Predicting per-lesion local recurrence in locally advanced non-small cell lung cancer following definitive radiation therapy using pre- and mid-treatment metabolic tumor volume

Background: We evaluated whether pre- and mid-treatment metabolic tumor volume (MTV) predicts per lesion local recurrence (LR) in patients treated with definitive radiation therapy (RT, dose≥60 Gy) for locally advanced non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed records of patients with stage III NSCLC treated from 2006 to 2018 with pre- and mid-RT PET-CT. We measured the MTV of treated lesions on the pre-RT (MTVpre) and mid-RT (MTVmid) PET-CT. LR was defined per lesion as recurrence within the planning target volume. Receiver operating characteristic (ROC) curves, cumulative incidence rates, and uni- and multivariable (MVA) competing risk regressions were used to evaluate the association between MTV and LR. Results: We identified 111 patients with 387 lesions (112 lung tumors and 275 lymph nodes). Median age was 68 years, 69.4% were male, 46.8% had adenocarcinoma, 39.6% had squamous cell carcinoma, and 95.5% received concurrent chemotherapy. Median follow-up was 38.7 months. 3-year overall survival was 42.3%. 3-year cumulative incidence of LR was 26.8% per patient and 11.9% per lesion. Both MTVpre and MTVmid were predictive of LR by ROC (AUC = 0.71 and 0.76, respectively) and were significantly associated with LR on MVA (P = 0.004 and P = 7.1e-5, respectively). Among lesions at lower risk of LR based on MTVpre, higher MTVmid was associated with LR (P = 0.001). Conclusion: Per-lesion, larger MTVpre and MTVmid predicted for increased risk of LR. MTVmid was more highly predictive of LR than MTVpre and if validated may allow for further discrimination of high-risk lesions at mid-RT informing dose painting strategies

Neuroinflammation and amyloid deposition in the progression of mixed Alzheimer and vascular dementia

BACKGROUND: Alzheimer\u27s disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) pathologies coexist in patients with cognitive impairment. Abnormal amyloid beta (Aβ) deposition is the hallmark pathologic biomarker for AD. Neuroinflammation may be a pathophysiological mechanism in both AD and VCID. In this study, we aimed to understand the role of neuroinflammation and Aβ deposition in white matter hyperintensities (WMH) progression and cognitive decline over a decade in patients with mixed AD and VCID pathologies. METHODS: Twenty-four elderly participants (median [interquartile range] age 78 [64.8, 83] years old, 14 female) were recruited from the Knight Alzheimer Disease Research Center. RESULTS: Fifteen participants (62.5%) had mixed AD (positive PiB) and VCID (at least one vascular risk factor) pathologies. Elevated CONCLUSIONS: Neuroinflammation and Aβ deposition may represent two distinct pathophysiological pathways, and both independently contributed to the progression of cognitive impairment in mixed AD and VCID pathologies. Neuroinflammation, but not Aβ deposition, contributed to WMH volume and progression

Loss of lag-response curvilinearity of indices of heart rate variability in congestive heart failure

BACKGROUND: Heart rate variability (HRV) is known to be impaired in patients with congestive heart failure (CHF). Time-domain analysis of ECG signals traditionally relies heavily on linear indices of an essentially non-linear phenomenon. Poincaré plots are commonly used to study non-linear behavior of physiologic signals. Lagged Poincaré plots incorporate autocovariance information and analysis of Poincaré plots for various lags can provide interesting insights into the autonomic control of the heart. METHODS: Using Poincaré plot analysis, we assessed whether the relation of the lag between heart beats and HRV is altered in CHF. We studied the influence of lag on estimates of Poincaré plot indices for various lengths of beat sequence in a public domain data set (PhysioNet) of 29 subjects with CHF and 54 subjects with normal sinus rhythm. RESULTS: A curvilinear association was observed between lag and Poincaré plot indices (SD1, SD2, SDLD and SD1/SD2 ratio) in normal subjects even for a small sequence of 50 beats (p value for quadratic term 3 × 10(-5), 0.002, 3.5 × 10(-5 )and 0.0003, respectively). This curvilinearity was lost in patients with CHF even after exploring sequences up to 50,000 beats (p values for quadratic term > 0.5). CONCLUSION: Since lagged Poincaré plots incorporate autocovariance information, these analyses provide insights into the autonomic control of heart rate that is influenced by the non-linearity of the signal. The differences in lag-response in CHF patients and normal subjects exist even in the face of the treatment received by the CHF patients

