bluuebunny/crossref_metadata_2025 huggingface dataset:
A practical overview of CT and MRI features of developmental, inflammatory, and neoplastic lesions of the sphenoid body and clivus
Authors: Nardi Cosimo , Maraghelli Davide , Pietragalla Michele , Scola Elisa , Locatello Luca Giovanni , Maggiore Giandomenico , Gallo Oreste , Bartolucci Maurizio
Published: June 2022

The sphenoid bone is an unpaired bone that contributes to the formation of the skull base. Despite the enormous progress in transnasal endoscopic visualisation, imaging techniques remain the cornerstones to characterise any pathological condition arising in this area. In the present review, we offer a bird’s-eye view of the developmental, inflammatory, and neoplastic alterations affecting the sphenoid body and clivus, with the aim to propose a practical diagnostic aid for radiologists based on clinico-epidemiological, computed tomography, and magnetic resonance imaging features.
The Super-large Ensemble Experiments of CAS FGOALS-g3
Authors: Lin Pengfei , Zhao Bowen , Wei Jilin , Liu Hailong , Zhang Wenxia , Chen Xiaolong , Jiang Jie , Ding Mengrong , Man Wenmin , Jiang Jinrong , Zhang Xu , Ding Yuewen , Bai Wenrong , Jin Chenyang , Yu Zipeng , Li Yiwen , Zheng Weipeng , Zhou Tianjun
Published: June 2022

A super-large ensemble simulation dataset with 110 members has been produced by the fully coupled model FGOALS-g3 developed by researchers at the Institute of Atmospheric Physics, Chinese Academy of Sciences. This is the first dataset of large ensemble simulations with a climate system model developed by a Chinese modeling center. The simulation has the largest realizations up to now worldwide in terms of single-model initial-condition large ensembles. Each member includes a historical experiment (1850–2014) and an experiment (2015–99) under the very high greenhouse gas emissions Shared Socioeconomic Pathway scenario (SSP5-8.5). The dataset includes monthly and daily temperature, precipitation, and other variables, requiring storage of 275 TB. Additionally, the surface air temperature (SAT) and land precipitation simulated by the FGOALS-g3 super-large ensemble have been validated and projected. The ensemble can capture the response of SAT and land precipitation to external forcings well, and the internal variabilities can be quantified. The availability of more than 100 realizations will help researchers to study rare events and improve the understanding of the impact of internal variability on forced climate changes.
Towards bridging the translational gap by improved modeling of human nociception in health and disease
Authors: Zeidler Maximilian , Kummer Kai K. , Kress Michaela
Published: June 2022

Despite numerous studies which have explored the pathogenesis of pain disorders in preclinical models, there is a pronounced translational gap, which is at least partially caused by differences between the human and rodent nociceptive system. An elegant way to bridge this divide is the exploitation of human-induced pluripotent stem cell (iPSC) reprogramming into human iPSC-derived nociceptors (iDNs). Several protocols were developed and optimized to model nociceptive processes in health and disease. Here we provide an overview of the different approaches and summarize the knowledge obtained from such models on pain pathologies associated with monogenetic sensory disorders so far. In addition, novel perspectives offered by increasing the complexity of the model systems further to better reflect the natural environment of nociceptive neurons by involving other cell types in 3D model systems are described.
Quality assurance and improvement in oncology using guideline-derived quality indicators – results of gynaecological cancer centres certified by the German cancer society (DKG)
Authors: Griesshammer E. , Wesselmann S. , Beckmann M. W. , Dannecker C. , Wagner U. , Sibert N. T. , Armbrust R. , Sehouli J.
Published: June 2022

Purpose

Based on the example of Gynaecological Cancer Centres (GCCs) certified by the German Cancer Society, this study evaluates the results of medical-guideline-derived quality indicators (QIs) for cervical cancer (CC) and ovarian cancer (OC), examines the development of indicator implementation over time as well as the status of guideline-compliant care and identifies improvement measures.

Methods

QI results for patients with CC and OC treated in GCCs between 2015 and 2019 are analysed. The median, overall proportion and standard deviation of each QI were calculated. Two-sided Cochran-Armitage tests were applied.

Results

QIs are divided into two categories: process-organization (PO-QIs) and treatment-procedures (TP-QIs), to allow a differentiated analysis for identifying improvement measures.

PO-QIs that reflect the implementation of processes and structures show a high degree of application. PO-QIs have a tremendous influence on the quality of care and are easy to implement through SOPs.

TP-QIs report on treatments that are performed in the GCC. TP-QIs that report on systemic therapies reach a plateau where the guideline is known, but patient-related-factors meaningfully prevent further increase. TP-QIs that report on surgical interventions fluctuate. The most relevant factors are practitioners’ personal skills. Besides the discussion of results amongst peers during the audit, improvement measures could include surgical courses or coaching.

