bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural resveratrol analogs differentially target endometriotic cells into apoptosis pathways
Authors: Gołąbek-Grenda Agata , Kaczmarek Mariusz , Juzwa Wojciech , Olejnik Anna
Published: July 2023

The specific characteristics of endometriotic cells are their ability to evade the apoptotic machinery and abnormal response to apoptotic stimuli. Natural-originated compounds may constitute a beneficial strategy in apoptosis modulation in endometriosis. We investigated and compared the potency of natural resveratrol analogs, including piceatannol, polydatin, and pterostilbene, in targeting cell death pathways, including apoptosis-related morphologic and biochemical processes, alongside the modulation of the critical genes expression. Upon resveratrol and pterostilbene treatment, a significant reduction of endometriotic cell viability and an increased apoptotic proportion of cells were noted. The lower antiproliferative potential was found for piceatannol and polydatin. Endometrial stromal T HESC cells were significantly more resistant than endometriotic epithelial 12Z cells to the cytotoxic activity of all analyzed compounds. They differentially affected endometriotic cell viability, cell cycle, anti- and proapoptotic genes regulation, caspases expression and enzymatic activity, and DNA fragmentation. Pterostilbene-mediated endometriotic cell apoptosis modulation was confirmed to be most effective but without evident caspase 3 upregulation. Our study provides valuable insight into the apoptogenic activity of resveratrol and its natural analogs in endometriotic cells. Data obtained revealed the highest therapeutic potential of pterostilbene by effectively targeting cell death determinants in endometriosis, strengthening its optimization in further extensive research.
Actionability classification of variants of unknown significance correlates with functional effect
Authors: Johnson Amber , Ng Patrick Kwok-Shing , Kahle Michael , Castillo Julia , Amador Bianca , Wang Yujia , Zeng Jia , Holla Vijaykumar , Vu Thuy , Su Fei , Kim Sun-Hee , Conway Tara , Jiang Xianli , Chen Ken , Shaw Kenna R. Mills , Yap Timothy A. , Rodon Jordi , Mills Gordon B. , Meric-Bernstam Funda
Published: July 2023

Genomically-informed therapy requires consideration of the functional impact of genomic alterations on protein expression and/or function. However, a substantial number of variants are of unknown significance (VUS). The MD Anderson Precision Oncology Decision Support (PODS) team developed an actionability classification scheme that categorizes VUS as either “Unknown” or “Potentially” actionable based on their location within functional domains and/or proximity to known oncogenic variants. We then compared PODS VUS actionability classification with results from a functional genomics platform consisting of mutant generation and cell viability assays. 106 (24%) of 438 VUS in 20 actionable genes were classified as oncogenic in functional assays. Variants categorized by PODS as Potentially actionable (N = 204) were more likely to be oncogenic than those categorized as Unknown (N = 230) (37% vs 13%, p = 4.08e-09). Our results demonstrate that rule-based actionability classification of VUS can identify patients more likely to have actionable variants for consideration with genomically-matched therapy.
Anomalous conductance quantization of a one-dimensional channel in monolayer WSe2
Authors: Boddison-Chouinard Justin , Bogan Alex , Barrios Pedro , Lapointe Jean , Watanabe Kenji , Taniguchi Takashi , Pawłowski Jarosław , Miravet Daniel , Bieniek Maciej , Hawrylak Pawel , Luican-Mayer Adina , Gaudreau Louis
Published: July 2023

Among quantum devices based on 2D materials, gate-defined quantum confined 1D channels are much less explored, especially in the high-mobility regime where many-body interactions play an important role. We present the results of measurements and theory of conductance quantization in a gate-defined one-dimensional channel in a single layer of transition metal dichalcogenide material WSe2. In the quasi-ballistic regime of our high-mobility sample, we report conductance quantization steps in units of e2/h for a wide range of carrier concentrations. Magnetic field measurements show that as the field is raised, higher conductance plateaus move to accurate quantized values and then shift to lower conductance values while the e2/h plateau remains locked. Based on microscopic atomistic tight-binding theory, we show that in this material, valley and spin degeneracies result in 2 e2/h conductance steps for noninteracting holes, suggesting that symmetry-breaking mechanisms such as valley polarization dominate the transport properties of such quantum structures.
Fronto-parietal networks shape human conscious report through attention gain and reorienting
Authors: Liu Jianghao , Bayle Dimitri J. , Spagna Alfredo , Sitt Jacobo D. , Bourgeois Alexia , Lehongre Katia , Fernandez-Vidal Sara , Adam Claude , Lambrecq Virginie , Navarro Vincent , Seidel Malkinson Tal , Bartolomeo Paolo
Published: July 2023

