Miracle-dz/UniFAR-FTUs huggingface dataset:
PLGA Nanofiber/PDMS Microporous Composite Membrane-Sandwiched Microchip for Drug Testing

Lung-on-a-chip devices could provide new strategies for a biomimetic lung cell microenvironment and construction of lung disease models in vitro, and are expected to greatly promote the development of drug evaluation, toxicological detection, and disease model building. In this study, we developed a novel poly (lactic-co-glycolic acid) (PLGA) nanofiber/polydimethylsiloxane (PDMS) microporous composite membrane-sandwiched lung-on-a-chip to perform anti-tumor drug testing. The composite membrane was characterized, and the results showed that it was permeable to molecules and thus could be used to study small-molecule drug diffusion. In addition, the microchip could apply perfusion fluids to simulate blood flow under extremely low fluid shear stress, and could also simulate the spherical-like shape of the alveoli by deformation of the composite membrane. Using this chip, we evaluated the anti-tumor drug efficacy of gefitinib in two kinds of non-small cell lung cancer cells, the lung adenocarcinoma NCI-H1650 cell line and the large cell lung cancer NCI-H460 cell line. We further probed the resistance of NCI-H460 cells to gefitinib under normoxic and hypoxic conditions. The established composite membrane-sandwiched lung chip can simulate more biochemical and biophysical factors in the lung physiological and pathological microenvironment, and it has important applications in the personalized treatment of lung tumors. It is expected to play a potential role in clinical diagnosis and drug screening.
Ionic dissolution products of Cerium-doped bioactive glass nanoparticles promote cellular osteogenic differentiation and extracellular matrix formation of human bone marrow derived mesenchymal stromal cells

Cerium (Ce) is a promising candidate ion for application in bone tissue engineering (BTE) since it reduces the presence of reactive oxygen species. Ce-doped mesoporous bioactive glass nanoparticles (MBGNs) serving as vectors for the local application of Ce already demonstrated stimulating effects on the expression of pro-osteogenic genes in Saos-2 cells. So far, there is no evidence available about the effects of Ce-doped MBGNs on the viability, osteogenic differentiation and the formation of the osseous extracellular matrix (ECM) of primary human bone marrow-derived mesenchymal stromal cells (BMSCs). Therefore, in this study, the biocompatibility of the ionic dissolution products (IDPs) of MBGNs containing increasing concentrations of CeO2 (0.05 MCe-MBGNs, composition in mol%: 86.6SiO2-12.1CaO-1.3CeO2; and 0.2 MCe-MBGNs, composition in mol%: 86.0SiO2-11.8CaO-2.2CeO2) and unmodified MBGNs (composition in mol%: 86SiO2-14CaO) was evaluated using human BMSCs. Eventually, the impact of the MBGNs’ IDPs on the cellular osteogenic differentiation and their ability to build and mature a primitive osseous ECM was assessed. The Ce-doped MBGNs had a positive influence on the viability and stimulated the cellular osteogenic differentiation of human BMSCs evaluated by analyzing the activity of alkaline phosphate as a marker enzyme for osteoblasts in the present setting. Furthermore, the formation and calcification of a primitive osseous ECM was significantly stimulated in the presence of Ce-doped MBGNs in a positive concentration-dependent manner as demonstrated by an elevated presence of collagen and increased ECM calcification. The results of this in-vitro study show that Ce-doped MBGNs are attractive candidates for further application in BTE.
Combined CDK2 and CDK4/6 Inhibition Overcomes Palbociclib Resistance in Breast Cancer by Enhancing Senescence

