Miracle-dz/UniFAR-FTUs huggingface dataset:
Repairing Volumetric Muscle Loss in the Ovine Peroneus Tertius Following a 3-Month Recovery.

Much effort has been made to fabricate engineered tissues on a scale that is clinically relevant to humans; however, scale-up remains one of the most significant technological challenges of tissue engineering to date. To address this limitation, our laboratory has developed tissue-engineered skeletal muscle units (SMUs) and engineered neural conduits (ENCs), and modularly scaled them to clinically relevant sizes for the treatment of volumetric muscle loss (VML). The goal of this study was to evaluate the SMUs and ENCs in vitro, and to test the efficacy of our SMUs and ENCs in restoring muscle function in a clinically relevant large animal (sheep) model. The animals received a 30% VML injury to the peroneus tertius (PT) muscle and were allowed to recover for 3 months. The animals were divided into three experimental groups: VML injury without a repair (VML only), repair with an SMU (VML+SMU), or repair with an SMU and ENC (VML+SMU+ENC). We evaluated the SMUs prior to implantation and found that our single scaled-up scaled SMUs were characterized by the presence of contracting myotubes, linearly aligned extracellular matrix proteins, and Pax7+ satellite cells. Three months after implantation, we found that the repair groups (VML+SMU and VML+SMU+ENC) had restored muscle mass and tetanic force production to a level that was statistically indistinguishable from the uninjured contralateral muscle after 3 months in vivo. Furthermore, we demonstrated the ability of our ENCs to effectively bridge the gap between native nerve and the repair site by eliciting a muscle contraction through direct electrical stimulation of the re-routed nerve.
Determination of norfloxacin residues in foods by exploiting the coffee-ring effect and paper-based microfluidics device coupling with smartphone-based detection.

By utilizing the coffee-ring effect and microfluidic paper-based analytical devices (µPADs), this study improved the sensitivity of the determination of norfloxacin in four different food matrices. Micro-PADs in this study were fabricated by designing and embedding wax channels onto cellulose-based filter paper through printing and subjecting the paper to heat to allow the wax to penetrate the paper. Determination of norfloxacin concentration in food samples was achieved by monitoring the colorimetric reaction that occurred between norfloxacin and the added iron (III) nitrate nonahydrate in 5 mM ammonia in each reaction chamber. A transition metal hydroxide was formed through this reaction that resulted in the formation of a solid precipitate to enable the antibiotic to bind to the iron molecule via coordination chemistry. This metal ion-antibiotic complex generated a visible color change. Following the colorimetric reaction, images were taken and subsequently analyzed via ImageJ to determine the relative pixel intensity that was used to infer norfloxacin concentration. The analytical sensitivity of this device was determined to be as low as 50 ppm when analyzing the inner-ring reaction, and as low as 5 ppm when analyzing the outer coffee ring thereby allowing for an alternative cheaper, faster, and more user-friendly method to detect norfloxacin than the conventional methods. PRACTICAL APPLICATION: This novel paper-based microfluidic device can achieve the detection of antibiotic residues in agrifoods in a faster, cheaper, and more user-friendly manner.
Arrhythmia mutations in calmodulin can disrupt cooperativity of Ca2+ binding and cause misfolding

Mutations in the calmodulin protein (CaM) are associated with arrhythmia syndromes. This study focuses on understanding the structural characteristics of CaM disease mutants and their interactions with the voltage‐gated calcium channel CaV1.2. Arrhythmia mutations in CaM can lead to loss of Ca2+ binding, uncoupling of Ca2+ binding cooperativity, misfolding of the EF‐hands and altered affinity for the calcium channel. These results help us to understand how different CaM mutants have distinct effects on structure and interactions with protein targets to cause disease.
C‐terminal residues of activated protein C light chain contribute to its anticoagulant and cytoprotective activities

Activated protein C (APC) is an important homeostatic blood coagulation protease that conveys anticoagulant and cytoprotective activities. Proteolytic inactivation of factors Va and VIIIa facilitated by cofactor protein S is responsible for APC's anticoagulant effects, whereas cytoprotective effects of APC involve primarily the endothelial protein C receptor (EPCR), protease activated receptor (PAR)1 and PAR3.
Experimental and Numerical Study of Electroporation Induced by Long Monopolar and Short Bipolar Pulses on Realistic 3D Irregularly Shaped Cells