Conclusion

The analysis shows that a combination of different measures is necessary to anchor quality sustainably in health care and thus improve it.
Population niche width is driven by within-individual niche expansion and individual specialization in introduced brook trout in mountain lakes
Authors: Baker H. K. , Bruggeman C. E. F. , Shurin J. B.
Published: June 2022

The width of a population's resource-use niche is determined by individual diet breadth (“within-individual component”) and the degree of niche partitioning between individuals (“between-individual component”). The balance between these two factors affects ecological stability and evolutionary trajectories, and may shift as ecological opportunity permits broader population niches. Lakes in California’s Sierra Nevada Mountains vary in resource diversity for introduced brook trout (Salvelinus fontinalis) due to elevation, lake morphometry, and watershed features. We compared the relative contributions of within- and between-individual niche components to two measures of the dietary niches of thirteen populations of brook trout: prey taxonomic composition and prey size distribution. For both taxonomic and size diversity of fish diets, population niche width was positively related to both the within- and between-individual components. For taxonomic diversity, the two components increased in parallel, while for size diversity, the between-individual component became more important relative to the within-individual component in populations with the greatest niche widths. Our results support the Niche Variation Hypothesis that populations with broader niches are more heterogeneous among individuals and show that individual niche width and individual specialization can operate in parallel to expand the population niche.
Oral symptom assessment tools in patients with advanced cancer: a scoping review
Authors: Cleary Niamh , Mulkerrin Olivia Munnelly , Davies Andrew
Published: June 2022

Purpose

Oral symptoms are common in patients with advanced cancer. The aim of this scoping review was to identify oral symptom assessment tools that have been specifically utilised in patients with “advanced cancer”.

Methods

The review was conducted/reported according to international guidelines for undertaking scoping reviews. PubMed, Embase, and CINAHL were searched for articles involving adult patients with advanced cancer, which involved assessment of ≥ 2 oral symptoms, and which involved patients with > 1 type of cancer.

Results

The review identified four validated symptom assessment scales, including one cancer-specific quality of life scale (EORTC QLQ OH-15), one generic tool for assessing the “social impact” of specific oral problems (OHIP), one cancer-specific generic symptom assessment scale (MSAS), and one cancer-specific oral symptom assessment scale (OSAS).

Conclusion

Symptom assessment tools can facilitate good symptom control in clinical practice, and are an integral component of clinical research. The review identified four validated symptom assessment scales that could be utilised to assess oral symptoms in patients with advanced cancer.
R2U++: a multiscale recurrent residual U-Net with dense skip connections for medical image segmentation
Authors: Mubashar Mehreen , Ali Hazrat , Grönlund Christer , Azmat Shoaib
Published: June 2022

U-Net is a widely adopted neural network in the domain of medical image segmentation. Despite its quick embracement by the medical imaging community, its performance suffers on complicated datasets. The problem can be ascribed to its simple feature extracting blocks: encoder/decoder, and the semantic gap between encoder and decoder. Variants of U-Net (such as R2U-Net) have been proposed to address the problem of simple feature extracting blocks by making the network deeper, but it does not deal with the semantic gap problem. On the other hand, another variant UNET++ deals with the semantic gap problem by introducing dense skip connections but has simple feature extraction blocks. To overcome these issues, we propose a new U-Net based medical image segmentation architecture R2U++. In the proposed architecture, the adapted changes from vanilla U-Net are: (1) the plain convolutional backbone is replaced by a deeper recurrent residual convolution block. The increased field of view with these blocks aids in extracting crucial features for segmentation which is proven by improvement in the overall performance of the network. (2) The semantic gap between encoder and decoder is reduced by dense skip pathways. These pathways accumulate features coming from multiple scales and apply concatenation accordingly. The modified architecture has embedded multi-depth models, and an ensemble of outputs taken from varying depths improves the performance on foreground objects appearing at various scales in the images. The performance of R2U++ is evaluated on four distinct medical imaging modalities: electron microscopy, X-rays, fundus, and computed tomography. The average gain achieved in IoU score is 1.5 ± 0.37% and in dice score is 0.9 ± 0.33% over UNET++, whereas, 4.21 ± 2.72 in IoU and 3.47 ± 1.89 in dice score over R2U-Net across different medical imaging segmentation datasets.
Peak Shear Strength of Natural, Unfilled Rock Joints in the Field Based on Data from Drill Cores – A Conceptual Study Based on Large Laboratory Shear Tests
Authors: Ríos-Bayona F. , Johansson F. , Larsson J. , Mas-Ivars D.
Published: June 2022

Significant uncertainties remain regarding the field assessment of the peak shear strength of rock joints. These uncertainties mainly originate from the lack of a verified methodology that would permit prediction of rock joints’ peak shear strength accounting for their surface area, while using information available from smaller samples. This paper investigates a methodology that uses objective observations of the 3D roughness and joint aperture from drill cores to predict the peak shear strength of large natural, unfilled rock joints in the field. The presented methodology has been tested in the laboratory on two natural, unfilled rock joint samples of granite. The joint surface area of the tested samples was of approximately 500 × 300 mm. In this study, the drill cores utilised to predict the peak shear strength of the rock joint samples are simulated based on a subdivision of their digitised surfaces obtained through high-resolution laser scanning. The peak shear strength of the tested samples based on the digitised surfaces of the simulated drill cores is predicted by applying a peak shear strength criterion that accounts for 3D roughness, matedness, and specimen size. The results of the performed analysis and laboratory experiments show that data from the simulated drill cores contain the necessary information to predict the peak shear strength of the tested rock joint samples. The main benefit of this approach is that it may enable the prediction of the peak shear strength in the field under conditions of difficult access.
Carbonatite-melilitite-phosphate immiscible melts from the aragonite stability field entrained from the mantle by a Pliocene basalt
Authors: Hurai Vratislav , Huraiová Monika , Habler Gerlinde , Horschinegg Monika , Milovský Rastislav , Milovská Stanislava , Hain Miroslav , Abart Rainer
Published: June 2022

