Miracle-dz/UniFAR-FTUs huggingface dataset:
Smooth extrapolation of unknown anatomy via statistical shape models

Several methods to perform extrapolation of unknown anatomy were evaluated. The primary application is to enhance surgical procedures that may use partial medical images or medical images of incomplete anatomy. Le Fort-based, face-jaw-teeth transplant is one such procedure. From CT data of 36 skulls and 21 mandibles separate Statistical Shape Models of the anatomical surfaces were created. Using the Statistical Shape Models, incomplete surfaces were projected to obtain complete surface estimates. The surface estimates exhibit non-zero error in regions where the true surface is known; it is desirable to keep the true surface and seamlessly merge the estimated unknown surface. Existing extrapolation techniques produce non-smooth transitions from the true surface to the estimated surface, resulting in additional error and a less aesthetically pleasing result. The three extrapolation techniques evaluated were: copying and pasting of the surface estimate (non-smooth baseline), a feathering between the patient surface and surface estimate, and an estimate generated via a Thin Plate Spline trained from displacements between the surface estimate and corresponding vertices of the known patient surface. Feathering and Thin Plate Spline approaches both yielded smooth transitions. However, feathering corrupted known vertex values. Leave-one-out analyses were conducted, with 5% to 50% of known anatomy removed from the left-out patient and estimated via the proposed approaches. The Thin Plate Spline approach yielded smaller errors than the other two approaches, with an average vertex error improvement of 1.46 mm and 1.38 mm for the skull and mandible respectively, over the baseline approach.
Downregulation of Na+/Ca2+ Exchanger Isoform 1 Protects Isolated Hearts by Sevoflurane Postconditioning but Not by Delayed Remote Ischemic Preconditioning in Rats

Background: Calcium regulatory proteins-L-type Ca2+ channels (LTCCs), ryanodine receptor 2 (RyR2), and Na+/Ca2+ exchanger isoform 1 (NCX1) have been recognized as important protective mechanisms during myocardial ischemia-reperfusion injury (I/RI). Both sevoflurane postconditioning (SevoPoC) and delayed remote ischemic preconditioning (DRIPC) have been shown to protect the heart against I/RI. In this study, we aimed to compare the effects of SevoPoC and DRIPC on the expression of the three calcium regulatory proteins in an isolated rat heart model. Methods: After 30-min balanced perfusion, isolated hearts from rats were subjected to 30-min ischemia followed by 60-min reperfusion. Totally 40 isolated hearts were randomly assigned to four groups (n = 10/group): time control group, I/RI group, SevoPoC group, and DRIPC group. The effect of SevoPoC (3% v/v) and DRIPC were observed. Myocardial infarct size (IS), cardiac troponin I level, and heart function were measured. The protein and messenger RNA levels of LTCCs, RyR2, and NCX1 were determined. Results: Both SevoPoC and DRIPC improved the recovery of myocardial function, and reduced cardiac troponin I release after I/RI. The decrease in IS was more significant in the SevoPoC group than that in the DRIPC group (16.50% ± 4.54% in the SevoPoC group [P = 0.0006], and 22.34% ± 4.02% in the DRIPC group [P = 0.0007] vs. 35.00% ± 5.24% in the I/RI group, respectively). SevoPoC, but not DRIPC significantly inhibited the activity of NCX1 (0.59 ± 0.09 in the I/RI group vs. 0.32 ± 0.16 in the SevoPoC group, P = 0.006; vs. 0.57 ± 0.14 in the DRIPC group, P = 0.072). No statistical significant differences were observed in the expression of LTCCs and RyR2 between SevoPoC and DRIPC. In addition, subsequent correlation analysis showed a significantly positive relationship between the cardiac troponin I level and the protein expression of NCX1 (r = 0.505, P = 0.023). Conclusion: SevoPoC may be more effective in the cardioprotection than DRIPC partly due to the deactivation of NCX1.
Epidermal growth factor receptor mutations are linked to skip N2 lymph node metastasis in resected non-small-cell lung cancer adenocarcinomas†