How do attention and consciousness interact in the human brain? Rival theories of consciousness disagree on the role of fronto-parietal attentional networks in conscious perception. We recorded neural activity from 727 intracerebral contacts in 13 epileptic patients, while they detected near-threshold targets preceded by attentional cues. Clustering revealed three neural patterns: first, attention-enhanced conscious report accompanied sustained right-hemisphere fronto-temporal activity in networks connected by the superior longitudinal fasciculus (SLF) II-III, and late accumulation of activity (>300 ms post-target) in bilateral dorso-prefrontal and right-hemisphere orbitofrontal cortex (SLF I-III). Second, attentional reorienting affected conscious report through early, sustained activity in a right-hemisphere network (SLF III). Third, conscious report accompanied left-hemisphere dorsolateral-prefrontal activity. Task modeling with recurrent neural networks revealed multiple clusters matching the identified brain clusters, elucidating the causal relationship between clusters in conscious perception of near-threshold targets. Thus, distinct, hemisphere-asymmetric fronto-parietal networks support attentional gain and reorienting in shaping human conscious experience.
Regional genetic correlations highlight relationships between neurodegenerative disease loci and the immune system
Authors: Lona-Durazo Frida , Reynolds Regina H. , Scholz Sonja W. , Ryten Mina , Gagliano Taliun Sarah A.
Published: July 2023

Neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are devastating complex diseases resulting in physical and psychological burdens on patients and their families. There have been important efforts to understand their genetic basis leading to the identification of disease risk-associated loci involved in several molecular mechanisms, including immune-related pathways. Regional, in contrast to genome-wide, genetic correlations between pairs of immune and neurodegenerative traits have not been comprehensively explored, but could uncover additional immune-mediated risk-associated loci. Here, we systematically assess the role of the immune system in five neurodegenerative diseases by estimating regional genetic correlations between these diseases and immune-cell-derived single-cell expression quantitative trait loci (sc-eQTLs). We also investigate correlations between diseases and protein levels. We observe significant (FDR < 0.01) correlations between sc-eQTLs and neurodegenerative diseases across 151 unique genes, spanning both the innate and adaptive immune systems, across most diseases tested. With Parkinson’s, for instance,RAB7L1in CD4+ naïve T cells is positively correlated andKANSL1-AS1is negatively correlated across all adaptive immune cell types. Follow-up colocalization highlight candidate causal risk genes. The outcomes of this study will improve our understanding of the immune component of neurodegeneration, which can warrant repurposing of existing immunotherapies to slow disease progression.
Classifying seismograms using the FastMap algorithm and support-vector machines
Authors: White Malcolm C. A. , Sharma Kushal , Li Ang , Kumar T. K. Satish , Nakata Nori
Published: July 2023

Neural networks and related deep learning methods are currently at the leading edge of technologies used for classifying complex objects such as seismograms. However they generally demand large amounts of time and data for model training and their learned models can sometimes be difficult to interpret. FastMapSVM is an interpretable machine learning framework for classifying complex objects, combining the complementary strengths of FastMap with support vector machines (SVMs) and extending the applicability of SVMs to domains with complex objects. FastMap is an efficient linear-time algorithm that maps complex objects to points in a Euclidean space while preserving pairwise domain-specific distances between them. Here we invoke FastMapSVM as a lightweight alternative to neural networks for classifying seismograms. We demonstrate that FastMapSVM outperforms other state-of-the-art methods for classifying seismograms when train data or time is limited. We also show that FastMapSVM can provide an insightful visualization of seismogram clustering behaviour and thus earthquake classification boundaries. We expect FastMapSVM to be viable for classification tasks in many other real-world domains.
Oxidative aromatization mechanism of ligustilide
Authors: Zhuang Yu-Qing , Zou Jian , Zhang Sheng-Yuan , Wu Jia-Ming , Long Liang , Chen Xian-Bo , Chen Guo-Dong , Hu Dan , Wang Yong-Heng , Gao Hao
Published: July 2023

The aromatization mechanisms of ligustilide (1), a versatile monomeric phthalide, were investigated.
An efficient bi-functional Ir-based catalyst for the acidic overall water splitting reaction
Authors: Wang Chunyan , Yang Fulin , Feng Ligang
Published: July 2023

An efficient bi-functional catalyst of Ir/Te for an overall water splitting reaction in an acid electrolyte was realized due to their electronic coupling and synergism.
Prediction of potential hard sodium carbaboride compounds assuming sp3-bonded covalent clathrates
Authors: Liu Ailing , Cheng Xiaoran , Wang Xingyu , Zou Yutong , Zhang Miao
Published: July 2023

We predicted six stoichiometric sodium carbaboride compounds (NaBC11, Na2B2C10, NaB2C10, Na2B4C8, NaB4C8, and Na2B6C6) based on Na-doped boron–carbon clathrates via first-principles calculations.
A PLA-tPU based magnesium ion incorporated CSH/nHA bioactive porous composite scaffold for critical bone defect repair
Authors: Shi Zhi , Huang Guobin , Li Zhongming , Lou Zhenkai , Gong Zhiqiang , Wang Xin , Li Chengyong , Wang Bing
Published: July 2023

This study use freeze-drying technology prepared a PT-M-CN bioactive porous composite scaffold for bone defects repairing. Results showed it has a great potential to promote osteogenic differentiation and new bone regeneration.
From intramolecular cyclization to intermolecular hydrolysis: TMSCF2Br-enabled carbonylation of aldehydes/ketones and amines to α-hydroxyamides
Authors: Liu An , Sun Shuo , Xie Qiqiang , Huang Rumin , Kong Taige , Ni Chuanfa , Hu Jinbo
Published: July 2023