A plagioclase megacryst containing composite crystal-glass inclusions was ejected in a Pliocene basaltic diatreme in the Carpathian back-arc basin (Pannonian Basin). The megacryst grew from phonolitic melt, relics of which are preserved in the crystal-glass inclusions. Most of the pristine melt has undergone substantial compositional resetting by interaction with several batches of a low-viscosity carbonated, P-rich melilitite melt, which infiltrated and largely replaced the original inclusion content. The melilitite melt also caused partial resorption of the host megacryst and crystallisation of new calcic plagioclase forming stringers and palisades. A P-rich calcic carbonatite melt exsolved from the melilitite and later crystallised to aragonite at ~ 800 °C and 1.9 GPa. The phosphate melt fraction exsolved from the carbonatite and solidified as CO32−-rich A-B type apatite. At a very late evolutionary stage, K- and Si-rich fluids caused potassic and silicic alteration of the solidified melilitite glass along cracks and interfaces between calcic carbonate globules and glass at temperatures below 680 °C. The oxygen isotope composition of the plagioclase megacryst (6.2 ‰ V-SMOW; Vienna Standard Mean Ocean Water) and the 87Sr/86Sr isotope ratio of carbonates in the inclusions (0.7034) are consistent with a mantle-derived melt. 87Sr/86Sr isotope ratios (0.7047–0.7051) in interstitial carbonates from associated syenite and carbonatite xenoliths indicate a metasomatised mantle source contaminated with radiogenic crustal material or altered marine carbonate. The O-isotope ratios in the carbonates, 22.7 ± 0.6 ‰ V-SMOW in calcite and 23.6 ± 0.7 ‰ V-SMOW in aragonite, are also consistent with a sedimentary precursor. Contrasting δ13C values in the calcite, -12.7 ± 0.5 ‰ V-PDB (Vienna PeeDee Belemnite), and the aragonite (-4.6 ± 0.5 ‰ V-PDB) indicate low-temperature modification of calcite assisted by $$\delta$$
δ
13C-depleted CO2 and preservation of primary magmatic $$\delta$$
δ
13C values in aragonite. The microstructural and geochemical evidence points towards heterogeneous silicate-carbonate melt fractions generated during the metasomatism and partial melting of a supra-subduction mantle wedge.
Multi-analyte HPLC–DAD Method for Concurrent Analysis of Six Antimicrobials and Three Proton Pump Inhibitors Frequently used in Management of Helicobacter pylori Infection: Application to Simulated Intestinal Fluid Samples
Authors: Gawad Dina A. , Elnaggar Mai M. , Belal Tarek S.
Published: June 2022

The present work deals with the optimization, validation and application of a versatile HPLC–DAD method for concurrent estimation of nine antimicrobials and proton pump inhibitors, namely amoxicillin (AMX), doxycycline (DOX), furazolidone (FRZ), lansoprazole (LNS), levofloxacin (LVF), metronidazole (MTZ), omeprazole (OMZ), pantoprazole (PNZ) and tinidazole (TNZ). The selected nine drugs are frequently included in various treatment regimens of Helicobacter pylori infection. Successful separation was accomplished using the analytical column Agilent Zorbax Eclipse plus-C18 (250 × 4.6 mm, 5 µm particle size) and a mobile phase prepared from phosphate buffer pH 5 and acetonitrile pumped at a flow rate 1 mL/min using a gradient elution program. The gradient elution started with buffer/acetonitrile ratio 90:10, then it was altered in 15 min to reach 40:60 by volume. Quantification of the analytes was based on measuring peak areas of AMX at 230 nm, LVF, LNS and PNZ at 290 nm, OMZ at 300 nm, MTZ and TNZ at 320 nm, and DOX and FRZ at 360 nm. The separated compounds eluted at retention times 5.68, 6.43, 7.82, 8.84, 9.42, 10.75, 12.82, 13.74 and 14.90 min for AMX, MTZ, LVF, TNZ, DOX, FRZ, OMZ, PNZ and LNS respectively. Validation of the proposed HPLC procedure was carefully studied according to the ICH items: ranges, precision, accuracy, linearity, robustness and limits of detection and quantitation. The linear dynamic ranges were 5–100, 5–50, 2–40, 10–100, 10–100, 5–50, 2.5–30, 3–30 and 2–30 µg/mL for AMX, MTZ, LVF, TNZ, DOX, FRZ, OMZ, PNZ and LNS, respectively with correlation coefficients > 0.9993. Application fields of the validated method included analysis of laboratory-prepared binary dosage forms along with analysis of several ternary mixtures in spiked simulated intestinal fluid.
Assessing the risk of establishment and transient populations of Spodoptera frugiperda in Europe
Authors: Gilioli Gianni , Sperandio Giorgio , Simonetto Anna , Ciampitti Mariangela , Gervasio Paola
Published: June 2022