Objectives The impact of skip N2 metastases (i.e. N2 lymph node metastases without N1) on survival in surgically resected non-small lung cancer remains an intriguing and rarely investigated topic. The goal of our study was to elucidate (i) skip N2 influence on overall survival (OS) and time to recurrence (TTR) in patients with resected lung adenocarcinoma and (ii) its link with epidermal growth factor receptor ( EGFR ) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations. Methods A retrospective analysis of 279 consecutive patients with lung pN2 adenocarcinoma, operated in two institutions between 2003 and 2013, was conducted. OS and TTR were calculated using the Kaplan-Meier method. Crude and multivariable-adjusted comparisons by skip N2 for OS and TTR were performed using the Cox method with shared frailty (accounting for the within-centre correlation). Associations between skip N2 metastasis, clinicopathological characteristics and EGFR and KRAS mutations were investigated using the Fisher exact test and Cramér's V -test. Results The mean age at the time of surgery was 63 years (±12), and the median follow-up time was 36 months (min 3; max 101). Skip N2 was observed in 54 patients (19%). EGFR mutations were observed in 38 patients (14%); KRAS mutations were seen in 86 patients (31%). Patients with skip N2 metastasis were predominantly non-smokers ( P = 0.001), underwent segmentectomy or limited resections ( P = 0.004) and were not submitted to adjuvant therapy ( P = 0.022). Moreover, there was a correlation between EGFR mutations and skip N2 (Cramér's V : 0.25, P < 0.001). Indeed, EGFR mutations were significantly more frequent in skip N2 tumours (33%) compared with non-skip tumours (10%), P < 0.001. No correlation between skip N2 and KRAS mutations was observed (Cramér's V : 0.05, P = 0.46). The multivariable-adjusted model showed a significant skip N2 protective effect on OS (hazard ratio, HR 0.503; P = 0.014; 95% confidence interval, CI: 0.291-0.8704) but not on TTR (HR 0.788; P = 0.446; 95% CI: 0.427-1.454). Conclusions In our series, lung adenocarcinoma skip N2 metastasis demonstrated a favourable prognosis. The presence of EGFR mutations could have significance in the better survival and in the specific anatomic pathway of lymphatic metastases exhibited by skip N2 tumours.
Social determinants of food choice

Food choice is influenced by a large number of factors, including social and cultural factors. One method for trying to understand the impact of these factors is through the study of attitudes. Research is described which utilizes social psychological attitude models of attitude-behaviour relationships, in particular the Theory of Planned Behaviour. This approach has shown good prediction of behaviour, but there are a number of possible extensions to this basic model which might improve its utility. One such extension is the inclusion of measures of moral concern, which have been found to be important both for the choice of genetically-modified foods and also for foods to be eaten by others. It has been found to be difficult to effect dietary change, and there are a number of insights from social psychology which might address this difficulty. One is the phenomenon of optimistic bias, where individuals believe themselves to be at less risk from various hazards than the average person. This effect has been demonstrated for nutritional risks, and this might lead individuals to take less note of health education messages. Another concern is that individuals do not always have clear-cut attitudes, but rather can be ambivalent about food and about healthy eating. It is important, therefore, to have measures for this ambivalence, and an understanding of how it might impact on behaviour.
Rational Design, Synthesis and Evaluation of γ-CD-Containing Cross-Linked Polyvinyl Alcohol Hydrogel as a Prednisone Delivery Platform

