After decades of research, improving the efficacy of adjuvant endocrine therapy (ET) for early-stage breast cancer becomes increasingly difficult. Beyond technological breakthroughs and the ...availability of new classes of drugs, further improvement of adjuvant ET will require applying a rigorous research approach in poorly investigated areas. We critically discuss some key principles that should inform future research to improve ET efficacy, including identifying specific subgroups of patients who can benefit from escalating or de-escalating approaches, optimizing available and new treatment strategies for different clinical contexts, and dissecting the direct and indirect biological effects of therapeutic interventions. Four main issues regarding adjuvant ET were identified as relevant areas, where a better application of such principles can provide positive results in the near future: (i) tailoring the optimal duration of adjuvant ET, (ii) optimizing ovarian function suppression for premenopausal women, (iii) dissecting the biological effects of estrogen receptor manipulation, and (iv) refining the selection of patients to candidate for treatments escalation.
Echocardiography frequently serves as the first-line treatment of diagnostic imaging for several pathological entities in cardiology. Artificial intelligence (AI) has been growing substantially in ...information technology and various commercial industries. Machine learning (ML), a branch of AI, has been shown to expand the capabilities and potential of echocardiography. ML algorithms expand the field of echocardiography by automated assessment of the ejection fraction and left ventricular function, integrating novel approaches such as speckle tracking or tissue Doppler echocardiography or vector flow mapping, improved phenotyping, distinguishing between cardiac conditions, and incorporating information from mobile health and genomics. In this review article, we assess the impact of AI and ML in echocardiography.
Plain Language Summary
Echocardiography is the most common test in cardiovascular imaging and helps diagnose multiple different diseases. Machine learning, a branch of artificial intelligence (AI), will reduce the workload for medical professionals and help improve clinical workflows. It can rapidly calculate a lot of important cardiac parameters such as the ejection fraction or important metrics during different phases of the cardiac cycle. Machine learning algorithms can include new technology in echocardiography such as speckle tracking, tissue Doppler echocardiography, vector flow mapping, and other approaches in a user-friendly manner. Furthermore, it can help find new subtypes of existing diseases in cardiology. In this review article, we look at the current role of machine learning and AI in the field of echocardiography.
The pathologic complete response (pCR) is supported by regulatory agencies as a surrogate end point for long-term patients' clinical outcomes in the accelerated approval process of new drugs tested ...in neoadjuvant randomized clinical trials (RCTs) for early breast cancer (BC). However, a meaningful association between pCR and patients' survival has been proven only at the patient level (ie, significantly better survival of patients who achieved pCR compared with those who did not), but not at trial level (ie, poor association between degree of improvement in pCR rate and survival reported across trials).
We critically discuss the potential reasons of such discrepancy between pCR surrogacy value at the patient and trial level, as well as the relevant implications for both clinical research and drug regulatory policy. We also describe alternative surrogate end points, including combined end points that jointly analyzed pathological response and event-free survival data, or the assessment of circulating tumor DNA (ctDNA). Such proposed surrogate end points could overcome limits of pCR and provide a reasonable trade-off between the 2 conflicting needs to have access to effective therapies rapidly, and to reliably assess patients' clinical benefit.
Using surrogate end points to grant drug approvals is justified only when they can provide accurate prediction of a drug's effect on the long-term patient outcomes. Evidence currently available does not support pCR used alone as a reliable surrogate end point in regulatory neoadjuvant RCTs for BC. The surrogacy value at trial level of potentially more robust surrogate end points needs to be urgently tested.
Diffusion of carriers under high electric field is studied using full-band Monte Carlo simulations. The diffusion of hot carriers is found to be strongly anisotropic with respect to the electric ...field direction and to be times higher than the one predicted by the Einstein's law. A new calibration of analytical models is proposed to account for the anisotropy of the diffusion coefficient as well of the impact of the electric field. The effect of the new model is illustrated by studying its impact on the lateral and longitudinal spread of the electronic avalanches that occur in single-photon avalanche diodes, using advection-diffusion Monte Carlo.
Abstract
Purpose
A study among Filipinos revealed that only 15% of patients with diabetes achieved glycemic control, and poor response to metformin could be one of the possible reasons. Recent ...studies demonstrate how genetic variations influence response to metformin. Hence, the present study aimed to determine genetic variants associated with poor response to metformin.
Methods
Using a candidate variant approach, 195 adult Filipino participants with newly diagnosed type 2 diabetes mellitus (T2DM) were enrolled in a case-control study. Genomic DNA from blood samples were collected. Allelic and genotypic associations of variants with poor response to metformin were determined using exact statistical methods.
Results
Several polymorphisms were nominally associated with poor response to metformin (Puncorr < 0.05). The most notable is the association of multiple variants in the SLC2A10 gene—rs2425911, rs3092412, and rs2425904—with common additive genetic mode of inheritance. Other variants that have possible associations with poor drug response include rs340874 (PROX-AS1), rs815815 (CALM2), rs1333049 (CDKN2B-AS1), rs2010963 (VEGFA), rs1535435 and rs9494266 (AHI1), rs11128347 (PDZRN3), rs1805081 (NPC1), and rs13266634 (SLC30A8).
Conclusion
In Filipinos, a trend for the association for several variants was noted, with further observation that several mechanisms may be involved. The results may serve as pilot data for further validation of candidate variants for T2DM pharmacotherapy.
This paper presents a systematic analysis of the use of the linear combination of bulk bands based on the empirical pseudopotential method to obtain the bandstructure of confined nanostructures. The ...relevance of interband coupling between conduction and valence bands in III-V materials is highlighted.
Rationale:
Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra ...until revascularization occurs.
Aims:
PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion.
Methods and design:
Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.
Study outcomes:
Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted.
Sample size:
Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation.
Discussion:
By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia.
Trial registrations:
ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31.
Abstract Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. E-Cadherin is an adhesion molecule that is thought to be involved in GC. Germline mutations in the ...E-Cadherin gene ( CDH 1) have been identified in hereditary diffuse GC. Also, a promoter polymorphism at position −160 C/A has been suggested to lead to transcriptional down regulation and has been shown to affect GC risk in some studies. However, very little information exists on the GC risk association of other CDH 1 polymorphisms and it is unclear whether any associations may be different by GC anatomical sites or histological types. Thus, a case–control study (cases = 245/controls = 950) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort was conducted to assess the GC risk association of eight CDH 1 gene polymorphisms. None of the CDH 1 polymorphisms or haplotypes analysed were associated with GC risk and no differences of effect were observed by Helicobacter pylori infection status. However, three CDH 1 polymorphisms in the same haplotype block, including the CDH 1−160C/A, interacted with smoking to increase GC risk in smokers but not in never smokers. These findings should be confirmed in larger independent studies.
PDF
