Miracle-dz/UniFAR-FTUs huggingface dataset:
Vacuum Energy Decay from a q-Bubble

We consider a finite-size spherical bubble with a nonequilibrium value of the q-field, where the bubble is immersed in an infinite vacuum with the constant equilibrium value q 0 for the q-field (this q 0 has already cancelled an initial cosmological constant). Numerical results are presented for the time evolution of such a q-bubble with gravity turned off and with gravity turned on. For small enough bubbles and a q-field energy scale sufficiently below the gravitational energy scale E Planck , the vacuum energy of the q-bubble is found to disperse completely. For large enough bubbles and a finite value of E Planck , the vacuum energy of the q-bubble disperses only partially and there occurs gravitational collapse near the bubble center.
Incidence and prognostic significance of receptor discordance between primary breast cancer and paired bone metastases

ER, PgR and HER‐2 status are the cornerstones of choosing systemic therapy for breast cancer, but can change during the disease course. Guidelines recommended the biopsy of the metastatic tumor to reassess receptor status. Bone is the most frequent metastatic site of breast cancer but remained technically difficult to biopsy. Our study aimed to evaluate the incidence and prognostic significance of receptor discordance between primary breast cancer and paired bone metastases. One hundred and fifty‐five breast cancer patients were diagnosed with pathology‐confirmed bone metastasis at Fudan University Shanghai Cancer Center. Ninety‐three patients with receptor status available on both primary tumor and bone metastases were included in our study. ER, PgR and HER‐2 status converted from positive to negative in 10.8% (10/93), 28.0% (26/93) and 8.6% (8/93) of the patients, while ER, PgR and HER‐2 status converted from negative to positive in 3.2% (3/93), 4.3% (4/93) and 1.1% (1/93) of the patients, respectively. 40.4% (17/42) of the HER2‐0 tumors converted to HER2‐low, which enabled them to receive the treatment of new antibody‐drug conjugates (ADCs). Prior endocrine and anti‐HER2 therapy were the independent risk factors for receptor conversion. Loss of HR expression in bone metastases was significantly associated with worse first‐line PFS (adjusted hazard ratio = 3.271, P‐value = .039) and OS (adjusted hazard ratio = 6.09, P‐value = .011). In conclusion, our study confirmed that patients may experience receptor conversion between primary breast cancer and bone metastases, possibly influenced by prior treatments, which significantly influenced prognosis. The rebiopsy of bone metastases in patients with primary HER2‐0 tumors may benefit from the new ADC drugs.
Antibiotics Limit Adaptation of Drug-Resistant Staphylococcus aureus to Hypoxia

Bacterial pathogens are confronted with a range of challenges at the site of infection, including exposure to antibiotic treatment and harsh physiological conditions, that can alter the fitness benefits and costs of acquiring antibiotic resistance. Here, we develop an experimental system to recapitulate resistance gene acquisition by Staphylococcus aureus and test how the subsequent evolution of the resistant bacterium is modulated by antibiotic treatment and oxygen levels, both of which are known to vary extensively at sites of infection. ABSTRACT Bacterial pathogens are confronted with a range of challenges at the site of infection, including exposure to antibiotic treatment and harsh physiological conditions, that can alter the fitness benefits and costs of acquiring antibiotic resistance. Here, we develop an experimental system to recapitulate resistance gene acquisition by Staphylococcus aureus and test how the subsequent evolution of the resistant bacterium is modulated by antibiotic treatment and oxygen levels, both of which are known to vary extensively at sites of infection. We show that acquiring tetracycline resistance was costly, reducing competitive growth against the isogenic strain without the resistance gene in the absence of the antibiotic, for S. aureus under hypoxic but not normoxic conditions. Treatment with tetracycline or doxycycline drove the emergence of enhanced resistance through mutations in an RluD-like protein-encoding gene and duplications of tetL, encoding the acquired tetracycline-specific efflux pump. In contrast, evolutionary adaptation by S. aureus to hypoxic conditions, which evolved in the absence of antibiotics through mutations affecting gyrB, was impeded by antibiotic treatment. Together, these data suggest that the horizontal acquisition of a new resistance mechanism is merely a starting point for the emergence of high-level resistance under antibiotic selection but that antibiotic treatment constrains pathogen adaptation to other important environmental selective forces such as hypoxia, which in turn could limit the survival of these highly resistant but poorly adapted genotypes after antibiotic treatment is ended.
A proportional hazards modeling of multisample reliability data