An unprecedented metal-free multicomponent reaction enables rapid and straightforward access to structurally diverse α-hydroxyamides from carbonyl compounds (aldehydes/ketones), difluorocarbene and amines.
Sulfonyl radical-triggered two/three-component tandem bicyclization of CN-containing 1,6-enynes under transition metal- and base-free conditions
Authors: Qiu Hui , Li Liu-Bin , Cai Xue-Er , Li Mu-Han , Lu Yue-Jiao , Wang Ling-Tao , Tang Keqi , Liu Hongxin , Chen Jin-Yang , Wei Wen-Ting
Published: July 2023

Sulfonyl radical-triggered two/three-component tandem bicyclization of CN-containing 1,6-enynes.
Enantioselective [3+2]-cycloaddition of 2,3-disubstituted cyclobutenones: vicinal quaternary stereocenters construction and skeletal functionalization
Authors: Lu Licheng , Lu Ping
Published: July 2023

An enantioselective [3+2]-cycloaddition of 2,3-disubstituted cyclobutenones and iminoesters was developed to synthesize an array of chiral azabicycles with up to three contiguous all-carbon quaternary centers.
An extremely low temperature environment operatable hybrid dual-functioning energy device driven by a supercapacitor/piezo–triboelectric generator system
Authors: Selvam Samayanan , Park Young-Kwon , Yim Jin-Heong
Published: July 2023

Self-chargeable power generator-supercapacitor coupled systems that can operate at extremely low temperatures for next-generation wearable devices are demonstrated.
A zero-strain Na-deficient NASICON-type Na2.8Mn0.4V1.0Ti0.6(PO4)3 cathode for wide-temperature rechargeable Na-ion batteries
Authors: Shen Xing , Su Yuefeng , He Shunli , Li Yali , Xu Lifeng , Yang Ni , Liao Yanshun , Wang Meng , Wu Feng
Published: July 2023

Na superionic conductor (NASICON) type cathode materials with high structural stability and fast Na+ diffusion have been considered as high-power candidates for the exploration of Na-ion batteries.
The importance of rational institutionalism in the analysis of informal international institutions
Authors: Roger Charles , Snidal Duncan , Vabulas Felicity
Published: July 2023

The study of informal international institutions has advanced considerably over the past decade. Much of this work, including our own, has approached this phenomenon from the perspective of rationalist institutionalism. Yet, existing work has also been criticized from several conceptual, theoretical, and empirical angles. The recent special issue of International Politics on the “cascading dynamics” of informality by Cooper et al. (Int Politics, 2022,https://doi.org/10.1057/s41311-022-00399-4) offers an important example of such critiques. It builds on earlier work in the field, advancing our understanding of a number of processes and institutions, but also partly casts itself as a reaction to the approach we have adopted. We argue that key aspects of this critique are misguided and that Cooper et al. exaggerate the differences that divide us. Our aim in this article is to respond to their criticisms, clarify the key research issues at stake, emphasize the complementarities among approaches, and outline ways of moving forward.
The global burden of alcoholic liver disease: a systematic analysis of the global burden of disease study 2019
Authors: Zhang Nan , Xue Feng , Wu Xiao-Ning , Zhang Wei , Hou Jing-Jing , Xiang Jun-Xi , Lv Yi , Zhang Xu-Feng
Published: July 2023

Alcohol use is a major risk factor for the burden of mortality and morbidity. Alcoholic cirrhosis (AC) and alcoholic liver cancer (ALC) are most important and severe liver disease outcomes caused by alcohol use. The objectives of the current study were to investigate the global prevalence and burden of disease in disability-adjusted life years (DALYs) for AC and ALC, based on data from the Global Burden of Disease (GBD). Incidence, prevalence, death, and DALYs for GBDs in different locations, years, sex, and age groups were estimated using DisMod-MR 2.1 and a generic Cause of Death Ensemble Modeling approach. The correlations between the age-standardized incidence rate or age-standardized death rate and gender, sociodemographic index (SDI), and alcohol usage were conducted by Generalized Linear Models. Globally, the changes of age-standardized rates of indicators were not much significant over the 30-year period. However, the changes varied widely across regions. Central Asia and East Europe contributed the highest age-standardized incidence, prevalence, death, and DALYs and increased sharply by past 30 years. Generalized Linear Models (GLMs) showed male gender as a risk factor of AC, with the relative risk of incidence of 1.521 and relative risk of death of 1.503. Globally, there were improvements in overall health with regard to GBDs over the 30 years. However, the prevention of AC and ALC should be promoted in middle and middle-high SDI regions, especially Central Asia and East Europe, whereas more medical resources should be provided to improve treatment levels in low SDI region.
The role of plasticity, trade-offs, and feedbacks in shaping behavioral correlations
Authors: Dochtermann Ned A
Published: July 2023

