Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of Radiation Responses by Pre-exposure to Irradiated Cell Conditioned Medium

Abstract Maguire, P., Mothersill, C. , McClean, B. , Seymour, C. and Lyng, F. M. Modulation of Radiation Responses by Pre-exposure to Irradiated Cell Conditioned Medium. Radiat. Res. 167, 485–492 (2007). The aim of this study was to investigate whether exposure of HPV-G cells to irradiated cell conditioned medium (ICCM) could induce an adaptive response if the cells were subsequently challenged with a higher ICCM dose. Clonogenic survival and major steps in the cascade leading to apoptosis, such as calcium influx and loss of mitochondrial membrane potential, were examined to determine whether these events could be modified by giving a priming dose of ICCM before the challenge dose. Clonogenic survival data indicated an ICCM-induced adaptive response in HPV-G cells “primed” with 5 mGy or 0.5 Gy ICCM for 24 h and then exposed to 0.5 Gy or 5 Gy ICCM. Reactive oxygen species (ROS) were found to be involved in the bystander-induced cell death. Calcium fluxes varied in magnitude across the exposed cell population, and a significant number of the primed HPV-G cells did not respond to the challenge ICCM dose. No significant loss of mitochondrial membrane potential was observed when HPV-G cells were exposed to 0.5 Gy ICCM for 24 h followed by exposure to 5 Gy ICCM for 6 h. Exposure of HPV-G cells to 5 mGy ICCM for 24 h followed by exposure to 0.5 Gy ICCM for 18 h caused a significant increase in mitochondrial mass and a change in mitochondrial location, events associated with the perpetuation of genomic instability. This study has shown that a priming dose of ICCM has the ability to induce an adaptive response in HPV-G cells subsequently exposed to a challenge dose of ICCM.
Lung Epithelial Cells Are a Major Site of Murine Gammaherpesvirus Persistence

It is currently believed that latently infected, resting B lymphocytes are central to gammaherpesvirus persistence, whereas mucosal epithelial cells are considered nonessential. We have readdressed the question of nonlymphoid persistence using murine gammaherpesvirus 68 (MHV-68). To dissect lymphoid from nonlymphoid persistence, we used μMT transgenic mice that are defective in B cells. MHV-68 DNA persisted in the lungs of intact and B cell–deficient mice. Both episomal and linear forms of the virus genome were present in lungs, implying the presence of both latency and productive replication. In situ hybridization for virus tRNA transcripts revealed latent MHV-68 in pulmonary epithelial cells. Infectious virus was recovered from the lungs of μMT mice after T cell depletion, showing that the persisting virus DNA was reactivatable. Finally, using adoptive transfer of B cells into B cell–deficient mice, it was shown that virus persisting in lungs seeded splenic B cells, and virus resident in the spleen seeded the lungs. These results show that mucosal epithelia can act as a nonlymphoid reservoir for gammaherpesvirus persistence, and that there is a two-way movement of virus between lymphoid and nonlymphoid compartments during persistence.
Same/Different Concept Learning by Capuchin Monkeys in Matching-to-Sample Tasks

The ability to understand similarities and analogies is a fundamental aspect of human advanced cognition. Although subject of considerable research in comparative cognition, the extent to which nonhuman species are capable of analogical reasoning is still debated. This study examined the conditions under which tufted capuchin monkeys (Cebus apella) acquire a same/different concept in a matching-to-sample task on the basis of relational similarity among multi-item stimuli. We evaluated (i) the ability of five capuchin monkeys to learn the same/different concept on the basis of the number of items composing the stimuli and (ii) the ability to match novel stimuli after training with both several small stimulus sets and a large stimulus set. We found the first evidence of same/different relational matching-to-sample abilities in a New World monkey and demonstrated that the ability to match novel stimuli is within the capacity of this species. Therefore, analogical reasoning can emerge in monkeys under specific training conditions.
Selection of Medical Diagnostic Codes for Analysis of Electronic Patient Records. Application to Stroke in a Primary Care Database

