Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequential Diffusion Spectra as a Tool for Studying Time-Dependent Translational Molecular Dynamics: A Cement Hydration Study

The translational molecular dynamics in porous materials are affected by the presence of the porous structure that presents an obstacle for diffusing molecules in longer time scales, but not as much in shorter time scales. The characteristic time scales have equivalent frequency ranges of molecular dynamics, where longer time scales correspond to lower frequencies while the shorter time scales correspond to higher frequencies of molecular dynamics. In this study, a novel method for direct measurement of diffusion at a given frequency of translational molecular dynamics is exploited to measure the diffusion spectra, i.e., distribution of diffusion in a wide range of frequencies. This method utilizes NMR modulated gradient spin-echo (MGSE) pulse sequence to measure the signal attenuation during the train of spin-echoes formed in the presence of a constant gradient. From attenuation, the diffusion coefficient at the frequency equal to the inverse double inter-echo time is calculated. The method was employed to study the white cement hydration process by the sequential acquisition of the diffusion spectra. The measured spectra were also analyzed by the diffusion spectra model to obtain the time-dependence of the best-fit model parameters. The presented method can also be applied to study other similar systems with the time evolution of porous structure.
Differences in Stability of Viral and Viral-Cellular Fusion Transcripts in HPV-Induced Cervical Cancers

HPV-DNA integration results in dysregulation of viral oncogene expression. Because viral-cellular fusion transcripts inherently lack the viral AU-rich elements of the 3’UTR, they are considered to be more stable than episome-derived transcripts. The aim of this study is to provide formal proof for this assumption by comparing the stability of viral early transcripts derived from episomal and integrated HPV16 DNA, respectively. Full-length cDNA of three fusion transcripts comprising viral and cellular sequences in sense orientation were amplified and cloned into the adeno-viral-vector pAd/CMV/V5-DEST. The most abundant HPV16 oncogene transcript E6*I-E7-E1vE4-E5 with and without 3’UTR, served as reference and control, respectively. Human primary keratinocytes were transduced using high titer virus stocks. qRT-PCR was performed to determine mRNA stability in relation to GAPDH in the presence of actinomycin-D. In four independent transduction experiments, all three viral-cellular fusion transcripts were significantly more stable compared to the episome-derived reference. Among the three viral-cellular fusion transcripts the most stable transcript was devoid of the instability core motif “AUUUA”. Unexpectedly, there was no significant difference in the stability between the episome-derived transcripts either with or without 3’UTR, indicating that the AU-rich elements of the 3’UTR are not contributing to RNA stability. Instead, the three “AUUUA” motifs located in the untranslated region between the viral E4 and E5 genes may be responsible for the instability. This is the first report showing that authentic viral-cellular fusion transcripts are more stable than episome-derived transcripts. The longer half-life of the fusion transcripts may result in increased levels of viral oncoproteins and thereby drive the carcinogenic process.
Understanding Adolescents’ Need Support, Need Satisfaction, and Health-Related Outcomes: A Self-Determination Health Behavior Perspective

School physical education (PE) as an important social context can promote adolescents’ physical health and contributes to their mental health. Guided by the self-determination health behavior model, the study aimed to examine a structural mediation model to investigate the relationships among perceived need support from PE teachers, psychological need satisfaction, and adolescents’ health-related outcomes. Participants were 300 adolescents (Mage = 14.48; 50.3% girls) recruited from five middle schools in Shanghai, China. They completed previously validated questionnaires assessing their perceived need support from PE teachers, psychological need satisfaction, leisure time physical activity (LTPA), and health-related quality of life (HRQOL). The hypothesized model demonstrated a good fit (χ2/df = 3.4, p < 0.01; Root Mean Square Error of Approximation (RMSEA) = 0.09; Standardized Root Mean Square Residual (SRMR) = 0.06; Bentler–Bonett Nonnormed Fit Index (NFI)= 0.92; Comparative Fit Index (CFI) = 0.94; 90% Confidence Interval (CI) [0.07, 0.11]). The findings indicated that three basic psychological needs can be satisfied by perceived need support from PE teachers, and psychological need satisfaction was positively associated with health-related outcomes such as LTPA and HRQOL. In addition, psychological need satisfaction mediated the relationship between perceived need support from PE teachers and health-related outcomes such as LTPA and HRQOL in the present study. The findings supported the theoretical tenets of the self-determination health behavior model and its generalizability among Chinese adolescent students.
Prediction of the Clinical Severity of Progressive Supranuclear Palsy by Diffusion Tensor Imaging