How behaviors vary among individuals and covary with other behaviors has been a major topic of interest over the last two decades, particularly in research on animal personality, behavioral syndromes, and trade-offs with life-history traits. Unfortunately, proposed theoretical and conceptual frameworks explaining the seemingly ubiquitous observation of behavioral (co)variation have rarely successfully generalized. For example, the “pace-of-life syndrome hypothesis” proposes that behaviors, life-history, and physiological traits should be correlated in a predictable manner. However, these predictions are not consistently upheld. Two observations perhaps explain this failure: First, phenotypic correlations between behaviors are more strongly influenced by correlated and reversible plastic changes in behavior than by among-individual correlations which stem from the joint effects of genetics and developmental plasticity. Second, while trait correlations are frequently assumed to arise via trade-offs, the observed pattern of correlations is not consistent with simple pair-wise trade-offs. A possible resolution to the apparent inconsistency between observed correlations and a role for trade-offs is provided by state-behavior feedbacks. This is critical because the inconsistency between data and theory represents a major failure in our understanding of behavioral evolution. These two primary observations emphasize the importance of an increased research focus on correlated reversible plasticity in behavior—frequently estimated and then disregarded as within-individual covariances.
RDBridge: a knowledge graph of rare diseases based on large-scale text mining
Authors: Xing Huadong , Zhang Dachuan , Cai Pengli , Zhang Rui , Hu Qian-Nan
Published: July 2023

Motivation

Despite low prevalence, rare diseases affect 300 million people worldwide. Research on pathogenesis and drug development lags due to limited commercial potential, insufficient epidemiological data, and a dearth of publications. The unique characteristics of rare diseases, including limited annotated data, intricate processes for extracting pertinent entity relationships, and difficulties in standardizing data, represent challenges for text mining.

Results

We developed a rare disease data acquisition framework using text mining and knowledge graphs and constructed the most comprehensive rare disease knowledge graph to date, Rare Disease Bridge (RDBridge). RDBridge offers search functions for genes, potential drugs, pathways, literature, and medical imaging data that will support mechanistic research, drug development, diagnosis, and treatment for rare diseases.

Availability and implementation

RDBridge is freely available at http://rdb.lifesynther.com/.
PABPN1 promotes clear cell renal cell carcinoma progression by suppressing the alternative polyadenylation of SGPL1 and CREG1
Authors: Xiong Ming , Liu Chunyu , Li Wencheng , Jiang Huiling , Long Wulin , Zhou Menghao , Yang Chenlu , Kazobinka Gallina , Sun Yi , Zhao Jun , Hou Teng
Published: July 2023

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism in cancer development and progression. Poly(A) binding protein nuclear 1 (PABPN1) is a gene that encodes abundant nuclear protein, binds with high affinity to nascent poly(A) tails, and is crucial for 3ʹ-UTR (3ʹ-untranslated region) APA. Although PABPN1 has been recently reported as a dominant master APA regulator in clear cell renal cell carcinoma (ccRCC), the underlying functional mechanism remain unclear and the genes subject to PABPN1 regulation that contribute to ccRCC progression have not been identified. Here, we found that PABPN1 is upregulated in ccRCC, and its expression is highly associated with the clinical prognosis of ccRCC patients. PABPN1 promotes ccRCC cell proliferation, migration, invasion, and exerts an influence on sphingolipid metabolism and cell cycle. Moreover, PABPN1 depletion significantly suppressed cancer cell growth via induction of cell cycle arrest and apoptosis. In particular, we characterized PABPN1-regulated 3ʹ-UTR APA of sphingosine-1-phosphate lyase 1 (SGPL1) and cellular repressor of E1A stimulated genes 1 (CREG1), which contribute to ccRCC progression. Collectively, our data revealed that PABPN1 promotes ccRCC progression at least in part, by suppressing SGPL1 and CREG1. Thus, PABPN1 may be a potential therapeutic target in ccRCC.
‘Suddenly I was with my people’: two South African choirs contributing to community development
Authors: Joseph Dawn , Lamprecht Dorathea J , van Niekerk Caroline
Published: July 2023

Singing is a rich and dynamic part of South African cultural and national identity. The authors explore the identity of two choirs in the Cape Town metropole against the background of response to ongoing social change. The disparate yet similar choirs enhance the well-being of their members as communities and who sing for community. Community development as an outcome of community music is understood as process-driven. The Identity Process Theory serves as a useful integrative framework in which identity, social action and social change can be collectively examined with qualitative thematic analysis to code and analyse questionnaire and interview data (2017–2022). Three overarching themes are discussed, focusing on the experiences as perceived by research participants from the two choirs in relation to ‘singing as a music community’, ‘having a place to belong’ and ‘singing during COVID-19’. The discussion highlights differences, similarities, challenges and opportunities for these choirs in relation to community musicians, identity and place. Although generalizations to other choirs cannot necessarily be made, recommendations are offered, both for further research and of a practical nature. This paper argues that diverse forms of communal singing continue to play an important role in South Africa’s group identity for choirs, fostering hope for communities and their development. Notions of community development and community music should not become narrowly defined, excluding many choral groups and their contributions to society from the global conversation.
Improved Related-Key Rectangle Attacks On GIFT
Authors: Yu Qingyuan , Qin Lingyue , Dong Xiaoyang , Jia Keting
Published: July 2023

