Adaptive and Dissipative Hierarchical Population Crowding of Synthetic Protocells through Click-PISA under Gradient Energy Inputs.

The ability of living objects to respond rapidly en masse to various stimuli or stress is an important function in response to externally applied changes in the local environment. This occurs across many length scales, for instance, bacteria swarming in response to different stimuli or stress and macromolecular crowding within cells. Currently there are few mechanisms to induce similar autonomous behaviors within populations of synthetic protocells. Herein, we report a system in which populations of individual objects behave in a coordinated manner in response to changes in the energetic environment by the emergent self-organization of large object swarms. These swarms contain protocell populations of approximately 60 000 individuals. We demonstrate the dissipative nature of the hierarchical constructs, which persist under appropriate UV stimulation. Finally, we identify the ability of the object populations to change behaviors in an adaptive population-wide response to the local energetic environment.

Phenanthroline Derived N-Doped Carbon Dots as Robust Metal-Free Photocatalysts for PET-RAFT Polymerization and Polymerization-Induced Self-Assembly.

Metal-free organic photocatalysts for photo-mediated reversible deactivation radical polymerization (photo-RDRP) are witnessed to make increasing advancement in the precise synthesis of polymers. However, challenges still exist in the development of high-efficiency and environmentally sustainable carbon dots (CDs)-based organocatalysts. Herein, N-doped CDs derived from phenanthroline derivative (Aphen) are prepared as metal-free photocatalysts for photoinduced electron transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The introduction of phenanthroline structure enhances the excited state lifetime of CDs and expands the conjugated length of their internal structure to enable the light-absorption to reach green light region, thereby enhancing photocatalytic activity. The as-designed CDs exhibit unprecedented photocatalytic capacity in photopolymerization even in large-volume reaction (100 mL) with high monomer conversion and narrow polymer dispersity (Mw/Mn < 1.20) under green light. The photocatalytic system is compatible with PET-RAFT polymerization of numerous monomers and the production of high molecular weight polyacrylate (Mn >250 000) with exquisite spatiotemporal control. Above results confirm the potential of CDs as photocatalyst, which has not been achieved with other CDs catalysts used in photo-RDRP. In addition, the construction of fluorescent polymer nanoparticles using CDs as both photocatalyst and phosphor through photoinitiated polymerization-induced self-assembly (Photo-PISA) technology is successfully demonstrated for the first time.

Polypeptide- and Protein-Based Conjugate Nanoparticles via Aqueous Ring-Opening Polymerization-Induced Self-Assembly (ROPISA).

Protein-polymer conjugates and polymeric nanomaterials hold great promise in many applications including biomaterials, medicine, or nanoelectronics. In this work, the first polymerization-induced self-assembly (PISA) approach performed in aqueous medium enabling protein-polymer conjugates and nanoparticles entirely composed of amino acids is presented by using ring-opening polymerization (ROP). It is indeed shown that aqueous ring-opening polymerization-induced self-assembly (ROPISA) can be used with protein or peptidic macroinitiators without prior chemical modification and afford the simple preparation of nanomaterials with protein-like property, for example, to implement biomimetic thermoresponsivity in drug delivery.

Long term (Minimum 10 Years) Survival and Outcomes of Pyrocarbon Interposition Shoulder Arthroplasty.