Progressive supranuclear palsy (PSP) is characterized by a rapid and progressive clinical course. A timely and objective image-based evaluation of disease severity before standard clinical assessments might increase the diagnostic confidence of the neurologist. We sought to investigate whether features from diffusion tensor imaging of the entire brain with a machine learning algorithm, rather than a few pathogenically involved regions, may predict the clinical severity of PSP. Fifty-three patients who met the diagnostic criteria for probable PSP were subjected to diffusion tensor imaging. Of them, 15 underwent follow-up imaging. Clinical severity was assessed by the neurological examinations. Mean diffusivity and fractional anisotropy maps were spatially co-registered, normalized, and parcellated into 246 brain regions from the human Brainnetome atlas. The predictors of clinical severity from a stepwise linear regression model were determined after feature reduction by the least absolute shrinkage and selection operator. Performance estimates were obtained using bootstrapping, cross-validation, and through application of the model in the patients who underwent repeated imaging. The algorithm confidently predicts the clinical severity of PSP at the individual level (adjusted R2: 0.739 and 0.892, p < 0.001). The machine learning algorithm for selection of diffusion tensor imaging-based features is accurate in predicting motor subscale of unified Parkinson’s disease rating scale and postural instability and gait disturbance of PSP.
Identification and Characterization of a New Platinum-Induced TP53 Mutation in MDAH Ovarian Cancer Cells

Platinum-based chemotherapy is the therapy of choice for epithelial ovarian cancer (EOC). Acquired resistance to platinum (PT) is a frequent event that leads to disease progression and predicts poor prognosis. To understand possible mechanisms underlying acquired PT-resistance, we have recently generated and characterized three PT-resistant isogenic EOC cell lines. Here, we more deeply characterize several PT-resistant clones derived from MDAH-2774 cells. We show that, in these cells, the increased PT resistance was accompanied by the presence of a subpopulation of multinucleated giant cells. This phenotype was likely due to an altered progression through the M phase of the cell cycle and accompanied by the deregulated expression of genes involved in M phase progression known to be target of mutant TP53. Interestingly, we found that PT-resistant MDAH cells acquired in the TP53 gene a novel secondary mutation (i.e., S185G) that accompanied the R273H typical of MDAH cells. The double p53S185G/R273H mutant increases the resistance to PT in a TP53 null EOC cellular model. Overall, we show how the selective pressure of PT is able to induce additional mutation in an already mutant TP53 gene in EOC and how this event could contribute to the acquisition of novel cellular phenotypes.
An Embedded, Multi-Modal Sensor System for Scalable Robotic and Prosthetic Hand Fingers

Grasping and manipulation with anthropomorphic robotic and prosthetic hands presents a scientific challenge regarding mechanical design, sensor system, and control. Apart from the mechanical design of such hands, embedding sensors needed for closed-loop control of grasping tasks remains a hard problem due to limited space and required high level of integration of different components. In this paper we present a scalable design model of artificial fingers, which combines mechanical design and embedded electronics with a sophisticated multi-modal sensor system consisting of sensors for sensing normal and shear force, distance, acceleration, temperature, and joint angles. The design is fully parametric, allowing automated scaling of the fingers to arbitrary dimensions in the human hand spectrum. To this end, the electronic parts are composed of interchangeable modules that facilitate the mechanical scaling of the fingers and are fully enclosed by the mechanical parts of the finger. The resulting design model allows deriving freely scalable and multimodally sensorised fingers for robotic and prosthetic hands. Four physical demonstrators are assembled and tested to evaluate the approach.
Analysis of the Relationship between the Levels of Androgens and Biochemical Bone Markers in Men Aged 60–75 Years

