Notes

A new Bayesian way for calibrating danger inclination within the Balloon Analogue Danger Task.
Objective observations, such as the patient's colour, pain-level changes, and behavioural observations, were identified as signs that would trigger nurses' concerns. Nurse's intuitive feelings or gut feelings when seeing a patient was also identified as an important factor for identifying a deteriorating paediatric patient. A "gut feeling" was described as both a reaction to patient signs and a feeling based on the nurse's intuition gained through experience. The signs or symptoms that would trigger this "gut feeling" were not identified.The active stages of intestinal inflammation and the pathogenesis of ulcerative colitis are associated with superficial mucosal damage and intermittent wounding that leads to epithelial barrier defects and increased permeability. The standard therapeutic interventions for colitis have focused mainly on maintaining the remission levels of the disease. Nonetheless, such treatment strategies (using anti-inflammatory, immunomodulatory agents) do not address colitis' root cause, especially the mucosal damage and dysregulated intestinal barrier functions. Restoration of barrier functionality by mucosal healing or physical barrier protecting strategies shall be considered as an initial event in the disease suppression and progression. Herein, a biphasic hyaluronan (HA) enema suspension, naïve-HA systems that protect the dysregulated gut epithelium by decreasing the inflammation, permeability, and helping in maintaining the epithelial barrier integrity in the dextran sodium sulfate-induced colitis mice model is reported. Furthermore, HA-based system modulates intestinal epithelial junctional proteins and regulatory signaling pathways, resulting in attenuation of inflammation and mucosal protection. The results suggest that HA-based system can be delivered as an enema to act as a barrier protecting system for managing distal colonic inflammatory diseases, including colitis.The aim of this study was to identify the epidemiology, aetiology as well as the knowledge, attitudes, and practices relating to burn injuries in Palestine. A mixed-method approach was used. A survey was distributed to a total of 1500 households selected by randomised approach. The survey was standardised based on World Health Organisation's guidelines for conducting community surveys on injury. Additionally, there were 12 focus group discussions and 10 key informant interviews to collect rich qualitative data. In the West Bank and Gaza, 1.5% of Palestinians had experienced serious burn injuries in the 12 months. The total sample of 1500 yields a margin of error (plus/minus) = 2.5% at a 95% level of confidence and a response distribution (P = 50%) with 3% non-response rate. Of the 1500 households approached, 184 reported a total of 196 burn injuries, with 87.2% occurring inside the home 69.4% were females and 39.3% were children. The main source of reported cause of burn was heat and flame (36%), electric current (31.6%), hot liquid (28.6%), and chemicals (2.7%). The most common first aid for burns was pouring water (74.7%). People in rural, refugee, and Bedouin settings had the highest incidence of burns. This study provides the burn prevalence rate, explanatory factors that contribute to the frequency of burns in Palestine. Making burn prevention a higher priority within the national policy is crucial.
Persistent vertebral artery occlusion caused by compression of cervical facet joint originated osteophyte is exceptional rare. The authors sought to achieve adequate decompression of the vertebral artery (VA) with less stability decrease and movement restriction via the anterior approach, and to the authors' knowledge, no case of anterior decompression of this condition has been reported, and combination of intraoperative indocyanine green (ICG) angiography in the setting of VA decompression is also rare.

A 77-year-old man presented continuous vertigo, unsteady gait and dysphagia with no relationship to the head movement. Preoperative computed tomography angiography (CTA) and digital substraction angiography (DSA) examination revealed the left vertebral artery was severely compressed at C
level with approximately 95% occlusion due to a left C
facet joint originated large osteophyte. Successful anterior decompression was performed without fusion and intraoperative ICG fluorescence angiography proved excellent blood flow. After surgery, vertebrobasilar insufficiency symptoms remarkably improved with no neurological deficits and no recurrence at 12 months' follow-up.