Simple Summary Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are widely used to treat metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. Despite the effectiveness of CDK4/6 inhibitors, acquired resistance occurs in almost all cases. Strategies to address this issue have not been developed yet. We investigated mechanisms of resistance to CDK4/6 inhibitor in breast cancer and potential therapeutic strategies. We found that cyclin E-CDK2 mediated phosphorylation of C-MYC is responsible for resistance to CDK4/6 inhibitor by suppressing C-MYC induced senescence. On the contrary, the synergistic anti-proliferative effect of the combined inhibition of CDK2 and CDK4/6 overcomes acquired resistance to CDK4/6 inhibitors by enhancing senescence. Our findings could pave the way for the development CDK2-specific kinase inhibitor for the treatment of breast cancers that are resistant to CDK4/6 inhibitor. Abstract Breast cancer represents the number one global cancer burden in women and the hormone receptor (HR)-positive subtype comprises approximately 70% of breast cancers. Unfortunately, acquired resistance ultimately occurs in almost all cases, even though cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a highly effective therapy for HR-positive/human epidermal growth factor receptor 2-negative subtype. Here, we investigated mechanisms of resistance to CDK4/6 inhibitor and potential therapeutic strategies using our palbociclib-resistant preclinical model. We observed that cyclin E was significantly overexpressed in palbociclib-resistant cells, and similar association was also confirmed in pleural effusion samples collected from HR-positive breast cancer patients. After confirmation of cyclin E-CDK2 interaction by co-immunoprecipitation, we demonstrated CDK2 inhibition combined with palbociclib synergistically suppressed proliferation of palbociclib-resistant cells and growth of palbociclib-resistant xenograft in mice. We also proved that enhancing C-MYC-mediated senescence is a novel mechanism behind the synergism created by targeting both CDK2 and CDK4/6. Furthermore, the clinical relevance of cyclin E as a therapeutic target was supported by significant association between CCNE1 overexpression and poor prognosis based on large-scale public gene expression data sets in HR-positive breast cancer patients. Therefore, we propose cyclin E-CDK2 signaling as a promising therapeutic target for overcoming cyclin E-associated resistance to CDK4/6 inhibitor.
The effects of COVID‐19 on hip fracture management and mortality in a regional trauma centre

Older patients and those with comorbidities have worse outcomes from both hip fracture and COVID-19. Furthermore, testing positive for COVID-19 can increase mortality for any surgical procedure [1]. In anticipation of the initial COVID-19 surge, theatre staff were re-allocated in order to meet the expected increase in local critical care bed requirements, resulting in reduced capacity to deliver surgical services. We analysed the impact of the initial COVID-19 surge on the hip fracture population in a high-volume tertiary trauma centre (approximately 900 hip fracture surgical procedures per year) in the UK [2]. The study included a 2month period following the onset of lockdown from 24 March 2020 until 23 May 2020, and we compared this with the same 2-month time period in 2015–2019. This included patients aged > 60 years who were admitted with a hip fracture. It did not include patients with high-energy injuries, pathological fractures and those who underwent surgery in other units before admission. Data were retrieved from the hospital’s inpatient fracture database, the Fracture Outcomes Research Department, which contributes to the National Hip FractureDatabase [2]. The study was approved by the Belfast Trust’s Quality Improvement and Patient Safety Department. During the study period in 2020, 126 hip fracture patients were included, compared with an average of 115 patients per year in 2015–2019. This suggests that, despite nationwide advice to avoid unnecessary social contact and remain at home where possible, a cohort of patients continued to fall and sustain hip fractures. Looking specifically at the 2020 cohort (Table 1), 68.0% of patients were aged 80 or above, and 86.9% of those operated on were deemed ASA physical status 3 or worse. These patients clearly remain at significant risk of sustaining a fall and subsequent hip fracture, despite the COVID-19 lockdown restrictions.
Entropy and Diversity: The Axiomatic Approach

The global biodiversity crisis is one of humanity's most urgent problems, but even quantifying biological diversity is a difficult mathematical and conceptual challenge. This book brings new mathematical rigour to the ongoing debate. It was born of research in category theory, is given strength by information theory, and is fed by the ancient field of functional equations. It applies the power of the axiomatic method to a biological problem of pressing concern, but it also presents new theorems that stand up as mathematics in their own right, independently of any application. The question 'what is diversity? ' has surprising mathematical depth, and this book covers a wide breadth of mathematics, from functional equations to geometric measure theory, from probability theory to number theory. Despite this range, the mathematical prerequisites are few: the main narrative thread of this book requires no more than an undergraduate course in analysis.
INFRARED STUDIES OF BIFUNCTIONAL EXTRACTANTS

