensities investigated in this study. Additionally, the strain LTPNA 01 produced more β-cyclocitral than LTPNA 08 at almost all times and LIs analyzed. However, the strain LTPNA 08 produced more β-ionone, mainly at the initial times. In addition, the experiment results with the external addition of β-ionone in the cultures showed that the strain LTPNA 01 produced more β-cyclocitral in control conditions than in treatment. Nonetheless, β-ionone production was higher in treatment conditions in LTPNA 08, indicating that the addition of β-ionone may favor the production of these compounds and inhibit the production of β-cyclocitral. Conclusion: Our results showed that some abiotic factors, such as different light intensities and external application of β-ionone, can be triggers that lead to the production of VOCs. [ABSTRACT FROM AUTHOR]

During normal aging, the brain undergoes structural and functional changes. Many studies applied static functional connectivity (FC) analysis on resting state functional magnetic resonance imaging (rs‐fMRI) data showing a link between aging and the increase of between‐networks connectivity. However, it has been demonstrated that FC is not static but varies over time. By employing the dynamic data‐driven approach of Hidden Markov Models, this study aims to investigate how aging is related to specific characteristics of dynamic brain states. Rs‐fMRI data of 88 subjects, equally distributed in young and old were analyzed. The best model resulted to be with six states, which we characterized not only in terms of FC and mean BOLD activation, but also uncertainty of the estimates. We found two states were mostly occupied by young subjects, whereas three other states by old subjects. A graph‐based analysis revealed a decrease in strength with the increase of age, and an overall more integrated topology of states occupied by old subjects. Indeed, while young subjects tend to cycle in a loop of states characterized by a high segregation of the networks, old subjects' loops feature high integration, with a crucial intermediary role played by the dorsal attention network. These results suggest that the employed mathematical approach captures the complex and rich brain's dynamics underpinning the aging process. [ABSTRACT FROM AUTHOR]

Background: Tumors with homologous recombination deficiency (HRD) show high sensitivity to platinum salts and poly(ADP-ribose) polymerase-inhibitors in several malignancies. In colorectal cancer (CRC), the role of HRD alterations is mostly unknown.Methods: Next-generation sequencing, whole transcriptome sequencing, and whole exome sequencing were conducted using CRC samples submitted to a commercial Clinical Laboratory Improvement Amendments certified laboratory. Tumors with pathogenic and/or presumed pathogenic mutations in 33 genes involved in the homologous recombination pathway were considered HRD, the others were homologous recombination proficient (HRP). Furthermore, tumor samples from patients enrolled in the phase III TRIBE2 study comparing upfront FOLFOXIRI+bevacizumab vs FOLFOX+bevacizumab were analyzed with next-generation sequencing. The analyses were separately conducted in microsatellite stable or proficient mismatch repair (MSS/pMMR) and microsatellite instable-high or deficient mismatch repair (MSI-H/dMMR) groups. All statistical tests were 2-sided.Results: Of 9321 CRC tumors, 1270 (13.6%) and 8051 (86.4%) were HRD and HRP, respectively. HRD tumors were more frequent among MSI-H/dMMR than MSS/pMMR tumors (73.4% vs 9.5%; P  < .001; q < 0.001). In MSS/pMMR group, HRD tumors were more frequently tumor mutational burden high (8.1% vs 2.2%; P  < .001; q < 0.001) and PD-L1 positive (5.0% vs 2.4%; P  < .001; q = 0.001), enriched in all immune cell and fibroblast populations and genomic loss of heterozygosity-high (16.2% vs 9.5%; P = .03). In the TRIBE2 study, patients with MSS/pMMR and HRD tumors (10.7%) showed longer overall survival compared with MSS/pMMR and HRP tumors (40.2 vs 23.8 months; hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.45 to 0.98; P = .04). Consistent results were reported in the multivariable model (HR = 0.67, 95% CI = 0.45 to 1.02; P = .07). No interaction effect was evident between homologous recombination groups and treatment arm.Conclusions: HRD tumors are a distinctive subgroup of MSS/pMMR CRCs with specific molecular and prognostic characteristics. The potential efficacy of agents targeting the homologous recombination system and immune checkpoint inhibitors in this subgroup is worthy of clinical investigation. [ABSTRACT FROM AUTHOR]