Introduction: The purpose of this study was to analyze the relationship between the parameters of bone turnover and the levels of hormonal parameters, such as total testosterone (TT), bioavailable and free testosterone (FT), and estradiol (E2) in men. Material and methods: The study group included 63 men with testosterone deficiency syndrome (TDS). The control group consisted of 112 patients without TDS. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of osteocalcin (OC), parathyroid hormone (PTH), E2, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS), insulin (I), Serum CrossLaps (CtX-I), human procollagen I N-terminal peptide (PINP), and TT. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Results: The groups with TSD and without TDS differed in terms of the following parameters: body weight (p = 0.001), BMI (p = 0.003), TT (p = 0.001), FT (p = 0.004), bioavailable testosterone (p = 0.001), E2 (p = 0.003), SHBG (p = 0.003), and PINP (p = 0.004). In the group without TDS, higher PINP levels were accompanied by higher levels of E2 (beta = 0.360, p = 0.002) and TT (beta = 0.389, p = 0.001). In the group without TDS, PINP was positively correlated with E2 (beta = 0.726, p <0.001). Patients with TDS had significantly lower PINP levels (p < 0.004). Conclusions: Analysis of sex hormones and biochemical bone markers in reflecting the quality of the bone tissue in men may suggest a relationship between these parameters. Nevertheless, further research based on a larger sample size is necessary to better describe this relationship.
The Relationship of Early-Life Adversity With Adulthood Weight and Cardiometabolic Health Status in the 1946 National Survey of Health and Development.

OBJECTIVE Evidence linking early-life adversity with an adverse cardiometabolic profile in adulthood is equivocal. This study investigates early-life adversity in relation to weight and cardiometabolic health status at ages 60 to 64 years. METHODS We included 1059 individuals from the 1946 National Survey of Health and Development. Data on adversity between ages 0 to 15 years were used to create a cumulative childhood psychosocial adversity score and a socioeconomic adversity score. Cardiometabolic and weight/height data collected at ages 60 to 64 years were used to create four groups: metabolically healthy normal weight, metabolically unhealthy normal weight, metabolically healthy overweight/obese, and metabolically unhealthy overweight/obese. Associations between the two exposure scores and weight/health status were examined using multinomial logistic regression, with adjustment for sex and age at the outcome visit. RESULTS Sixty-two percent of normal-weight individuals were metabolically healthy, whereas only 34% of overweight/obese individuals were metabolically healthy. In a mutually adjusted model including both exposure scores, a psychosocial score of ≥3 (compared with 0) was associated with increased risk of being metabolically unhealthy (compared with healthy) in both normal-weight adults (relative risk = 2.49; 95% confidence interval = 0.87-7.13) and overweight/obese adults (1.87; 0.96-3.61). However, the socioeconomic adversity score was more strongly related to metabolic health status in overweight/obese adults (1.60; 0.98-2.60) than in normal-weight adults (0.95; 0.46-1.96). CONCLUSIONS Independently of socioeconomic adversity, psychosocial adversity in childhood may be associated with a poor cardiometabolic health profile, in both normal-weight and overweight/obese adults.
Spatial Distribution of Lycorma delicatula (Hemiptera: Fulgoridae) Egg Masses on Tree-of-Heaven, Black Walnut, and Siberian Elm in North America