Background Electronic patient records from primary care databases are increasingly used in public health and health services research but methods used to identify cases with disease are not well described. This study aimed to evaluate the relevance of different codes for the identification of acute stroke in a primary care database, and to evaluate trends in the use of different codes over time. Methods Data were obtained from the General Practice Research Database from 1997 to 2006. All subjects had a minimum of 24 months of up-to-standard record before the first recorded stroke diagnosis. Initially, we identified stroke cases using a supplemented version of the set of codes for prevalent stroke used by the Office for National Statistics in Key health statistics from general practice 1998 (ONS codes). The ONS codes were then independently reviewed by four raters and a restricted set of 121 codes for ‘acute stroke’ was identified but the kappa statistic was low at 0.23. Results Initial extraction of data using the ONS codes gave 48,239 cases of stroke from 1997 to 2006. Application of the restricted set of codes reduced this to 39,424 cases. There were 2,288 cases whose index medical codes were for ‘stroke annual review’ and 3,112 for ‘stroke monitoring’. The frequency of stroke review and monitoring codes as index codes increased from 9 per year in 1997 to 1,612 in 2004, 1,530 in 2005 and 1,424 in 2006. The one year mortality of cases with the restricted set of codes was 29.1% but for ‘stroke annual review,’ 4.6% and for ‘stroke monitoring codes’, 5.7%. Conclusion In the analysis of electronic patient records, different medical codes for a single condition may have varying clinical and prognostic significance; utilisation of different medical codes may change over time; researchers with differing clinical or epidemiological experience may have differing interpretations of the relevance of particular codes. There is a need for greater transparency in the selection of sets of codes for different conditions, for the reporting of sensitivity analyses using different sets of codes, as well as sharing of code sets among researchers.
Genetic prediction of type 2 diabetes using deep neural network

Type 2 diabetes (T2DM) has strong heritability but genetic models to explain heritability have been challenging. We tested deep neural network (DNN) to predict T2DM using the nested case‐control study of Nurses’ Health Study (3326 females, 45.6% T2DM) and Health Professionals Follow‐up Study (2502 males, 46.5% T2DM). We selected 96, 214, 399, and 678 single‐nucleotide polymorphism (SNPs) through Fisher’s exact test and L1‐penalized logistic regression. We split each dataset randomly in 4:1 to train prediction models and test their performance. DNN and logistic regressions showed better area under the curve (AUC) of ROC curves than the clinical model when 399 or more SNPs included. DNN was superior than logistic regressions in AUC with 399 or more SNPs in male and 678 SNPs in female. Addition of clinical factors consistently increased AUC of DNN but failed to improve logistic regressions with 214 or more SNPs. In conclusion, we show that DNN can be a versatile tool to predict T2DM incorporating large numbers of SNPs and clinical information. Limitations include a relatively small number of the subjects mostly of European ethnicity. Further studies are warranted to confirm and improve performance of genetic prediction models using DNN in different ethnic groups.
The impact of a Role Emerging Placement while a student occupational therapist, on subsequent qualified employability, practice and career path

BACKGROUND Although Role Emerging Placements (REP) are now a common feature in pre-registration occupational therapy curricula, there is a need to expand the understanding of the impact of this experience on employability, practice and career path of qualified occupational therapists. METHOD A case finding online survey was used to create a purposive sample for Thematic Analysis of semi-structured interviews with practising occupational therapists from one UK Masters' level pre-registration occupational therapy program. RESULTS The case finding survey (n = 19) led to recruitment of six participants to be interviewed. The qualitative findings reflected the impact of a REP experience on occupational therapists' employability, practice and career path. The complementary features of the more traditional placement and the role emergent type of placement were considered as being useful and beneficial to qualified practice regardless of setting. However, the REP additionally, had an internal and outward impact. Internally, the therapist gains a passion for occupation-focussed practice and builds confidence to promote both self and the profession. Outwardly, the therapist can offer extra skills in qualified practice, particularly in innovative service development and delivery, thereby offering added value for employability. CONCLUSION A REP experience as an occupational therapy student, can develop additional skills for qualified professional practice than traditional practice placements alone. The impact of such a placement matches with the 'Generation Y' traits of young adults who are now starting to emerge into training and the work place, translates well into a variety of working environments and lasts into career development. The placement model of occupation-focussed project development and the less apprentice style learning of a REP may be influential, and could be a suitable model within traditional placements.
RhoA inhibits neural differentiation in murine stem cells through multiple mechanisms