In this article, the reversible electroporation induced by rectangular long unipolar and short bipolar voltage pulses on 3D cells is studied. The cell geometry was reconstructed from 3D images of real cells obtained using the confocal microscopy technique. A numerical model based on the Maxwell and the asymptotic Smoluchowski equations has been developed to calculate the induced transmembrane voltage and pore density on the plasma membrane of real cells exposed to the pulsed electric field. Moreover, in the case of the high-frequency pulses, the dielectric dispersion of plasma membranes has been taken into account using the second-order Debye-based relationship. Several numerical simulations were performed and we obtained suitable agreement between the numerical and experimental results.
Improved work environments and staffing lead to less missed nursing care: A panel study.

AIM To document how changes in the hospital work environment and nurse staffing over time are associated with changes in missed nursing care. BACKGROUND Missed nursing care is considered an indicator of poorer care quality and has been associated with worse patient care experiences and health outcomes. Several systematic reviews of cross-sectional studies report that nurses in hospitals with supportive work environments and higher staffing miss less care. Causal evidence demonstrating these relationships is needed. METHOD This panel study utilized secondary data from 23,650 nurses surveyed in 2006 and 14,935 surveyed in 2016 in 458 hospitals from a four-state survey of random samples of licensed nurses. RESULTS Over the ten-year period, most hospitals exhibited improved work environments, better nurse staffing, and more missed care. In hospitals with improved work environments or nurse staffing, the prevalence and frequency of missed care decreased significantly. The effect on missed care of changes in the work environment was greater than that of nurse staffing. CONCLUSIONS Changes in the hospital work environment and staffing influence missed care. IMPLICATIONS FOR NURSING MANAGEMENT Modifications in the work environment and staffing are strategies to mitigate care compromise. Nurse managers should investigate work settings in order to identify weaknesses.
Declining Use of Primary Care Among Commercially Insured Adults in the United States, 2008–2016

Background Primary care is known to improve outcomes and lower health care costs, prompting recent U.S. policy efforts to expand its role. Nonetheless, there is early evidence of a decline in per capita primary care visit rates, and little is understood about what is contributing to the decline. Objective To describe primary care provider (PCP) visit trends among adults enrolled with a large, national, commercial insurer and assess factors underlying a potential decline in PCP visits. Design Descriptive repeated cross-sectional study using 100% deidentified claims data from the insurer, 2008-2016. A 5% claims sample was used for Poisson regression models to quantify visit trends. Setting National, population-based. Participants Adult health plan members aged 18 to 64 years. Measurements PCP visit rates per 100 member-years. Results In total, 142 million primary care visits among 94 million member-years were examined. Visits to PCPs declined by 24.2%, from 169.5 to 134.3 visits per 100 member-years, while the proportion of adults with no PCP visits in a given year rose from 38.1% to 46.4%. Rates of visits addressing low-acuity conditions decreased by 47.7% (95% CI, -48.1% to -47.3%). The decline was largest among the youngest adults (-27.6% [CI, -28.2% to -27.1%]), those without chronic conditions (-26.4% [CI, -26.7% to -26.1%]), and those living in the lowest-income areas (-31.4% [CI, -31.8% to -30.9%]). Out-of-pocket cost per problem-based visit rose by $9.4 (31.5%). Visit rates to specialists remained stable (-0.08% [CI, -0.56% to 0.40%]), and visits to alternative venues, such as urgent care clinics, increased by 46.9% (CI, 45.8% to 48.1%). Limitation Data were limited to a single commercial insurer and did not capture nonbilled clinician-patient interactions. Conclusion Commercially insured adults have been visiting PCPs less often, and nearly one half had no PCP visits in a given year by 2016. Our results suggest that this decline may be explained by decreased real or perceived visit needs, financial deterrents, and use of alternative sources of care. Primary Funding Source None.
Association of coincident self-reported mental health problems and alcohol intake with all-cause and cardiovascular disease mortality: A Norwegian pooled population analysis