Abstract The spatial distribution of Lycorma delicatula (White) egg masses on three species of trees were studied in Pennsylvania. Five tree-of-heaven, five black walnut, and one Siberian elm trees were felled in early spring 2019 to sample for egg masses. Each egg mass was marked for its cardinal direction, position in the tree, height above ground, and spread from the bole. A total of 214 egg masses were found on tree-of-heaven and black walnut, with 38.3, 29.4, 22.0, and 10.3% on the north, west, south, and east quadrant, respectively. No significant difference in cardinal direction was found for either species. Equal number of egg masses were found on branches and boles on tree-of-heaven. However, significantly more egg masses were found on branches (96.5%) compared to boles (3.5%) on black walnut. Egg masses were laid at 0.30–12.92 and 0.70–17.00 m above ground, with most on boles/higher branches and middle/lower branches for tree-of-heaven and black walnut, respectively. Significant effect of height above ground was found for black walnut, with more egg masses found at 4–6 m compared to 0–2, 12–14, and 14–16 m. Significant effect of spread from the bole was found for tree-of-heaven, with more egg masses found at 0–2 m compared to 2–4 and 4–6 m. The 24 egg masses on the Siberian elm were mostly found on east quadrant branches 0–2 m above ground and within 2 m from the bole. Variation in tree branching patterns and difference in egg mass distribution of other forest pests were discussed.
Pediatric Safety of Polysorbates in Drug Formulations

Polysorbates 20 and 80 are the most frequently used excipients in biotherapeutics, the safety data for which have been well documented in adults. The polysorbate content in therapeutic formulations that are administered to children, however, has been less clearly regulated or defined with regard to safety. In pediatric patients, excessive amounts of polysorbate in biotherapeutics have been linked to hypersensitivity and other toxicity-related effects. To determine safe levels of polysorbates for young patients, we have developed the progressive pediatric safety factor (PPSF), an age- and weight-based tool that estimates the amount of parenterally administered polysorbates 20 and 80 in formulations that will avoid excipient-related adverse events. Compared with existing modalities for calculating maximum acceptable doses of excipients for initial clinical trials in pediatrics, the PPSF is far more conservative, thus constituting an added margin of safety for excipient exposure in the most sensitive subpopulations—i.e., neonates and infants. Further, the PPSF may be applied to any relevant excipient, aiding pharmaceutical developers and regulatory authorities in conservatively estimating the safety assessment of a biotherapeutic’s formulation, based on excipient levels.
Model-Based Iterative Reconstruction for Propagation-Based Phase-Contrast X-Ray CT including Models for the Source and the Detector

Propagation-based phase-contrast X-ray computed tomography is a valuable tool for high-resolution visualization of biological samples, giving distinct improvements in terms of contrast and dose requirements compared to conventional attenuation-based computed tomography. Due to its ease of implementation and advances in laboratory X-ray sources, this imaging technique is increasingly being transferred from synchrotron facilities to laboratory environments. This however poses additional challenges, such as the limited spatial coherence and flux of laboratory sources, resulting in worse resolution and higher noise levels. Here we extend a previously developed iterative reconstruction algorithm for this imaging technique to include models for the reduced spatial coherence and the signal spreading of efficient scintillator-based detectors directly into the physical forward model. Furthermore, we employ a noise model which accounts for the full covariance statistics of the image formation process. In addition, we extend the model describing the interference effects such that it now matches the formalism of the widely-used single-material phase-retrieval algorithm, which is based on the sample-homogeneity assumption. We perform a simulation study as well as an experimental study at a laboratory inverse Compton source and compare our approach to the conventional analytical approaches. We find that the modeling of the source and the detector inside the physical forward model can tremendously improve the resolution at matched noise levels and that the modeling of the covariance statistics reduces overshoots (i.e. incorrect increase / decrease in sample properties) at the sample edges significantly.
Gene Expression Alterations during Development of Castration-Resistant Prostate Cancer Are Detected in Circulating Tumor Cells