The authors' therapeutic strategy of anterior decompression was successful in treating VA compression due to facet joint overgrowth with adequate exposure, no stability decrease and movement restriction, and lower rates of neck pain and blood loss.
The authors' therapeutic strategy of anterior decompression was successful in treating VA compression due to facet joint overgrowth with adequate exposure, no stability decrease and movement restriction, and lower rates of neck pain and blood loss.The hybridization of conductive nanospecies has garnered significant research interest because of its high efficacy in improving the diverse functionalities of nanostructured materials. In this study, a novel synthetic strategy is developed to optimize the defect structure, structural ordering, and energy-related functionality of nanostructured-materials by employing a multilayer multicomponent two-dimenstional (2D) graphene/metal oxide/graphene nanosheet (NS) as a versatile hybridization matrix. The hybridization of the robust trilayer, polydiallyldiammonium (PDDA)-anchored reduced-graphene oxide (prGO)/metal oxide/prGO NS effectively enhance the structural ordering and porosity of the hybridized MoS2 /MnO2 NS through suppression of defect formation and tight stacking. In comparison with monolayer rGO/RuO2 NS-based homologs, the 2D superlattice trilayer prGO/RuO2 /prGO NS hybrids deliver better functionalities as a hydrogen evolution electrocatalyst and as a supercapacitor electrode, demonstrating the merits of hybridization with multilayer NSs. The advantages of using multilayer multicomponent conductive NSs as hybridization matrices arise from the enhancement of charge and mass transport through the layer flattening or defect suppression of the hybridized NSs and the increase in porosity, as evidenced by density functional theory calculations. Finally, the universal utility of multilayer NSs is confirmed by investigating the strong effect of the stacking order on the electrocatalytic functionality of MoS2 /rGO/RuO2 films fabricated through layer-by-layer deposition.Nuclear receptors influence nearly every system of the body and our lives depend on correct nuclear receptor signaling. Thus, a key environmental and pharmaceutical quest is to identify and detect chemicals which interact with nuclear hormone receptors, including endocrine disrupting chemicals, therapeutic receptor modulators, and natural hormones. Previously reported biosensors of nuclear hormone receptor ligands facilitated rapid detection of nuclear receptor ligands using cell-free protein synthesis (CFPS). In this work, the advantages of CFPS are further leveraged and combined with kinetic analysis, autoradiography, and western blot to elucidate the molecular mechanism of this biosensor. Additionally, mathematical simulations of enzyme kinetics are used to optimize the biosensor assay, ultimately lengthening its readable window by five-fold and improving sensor signal strength by two-fold. This approach enabled the creation of an on-demand thyroid hormone biosensor with an observable color-change readout. This mathematical and experimental approach provides insight for engineering rapid and field-deployable CFPS biosensors and promises to improve methods for detecting natural hormones, therapeutic receptor modulators, and endocrine disrupting chemicals. This article is protected by copyright. All rights reserved.Diadenosine-5',5'''-P1, P4-tetraphosphate (Ap4A) is a second messenger playing a crucial role in various life activities of bacteria. The increase of Ap4A expression is pleiotropic, resulting in an impairment in the formation of biofilm and other physiological functions in some bacteria. However, Ap4A function in Streptococcus mutans, an important pathogen related to dental caries, remains unknown. In this work, the Ap4A hydrolase, YqeK, was identified and characterized in S. mutans. Then, the effects of yqeK deletion on the growth, biofilm formation, and exopolysaccharide (EPS) quantification in S. mutans were determined by the assessment of the growth curve, crystal violet, and anthrone-sulfuric acid, respectively, and visualized by microscopy. The results showed that the in-frame deletion of the yqeK gene in S. mutans UA159 led to an increase in Ap4A levels, lag phase in the early growth, as well as decrease in biofilm formation and water-insoluble exopolysaccharide production. Global gene expression profile showed that the expression of 88 genes was changed in the yqeK mutant, and among these, 42 were upregulated and 46 were downregulated when compared with the wild-type S. mutans UA159. Upregulated genes were mainly involved in post-translational modification, protein turnover, and chaperones, while downregulated genes were mainly involved in carbohydrate transport and metabolism. Important virulence genes related to biofilms, such as gtfB, gtfC, and gbpC, were also significantly downregulated. In conclusion, these results indicated that YqeK affected the formation of biofilms and the expression of biofilm-related genes in S. mutans.In March 2021, Lao People's Democratic Republic (Laos) reported an avian influenza A(H5N6) virus infection in a 5-year-old child identified through sentinel surveillance. This was the first human A(H5N6) infection reported outside of China. A multidisciplinary investigation undertook contact tracing and enhanced human and animal surveillance in surrounding villages and live bird markets. Seven Muscovy ducks tested positive for highly pathogenic avian influenza A(H5N6) viruses. Sequenced viruses belonged to clade 2.3.4.4h and were closely related to viruses detected in poultry in Vietnam and to previous viruses detected in Laos. Surveillance and coordinated outbreak response remain essential to global health security.Lignocellulose-based hierarchical porous carbon is a very promising electrode material for supercapacitors, but lower volumetric energy density and yield have hindered its practical applications. Herein, a low-temperature dehydration carbon-fixation method using NH 4 Cl as modification reagent was developed to prepare rice husk-based hierarchical porous carbon (RHPC) with high volumetric performance and yield. RHPC-N electrode exhibits higher volumetric specific capacitance of 134.4 F cm -3 than that of RHPC electrode (98.4 F cm -3 ) in the 1 M Et 4 NBF 4 /PC electrolyte. The volumetric energy density (28.8 Wh L -1 ) of RHPC-N electrode is 37.1% higher than that of RHPC electrode (21.0 Wh L -1 ), which greatly enhances the practical application potential of RHPC in supercapacitors. Moreover, the yield of RHPC increases 1.2 times by this method, which greatly improves the production capacity and reduces the cost. This research establishes a simple and highly efficient method to improve the volumetric energy density and the yield of lignocellulose-based hierarchical porous carbon.
Molluscum contagiosum (MC) is a common viral infection. Hypersensitivity reactions reminiscent of Gianotti-Crosti syndrome, termed Gianotti-Crosti syndrome-like reaction (GCLR), have been reported in a subset of patients. We report a series of patients with GCLR, better delineating its clinical presentation and course.

Retrospective chart review of all children presenting with GCLR at our Pediatric Skin Center between 2015 and 2020.

26 children (14 boys) with a median age of 6.5 (3-11.3) years were included. GCLR involved the extensor surfaces of the extremities in all patients. More widespread eruptions also affected the trunk and face in 7 (27%) and 6 (23%) children respectively. Involvement of the skin overlying the Achilles tendons was a new finding in 4 (15%) children. Itch was the predominant symptom in 20 (77%) patients. The rash responded to topical and/or systemic corticosteroids and resolved within four weeks. GCLR was followed by clearance of MC in all patients within 9 (4-24) weeks.

GCLR is a characteristic acute, wide-spread, pruritic papular eruption, which often leads to emergency consultations and anxiety in affected patients. GCLR responds well to corticosteroid treatment, has a benign course, and heralds the healing of MC.
GCLR is a characteristic acute, wide-spread, pruritic papular eruption, which often leads to emergency consultations and anxiety in affected patients. GCLR responds well to corticosteroid treatment, has a benign course, and heralds the healing of MC.
This study aimed to evaluate the comorbidities among severe and non-severe COVID-19 patients in Asian versus non-Asian populations.

