Transcription factors (TFs) regulate the expression of genes through sequence-specific interactions with DNA-binding sites. However, despite recent progress in identifying in vivo TF binding sites by microarray readout of chromatin immunoprecipitation (ChIP-chip), nearly half of all known yeast TFs are of unknown DNA-binding specificities, and many additional predicted TFs remain uncharacterized. To address these gaps in our knowledge of yeast TFs and their cis regulatory sequences, we have determined high-resolution binding profiles for 89 known and predicted yeast TFs, over more than 2.3 million gapped and ungapped 8-bp sequences (''k-mers''). We report 50 new or significantly different direct DNA-binding site motifs for yeast DNA-binding proteins and motifs for eight proteins for which only a consensus sequence was previously known; in total, this corresponds to over a 50% increase in the number of yeast DNA-binding proteins with experimentally determined DNA-binding specificities. Among other novel regulators, we discovered proteins that bind the PAC (Polymerase A and C) motif (GATGAG) and regulate ribosomal RNA (rRNA) transcription and processing, core cellular processes that are constituent to ribosome biogenesis. In contrast to earlier data types, these comprehensive k-mer binding data permit us to consider the regulatory potential of genomic sequence at the individual word level. These k-mer data allowed us to reannotate in vivo TF binding targets as direct or indirect and to examine TFs' potential effects on gene expression in ;1700 environmental and cellular conditions. These approaches could be adapted to identify TFs and cis regulatory elements in higher eukaryotes.

Highlights Typically encountered CT exposure variations result in radiomics values distortion. Proposed correction method suppresses the non-tumor related variation in radiomics. The clinical relevance was shown using a 221 lung cancer patient cohort.

Prediction modelling with radiomics is a rapidly developing research topic that requires access to vast amounts of imaging data. Methods that work on decentralized data are urgently needed, because of concerns about patient privacy. Previously published computed tomography medical image sets with gross tumour volume (GTV) outlines for non-small cell lung cancer have been updated with extended follow-up. In a previous study, these were referred to as Lung1 (n = 421) and Lung2 (n = 221). The Lung1 dataset is made publicly accessible via The Cancer Imaging Archive (TCIA; https://www.cancerimagingarchive.net). We performed a decentralized multi-centre study to develop a radiomic signature (hereafter “ZS2019”) in one institution and validated the performance in an independent institution, without the need for data exchange and compared this to an analysis where all data was centralized. The performance of ZS2019 for 2-year overall survival validated in distributed radiomics was not statistically different from the centralized validation (AUC 0.61 vs 0.61; p = 0.52). Although slightly different in terms of data and methods, no statistically significant difference in performance was observed between the new signature and previous work (c-index 0.58 vs 0.65; p = 0.37). Our objective was not the development of a new signature with the best performance, but to suggest an approach for distributed radiomics. Therefore, we used a similar method as an earlier study. We foresee that the Lung1 dataset can be further re-used for testing radiomic models and investigating feature reproducibility.

Background: Postoperative delirium is one of the most common complications in the elderly surgical population. However, its long-term outcomes remain largely to be determined. Therefore a prospective cohort study was conducted to determine the association between postoperative delirium and long-term decline in activities of daily living and postoperative mortality. The hypothesis in the present study was that postoperative delirium was associated with a greater decline in activities of daily living and higher mortality within 24 to 36 months after anesthesia and surgery. Methods: The participants (at least 65 yr old) having the surgeries of (1) proximal femoral nail, (2) hip replacement, or (3) open reduction and internal fixation under general anesthesia were enrolled. The Confusion Assessment Method algorithm was administered to diagnose delirium before and on the first, second, and fourth days after the surgery. Activities of daily living were evaluated by using the Chinese version of the activities of daily living scale (range, 14 to 56 points), and preoperative cognitive function was assessed by using the Chinese Mini-Mental State Examination (range, 0 to 30 points). The follow-up assessments, including activities of daily living and mortality, were conducted between 24 and 36 months after anesthesia and surgery.