The fall armyworm, Spodoptera frugiperda (J.E. Smith), is an invasive pest threatening crop production and food security worldwide. High concerns are linked to the potential establishment of the species in Europe. The high migratory capacity of S. frugiperda causes concerns about the potential impacts of transient populations invading new areas from suitable hotspots. In the present work, we developed and used a physiologically-based demographic model to quantitatively assess the risks of S. frugiperda in Europe. The risks were assessed considering a best-, a median-, and a worst-case scenario. The Mediterranean coastal areas of Southern Europe resulted particularly suitable for the establishment of the species, with suitable areas reaching even higher latitudes, in the worst-case scenario. In Europe, up to four generations per year were predicted. The predicted yearly average number of moths per trap per week (± standard deviation) was 5 (± 4), 17 (± 5), and 139 (± 22) in the best, median-, and worst-case assessment scenarios, respectively. Model results showed that Southern and Central Europe up to the 48th parallel north might be exposed to the risk of transient populations. Depending on the latitude and on the period of arrival of the propagule, 1–2 transient generations per year might be expected. The model can be used to define strategies for reducing the risks of establishment of the pest at the country level. Predictions on the dynamics and phenology of the pest can also be used to support its management at the local level.
Arenas of Contestation: A Senian Social Justice Perspective on the Nature of Materiality in Impact Measurement
Authors: Lehner Othmar Manfred , Nicholls Alex , Kapplmüller Sarah Beatrice
Published: June 2022

Although the importance of measuring and reporting the social and environmental impact of organisational action is increasingly well recognised by both organisations and society at large, existing approaches to impact measurement are still far from being universally accepted. In this context, the stakeholder dynamics within the nascent field of impact investing demonstrate the complexity of resolving potentially differing perspectives on key impact measurement issues such as materiality. This paper argues, from an organisational perspective, that such arenas of contestation can be conceptualised in terms of social justice. Specifically, we draw upon Sen’s notions of ‘arrangement and realisation’ to explore the dynamics of contestation across a range of stakeholders concerning materiality judgements to suggest that such ‘arrangements’ may lead to suboptimal impact outcomes as ‘realisations.’ Our analysis of the nature of materiality contestations in impact measurement reveals the conflicts, tensions and paradoxes evident in this field of action. Empirically, we examine data drawn from 19 cases and 33 interviews. The analysis suggests three arenas of contestation around the materiality of impact measurement: the power dynamics between economically powerful investors and objectified investees; the conflicts between materiality norms and standards; and the interactions between all stakeholders with differing motivations towards radical or incremental materiality. Building upon this analysis, we then discuss how arenas of contested materiality may be mediated by drawing upon Sen’s notions of transcending the individual interests of the invested parties for the greater good via processes of contextualisation and case-specificity.
Effects of resistance training on body composition and physical function in elderly patients with osteosarcopenic obesity: a systematic review and meta-analysis
Authors: Yang Jia-ming , Ye Hua , Zhu Qiang , Zhang Jia-hong , Liu Qin-qin , Xie Hui-yong , Long Yi , Huang Hui , Niu Yan-long , Luo Yun , Wang Mao-yuan
Published: June 2022

Summary

Osteosarcopenic obesity (OSO) is a complex disease commonly seen in the elderly. We found that resistance training may improve bone mineral density, skeletal muscle mass, and body fat percentage in patients with OSO. Therefore, resistance training is beneficial for elderly OSO patients and is worth being promoted.

Purpose

Investigate effects of resistance training on body composition and physical function in elderly osteosarcopenic obesity (OSO) patients.

Methods

PubMed, Web of Science, Embase, Cochrane Library, Medline, SinoMed, CNKI, and Wanfang Database were searched from inception until October 13, 2021.Two independent researchers extracted the key information from each eligible study. The methodological quality of included studies was assessed using the Physiotherapy Evidence Database (PEDro) scale. The Cochrane Risk of Bias Tool was used to assess the risk of bias. Grading of Recommendations Assessment Development and Evaluation (GRADE) was used to evaluate the quality of the outcomes. Sensitivity analysis indicated the stability of the results. Statistical analysis was performed using Review Manager 5.3.

Results

Four randomized controlled studies meeting the inclusion criteria were included, with 182 participants. Twelve weeks of resistance training improved bone mineral density (BMD, mean difference (MD) = 0.01 g/cm2, 95% confidence interval (CI): 0.001, 0.02, P = 0.03, I2 = 0%), skeletal muscle mass (SMM, MD = 1.19 kg, 95% CI: 0.50, 1.89, P = 0.0007, I2 = 0%), Z score, timed chair rise test (TCR), and body fat percentage (BFP, MD =  − 1.61%, 95% CI: − 2.94, − 0.28, P = 0.02, I2 = 50%) but did not significantly affect skeletal muscle mass index (SMI, MD = 0.20 kg/m2, 95% CI: − 0.25, 0.64, P = 0.38, I2 = 0%) or gait speed (GS).

Conclusions

Resistance training is a safe and effective intervention that can improve many parameters, including BFP, SMM, and Z score, among OSO patients and is a good option for elderly individuals to improve their physical fitness.
A Pilot Randomized Controlled Trial Investigating MBSR for Parkinson’s Disease Patients and Their Caregiving Partners: Effects on Distress, Social support, Cortisol, and Inflammation
Authors: Siwik Chelsea J. , Phillips Kala , Litvan Irene , Salmon Paul , Rodgers Allison , Jablonski Megan , Sephton Sandra E.
Published: June 2022

Objectives

To examine the preliminary effects of the mindfulness-based stress reduction (MBSR) program in the management of biopsychosocial stress–related changes associated with Parkinson’s disease (PD) among patient/caregiving-partner dyads.