Systemic review and Meta-analysis.

A systematic literature search was conducted using PubMed, Embase, Scopus and the web of science Database up to 24 March 2021. Odds ratios were calculated using a random-effects model.

We identified 66 studies including 39 Asian and 27 non-Asian studies. This study demonstrated that the proportion of hypertension was significantly higher in severe group than in non-severe group for Asian (OR=2.46) and non-Asian (OR=1.60, 95% CI 1.37-1.86, I
=84%; p<.00001) patients. Similarly, the proportion of diabetes, cardiovascular disease and chronic kidney disease was significantly higher in severe group than in non-severe group for both Asian and non-Asian studies. We found no statistically significant difference between the severe versus non-severe group for cancer (OR=1.26) and chronic obstructive pulmonary disease (OR=1.32) among non-Asian patients.
We identified 66 studies including 39 Asian and 27 non-Asian studies. This study demonstrated that the proportion of hypertension was significantly higher in severe group than in non-severe group for Asian (OR = 2.46) and non-Asian (OR = 1.60, 95% CI 1.37-1.86, I2 = 84%; p less then .00001) patients. Similarly, the proportion of diabetes, cardiovascular disease and chronic kidney disease was significantly higher in severe group than in non-severe group for both Asian and non-Asian studies. We found no statistically significant difference between the severe versus non-severe group for cancer (OR = 1.26) and chronic obstructive pulmonary disease (OR = 1.32) among non-Asian patients.
The COVID-19 pandemic has highlighted the need for targeted local interventions given substantial heterogeneity within cities and counties. Publicly available case data are typically aggregated to the city or county level to protect patient privacy, but more granular data are necessary to identify and act upon community-level risk factors that can change over time.

Individual COVID-19 case and mortality data from Massachusetts were geocoded to residential addresses and aggregated into two time periods "Phase 1" (March-June 2020) and "Phase 2" (September 2020 to February 2021). Institutional cases associated with long-term care facilities, prisons, or homeless shelters were identified using address data and modeled separately. Census tract sociodemographic and occupational predictors were drawn from the 2015-2019 American Community Survey. We used mixed-effects negative binomial regression to estimate incidence rate ratios (IRRs), accounting for town-level spatial autocorrelation.

Case incidence was elevated in census tracts with higher proportions of Black and Latinx residents, with larger associations in Phase 1 than Phase 2. Case incidence associated with proportion of essential workers was similarly elevated in both Phases. Mortality IRRs had differing patterns from case IRRs, decreasing less substantially between Phases for Black and Latinx populations and increasing between Phases for proportion of essential workers. Mortality models excluding institutional cases yielded stronger associations for age, race/ethnicity, and essential worker status.

Geocoded home address data can allow for nuanced analyses of community disease patterns, identification of high-risk subgroups, and exclusion of institutional cases to comprehensively reflect community risk.
Geocoded home address data can allow for nuanced analyses of community disease patterns, identification of high-risk subgroups, and exclusion of institutional cases to comprehensively reflect community risk.
Many people with diabetes will develop foot ulcers. To reduce risk, it is recommended that the feet are protected against harm and checked daily. Spouses can help people with diabetes care for their feet.

A randomized parallel arm design compared information sheets given to participants with diabetes and their spouses (dyad group; n = 64) to an information sheet given only to participants with diabetes (individual group; n = 69). The self-reported number of days that the participant with diabetes' feet were (1) checked for problems and (2) protected against problems occurring (by the person with diabetes and/or the spouse) were summed for the week after receiving the information sheet. ANCOVAs tested the effects of group.

Frequency of foot detection behavior (Participant + Spouse) was significantly higher in the dyad group compared with the individual group. This was not the case for foot protection behavior (Participant + Spouse). Findings revealed greater levels of spousal support (for both protection and detection behavior) in the dyad group compared to the individual group.

Clinical recommendations and advice on foot care delivered both to people with diabetes and their spouses can encourage greater foot care than if delivered to the patient alone.
Clinical recommendations and advice on foot care delivered both to people with diabetes and their spouses can encourage greater foot care than if delivered to the patient alone.The first step in photosynthesis is an extremely efficient energy transfer mechanism that led to the debate to which extent quantum coherence may be involved in the energy transfer between the photosynthetic pigments. In search of such a coherent behavior, we have embedded living cyanobacteria between the parallel mirrors of an optical microresonator irradiated with low intensity white light. As a consequence, we observe vacuum Rabi splitting in the transmission and fluorescence spectra as a result of strong light matter coupling of the chlorophyll a molecules in the photosystems (PSs) and the cavity modes. The Rabi-splitting scales with the number of the PSs chlorophyll a pigments involved in strong coupling indicating a delocalized polaritonic state. Our data provide evidence that a delocalized polaritonic state can be established between the chlorophyll a molecule of the PSs in living cyanobacterial cells at ambient conditions in a microcavity.Spatial confinement of matter in functional nanostructures has propelled these systems to the forefront of nanoscience, both as a playground for exotic physics and quantum phenomena and in multiple applications including plasmonics, optoelectronics, and sensing. In parallel, the emergence of monochromated electron energy loss spectroscopy (EELS) has enabled exploration of local nanoplasmonic functionalities within single nanoparticles and the collective response of nanoparticle assemblies, providing deep insight into associated mechanisms. However, modern synthesis processes for plasmonic nanostructures are often limited in the types of accessible geometry, and materials and are limited to spatial precisions on the order of tens of nm, precluding the direct exploration of critical aspects of the structure-property relationships. Here, the atomic-sized probe of the scanning transmission electron microscope is used to perform precise sculpting and design nanoparticle configurations. Using low-loss EELS, dynamic analyses of the evolution of the plasmonic response are provided. It is shown that within self-assembled systems of nanoparticles, individual nanoparticles can be selectively removed, reshaped, or patterned with nanometer-level resolution, effectively modifying the plasmonic response in both space and energy. This process significantly increases the scope for design possibilities and presents opportunities for unique structure development, which are ultimately the key for nanophotonic design.
GATA1 mutation plays an important role in initiating transient abnormal myelopoiesis (TAM) and in the clonal evolution towards acute megakaryoblastic leukaemia (AMKL) associated with Down syndrome (DS). This study aimed to develop and validate the clinical utility of a complementary DNA (cDNA) analysis in parallel with the conventional genomic DNA (gDNA) Sanger sequencing (Ss), as an initial screening test for GATA1 mutations.

