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Hamann Hartvigsen opublikował 5 miesięcy, 2 tygodnie temu
Acute esophagitis (AE) is a common dose-limiting toxicity in radiation therapy of locally advanced non-small cell lung cancer (LA-NSCLC). We developed an early AE prediction model from weekly accumulated esophagus dose and its associated local volumetric change.
Fifty-one patients with LA-NSCLC underwent treatment with intensity modulated radiation therapy to 60 Gy in 2-Gy fractions with concurrent chemotherapy and weekly cone beam computed tomography (CBCT). Twenty-eight patients (55%) developed grade ≥2 AE (≥AE2) at a median of 4 weeks after the start of radiation therapy. For early ≥AE2 prediction, the esophagus on CBCT of the first 2 weeks was deformably registered to the planning computed tomography images, and weekly esophagus dose was accumulated. Week 1-to-week 2 (w1→w2) esophagus volume changes including maximum esophagus expansion (MEex%) and volumes with ≥x% local expansions (VEx%; x = 5, 10, 15) were calculated from the Jacobian map of deformation vector field gradients. Logistic regression moapy significantly improved AE prediction compared with conventional models using only the planned dose. This model could inform plan adaptation early to lower the risk of esophagitis.
A CBCT-based, cross-validated, and internally validated model on MRI with a combination of accumulated esophagus dose and local volume change from the first 2 weeks of chemotherapy significantly improved AE prediction compared with conventional models using only the planned dose. This model could inform plan adaptation early to lower the risk of esophagitis.
Prospective clinical trials have demonstrated the safety and efficacy of active surveillance for men with localized prostate cancer but also suggested that inadequate surveillance may risk missing an opportunity for cure.
We used data from a population-based cohort of active-surveillance patients to examine the rigor of surveillance monitoring in the general population.
Among 1419 patients enrolled from 2011 to 2013 throughout the state of North Carolina in collaboration with the state cancer registry and followed prospectively, 346 pursued active surveillance. Only 13% received all guideline-recommended surveillance testing (including prostate-specific antigen, digital rectal examination, and prostate biopsy) within the first 2 years. Furthermore, adherence was <20% in all patient subgroups.
These findings suggest that „active surveillance” as implemented in the general population may not represent the rigorous monitoring regimens used in the studies that demonstrated the safety of this management approach. More real-world studies on active surveillance are needed.
These findings suggest that „active surveillance” as implemented in the general population may not represent the rigorous monitoring regimens used in the studies that demonstrated the safety of this management approach. More real-world studies on active surveillance are needed.Prediction error, defined by the discrepancy between real and expected outcomes, lies at the core of associative learning. Behavioural investigations have provided evidence that prediction error up- and down-regulates associative relationships, and allocates attention to stimuli to enable learning. These behavioural advances have recently been followed by investigations into the neurobiological substrates of prediction error. In the present paper, we review neuroscience data obtained using causal and recording neural methods from a variety of key behavioural designs. We explore the neurobiology of both appetitive (reward) and aversive (fear) prediction error with a focus on the mesolimbic dopamine system, the amygdala, ventrolateral periaqueductal gray, hippocampus, cortex and locus coeruleus noradrenaline. New questions and avenues for research are considered.Recognising conspecifics’ emotional expressions is important for nonhuman primates to navigate their physical and social environment. We address two possible mechanisms underlying emotion recognition emotional contagion, the automatic matching of the observer’s emotions to the emotional state of the observed individual, and cognitive empathy, the ability to understand the meaning and cause of emotional expressions while maintaining a distinction between own and others’ emotions. We review experimental research in nonhuman primates to gain insight into the evolution of emotion recognition. Importantly, we focus on how emotional contagion and cognitive empathy can be studied experimentally. Evidence for aspects of cognitive empathy in different nonhuman primate lineages suggests that a wider range of primates than commonly assumed can infer emotional meaning from emotional expressions. Possibly, analogous rather than homologous evolution underlies emotion recognition. However, conclusions regarding its exact evolutionary course require more research in different modalities and species.
Disorders of mitochondrial Ca
homeostasis play a key role in the glutamate excitotoxicity of brain neurons. DS16570511 (DS) is a new penetrating inhibitor of mitochondrial Ca
uniporter complex (MCUC). The paper examines the effects of DS on the cultivated cortical neurons and isolated mitochondria of the rat brain.
The functions of neurons and mitochondria were examined using fluorescence microscopy, XF24 microplate-based сell respirometry, ion-selective microelectrodes, spectrophotometry, and polarographic technique.