Methods

PD patient/caregiving-partner dyads (N = 18) early in the disease trajectory were recruited from a university-affiliated movement disorders clinic and were randomized (1:1) to either the MBSR intervention or the control condition (treatment as usual [TAU]). Mixed methods ANOVAs were conducted to examine primary outcomes (disease-specific distress, perceived social support, circadian rhythmicity [cortisol], and markers of inflammation [IL-6, TNF-alpha, IL-1beta]) between groups (MBSR vs. TAU) among patients and caregiving partners separately.

Results

No participants were lost to follow-up. Given the pilot nature of the current investigation, findings should be interpreted as exploratory opposed to confirmatory. Following MBSR, PD patients reported an increase in disease-specific distress and intrusive thoughts and demonstrated a decrease in mean bedtime cortisol and IL-1beta from baseline to follow-up compared to TAU. Caregiving partners who received MBSR reported an increase in perceived social support and demonstrated improved rhythmicity of diurnal cortisol slopes from baseline to follow-up compared to TAU.

Conclusions

Both patients and caregiving partners who received MBSR demonstrated improvements in biomarkers of circadian function, and patients evidenced a decrease in a biomarker of systemic inflammation, pointing to an important area of further investigation. Given that patients reported an increase in disease-specific distress and intrusive thoughts, the salutary effects of MBSR may be experienced physiologically prior to, or in lieu of, psychological effects, although this should be explored further, especially given the improvement in perceived social support reported by caregiving partners.
Groundwater contamination in public water supply wells: risk assessment, evaluation of trends and impact of rainfall on groundwater quality
Authors: Nemčić-Jurec Jasna , Ruk Damir , Oreščanin Višnja , Kovač Ivan , Ujević Bošnjak Magdalena , Kinsela Andrew Stephen
Published: June 2022

This study investigates the risk to contamination of groundwater in public water supply wells in the Koprivnica-Križevci county (northwest Croatia). Five physicochemical parameters were monitored in all groundwater samples from 2008 to 2017 to identify major differences between the wells, assess temporal variations and understand the capacity for rainfall to alter groundwater pollution loadings. Multivariate discriminant analysis showed statistically significant differences between the six sampled wells based on the analyzed parameters (Wilks' lambda: 0.001; F = 26.2; p < 0.0000). Principal component analysis revealed two significant factors, including factor 1 which explained 32.8% of the variance (suggesting that the quality of the groundwater was mainly controlled by nitrate) and factor 2, accounting for 16.2% of the total variance (which corresponded to KMnO4/oxidizability and to a lesser extent, pH). The time series data showed disparate trends, with nitrate concentrations increasing, whereas pH and KMnO4 decreased, while electrical conductivity and chloride levels remained stable. Although rainfall can impact groundwater pollution loadings through dilution processes in aquifers, the resulting fluctuations in physicochemical parameters are complicated by variations in rainfall events and local topography, as well as from climate change. Therefore, it is important to predict the contamination of groundwater quality in the future using machine learning algorithms using artificial neural network or similar methods. Multivariate statistical techniques are useful in verifying temporal and spatial variations caused by anthropogenic factors and natural processes linked to rainfall. The resulting identified risks to groundwater quality would provide the basis for further groundwater protection, particularly for decisions regarding permitted land use in recharge zones.
Dopamine-triggered one-step functionalization of hollow silica nanospheres for simultaneous lubrication and drug release
Authors: Wei Qiangbing , Fu Tian , Lei Lele , Liu Huan , Zhang Yixin , Ma Shuanhong , Zhou Feng
Published: June 2022

Osteoarthritis (OA) has been regarded as a lubrication deficiency related joint disease. Combination of both joint lubrication and drug intervention may provide a promising nonsurgical strategy for treatment of OA. Developing novel and simple approaches to fabricate superlubricating nanoparticles with drug release property is highly required. Herein, dopamine triggered one-step polymerization method was employed to fabricate polydopamine/poly(3-sulfopropyl methacrylate potassium salt) (PDA—PSPMA) conjugate coating on hollow silica (h-SiO2) nanosphere surfaces to engineer functional nanoparticles (h-SiO2/PDA—PSPMA). The as-prepared h-SiO2/PDA—PSPMA exhibits excellent aqueous lubrication performance on biomaterial substrates as well as natural bovine articular cartilage based on hydration effect of negatively charged PDA—PSPMA coating and “rolling” effect of h-SiO2 nanospheres. In vitro drug loading-release experiments demonstrate that PDA—PSPMA coating functionalized h-SiO2 nanospheres show high drug-loading and sustained-release capability of an anti-inflammatory drug, diclofenac sodium (DS). Such h-SiO2/PDA—PSPMA nanospheres can be potentially used as a synergistic therapy agent for OA treatment combining by simultaneous joint lubrication and drug release.
Children's Imagination
Authors: Harris Paul L.
Published: June 2022