GATA1 mutations were evaluated using both gDNA and cDNA in 14 DS patients using Ss and fragment analysis (FA), respectively.

The detection sensitivity of conventional gDNA sequencing was limited in low blast percentage TAM (LBP-TAM); however, cDNA-based Ss readily detected all the pathognomonic GATA1 mutations. The cDNA-based FA readily detected GATA1 frameshift mutation with a reliable sensitivity ranging from 0.005% to 0.01% of clonal cells.

GATA1 mutations are heterogeneous; therefore, we would like to propose a dual cDNA and gDNA analysis as a standard diagnostic approach, especially for LBP-TAM. cDNA-based FA promises an excellent sensitivity for detecting frameshift GATA1 mutations in the longitudinal clonal evolution towards AMKL without using a patient specific primer.
GATA1 mutations are heterogeneous; therefore, we would like to propose a dual cDNA and gDNA analysis as a standard diagnostic approach, especially for LBP-TAM. cDNA-based FA promises an excellent sensitivity for detecting frameshift GATA1 mutations in the longitudinal clonal evolution towards AMKL without using a patient specific primer.Impaired white adipose tissue (WAT) function has been recognized as a critical early event in obesity-driven disorders, but high buoyancy, fragility, and heterogeneity of primary adipocytes have largely prevented their use in drug discovery efforts highlighting the need for human stem cell-based approaches. Here, human stem cells are utilized to derive metabolically functional 3D adipose tissue (iADIPO) in a microphysiological system (MPS). Surprisingly, previously reported WAT differentiation approaches create insulin resistant WAT ill-suited for type-2 diabetes mellitus drug discovery. Using three independent insulin sensitivity assays, i.e., glucose and fatty acid uptake and suppression of lipolysis, as the functional readouts new differentiation conditions yielding hormonally responsive iADIPO are derived. Through concomitant optimization of an iADIPO-MPS, it is abled to obtain WAT with more unilocular and significantly larger (≈40%) lipid droplets compared to iADIPO in 2D culture, increased insulin responsiveness of glucose uptake (≈2-3 fold), fatty acid uptake (≈3-6 fold), and ≈40% suppressing of stimulated lipolysis giving a dynamic range that is competent to current in vivo and ex vivo models, allowing to identify both insulin sensitizers and desensitizers.The enhancement of the catalytic activity of gold nanoparticles with their decreasing size is often attributed to the increasing proportion of low-coordinated surface sites. This correlation is based on the paradigmatic picture of working gold nanoparticles as perfect crystal forms having complete and static outer surface layers whatever their size. This picture is incomplete as catalysts can dynamically change their structure according to the reaction conditions and as such changes can be eventually size-dependent. In this work, using aberration-corrected environmental electron microscopy, size-dependent crystal structure and morphological evolution in gold nanoparticles exposed to hydrogen at atmospheric pressure, with loss of the face-centered cubic crystal structure of gold for particle size below 4 nm, are revealed for the first time. Theoretical calculations highlight the role of mobile gold atoms in the observed symmetry changes and particle reshaping in the critical size regime. An unprecedented stable surface molecular structure of hydrogenated gold decorating a highly distorted core is identified. By combining atomic scale in situ observations and modeling of nanoparticle structure under relevant reaction conditions, this work provides a fundamental understanding of the size-dependent reactivity of gold nanoparticles with a precise picture of their surface at working conditions.Cancer immunotherapy based on natural killer (NK) cells is demonstrated to be a promising strategy. However, NK cells are deficient in ligands that target specific tumors, resulting in limited antitumor efficacy. Here, a glycoengineering approach to imitate the chimeric antigen receptor strategy and decorate NK cells with nanobodies to promote NK-based immunotherapy in solid tumors is proposed. Nanobody 7D12, which specifically recognizes the human epidermal growth factor receptor (EGFR) that is overexpressed on many solid tumors, is coupled to the chemically synthesized DBCO-PEG4 -GGG-NH2 by sortase A-mediated ligation to generate DBCO-7D12. The NK92MI cells bearing azide groups are then equipped with DBCO-7D12 via bioorthogonal click chemistry. The resultant 7D12-NK92MI cells exhibit high specificity and affinity for EGFR-overexpressing tumor cells in vitro and in vivo by the 7D12-EGFR interaction, causing increased cytokine secretion to more effectively kill EGFR-positive tumor cells, but not EGFR-negative cancer cells. Importantly, the 7D12-NK92MI cells also show a wide anticancer spectrum and extensive tumor penetration. Furthermore, mouse experiments reveal that 7D12-NK92MI treatment achieves excellent therapeutic efficacy and outstanding safety. The authors' works provide a cell modification strategy using specific protein ligands without genetic manipulation and present a potential novel method for cancer-targeted immunotherapy by NK cells.Healable stretchable conductive nanocomposites have received considerable attention. However, there has been a trade-off between the filler-induced electrical conductivity (σ) and polymer-driven mechanical strength. Here significant enhancements in both σ and mechanical strength by designing reversible covalent bonding of the polymer matrix and filler-matrix covalent bifunctionalization are reported. A polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene grafted with maleic anhydride forms the strong reversible covalent bonding with furfuryl alcohol through the Diels-Alder reaction. Small (7.5 nm) and medium (117 nm) nanosatellite particles are generated by in situ etching of silver flakes, enabling electron tunneling-assisted percolation. The filler-polymer covalent bifunctionalization is achieved by 3-mercaptopropanoic acid. Altogether, this results in high σ (108 300 S m-1 ) and tensile strength (16.4 MPa), breaking the trade-off behavior. A nearly perfect (≈100%) healing efficiency is achieved in both σ and tensile strength. The conductive nanocomposite figure of merit (1.78 T Pa S m-1 ), defined by the product of σ and tensile strength, is orders of magnitude greater than the data in literature. The nanocomposite may find applications in healable strain sensors and electronic materials.The double network (DN) hydrogel has attracted great attention due to its wide applications in daily life. However, synthesis DN hydrogel with excellent mechanical properties is still a big challenge. Here, polyacrylamide/copper-alginate double network (PAM/Cu-alg DN) hydrogel electrolyte is successfully synthesized by radiation-induced polymerization and cross-linking process of acrylamide with N, N'-methylene-bis-acrylamide and subsequent cupric ion (Cu2+ ) crosslinking of alginate. The content of sodium alginate, absorbed dose, and the concentration of Cu2+ are investigated in detail for improving the overall properties of PAM/Cu-alg DN hydrogel electrolyte. The PAM/Cu-alg DN hydrogel electrolyte synthesizes by radiation technique and Cu2+ crosslinking shows superior mechanical properties with a tensile strength of 2.25 ± 0.02 MPa, excellent energy dissipation mechanism, and the high ionic conductivity of 4.08 ± 0.17 mS cm-1 . PAM/Cu-alg DN hydrogel is characterized with attenuated total reflection Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and X-ray photoelectron spectroscopy analyses and the reason for the improvement of mechanical properties is illustrated. Furthermore, PAM/Cu-alg DN hydrogel electrolyte exhibits excellent strain-sensitivity, cyclic stability, and durability. This work paves for the new way for the preparation of DN hydrogel electrolytes with excellent properties.The purpose of this study was to investigate the potential clinical relevance of estimating the apparent clearance (CL/F) of atorvastatin through population pharmacokinetic (PopPK) modeling with samples collected in a real-life setting in a cohort of ambulatory patients at risk of cardiovascular disease by using an opportunistic sampling strategy easily accessible in clinical routine. A total of 132 pharmacokinetic (PK) samples at a maximum of three visits were collected in the 70 included patients. The effects of demographic, genetic, and clinical covariates were also considered. With the