Background The disease burden attributable to mental health problems and to excess or harmful alcohol use is considerable. Despite a strong relationship between these 2 important factors in population health, there are few studies quantifying the mortality risk associated with their co-occurrence in the general population. The aim of this study was therefore to investigate cardiovascular disease (CVD) and all-cause mortality according to self-reported mental health problems and alcohol intake in the general population. Methods and findings We followed 243,372 participants in Norwegian health surveys (1994–2002) through 2014 for all-cause and CVD mortality by data linkage to national registries. The mean (SD) age at the time of participation in the survey was 43.9 (10.6) years, and 47.8% were men. During a mean (SD) follow-up period of 16.7 (3.2) years, 6,587 participants died from CVD, and 21,376 died from all causes. Cox models estimated hazard ratios (HRs) with 95% CIs according to a mental health index (low, 1.00–1.50; high, 2.01–4.00; low score is favourable) based on the General Health Questionnaire and the Hopkins Symptom Checklist, and according to self-reported alcohol intake (low, <2; light, 2–11.99; moderate, 12–23.99; high, ≥24 grams/day). HRs were adjusted for age, sex, educational level, marital status, and CVD risk factors. Compared to a reference group with low mental health index score and low alcohol intake, HRs (95% CIs) for all-cause mortality were 0.93 (0.89, 0.97; p = 0.001), 1.00 (0.92, 1.09; p = 0.926), and 1.14 (0.96, 1.35; p = 0.119) for low index score combined with light, moderate, and high alcohol intake, respectively. HRs (95% CIs) were 1.22 (1.14, 1.31; p < 0.001), 1.24 (1.15, 1.33; p < 0.001), 1.43 (1.23, 1.66; p < 0.001), and 2.29 (1.87, 2.80; p < 0.001) for high index score combined with low, light, moderate, and high alcohol intake, respectively. For CVD mortality, HRs (95% CIs) were 0.93 (0.86, 1.00; p = 0.058), 0.90 (0.76, 1.07; p = 0.225), and 0.95 (0.67, 1.33; p = 0.760) for a low index score combined with light, moderate, and high alcohol intake, respectively, and 1.11 (0.98, 1.25; p = 0.102), 0.97 (0.83, 1.13; p = 0.689), 1.01 (0.71, 1.44; p = 0.956), and 1.78 (1.14, 2.78; p = 0.011) for high index score combined with low, light, moderate, and high alcohol intake, respectively. HRs for the combination of a high index score and high alcohol intake (HRs: 2.29 for all-cause and 1.78 for CVD mortality) were 64% (95% CI 53%, 74%; p < 0.001) and 69% (95% CI 42%, 97%; p < 0.001) higher than expected for all-cause mortality and CVD mortality, respectively, under the assumption of a multiplicative interaction structure. A limitation of our study is that the findings were based on average reported intake of alcohol without accounting for the drinking pattern. Conclusions In the general population, the mortality rates associated with more mental health problems and a high alcohol intake were increased when the risk factors occurred together.
Mutational analysis of genes with ureteric progenitor cell‐specific expression in branching morphogenesis of the mouse kidney

Ureteric progenitor cells (UPCs) within the branch tips of the arborizing ureteric epithelium of the kidney's developing collecting system establish the shape and cellular organization of the collecting network, and drive the nephrogenic program through their interactions with nephron progenitor cells. In a previous study, expression screening identified a cohort of genes showing UPC‐enriched expression including D17H6S56E‐5, Hs3st3a1, Hs3st3b1, and Tmem59l. Each of these is also enriched in branch tips of assembling airways of the developing lungs. Here, we used Crispr‐CAS9 directed gene editing to mutate each of these targets to address their potential role(s) in UPC programs.
Electrophoretic Deposition of Layer-by-Layer Unsheathed Carbon Nanotubes—A Step Towards Steerable Surface Roughness and Wettability