This study describes the in-silico rational design, synthesis and evaluation of cross-linked polyvinyl alcohol hydrogels containing γ-cyclodextrin (γ-CDHSAs) as platforms for the sustained release of prednisone (PDN). Through in-silico studies using semi-empirical quantum mechanical calculations, the effectiveness of 20 dicarboxylic acids to generate a specific cross-linked hydrogel capable of supporting different amounts of γ-cyclodextrin (γ-CD) was evaluated. According to the interaction energies calculated with the in-silico studies, the hydrogel made from PVA cross-linked with succinic acids (SA) was shown to be the best candidate for containing γ-CD. Later, molecular dynamics simulation studies were performed in order to evaluate the intermolecular interactions between PDN and three cross-linked hydrogel formulations with different proportions of γ-CD (2.44%, 4.76% and 9.1%). These three cross-linked hydrogels were synthesized and characterized. The loading and the subsequent release of PDN from the hydrogels were investigated. The in-silico and experimental results showed that the interaction between PDN and γ-CDHSA was mainly produced with the γ-CDs linked to the hydrogels. Thus, the unique structures and properties of γ-CDHSA demonstrated an interesting multiphasic profile that could be utilized as a promising drug carrier for controlled, sustained and localized release of PDN.
Silencing Mediated by the Schizosaccharomyces pombe HIRA Complex Is Dependent upon the Hpc2-Like Protein, Hip4

Background HIRA (or Hir) proteins are conserved histone chaperones that function in multi-subunit complexes to mediate replication-independent nucleosome assembly. We have previously demonstrated that the Schizosaccharomyces pombe HIRA proteins, Hip1 and Slm9, form a complex with a TPR repeat protein called Hip3. Here we have identified a new subunit of this complex. Methodology/Principal Findings To identify proteins that interact with the HIRA complex, rapid affinity purifications of Slm9 were performed. Multiple components of the chaperonin containing TCP-1 complex (CCT) and the 19S subunit of the proteasome reproducibly co-purified with Slm9, suggesting that HIRA interacts with these complexes. Slm9 was also found to interact with a previously uncharacterised protein (SPBC947.08c), that we called Hip4. Hip4 contains a HRD domain which is a characteristic of the budding yeast and human HIRA/Hir-binding proteins, Hpc2 and UBN1. Co-precipitation experiments revealed that Hip4 is stably associated with all of the other components of the HIRA complex and deletion of hip4+ resulted in the characteristic phenotypes of cells lacking HIRA function, such as temperature sensitivity, an elongated cell morphology and hypersensitivity to the spindle poison, thiabendazole. Moreover, loss of Hip4 function alleviated the heterochromatic silencing of reporter genes located in the mating type locus and centromeres and was associated with increased levels of non-coding transcripts derived from centromeric repeat sequences. Hip4 was also found to be required for the distinct form of silencing that controls the expression of Tf2 LTR retrotransposons. Conclusions/Significance Overall, these results indicate that Hip4 is an integral component of the HIRA complex that is required for transcriptional silencing at multiple loci.
Nanoluciferase signal brightness using furimazine substrates opens bioluminescence resonance energy transfer to widefield microscopy

Fluorescence and bioluminescence resonance energy transfer (FRET, BRET) techniques are powerful tools for studying protein–protein interactions in cellular assays. In contrast to fluorescent proteins, chemiluminescent proteins do not require excitation light, known to trigger autofluorescence, phototoxicity, and photobleaching. Regrettably, low signal intensity of luciferase systems restricts their usage as they require specialized microscopes equipped with ultra low‐light imaging cameras. In this study, we report that bioluminescence quantification in living cells using a standard widefield automated microscope dedicated to screening and high content analysis is possible with the newer luciferase systems, Nanoluciferase (Nluc). With such equipment, we showed that robust intramolecular BRET can be measured using a combination of Nluc and yellow fluorescent protein (YFP). Using the human Superoxide Dismutase 1 (SOD1) dimer model, we next validated that intermolecular BRET could be quantified at a single cell level. The enhanced signal brightness of Nluc enabling BRET imaging to widefield microscopy shows strong potential to open up single cell protein–protein interactions studies to a wider audience. © 2016 International Society for Advancement of Cytometry
The incidence, predictive factors and prognosis of acute pulmonary complications after transcatheter aortic valve implantation.