GIFT is a lightweight cipher proposed by Banik et al. at CHES’17, motivated by the design strategy of PRESENT. GIFT-64[2021] is a variant of GIFT proposed by Sun et al. at EUROCRYPT’22 to achieve better resistance against differential attack while maintaining a similar security level against linear attack. At EUROCRYPT’22, Dong et al. proposed a new rectangle framework considering the key guessing strategies for linear key-schedule ciphers, and established a uniform automatic search model for the whole rectangle attack. In this paper, we extend it to be applicable to bit-oriented ciphers, and construct an automatic search model involved in the distinguisher and key-recovery phase for GIFT. Moreover, we utilize the key relations of the linear key-schedule to the model, and find some new distinguishers both for GIFT-64 and GIFT-64[2021]. To evaluate the probability more accurately, we propose a method to calculate the probability of the 2-round middle part which connects the boomerang distinguisher for GIFT, and apply it with the SAT method to evaluate the probability of the whole distinguishers. As a result, we search out a new 20-round related-key boomerang distinguisher for GIFT-64, and achieve a 26-round attack with better time complexity than the best previous attack. For GIFT-64[2021], we find a 20-round boomerang distinguisher and give the first 26-round rectangle attack under related-key scenario.
Cohort profile: Evaluation of the Methods and Management of Acute Coronary Events (EMMACE) longitudinal cohort
Authors: Munyombwe Theresa , Dondo Tatendashe B , Hall Marlous , Nadarajah Ramesh , Hurdus Ben , Aktaa Suleman , Haris Mohammad , Keeley Adam , West Robert , Hall Alistair , Soloveva Anzhela , Norman Paul , Gale Chris P
Published: July 2023

Aims

The Evaluation of the Methods and Management of Acute Coronary Events (EMMACE) longitudinal cohort study aims to investigate health trajectories of individuals following hospitalization for myocardial infarction (MI).

Methods and results

EMMACE is a linked multicentre prospective cohort study of 14 899 patients with MI admitted to 77 hospitals in England who participated in the EMMACE-3 and -4 studies between 1st November 2011 and 24th June 2015. Long-term follow-up of the EMMACE cohorts was conducted through the EMMACE-XL (27th September 2020 to 31st March 2022) and EMMACE-XXL (1st July 2021 to 1st July 2023) studies. EMMACE collected individual participant data for health-related quality of life (HRQoL) measured by three-level EuroQol five-dimension and visual analogy scale at admission, 1 month, 6 months, 12 months, and 10 years follow-up, as well as medications, medication adherence, beliefs about medicines, Satisfaction with Information about Medicines Scale, and illness perceptions. Participant data were deterministically linked to the Myocardial Infarction National Audit Project (MINAP) for information on baseline treatments and comorbidities, Hospital Episode Statistics Admitted Patient Care (for cause-specific hospitalization data), and the Office for National Statistics (for mortality data) up to 2020.

Conclusion

EMMACE is a nationwide prospective cohort that will provide unique insights into fatal and non-fatal outcomes, medication adherence, and HRQoL following MI.

Trial registration: ClinicalTrials.gov NCT01808027 and NCT01819103
Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis
Authors: van Es Nick , Takada Toshihiko , Kraaijpoel Noémie , Klok Frederikus A , Stals Milou A M , Büller Harry R , Courtney D Mark , Freund Yonathan , Galipienzo Javier , Le Gal Grégoire , Ghanima Waleed , Huisman Menno V , Kline Jeffrey A , Moons Karel G M , Parpia Sameer , Perrier Arnaud , Righini Marc , Robert-Ebadi Helia , Roy Pierre-Marie , Wells Phil S , de Wit Kerstin , van Smeden Maarten , Geersing Geert-Jan
Published: July 2023

Aims

Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations.

Methods and results

An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10. Discrimination (c-statistic with 95% confidence intervals [CI] and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was subsequently compared with algorithms based on the Wells score and D-dimer testing. The final model included age (in years), sex, previous VTE, recent surgery or immobilization, haemoptysis, cancer, clinical signs of deep vein thrombosis, inpatient status, D-dimer (in µg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95% CI, 0.85–0.89; 95% PI, 0.77–0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87–1.14; 95% PI, 0.55–1.79). The model slightly overestimated VTE probability in the lower range of estimated probabilities. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c-statistic 0.73; 95% CI, 0.70–0.75) or structured clinical pretest probability (c-statistic 0.79; 95% CI, 0.76–0.81).

Conclusion

The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study.