BACKGROUND: There is major controversies surrounding the use and longevity of Pyrocarbon Interposition Shoulder Arthroplasty (PISA). The objective of this study was to investigate the long-term survival and outcomes (minimum 10-year) following PISA for osteoarthritis (OA) in young /active patients. METHODS: This was a retrospective review of prospectively collected data of patients who underwent PISA (InSpyre, Tornier-Stryker, USA) for OA between 2009 and 2012. Arthroplasty survival was known for 71 patients followed longitudinally for a minimum of 10 years. The clinical and radiological outcomes were assessed in 62 patients (62 shoulders) reviewed with radiographs. The mean age at surgery was 60 years (range, 23-72 years) and 31 shoulders (50%) underwent prior surgery before PISA. The diagnosis was primary osteoarthritis (POA=29), post-traumatic osteoarthritis (PTOA=23), post-instability osterarthritis (PIOA=10). Clinical failure was defined as repeat surgical intervention involving prosthesis revision. Clinical outcomes were assessed with Constant score (CS) and Subjective shoulder Value (SSV). The mean duration of follow-up was 11 ± 0.6 years (range, 10 to 14 years). RESULTS: Overall, the survival rate was 90% (95% CI: 82.8-96.8) at 5 years and 87% (95% CI: 79-94.8) at 10 years follow-up. Survival was 100% in PTOA (type 1 fracture sequelae) and in PIOA as well as 95% in primary OA with type-A glenoid. Revision surgery was significantly higher in biconcave (type-B2) glenoid (44%) compared to concentric (type-A) glenoid (2%), respectively (p=0.002). Among the 7 patients who were revised to RSA, 5 had painful glenoid erosion and 2 had bipolar (glenoid and humeral) erosion with thinning and finally fracture of the greater tuberosity (GT). Two shoulders with glenohumeral erosion were associated with secondary rotator cuff tears (one supraspinatus and one subscapularis tear). The mean time to revision and revision was 4 ± 1.7 years. Glenoid wear was more often superior (81%) than central (19%), p<0.001. For those shoulders not revised, the mean CS and SSV significantly increased from 39 ±14 to 70 ±14 points and 34% ±15 to 75% ±17, respectively (p<0.001). CONCLUSION: PISA is an efficient and durable surgical procedure for the treatment of young/active patients with post-traumatic OA, post-instability OA, and primary OA with concentric (type A) glenoid erosion, but not for those with biconcave (type B2) glenoid. Biconcave (type B2) glenoid and subscapularis tear or insufficiency are risk factors for failure and revision.

Binding Pattern and Structural Interactome of the Anticancer Drug 5-Fluorouracil: A Critical Review.

5-Fluorouracil (5-FU) stands as one of the most widely prescribed chemotherapeutics. Despite over 60 years of study, a systematic synopsis of how 5-FU binds to proteins has been lacking. Investigating the specific binding patterns of 5-FU to proteins is essential for identifying additional interacting proteins and comprehending their medical implications. In this review, an analysis of the 5-FU binding environment was conducted based on available complex structures. From the earliest complex structure in 2001 to the present, two groups of residues emerged upon 5-FU binding, classified as P- and R-type residues. These high-frequency interactive residues with 5-FU include positively charged residues Arg and Lys (P type) and ring residues Phe, Tyr, Trp, and His (R type). Due to their high occurrence, 5-FU binding modes were simplistically classified into three types, based on interactive residues (within <4 Å) with 5-FU: Type 1 (P-R type), Type 2 (P type), and Type 3 (R type). In summary, among 14 selected complex structures, 8 conform to Type 1, 2 conform to Type 2, and 4 conform to Type 3. Residues with high interaction frequencies involving the N1, N3, O4, and F5 atoms of 5-FU were also examined. Collectively, these interaction analyses offer a structural perspective on the specific binding patterns of 5-FU within protein pockets and contribute to the construction of a structural interactome delineating the associations of the anticancer drug 5-FU.

What Fosters School Connectedness? The Roles of Classroom Interactions and Parental Support.

Although research has identified the impact of school connectedness on a variety of outcomes for adolescents, much less work has focused on identifying its precursors. This study examined the relative influences of classroom interactions and parental support on elements of school connectedness among a sample of 4838 students (Mage = 15.84, SD = 0.29; 49.1% female) in the United States from the Programme for International Student Assessment (PISA) 2018 data. The results showed that three domains of classroom interactions (i.e., classroom management, instructional support, and emotional support) and parental support played unique roles in predicting school connectedness (i.e., teacher support and school belonging). Specifically, classroom management positively predicted both teacher support and school belonging; instructional support, especially directed instruction, positively predicted teacher support; emotional support was unrelated to teacher support and school belonging. Parental support positively predicted school belonging, but not teacher support. Overall, these findings highlight the roles of both teachers and parents in providing developmentally appropriate support to facilitate school connectedness.

Degradable Block Copolymer Nanoparticles Synthesized by Polymerization-Induced Self-Assembly.

