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support reimbursement systems that mirror the actual cost of evidence-based practice.

Quality of automatic contouring is generally assessed by comparison with manual delineations, but the effect of contour differences on the resulting dose distribution remains unknown. This study evaluated dosimetric differences between treatment plans optimized using various organ-at-risk (OAR) contouring methods.

OARs of twenty lung cancer patients were manually and automatically contoured, after which user-adjustments were made. For each contour set, an automated treatment plan was generated. The dosimetric effect of intra-observer contour variation and the influence of contour variations on treatment plan evaluation and generation were studied using dose-volume histogram (DVH)-parameters for thoracic OARs.

Dosimetric effect of intra-observer contour variability was highest for Heart D

(3.4±6.8Gy) and lowest for Lungs-GTV D

(0.3±0.4Gy). The effect of contour variation on treatment plan evaluation was highest for Heart D

(6.0±13.4Gy) and Esophagus D

(8.7±17.2Gy). Dose differences for the variouontours if the distance is close to PTV ( less then 5 cm). For the lungs, only obvious large errors need to be adjusted.

To assess the rate of positive non-sentinel lymph nodes (non-SLNs) after neoadjuvant systemic therapy (NAST) in breast cancer (BC) following positive sentinel lymph node biopsy (SLNB).

From institutional database, 265 consecutive patients receiving NAST for cT1-3, any N, M0 BC between 2001 and 2018 were identified. https://www.selleckchem.com/products/plerixafor-8hcl-db06809.html Patients presented clinically negative axilla before surgery and were candidate for SLNB. Following metastatic SLNB, completion axillary lymph node dissection (AxLND) was performed. Non-SLNs rate was investigated using multivariate (MV) logistic regression models. The distribution of non-SLNs across the axilla was observed.

Positive non-SLNs were found in 62.3% of cases and showed no correlation with SLN metastasis size. At MV, statistically significant variables associated with non-SLNs were older age (p=0.025), clinically positive lymph nodes (p=0.002), SLN extracapsular extension (ECE, p=0.001), and higher ratio of positive SLNs/total SLNs (p=0.016). ECE and higher nodal ratio were indepenel up to 31% of the cases seems to require some additional treatment, while the omission in selected cases needs further investigation.

We investigated the relationship between RBE-weighted dose (DRBE) calculated with constant (cRBE) and variable RBE (vRBE), dose-averaged linear energy transfer (LETd) and the risk of radiographic changes in skull base patients treated with protons.

Clinical treatment plans of 45 patients were recalculated with Monte Carlo tool FRED. Radiographic changes (i.e. edema and/or necrosis) were identified by MRI. Dosimetric parameters for cRBE and vRBE were computed. Biological margin extension and voxel-based analysis were employed looking for association of DRBE(vRBE) and LETd with brain edema and/or necrosis.

When using vRBE, Dmax in the brain was above the highest dose limits for 38% of patients, while such limit was never exceeded assuming cRBE. Similar values of Dmax were observed in necrotic regions, brain and temporal lobes. Most of the brain necrosis was in proximity to the PTV. The voxel-based analysis did not show evidence of an association with high LETd values.

When looking at standard dosimetric parameters, the higher dose associated with vRBE seems to be responsible for an enhanced risk of radiographic changes. However, as revealed by a voxel-based analysis, the large inter-patient variability hinders the identification of a clear effect for high LETd.