In the northern slope of the Ventania System (province of Buenos Aires), flooding and waterlogging events occur with high frequency, configuring risk situations. Determining hydric excess events towards vulnerability is a complex task, given the large number of variables involved and their respective associated indicators. In this context, the aim of this paper is to evaluate and represent the spatial distribution of social vulnerability in Coronel Suárez's distric at the census radio scale. Census official data were used, grouped into three categories: demography, quality of life and working conditions. A multivariate classification analysis of spatial units was performed using the standardized averages method. The 53.33 % of the district's population presents medium and high vulnerability, registered in both urban and rural areas, which will be affected by the occurrence of floods and waterlogging due to deficient socio-economic and demographic conditions. The cartographic representation of vulnerability is an instrument of great relevance for the actors involved in the processes of flood and waterlogging risk management of the different administrative levels. [ABSTRACT FROM AUTHOR]

While there is abundant anecdotal evidence of political polarization in Brazil, empirical studies have largely focused on voting patterns. Based on two historical series of opinion polls (Latin American Public Opinion Project and World Values Survey), we investigate the occurrence of political polarization in four established ways: polarization of opinions on political issues, polarization of political identities, sorting of opinions and identities and affective polarization. We found that there is polarization of opinion about gay rights and about divorce both as a process and as a state. Political identities have also been polarized since 2010, especially among the elderly and the less educated, without any significant increase in ideological sorting. Finally, we found that, among the politically engaged, there is affective polarization around some identities. [ABSTRACT FROM AUTHOR]

This article presents the case of a Telemedicine platform that integrated technology, health and co-production to serve the population. Lauduz was the first telemedicine platform created in a Brazilian city to respond to the COVID-19 health emergency. The objective of the research is to show how the interfaces between technology and health together with the coproduction of public goods and services contributed to face the public health crisis generated by the pandemic. A qualitative analysis and a questionnaire to the CEO of Lauduz were carried out, which showed that coproduction was fundamental for the success of the actions carried out; precisely because there was a great collaboration to provide on line health care to patients with flu symptoms to prevent the further spread of the SARS-CoV-2 virus, all of which represented an innovation in the area of public health. [ABSTRACT FROM AUTHOR]

The use of indicators for political planning gained new impulse in Brazil in the 1990s, with the implementation and evaluation of social policies. The present work discusses the concept, scope and limits of the use of these planning tools in the management of public policies at the Municipal level in Brazil. The emergence and development of social indicators and indices is addressed, as well as their role in the formulation, monitoring and evaluation of public policies. The use of social indicators to evaluate the performance of education policies in municipalities of the State of Paraná is presented as a case study. Finally, positive aspects and limitations in the use of synthetic indices in public policies at the local level are highlighted. [ABSTRACT FROM AUTHOR]

Subantarctic Nothofagus forests are the southernmost forests in the world, with negligible atmospheric nitrogen (N) deposition. Most paradigms about the role of ectomycorrhizal (ECM) fungi in N cycling and plant N uptake at high latitudes have been tested in boreal coniferous forests, while in the southern hemisphere, ECM hosts are primarily angiosperms. Using ITS1 meta‐barcoding, we characterized ECM and saprotrophic fungal communities in evergreen and deciduous Nothofagus forests forming monodominant and mixed stands in the archipelago of Tierra del Fuego (Chile and Argentina). We assessed the N economy of Nothofagus by correlating host species with fungal relative abundances, edaphic variables, net N mineralization, microbial biomass N and the activity of eight extracellular soil enzymes activities. The N economy of deciduous N. pumilio forests was strikingly similar to boreal coniferous forests, with the lowest inorganic N availability and net N mineralization, in correlation to higher relative abundances of ECM fungi with enzymatic capacity for organic N mobilization (genus Cortinarius). In contrast, the N economy of evergreen N. betuloides forests was predominantly inorganic and correlated with ECM lineages from the family Clavulinaceae, in acidic soils with poor drainage. Grassy understory vegetation in deciduous N. antarctica forests likely promoted saprotrophic fungi (i.e., genus Mortierella) in correlation with higher activities of carbon‐degrading enzymes. Differences between Nothofagus hosts did not persist in mixed forests, illustrating the range of soil fertility of these ECM angiosperms and the underlying effects of soil and climate on Nothofagus distribution and N cycling in southern Patagonia. [ABSTRACT FROM AUTHOR]