The Weibull distribution, the most commonly used reliability model, accomodates only certain increasing only certain increasing and decreasing hazard functions, but nonmonotone, especially bathtub, shaped hazard functions are often encountered in reliability studies. The generalized Weibull family introduced in Mudholkar and Kollia (1994) contains distributions with unimodal, bathtub shaped, and a broader variety of monotone hazard functions. Moreover, it is closed under proportional hazards meodeling, which is desirable, interesting and convenient in studies involving multiple samples occurring in repair-reuse type reliability situations. The analysis of multisample data is illustrated using the bus motor failure mileages first studied by Davis(l952).
3D differential interference contrast microscopy using polarisation‐sensitive tomographic diffraction microscopy

Tomographic diffraction microscopy (TDM) is a generalisation of digital holographic microscopy (DHM), for which the illumination angle onto the sample is fully controlled, which has become a tool of choice for 3D, high‐resolution imaging of unlabelled samples. TDM makes it possible to obtain the optical field in both amplitude and phase for each illumination angle. Proper information reallocation eventually allows for 3D reconstruction of the complex refractive index map. On the other hand, polarisation array sensors (PAS) paves new way for TDM, as vectorial information assessment about the investigated sample. In this contribution, we show an alternative use of this polarisation information based on the phase sensitive nature of TDM. Here, we demonstrated that TDM coupled with PAS can lead to a 3D differential interference contrast (DIC) microscope with almost no experimental configuration modification.
Advancing Telehealth Competency in Physician Assistant Education: Stakeholder Perspectives and a Curricular Model for PA Programs

The COVID-19 pandemic has illuminated the relevance of telehealth-enabled clinical practice and has underscored the necessityofpreparingphysicianassistant/associate (PA) learners for a digital healthcare world. Telehealth is an innovative approach that increases access, flexibility, safety, and efficiency within clinical practice and supervised clinical training experiences. The 2021 Physician Assistant Education Association (PAEA) report on COVID-19 indicates that one-third of PA programs offer a telehealth curriculum in the didactic year of training, and an additional 37% plan to implement a telehealth curriculum. In clinical practice, currently, about 20% of certified PAs participate in telemedicine delivery in their practice, with about 60% employed in practices or institutions that provide telemedicine services. While the COVID-19 pandemic has stabilized, this telehealth trend is expected to continue to expand. With growing interest in telehealth-facilitated medical practice, there is a need to understand the status of telehealth educational training and exposure in health professions education. The PA Leadership and Learning Academy (PALLA), a statefunded regional academic initiative in Maryland, has explored opportunities to enhance telehealth competency in the PA workforce. This article reviews the results of an environmental scan of telehealth training opportunities for PA programs within Maryland and provides a curricular model for implementing telehealth education to support didactic and clinical training for PAs.
Real‐time in‐situ electrochemical monitoring of Pseudomonas aeruginosa biofilms grown on air–liquid interface and its antibiotic susceptibility using a novel dual‐chamber microfluidic device