Changes in retinal nerve fiber layer (RNFL) thickness have been reported in patients with mild cognitive impairment (MCI), the pre-dementia stage of Alzheimer's disease (AD). However, whether RNFL thickness is associated with specific cognitive impairment of MCI patients remains unknown. Therefore, we set out to investigate the potential association between RNFL thickness and episodic memory in MCI patients. Seventy five older adults (mean age 74 ± 3 years, 55% men) were included in the study. Fifty-two participants had normal cognition (NC), and 23 participants were diagnosed with MCI. RNFL thickness was obtained by optical coherence tomography measurement. Cognitive function was evaluated by the Repeatable Battery for the Assessment of Neuropsychological Status on the same day of the optical examination. We found that nasal quadrant RNFL thickness was positively associated with episodic memory scores in the participants with normal cognition: word list learning (r=0.392, p=0.004) and story recall (r=0.307, p=0.027). In the participants with MCI, however, the inferior quadrant RNFL thickness was inversely associated with the episodic memory score: word list learning (r=-0.652, p=0.001), story memory (r=-0.429, p=0.041), and story recall (r=-0.502, p=0.015,). The findings from this pilot study suggest that the inferior quadrant RNFL thickness was associated with specific episodic memory in MCI patients and could serve as a biomarker of MCI and AD. These findings would promote more studies to determine the potential application of RNFL as an AD biomarker.

Thinning of retinal nerve fiber layer (RNFL) may reflect neurodegeneration of the central nervous system, which has been reported as part of the neuropathogenesis of Alzheimer's disease (AD). Specifically, AD patients have thinner RNFL as compared to age-matched normal controls. However, whether reduction of RNFL over time can predict those at higher risk to develop cognitive deterioration remains unknown. We therefore set out a prospective clinical investigation to determine both the reduction of RNFL thickness and the deterioration of cognitive function over a period of 25 months in 78 participants (mean age 72.31 ± 3.98 years, 52% men). The participants were categorized as stable participants whose cognitive status remained unchanged (n = 60) and converted participants whose cognitive status deteriorated, which was diagnosed by DSM-VI (for AD) and Petersen's definition (for mild cognitive impairment) (n = 18). Here we show for the first time that the converted participants had greater reduction of RNFL thickness than the stable participants. Specifically, the reduction in the thickness of the inferior quadrant RNFL in the converted participants was greater than that in stable participants [-11.0 ± 12.8 (mean ± standard deviation) μm versus 0.4 ± 15.7 μm, p = 0.009]. These data showed that greater reduction in the inferior quadrant of RNFL thickness might indicate a higher risk for the old adults to develop cognitive deterioration. These findings have established a system to embark on a larger scale study to further test whether changes in RNFL thickness can serve as a biomarker of AD.

No abstract

Objective: Memorial Delirium Assessment Scale (MDAS) assesses severity of delirium. However, whether the MDAS can be used in a Chinese population is unknown. Moreover, the optimal postoperative MDAS cutoff point for describing postoperative delirium in Chinese remains largely to be determined. We therefore performed a pilot study to validate MDAS in the Chinese language and to determine the optimal postoperative MDAS cutoff point for delirium.Methods: Eighty-two patients (80 ± 6 years, 21.9% male), who had hip surgery under general anesthesia, were enrolled. The Confusion Assessment Method (CAM) and Mini-Mental State Examination (MMSE) were administered to the patients before surgery. The CAM and MDAS were performed on the patients on the first, second and fourth postoperative days. The reliability and validity of the MDAS were determined. A receiver operating characteristic (ROC) curve was used to determine the optimal Chinese version MDAS cutoff point for the identification of delirium.Results: The Chinese version of the MDAS had satisfactory internal consistency (α = 0.910). ROC analysis obtained an average optimal MDAS cutoff point of 7.5 in describing the CAM-defined postoperative delirium, with an area under the ROC of 0.990 (95% CI 0.977–1.000, P < 0.001).Conclusions: The Chinese version of the MDAS had good reliability and validity. The patients whose postoperative Chinese version MDAS cutoff point score was 7.5 would likely have postoperative delirium. These results have established a system for a larger scale study in the future.