Registration

PROSPERO ID 89366.
Seismic stereometry: an alternative two-station algorithm to seismic interferometry for analysing car-generated seismic signals
Authors: Sheng Y
Published: July 2023

Human activities generate seismic waves, which have been traditionally analysed by seismic interferometry. However, this processing technique often neglects the seismic source distribution and is prone to introducing biases in interpretations. This study proposes an alternative processing technique known as seismic stereometry to analyse seismic signals generated by cars. The proposed algorithm exploits the highly coherent wavefields recorded by dense seismic arrays and directly measures the seismic wave traveltime differences between sensors. By doing so, it intrinsically considers the seismic source distribution. Traveltime differences can be used to invert the positions of vehicles and the near-surface velocity structures. We demonstrate the analysis using a dense seismic array deployed atop a southern San Andreas Fault segment and invert the shallow S-wave velocity using seismic waves generated by only one car. The velocity inversion result reveals a clear contrast across the fault, consistent with previous studies. The developed technique, combined with the distributed acoustic sensing technology, has great potential for applications in the urban environment.
The development of a marker system for Pharmacists’ Behavioural Skills
Authors: Smith Samantha Eve , Kerins Joanne , McColgan-Smith Scott , Stewart Fiona , Power Ailsa , Mardon Julie , Tallentire Victoria Ruth
Published: July 2023

Objectives

Pharmacists increasingly require complex behavioural skills to fulfil enhanced roles within healthcare teams. Behavioural marker systems are used to assess behavioural (or non-technical) skills during immersive simulation. This study aimed to develop a marker system for pharmacists’ behavioural skills in patient-focussed care scenarios, and to investigate its content validity.

Methods

Literature describing existing marker systems and the requisite behavioural skills of pharmacists were presented to two expert panels, alongside video examples of pharmacists in patient-focussed care simulations. The expert panels used this information to develop a new behavioural marker system. A third expert panel assessed the content validity, and the item- and scale-content validity indices were calculated.

Key findings

The resulting tool contains four categories, each with three or four skill elements: situation awareness (gathering information; recognising and understanding information; anticipating, preparing and planning), decision-making and prioritisation (identifying options; prioritising; dealing with uncertainty; implementing or reviewing decisions), collaborative working (involving the patient; information sharing; leadership or followership), self-awareness (role awareness; speaking up; escalating care; coping with stress). The scale-content validity index was 0.95 (ideal) and the only item below the acceptable cut-off was ‘leadership or followership’ (0.7).

Conclusions

This tool is the first marker system designed to assess the behavioural skills of pharmacists in patient-focussed care scenarios. There is evidence of good content validity. It is hoped that once validated, the Pharmacists’ Behavioural Skills marker system will enable pharmacy educators to provide individualised and meaningful feedback on simulation participants’ behavioural skills.
Optimal reinsurance contract and investment strategy for multiple competitive-cooperative insurers and a reinsurer
Authors: Wang Tao , Chen Zhiping , Yang Peng
Published: July 2023

Accepted by: Giorgio Consigli

In this article, we consider a reinsurance contract design by taking into account the joint interests of multiple insurers and a reinsurer. The reinsurance contract consists of optimal reinsurance strategies and reinsurance prices. The former are chosen by the competitive–cooperative insurers and the latter are determined by a reinsurer. Both insurers and the reinsurer can invest in the common risk-free asset and one different risky asset. The optimal time-consistent reinsurance–investment strategies of the insurers and the optimal reinsurance prices and investment strategy of the reinsurer are derived analytically. Numerical experiments are carried out to illustrate the influences of model parameters on the optimal reinsurance contract and optimal investment strategies. We find that the establishment of the reinsurance contract is affected by the correlation between the claim sizes of insurers as well as that of claim numbers. The results reveal that competition and cooperation will lead to a decrease and increase of the reinsurance price, respectively, showing the importance of opting for cooperation among insurers. Both competition and cooperation are beneficial to insurers, especially for those with high risk aversion.
Rapid expansion of Neisseria gonorrhoeae ST7827 clone in Australia, with variable ceftriaxone phenotype unexplained by genotype
Authors: van Hal S J , Whiley D M , Le T , Ray S , Kundu R L , Kerr E , Lahra M M
Published: July 2023

Background

Neisseria gonorrhoeae is identified as a priority pathogen due to its capacity to rapidly develop antimicrobial resistance (AMR). Following the easing of SARS-CoV-2 pandemic travel restrictions across international borders in the state of New South Wales (NSW), Australia, a surge of gonococcal isolates with raised ceftriaxone MIC values were detected.

Methods

All N. gonorrhoeae isolates (n = 150) with increased ceftriaxone MIC values in NSW between 1 January 2021 and July 2022 from males and females from all sites were sequenced.

Results

A new emergence and rapid expansion of an N. gonorrhoeae ST7827 clone was documented within NSW, Australia and provides further evidence of the ability of N. gonorrhoeae to undergo sufficient genomic changes and re-emerge as a geographically restricted subclone. Mapping AMR determinants to MIC results did not reveal any genomic pattern that correlated with MIC values.