Polymerization-induced self-assembly (PISA) combines polymerization and in situ self-assembly of block copolymers in one system and has become a widely used method to prepare block copolymer nanoparticles at high concentrations. The persistence of polymers in the environment poses a huge threat to the ecosystem and represents a significant waste of resources. There is an urgent need to develop novel chemical approaches to synthesize degradable polymers. To meet with this demand, it is crucial to install degradability into PISA nanoparticles. Most recently, degradable PISA nanoparticles have been synthesized by introducing degradation mechanisms into either shell-forming or core-forming blocks. This Minireview summarizes the development in degradable block copolymer nanoparticles synthesized by PISA, including shell-degradable, core-degradable, and all-degradable nanoparticles. Future development will benefit from expansion of polymerization techniques with new degradation mechanisms and adaptation of high-throughput approaches for both PISA syntheses and degradation studies.

Light-Triggered Reversible Swelling of Polymeric Spheres via Surfactant-Free RAFT Emulsion Polymerization-Induced Self-Assembly.

Responsive photonic crystals (RPCs) assembled by monodisperse colloidal particles have attracted enormous interest recently due to their tremendous applications in smart devices. Their structural colors can be determined by particle sizes. However, the lack of a reliable way to tune the sizes in situ limits their development. Herein, we present an efficient route to solve this problem through the fabrication of spherical polymeric particles with light-triggered reversible swelling behavior via surfactant-free reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization-induced self-assembly (PISA). Amphiphilic macro-RAFT agents containing azobenzene groups were synthesized and subsequently employed to mediate the polymerization of methyl methacrylate. Uniform submicron spheres were obtained by modulating solid contents and other parameters. Benefiting from the photoisomerization of azobenzene moieties, the particle sizes expanded and contracted upon alternative ultraviolet/visible-light irradiation accordingly. This strategy will be a supplement to the emulsion PISA and especially give aid to the progress of the RPC materials.

Axial postural abnormalities and pain in Parkinson's disease.

Axial postural abnormalities and pain are two main determinants of poor quality of life in patients with Parkinson's disease (PD). Indeed, a detailed characterization of pain and other non-motor symptoms in patients with PAs has not been provided yet. The aim of this study is to assess the phenomenology of pain and other non-motor symptoms in PD patients with Pisa syndrome and camptocormia compared to PD patients without axial postural abnormality. Forty-five PD participants were equally distributed in three groups: patients with Pisa syndrome (PS), patients with Camptocormia (CC), and patients without postural abnormalities (PD). Pain characteristics were assessed by Kings Parkinson's Pain Scale (KPPS), brief pain inventory (BPI), and numeric pain rating scale (NRS). All participants completed clinical assessments by non-motor symptom scale (NMSS), and movement disorder society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts II-III. Patients with and without axial postural abnormalities showed one or more types of pain, being fluctuation, nocturnal, chronic, and musculoskeletal the most frequently reported in Pisa Syndrome and camptocormia. PD group compared with PS and CC groups showed differences in the KPPS, NMSS, BPI pain severity and interference, and NRS total scores. No significant differences were found between PS group compared with CC group with exception of the NMSS total scores. PD patients with Pisa syndrome or camptocormia have a higher burden of musculoskeletal, chronic and fluctuation pain than PD patients without axial postural abnormalities, suggesting different etiologies of pain and possible different treatments.

Analysis of applying a patient safety taxonomy to patient and clinician-reported incident reports during the COVID-19 pandemic: a mixed methods study.