Biofilms are communities of bacterial cells encased in a self‐produced polymeric matrix that exhibit high tolerance toward environmental stress. Despite the plethora of research on biofilms, most P. aeruginosa biofilm models are cultured on a solid–liquid interface, and the longitudinal growth characteristics of P. aeruginosa biofilm are unclear. This study demonstrates the real‐time and noninvasive monitoring of biofilm growth using a novel dual‐chamber microfluidic device integrated with electrochemical detection capabilities to monitor pyocyanin (PYO). The growth of P. aeruginosa biofilms on the air–liquid interface (ALI) was monitored over 48 h, and its antibiotic susceptibility to 6 h exposure of 50, 400, and 1600 µg/ml of ciprofloxacin solutions was analyzed. The biofilm was treated directly on its surface and indirectly from the substratum by delivering the CIP solution to the top or bottom chamber of the microfluidic device. Results showed that P. aeruginosa biofilm developed on ALI produces PYO continuously, with the PYO production rate varying longitudinally and peak production observed between 24 and 30 h. In addition, this current study shows that the amount of PYO produced by the ALI biofilm is proportional to its viable cell numbers, which has not been previously demonstrated. Biofilm treated with ciprofloxacin solution above 400 µg/ml showed significant PYO reduction, with biofilms being killed more effectively when treatment was applied to their surfaces. The electrochemical measurement results have been verified with colony‐forming unit count results, and the strong correlation between the PYO electrical signal and the viable cell number highlights the usefulness of this approach for fast and low‐cost ALI biofilm study and antimicrobial tests.
Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure

Background: Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk. Methods: TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling. Results: Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78–2.57) unadjusted, 1.96 (1.49–2.53) after adjustment for clinical confounders and 1.44 (1.05–1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78–3.33) and 1.52 (1.15–2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785). Conclusions: Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice. Registration: URL: https://www.trialregister. nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx? TrialID=NTR1893.)
Economic evaluation of digitally enabled aged and neurological rehabilitation care in the Activity and MObility UsiNg Technology (AMOUNT) trial

Objective To investigate the trial-based cost-effectiveness of the addition of a tailored digitally enabled exercise intervention to usual care shown to be clinically effective in improving mobility in the Activity and MObility UsiNg Technology (AMOUNT) rehabilitation trial compared to usual care alone. Design Economic evaluation alongside a pragmatic randomized controlled trial. Participants 300 people receiving inpatient aged and neurological rehabilitation were randomized to the intervention (n = 149) or usual care control group (n = 151). Main measures Incremental cost effectiveness ratios were calculated for the additional costs per additional person demonstrating a meaningful improvement in mobility (3-point in Short Physical Performance Battery) and quality-adjusted life years gained at 6 months (primary analysis). The joint probability distribution of costs and outcomes was examined using bootstrapping. Results The mean cost saving for the intervention group at 6 months was AU$2286 (95% Bootstrapped cost CI: −$11,190 to $6410) per participant; 68% and 67% of bootstraps showed the intervention to be dominant (i.e. more effective and cost saving) for mobility and quality-adjusted life years, respectively. The probability of the intervention being cost-effective considering a willingness to pay threshold of AU$50,000 per additional person with a meaningful improvement in mobility or quality-adjusted life year gained was 93% and 77%, respectively. Conclusions The AMOUNT intervention had a high probability of being cost-effective if decision makers are willing to pay AU$50,000 per meaningful improvement in mobility or per quality-adjusted life year gained, and a moderate probability of being cost-saving and effective considering both outcomes at 6 months post randomization.
X-ray/UV/optical variability of NGC 4593 with Swift: reprocessing of X-rays by an extended reprocessor