collected data, we developed a two-compartment PopPK model that allowed estimating atorvastatin CL/F relatively precisely and considering the genotype of the patient for SLCO1B1 c.521T>C single-nucleotide polymorphism (SNP). Our results indicate that the estimation of the CL/F of atorvastatin through our PopPK model might help in identifying patients at risk of myalgia. Indeed, we showed that a patient presenting a CL/F lower than 414.67 L h-1 is at risk of suffering from muscle discomfort. We also observed that the CL/F was correlated with the efficacy outcomes, suggesting that a higher CL/F is associated with a better drug efficacy (i.e., a greater decrease in total and LDL-cholesterol levels). In conclusion, our study demonstrates that PopPK modeling can be useful in daily clinics to estimate a patient' atorvastatin clearance. Notifying the clinician with this information can help in identifying patients at risk of myalgia and gives indication about the potential responsiveness to atorvastatin therapy.Plasmonic nanostructures have raised the interest of biomedical applications of surface-enhanced Raman scattering (SERS). To improve the enhancement and produce sensitive SERS probes, porous Au-Ag alloy nanoparticles (NPs) are synthesized by dealloying Au-Ag alloy NP-precursors with Au or Ag core in aqueous colloidal environment through galvanic replacement reaction. The novel designed core-shell Au-Ag alloy NP-precursors facilitate controllable synthesis of porous nanostructure, and dealloying degree during the reaction has significant effect on structural and spectral properties of dealloyed porous NPs. Narrow-dispersed dealloyed NPs are obtained using NPs of Au/Ag ratio from 10/90 to 40/60 with Au and Ag core to produce solid core@porous shell and porous nanoshells, having rough surface, hollowness, and porosity around 30-60%. The clean nanostructure from colloidal synthesis exhibits a redshifted plasmon peak up to near-infrared region, and the large accessible surface induces highly localized surface plasmon resonance and generates robust SERS activity. Thus, the porous NPs produce intensely enhanced Raman signal up to 68-fold higher than 100 nm AuNP enhancement at single-particle level, and the estimated Raman enhancement around 7800, showing the potential for highly sensitive SERS probes. The single-particle SERS probes are effectively demonstrated in quantitative monitoring of anticancer drug Doxorubicin release.Cardiovascular disease is a leading cause of death and disability worldwide. Although genetically modified mouse models offer great potential for robust research in vivo, in vitro studies using isolated cardiomyocytes also provide an important approach for investigating the mechanisms underlying cardiovascular disease pathogenesis and drug actions. Currently, isolation of mouse adult cardiomyocytes often relies on aortic retrograde intubation under a stereoscopic microscope, which poses considerable technical barriers and requires extensive training. Although a simplified, Langendorff-free method has been used to isolate viable cardiomyocytes from the adult mouse heart, the system requires enzymatic digestions and continuous manual technical operation. This study established an optimized approach that allows isolation of adult mouse cardiomyocytes and epicardial activation mapping of mouse hearts using a Langendorff device. We used retrograde puncture through the abdominal aorta in vivo and enzymatic digestion on the Langendorff perfusion device to isolate adult mouse cardiomyocytes without using a microscope. The yields of isolated cardiomyocytes were amenable to patch clamp techniques. Furthermore, this approach allowed epicardial activation mapping. We used a novel, simplified method to isolate viable cardiomyocytes from adult mouse hearts and to map epicardial activation. This novel approach could be beneficial in more extensive research in the cardiac field.Cobalt phosphides electrocatalysts have great potential for water splitting, but the unclear active sides hinder the further development of cobalt phosphides. Wherein, three different cobalt phosphides with the same hollow structure morphology (CoP-HS, CoP2 -HS, CoP3 -HS) based on the same sacrificial template of ZIF-67 are prepared. Surprisingly, these cobalt phosphides exhibit similar OER performances but quite different HER performances. The identical OER performance of these CoPx -HS in alkaline solution is attributed to the similar surface reconstruction to CoOOH. CoP-HS exhibits the best catalytic activity for HER among these CoPx -HS in both acidic and alkaline media, originating from the adjusted electronic density of phosphorus to affect absorption-desorption process on H. Moreover, the calculated ΔGH* based on P-sites of CoP-HS follows a quite similar trend with the normalized overpotential and Tafel slope, indicating the important role of P-sites for the HER process. Moreover, CoP-HS displays good performance (cell voltage of 1.67 V at a current density of 50 mA cm-2 ) and high stability in 1 M KOH. For the first time, this work detailly presents the critical role of phosphorus in cobalt-based phosphides for water splitting, which provides the guidance for future investigations on transition metal phosphides from material design to mechanism understanding.SMG8 (MIM *617315) is a regulatory subunit involved in nonsense-mediated mRNA decay (NMD), a cellular protective pathway that regulates mRNA transcription, transcript stability, and degrades transcripts containing premature stop codons. SMG8 binds SMG9 and SMG1 to form the SMG1C complex and inhibit the kinase activity of SMG1. Biallelic deleterious variants in SMG9 are known to cause a heart and brain malformation syndrome (HBMS; MIM #616920), whereas biallelic deleterious variants in SMG8 were recently described to cause a novel neurodevelopmental disorder (NDD) with dysmorphic facies and cataracts, now defined as Alzahrani-Kuwahara syndrome (ALKUS MIM #619268). Only eight subjects from four families with ALKUS have been described to date. Through research reanalysis of a nondiagnostic clinical exome, we identified a subject from a fifth unrelated family with a homozygous deleterious variant in SMG8 and features consistent with ALKUS. Interestingly, the subject also had unilateral microphthalmia, a clinical feature that has been described in SMG9-related disorder. Our study expands the phenotypic spectrum of SMG8-related disorder, demonstrates an overlapping phenotype between SMG8- and SMG9-related rare disease traits, provides further evidence for the SMG8 and SMG9 protein interactions, and highlights the importance of revisiting nondiagnostic exome data to identify and affirm emerging novel genes for rare disease traits.Understanding climate change impacts on top predators is fundamental to marine biodiversity conservation, due to their increasingly threatened populations and their importance in marine ecosystems. We conducted a systematic review of the effects of climate change (prolonged, directional change) and climate variability on seabirds and marine mammals. We extracted data from 484 studies (4808 published studies were reviewed), comprising 2215 observations on demography, phenology, distribution, diet, behaviour, body condition and physiology. The likelihood of concluding that climate change had an impact increased with study duration. However, the temporal thresholds for the effects of climate change to be discernibly varied from 10 to 29 years depending on the species, the biological response and the oceanic study region. Species with narrow thermal ranges and relatively long generation times were more often reported to be affected by climate change. This provides an important framework for future assessments, with guidance on response- and region-specific temporal dimensions that need to be considered when reporting effects of climate change. Finally, we found that tropical regions and non-breeding life stages were poorly covered in the literature, a concern that should be addressed to enable a better understanding of the vulnerability of marine predators to climate change.
Classification of lupus erythematosus (LE) is conflicting as it is carried out from different starting points. Whereas dermatological classifications categorize LE morphologically based on specific cutaneous lesions, rheumatologic classifications are based on symptomatic aspects. Indeed, LE is a systemic autoimmune disease with variable acuity and organ involvement. All cutaneous disease patterns may occur in both limited-cutaneous and systemic LE.