OBJECTIVES Although acute pulmonary complications (APCs), such as the exacerbation of pulmonary disease (PD) or a newly developed pulmonary event, are thought to be catastrophic after invasive therapy, little is known about the occurrence of APCs after transcatheter aortic valve implantation (TAVI). This study aims to clarify the incidence, predictive factors and impact of APCs on prognosis after TAVI. METHODS We identified 749 patients who underwent TAVI, using data from the Optimized CathEter vAlvular iNtervention (OCEAN-TAVI) Japanese multicentre registry. APCs were defined as exacerbation of a comorbidity or newly developed PD during hospitalization. Patients were divided into 2 groups: an APC group (1.5%, 11/749) and a non-APC group (98.5%, 738/749). Clinical and prognostic outcomes were compared, and predictive factors for APCs were assessed. RESULTS Procedure-related death did not differ between the groups (0.4% vs 0.0%, P = 1.00), although 30-day mortality was significantly higher in the APC group than in the non-APC group (27.3% vs 1.6%, P = 0.001) and the difference in cumulative 1-year mortality increased further (72.7% vs 8.6%, log-rank test: P < 0.001). In particular, concomitant PD and transapical (TA) approach were identified as predictors of APCs after TAVI [univariable odds ratio (uOR) = 24.2, 95% confidence interval (CI) = 3.08-189.9, P = 0.002; uOR = 3.69, 95% CI = 1.11-12.3, P = 0.033, respectively]. CONCLUSIONS Although rare, the occurrence of APCs after TAVI was associated with extremely poor prognosis. Patients undergoing TAVI with concomitant PD and/or TA require careful consideration to avoid the risk of APCs.
Differences in the structural characteristics and distribution of epicardial adipose tissue between left and right atrial fibrillation

Aims Right atrial (RA) fibrillation (RAF) was previously characterized by initiation from RA ectopies, presence of a right-to-left dominant frequency gradient during atrial fibrillation (AF), and augmentation of the gradient by adenosine triphosphate infusion. We investigated structural characteristics of the bi-atria and epicardial adipose tissue (EAT) volume in patients with RAF. Methods and results By using multidetector computed tomography, RA, left atrial (LA), right and LA appendage (RAA and LAA, respectively) volumes, pulmonary vein (PV) sizes, and EAT volumes were compared between the RAF group (n = 8) and LA fibrillation (LAF) group (n = 32). Compared with the LAF group, the LA volume was smaller (median 81.3 [95% CI, 74.2-88.5] vs. 64.5 [54.8-74.2] mL/m2; P = 0.04), the LAA volume was smaller (10.1 [9.0-11.3] vs. 6.5 [4.5-8.5] mL/m2; P = 0.008), and the RAA volume was larger (10.8 [9.1-12.4] vs. 14.1 [11.6-16.6] mL/m2; P = 0.044) in the RAF group. The RA volume was not significantly different between the groups (73.6 [66.8-80.3] vs. 68.1 [57.1-79.1] mL/m2; P = 0.47). The RAF group had smaller PVs (1.44 [1.33-1.55] vs. 1.12 [0.94-1.30] cm2/m2 for the left inferior PV; P = 0.01). Both the LA-EAT and RA-EAT volumes were smaller in the RAF group than the LAF group (4.2 [2.8-5.6] vs. 9.1 [7.8-10.4] mL/m2; P < 0.001 and 5.3 [4.3-6.3] vs. 9.5 [8.4-10.6] mL/m2; P < 0.001, respectively). Conclusion RAF was structurally characterized by predominant RAA enlargement, small left atrium, and less EAT surrounding the atria. Electrical properties that determine the features of AF (RAF vs. LAF) may be genetically linked to structural properties.
Psoriasis and subclinical atherosclerosis in a Chinese population

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Insurance Receipt and Readiness for Opportunities under the Affordable Care Act: A National Survey of Treatment Providers for Substance Use Disorders

