DSM-5 Autism Spectrum Disorder (ASD) comprises a set of neurodevelopmental disorders characterized by deficits in social communication and interaction and repetitive behaviors or restricted ...interests, and may both affect and be affected by multiple cognitive mechanisms. This study attempts to identify and characterize cognitive subtypes within the ASD population using our Functional Random Forest (FRF) machine learning classification model. This model trained a traditional random forest model on measures from seven tasks that reflect multiple levels of information processing. 47 ASD diagnosed and 58 typically developing (TD) children between the ages of 9 and 13 participated in this study. Our RF model was 72.7% accurate, with 80.7% specificity and 63.1% sensitivity. Using the random forest model, the FRF then measures the proximity of each subject to every other subject, generating a distance matrix between participants. This matrix is then used in a community detection algorithm to identify subgroups within the ASD and TD groups, and revealed 3 ASD and 4 TD putative subgroups with unique behavioral profiles. We then examined differences in functional brain systems between diagnostic groups and putative subgroups using resting-state functional connectivity magnetic resonance imaging (rsfcMRI). Chi-square tests revealed a significantly greater number of between group differences (p < .05) within the cingulo-opercular, visual, and default systems as well as differences in inter-system connections in the somato-motor, dorsal attention, and subcortical systems. Many of these differences were primarily driven by specific subgroups suggesting that our method could potentially parse the variation in brain mechanisms affected by ASD.
Objectives
Sjögren’s disease (SjD) patients use various interventions to relief their oral dryness. However, the use and efficacy of these interventions have only partially been evaluated. The ...present study aims to investigate whether there is an association between the perceived oral dryness and discomfort of SjD patients and their use of specific interventions.
Materials and methods
A cross-sectional study was performed among SjD patients, who completed several questionnaires to assess the severity of their oral dryness and an inventory of dry-mouth interventions. The perceived efficacy of each intervention was reported on a 5-point Likert-scale.
Results
The questionnaires were returned by 92 SjD patients. For relief of oral dryness, they mostly used “eating fruit”, “drinking tea”, “moistening the lips”, “drinking water, and “drinking small volumes” (> 50%). Three interventions had a frequency of use ranging from 2–6 times/day, whereas, “drinking water” and “drinking small volumes” showed higher frequencies (> 14). The highest overall efficacy (≥ 3.5) was reported for “chewing gum” and “using a mouth gel”. Furthermore, various dry-mouth interventions showed significant associations with oral dryness scores and/or patients’ discomfort. For example, “drinking small volumes” and “using XyliMelts” were associated with the Bother Index score.
Conclusion
Great variation was found in the use of dry-mouth interventions by the participants and the severity of the oral dryness and/or patients’ discomfort seemed to affect their choice of intervention. Notably, the mostly used interventions did not show the highest reported efficacy.
Clinical relevance
These findings might help SjD patients and clinicians in their choice of effective dry-mouth interventions.
Highlights ► Real Time Medication Monitoring provides detailed and accurate data on patients’ medication use. ► SMS reminders sent only if patients forget medication improve adherence to oral ...antidiabetics. ► SMS reminders are appreciated by patients. ► Real Time Medication Monitoring with SMS reminders provide opportunities for other patient groups as well.
Abstract
Neutrinos offer a unique window to the distant, high-energy
universe. Several next-generation instruments are being designed and
proposed to characterize the flux of TeV–EeV neutrinos. The
...projected physics reach of the detectors is often quantified with
simulation studies. However, a complete Monte Carlo estimate of
detector performance is costly from a computational perspective,
restricting the number of detector configurations considered when
designing the instruments. In this paper, we present a new
Python-based software framework,
toise
, which forecasts the
performance of a high-energy neutrino detector using
parameterizations of the detector performance, such as the effective
areas, angular and energy resolutions, etc. The framework can be
used to forecast performance of a variety of physics analyses,
including sensitivities to diffuse fluxes of neutrinos and
sensitivity to both transient and steady state point sources. This
parameterized approach reduces the need for extensive simulation
studies in order to estimate detector performance, and allows the
user to study the influence of single performance metrics, like the
angular resolution, in isolation. The framework is designed to
allow for multiple detector components, each with different
responses and exposure times, and supports paramterization of both
optical- and radio-Cherenkov (Askaryan) neutrino telescopes. In the
paper, we describe the mathematical concepts behind
toise
and introduce the reader to the use of the framework.