76 LE-patients with complete clinical data, clinical photographs and biopsy of cutaneous manifestations as well as paraclinical findings were retrospectively analyzed. Based on a published two-dimensional classification system that considers disease-specific skin manifestations and final disease diagnosis separately, patients' diagnoses were revised and compared with those in medical records. In addition, the extent to which patients could be clustered by diagnosis based on their LE-specific skin manifestations, corresponding histopathological changes, and paraclinical data was investigated.

After re-evaluation, the proportion of patients with limited-cutaneous LE decreased from 82% previously to 24%. More than two-thirds of patients indeed showed intermediate or systemic LE. Disease-specific skin manifestations, histologic characteristics and paraclinical data did not cluster with final diagnoses.

First, the work underlines the systemic character of the disease. Second, a two-dimensional approach can help overcome classification difficulties in LE, as skin-morphologic and symptomatic aspects can be considered separately.
First, the work underlines the systemic character of the disease. Second, a two-dimensional approach can help overcome classification difficulties in LE, as skin-morphologic and symptomatic aspects can be considered separately.This study aims to evaluate the effect of non-alcoholic fatty liver disease (NAFLD) on the susceptibility and consequences of coronavirus disease 2019 (COVID-19). We retrospectively collected data from 218 adult COVID-19 patients who showed no evidence of excessive alcohol consumption and underwent abdominal ultrasound examinations. Of these patients, 39.4% patients had been diagnosed with NAFLD, which indicates a much higher prevalence of NAFLD than that reported in the general population. Significantly elevated white blood cell count (p = 0.008), alanine aminotransferase (p = 0.000), aspartate aminotransferase (p = 0.006) and C reactive protein (p = 0.012) were found in the patients with NAFLD. These patients also had significantly higher proportions of hypertension (p = 0.006) and diabetes (p = 0.049) than the non-NAFLD cases. No significant differences existed in the severity, mortality, viral shedding time and length of hospital stay between patients with or without NAFLD in the sample population. However, subgroup analyses found that in patients with normal body mass index (BMI), NAFLD sufferers were more likely to experience a severe event (30.0% vs 11.5%, p = 0.021). Kaplan-Meier curve (log-rank p = 0.017) and Cox regression (HR = 3.26, 95% CI 1.17-9.04, p = 0.023) analyses confirmed that before and after adjusting for gender, age and comorbidities, NAFLD patients with normal BMI had a higher incidence of suffering severe events. People with NAFLD may have a higher proportion of COVID-19. NAFLD may be correlated with the severity of COVID-19 patients in the normal BMI group.The use of consistent and evidence-based practices is essential in terms of patient safety and quality of care. The purpose of this study was to describe the use of consistent practices in PU prevention based on international care guidelines and to assess the validity and reliability of the pressure ulcer prevention practice (PUPreP) instrument. The data (n = 554) were collected between 2018 and 2019 from nursing professionals working at two hospital districts in Finland using the PUPreP instrument. The instrument consisted of 42 items assessing participants' perceptions of the frequencies of pressure ulcer prevention practices with the following scale never, sometimes, often, always. The data were analysed using statistical analysis. According to the results, the use of pressure ulcer prevention practices was more frequently described as often. The most frequently used prevention practice was repositioning, and the least frequently used practice was nutrition. Factors related to nursing professionals' pressure ulcer prevention practices were the working sector, education and working frequency in pressure ulcer prevention, and early identification of pressure ulcers. The study results suggest that the evidence-based pressure ulcer prevention practices were followed at a moderate level by nurses. The PuPreP instrument demonstrated validity and reliability, but further development is needed.Understanding the unique experience of nursing students providing frontline support in COVID-19 hospital wards is crucial for the design of strategies to improve crisis management and mitigate future pandemic outbreaks. Limited research concerning this phenomenon has been published. This qualitative study aimed to understand the experience of providing support from COVID-19 frontline nursing students' perspective. Online interviews were conducted with nine nursing students from April to May 2020; interview data were analyzed by content analysis using Burnard's method. Six main categories emerged from the data analysis "experiencing a rapid transition from student to professional," "fear and uncertainty of the unknown," "resilience throughout the crisis," "sense of belonging to a team," "shared responsibility," and "importance of the profession." Based on these findings, multicomponent strategies that function in parallel with practical contexts should be developed to enable students to diligently adapt their abilities to their new role and cope with health crises.Aqueous rechargeable zinc-ion batteries (ARZIBs) are promising energy storage systems owing to