RhoA signaling prevents the neural differentiation of embryonic stem cells by inhibiting both the production and secretion of the BMP antagonist Noggin. Halting neural differentiation with RhoA Bone morphogenetic proteins (BMPs) are important for maintaining the pluripotency and self-renewal of embryonic stem cells (ESCs). Spontaneous differentiation of ESCs into neurons involves the production of Noggin, a secreted protein that inhibits BMP signaling. The GTPase RhoA maintains ESC pluripotency by preventing neural differentiation. Yang et al. found that the RhoA-specific guanine nucleotide exchange factor Syx prevented neural differentiation of murine ESCs (mESCs) by limiting both the abundance of Noggin and its secretion. Thus, regulation of secretion, as well as production of differentiation-promoting factors, provides multiple layers of control over stem cell fate. Spontaneous neural differentiation of embryonic stem cells is induced by Noggin-mediated inhibition of bone morphogenetic protein 4 (BMP4) signaling. RhoA is a guanosine triphosphatase (GTPase) that regulates cytoskeletal dynamics and gene expression, both of which control stem cell fate. We found that disruption of Syx, a gene encoding a RhoA-specific guanine nucleotide exchange factor, accelerated retinoic acid–induced neural differentiation in murine embryonic stem cells aggregated into embryoid bodies. Cells from Syx+/+ and Syx−/− embryoid bodies had different abundances of proteins implicated in stem cell pluripotency. The differentiation-promoting proteins Noggin and RARγ (a retinoic acid receptor) were more abundant in cells of Syx−/− embryoid bodies, whereas the differentiation-suppressing proteins SIRT1 (a protein deacetylase) and the phosphorylated form of SMAD1 (the active form of this transcription factor) were more abundant in cells of Syx+/+ embryoid bodies. These differences were blocked by the overexpression of constitutively active RhoA, indicating that the abundance of these proteins was maintained, at least in part, by RhoA activity. The peripheral stress fibers in cells from Syx−/− embryoid bodies were thinner than those in Syx+/+ cells. Furthermore, less Noggin and fewer vesicles containing Rab3d, a GTPase that mediates Noggin trafficking, were detected in cells from Syx−/− embryoid bodies, which could result from increased Noggin exocytosis. These results suggested that, in addition to inhibiting Noggin transcription, RhoA activity in wild-type murine embryonic stem cells also prevented neural differentiation by limiting Noggin secretion.
Assessing Change Proneness at the Architecture Level: An Empirical Validation

Change proneness is a characteristic of software artifacts that represents their probability to change in future. Change proneness can be assessed at different levels of granularity, ranging from classes to modules. Although change proneness can be successfully assessed at the source code level (i.e., methods and classes), it remains rather unexplored for architectures. Additionally, the methods that have been introduced at the source code level are not directly transferable to the architecture level. In this paper, we propose and empirically validate a method for assessing the change proneness of architectural modules. Assessing change proneness at the level of architectural modules requires information from two sources: (a) the history of changes in the module, as a proxy of how frequently the module itself undergoes changes; and (b) the dependencies with other modules that affect the probability of a change being propagated from one module to the other. To validate the proposed approach, we performed a case study on five open-source projects. Specifically, we compared the accuracy of the proposed approach to the use of software package metrics as assessors of modules change proneness, based on the 1061-1998 IEEE Standard. The results suggest that compared to examined metrics, the proposed method is a better assessor of change proneness. Therefore, we believe that the method and accompanying tool can effectively aid architects during software maintenance and evolution.
Continuous activity understanding based on accumulative pose-context visual patterns