BACKGROUND: The COVID-19 pandemic resulted in major disruption to healthcare delivery worldwide causing medical services to adapt their standard practices. Learning how these adaptations result in unintended patient harm is essential to mitigate against future incidents. Incident reporting and learning system data can be used to identify areas to improve patient safety. A classification system is required to make sense of such data to identify learning and priorities for further in-depth investigation. The Patient Safety (PISA) classification system was created for this purpose, but it is not known if classification systems are sufficient to capture novel safety concepts arising from crises like the pandemic. We aimed to review the application of the PISA classification system during the COVID-19 pandemic to appraise whether modifications were required to maintain its meaningful use for the pandemic context. METHODS: We conducted a mixed-methods study integrating two phases in an exploratory, sequential design. This included a comparative secondary analysis of patient safety incident reports from two studies conducted during the first wave of the pandemic, where we coded patient-reported incidents from the UK and clinician-reported incidents from France. The findings were presented to a focus group of experts in classification systems and patient safety, and a thematic analysis was conducted on the resultant transcript. RESULTS: We identified five key themes derived from the data analysis and expert group discussion. These included capitalising on the unique perspective of safety concerns from different groups, that existing frameworks do identify priority areas to investigate further, the objectives of a study shape the data interpretation, the pandemic spotlighted long-standing patient concerns, and the time period in which data are collected offers valuable context to aid explanation. The group consensus was that no COVID-19-specific codes were warranted, and the PISA classification system was fit for purpose. CONCLUSIONS: We have scrutinised the meaningful use of the PISA classification system's application during a period of systemic healthcare constraint, the COVID-19 pandemic. Despite these constraints, we found the framework can be successfully applied to incident reports to enable deductive analysis, identify areas for further enquiry and thus support organisational learning. No new or amended codes were warranted. Organisations and investigators can use our findings when reviewing their own classification systems.

Obesity Is Associated with the Severity of Periodontal Inflammation Due to a Specific Signature of Subgingival Microbiota.

The aim of this study was to analyze the link between periodontal microbiota and obesity in humans. We conducted a cohort study including 45 subjects with periodontitis divided into two groups: normo-weighted subjects with a body mass index (BMI) between 20 and 25 kg/m2 (n = 34) and obese subjects with a BMI > 30 kg/m2 (n = 11). Our results showed that obesity was associated with significantly more severe gingival inflammation according to Periodontal Inflamed Surface Area (PISA index). Periodontal microbiota taxonomic analysis showed that the obese (OB) subjects with periodontitis were characterized by a specific signature of subgingival microbiota with an increase in Gram-positive bacteria in periodontal pockets, associated with a decrease in microbiota diversity compared to that of normo-weighted subjects with periodontitis. Finally, periodontal treatment response was less effective in OB subjects with persisting periodontal inflammation, reflecting a still unstable periodontal condition and a risk of recurrence. To our knowledge, this study is the first exploring both salivary and subgingival microbiota of OB subjects. Considering that OB subjects are at higher periodontal risk, this could lead to more personalized preventive or therapeutic strategies for obese patients regarding periodontitis through the specific management of oral microbiota of obese patients.

Massive Solubility Changes in Neuronal Proteins upon Simulated Traumatic Brain Injury Reveal the Role of Shockwaves in Irreversible Damage.

We investigated the immediate molecular consequences of traumatic brain injuries (TBIs) using a novel proteomics approach. We simulated TBIs using an innovative laboratory apparatus that employed a 5.1 kg dummy head that held neuronal cells and generated a ≤4000 g-force acceleration upon impact. A Proteome Integral Solubility Alteration (PISA) assay was then employed to monitor protein solubility changes in a system-wide manner. Dynamic impacts led to both a reduction in neuron viability and massive solubility changes in the proteome. The affected proteins mapped not only to the expected pathways, such as those of cell adhesion, collagen, and laminin structures, as well as the response to stress, but also to other dense protein networks, such as immune response, complement, and coagulation cascades. The cellular effects were found to be mainly due to the shockwave rather than the g-force acceleration. Soft materials could reduce the impact's severity only until they were fully compressed. This study shows a way of developing a proteome-based meter for measuring irreversible shockwave-induced cell damage and provides a resource for identifying protein biomarkers of TBIs and potential drug targets for the development of products aimed at primary prevention and intervention.

The Association Between Perceived Discriminatory Climate in School and Student Performance in Math and Reading: A Cross-National Analysis Using PISA 2018.