their ecofriendliness, safety, and cost-efficiency. However, the sluggish Zn2+ diffusion kinetics originated from its inherent large atomic mass and high polarization remains an ongoing challenge. To this end, electrodes with 3D architectures and high porosity are highly desired. This work reports a rational design and fabrication of hierarchical core-shell structured cathodes (3D@V2 O5 ) for ARZIBs by integrating fused deposition modeling (FDM) 3D-printing with atomic layer deposition (ALD). The 3D-printed porous carbon network provides an entangled electron conductive core and interconnected ion diffusion channels, whereas ALD-coated V2 O5 serves as an active shell without sacrificing the porosity for facilitated Zn2+ diffusion. This endows the 3D@V2 O5 cathode with high specific capacity (425 mAh g-1 at 0.3 A g-1 ), competitive energy and power densities (316 Wh Kg-1 at 213 W kg-1 and 163 Wh Kg-1 at 3400 W kg-1 ), and good rate performance (221 mAh g-1 at 4.8 A g-1 ). The developed 3D@V2 O5 cathode provides a promising model for customized and scalable battery electrode engineering technology. As the ALD-coated layer determines the functional properties, the proposed strategy shows a promising prospect of FDM 3D printing using 1D carbon materials for future energy storage.Chronic kidney disease (CKD) increases the risk of arrhythmia. The right ventricular outflow tract (RVOT) is a crucial site of ventricular tachycardia (VT) origination. We hypothesize that CKD increases RVOT arrhythmogenesis through its effects on calcium dysregulation. We analysed measurements obtained using conventional microelectrodes, patch clamp, confocal microscopy, western blotting, immunohistochemical examination and lipid peroxidation for both control and CKD (induced by 150 mg/kg neomycin and 500 mg/kg cefazolin daily) rabbit RVOT tissues or cardiomyocytes. The RVOT of CKD rabbits exhibited a short action potential duration, high incidence of tachypacing (20 Hz)-induced sustained VT, and long duration of isoproterenol and tachypacing-induced sustained and non-sustained VT. Tachypacing-induced sustained and non-sustained VT in isoproterenol-treated CKD RVOT tissues were attenuated by KB-R7943 and partially inhibited by KN93 and H89. The CKD RVOT myocytes had high levels of phosphorylated CaMKII and PKA, and an increased expression of tyrosine hydroxylase-positive neural density. The CKD RVOT myocytes exhibited large levels of Ito , IKr , NCX and L-type calcium currents, calcium leak and malondialdehyde but low sodium current, SERCA2a activity and SR calcium content. The RVOT in CKD with oxidative stress and autonomic neuron hyperactivity exhibited calcium handling abnormalities, which contributed to the induction of VT.Herein the effective electrical propulsion, cargo trapping, and transport capabilities of microbowl-shaped Janus particles (JPs) are demonstrated and evaluated. These active JPs are made by deposition of Au and Ti layers onto sacrificial spherical polystyrene particles, followed by oxidation of the Ti to TiO2 . In contrast to the commonly studied spherical JP, the dual broken symmetry of both geometrical and electrical properties of the microbowl renders a strong dependence of its mobility and cargo loading on the order of the layering of Au and TiO2 . Specifically, an opposite direction of motion is obtained for interchanged layers of Au and TiO2 , using only electrical propulsion as the sole mechanism of motion. The concave side of the microbowl exhibits a negative dielectrophoretic trap of large size wherein trapped cargo is protected from hydrodynamic shearing, leading to an enhanced cargo loading capacity compared to that obtained using common spherical JP. Such enhanced cargo capability of the microbowl along with the ease of engineering it by interchanging the order of the layers are very attractive for future in vitro biological and biomedical applications.Apolipoproteins are an important class of proteins because they provide a so-called stealth effect to nanoparticles. The stealth effect on nanocarriers leads to a reduced unspecific uptake into immune cells and thereby to a prolonged blood circulation time. Herein, a novel strategy to bind apolipoproteins specifically on nanoparticles by adjusting the temperature during their incubation in human plasma is presented. This specific binding, in turn, allows a control of the stealth behavior of the nanoparticles. Nanoparticles with a well-defined poly(N-isopropylacrylamide) shell are prepared, displaying a reversible change of hydrophobicity at a temperature around 32 °C. It is shown by label-free quantitative liquid chromatography-mass spectrometry that the nanoparticles are largely enriched with apolipoprotein J (clusterin) at 25 °C while they are enriched with apolipoprotein A1 and apolipoprotein E at 37 °C. The temperature-dependent protein binding is found to significantly influence the uptake of the nanoparticles by RAW264.7 and HeLa cells. The findings imply that the functionalization of nanoparticles with temperature-responsive materials is a suitable method for imparting stealth properties to nanocarriers for drug-delivery.
The common armyworm Mythimna convecta is an important pest of pastures and graminaceous crops in Australia but materials currently registered for its control are limited to broad-spectrum compounds incompatible with integrated pest management (IPM) systems. In this study we assessed the response of M. convecta larvae to four alternative compounds using topical and dietary bioassays.