Children's imagination was traditionally seen as a wayward, desire-driven faculty that is eventually constrained by rationality. A more recent, Romantic view claims that young children's fertile imagination is increasingly dulled by schooling. Contrary to both perspectives, this Element argues that, paradoxically, children's imagination draws much inspiration from reality. Hence, when they engage in pretend play, envision the future, or conjure up counterfactual possibilities, children rarely generate fantastical possibilities. Their reality-guided imagination enables children to plan ahead and to engage in informative thought experiments. Nevertheless, when adults present children with less reality-based possibilities – via biblical narratives or the endorsement of special beings – children are receptive. Indeed, such imaginary possibilities can infuse their otherwise commonsensical appraisal of reality. Finally, like adults, young children enjoy being absorbed into a make-believe, fictional world but faced with real-world problems calling for creativity, they often need guidance, given their limited knowledge of prior solutions.
Investor Heterogeneity and Liquidity
Authors: Chan Kalok , Cheng Si , Hameed Allaudeen
Published: June 2022

Fund flows are more correlated among funds with similar investment horizon, consistent with correlated demand for liquidity. We find that stocks held by institutions with more heterogeneous investment horizon are more liquid and have lower volatility of liquidity. Identification tests confirm that the improvement in stock liquidity holds when the increase in investor heterogeneity arises from an exogenous shock due to the 2003 tax reform. In addition, extreme flow-induced trading by institutional funds has a bigger price impact when stocks have a less heterogeneous investor base. Moreover, the premium associated with stock illiquidity is concentrated in stocks with low investor heterogeneity.
Staging of unipolar depression: systematic review and discussion of clinical implications
Authors: Cosci Fiammetta , Fava Giovanni A.
Published: June 2022

Staging has been increasingly used in unipolar depression since its introduction in the nineties. Several models are available, but their differential features and implications are not completely clear. We systematically reviewed: (a) staging models of longitudinal development of unipolar depression; (b) staging models of treatment-resistant unipolar depression; (c) their applications. MEDLINE, PsycINFO, EMBASE, and Web of Science were examined according to PRISMA guidelines from inception to December 2021. Search terms were: ‘stage/staging’, combined using the Boolean ‘AND’ operator with ‘psychiatric disorder/mental disorder/depressive/mood disorder’. A total of 169 studies were identified for inclusion: 18 described staging models or applications, 151 described treatment-resistant staging models or applications. Staging models of longitudinal development were found to play a key role in formulating sequential treatment, with particular reference to the use of psychotherapy after pharmacotherapy. Staging methods based on treatment resistance played a crucial role in setting entry criteria for randomized clinical trials and neurobiological investigations. Staging is part of clinimetrics, the science of clinical measurements, and its role can be enhanced by its association with other clinimetric strategies, such as repeated assessments, organization of problematic areas, and evaluation of phenomena that may affect responsiveness. In research, it may allow to identify more homogeneous populations in terms of treatment history that may diminish the likelihood of spurious results in comparisons. In clinical practice, the use of staging in a clinimetric perspective allows clinicians to make full use of the information that is available for an individual patient at a specific time.
Single ventricle palliation of truncus arteriosus with mitral atresia, interrupted aortic arch, and aberrant right subclavian artery
Authors: Pizarro Christian , Shillingford Amanda J. , Pizarro Sebastian D. , Beaty Claude A.
Published: June 2022

The association of truncus arteriosus communis with interrupted aortic arch and mitral atresia is an exceptionally rare congenital defect. We describe the initial decision-making and management of this lesion, which eventually achieved a Fontan palliation.
Suicide Prevention Outreach on Social Media Delivered by Trained Volunteers
Authors: Keasar Vered , Sznitman Sharon , Baumel Amit
Published: June 2022

Abstract. Background: There is a need to develop new ways to reach and engage people at risk for suicidal behavior. Suicide prevention outreach on social media (SPOSM) represents a promising strategy, and trained volunteers could potentially provide the needed human resources. Aims: We aimed to investigate users' perception of SPOSM delivered by volunteers of the Israeli Sahar organization and its potential to promote help-seeking behavior. Methods: Outreach messages written by Sahar volunteers between July 2015 and June 2020 in response to suicidal posts on a social media site were screened. User responses were analyzed using inductive thematic analysis. Results: One hundred sixteen user responses were analyzed. Positive impact themes were identified in 69.8% of responses, while 16.4% of responses mentioned barriers to care and 10.3% were negative. Limitations: As the study is based on real-life data, the data are limited to users who chose to respond to outreach. Conclusion: The findings suggest that volunteer-based SPOSM is viewed positively by many users and may foster help-seeking behavior. The findings also outline challenges such as emotional barriers to care and privacy concerns.
Monitoring Earthquakes at the Speed of Light
Authors: El-Said Mohammed
Published: June 2022

New research uses gravity and a machine learning model to instantaneously estimate the magnitude and location of large earthquakes.
SGLT2 inhibitor activates the STING/IRF3/IFN-β pathway and induces immune infiltration in osteosarcoma
Authors: Wu Wei , Zhang Zhenhao , Jing Doudou , Huang Xin , Ren Dianyun , Shao Zengwu , Zhang Zhicai
Published: June 2022

