Miracle-dz/UniFAR-FTUs huggingface dataset:
Revisiting the "radial-drift barrier" of planet formation and its relevance in observed protoplanetary discs

Context. To form metre-sized pre-planetesimals in protoplanetary discs, growing grains have to decouple from the gas before they are accreted onto the central star during their phase of fast radial migration and thus overcome the so-called “radial-drift barrier” (often inaccurately referred to as the “metre-size barrier”). Aims. We predict the outcome of the radial motion of dust grains in protoplanetary discs whose surface density and temperature follow power-law profiles, with exponent p and q respectively. We investigate both the Epstein and the Stokes drag regimes which govern the motion of the dust. Methods. We analytically integrate the equations of motion obtained from perturbation analysis. We compare these results with those from direct numerical integration of the equations of motion. Then, using data from observed discs, we predict the fate of dust grains in real discs. Results. When a dust grain reaches the inner regions of the disc, the acceleration due to the increase of the pressure gradient is counterbalanced by the increase of the gas drag. We find that most grains in the Epstein (resp. the Stokes) regime survive their radial migration if −p + q + 1 ≤ 0 (resp. if q ≤ 2 ). The majority of observed discs satisfies both −p + q + 1 ≤ 0a ndq ≤ 2 : a large fraction of both their small and large grains remain in the disc, for them the radial drift barrier does not exist.
Diversified Expression of NG2/CSPG4 Isoforms in Glioblastoma and Human Foetal Brain Identifies Pericyte Subsets

NG2/CSPG4 is a complex surface-associated proteoglycan (PG) recognized to be a widely expressed membrane component of glioblastoma (WHO grade IV) cells and angiogenic pericytes. To determine the precise expression pattern of NG2/CSPG4 on glioblastoma cells and pericytes, we generated a panel of >60 mouse monoclonal antibodies (mAbs) directed against the ectodomain of human NG2/CSPG4, partially characterized the mAbs, and performed a high-resolution distributional mapping of the PG in human foetal, adult and glioblastoma-affected brains. The reactivity pattern initially observed on reference tumour cell lines indicated that the mAbs recognized 48 immunologically distinct NG2/CSPG4 isoforms, and a total of 14 mAbs was found to identify NG2/CSPG4 isoforms in foetal and neoplastic cerebral sections. These were consistently absent in the adult brain, but exhibited a complementary expression pattern in angiogenic vessels of both tumour and foetal tissues. Considering the extreme pleomorphism of tumour areas, and with the aim of subsequently analysing the distributional pattern of the NG2/CSPG4 isoforms on similar histological vessel typologies, a preliminary study was carried out with endothelial cell and pericyte markers, and with selected vascular basement membrane (VBM) components. On both tumour areas characterized by 'glomeruloid' and 'garland vessels', which showed a remarkably similar cellular and molecular organization, and on developing brain vessels, spatially separated, phenotypically diversified pericyte subsets with a polarized expression of key surface components, including NG2/CSPG4, were disclosed. Interestingly, the majority of the immunolocalized NG2/CSPG4 isoforms present in glioblastoma tissue were present in foetal brain, except for one isoform that seemed to be exclusive of tumour cells, being absent in foetal brain. The results highlight an unprecedented, complex pattern of NG2/CSPG4 isoform expression in foetal and neoplastic CNS, discriminating between phenotype-specific and neoplastic versus non-neoplastic variants of the PG, thus opening up vistas for more selective immunotherapeutic targeting of brain tumours.
Anti-tumor activity of an immunotoxin (TGFα-PE38) delivered by attenuated Salmonella typhimurium