During myofiber regeneration, myoblasts are continuously subjected to shear stress. It is currently not known whether shear stress affects the regenerative capacity of myoblasts when extracellular ...matrix (ECM) stiffness increases (e.g. upon aging). Therefore, we aimed to assess (1) whether matrix stiffness and pulsating fluid shear stress affect myoblast proliferation and/or expression of differentiation-associated genes in myoblasts, and (2) whether matrix stiffness modulates the mechanoresponse of myoblasts to pulsating fluid shear stress. Myoblasts were seeded on matrigel-coated polyacrylamide gel matrices of varying stiffness, mimicking young (“soft”, 0.5 kPa) and old ECM (“stiff”, 20 kPa), as well as on matrigel-coated glass matrices with very high stiffness (40 ϺPa), and subjected to 1 h pulsating fluid shear stress (3 Pa/s or 4 Pa/s, 1 Hz). We found enhanced proliferation of myoblasts on stiff matrices, but reduced differentiation compared to myoblasts on soft matrices. Pulsating fluid shear stress significantly upregulated gene expression of proliferation-associated genes
C-fos
and
Il-6
, as well as expression of cytoskeletal α-actin in myoblasts seeded on glass. In contrast, pulsating fluid shear stress significantly downregulated gene expression of α-actin and Myogenin in myoblasts seeded on soft matrices. In conclusion, these results suggest that age and disease-associated increased ECM stiffness may contribute to declined regenerative capacity of myoblasts, by reducing their capacity to differentiate into new muscular tissue, at least in the absence of mechanical stimulation.
Context. Both multi-messenger astronomy and new high-throughput wide-field surveys require flexible tools for the selection and analysis of astrophysical transients. Aims. Here we introduce the alert ...management, photometry, and evaluation of light curves (AMPEL) system, an analysis framework designed for high-throughput surveys and suited for streamed data. AMPEL combines the functionality of an alert broker with a generic framework capable of hosting user-contributed code; it encourages provenance and keeps track of the varying information states that a transient displays. The latter concept includes information gathered over time and data policies such as access or calibration levels. Methods. We describe a novel ongoing real-time multi-messenger analysis using AMPEL to combine IceCube neutrino data with the alert streams of the Zwicky Transient Facility (ZTF). We also reprocess the first four months of ZTF public alerts, and compare the yields of more than 200 different transient selection functions to quantify efficiencies for selecting Type Ia supernovae that were reported to the Transient Name Server (TNS). Results. We highlight three channels suitable for (1) the collection of a complete sample of extragalactic transients, (2) immediate follow-up of nearby transients, and (3) follow-up campaigns targeting young, extragalactic transients. We confirm ZTF completeness in that all TNS supernovae positioned on active CCD regions were detected. Conclusions. AMPEL can assist in filtering transients in real time, running alert reaction simulations, the reprocessing of full datasets as well as in the final scientific analysis of transient data. This is made possible by a novel way of capturing transient information through sequences of evolving states, and interfaces that allow new code to be natively applied to a full stream of alerts. This text also introduces a method by which users can design their own channels for inclusion in the AMPEL live instance that parses the ZTF stream and the real-time submission of high-quality extragalactic supernova candidates to the TNS.
Once prostate cancer cells metastasize to bone, they perceive approximately 2 kPa compression. We hypothesize that 2 kPa compression stimulates the epithelial-to-mesenchymal transition (EMT) of ...prostate cancer cells and alters their production of paracrine signals to affect osteoclast and osteoblast behavior. Human DU145 prostate cancer cells were subjected to 2 kPa compression for 2 days. Compression decreased expression of 2 epithelial genes, 5 out of 13 mesenchymal genes, and increased 2 mesenchymal genes by DU145 cells, as quantified by qPCR. Conditioned medium (CM) of DU145 cells was added to human monocytes that were stimulated to differentiate into osteoclasts for 21 days. CM from compressed DU145 cells decreased osteoclast resorptive activity by 38% but did not affect osteoclast size and number compared to CM from non-compressed cells. CM was also added to human adipose stromal cells, grown in osteogenic medium. CM of compressed DU145 cells increased bone nodule production (Alizarin Red) by osteoblasts from four out of six donors. Compression did not affect IL6 or TNF-α production by PC DU145 cells. Our data suggest that compression affects EMT-related gene expression in DU145 cells, and alters their production of paracrine signals to decrease osteoclast resorptive activity while increasing mineralization by osteoblasts is donor dependent. This observation gives further insight in the altered behavior of PC cells upon mechanical stimuli, which could provide novel leads for therapies, preventing bone metastases.
Aims
To investigate short‐ and long‐term effects of real‐time monitoring medication use combined with short message service (SMS) reminders for missed doses on refill adherence to oral anti‐diabetic ...medication.
Methods
A randomized controlled trial with two intervention groups and one control group involving 161 participants with Type 2 diabetes with suboptimal adherence. For 6 months, participants in the SMS group (n = 56) were monitored and received SMS reminders if they missed their medication. Participants in the non‐SMS group (n = 48) were only monitored. The control group (n = 57) was not exposed to any intervention. Primary outcome measure was refill adherence to oral anti‐diabetic medication. Multi‐level regression analyses were performed to examine intervention effects on adherence between and within groups after 1 and 2 years of follow‐up.