Development of castration-resistant prostate cancer (CRPC) is associated with alterations in gene expression involved in steroidogenesis and androgen signaling. This study investigates whether gene expression changes related to CRPC development can be identified in circulating tumor cells (CTCs). Gene expression in paired CTC samples from 29 patients, before androgen deprivation therapy (ADT) and at CRPC relapse, was compared using a panel including 47 genes related to prostate cancer progression on a qPCR platform. Fourteen genes displayed significantly changed gene expression in CTCs at CRPC relapse compared to before start of ADT. The genes with increased expression at CRPC relapse were related to steroidogenesis, AR-signaling, and anti-apoptosis. In contrast, expression of prostate markers was downregulated at CRPC. We also show that midkine (MDK) expression in CTCs from metastatic hormone-sensitive prostate cancer (mHSPC) was associated to short cancer-specific survival (CSS). In conclusion, this study shows that gene expression patterns in CTCs reflect the development of CRPC, and that MDK expression levels in CTCs are prognostic for cancer-specific survival in mHSPC. This study emphasizes the role of CTCs in exploring mechanisms of therapy resistance, as well as a promising biomarker for prognostic and treatment-predictive purposes in advanced mHSPC.
Effects of MYBPC3 loss of function mutations preceding hypertrophic cardiomyopathy.

Mutations in cardiac myosin binding protein (MyBP-C, encoded by MYBPC3) are the most common cause of hypertrophic cardiomyopathy (HCM). Most MYBPC3 mutations result in premature termination codons (PTCs) that cause RNA degradation and a reduction of MyBP-C in HCM patient hearts. However, a reduction in MyBP-C has not been consistently observed in MYBPC3 mutant induced pluripotent stell cell cardiomyocytes (iPSCMs). To determine early MYBPC3 mutation effects, we utilized both patient and genome-engineered iPSCMs. iPSCMs with frameshift mutations were compared to iPSCMs with MYBPC3 promoter and translational start site deletions, revealing that allelic loss of function is the primary inciting consequence of mutations that cause PTCs. Despite a reduction in wild type mRNA in all heterozygous iPSCMs, no reduction in MyBP-C protein was observed, indicating protein-level compensation through a previously uncharacterized mechanism. Although homozygous mutant iPSCMs exhibited contractile dysregulation, heterozygous mutant iPSCMs had normal contractile function in the context of compensated MyBP-C levels. Agnostic RNA-seq analysis revealed differential expression in protein chaperone genes as the only dysregulated gene set. To determine how MYBPC3 mutant iPSCMs achieve compensated MyBP-C levels, sarcomeric protein synthesis and degradation were measured with stable isotope-labeling. Heterozygous mutant iPSCMs showed reduced MyBP-C synthesis rates but with a corresponding reduction in MyBP-C degradation. These findings indicate that cardiomyocytes have an innate capacity to attain normal MyBP-C stoichiometry despite MYBPC3 allelic loss of function due to truncating mutations. Modulating MyBP-C degradation to maintain MyBP-C protein levels may be a novel treatment approach upstream of contractile dysfunction for HCM patients.
Redefining the core values and tasks of GPs in the Netherlands (Woudschoten 2019).

In the last decade GPs in the Netherlands have been confronted with an increasing workload and administrative pressure, as is the case in the UK.1–3 Traditionally, general practice holds a firm position in the Dutch healthcare system, addressing 90% of healthcare problems using only 3% of the national healthcare budget. The accessibility, the broad expertise of GPs, and the longitudinal care are highly appreciated by patients, and both government and health insurance companies consider general practice essential for sustainable and affordable health care.4 However, major healthcare system changes in the last years have led to a growing demand for GPs’ services, as a large part of the care traditionally delivered by hospitals and outpatient clinics, such as diabetes care, chronic obstructive pulmonary disease, and heart failure care, is being transferred to general practice.5 Preventive tasks, for example, cardiovascular risk management and lifestyle coaching, as well as proactive care for the old and mental health care, have been added to the workload of general practice. Based on data from 34 countries gathered in the Quality and costs of primary care in Europe (QUALICOPC) project, Schafer et al showed that the workload and diversity of duties of Dutch GPs are among the highest.6,7 In addition, the workforce is changing, with a new generation of GPs trying to restrict their working hours, pursuing a better balance between professional and private life. One of the tasks most jeopardised is the out-of-hours GP emergency service in which all practices participate. Because of the increasing workload during office hours, many GPs are reluctant to participate in this emergency service, jeopardising the sustainability of the out-of-hours service. Although every GP in the Netherlands has to do a minimal number of shifts for the GP registration, this is not enough …