Background: The Hugo™ Robotic-Assisted Surgery (Hugo™ RAS) system represents a novel advancement in robotic surgical technology. Despite this, there remains a scarcity of data regarding extraperitoneal robot-assisted radical prostatectomy (eRARP) using this system. Methods: We conducted a prospective study at Ospedale Regionale "F. Miulli" from June 2023 to January 2024, enrolling consecutive patients diagnosed with prostate cancer (PCa) undergoing eRARP ± lymph node dissection. All procedures employed a modular four-arm setup performed by two young surgeons with limited prior robotic surgery experience. This study aims to evaluate the safety and feasibility of eRARP using the Hugo™ RAS system, reporting comprehensive preoperative, intraoperative, and postoperative outcomes in the largest reported cohort to date. Results: A total of 50 cases were analyzed, with a mean patient age of 65.76 (±5.57) years. The median operative time was 275 min (Q1–Q3 150–345), and the console time was 240 min (Q1–Q3 150–300). The docking time averaged 10 min (Q1–Q3 6–20). There were no intraoperative complications recorded. Two major complications occurred within the first 90 days. At the 3-month mark, 36 patients (72%) achieved undetectable PSA levels (<0.1 ng/mL). Social continence was achieved by 66% of patients, while 40% maintained erectile function. Conclusions: eRARP utilizing the Hugo™ RAS system demonstrated effectiveness and safety in our study cohort. However, more extensive studies with larger cohorts and longer follow-up periods are necessary to thoroughly evaluate long-term outcomes. [ABSTRACT FROM AUTHOR]

To evaluate the effect of Er:YAG laser conditioning of a glass-infiltrated alumina-based zirconia-reinforced ceramic on its flexural strength and on bonding to a resin cement. Sixteen blocks (5 × 5 × 4 mm) and 50 discs (Ø 12 mm, 1 mm thickness) of In-Ceram Zirconia (ICZ) obtained from CAD-CAM blocks were infiltrated with glass. For the microtensile bond strength (μTBS) test, all blocks were treated with aluminum oxide (AOX) and divided into 4 groups (n = 4): G1 (AOX), no combined surface treatment; G2 (ROC), tribochemical silica-coating; G3 (EY200), Er:YAG laser 200 mJ/15 Hz; and G4 (EY250), Er:YAG laser 250 mJ/10 Hz. The ceramic blocks were silanated and cemented with a resin cement (Panavia F2.0/Kuraray) to composite resin blocks and subjected to the μTBS test. For the flexural strength evaluation, the discs were divided into 5 groups (n = 10) as described above, in addition to a control group (G5 – CTRL, mirror-polished without further treatment). Each surface treatment was submitted to qualitative evaluation under SEM. One-way ANOVA (α = 5%) revealed the highest bond strength value for EY200 with no significant difference from ROC. The groups AOX and EY250 showed similar μTBS values that were statistically lower than those of EY200. For flexural strength, ROC was the only group with significantly lower values when compared with the CTRL. The use of Er:YAG laser at 200 mJ/15 Hz can be considered an innovative and effective alternative for surface conditioning of ICZ since it did not reduce the flexural strength of the ceramic and improved the resin cement bond to this substrate. [ABSTRACT FROM AUTHOR]

Background: In mCRC, CEA is used to monitor response to systemic therapy together with imaging. After the end of induction, no major improvement in tumour shrinkage is expected, and the availability of a marker able to predict progressive disease (PD) versus no-PD might allow avoiding CT scans.Methods: We pooled data from patients with baseline CEA ≥ 10 ng/mL included in TRIBE and TRIBE2 studies with the aim of identifying a threshold for percent increase of CEA from nadir able to predict PD after the end of the induction therapy.Results: In total, 1178 paired CEA and radiological assessments from 434 patients were included. According to the optimal cut-off determined by ROC, a CEA increase of at least 120% from nadir differentiated between PD and no-PD with a sensitivity of 74% and a specificity of 78%, excluding PD in the 92% of radiological assessments and allowing to avoid the 67% of CT scans. However, CEA cut-off of 120% was not able to detect radiological PD in 26% of cases. In order to mitigate this issue, a different clinically relevant threshold was evaluated based on the best sensitivity cut-off. Therefore, using any CEA increase from nadir as a threshold, the sensitivity grew to 93% and only in the 7% of cases the radiological PD was not detected.Conclusions: In mCRC with baseline CEA ≥ 10 ng/mL, CEA values can accurately predict PD versus no-PD after the end of the first-line induction therapy. [ABSTRACT FROM AUTHOR]

