Miracle-dz/UniFAR-FTUs huggingface dataset:
Mathematical models of tumor growth using Voronoi tessellations in pathology slides of kidney cancer

The impact of patient-specific spatial distribution features of cell nuclei on tumor growth characteristics was analyzed. Tumor tissues from kidney cancer patients were allowed to grow in mice to apply H&E staining and to measure tumor volume during preclinical phase of our study. Imaging the H&E stained slides under a digital light microscope, the morphological characteristics of nuclei positions were determined. Using artificial intelligence based techniques, Voronoi features were derived from diagrams, where cell nuclei were considered as distinct nodes. By identifying the effect of each Voronoi feature, tumor growth was expressed mathematically. Consistency between the computed growth curves and preclinical measurements indicates that the information obtained from the H&E slides can be used as biomarkers to build personalized mathematical models for tumor growth.
Involvement of serotonin 2C receptor RNA editing in accumbal neuropeptide Y expression and behavioural despair

Serotonin 2C receptors (5‐HT2CRs) are widely expressed in the central nervous system, and are associated with various neurological disorders. 5‐HT2CR mRNA undergoes adenosine‐to‐inosine RNA editing at five sites within its coding sequence, resulting in expression of 24 different isoforms. Several edited isoforms show reduced activity, suggesting that RNA editing modulates serotonergic systems in the brain with causative relevance to neuropsychiatric disorders. Transgenic mice solely expressing the non‐edited 5‐HT2CR INI‐isoform (INI) or the fully edited VGV‐isoform exhibit various phenotypes including metabolic abnormalities, aggressive behaviour, anxiety‐like behaviour, and depression‐like behaviour. Here, we examined the behavioural phenotype and molecular changes of INI mice on a C57BL/6J background. INI mice showed an enhanced behavioural despair in the forced swimming test, elevated sensitivity to the tricyclic antidepressant desipramine, and significantly decreased serotonin in the nucleus accumbens (NAc), amygdala, and striatum. They also showed reduced expression of neuropeptide Y (NPY) mRNA in the NAc. In addition, by stereotactic injection of adeno‐associated virus encoding NPY into the NAc, we demonstrated that accumbal NPY overexpression relieved behavioural despair. Our results suggest that accumbal NPY expression may be regulated by 5‐HT2CR RNA editing, and its impairment may be linked to mood disorders.
Palliative home-based technology from a practitioner's perspective: benefits and disadvantages

This critical review paper explores the concept of palliative home-based technology from a practitioner's perspective. The aim of the critical review was to scope information available from published and unpublished research on the current state of palliative home-based technology, practitioner-focused perspectives, patient-focused perspectives, quality of life, and the implications for clinical practice. Published and unpublished studies were included. An example of one UK patient-centered home-based technology is explored as an exemplar. The evidence suggests that despite the challenges, there are numerous examples of good practice in relation to palliative home-based technology. Improvements in technology mean that telehealth has much to offer people being cared for at home with palliative needs. However, some of the evaluative evidence is limited, and further rigor is needed when evaluating future technology-based solutions innovations.
Rare Variation in TET2 Is Associated with Clinically Relevant Prostate Carcinoma in African Americans