In application domains, such as human-robot interaction and ambient intelligence, it is expected that an intelligent agent can respond to the person's actions efficiently or make predictions while the person's activity is still ongoing. In this paper, we investigate the problem of continuous activity understanding, based on a visual pattern extraction mechanism which fuses decomposed body pose features from estimated 2D skeletons (based on deep learning skeleton inference) and localized appearance-motion features around spatiotemporal interest points (STIPs). Considering that human activities are observed and inferred gradually, we partition the video into snippets, extract the visual pattern accumulatively and infer the activities in an online fashion. We evaluated the proposed method on two benchmark datasets and achieved 92.6% on the KTH dataset and 92.7% on the Rochester Assisted Daily Living dataset in the equilibrated inference states. In parallel, we discover that context information mainly contributed by STIPs is probably more favourable to activity recognition than the pose information, especially in scenarios of daily living activities. In addition, incorporating the visual patterns of activities from early stages to train the classifier can improve the performance of early recognition; however, it could degrade the recognition rate in later time. To overcome this issue, we propose a mixture model, where the classifier trained with early visual patterns are used in early stages while the classifier trained without early patterns are used in later stages. The experimental results show that this straightforward approach can improve early recognition while retaining the recognition correctness of later times.
Model-Derived Dispersal Pathways from Multiple Source Populations Explain Variability of Invertebrate Larval Supply

Background Predicting the spatial and temporal patterns of marine larval dispersal and supply is a challenging task due to the small size of the larvae and the variability of oceanographic processes. Addressing this problem requires the use of novel approaches capable of capturing the inherent variability in the mechanisms involved. Methodology/Principal Findings In this study we test whether dispersal and connectivity patterns generated from a bio-physical model of larval dispersal of the crab Carcinus maenas, along the west coast of the Iberian Peninsula, can predict the highly variable daily pattern of wind-driven larval supply to an estuary observed during the peak reproductive season (March–June) in 2006 and 2007. Cross-correlations between observed and predicted supply were significant (p<0.05) and strong, ranging from 0.34 to 0.81 at time lags of −6 to +5 d. Importantly, the model correctly predicted observed cross-shelf distributions (Pearson r = 0.82, p<0.001, and r = 0.79, p<0.01, in 2006 and 2007) and indicated that all supply events were comprised of larvae that had been retained within the inner shelf; larvae transported to the outer shelf and beyond never recruited. Estimated average dispersal distances ranged from 57 to 198 km and were only marginally affected by mortality. Conclusions/Significance The high degree of predicted demographic connectivity over relatively large geographic scales is consistent with the lack of genetic structuring in C. maenas along the Iberian Peninsula. These findings indicate that the dynamic nature of larval dispersal can be captured by mechanistic biophysical models, which can be used to provide meaningful predictions of the patterns and causes of fine-scale variability in larval supply to marine populations.
Functional connectivity pattern underlies individual differences in independent self-construal

Abstract Independent vs interdependent self-construal is a concept that reflects how people perceive the relationship between self and other people, which has been extensively examined across disciplines. However, little evidence on the whole-brain functional connectivity (FC) pattern of independent vs interdependent self-construal has been reported. Here, in a sample of 51 healthy participants, we used resting-state functional magnetic resonance imaging and voxel-based FC analysis (i.e. FC strength and seed-based FC) by measuring the temporal correlation of blood oxygen level-dependent signals between spatially separate brain regions to investigate the neural mechanism of independent vs interdependent self-construal. First, we found that FC strength of bilateral posterior cingulate cortex and precuneus, and left inferior frontal gyrus were positively correlated with the independent vs interdependent score. Seed-based FC analysis with these three regions as seeds revealed that, FC within default mode network and executive control network was positively correlated with the independent vs interdependent score. Negative correlation with independent vs interdependent score was shown in the connections between default mode network and executive control regions. Taking together, our results provide a comprehensive FC architecture of the independent vs interdependent self-construal and advance the understanding of the interplay between culture, mind and brain.
Early pregnancy folate-cobalamin interactions and their effects on cobalamin status and hematologic variables throughout pregnancy.