The negative consequences of perceived ethnic discrimination on adolescent adjustment are well documented. Less is known, however, about the consequences of discriminatory climates in school, beyond the individual experiences of discrimination. This study investigated whether a perceived discriminatory climate in school is associated with lower academic performance across adolescents from ethnic minority and majority groups, and which psychological mechanisms may account for this link. Using the 2018 Programme for International Student Assessment (PISA) data, the participants were 445,534 adolescents (aged 15-16, 50% girls) in 16,002 schools across 60 countries. In almost all countries, a discriminatory climate-i.e., student perceptions of teachers' discriminatory beliefs and behaviors in school-was associated with lower math and reading scores across all pupils, although minorities perceived a more discriminatory climate. Lower school belonging and lower values attributed to learning partially mediated these associations. The findings demonstrate that schools' ethnic and racial climates predict standardized academic performance across schools and countries among pupils from both ethnic majority and minority groups.

From asking to observing. Behavioural measures of socio-emotional and motivational skills in large-scale assessments.

Socio-emotional and motivational skills are routinely measured using self-reports in large-scale educational assessments. Measures exploiting test-takers' behaviour during the completion of questionnaires or cognitive tests are increasingly used as alternatives to self-reports in the economics of education literature. We compute behavioural measures of socio-emotional and motivational skills using data from the Programme for International Student Assessment (PISA). We find that these measures capture important aspects of students' academic profiles: some are importantly associated with contemporaneous performance and educational attainment and most measures have a high degree of stability over time. However, these measures are only limitedly correlated among themselves and have low correlations with self-report measures of the same constructs. This is likely a reflection of the fact that behavioural measures are representations of the test taker current 'state', rather than descriptions of the participant view of their own 'trait' like the self-report measures. Moreover, the low correlation across measures suggests that they capture different behavioural responses to the test-taking situation. These differences are still limitedly understood because the measures are constructed ex-post using collateral information collected during the administration of assessments rather than developed ex ante in line with theoretical models of human cognition and affect.

RAFT-Mediated Emulsion Polymerization-Induced Self-Assembly for the Synthesis of Core-Degradable Waterborne Particles.

Poly(N-acryloylmorpholine) (PNAM)-decorated waterborne nanoparticles comprising a core of either degradable polystyrene (PS) or poly(n-butyl acrylate) (PBA) were synthesized by polymerization-induced self-assembly (PISA) in water. A PNAM bearing a trithiocarbonate chain end (PNAM-TTC) was extended via reversible addition-fragmentation chain transfer (RAFT)-mediated emulsion copolymerization of either styrene (S) or n-butyl acrylate (BA) with dibenzo[c,e]oxepane-5-thione (DOT). Well-defined amphiphilic block copolymers were obtained. The in situ self-assembly of these polymers resulted in the formation of stable nanoparticles. The insertion of thioester units in the vinylic blocks enabled their degradation under basic conditions. The same strategy was then applied to the emulsion copolymerization of BA with DOT using a poly(ethylene glycol) (PEG) equipped with a trithiocarbonate end group, resulting in PEG-decorated nanoparticles with degradable PBA-based cores.

Unimer Exchange Is not Necessary for Morphological Transitions in Polymerization-Induced Self-Assembly.

Polymerization-induced self-assembly (PISA) has established itself as a powerful and straightforward method to produce polymeric nano-objects of various morphologies in (aqueous) solution. Generally, spheres are formed in the early stages of polymerization that may evolve to higher order morphologies (worms or vesicles), as the solvophobic block grows during polymerization. Hitherto, the mechanisms involved in these morphological transitions during PISA are still not well understood. Combining a systematic study of a representative PISA system with rheological measurements, we demonstrate that-unexpectedly-unimer exchange is not necessary to form higher order morphologies during radical RAFT-mediated PISA. Instead, in the investigated aqueous PISA, the monomer present in the polymerization medium is responsible for the morphological transitions, even though it slows down unimer exchange.

Group-Transfer Polymerization-Induced Self-Assembly (GTPISA) in Non-polar Media: An Organocatalyzed Route to Block Copolymer Nanoparticles at Room Temperature.