At the doses of 30 and 45μM, DS reliably slowed down the onset of glutamate-induced delayed calcium deregulation of neurons and suppressed their death. 30μM DS caused hyperpolarization of mitochondria of resting neurons, and 45μM DS temporarily depolarized neuronal mitochondria. It was also demonstrated that 30-60μM DS stimulated cellular respiration. DS was shown to suppress Ca
uptake by isolated brain mitochondria. In addition, DS inhibited ADP-stimulated mitochondrial respiration and ADP-induced decrease in the mitochondrial membrane potential. It was found that DS inhibited the activity of complex II of the respiratory chain. In the presence of Ca
, high DS concentrations caused a collapse of the mitochondrial membrane potential.
The data obtained indicate that, in addition to the inhibition of MCUC, DS affects the main energy-transducing functions of mitochondria.
The using DS as a tool for studying MCUC and its functional role in neuronal cells should be done with care, bearing in mind multiple effects of DS, a proper evaluation of which would require multivariate analysis.
The using DS as a tool for studying MCUC and its functional role in neuronal cells should be done with care, bearing in mind multiple effects of DS, a proper evaluation of which would require multivariate analysis.Lung cancer is one of the most common solid tumors worldwide and the leading cause of cancer-related deaths, causing a devastating impact on human health. The clinical prognosis of lung cancer is usually restricted by delayed diagnosis and resistance to anticancer therapies. MicroRNAs, a range of small endogenous noncoding RNAs 22 nucleotides in length, have emerged as one of the most important players in cancer initiation and progression in recent decades. Current evidence reveals pivotal roles of microRNAs in regulating cell proliferation, migration, invasion and metastasis in lung cancer. An increasing number of preclinical and clinical studies have also explored the potential of microRNAs as promising biomarkers and new therapeutic targets for lung cancer. The current review summarizes the most recent progress on the functional mechanisms of microRNAs involved in lung cancer development and progression and further discusses the clinical application of miRNAs as putative therapeutic targets for molecular diagnosis and prognostic prediction in lung cancer.
Mismatch negativity (MMN) and P3a are event-related potential measures of early auditory information processing that are increasingly used as translational biomarkers in the development of treatments for neuropsychiatric disorders. These responses are reduced in schizophrenia patients over the frontocentral scalp electrodes and are associated with important domains of cognitive and psychosocial functioning. While MMN and P3a responses are generated by a dynamic network of cortical sources distributed across the temporal and frontal brain regions, it is not clear how these sources independently contribute to MMN and P3a at the primary frontocentral scalp electrode or to abnormalities observed in schizophrenia. This study aimed to determine the independent source contributions and characterize the magnitude of impairment in source-level MMN and P3a responses in schizophrenia patients.
A novel method was applied to back-project the contributions of 11 independent cortical source components to Fz, the primaryof source contributions and source-level responses accelerates clarification of the neural networks underlying MMN reduction at Fz in schizophrenia patients.The aim of the study was to explore the role of interoceptive accuracy (IA) on exogenous attention to disgusting and fearful distractors of a main concurrent task. Participants were thirty university students previously identified as high (N = 16) or normal IA according their performance in a heartbeat detection task. Event-related potentials and behavioural responses were recorded. The results showed that disgusting stimuli capture exogenous attention in a first stage as reflected by the augmented amplitude of the P100 component of the ERPs in high IA participants. Fearful distractors may capture attention in a later moment in all participants as revealed by a marginally significant effect on the amplitude of N200. At behavioural level, disgusting distractors provoked a higher number of errors than neutral in normal IA participants. The time course of the effect of disgust and fearful eliciting distractors on exogenous attention appeared to depend on the individual characteristic of participants.
Estimation of hepatitis B (HBV) viral load (VL) is critical in hepatitis-B cascade-of-care and at present there is no point of care (POC) molecular assay available for the same. This study evaluated the performance of a new near point of care molecular assay Xpert HBV- VL assay against the approved assays.
In this study 172 archived previously tested samples, were simultaneously re-tested for HBV DNA on 3 real-time PCR assays Abbott Real-Time HBV, Roche TaqMan® HBV and Xpert HBV assay.
Out of 172 samples, 119 were previously positive for HBV DNA with a median VL 4.46 (IQR 1-8.76)log
IU/mL and 53 were HBV DNA negative. Genotyping could be done in 95 (79.8 %) samples and genotype D (83; 87.3 %) was the commonest type. The Xpert assay demonstrated a good correlation with Abbott (R
= 0.94) and Roche (R
= 0.96). On comparison, the mean difference with 95 % Confidence Interval of Xpert assay was -0.018 and -0.043 log
IU/mL with Abbott and Roche assay, respectively. The overall sensitivity, specificity, negative predictive value, and positive predictive value of the Xpert assay was found 97.5 %, 100 %, 94.65 & 100 % respectively.
Xpert HBV-VL assay which has a potential for near point of care molecular testing has shown excellent performance and found to be a reliable method for HBV DNA quantification.
Xpert HBV-VL assay which has a potential for near point of care molecular testing has shown excellent performance and found to be a reliable method for HBV DNA quantification.