Background Periconception folic acid supplementation is widespread, but how it interacts with cobalamin status is rarely considered. Objective The aim of this study was to investigate whether first-trimester folate-cobalamin interactions affect pregnancy cobalamin status, hematologic variables, and pregnancy outcomes. Design In the longitudinal Reus-Tarragona Birth Cohort study from <12 gestational weeks throughout pregnancy, fasting plasma and red blood cell (RBC) folate, plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), total homocysteine (tHcy), hemoglobin, mean cell volume (MCV), postglucose-load serum glucose, gestational hypertension, gestational age at birth, and birth weight were recorded in 563 participants. Results The highest plasma folate concentrations occurred in the first trimester when folic acid supplement use was extensive. Supplementation beyond the first trimester interacted with time of pregnancy on plasma folate, RBC folate, and tHcy throughout pregnancy (P-interaction <0.001). Plasma folate and RBC folate were higher and tHcy was lower in continued supplement users than in nonusers. Elevated plasma folate (≥30 nmol/L) occurred in 78.9% of women who exceeded the recommended 400 µg folic acid/d. First-trimester folate-cobalamin status interactions were associated with MMA (P-interaction <0.001) throughout pregnancy. When plasma cobalamin was suboptimal (≤221 pmol/L; n = 36), participants with elevated plasma folate (n = 11) had higher MMA concentrations than did those with nonelevated plasma folate (n = 23). First-trimester folate-MMA status interactions were associated with MCV throughout pregnancy (P-interaction <0.01) and with cord plasma holoTC (P-interaction <0.05). The mean difference (95% CI) in MCV (fL) between women with elevated and nonelevated plasma folate status was -2.12 (-3.71, -0.52) for top-quartile plasma MMA (≥0.139 µmol/L) and 0.60 (-0.39, 1.60) for plasma MMA <0.139 µmol/L. Cord plasma holoTC was higher in women with elevated compared with nonelevated plasma folate status only for MMA <0.139 µmol/L. Folate-cobalamin interactions were not associated with the other investigated outcomes. Conclusion First-trimester folate-cobalamin status interactions were associated with plasma MMA and MCV throughout pregnancy. This trial was registered at www.clinicaltrials. gov as NCT01778205.
The Effect of Pregnancy on the Long-term Risk of Graft Loss, Cardiovascular Disease, and Death in Kidney Transplanted Women in Norway: A Retrospective Cohort Study

Background Kidney transplant recipients have now conceived for almost 50 years. Nevertheless, few studies have evaluated long-term health outcomes for kidney transplanted women after pregnancies. Methods We conducted a retrospective cohort study of all Norwegian women receiving a kidney transplant before the age of 50 years between 1969 and 2013, with graft loss, cardiovascular disease, and death as outcomes. Baseline characteristics for all women were ascertained at first transplantation, with information about exposure, outcomes, and potential confounders collected from medical records. To account for changes in pregnancy status, data were analyzed using proportional hazard Cox regression with pregnancy status as a time-dependent covariate changing at the time of pregnancy. Results Of 650 women studied, 124 had a pregnancy after kidney transplantation. During the study period, graft loss, cardiovascular disease, and death occurred in 237, 73, and 274 women, respectively. Pregnancy was associated with 54% lower risk of graft loss (95% confidence interval [CI]: 25% to 71%) and 72% lower risk of death (95% CI, 53%-84%). Adjusting for possible confounders had a minimal impact on estimated values. There were considerable uncertainties and no statistically significant results regarding the estimated risk of cardiovascular disease after pregnancy (univariate hazard ratio, 0.91; 95% CI, 0.43-1.92; multivariate hazard ratio, 0.71; 95% CI, 0.32-1.60). Conclusions Kidney transplanted women with pregnancies have a low risk of subsequent graft loss or death. These results are reassuring for the current clinical practice.