ABSTRACT The infrared spectra of a series of neutral bifunctional extractants were examined. The carbonyl and phosphoryl stretching regions were monitored for changes as nitric or hydrocloric acid was extracted and as Nd(III) or Sm(III) was extracted. It was found that the phosphoryl group is the primary site of extraction as was predicted from solvent extraction measurements. Upon heavy loading of the metal ion in the organic phase, the extractant OφD(iB)CMP0 (octyl(phenyl)-diisobutylcarbamoylmethylphosphine oxide) can behave as a bidentate ligand as does the analogous di-hexyl-N,N-diethylcarbamoylmethylphosphonate solid state complex. The tendency for the carbonyl oxygen to form a bond directly to the metal ion is enhanced in chloride media at low acidity. The spectra of mixtures of 0φD(iB)CMP0 with the phase modifier TBP indicate no interaction between the two extractants and TBP does not appear to be part of the primary metal-extractant complex.
The pre-exponential voltage-exponent as a sensitive test parameter for field emission theories

For field electron emission (FE), an empirical equation for measured current Im as a function of measured voltage Vm has the form Im = CVmk exp[–B/Vm], where B is a constant and C and k are constants or vary weakly with Vm. Values for k can be extracted (i) from simulations based on some specific FE theory, and in principle (ii) from current–voltage measurements of sufficiently high quality. This paper shows that a comparison of theoretically derived and experimentally derived k-values could provide a sensitive and useful tool for comparing FE theory and experiment, and for choosing between alternative theories. Existing methods of extracting k-values from experimental or simulated current–voltage data are discussed, including a modernized ‘least residual’ method, and existing knowledge concerning k-values is summarized. Exploratory simulations are reported. Where an analytical result for k is independently known, this value is reliably extracted. More generally, extracted k-values are sensitive to details of the emission theory used, but also depend on assumed emitter shape; these two influences will need to be disentangled by future research, and a range of emitter shapes will need examination. Other procedural conclusions are reported. Some scientific issues that this new tool may eventually be able to help investigate are indicated.
Beyond-mean-field description of a trapped unitary Fermi gas with mass and population imbalance

A detailed description is given of the phase diagram for a two-component unitary Fermi gas with mass and population imbalance, for both homogeneous and trapped systems. This aims at providing quantitative benchmarks for the normal-to-superfluid phase transition of a mass-imbalanced Fermi gas in the temperature-polarization parameter space. A self-consistent $t$-matrix approach is adopted, which has already proven to accurately describe the thermodynamic properties of the mass- and population-balanced unitary Fermi gas. Our results provide a guideline for the ongoing experiments on heteronuclear Fermi mixtures.
Multi-Label Contrastive Learning for Abstract Visual Reasoning

For a long time, the ability to solve abstract reasoning tasks was considered one of the hallmarks of human intelligence. Recent advances in the application of deep learning (DL) methods led to surpassing human abstract reasoning performance, specifically in the most popular type of such problems—Raven’s progressive matrices (RPMs). While the efficacy of DL systems is indeed impressive, the way they approach the RPMs is very different from that of humans. State-of-the-art systems solving RPMs rely on massive pattern-based training and sometimes on exploiting biases in the dataset, whereas humans concentrate on the identification of the rules/concepts underlying the RPM to be solved. Motivated by this cognitive difference, this work aims at combining DL with the human way of solving RPMs. Specifically, we cast the problem of solving RPMs into a multilabel classification framework where each RPM is viewed as a multilabel data point, with labels determined by the set of abstract rules underlying the RPM. For efficient training of the system, we present a generalization of the noise contrastive estimation algorithm to the case of multilabel samples and a new sparse rule encoding scheme for RPMs. The proposed approach is evaluated on the two most popular benchmark datasets [I-RAVEN and procedurally generated matrices (PGM)] and on both of them demonstrate an advantage over the state-of-the-art results.
A Stochastic Path-Integrated Differential EstimatoR Expectation Maximization Algorithm