The anticancer strategy underlying the use of immunotoxins is as follows: the cancer-binding domain delivers the toxin to a cancer cell, after which the toxin enters and kills the cell. TGFα-PE38 is an immunotoxin comprising transforming growth factor alpha (TGFα), a natural ligand of epidermal growth factor receptor (EGFR), and a modified Pseudomonas exotoxin A (PE38) lacking N terminal cell-binding domain, a highly potent cytotoxic protein moiety. Tumor cells with high level of EGFR undergo apoptosis upon treatment with TGFα-PE38. However, clinical trials demonstrated that this immunotoxin delivered by an intracerebral infusion technique has only a limited inhibitory effect on intracranial tumors mainly due to inconsistent drug delivery. To circumvent this problem, we turned to tumor-seeking bacterial system. Here, we engineered Salmonella typhimurium to selectively express and release TGFα-PE38. Engineered bacteria were administered to mice implanted with mouse colon or breast tumor cells expressing high level of EGFR. We observed that controlled expression and release of TGFα-PE38 from intra-tumoral Salmonellae by either an engineered phage lysis system or by a bacterial membrane transport signal led to significant inhibition of solid tumor growth. These results demonstrated that delivery by tumor-seeking bacteria would greatly augment efficacy of immunotoxin in cancer therapeutics.
A Review of Emerging Technologies for the Management of Diabetes Mellitus

Objective: High prevalence of diabetes mellitus (DM) along with the poor health outcomes and the escalated costs of treatment and care poses the need to focus on prevention, early detection and improved management of the disease. The aim of this paper is to present and discuss the latest accomplishments in sensors for glucose and lifestyle monitoring along with clinical decision support systems (CDSSs) facilitating self-disease management and supporting healthcare professionals in decision making. Methods: A critical literature review analysis is conducted focusing on advances in: 1) sensors for physiological and lifestyle monitoring, 2) models and molecular biomarkers for predicting the onset and assessing the progress of DM, and 3) modeling and control methods for regulating glucose levels. Results: Glucose and lifestyle sensing technologies are continuously evolving with current research focusing on the development of noninvasive sensors for accurate glucose monitoring. A wide range of modeling, classification, clustering, and control approaches have been deployed for the development of the CDSS for diabetes management. Sophisticated multiscale, multilevel modeling frameworks taking into account information from behavioral down to molecular level are necessary to reveal correlations and patterns indicating the onset and evolution of DM. Conclusion: Integration of data originating from sensor-based systems and electronic health records combined with smart data analytics methods and powerful user centered approaches enable the shift toward preventive, predictive, personalized, and participatory diabetes care. Significance: The potential of sensing and predictive modeling approaches toward improving diabetes management is highlighted and related challenges are identified.
Olive Oil is Made of Olives, Baby Oil is Made for Babies: Interpreting Noun Compounds Using Paraphrases in a Neural Model

Automatic interpretation of the relation between the constituents of a noun compound, e.g. olive oil (source) and baby oil (purpose) is an important task for many NLP applications. Recent approaches are typically based on either noun-compound representations or paraphrases. While the former has initially shown promising results, recent work suggests that the success stems from memorizing single prototypical words for each relation. We explore a neural paraphrasing approach that demonstrates superior performance when such memorization is not possible.
The International Heart Transplant Survival Algorithm (IHTSA): A New Model to Improve Organ Sharing and Survival

Background Heart transplantation is life saving for patients with end-stage heart disease. However, a number of factors influence how well recipients and donor organs tolerate this procedure. The main objective of this study was to develop and validate a flexible risk model for prediction of survival after heart transplantation using the largest transplant registry in the world. Methods and Findings We developed a flexible, non-linear artificial neural networks model (IHTSA) and classification and regression tree to comprehensively evaluate the impact of recipient-donor variables on survival over time. We analyzed 56,625 heart-transplanted adult patients, corresponding to 294,719 patient-years. We compared the discrimination power with three existing scoring models, donor risk index (DRI), risk-stratification score (RSS) and index for mortality prediction after cardiac transplantation (IMPACT). The accuracy of the model was excellent (C-index 0.600 [95% CI: 0.595–0.604]) with predicted versus actual 1-year, 5-year and 10-year survival rates of 83.7% versus 82.6%, 71.4% – 70.8%, and 54.8% – 54.3% in the derivation cohort; 83.7% versus 82.8%, 71.5% – 71.1%, and 54.9% – 53.8% in the internal validation cohort; and 84.5% versus 84.4%, 72.9% – 75.6%, and 57.5% – 57.5% in the external validation cohort. The IHTSA model showed superior or similar discrimination in all of the cohorts. The receiver operating characteristic area under the curve to predict one-year mortality was for the IHTSA: 0.650 (95% CI: 0.640–0.655), DRI 0.56 (95% CI: 0.56–0.57), RSS 0.61 (95% CI: 0.60–0.61), and IMPACT 0.61 (0.61–0.62), respectively. The decision-tree showed that recipients matched to a donor younger than 38 years had additional expected median survival time of 2.8 years. Furthermore, the number of suitable donors could be increased by up to 22%. Conclusions We show that the IHTSA model can be used to predict both short-term and long-term mortality with high accuracy globally. The model also estimates the expected benefit to the individual patient.
Vaccine priming is restricted to draining lymph nodes and controlled by adjuvant-mediated antigen uptake