SGLT2 (sodium-glucose cotransporter 2) is an important mediator of epithelial glucose transport and has been reported that SGLT2, robustly and diffusely expressed in malignant cancer cells, was overexpressed in various tumors, and inhibiting the SGLT2 expression significantly inhibited tumor progression. By blocking the functional activity of SGLT2, SGLT2 inhibitors have shown anticancer effects in several malignant cancers, including breast cancer, cervical cancer, hepatocellular cancer, prostate cancer, and lung cancer. However, the anticancer effect of SGLT2 inhibitors in osteosarcoma and the specific mechanism are still unclear. In the present study, we found that SGLT2 was overexpressed at the protein level in osteosarcoma. Furthermore, our results showed that the SGLT2 inhibitor significantly inhibited osteosarcoma tumor growth and induced infiltration of immune cells in vivo by upregulating STING expression and activating the IRF3/IFN-β pathway, which could attribute to the suppression of AKT phosphorylation. In addition, the combined treatment with SGLT2 inhibitor and STING agonist 2’3’-cGAMP exerted synergistic antitumor effects in osteosarcoma. Furthermore, the overexpression of SGLT2 at the protein level was correlated with the degradation of SGLT2 induced by TRIM21. This result demonstrated that SGLT2 is a novel therapeutic target of osteosarcoma, and that the SGLT2 inhibitor, especially in combination with 2’3’-cGAMP, is a potential therapeutic drug.
High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing
Authors: Ronteix Gustave , Jain Shreyansh , Angely Christelle , Cazaux Marine , Khazen Roxana , Bousso Philippe , Baroud Charles N.
Published: June 2022

Cytotoxic T cells are important components of natural anti-tumor immunity and are harnessed in tumor immunotherapies. Immune responses to tumors and immune therapy outcomes largely vary among individuals, but very few studies examine the contribution of intrinsic behavior of the T cells to this heterogeneity. Here we show the development of a microfluidic-based in vitro method to track the outcome of antigen-specific T cell activity on many individual cancer spheroids simultaneously at high spatiotemporal resolution, which we call Multiscale Immuno-Oncology on-Chip System (MIOCS). By combining parallel measurements of T cell behaviors and tumor fates with probabilistic modeling, we establish that the first recruited T cells initiate a positive feedback loop to accelerate further recruitment to the spheroid. We also provide evidence that cooperation between T cells on the spheroid during the killing phase facilitates tumor destruction. Thus, we propose that both T cell accumulation and killing function rely on collective behaviors rather than simply reflecting the sum of individual T cell activities, and the possibility to track many replicates of immune cell-tumor interactions with the level of detail our system provides may contribute to our understanding of immune response heterogeneity.
Hydrophobic-cationic peptides modulate RNA polymerase ribozyme activity by accretion
Authors: Li Peiying , Holliger Philipp , Tagami Shunsuke
Published: June 2022

Accretion and the resulting increase in local concentration is a widespread mechanism in biology to enhance biomolecular functions (for example, in liquid-liquid demixing phases). Such macromolecular aggregation phases (e.g., coacervates, amyloids) may also have played a role in the origin of life. Here, we report that a hydrophobic-cationic RNA binding peptide selected by phage display (P43: AKKVWIIMGGS) forms insoluble amyloid-containing aggregates, which reversibly accrete RNA on their surfaces in an RNA-length and Mg2+-concentration dependent manner. The aggregates formed by P43 or its sequence-simplified version (K2V6: KKVVVVVV) inhibited RNA polymerase ribozyme (RPR) activity at 25 mM MgCl2, while enhancing it significantly at 400 mM MgCl2. Our work shows that such hydrophobic-cationic peptide aggregates can reversibly concentrate RNA and enhance the RPR activity, and suggests that they could have aided the emergence and evolution of longer and functional RNAs in the fluctuating environments of the prebiotic earth.
CCN1 interacts with integrins to regulate intestinal stem cell proliferation and differentiation
Authors: Won Jong Hoon , Choi Jacob S. , Jun Joon-Il
Published: June 2022

Intestinal stem cells (ISCs) at the crypt base contribute to intestinal homeostasis through a balance between self-renewal and differentiation. However, the molecular mechanisms regulating this homeostatic balance remain elusive. Here we show that the matricellular protein CCN1/CYR61 coordinately regulates ISC proliferation and differentiation through distinct pathways emanating from CCN1 interaction with integrins αvβ3/αvβ5. Mice that delete Ccn1 in Lgr5 + ISCs or express mutant CCN1 unable to bind integrins αvβ3/αvβ5 exhibited exuberant ISC expansion and enhanced differentiation into secretory cells at the expense of absorptive enterocytes in the small intestine, leading to nutrient malabsorption. Analysis of crypt organoids revealed that through integrins αvβ3/αvβ5, CCN1 induces NF-κB-dependent Jag1 expression to regulate Notch activation for differentiation and promotes Src-mediated YAP activation and Dkk1 expression to control Wnt signaling for proliferation. Moreover, CCN1 and YAP amplify the activities of each other in a regulatory loop. These findings establish CCN1 as a niche factor in the intestinal crypts, providing insights into how matrix signaling exerts overarching control of ISC homeostasis.
Peptide vaccine-treated, long-term surviving cancer patients harbor self-renewing tumor-specific CD8+ T cells
Authors: Mizukoshi Eishiro , Nakagawa Hidetoshi , Tamai Toshikatsu , Kitahara Masaaki , Fushimi Kazumi , Nio Kouki , Terashima Takeshi , Iida Noriho , Arai Kuniaki , Yamashita Tatsuya , Yamashita Taro , Sakai Yoshio , Honda Masao , Kaneko Shuichi
Published: June 2022