The Expectation Maximization (EM) algorithm is of key importance for inference in latent variable models including mixture of regressors and experts, missing observations. This paper introduces a novel EM algorithm, called \texttt{SPIDER-EM}, for inference from a training set of size $n$, $n \gg 1$. At the core of our algorithm is an estimator of the full conditional expectation in the {\sf E}-step, adapted from the stochastic path-integrated differential estimator ({\tt SPIDER}) technique. We derive finite-time complexity bounds for smooth non-convex likelihood: we show that for convergence to an $\epsilon$-approximate stationary point, the complexity scales as $K_{\operatorname{Opt}} (n,\epsilon )={\cal O}(\epsilon^{-1})$ and $K_{\operatorname{CE}}( n,\epsilon ) = n+ \sqrt{n} {\cal O}(\epsilon^{-1} )$, where $K_{\operatorname{Opt}}( n,\epsilon )$ and $K_{\operatorname{CE}}(n, \epsilon )$ are respectively the number of {\sf M}-steps and the number of per-sample conditional expectations evaluations. This improves over the state-of-the-art algorithms. Numerical results support our findings.
Calcium Carbonate Microparticles as Carriers of 224Ra: Impact of Specific Activity in Mice with Intraperitoneal Ovarian Cancer.

BACKGROUND Patients with advanced-stage ovarian cancer face a poor prognosis because of recurrent peritoneal cavity metastases following surgery and chemotherapy. Alpha-emitters may enable the efficient treatment of such disseminated diseases because of their short range and highly energetic radiation. Radium-224 is a candidate αemitter due to its convenient 3.6-day half-life, with more than 90% of the decay energy originating from α-particles. However, its inherent skeletal accumulation must be overcome to facilitate intraperitoneal delivery of the radiation dose. Therefore, 224Ra-labeled CaCO3 microparticles have been developed. OBJECTIVE The antitumor effect of CaCO3 microparticles as a carrier for 224Ra was investigated, with an emphasis on the ratio of activity to mass dose of CaCO3, that is, specific activity. METHODS Nude athymic mice were inoculated intraperitoneally with human ovarian cancer cells (ES-2) and treated with a single intraperitoneal injection of 224Ra-labeled CaCO3 microparticles with varying combinations of mass and activity dose, or cationic 224Ra in solution. Survival and ascites volume at sacrifice were evaluated. RESULTS Significant therapeutic effect was achieved for all tested specific activities ranging from 0.4 to 4.6 kBq/mg. Although treatment with a mean activity dose of 1305 kBq/kg of cationic 224Ra prolonged the survival compared with the control, equivalent median survival could be achieved with 224Ra-labeled microparticles with a mean dose of only 420 kBq/kg. The best outcome was achieved with the highest specific activities (2.6 and 4.6 kBq/mg). CONCLUSION Radium-224-labeled CaCO3 microparticles present a promising therapy against cancer dissemination in body cavities.
Word learning from a tablet app: Toddlers perform better in a passive context

In recent years, the popularity of tablets has skyrocketed and there has been an explosive growth in apps designed for children. Howhever, many of these apps are released without tests for their effectiveness. This is worrying given that the factors influencing children’s learning from touchscreen devices need to be examined in detail. In particular, it has been suggested that children learn less from passive video viewing relative to equivalent live interaction, which would have implications for learning from such digital tools. However, this so-called video deficit may be reduced by allowing children greater influence over their learning environment. Across two touchscreen-based experiments, we examined whether 2- to 4-year-olds benefit from actively choosing what to learn more about in a digital word learning task. We designed a tablet study in which “active” participants were allowed to choose which objects they were taught the label of, while yoked “passive” participants were presented with the objects chosen by their active peers. We then examined recognition of the learned associations across different tasks. In Experiment 1, children in the passive condition outperformed those in the active condition (n = 130). While Experiment 2 replicated these findings in a new group of Malay-speaking children (n = 32), there were no differences in children’s learning or recognition of the novel word-object associations using a more implicit looking time measure. These results suggest that there may be performance costs associated with active tasks designed as in the current study, and at the very least, there may not always be systematic benefits associated with active learning in touchscreen-based word learning tasks. The current studies add to the evidence that educational apps need to be evaluated before release: While children might benefit from interactive apps under certain conditions, task design and requirements need to consider factors that may detract from successful performance.
Effects of Sintering Temperature Variation on Synthesis of Glass-Ceramic Phosphor Using Rice Husk Ash as Silica Source

