bluuebunny/crossref_metadata_2025 huggingface dataset:
Historical transboundary ozone health impact linked to affluence
Authors: Chen Lulu , Lin Jintai , Ni Ruijing , Kong Hao , Du Mingxi , Yan Yingying , Liu Mengyao , Wang Jingxu , Weng Hongjian , Zhao Yuanhong , Li Chunjin , Martin Randall V
Published: September 2022

Ozone pollution is a major transboundary threat to global health. Systematic improvement of mitigation strategy for transboundary ozone requires a socioeconomic understanding of historical lessons in countries at different affluence levels. Here, we explore the changes in transboundary ozone related premature deaths over 1951–2019 driven by anthropogenic emissions of four country groups categorized by income level. By integrating global emission datasets, a chemical transport model (GEOS-Chem), in situ ozone measurements worldwide and an ozone exposure-response model, we find that mortality caused by transboundary anthropogenic ozone increases by 27 times from 1951 to 2019, and on average contributes about 27% of global anthropogenic ozone related deaths. All groups exert and suffer from substantial transboundary ozone related mortality. The high-income and upper middle groups have each experienced an inverted U-shaped relationship between its affluence and per-million-people contribution to mortality caused by transboundary ozone, with the turning point around 23 000 USD and 6300 USD, respectively. The lower middle group has gradually matched the growth pathway of the upper middle group with a turning point less clear. Concerted efforts to ensure early turning points in less affluent countries will have considerable global health benefits.
Integrable boundaries for the q-Hahn process
Authors: Frassek Rouven
Published: September 2022

Taking inspiration from the harmonic process with reservoirs introduced by Frassek, Giardinà and Kurchan in (2020 J. Stat. Phys.
180 135–71), we propose integrable boundary conditions for its trigonometric deformation, which is known as the q-Hahn process. Following the formalism established by Mangazeev and Lu in (2019 Nucl. Phys. B 945 114665) using the stochastic R-matrix, we argue that the proposed boundary conditions can be derived from a transfer matrix constructed in the framework of Sklyanin’s extension of the quantum inverse scattering method and consequently preserve the integrable structure of the model. The approach avoids the explicit construction of the K-matrix.
Controlled release of gallium maltolate complex from injectable phosphocalcic cements
Authors: Dupleichs Manon , Limelette Maxence , Mellier Charlotte , Montouillout Valérie , Lefevre François-Xavier , Quillard Sophie , Mevellec Jean-Yves , Janvier Pascal
Published: September 2022

Some cancers have tropism for bone: breast, prostate, lung, kidney, and thyroid cancers are the most common. Bone metastases can be treated with surgical resection and the resulting bone defects can be filled with injectable biomaterials. Among these, calcium phosphates may be the biomaterials of choice because of their ability to locally release anticancer active ingredients. Herein, we propose the synthesis of injectable calcium phosphate cement (CPC) loaded with gallium maltolate (GaM). It is an extremely promising anticancer drug with also antibiotic and anti-inflammatory properties. This synthesis was based on commercial cement whose main component was α-tri-calcium phosphate (α-TCP), and the final product obtained after hardening was calcium-deficient apatite (CDA). Two formulations were prepared, containing 3.5% and 7% by mass of GaM (CPC-3.5G and CPC-7G respectively). Powder x-ray diffraction (pXRD), Fourier transform infrared (FTIR) spectroscopy, and magic-angle spinning nuclear magnetic resonance (NMR MAS) 31P analyses showed that the direct incorporation of GaM did not modify the final cement composition. Textural properties, such as setting time, injectability, workability, and cohesiveness, were well preserved or even improved. Additionally, the mechanical strength, although slightly reduced, remained perfectly compatible with surgical use. In vitro kinetics studies of GaM-loaded CPCs showed a controlled release of GaM (49% at 60 days for CPC-3.5G and 58% at 116 days for CPC-7G) following Fick’s law. Raman imaging was used to visualize its diffusion within the cement during in vitro release experiments. Finally, the structural integrity of the gallium complex in the CPC was confirmed using NMR MAS 71Ga.
Square grid pattern with direction-selective surface discharges in dielectric barrier discharge
Authors: ZHANG Jianhua , PAN Yuyang , FENG Jianyu , HE Yunan , CHU Jiahui , DONG Lifang
Published: September 2022