Background: Common variants have been associated with prostate cancer risk. Unfortunately, few are reproducibly linked to aggressive disease, the phenotype of greatest clinical relevance. One possible explanation is that rare genetic variants underlie a significant proportion of the risk for aggressive disease. Method: To identify such variants, we performed a two-stage approach using whole-exome sequencing followed by targeted sequencing of 800 genes in 652 aggressive prostate cancer patients and 752 disease-free controls in both African and European Americans. In each population, we tested rare variants for association using two gene-based aggregation tests. We established a study-wide significance threshold of 3.125 × 10−5 to correct for multiple testing. Results: TET2 in African Americans was associated with aggressive disease, with 24.4% of cases harboring a rare deleterious variant compared with 9.6% of controls (FET P = 1.84 × 10−5, OR = 3.0; SKAT-O P = 2.74 × 10−5). We report 8 additional genes with suggestive evidence of association, including the DNA repair genes PARP2 and MSH6. Finally, we observed an excess of rare truncation variants in 5 genes, including the DNA repair genes MSH6, BRCA1, and BRCA2. This adds to the growing body of evidence that DNA repair pathway defects may influence susceptibility to aggressive prostate cancer. Conclusions: Our findings suggest that rare variants influence risk of clinically relevant prostate cancer and, if validated, could serve to identify men for screening, prophylaxis, and treatment. Impact: This study provides evidence that rare variants in TET2 may help identify African American men at increased risk for clinically relevant prostate cancer. Cancer Epidemiol Biomarkers Prev; 25(11); 1456–63. ©2016 AACR.
Integrating Remote Attestation with Transport Layer Security

Intel(R) Software Guard Extensions (Intel(R) SGX) is a promising technology to securely process information in otherwise untrusted environments. An important aspect of Intel SGX is the ability to perform remote attestation to assess the endpoint's trustworthiness. Ultimately, remote attestation will result in an attested secure channel to provision secrets to the enclave. We seamlessly combine Intel SGX remote attestation with the establishment of a standard Transport Layer Security (TLS) connection. Remote attestation is performed during the connection setup. To achieve this, we neither change the TLS protocol, nor do we modify existing protocol implementations. We have prototype implementations for three widely used open-source TLS libraries: OpenSSL, wolfSSL and mbedTLS. We describe the requirements, design and implementation details to seamlessly bind attested TLS endpoints to Intel SGX enclaves.
Depressive Symptoms, Cognition, and Everyday Function Among Community-Residing Older Adults

Objective: The aim of this study was to understand the relationships among depressive symptoms, cognition, and functional performance in a community-based sample of older adults. Method: Older adults (N = 885) from the Staying Keen in Later Life study completed tests of executive function, speed of processing, and memory. The Center for Epidemiologic Depression Scale assessed depressive symptoms. The Timed Instrumental Activities of Daily Living Test assessed participants’ everyday functional performance. Results: Depressive symptoms had significant associations with measures of executive function, speed of processing, memory, and everyday functional performance. Cognitive performance completely mediated the association between depressive symptoms and everyday function. Discussion: Among community-dwelling older adults, depressive symptoms were associated with impaired cognition across multiple domains, which detrimentally affected everyday function. Health care providers should be aware of these associations to monitor and manage changes in depressive symptoms and cognitive performance and thereby potentially mitigate functional decline.
Does Real Exchange Rate Volatility Affect Foreign Direct Investment? Evidence from Four Developed Economies

This study examines the impact of shocks to exchange rate uncertainty (volatility) on foreign direct investment (FDI) in Canada, Japan, the United Kingdom, and the United States. The analysis is conducted using vector autoregressive models that contain the price level, real output, the real exchange rate, the volatility of the real exchange rate, the interest rate, and FDI. The results from variance decompositions yield public policy implications. In Canada, Japan, and the United States, innovations to exchange rate uncertainty explain significant portions of the forecast error variance in FDI at longer time horizons. The impulse response functions indicate that, to the extent that shocks to exchange rate volatility have an impact on FDI, the impact is positive and takes place with a lag.
The epidemiology of Sjögren’s syndrome