We report the results of intensive X-ray, UV, and optical monitoring of the Seyfert 1 galaxy NGC 4593 with Swift. There is no intrinsic flux-related spectral change in any variable component with small apparent variations being due to contamination by a constant hard (reflection) component in the X-rays and the red host galaxy in the UV/optical. Relative to the shortest wavelength band, UVW2, the lags of the other UV/optical bands mostly agree with the predictions of reprocessing of high energy emission by an accretion disc. The U-band lag is, however, larger than expected, probably because of reprocessed Balmer continuum emission from the distant broad line region (BLR). The UVW2 band is well correlated with the X-rays but lags by ∼6× more than expected if the UVW2 results only from reprocessing of X-rays by the disc. However, if the light curves are filtered to remove variations on time-scales >5 d, the lag approaches the expectation from disc reprocessing. MEMECHO analysis shows that direct X-rays can be the driver of most of the UV/optical variations if the response functions have tails up to 10 d, from BLR reprocessing, together with strong peaks at short lag (<1 d) from disc reprocessing. For the 5 AGN monitored so far, the observed UVW2 to V-band lags are ∼<2 of disc reprocessing expectations and vary little between AGN. However, the X-ray to UVW2 lags greatly exceed disc reprocessing expectations and differ between AGN. The two most absorbed AGN have the largest excesses, so absorption and scattering may affect these lags, but there is no simple relationship between excess and absorption.
The effect of medical/therapeutic clowns on the playfulness of children with intellectual disabilities

Abstract Background Play is an essential component of children's development. Children with intellectual disability tend to have poor socioemotional abilities and impaired play. This study examined the effects of a medical/therapeutic clowning play intervention on the playfulness of children with intellectual disability. Method Two medical clowns facilitated a play intervention in a preschool classroom setting with a total of 52 children with intellectual disability. We compared before and after two groups that received the intervention: group 1 met the medical clowns once a week for 6 months (long‐intervention group) and group 2 for 3 months (short intervention group). Children's functioning was assessed using the Vineland Adaptive Behaviour Scales. Children's playfulness was scored using the Test of Playfulness observational assessment. A teachers' focus‐ group was used to gather additional information on the clowns' work. Results Children's playfulness increased significantly at the end of the intervention, whereas the improvement in the playfulness scores of group 1 was significantly larger than those of group 2 (t 50 = −4.82, p < .001). The teachers' focus group revealed additional benefits of the medical clowns' work. Conclusion The results shed light on the play and playfulness of children with intellectual disability and the possible contribution of a clowning play intervention to their development.
Plasma levels of E‐selectin are associated with retinopathy in sickle cell disease

The vascular endothelium is markedly disrupted in sickle cell disease (SCD) and is the converging cascade of the complex pathophysiologic processes linked to sickle cell vasculopathy. Circulating endothelial activation and/or apoptotic markers may reflect this endothelial activation/damage that contributes to the pathophysiology of the SCD vascular complications.
Metagenome-Assembled Genomes for “Candidatus Phormidium sp. Strain AB48” and Co-occurring Microorganisms from an Industrial Photobioreactor Environment

Here, we report metagenome-assembled genomes for “Candidatus Phormidium sp. strain AB48” and three cooccurring microorganisms from a biofilm-forming industrial photobioreactor environment, using the PacBio sequencing platform. Several mobile genetic elements, including a double-stranded DNA phage and plasmids, were also recovered, with the potential to mediate gene transfer within the biofilm community. ABSTRACT Here, we report metagenome-assembled genomes for “Candidatus Phormidium sp. strain AB48” and three cooccurring microorganisms from a biofilm-forming industrial photobioreactor environment, using the PacBio sequencing platform. Several mobile genetic elements, including a double-stranded DNA phage and plasmids, were also recovered, with the potential to mediate gene transfer within the biofilm community.
Northern Sky Galactic Cosmic Ray Anisotropy between 10 and 1000 TeV with the Tibet Air Shower Array

We report on the analysis of the 10–1000 TeV large-scale sidereal anisotropy of Galactic cosmic rays (GCRs) with the data collected by the Tibet Air Shower Array from 1995 October to 2010 February. In this analysis, we improve the energy estimate and extend the decl. range down to −30°. We find that the anisotropy maps above 100 TeV are distinct from that at a multi-TeV band. The so-called tail-in and loss-cone features identified at low energies get less significant, and a new component appears at ∼100 TeV. The spatial distribution of the GCR intensity with an excess (7.2σ pre-trial, 5.2σ post-trial) and a deficit (−5.8σ pre-trial) are observed in the 300 TeV anisotropy map, in close agreement with IceCube’s results at 400 TeV. Combining the Tibet results in the northern sky with IceCube’s results in the southern sky, we establish a full-sky picture of the anisotropy in hundreds of TeV band. We further find that the amplitude of the first order anisotropy increases sharply above ∼100 TeV, indicating a new component of the anisotropy. All these results may shed new light on understanding the origin and propagation of GCRs.
Diastolic function and cardiovascular risk among patients with severe obesity referred to a lifestyle-program – a pilot study