ABSTRACT This study measures the readiness of substance use disorder (SUD) treatment to use opportunities under the Affordable Care Act by examining Medicaid and private insurance acceptance between 2011 and 2013, as well as center characteristics associated with acceptance. Data for this study were from a random sample of SUD treatment centers in the United States. Interviews were conducted on site and face to face, with administrative and clinical directors. We employed logistic regression analyses to examine Medicaid acceptance and private insurance acceptance. We found that 59% of centers accepted Medicaid and 55% accepted private insurance. Accredited centers were more likely to accept Medicaid. A 12-step orientation and greater reliance on female clients were negatively associated with Medicaid acceptance. Larger centers and centers with a greater percentage of counselors with advanced degrees had greater odds of accepting private insurance. Centers that offered residential treatment had lower odds of accepting either Medicaid or private insurance. For private insurance acceptance, having a specific track for homeless patients lowered the odds of acceptance, as did having a greater percentage of Hispanic clients. Newly insured individuals under the ACA may have difficulty finding a program that accepts insurance. Future research should examine effects of Medicaid expansion on SUD treatment delivery.
Query expansion using MeSH terms for dataset retrieval: OHSU at the bioCADDIE 2016 dataset retrieval challenge

Abstract Scientific data are being generated at an ever-increasing rate. The Biomedical and Healthcare Data Discovery Index Ecosystem (bioCADDIE) is an NIH-funded Data Discovery Index that aims to provide a platform for researchers to locate, retrieve, and share research datasets. The bioCADDIE 2016 Dataset Retrieval Challenge was held to identify the most effective dataset retrieval methods. We aimed to assess the value of Medical Subject Heading (MeSH) term-based query expansion to improve retrieval. Our system, based on the open-source search engine, Elasticsearch, expands queries by identifying synonyms from the MeSH vocabulary and adding these to the original query. The number and relative weighting of MeSH terms is variable. The top 1000 search results for the 15 challenge queries were submitted for evaluation. After the challenge, we performed additional runs to determine the optimal number of MeSH terms and weighting. Our best overall score used five MeSH terms with a 1:5 terms:words weighting ratio, achieving an inferred normalized distributed cumulative gain (infNDCG) of 0.445, which was the third highest score among the 10 research groups who participated in the challenge. Further testing revealed our initial combination of MeSH terms and weighting yielded the best overall performance. Scores varied considerably between queries as well as with different variations of MeSH terms and weights. Query expansion using MeSH terms can enhance search relevance of biomedical datasets. High variability between queries and system variables suggest room for improvement and directions for further research. Database URL: https://biocaddie.org/benchmark-data
University of Birmingham A novel method for automated assessment of megakaryocyte differentiation and proplatelet formation

Transfusion of platelet concentrates represents an important treatment for various bleeding complications. However, the short half-life and frequent contaminations with bacteria restrict the availability of platelet concentrates and raise a clear demand for platelets generated ex vivo . Therefore, in vitro platelet generation from megakaryocytes represents an important research topic. A vital step for this process represents accurate analysis of thrombopoiesis and proplatelet formation, which is usually conducted manually. We aimed to develop a novel method for automated classification and analysis of proplatelet-forming megakaryocytes in vitro . After fluorescent labelling of surface and nucleus, MKs were automatically categorized and analysed with a novel pipeline of the open source software CellProfiler . Our new workflow is able to detect and quantify four subtypes of megakaryocytes undergoing thrombopoiesis: proplatelet-forming, spreading, pseudopodia-forming and terminally differentiated, anucleated megakaryocytes. Furthermore, we were able to characterize the inhibitory effect of dasatinib on thrombopoiesis in more detail. Our new workflow enabled rapid, unbiased, quantitative and qualitative in-depth analysis of proplatelet formation based on morphological characteristics. Clinicians and basic researchers alike will benefit from this novel technique that allows reliable and unbiased quantification of proplatelet formation. It thereby provides a valuable tool for the development of methods to generate platelets ex vivo and to detect effects of drugs on megakaryocyte differentiation.