Sjögren’s syndrome is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. It can present as an entity by itself, primary Sjögren’s syndrome (pSS), or in addition to another autoimmune disease, secondary Sjögren’s syndrome (sSS). pSS has a strong female propensity and is more prevalent in Caucasian women, with the mean age of onset usually in the 4th to 5th decade. Clinical presentation varies from mild symptoms, such as classic sicca symptoms of dry eyes and dry mouth, keratoconjunctivitis sicca, and xerostomia, to severe systemic symptoms, involving multiple organ systems. Furthermore, a range of autoantibodies can be present in Sjögren’s syndrome (anti-SSA/Ro and anti-SSB/La antibodies, rheumatoid factor, cryoglobulins, antinuclear antibodies), complicating the presentation. The heterogeneity of signs and symptoms has led to the development of multiple classification criteria. However, there is no accepted universal classification criterion for the diagnosis of Sjögren’s syndrome. There are a limited number of studies that have been published on the epidemiology of Sjögren’s syndrome, and the incidence and prevalence of the disease varies according to the classification criteria used. The data is further confounded by selection bias and misclassification bias, making it difficult for interpretation. The aim of this review is to understand the reported incidence and prevalence on pSS and sSS, the frequency of autoantibodies, and the risk of malignancy, which has been associated with pSS, taking into account the different classification criteria used.
Investigation of pitting corrosion of carbon steel in sweet and sour oilfield corrosion conditions : a parametric study

The challenges in managing localised corrosion failures in oilfields are large. In environments containing both CO2 and H2S gas, pitting corrosion of carbon steel is considered to be a common occurrence and particularly complex. The consequences of pitting corrosion failures are usually severe in terms of the health and safety or the environment as well as economic cost to the operators. The actual mechanisms and sequence of electrochemical activities for pitting corrosion in these environments is still not fully understood. The film formation characteristics and morphology in CO2 and H2S-containing systems are also known to influence the general and pitting corrosion behavior of carbon steel. However, questions still remain as to how different oilfield process parameters such as temperature, chloride ion concentration, in-situ pH of corrosion environment and the combined presence of CO2 and H2S gas could be influencing the corrosion kinetics and pitting corrosion process; pit initiation and pit propagation of carbon steel materials exposed to oilfield corrosion environments. A comprehensive and systematic investigation of the pitting corrosion behaviour of X65 carbon steel in sweet and sour corrosion environment has been carried out using a combination of electrochemical techniques and a robust set of post-experiment surface analysis techniques. The results confirms the notion that pitting corrosion process of carbon steel is very different from pitting corrosion in passive alloys and that the evolution of pitting corrosion of active materials in sweet and sour corrosion environments is governed by; the uniform corrosion contribution, the local environments; corrosion products and active ionic species and environmental parameters. In sour corrosion environments, pitting corrosion characterisation using the NPFLEX 3D interferometer and extensive analysis of corrosion product morphologies using the transmission electron microscope was able to show that FeS corrosion product formation occurs faster than FeCO3 in H2S-CO2-containing corrosion system leading to pit initiation and also that in scenarios where competitive precipitation of FeCO3 and FeS is likely, the risk of pitting corrosion is increased.
Size-controlled silver nanoparticles synthesized over the range 5–100 nm using the same protocol and their antibacterial efficacy

A systematic and detailed study for size-specific antibacterial efficacy of silver nanoparticles (AgNPs) synthesized using a co-reduction approach is presented here. Nucleation and growth kinetics during the synthesis process was precisely controlled and AgNPs of average size 5, 7, 10, 15, 20, 30, 50, 63, 85, and 100 nm were synthesized with good yield and monodispersity. We found the bacteriostatic/bactericidal effect of AgNPs to be size and dose-dependent as determined by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of silver nanoparticles against four bacterial strains. Out of the tested strains, Escherichia coli MTCC 443 and Staphylococcus aureus NCIM 5201 were found to be the most and least sensitive strains regardless of AgNP size. For AgNPs with less than 10 nm size, the antibacterial efficacy was significantly enhanced as revealed through delayed bacterial growth kinetics, corresponding MIC/MBC values and disk diffusion tests. AgNPs of the smallest size, i.e., 5 nm demonstrated the best results and mediated the fastest bactericidal activity against all the tested strains compared to AgNPs having 7 nm and 10 nm sizes at similar bacterial concentrations. TEM analysis of AgNP treated bacterial cells showed the presence of AgNPs on the cell membrane, and AgNPs internalized within the cells.
Adherence to the WCRF/AICR Dietary Recommendations for Cancer Prevention and Risk of Cancer in Elderly from Europe and the United States: A Meta-Analysis within the CHANCES Project