Polymerization-induced self-assembly (PISA) enables the synthesis at large scale of a wide variety of functional nanoparticles. However, a large number of works are related to controlled radical polymerization (CRP) methods and are generally undertaken at elevated temperatures (>50 °C). Here is the first report on methacrylate-based nanoparticles fabricated by group transfer polymerization-induced self-assembly (GTPISA) in non-polar media (n-heptane). This GTPISA process is achieved at room temperature (RT) using 1-methoxy-1-(trimethylsiloxy)-2-methylprop-1-ene (MTS) and tetrabutylammonium bis-benzoate (TBABB) as initiator and organic catalyst, respectively. Under these conditions, well-defined metal-free and colorless diblock copolymers are produced with efficient crossover from the non-polar stabilizing poly(lauryl methacrylate) (PLMA) block to the non-soluble poly(benzyl methacrylate) (PBzMA) segment. The resulting PLMA-b-PBzMA block copolymers simultaneously self-assemble into nanostructures of various sizes and morphologies. GTPISA in non-polar solvent proceeds rapidly at RT and avoids the use of sulfur or halogenated compounds or metallic catalysts associated with the implementation of CRP methods, thus expanding the potential of PISA formulations for applications in non-polar environments.

Beyond the Covid-19 pandemic: remote learning and education inequalities.

Is remote learning associated with education inequalities? We use PISA 2018 data from five European countries-France, Germany, Italy, Spain and the United Kingdom-to investigate whether education outcomes are related to the possession of the resources needed for distance learning. After controlling for a wide set of covariates, fixed effects, different specifications and testing the stability of coefficients, we find that remote learning is positively associated with average education outcomes, but also with strong and significant education inequalities. Our results show that negative gaps are larger where online schooling is more widespread, across countries, locations, and school types. More generally, remote learning inequalities appear to be associated with technological network externalities: they increase as digital education spreads. Policy makers must guarantee to all students and schools the possession of the resources needed for remote learning, but to reach this goal efficiently they must adapt their actions to the characteristics of countries, areas and school systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s10663-022-09556-7.

Galilean resonances: the role of experiment in Turing's construction of machine intelligence.

In 1950, Alan Turing proposed his iconic imitation game, calling it a 'test', an 'experiment', and the 'the only really satisfactory support' for his view that machines can think. Following Turing's rhetoric, the 'Turing test' has been widely received as a kind of crucial experiment to determine machine intelligence. In later sources, however, Turing showed a milder attitude towards what he called his 'imitation tests'. In 1948, Turing referred to the persuasive power of 'the actual production of machines' rather than that of a controlled experiment. Observing this, I propose to distinguish the logical structure from the rhetoric of Turing's argument. I argue that Turing's proposal of a crucial experiment may have been a concession to meet the standards of his interlocutors more than his own, while his construction of machine intelligence rather reveals a method of successive idealizations and exploratory experiments. I will draw a parallel with Galileo's construction of idealized fall in a void and the historiographical controversies over the role of experiment in Galilean science. I suggest that Turing, like Galileo, relied on certain kinds of experiment, but also on rhetoric and propaganda to inspire further research that could lead to convincing scientific and technological progress.

Impact of extracurricular synchronous and asynchronous computer-mediated communication between students and teachers on digital reading performance: Evidence from 53 countries/regions.

This study compared the effects of extracurricular synchronous computer-mediated communication (SCMC) and asynchronous computer-mediated communication (ASCMC) between students and teachers on students' digital reading performance at different frequencies. 392,269 samples from 53 countries/regions that participated in the Programme for International Student Assessment 2018 were collected. Multilevel regression analysis showed that SCMC negatively influenced digital reading performance across countries/regions. As the frequency decreased, the negative effect of SCMC diminished. In contrast, ASCMC at a moderately low frequency could facilitate digital reading performance in some countries/regions; however, as frequency increased, the positive effect became negative. These results showed that synchronicity played a role in predicting students' digital reading performance. This study also explored the mediating effect of metacognition with Nelson and Naren's metacognitive control-monitoring model. A multilevel mediation analysis proved that the effects of SCMC and ASCMC on digital reading performance were mediated by students' metacognition of assessing credibility. Practical implications and suggestions for students' self-paced learning were discussed with the purpose of promoting the effective use of extracurricular CMC between students and teachers and improving students' digital reading achievement in the post-COVID-19 pandemic era.