Vaccine responses are initiated in vaccine-draining lymph nodes and depend on the efficiency by which adjuvants influence antigen uptake. Moving beyond mice for vaccine studies Vaccine enhancement by adjuvants has been known for decades, but the mechanistic differences in how specific adjuvants influence the immune response are just beginning to be elucidated. Liang et al. sought a model that closely mimics humans, so they intramuscularly immunized nonhuman primates with a prototypical HIV antigen in combination with various adjuvants. They then inspected the muscles and lymph nodes to characterize antigen-presenting cells and resulting adaptive immune responses. Their findings should provide valuable information on adjuvant selection for vaccine development in humans. The innate immune mechanisms by which adjuvants enhance the potency and protection of vaccine-induced adaptive immunity are largely unknown. We introduce a model to delineate the steps of how adjuvant-driven innate immune activation leads to priming of vaccine responses using rhesus macaques. Fluorescently labeled HIV-1 envelope glycoprotein (Env) was administered together with the conventional aluminum salt (alum) adjuvant. This was compared to Env given with alum with preabsorbed Toll-like receptor 7 (TLR7) ligand (alum-TLR7) or the emulsion MF59 because they show superiority over alum for qualitatively and quantitatively improved vaccine responses. All adjuvants induced rapid and robust immune cell infiltration to the injection site in the muscle. This resulted in substantial uptake of Env by neutrophils, monocytes, and myeloid and plasmacytoid dendritic cells (DCs) and migration exclusively to the vaccine-draining lymph nodes (LNs). Although less proficient than monocytes and DCs, neutrophils were capable of presenting Env to memory CD4+ T cells. MF59 and alum-TLR7 showed more pronounced cell activation and overall higher numbers of Env+ cells compared to alum. This resulted in priming of higher numbers of Env-specific CD4+ T cells in the vaccine-draining LNs, which directly correlated with increased T follicular helper cell differentiation and germinal center formation. Thus, strong innate immune activation promoting efficient vaccine antigen delivery to infiltrating antigen-presenting cells in draining LNs is an important mechanism by which superior adjuvants enhance vaccine responses.
Development and psychometric validation of the verbal affective memory test

ABSTRACT We here present the development and validation of the Verbal Affective Memory Test-24 (VAMT-24). First, we ensured face validity by selecting 24 words reliably perceived as positive, negative or neutral, respectively, according to healthy Danish adults’ valence ratings of 210 common and non-taboo words. Second, we studied the test's psychometric properties in healthy adults. Finally, we investigated whether individuals diagnosed with Seasonal Affective Disorder (SAD) differed from healthy controls on seasonal changes in affective recall. Recall rates were internally consistent and reliable and converged satisfactorily with established non-affective verbal tests. Immediate recall (IMR) for positive words exceeded IMR for negative words in the healthy sample. Relatedly, individuals with SAD showed a significantly larger decrease in positive recall from summer to winter than healthy controls. Furthermore, larger seasonal decreases in positive recall significantly predicted larger increases in depressive symptoms. Retest reliability was satisfactory, rs ≥ . 77. In conclusion, VAMT-24 is more thoroughly developed and validated than existing verbal affective memory tests and showed satisfactory psychometric properties. VAMT-24 seems especially sensitive to measuring positive verbal recall bias, perhaps due to the application of common, non-taboo words. Based on the psychometric and clinical results, we recommend VAMT-24 for international translations and studies of affective memory.
Coping and resiliency enhancement program (CARE): a pilot study for interpreters in cancer care