A new phenomenon that a filament discharged only once instead of twice in a cycle of the applied voltage is observed in a square grid pattern in a dielectric barrier discharge (DBD) with a larger gas gap, which is named intermittent discharge. Its spatiotemporal dynamics and the formation mechanism are studied by the multiple photomultiplier tubes and an intensified charge-coupled device. Corresponding to the positions of spots in the picture with an exposure time of 40 ms, there are some bright spots (discharge spots) and black spots (non-discharged spots) in the instantaneous image with an exposure time of 10 μs (a half cycle of the applied voltage). There are at least two bright spots around one black spot and vice versa. The surface discharges (SDS) can be observed between any two adjacent spots. The intensity of the SDS between the bright spot and the black spot is 2.5 times greater than that between two adjacent bright spots, which indicates that the SDS are directional-selective. The intermittent discharge with positive (negative) current polarity changes to that with negative (positive) current polarity, after it sustains up to 14 voltage cycles at the longest. The spatial distribution of the electric field component is calculated through COMSOL software to solve the Poisson equation numerically. It is found that the inhomogeneous distribution of surface electric field is caused by the inhomogeneous distribution of wall charges, which leads to direction-selective SDS. The intermittent discharge is formed by the competition between the direction-selective SDS and volume discharges (VDS) in DBD. This is the reason why the intermittent discharge is generated.
Expectation values from the single-layer quantum approximate optimization algorithm on Ising problems
Authors: Ozaeta Asier , van Dam Wim , McMahon Peter L
Published: September 2022

We report on the energy-expectation-value landscapes produced by the single-layer (p = 1) quantum approximate optimization algorithm (QAOA) when being used to solve Ising problems. The landscapes are obtained using an analytical formula that we derive. The formula allows us to predict the landscape for any given Ising problem instance and consequently predict the optimal QAOA parameters for heuristically solving that instance using the single-layer QAOA. We have validated our analytical formula by showing that it accurately reproduces the landscapes published in recent experimental reports. We then applied our methods to address the question: how well is the single-layer
QAOA
able to solve large benchmark problem instances? We used our analytical formula to calculate the optimal energy-expectation values for benchmark MAX-CUT problems containing up to 7000 vertices and 41 459 edges. We also calculated the optimal energy expectations for general Ising problems with up to 100 000 vertices and 150 000 edges. Our results provide an estimate for how well the single-layer QAOA may work when run on a quantum computer with thousands of qubits. In addition to providing performance estimates when optimal angles are used, we are able to use our analytical results to investigate the difficulties one may encounter when running the QAOA in practice for different classes of Ising instances. We find that depending on the parameters of the Ising Hamiltonian, the expectation-value landscapes can be rather complex, with sharp features that necessitate highly accurate rotation gates in order for the QAOA to be run optimally on quantum hardware. We also present analytical results that explain some of the qualitative landscape features that are observed numerically.
Cardiac inducing colonies halt fibroblast activation and induce cardiac/endothelial cells to move and expand via paracrine signaling
Authors: Mahapatra Samiksha , Sharma Michael V. R. , Brownson Breanna , Gallicano Vaughn E. , Gallicano G. Ian
Published: September 2022

Cardiac inducing colonies generated from germline stem cells secrete at least 18 paracrine factors that promote a full spectrum of events involved in cardiac regeneration. Events include preventing fibroblast activation (scarring), myocyte movement, and myocyte cell cycle up-regulation.
Phosphorylation of the small heat shock protein HspB1 regulates cytoskeletal recruitment and cell motility
Authors: Hoffman Laura M. , Jensen Christopher C. , Beckerle Mary C.
Published: September 2022

Mechanical cues activate p38 MAPK signaling to phosphorylate the small heat shock protein HspB1 which is required for normal mechanically stimulated actin remodeling, cell spreading, and cell motility.
α–Catenin-dependent vinculin recruitment to adherens junctions is antagonistic to focal adhesions
Authors: Bejar-Padilla Vidal , Cabe Jolene I. , Lopez Santiago , Narayanan Vani , Mezher Mazen , Maruthamuthu Venkat , Conway Daniel E.
Published: September 2022