Background: It is unknown whether dietary recommendations for cancer prevention are applicable to the elderly. We analyzed WCRF/AICR recommendations in cohorts of European and U.S. adults ages 60 years and above. Methods: Individual participant data meta-analysis included 362,114 participants (43% women), from seven prospective cohort studies, free from cancer at enrollment. The WCRF/AICR diet score was based on: (i) energy-dense foods and sugary drinks, (ii) plant foods, (iii) red and processed meat, and (iv) alcoholic drinks. Cox proportional hazards regression was used to examine the association between the diet score and cancer risks. Adjusted, cohort-specific HRs were pooled using random-effects meta-analysis. Risk advancement periods (RAP) were calculated to quantify the time period by which the risk of cancer was postponed among those adhering to the recommendations. Results: After a median follow-up of 11 to 15 years across cohorts, 70,877 cancer cases were identified. Each one-point increase in the WCRF/AICR diet score [range, 0 (no) to 4 (complete adherence)] was significantly associated with a lower risk of total cancer [HR, 0.94; 95% confidence interval (CI), 0.92–0.97], cancers of the colorectum (HR, 0.84; 95% CI, 0.80–0.89) and prostate (HR, 0.94; 95% CI, 0.92–0.97), but not breast or lung. Adherence to an additional component of the WCRF/AICR diet score significantly postponed the incidence of cancer at any site by 1.6 years (RAP, −1.6; 95% CI, −4.09 to −2.16). Conclusions: Adherence to WCRF/AICR dietary recommendations is associated with lower risk of cancer among older adults. Impact: Dietary recommendations for cancer prevention are applicable to the elderly. Cancer Epidemiol Biomarkers Prev; 26(1); 136–44. ©2016 AACR.
Substitute Teacher Networks: Learning with Almost No Supervision

Learning through experience is time-consuming, inefficient and often bad for your cortisol levels. To address this problem, a number of recently proposed teacher-student methods have demonstrated the benefits of private tuition, in which a single model learns from an ensemble of more experienced tutors. Unfortunately, the cost of such supervision restricts good representations to a privileged minority. Unsupervised learning can be used to lower tuition fees, but runs the risk of producing networks that require extracurriculum learning to strengthen their CVs and create their own LinkedIn profiles. Inspired by the logo on a promotional stress ball at a local recruitment fair, we make the following three contributions. First, we propose a novel almost no supervision training algorithm that is effective, yet highly scalable in the number of student networks being supervised, ensuring that education remains affordable. Second, we demonstrate our approach on a typical use case: learning to bake, developing a method that tastily surpasses the current state of the art. Finally, we provide a rigorous quantitive analysis of our method, proving that we have access to a calculator. Our work calls into question the long-held dogma that life is the best teacher.
Proteomics to predict the response to tumour necrosis factor-α inhibitors in rheumatoid arthritis using a supervised cluster-analysis based protein score

Objective: In rheumatoid arthritis (RA), it is of major importance to identify non-responders to tumour necrosis factor-α inhibitors (TNFi) before starting treatment, to prevent a delay in effective treatment. We developed a protein score for the response to TNFi treatment in RA and investigated its predictive value. Method: In RA patients eligible for biological treatment included in the BiOCURA registry, 53 inflammatory proteins were measured using xMAP® technology. A supervised cluster analysis method, partial least squares (PLS), was used to select the best combination of proteins. Using logistic regression, a predictive model containing readily available clinical parameters was developed and the potential of this model with and without the protein score to predict European League Against Rheumatism (EULAR) response was assessed using the area under the receiving operating characteristics curve (AUC-ROC) and the net reclassification index (NRI). Results: For the development step (n = 65 patient), PLS revealed 12 important proteins: CCL3 (macrophage inflammatory protein, MIP1a), CCL17 (thymus and activation-regulated chemokine), CCL19 (MIP3b), CCL22 (macrophage-derived chemokine), interleukin-4 (IL-4), IL-6, IL-7, IL-15, soluble cluster of differentiation 14 (sCD14), sCD74 (macrophage migration inhibitory factor), soluble IL-1 receptor I, and soluble tumour necrosis factor receptor II. The protein score scarcely improved the AUC-ROC (0.72 to 0.77) and the ability to improve classification and reclassification (NRI = 0.05). In validation (n = 185), the model including protein score did not improve the AUC-ROC (0.71 to 0.67) or the reclassification (NRI = −0.11). Conclusion: No proteomic predictors were identified that were more suitable than clinical parameters in distinguishing TNFi non-responders from responders before the start of treatment. As the results of previous studies and this study are disparate, we currently have no proteomic predictors for the response to TNFi.
A low offset dynamic comparator with morphing amplifier