Results
At baseline, mean refill adherence was comparable between the groups. After 1 year, adherence in the SMS group was significantly higher than in the control group (79.5% vs. 64.5%; P < 0.001) and showed a significant improvement from baseline (+16.3%; P < 0.001). Mean adherence in the non‐SMS group reached 73.1% (+7.3%; P < 0.05), but did not differ from the control group (P = 0.06). After 2 years, the improved adherence in the SMS group persisted and remained significantly higher than in the control group (80.4% vs. 68.4%; P < .01), contrary to the non‐SMS group whose adherence approached baseline level again (65.5%).
Conclusions
This study shows the long‐term effectiveness of real‐time medication monitoring combined with SMS reminders in improving refill adherence. This new reminder system can strengthen the self‐management of people with diabetes.
What's new?
The innovative real‐time medication monitoring system evaluated in this study is the first to provide the opportunity to intervene only when patients forget to take their medication.
This study showed that receiving short message service (SMS) reminders only when a dose is missed results in a higher refill adherence, and is the first to demonstrate long‐term effectiveness of electronic reminders on adherence.
The real‐time medication monitoring reminder system can especially provide support for people who have problems taking their medication because of forgetfulness.
This system can also strengthen a person's self‐management, as medication management is an important aspect of self‐management.
Standard cell cultures may not predict the proliferation and differentiation potential of human mesenchymal stromal cells (MSCs) after seeding on a scaffold and implanting this construct in a bone ...defect. We aimed to develop a more biologically relevant in vitro 3D-model for preclinical studies on the bone regeneration potential of MSCs. Human adipose tissue-derived mesenchymal stromal cells (hASCs; five donors) were seeded on biphasic calcium phosphate (BCP) granules and cultured under hypoxia (1% O
) for 14 days with pro-inflammatory TNFα, IL4, IL6, and IL17F (10 mg/mL each) added during the first three days, simulating the early stages of repair (bone construct model). Alternatively, hASCs were cultured on plastic, under 20% O
and without cytokines for 14 days (standard cell culture). After two days, the bone construct model decreased total DNA (3.9-fold),
(9.8-fold), and
expression (19.6-fold) and metabolic activity (4.6-fold), but increased
expression (38.6-fold) in hASCs compared to standard cultures. After seven days, the bone construct model decreased
expression (64-fold) and metabolic activity (2.3-fold), but increased
(54.5-fold) and
expression (5.7-fold) in hASCs compared to standard cultures. The effect of the bone construct model on hASC proliferation and metabolic activity could be largely mimicked by culturing on BCP alone (20% O
, no cytokines). The effect of the bone construct model on
expression could be mimicked by culturing hASCs under hypoxia alone (plastic, no cytokines). In conclusion, we developed a new, biologically relevant in vitro 3D-model to study the bone regeneration potential of MSCs. Our model is likely more suitable for the screening of novel factors to enhance bone regeneration than standard cell cultures.
Once prostate cancer (PC) metastasizes towards bone the 5-year survival rates drop with 70%, but it is largely unknown why. Bone is continuously mechanically loaded, which likely modulates the ...paracrine signaling from osteocytes towards PC cells to affect tumor behavior. We hypothesize that shear loaded osteocytes affect PC cell proliferation, invasion and epithelial and mesenchymal-related gene and protein expression. We cultured human DU145 cells, a commonly used cell line for prostate cancer metastases, in the conditioned medium (CM) from shear loaded or unloaded human osteocyte-like-cells (OCYLCs) for 1 and 3 days and assessed their number by staining nuclei with DAPI, their invasion by performing an invasion assay, and epithelial-to-mesenchymal (EMT)-related gene and protein expression by qPCR and immunocytochemistry. CM of shear loaded OCYLCs did not affect DU145 cell number compared to CM of static cultured OCYLCs, but decreased their invasion 1.34-fold. CM of shear loaded OCYLCs enhanced expression of epithelial genes: SYND1 and CDH1 after day 1, while it also enhanced CDH1 after day 3. CM of shear loaded osteocytes enhanced mesenchymal genes: VMN, Snail and MIP2 after day 1, while it decreased expression of mesenchymal CYR61 after day 3. We conclude that CM of shear loaded OCYLCs does not affect DU145 cell proliferation, but decreases their invasion, and differentially affects their EMT-related gene expression. Identifying paracrine signals from shear loaded osteocytes that decrease PC cell invasion may provide novel leads in developing treatments for bone metastases from PC.
•Shear loaded osteocyte-like-cells decrease prostate cancer cell invasion.•Shear loaded osteocyte-like-cells affect EMT-related gene expression in prostate cancer cells.•Shear loaded osteocyte-like-cells do not affect prostate cancer cell proliferation.
PDF