Conclusions

The rapid dissemination and establishment of this clone at the population level is a new and concerning demonstration of the agility of this pathogen, and underscores concerns about similar incursions and establishment of MDR clones. Moreover, it is notable that in this context the AMR genotype–phenotype correlates remain unclear, which requires further investigation to enable better understanding of genomic aspects of AMR in N. gonorrhoeae.
In vitro inactivation of SARS-CoV-2 by ozonated water via novel hand hygiene device
Authors: Lubitz Robert M , Leon Brian R , Bradner K Nicole , Romary Daniel J , Landsberger Sarah A
Published: July 2023

Aims

The COVID-19 pandemic has heightened awareness of the need for novel surface disinfectants and hand-hygiene modalities. Ozone gas is an effective surface disinfectant, but toxicity limits its use in human applications. Ozonated water is a safer means to use ozone for disinfection, especially for human antisepsis. However, there are little data available regarding the effectiveness of ozonated water in eliminating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Methods and results

This study utilizes a novel hand hygiene device that produces a stable ozone concentration of 0.5 +/−0.1 ppm in water and applies it using a proprietary spray that controls droplet size, velocity, and direction. The Device was used to apply ozonated water to a known quantity of SARS-CoV-2 Delta Variant viral particles on a non-porous surface (glass) for seven seconds. Post-exposure growth was compared to the unexposed matched control utilizing the Spearman–Karber method. Compared to control, ozonated water decreased SARS-CoV-2 viral growth by a mean log10 reduction of 4.33, or >99.99% reduction.

Conclusions

These results suggest that the ozonated water, when applied by a spray hand hygiene device, is highly effective at surface disinfection of SARS-CoV-2.
Rediscovering John Martin
Authors: Anguix-Vilches Laia
Published: July 2023

The imposing and melodramatic landscapes painted by John Martin (1789–1854) were widely celebrated in the early nineteenth century. However, mid-Victorian aesthetic shifts sent them into oblivion shortly after the artist’s death. By the 1920s they had completely lost their market value, and many lay rolled up in warehouses. This article investigates the rediscovery of Martin’s work in the immediate aftermath of the Second World War. Uncovering archival documents, primary sources and historical press reviews, it brings to light the joint efforts of connoisseurs, dealers and gallery directors in 1940s–1950s Britain in promoting, exhibiting and collecting Martin’s work. It also links those magnificent and catastrophic scenes with the post-war group of figurative artists dubbed neo-Romantics, documenting their attempts to get Martin’s work into the Tate collection. Ultimately, the article pays tribute to the collective enterprise of rescuing Martin’s masterpieces from ‘the waters of oblivion’, allowing them to survive till the present day.
The Senator and the Sting Operation: Politics, the Media, and Frank Moss’s Exposé of “Medicaid Mills”
Authors: Dolan Brian , Beitler Stephen , Johnson Antoine
Published: July 2023

In September 1975, Frank Moss, an eighteen-year veteran of the Senate from Utah, donned the scruffiest clothes he could find and walked into a small clinic in New York that catered to Medicaid patients. Using a phony Medicaid card supplied to him by a New York District Attorney, he posed as a patient with symptoms he feigned to assess the quality of care he would receive. Appalled by what he experienced, he and a team of staffers from his office embarked on a four-state tour of what he termed “Medicaid mills,” visiting more than 200 clinics in an undercover investigation that exposed alarming levels of provider fraud and abuse of the government health insurance system. This dramatic expose was covered by CBS’s widely watched Sunday-night news program 60 Minutes. The subsequent Senate hearings were a media sensation, leading to accusations that the Senator was “grandstanding.”

This article looks at the political climate in which the congressional sting operation, the media attention it garnered, and the subsequent legislation enacted sought to address a persistent, growing problem of fraud and abuse in Medicare and Medicaid. The article argues that Moss’s effort was an example of entrepreneurial politics, as defined by Craig Volden and Alan Wiseman in 2016, and something more as well. Moss was reacting to a political setting in which the legitimate authority of political institutions, including Congress, had been called into question by the Watergate scandal and other revelations. At the same time, organized medicine in America was dealing with its own version of this challenge to its authority. The result was a dramatic episode that focused on fraud and abuse in the ten-year-old Medicare program and that raised wider questions about changes in cultural authority in politics and medicine.
Divergent or convergent: how do forest carnivores use time in the Greater Yellowstone Ecosystem?
Authors: Smith Austin B , Squires John R , Bjornlie Nichole L , Holbrook Joseph D
Published: July 2023

Divergent activity can change the intensity of species interactions, largely affecting species distributions and abundances, and consequently influencing the composition and function of ecological communities. Few assessments of activity patterns have focused questions around different resource constraints or have examined varying time frames when interaction strengths are expected to increase. We evaluated how activity among carnivores and their prey shifted from early to late winter, coinciding with a presumed decrease in food resources for carnivores, and we measured time between species detections within a camera station. Our study species were three forest carnivores—Pacific martens (Martes caurina), Rocky Mountain red foxes (Vulpes vulpes macroura), coyotes (Canis latrans); and two of their prey—American red squirrels (Tamiasciurus hudsonicus), and snowshoe hares (Lepus americanus). We sampled these species across an extensive network of cameras (n = 107) during the 2014–2017 winter seasons in the Greater Yellowstone Ecosystem, Wyoming. We generated kernel density plots for timing of photographs and calculated the coefficient of overlap among density plots for our predators and prey during early and late winter. Furthermore, we calculated the time-between-detections (i.e., hours) among forest carnivores. We found no consistent trends in time-between-detections across our species pairs. Pacific martens exhibited cathemeral activity that aligned with the peaks in activity of the two prey species. Temporal overlap between coyote and red fox activities was small in early winter, whereas coyotes modified activity in late winter such that they more closely aligned with red foxes. This intraguild convergence of activity may reflect an increase in resource constraints and have consequences for competitive interactions between these two canids. Our study supports the notion that variation in time is an important axis in facilitating coexistence among these forest carnivores and prey species.
Stability and function of RCL1 are dependent on the interaction with BMS1
Authors: Wang Yong , Zhao Zhenyu , Yu Hongyan , Shi Hui , Tao Boxiang , He Yinan , Chen Jun , Peng Jinrong , Gan Meifu , Lo Li Jan
Published: July 2023