When looking at standard dosimetric parameters, the higher dose associated with vRBE seems to be responsible for an enhanced risk of radiographic changes. However, as revealed by a voxel-based analysis, the large inter-patient variability hinders the identification of a clear effect for high LETd.Sunitinib is the first-line drug for treating renal cell carcinoma (RCC), and it functions mainly through inhibition of tumor angiogenesis. However, the patients may become insensitive or develop resistance toward sunitinib treatment, but the underlying mechanisms have not yet been fully elucidated. Herein, it was found that sunitinib could have adverse effects of promoting RCC progression by increasing vascular mimicry (VM) formation of RCC cells. Mechanism dissection revealed that sunitinib can increase the expression of a long non-coding RNA (lncRNA), lncRNA-ECVSR, thereby enhancing the stability of estrogen receptor β (ERβ) mRNA. Subsequently, the increased ERβ expression can then function via transcriptional up-regulation of Hif2-α. Notably, sunitinib-increased lncRNA-ECVSR/ERβ/Hif2-α signaling resulted in an increased cancer stem cell (CSC) phenotype, thereby promoting VM formation. Furthermore, the sunitinib/lncRNA-ECVSR-increased ERβ expression can transcriptionally regulate lncRNA-ECVSR expression via a positive-feedback loop. Supportively, preclinical studies using RCC mouse xenografts demonstrated that combining sunitinib with the small molecule anti-estrogen PHTPP can increase sunitinib efficacy with reduced VM formation. Collectively, the findings of this study may aid in the development of potential biomarker(s) and novel therapies to better monitor and suppress RCC progression.Pancreatic ductal adenocarcinoma (PDAC) is a solid malignant tumor with a very low operative rate and a poor patient prognosis. Therefore, gemcitabine (GEM)-based chemotherapy remains one of the most important treatment choices for PDAC. However, the efficacy of GEM monotherapy or GEM combination chemotherapy in improving the survival of patients with advanced PDAC is very limited, primarily due to GEM resistance. The mechanism of GEM resistance is complex and unclear. An extensive and dense fibrous matrix in the tumor microenvironment (TME) is an important feature of PDAC. Increasing evidence indicates that this fibrotic TME not only actively participates in the growth and spread of PDAC but also contributes to the induction of GEM resistance. Metabolic remodeling reduces GEM transport and synthesis in PDAC. This review focuses on the main cellular and molecular mechanisms underlying the involvement of the extracellular matrix (ECM), immune cells, and metabolic remodeling in the induction of GEM resistance; highlights the prospect of targeting the TME as an essential strategy to overcome GEM resistance; and provides new precise interventions for chemotherapy sensitization and improving the overall prognosis of patients with PDAC.Dysbiosis of the human microbiome has long been reported to be closely associated with various cancers. Accumulating studies have shown that microbial dysbiosis can accelerate tumorigenesis through tumor-promoting inflammation, DNA damage, and inducing immune evasion. Differential composition of microbiome could be novel biomarkers for cancer detection or biomarkers of successful immunotherapy. More importantly, emerging evidence demonstrates that alterations of circulating microbiome DNA (cmDNA) could serve as promising noninvasive biomarkers for cancer detection. It has been reported that distinct circulating bacterial DNA could distinguish prostate cancer, lung cancer, and melanoma patients from healthy populations. Therefore, in this review, we summarized current literature on microbial biomarkers for cancer detection and unraveled the potential of cmDNA as a promising cancer detection tool.The maintenance and expansion of cancer stem-like cells (CSCs) is necessary for metastasis. Although protease-activated receptor 2 (PAR2) is strongly associated with colorectal cancer (CRC) progression, it is unclear how it regulates distal metastasis, and no studies have shown the involvement of CSCs. In this study, we demonstrated that high PAR2 protein expression was correlated with metastatic CRC and poor prognosis in patients with stage III-IV CRC. CSCs from cell lines and patients showed higher levels of PAR2 than that of corresponding non-CSCs, and PAR2 inhibition reduced the CSC properties of the cell lines. Mechanistically, PAR2 inhibition switched the division mode of CSCs from symmetrical to asymmetrical via the ERK/GSK-3β/β-catenin pathway. We also identified periostin as a direct transcriptional target of β-catenin that mediates CSC self-renewal via PAR2 signaling. In a mouse xenograft model, PAR2 knockdown significantly attenuated liver metastasis. Finally, PAR2 expression was positively correlated with β-catenin and periostin in the primary sites of CRC with distant metastasis. Overall, our results indicate that PAR2 activation enhances CSC self-renewal and promotes metastasis through β-catenin and its target gene, periostin, in CRC.This letter describes synthesis and evaluation of two series of dual mGlu2/mGlu3 positive allosteric modulators with moderate mGlu3 potency and robust mGlu2 potency in thallium flux assays. These compounds were profiled their ability to modulate mGlu3-mediated signaling in central neurons by co-application of a selective mGlu2 NAM to isolate mGlu3-selective effects. Using acute mouse brain slices from the prefrontal cortex, potentiation of group II mGlu receptor agonist Ca2+ signaling in PFC pyramidal cells with either the dual mGlu2/mGlu3 PAM 16e or 23d demonstrated effects mediated selectively via mGlu3.

Nosocomial outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are frequent despite implementation of conventional infection control measures. We performed an outbreak investigation using advanced genomic and statistical techniques to reconstruct likely transmission chains and assess the role of healthcare workers (HCWs) in SARS-CoV-2 transmission.

We investigated a nosocomial SARS-CoV-2 outbreak in a university-affiliated rehabilitation clinic, involving patients and HCWs, with high coverage of pathogen whole genome sequences (WGS). We estimated the time-varying reproduction number from epidemiological data (Rt) and produced a maximum likelihood phylogeny to assess genetic diversity of the pathogen. We combined genomic and epidemiological data into a Bayesian framework to model directionality of transmission. We performed a Case-control study to investigate risk factors for nosocomial SARS-CoV-2 acquisition in patients.

The outbreak spanned from March 14 to April 12, 2020 and invotransmission dynamics in healthcare settings. Limited genetic diversity in pathogen genomes hampered the reconstruction of individual transmission events, resulting in substantial uncertainty in who infected whom. However, our study shows that despite such uncertainty, significant transmission patterns can be observed.

This outbreak report highlights the essential role of HCWs in SARS-CoV-2 transmission dynamics in healthcare settings. Limited genetic diversity in pathogen genomes hampered the reconstruction of individual transmission events, resulting in substantial uncertainty in who infected whom. However, our study shows that despite such uncertainty, significant transmission patterns can be observed.

Gaseous by-products generated by surgical devices-collectively referred to as "surgical smoke"-present the hazard of transmitting infective viruses from patients to surgical teams. However, insufficient evidence exists to evaluate and mitigate the risks of SARS-CoV-2 transmission via surgical smoke.

To demonstrate the existence and infectivity of human coronavirus RNA in surgical smoke using a model experiment and to evaluate the possibility of lowering transmission risk by filtration through a surgical mask.

Pelleted HeLa-ACE2-TMPRSS2 cells infected with human coronavirus were incised by electric scalpel and ultrasonic scalpel, separately. A vacuum system was used to obtain surgical smoke in the form of hydrosol. RT-qPCR was used to analyse samples for the presence of viral RNA, and infectivity was determined through plaque assay. Furthermore, a surgical mask was placed centrally in the vacuum line to evaluate its ability to filter viral RNA present in the surgical smoke.

In this model, 1/10

- 1/10

of the viral RNA contained in the incision target was detected in the collected surgical smoke.