It is well known that carbon nanotube (CNT) oxidation (usually with concentrated HNO3) is a major step before the electrophoretic deposition (EPD). However, the recent discovery of the “onion effect” proves that multiwalled carbon nanotubes are not only oxidized, but a simultaneous unsheathing process occurs. We present the first report concerning the influence of unsheathing on the properties of the thus-formed CNT surface layer. In our study we examine how the process of gradual oxidation/unsheathing of a series of multiwalled carbon nanotubes (MWCNTs) influences the morphology of the surface formed via EPD. Taking a series of well-characterized and gradually oxidized/unsheathing Nanocyl™ MWCNTs and performing EPD on a carbon fiber surface, we analyzed the morphology and wettability of the CNT surfaces. Our results show that the water contact angle could be gradually changed in a wide range (125–163°) and the major property determining its value was the diameter of aggregates formed before the deposition process in the solvent. Based on the obtained results we determined the parameters having a crucial influence on the morphology of created layers. Our results shed new light on the deposition mechanism and enable the preparation of surfaces with steerable roughness and wettability.
The Quality of Assessment of Learning (Qual) Score: Validity Evidence for a Scoring System Aimed at Rating Short, Workplace-Based Comments on Trainee Performance

Abstract Construct: This study seeks to determine validity evidence for the Quality of Assessment for Learning score (QuAL score), which was created to evaluate short qualitative comments that are related to specific scores entered into a workplace-based assessment, common within the competency-based medical education (CBME) context. Background: In the age of CBME, qualitative comments play an important role in clarifying the quantitative scores rendered by observers at the bedside. Currently there are few practical tools that evaluate mixed data (e.g. associated score-and-comment data), other than the comprehensive Completed Clinical Evaluation Report Rating tool (CCERR) that was originally derived to rate end-of-rotation reports. Approach: A multi-center, randomized cohort-based rating exercise was conducted to evaluate the rating properties of the QuAL score as compared to the CCERR. One group rated comments using the QuAL score, and the other group rated comments using the CCERR. A generalizability study (G-Study) and a decision study (D-study) were conducted to determine the number of meta-raters for a reliable rating (phi-coefficient target of >0.80). Both scores were correlated against rater’s gestalt perceptions of utility for both faculty and residents reading the scores. Results: Twenty-five meta-raters from 20 sites participated in this rating exercise. The G-study revealed that the CCERR group (n = 13) rated the comments with a very high reliability (Phi = 0.97). Meanwhile, the QuAL group (n = 12) rated the comments with a similarly high reliability (Phi = 0.97). The QuAL score required only two raters to reach an acceptable target reliability of >0.80, while the CCERR required three. The QuAL score correlated with perceptions of utility (Meta-rater usefulness, Pearson’s r = 0.69, p < 0.001; Perceived usefulness for trainee, r = 0.74, p < 0.001). The CCERR performed similarly, correlating with perceived faculty (r = 0.67, <0.001) and resident utility (0.79, <0.001). Conclusions: The QuAL score is reliable rating score that correlates well with perceptions of utility. The QuAL score may be useful for rating shorter comments generated by workplace-based assessments.
Self-reported traumatic brain injury during key developmental stages: examining its effect on co-occurring psychological symptoms in an adjudicated sample

ABSTRACT Primary Objective: Prior research has demonstrated that traumatic brain injury (TBI) is associated with individual psychological symptoms. These findings, however, may not pertain to the influence of TBI during key developmental stages on the co-occurrence of negative psychological symptoms. Research Design: It was hypothesized that (H1) self-reported TBI is associated with adverse psychological effects, that (H2) self-reported TBI during adolescences is associated with both immediate and delayed adverse psychological effects, and finally, (H3) self-reported TBI during the early stages of adulthood is not associated with immediate psychological effects. Methods and Procedures: The current study employed a sample of adjudicated youth (N: 419 to 562) and structural equation modeling to estimate the association between self-reported TBI and subsequent adverse psychological effects. Results: Findings suggested that higher levels of self-reported TBI during adolescence were associated with higher levels of adverse psychological effects. These effects were both immediate and delayed. However, higher levels of self-reported TBI during adulthood were not associated with immediate adverse psychological effects. Conclusion: Overall, the findings suggest that deleterious outcomes related to self-reported TBI during key developmental stages include proximal and long-term adverse psychological effects.
Sleep duration and risk of cardiovascular events: The SAVE study