During ribosome biogenesis, the small subunit (SSU) processome is responsible for 40S assembly. The BMS1/RCL1 complex is a core component of the SSU processome that plays an important role in 18S rRNA processing and maturation. Genetic studies using zebrafish mutants indicate that both Bms1-like (Bms1l) and Rcl1 are essential for digestive organ development. In spite of vital functions of this complex, the mutual dependence of these two nucleolar proteins for the stability and function remains elusive. In this study, we identified an RCL1-interacting domain in BMS1, which is conserved in zebrafish and humans. Moreover, both the protein stability and nucleolar entry of RCL1 depend on its interaction with BMS1, otherwise RCL1 degraded through the ubiquitination–proteasome pathway. Functional studies revealed that overexpression of RCL1 in BMS1-knockdown cells can partially rescue the defects in 18S rRNA processing and cell proliferation, and hepatocyte-specific overexpression of Rcl1 can resume zebrafish liver development in the bms1l substitution mutant bms1lsq163/sq163but not in the knockout mutant bms1lzju1/zju1, which is attributed to the nucleolar entry of Rcl1 in the former mutant. Our data demonstrate that BMS1 and RCL1 interaction is essential for not only pre-rRNA processing but also the communication between ribosome biogenesis and cell cycle regulation.
Iconicity in the emergence of a phonological system?
Authors: Moita Mara , Abreu Ana Maria , Mineiro Ana
Published: July 2023

Iconicity has been described as an impetus for creating sign forms in emerging sign languages and forming signs in established sign languages. Iconic signs are defined as spontaneous or stable signs that directly reflect the representation of their referent. In established sign languages, iconic signs have phonological features. Regarding the link between the motivation for iconic signs and phonological features, we aim to investigate how iconicity might influence the emergence of a phonological system along with the evolution of a new sign language by observing how the rise of a phonological system might be revealed by the evolution of emerging iconic gestures and signs in a new sign language. For this purpose, we inventoried and coded the iconicity nature and phonological structure of 200 signed lexical items collected in two moments of Sao Tome and Principe Sign Language (LGSTP) emergence: at T1 (after 2 years since the deaf habitants initiated their social meetings) and T2 (8 years subsequent to T1 data collection). In the 8 years of LGSTP’s emergence, we found a dominance of iconic signs in tandem with changes in the signs’ internal structure. The handshape is revealed to be the phonological parameter with the greatest development, presenting itself as more complex. The LGSTP lexicon reveals that iconicity seems to prompt the emergence of sign forms. However, iconic strategies remain stable across the evolution of the emergent signs and are independent of the internal structure change of the sign.
A novel agreement statistic using data on uncertainty in ratings
Authors: Zee Jarcy , Mariani Laura , Barisoni Laura , Mahajan Parag , Gillespie Brenda
Published: July 2023

Many existing methods for estimating agreement correct for chance agreement by adjusting the observed proportion agreement by the probability of chance agreement based on different assumptions. These assumptions may not always be appropriate, as demonstrated by pathologists’ ratings of kidney biopsy descriptors. We propose a novel agreement statistic that accounts for the empirical probability of chance agreement, estimated by collecting additional data on rater uncertainty for each rating. A standard error estimator for the proposed statistic is derived. Simulation studies show that in most cases, our proposed statistic is unbiased in estimating the probability of agreement after removing chance agreement.
Flexor pollicis longus tendon rupture: a case series on palmaris longus tendon graft reconstruction after volar plate fixation
Authors: Shih Yi-Sheng , Chang Yao-Jen , Cheng Yu-Ting , Chang Chia-Sung , Lin Yu-Hsien
Published: July 2023

Flexor pollicis longus (FPL) tendon rupture is a debilitating condition that can impair hand function. This case series study aimed to evaluate the outcomes of FPL tendon rupture and subsequent palmaris longus (PL) tendon graft reconstruction. Three cases of FPL tendon rupture in patients who had previously undergone open reduction and internal fixation with a volar plate were included. The surgical intervention involved volar plate removal, tenolysis and PL tendon graft reconstruction. Follow-up assessments showed gradual improvement in wrist function, with no post-operative complications or infections observed. These findings suggest that PL tendon grafting can be an effective surgical technique for FPL tendon rupture. Further research is needed to determine optimal surgical approaches and post-operative rehabilitation protocols for this condition.