In this study, the authors attempted to propose the very first study on fabrication and characterization of zinc-boro-silicate (ZBS) glass-ceramics derived from the ternary zinc-boro-silicate (ZnO)0.65(B2O3)0.15(RHA)0.2 glass system through a conventional melt-quenching method by incorporating rice husk ash (RHA) as the silica (SiO2) source, followed by a sintering process. Optimization of sintering condition has densified the sintered samples while embedded beta willemite (β-Zn2SiO4) and alpha willemite (α-Zn2SiO4) were proven in X-ray diffraction (XRD) analysis. Field emission scanning electron microscopy (FESEM) has shown the distribution of willemite crystals in rhombohedral shape crystals and successfully form closely-packed grains due to intense crystallization. The photoluminescence (PL) spectra of all sintered ZBS glasses presented various emission peaks at 425, 463, 487, 531, and 643 nm corresponded to violet, blue, green, and red emission, respectively. The correlation between the densification, phase transformation, microstructure, and photoluminescence of Zn2SiO4 glass-ceramic phosphor is discussed in detail.
Performance Indicators Contributing To Success At The Group And Play-Off Stages Of The 2019 Rugby World Cup

Performance indicators that contributed to success at the group and play-off stages of the 2019 Rugby World Cup were analysed using publicly available data obtained from the official tournament website using both a non-parametric statistical technique, Wilcoxon’s signed rank test, and a decision rules technique from machine learning called RIPPER. Our statistical results found that ball carry effectiveness (percentage of ball carries that penetrated the opposition gain-line) and total metres gained (kick metres plus carry metres) were found to contribute to success at both stages of the tournament and that indicators that contributed to success during group stages (dominating possession, making more ball carries, making more passes, winning more rucks, and making less tackles) did not contribute to success at the play-off stage. Our results using RIPPER found that low ball carries and a low lineout success percentage jointly contributed to losing at the group stage, while winning a low number of rucks and carrying over the gain-line a sufficient number of times contributed to winning at the play-off stage of the tournament. The results emphasise the need for teams to adapt their playing strategies from group stage to the play-off stage at the tournament in order to be successful.
Relationship between N95 Amplitude of Pattern Electroretinogram and Optical Coherence Tomography Angiography in Open-Angle Glaucoma

Purpose: The pattern electroretinogram (PERG) is useful to detect retinal ganglion cell (RGC) damage in patients with glaucoma. Optical coherence tomography angiography (OCTA) measures retinal vessel density (VD), which is known to be reduced in glaucoma. There may be correlations between parameters of the PERG and OCTA in open-angle glaucoma (OAG). Methods: In total, 95 eyes of 95 OAG patients and 102 eyes of 102 normal controls were included in this study. N35, P50, and N95 latency along with P50 and N95 amplitude were obtained using the PERG. Retinal VD was measured around the peripapillary and macular area according to the ETDRS grid (concentric circles with diameters of 1, 3, and 6 mm), which is named a center (≤1 mm), an inner (1–3 mm), an outer (3–6 mm), and a full (≤6 mm) area. Pearson correlation analysis was done between parameters, and partial correlation analysis was done after adjusting confounding factors. Results: P50 amplitude, N95 amplitude, and VD of most measured areas were significantly lower in the OAG group compared to the normal group. N95 amplitude showed a statistically significant correlation with parameters of optical coherence tomography and visual field, peripapillary outer and full VD, and macular outer and full VD even after adjusting confounding factors. There was no significant correlation between parameters in the normal group. Conclusions: N95 amplitude was associated with structural and functional change including VD reduction in OAG. Microvascular alterations may be associated with dysfunctional changes of RGC recorded by the PERG in OAG.