Background and aim Controversy exists regarding cardiovascular risk in relation to sleep duration. We determined sleep duration and major recurrent cardiovascular event associations in patients with obstructive sleep apnoea and established cardiovascular disease. Methods Secondary analyses of the international, multicenter, Sleep Apnea Cardiovascular Endpoints trial. Sleep duration was estimated from overnight home oximetry (ApneaLink monitor) used for obstructive sleep apnoea diagnosis. Cox proportional hazards models were used to determine associations of categorized sleep duration (<6 h, 6–8 h (reference), and >8 h) and major cardiovascular outcomes: primary composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and any hospitalization for unstable angina, heart failure, or transient ischemic attack; secondary composite of cardiac and cerebral (stroke/transient ischemic attack) events. Results Oximetry-derived sleep duration estimates were available in 2687 participants (mean 61.2 years, 80.9% males) who experienced a total of 436 cardiovascular events over a mean follow-up of 3.7 years. Compared to the reference category, sleep duration was not associated with risk of the primary composite cardiovascular outcome (adjusted hazard ratio (HR) 1.00, 95% confidence interval 0.76–1.33, and HR 1.22, 95% confidence interval 0.98–1.52, for sleep duration <6 and >8 h, respectively). However, long sleep was associated with increased cerebral events (HR 1.67, 95% confidence interval 1.17–2.39; P = 0.005) and stroke alone (HR 1.79, 95% confidence interval 1.22–2.63; P = 0.003). Conclusions Long sleep duration is associated with an increased risk of stroke but not cardiac events in obstructive sleep apnoea patients with existing cardiovascular disease. Clinical trial registration The trial is registered at ClinicalTrials.gov (NCT00738179).
The Role of Immune Checkpoint Blockade in Uveal Melanoma

Uveal melanoma (UM) represents the most common intraocular malignancy in adults and accounts for about 5% of all melanomas. Primary disease can be effectively controlled by several local therapy options, but UM has a high potential for metastatic spread, especially to the liver. Despite its clinical and genetic heterogeneity, therapy of metastatic UM has largely been adopted from cutaneous melanoma (CM) with discouraging results until now. The introduction of antibodies targeting CTLA-4 and PD-1 for immune checkpoint blockade (ICB) has revolutionized the field of cancer therapy and has achieved pioneering results in metastatic CM. Thus, expectations were high that patients with metastatic UM would also benefit from these new therapy options. This review provides a comprehensive and up-to-date overview on the role of ICB in UM. We give a summary of UM biology, its clinical features, and how it differs from CM. The results of several studies that have been investigating ICB in metastatic UM are presented. We discuss possible reasons for the lack of efficacy of ICB in UM compared to CM, highlight the pitfalls of ICB in this cancer entity, and explain why other immune-modulating therapies could still be an option for future UM therapies.
Electrotransfer of siRNA to Silence Enhanced Green Fluorescent Protein in Tumor Mediated by a High Intensity Pulsed Electromagnetic Field

The contactless high intensity pulsed electromagnetic field (HI-PEMF)-induced increase of cell membrane permeability is similar to conventional electroporation, with the important difference of inducing an electric field non-invasively by exposing a treated tissue to a time-varying magnetic field. Due to the limited number of studies in the field of electroporation induced by HI-PEMF, we designed experiments to explore the feasibility of such a contactless delivery technique for the gene electrotransfer of nucleic acids in tissues in vivo. By using HI-PEMF for gene electrotransfer, we silenced enhanced green fluorescent protein (EGFP) with siRNA molecules against EGFP in B16F10-EGFP tumors. Six days after the transfer, the fluorescent tumor area decreased by up to 39% as determined by fluorescence imaging in vivo. In addition, the silencing of EGFP to the same extent was confirmed at the mRNA and protein level. The results obtained in the in vivo mouse model demonstrate the potential use of HI-PEMF-induced cell permeabilization for gene therapy and DNA vaccination. Further studies are thus warranted to improve the equipment, optimize the protocols for gene transfer and the HI-PEMF parameters, and demonstrate the effects of HI-PEMF on a broader range of different normal and tumor tissues.