The behaviors and fates of immune cells in cancer patients, such as dysfunction and stem-like states leading to memory formation in T cells, are in intense focus of investigation. Here we show, by post hoc analysis of peripheral blood lymphocytes of hepatocellular carcinoma patients previously undergoing vaccination with tumour-associated antigen-derived peptides in our clinical trials (registration numbers UMIN000003511, UMIN000004540, UMIN000005677, UMIN000003514 and UMIN000005678), that induced peptide-specific T cell responses may persist beyond 10 years following vaccination. Tracking TCR clonotypes at the single cell level reveals in two patients that peptide-specific long-lasting CD8+ T cells acquire an effector memory phenotype that associates with cell cycle-related genes (CCNA2 and CDK1), and are characterized by high expression of IL7R, SELL, and NOSIP along with a later stage promotion of the AP-1 transcription factor network (5 years or more past vaccination). We conclude that effective anti-tumor immunity is governed by potentially proliferative memory T cells, specific to cancer antigens.
Structures of a mammalian TRPM8 in closed state
Authors: Zhao Cheng , Xie Yuan , Xu Lizhen , Ye Fan , Xu Ximing , Yang Wei , Yang Fan , Guo Jiangtao
Published: June 2022

Transient receptor potential melastatin 8 (TRPM8) channel is a Ca2+-permeable non-selective cation channel that acts as the primary cold sensor in humans. TRPM8 is also activated by ligands such as menthol, icilin, and phosphatidylinositol 4,5-bisphosphate (PIP2), and desensitized by Ca2+. Here we have determined electron cryo-microscopy structures of mouse TRPM8 in the absence of ligand, and in the presence of Ca2+ and icilin at 2.5–3.2 Å resolution. The ligand-free state TRPM8 structure represents the full-length structure of mammalian TRPM8 channels with a canonical S4-S5 linker and the clearly resolved selectivity filter and outer pore loop. TRPM8 has a short but wide selectivity filter which may account for its permeability to hydrated Ca2+. Ca2+ and icilin bind in the cytosolic-facing cavity of the voltage-sensing-like domain of TRPM8 but induce little conformational change. All the ligand-bound TRPM8 structures adopt the same closed conformation as the ligand-free structure. This study reveals the overall architecture of mouse TRPM8 and the structural basis for its ligand recognition.
Conformational change of Syntaxin-3b in regulating SNARE complex assembly in the ribbon synapses
Authors: Gething Claire , Ferrar Joshua , Misra Bishal , Howells Giovanni , Andrzejewski Alexa L. , Bowen Mark E. , Choi Ucheor B.
Published: June 2022

Neurotransmitter release of synaptic vesicles relies on the assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, consisting of syntaxin and SNAP-25 on the plasma membrane and synaptobrevin on the synaptic vesicle. The formation of the SNARE complex progressively zippers towards the membranes, which drives membrane fusion between the plasma membrane and the synaptic vesicle. However, the underlying molecular mechanism of SNARE complex regulation is unclear. In this study, we investigated the syntaxin-3b isoform found in the retinal ribbon synapses using single-molecule fluorescence resonance energy transfer (smFRET) to monitor the conformational changes of syntaxin-3b that modulate the SNARE complex formation. We found that syntaxin-3b is predominantly in a self-inhibiting closed conformation, inefficiently forming the ternary SNARE complex. Conversely, a phosphomimetic mutation (T14E) at the N-terminal region of syntaxin-3b promoted the open conformation, similar to the constitutively open form of syntaxin LE mutant. When syntaxin-3b is bound to Munc18-1, SNARE complex formation is almost completely blocked. Surprisingly, the T14E mutation of syntaxin-3b partially abolishes Munc18-1 regulation, acting as a conformational switch to trigger SNARE complex assembly. Thus, we suggest a model where the conformational change of syntaxin-3b induced by phosphorylation initiates the release of neurotransmitters in the ribbon synapses.
Paper-based colorimetric sensor array for the rapid and on-site discrimination of green tea samples based on the flavonoid composition
Authors: Gomes Jéssica Santos , de Sousa Raquel Maria Ferreira , Petruci João Flávio da Silveira
Published: June 2022

An alternative yet powerful methodology based on the colorimetric sensor array concept to distinguish green tea extract through the flavonoid composition.
A family of superconducting boron crystals made of stacked bilayer borophenes
Authors: Mu Yuewen , Wang Bao-Tian , Li Si-Dian , Ding Feng
Published: June 2022

We proposed four novel stable metallic boron crystals by stacking the experimentally reported borophenes, indicating a preparation method for superconducting boron crystals dispensing with high pressure.
Flex-activated CO mechanochemical production for mechanical damage detection
Authors: Nijem Sally , Song Ying , Schwarz Rony , Diesendruck Charles E.
Published: June 2022

New flex-activated mechanophore allows for mechanical damage in polymers using a simple household CO detectors, in addition to the formation of an extended and fluorescent π system.
Thiol–acrylate side-chain liquid crystal elastomers
Authors: Guo Hongye , Saed Mohand O. , Terentjev Eugene M.
Published: June 2022

The Michael addition ‘click’ chemistry was used to graft acrylate-terminated mesogenic groups onto the polysiloxane backbone polymer chain with thiol functional groups, with a constant 15% fraction of diacrylate reacting monomers as crosslinkers.