Expanded protein information at SGD: new pages and proteome browser

The recent explosion in protein data generated from both directed small-scale studies and large-scale proteomics efforts has greatly expanded the quantity of available protein information and has prompted the Saccharomyces Genome Database (SGD; ) to enhance the depth and accessibility of protein annotations. In particular, we have expanded ongoing efforts to improve the integration of experimental information and sequence-based predictions and have redesigned the protein information web pages. A key feature of this redesign is the development of a GBrowse-derived interactive Proteome Browser customized to improve the visualization of sequence-based protein information. This Proteome Browser has enabled SGD to unify the display of hidden Markov model (HMM) domains, protein family HMMs, motifs, transmembrane regions, signal peptides, hydropathy plots and profile hits using several popular prediction algorithms. In addition, a physico-chemical properties page has been introduced to provide easy access to basic protein information. Improvements to the layout of the Protein Information page and integration of the Proteome Browser will facilitate the ongoing expansion of sequence-specific experimental information captured in SGD, including post-translational modifications and other user-defined annotations. Finally, SGD continues to improve upon the availability of genetic and physical interaction data in an ongoing collaboration with BioGRID by providing direct access to more than 82 000 manually-curated interactions

Genome Snapshot: a new resource at the Saccharomyces Genome Database (SGD) presenting an overview of the Saccharomyces cerevisiae genome

Sequencing and annotation of the entire Saccharomyces cerevisiae genome has made it possible to gain a genome-wide perspective on yeast genes and gene products. To make this information available on an ongoing basis, the Saccharomyces Genome Database (SGD) () has created the Genome Snapshot (). The Genome Snapshot summarizes the current state of knowledge about the genes and chromosomal features of S.cerevisiae. The information is organized into two categories: (i) number of each type of chromosomal feature annotated in the genome and (ii) number and distribution of genes annotated to Gene Ontology terms. Detailed lists are accessible through SGD's Advanced Search tool (), and all the data presented on this page are available from the SGD ftp site ()

Fungal BLAST and Model Organism BLASTP Best Hits: new comparison resources at the Saccharomyces Genome Database (SGD)

The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/) is a scientific database of gene, protein and genomic information for the yeast Saccharomyces cerevisiae. SGD has recently developed two new resources that facilitate nucleotide and protein sequence comparisons between S.cerevisiae and other organisms. The Fungal BLAST tool provides directed searches against all fungal nucleotide and protein sequences available from GenBank, divided into categories according to organism, status of completeness and annotation, and source. The Model Organism BLASTP Best Hits resource displays, for each S.cerevisiae protein, the single most similar protein from several model organisms and presents links to the database pages of those proteins, facilitating access to curated information about potential orthologs of yeast proteins

Nuggets, Pearls, and Vignettes of Master Heart Failure Clinicians

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73696/1/j.1527-5299.2001.00307.x.pd

Vitamin D deficiency is associated with orthostatic hypotension in older men: a cross-sectional analysis from the British Regional Heart Study.

BACKGROUND: orthostatic hypotension (OH) that occurs within, or at, 1 minute of standing is associated with higher risk of falls, myocardial infarction, syncope and mortality, compared to OH that occurs after 1 minute of standing. Whether vitamin D deficiency increases the risk of OH is controversial. METHODS: this was a cross-sectional analysis of 3,620 older, community-dwelling men. Multinomial, multiple logistic regression models were used to calculate the risk of OH across categories of vitamin D status (deficient [<25 nmol/l], insufficient [≥25-<50 nmol/l] and sufficient [≥50 nmol/l]) and parathyroid hormone quintile. RESULTS: men with vitamin D deficiency were more likely to have OH that occurred within 1 minute of standing in univariate logistic regression (OR 1.88, 95% CI 1.40-2.53) and multinomial, multiple logistic regression (OR 1.51, 95% CI 1.06-2.15), compared to men with sufficient levels of vitamin D. Vitamin D insufficiency was not associated with the risk of OH. Elevated parathyroid hormone was not associated with risk of OH. CONCLUSION: the absence of an association between vitamin D insufficiency and risk of OH and the presence of an association between vitamin D deficiency and risk of OH suggest that there may be a threshold effect; it is only below a particular level of vitamin D that risk of OH is increased. In this cohort, the threshold was <25 nmol/l. Future work should investigate whether treating vitamin D deficiency can improve postural blood pressure or if preventing vitamin D deficiency reduces the incidence of OH