Dynamic comparators are popular structures used in analog circuits such as RFID tags, ADC, memory modules, etc. Compared with traditional open-loop amplifiers that can be used as a comparator, well-designed dynamic comparators are usually faster and more powerefficient, but dynamic CMPs also have some problems. Device mismatch-induced offset voltages is a major challenge when designing dynamic comparators because device mismatch is a random variable that is non-predictable during the design stage. There are many popular dynamic CMP structures; one of them is the Lewis-Gray dynamic comparator [1]. Many authors have introduced alternative dynamic comparator structures which they claim are less affected by device mismatch than the Lewis-Gray circuit but few present a comprehensive and reasonable comparison method. In those papers, different modifications are implemented in order to minimize device mismatch offset, one popular way is to add an amplifier stage before the dynamic comparator. The input signals are amplified in the first amplifier stage before going into the second dynamic comparator stage. Since the outputs of the first stage have a larger difference comparing with the inputs, the offset requirement for the dynamic comparator is loosened. However, the offset still has room for improvement. In this work, a low offset dynamic comparator with morphing amplifier is proposed. It doesn’t have two independent stages. Instead, the amp is inherently integrated into a dynamic comparator, and it yields better offset performance. Moreover, a new fair and comprehensive offset comparison method is also introduced.
Patent foramen ovale (PFO), stroke and pregnancy

Patent foramen ovale (PFO)-related stroke is increasingly recognized as an important etiology of ischemic embolic stroke—accounting for up to 50% of strokes previously considered ‘cryptogenic’ or with an unknown mechanism. As a ‘back door to the brain,’ PFO can allow venous clots to enter arterial circulation via interatrial right-to-left shunting, potentially resulting in ischemic stroke. We observe that clinically, PFO-related stroke affects women of childbearing age, and that pregnancy—owing to major changes in hemocoagulative, hormonal, and cardiovascular parameters—can enhance stroke risks. However, no systematic study has been performed and little is known regarding complications, pregnancy outcomes and treatment for PFO-related stroke during pregnancy. To identify and characterize the complications and clinical outcomes related to PFOs during pregnancy, we performed a literature review and analysis from all reported cases of pregnancy with PFO-related complications in the medical literature from 1970 to 2015. We find that during pregnancy and post-partum, PFO is associated with complications affecting multiple organs, including the brain, heart and lung. The three principal complications reported are stroke, pulmonary emboli and myocardial infarction. In contrast to other pregnancy-related stroke etiologies, which peak during later pregnancy and postpartum, PFO-related stroke peaks during early pregnancy (first and second trimester—60%), and most patients had good neurological outcome (77%). In patients with PFO with recurrent stroke during pregnancy, additional key factors include high-risk PFO morphology (atrial septal aneurysm), larger right-to-left shunt, multiple gestation and concurrent hypercoagulability. Compared to strokes of other etiologies during pregnancy, most PFO stroke patients experienced uneventful delivery (93%) of healthy babies with a good clinical outcome. We conclude with recommended clinical treatment strategies for pregnant patients with PFO suggested by the data from these cases, and the clinical experience of our Cardio-Neurology Clinic.