There is a growing demand for interpreters in the cancer setting. Interpreters, the link to quality care for limited English proficiency patients, face many psychosocial stressors in their work. This project assessed interpreters' experiences of stress and piloted a resiliency program to help interpreters cope with stressors.
Phone behaviour and its relationship to loneliness in older adults

Objectives: Loneliness and social isolation are two important health outcomes among older adults. Current assessment of these outcomes relies on self-report which is susceptible to bias. This paper reports on the relationship between loneliness and objective measures of isolation using a phone monitoring device. Method: Phone monitors were installed in the homes of 26 independent elderly individuals from the ORCATECH Life Laboratory cohort (age 86 ± 4.5, 88% female) and used to monitor the daily phone usage for an average of 174 days. Loneliness was assessed using the 20-item University of California Los Angeles (UCLA) Loneliness scale. A mixed effects negative binomial regression was used to model the relationship between loneliness and social isolation, as assessed using the total number of calls, controlling for cognitive function, pain, age, gender, and weekday. A secondary analysis examined the differential effect of loneliness on incoming and outgoing calls. Results: The average UCLA Loneliness score was 35.3 ± 7.6, and the median daily number of calls was 4. Loneliness was negatively associated with telephone use (IRR = 0.99, p < 0.05). Daily phone use was also associated with gender (IRR = 2.03, p < 0.001) and cognitive status (IRR = 1.51, p < 0.001). The secondary analysis revealed that loneliness was significantly related to incoming (IRR = 0.98, p < 0.01) but not outgoing calls. Conclusions: These results demonstrate the close relationship between loneliness and social isolation, showing that phone behaviour is associated with emotional state and cognitive function. Because phone behaviour can be monitored unobtrusively, it may be possible to sense loneliness levels in older adults using objective assessments of key aspects of behaviour.
Survey Study of Members of the Canadian Orthopaedic Association on the Natural History and Treatment of Anterior Cruciate Ligament Injury

Objective:To describe current preferences and opinions of members of the Canadian Orthopaedic Association (COA) pertaining to anterior cruciate ligament (ACL) reconstruction. Design:Survey study. Participants:All orthopedic surgeon members of the COA residing in Canada were invited to participate. Main Outcome Measures:The primary measure was a survey completed via an Internet-based survey manager. It was composed of 30 questions on the natural history of ACL-injured knees, and surgical and postsurgical treatment choices. Results:Two hundred eighty-three surgeons (50%) responded to the survey. One hundred forty-four performed ACL reconstruction in the past year. In terms of natural history, the only area of agreement was that hamstring and quadricep strength affects function in ACL-deficient knees (92%). A majority of surgeons indicated preference for hamstring autograft (73%), transtibial versus anteromedial portal for establishment of the femoral tunnel (70% vs 28%), and promotion of full weight bearing and range of motion immediately after surgery (72% and 75%, respectively). The most frequent surgeon-reported complication was tunnel widening (10%). A greater proportion of high-volume surgeons permitted earlier return to sport (P < 0.008). Conclusions:In the rapidly evolving area of ACL reconstruction, no recent surveys of opinions and preferences of Canadian orthopedic surgeons have been published. In addition to providing information from a Canadian perspective, the findings from this study will allow surgeons to evaluate a range of treatment decisions based on the general opinions of their colleagues and also highlights areas of dissimilarity that can be targeted for more extensive research.
Expansion of Sphingosine Kinase and Sphingosine-1-Phosphate Receptor Function in Normal and Cancer Cells: From Membrane Restructuring to Mediation of Estrogen Signaling and Stem Cell Programming