Emamectin benzoate (LC
values 2.69 μg mL
topical, 0.017 μg AI g
dietary) and chlorantraniliprole (LC
values 4.87 μg mL
topical, 0.080 μg AI g
dietary) were significantly more active than either indoxacarb or cyantraniliprole. Our results showed strong parallels with data on the more extensively studied Australian strains of Helicoverpa armigera, with the most notable differences being the higher contact toxicity of emamectin benzoate to M. convecta and the lower acute dietary activity of formulated cyantraniliprole to this species, which was linked to feeding deterrence. Cyantraniliprole at dietary concentrations o is protected by copyright. All rights reserved.Photomechanical molecular crystals that expand under illumination could potentially be used as photon-powered actuators. In this study, we find that the use of high-quality single crystals of 9-methylanthracene ( 9MA ) leads to more homogeneous reaction kinetics than that previously seen for polycrystalline samples, presumably due to a lower concentration of defects. Furthermore, simultaneous observation of absorbance and shape changes in single crystals revealed that the dimensional change mirrors the reaction progress, resulting in a smooth expansion of 7% along the c -axis that is linearly correlated with reaction progress. The same expansion dynamics are highly reproducible across different single crystal samples. Organic single crystals exhibit well-defined linear expansions during 100% photoconversion, suggesting that this class of solid-state phase change material that could be used for actuation.Inflammaging, characterized by an increase in low-grade chronic inflammation with age, is a hallmark of aging and is strongly associated with various age-related diseases, including chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Because necroptosis is a cell death pathway that induces inflammation through the release of DAMPs, we tested the hypothesis that age-associated increase in necroptosis contributes to chronic inflammation in aging liver. Phosphorylation of MLKL and MLKL oligomers, markers of necroptosis, as well as phosphorylation of RIPK3 and RIPK1 were significantly upregulated in the livers of old mice relative to young mice and this increase occurred in the later half of life (i.e., after 18 months of age). Markers of M1 macrophages, expression of pro-inflammatory cytokines (TNFα, IL6 and IL1β), and markers of fibrosis were all significantly upregulated in the liver with age and the change in necroptosis paralleled the changes in inflammation and fibrosis. Hepatocytes and liver macrophages isolated from old mice showed elevated levels of necroptosis markers as well as increased expression of pro-inflammatory cytokines relative to young mice.
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