Recent data from the TRIBE2 study have failed to suggest a higher magnitude of benefit from upfront FOLFOXIRI/bevacizumab in patients with BRAF -mutant metastatic colorectal cancer (mCRC) as previously reported in the TRIBE study. Clinical characteristics and gene expression signatures of patients with BRAF-mutant mCRC enrolled in the TRIBE2 study were evaluated with the aim of understanding that patients may derive benefit from the intensification of the upfront chemotherapy. Of 46 BRAF-mutant tumour samples analysed, 24 (52%) and 22 (48%) were classified as BM1 and BM2, respectively, and 27 (59%) and 19 (41%) were assigned to ligand-independent (LI) and ligand-dependent (LD) Wnt pathway subgroups, respectively. No prognostic impact was shown for both BM1/BM2 and LI/LD subtypes. No interaction was evident between BM1/BM2 or LI/LD signatures and the benefit provided by FOLFOXIRI/bevacizumab. Significant interaction effect was evident in terms of progression-free survival between treatment arm and primary tumour sidedness (P = 0.05) and Eastern Cooperative Oncology Group performance status (ECOG-PS; P < 0.001). Gene expression analysis failed to identify patients with BRAF-mutant mCRC candidate to upfront FOLFOXIRI/bevacizumab. ECOG-PS >0 and left-sidedness seem associated with no benefit from the intensified treatment. • A restricted panel of 44 genes discerns BM1/BM2 subtypes of BRAF mut mCRC. • AXIN2 expression distinguishes LI versus LD Wnt pathway activation of BRAF mut mCRC. • No prognostic impact was shown for both BM1/BM2 and LI/LD subtypes. • No predictive effect of both BM1/BM2 and LI/LD subtypes was shown for FOLFOXIRI/bev. • ECOG-PS >0 and left-sidedness seem associated with no benefit from FOLFOXIRI/bev. [ABSTRACT FROM AUTHOR]

Today's internal combustion engines are subject to strict regulations of pollutant emissions and to ambitious fuel consumption reduction targets. For direct-injection compression-ignition engines, multiple injections offer additional degrees of freedom that help to achieve these goals. Thus far, the calibration of multiple injections has been based on data-driven approaches using design of experiments. However, an ever increasing number of actuators causes the calibration of the engine to require much more time. In this paper, we propose a model-based calibration method for multiple injections. The model, which is based on first principles, is identified by a low number of measurements and extrapolates well to various operating points. An optimal control problem which includes that model is then formulated to calculate the efficiency-optimal injector inputs while respecting constraints on cylinder pressure, pressure gradient, engine-out temperature, and engine-out NOx emissions. The optimal control problem is implemented on a rapid prototyping control system and is solved with the nonlinear optimal control framework acados. Due to the simple zero-dimensional formulation of the model and the fast convergence of the solver, the method allows for a fast calibration of two injections for an engine at steady-state operation. The method is used at various engine operating points to find various trade-offs of relevant engine-out quantities. An experimental validation shows that the calibration time is reduced significantly compared to an approach based on a design of experiments. When compared to a full-factorial design of experiment, a reduction in measurements of up to 60% is possible. • We propose a model-based calibration method for multiple injections in a CI engine. • We use nonlinear optimal control to calculate efficiency-optimal solutions. • New solutions are computed within 50 ms on a rapid prototyping hardware. • The new method is validated on an engine test bench. • A significant reduction in calibration time is achieved with the new method. [ABSTRACT FROM AUTHOR]

A considerable increase in endocrine abnormalities has been reported over the last few decades worldwide. A growing exposure to endocrine-disrupting chemicals (EDCs) can be one of the causes of endocrine disorders in populations, and these disorders are not only restricted to the metabolic hormone system but can also cause abnormal functions. Thyroid hormone (TH) disruption is defined as an abnormal change in TH production, transport, function, or metabolism, which results in some degree of impairment in body homeostasis. Many EDCs, including organotin compounds (OTCs), are environmental contaminants that are commonly found in antifouling paints used on ships and in several other industrial procedures. OTCs are obesogenic and can disrupt TH metabolism; however, abnormalities in thyroid function resulting from OTC exposure are less well understood. OTCs, one of the most prevalent EDCs that are encountered on a daily basis, modulate the thyroid axis. In most toxicology studies, it has been reported that OTCs might contribute to hypothyroidism. [ABSTRACT FROM AUTHOR]

This contribution discusses the early years of Italian immigration in the uplands of southern Brazil, known as the Serra Gaucha (1875–1915). Tracing back early agrarian practices and deforestation techniques of the early settlement years, we investigate the consolidation of this human group in the southernmost Brazilian state of Rio Grande do Sul. In addition, analysing the development of both wood logging and winemaking industries in the region, the essay frames the identitarian construction of this social group, looking at the intersection between cultural traditions from the homeland, socioeconomic drives and local environmental factors. This analysis builds upon primary sources from both Brazilian and Italian institutions, local newspapers, and scholarly publications on environmental history, as well as Brazilian and Italian migration history. [ABSTRACT FROM AUTHOR]