Sphingolipids, sphingolipid metabolizing enzymes, and their receptors network are being recognized as part of the signaling mechanisms, which govern breast cancer cell growth, migration, and survival during chemotherapy treatment. Approximately 70% of breast cancers are estrogen receptor (ER) positive and, thus, rely on estrogen signaling. Estrogen activates an intracellular network composed of many cytoplasmic and nuclear mediators. Some estrogen effects can be mediated by sphingolipids. Estrogen activates sphingosine kinase 1 (SphK1) and amplifies the intracellular concentration of sphingosine-1-phosphate (S1P) in breast cancer cells during stimulation of proliferation and survival. Specifically, Estrogen activates S1P receptors (S1PR) and induces growth factor receptor transactivation. SphK, S1P, and S1PR expression are causally associated with endocrine resistance and progression to advanced tumor stages in ER-positive breast cancers in vivo. Recently, the network of SphK/S1PR was shown to promote the development of ER-negative cancers and breast cancer stem cells, as well as stimulating angiogenesis. Novel findings confirm and broaden our knowledge about the cross-talk between sphingolipids and estrogen network in normal and malignant cells. Current S1PRs therapeutic inhibition was indicated as a promising chemotherapy approach in non-responsive and advanced malignancies. Considering that sphingolipid signaling has a prominent role in terminally differentiated cells, the impact should be considered when designing specific SphK/S1PR inhibitors. This study analyzes the dynamic of the transformation of sphingolipid axis during a transition from normal to pathological condition on the level of the whole organism. The sphingolipid-based mediation and facilitation of global effects of estrogen were critically accented as a bridging mechanism that should be explored in cancer prevention.
Serum IL-1β and IL-17 levels in patients with COPD: associations with clinical parameters

COPD is a chronic airway inflammatory disease characterized mainly by neutrophil airway infiltrations. Interleukin (IL)-1β and IL-17 are the key mediators of neutrophilic airway inflammation in COPD. This study was undertaken to evaluate the serum IL-1β and IL-17 levels and associations between these two key mediators with clinical parameters in COPD patients. Serum samples were collected from 60 COPD subjects during the acute exacerbation of COPD, 60 subjects with stable COPD and 40 healthy control subjects. Commercial enzyme-linked immunosorbent assay kits were used to measure the serum IL-1β and IL-17 concentrations. The association between serum IL-1β and IL-17 with FEV1% predicted, C-reactive protein, neutrophil percentage and smoking status (pack-years) was assessed in the COPD patients. We found that serum IL-1β and IL-17 levels in acute exacerbation of COPD subjects were significantly higher than that in stable COPD or control subjects and were positively correlated to serum C-reactive protein levels, neutrophil % and smoking status (pack-years) but negatively correlated with FEV1% predicted in COPD patients. More importantly, serum IL-1β levels were markedly positively associated with serum IL-17 levels in patients with COPD (P=0.741, P<0.001). In conclusion, elevated serum IL-1β and IL-17 levels may be used as a biomarker for indicating persistent neutrophilic airway inflammation and potential ongoing exacerbation of COPD.
Implementation of a Structured Diabetes Consultation Model to Facilitate a Person-Centered Approach: Results From a Nationwide Dutch Study

OBJECTIVE We assessed both from a patient and provider perspective the usefulness and added value of a consultation model that facilitates person-centered diabetes care. RESEARCH DESIGN AND METHODS The model consists of 1) inventory of disease and patient-related factors; 2) setting personal goals; 3) choosing treatment; and 4) determination of required care. It was implemented in 47 general practices and 6 hospital outpatient clinics. Providers were trained, and patients were recommended to prepare their visit. All filled out a questionnaire after every consultation. Differences between primary and secondary care practices and between physician-led and nurse-led consultations were analyzed. RESULTS Seventy-four physicians and thirty-one nurses participated, reporting on 1,366 consultations with type 2 diabetes patients. According to providers, the model was applicable in 72.4% (nurses 79.3% vs. physicians 68.5%, P < 0.001). Physicians more often had a consultation time <25 min (80.4% vs. 56.9%, P < 0.001). According to providers, two of three patients spoke more than half of the consultation time (outpatient clinics 75.2% vs. general practices 66.6%, P = 0.002; nurses 73.2% vs. physicians 64.4%, P = 0.001). Providers stated that person-related factors often determined treatment goals. Almost all patients (94.4%) reported that they made shared decisions; they felt more involved than before (with physicians 45.1% vs. with nurses 33.6%, P < 0.001) and rated the consultation 8.6 of 10. After physician-led consultations, 52.5% reported that the consultation was better than before (nurse visit 33.7%, P < 0.001). CONCLUSIONS A consultation model to facilitate person-centered care seems well applicable and results in more patient involvement, including shared decision making, and is appreciated by a substantial number of patients.