Abstract Objectives. Severe obesity is associated with a high risk of comorbidities and alterations of cardiac structure and function. The primary aim of the study was to investigate the proportion of diastolic dysfunction (DD) at baseline, and changes in cardiac function from baseline (T1) to 6 months follow-up (T2) among participants with severe obesity attending a lifestyle-intervention. The secondary aim was to explore changes in body mass index (BMI), physical fitness (VO2peak) and cardiovascular risk from T1 to T2 and 12 months follow-up (T3). Design. This was an open single-site prospective observational study. Patients were recruited from an obesity clinic to a lifestyle-intervention consisting of three 3-weeks intermittent stays over 12-months period. Echocardiography was performed at T1 and T2 and BMI, VO2peak and cardiovascular risk measured at T1, T2 and T3. Results. Fifty-six patients were included (mean age 45.1 years; BMI 41.9). Six of 52 patients (12%) had grade 1 DD at T1, while five subjects had DD at T2. E/A ratio (11%, p = .005) and mitral deceleration time (9%, p = .014) were improved at T2. A reduction in BMI (–1.8, p < .001) and improvement in VO2peak (1.6 mL/kg min, p = .026) were assessed at T2 and this improvement persisted at T3. The total cardiovascular risk score was not significantly changed. Conclusion. The patients with severe obesity had low prevalence of DD. For all participants, an improvement in diastolic parameters, and an important initial weight loss was observed. Clinical Trial number: NCT02826122
Finnish-specific AKT2 gene variant leads to impaired insulin signalling in myotubes

Finnish-specific gene variant p.P50T/AKT2 (minor allele frequency (MAF) = 1.1%) is associated with insulin resistance and increased predisposition to type 2 diabetes. Here, we have investigated in vitro the impact of the gene variant on glucose metabolism and intracellular signalling in human primary skeletal muscle cells, which were established from 14 male p.P50T/AKT2 variant carriers and 14 controls. Insulin-stimulated glucose uptake and glucose incorporation into glycogen were detected with 2-[1,2-3H]-deoxy-D-glucose and D-[14C]-glucose, respectively, and the rate of glycolysis was measured with a Seahorse XFe96 analyzer. Insulin signalling was investigated with Western blotting. The binding of variant and control AKT2-PH domains to phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) was assayed using PIP StripsTM Membranes. Protein tyrosine kinase and serine-threonine kinase assays were performed using the PamGene® kinome profiling system. Insulin-stimulated glucose uptake and glycogen synthesis in myotubes in vitro were not significantly affected by the genotype. However, the insulin-stimulated glycolytic rate was impaired in variant myotubes. Western blot analysis showed that insulin-stimulated phosphorylation of AKT-Thr308, AS160-Thr642 and GSK3β-Ser9 was reduced in variant myotubes compared to controls. The binding of variant AKT2-PH domain to PI(3,4,5)P3 was reduced as compared to the control protein. PamGene® kinome profiling revealed multiple differentially phosphorylated kinase substrates, e.g. calmodulin, between the genotypes. Further in silico upstream kinase analysis predicted a large-scale impairment in activities of kinases participating, for example, in intracellular signal transduction, protein translation and cell cycle events. In conclusion, myotubes from p.P50T/AKT2 variant carriers show multiple signalling alterations which may contribute to predisposition to insulin resistance and T2D in the carriers of this signalling variant.