Vinculin is a mechanosensitive protein found at both focal adhesions (FAs) and adherens junctions (AJs). Recruitment of vinculin to AJs results in impaired FA formation, occurring as a result of a structural rearrangement of the actin cytoskeleton. Vinculin translocation between AJs and FAs is necessary for efficient collective cell migration.
Association Between ABO Blood Group System and COVID-19 Severity
Authors: Bshaena Amina M , Almajdoub Osama H , Alshwesh Rajaa A , Omran Entesar A , Haq Soghra , Ismail Faisal
Published: September 2022

Objectives

A possible association between blood group systems (ABO and Rh) and coronavirus disease 2019 (COVID-19) severity has recently been investigated by various studies with conflicting results. However, due to variations in the prevalence of the ABO and Rh blood groups in different populations, their association with COVID-19 might be varied as well. Therefore, we conducted this study on Libyan participants to further investigate this association and make population-based data available to the worldwide scientific community.

Methods

In this case-control study, ABO and Rh blood groups in 419 confirmed COVID-19 cases in Zawia, Libya, and 271 healthy controls were compared using descriptive statistics and χ 2 tests.

Results

Blood group A was significantly more prevalent in patients with severe COVID-19 (64/125; 51.2%) than in patients with nonsevere COVID-19 (108/294, 36.7%) (P < .034), whereas the O blood group prevalence was higher in nonsevere COVID-19 cases (131/294, 44.5%) compared with severe cases (43/125, 34.4%) (P < .001).

Conclusions

The results showed a significant association between blood group A and the severity of COVID-19, whereas patients with blood group O showed a low risk of developing severe COVID-19 infection. No significant association was found between Rh and susceptibility/severity of the disease.
The Reemergence of Measles
Authors: Klassen-Fischer Mary K , Nelson Ann M , Neafie Ronald C , Neafie Fides A , Auerbach Aaron , Baker Thomas P , Burke Allen P , Datta Anandita A , Franks Teri J , Horkayne-Szakaly Iren , Lack Ernest E , Lewin-Smith Michael R , Luiña Contreras Alejandro , Mattu Rubina H , Rush Walter L , Shick Paul C , Zhang Yang , Rentas Francisco J , Moncur Joel T
Published: September 2022

Objectives

Present-day pathologists may be unfamiliar with the histopathologic features of measles, which is a reemerging disease. Awareness of these features may enable early diagnosis of measles in unsuspected cases, including those with an atypical presentation. Using archived tissue samples from historic patients, a unique source of histopathologic information about measles and other reemerging infectious diseases, we performed a comprehensive analysis of the histopathologic features of measles seen in commonly infected tissues during prodrome, active, and late phases of the disease.

Methods

Subspecialty pathologists analyzed H&E-stained slides of specimens from 89 patients accessioned from 1919 to 1998 and correlated the histopathologic findings with clinical data.

Results

Measles caused acute and chronic histopathologic changes, especially in the respiratory, lymphoid (including appendix and tonsils), and central nervous systems. Bacterial infections in lung and other organs contributed significantly to adverse outcomes, especially in immunocompromised patients.

Conclusions

Certain histopathologic features, especially Warthin-Finkeldey cells and multinucleated giant cells without inclusions, allow pathologists to diagnose or suggest the diagnosis of measles in unsuspected cases.
Exploring the effects of a smartphone-based meditation app on stress, mindfulness, well-being, and resilience in pharmacy students
Authors: Truhlar Laura M , Durand Cheryl , Cooper Maryann R , Goldsmith Carroll-Ann W
Published: September 2022

Purpose

The purpose of this study was to investigate the effects of the smartphone-based meditation app Ten Percent Happier on stress, mindfulness, well-being, and resilience in pharmacy students.

Methods

Pharmacy students in a professional year of study were recruited to participate. Students were instructed to meditate using the Ten Percent Happier app for at least 5 days a week for 4 weeks. Students could use the app at their discretion for weeks 5 to 12. Baseline, week 4, and week 12 responses were collected from the following instruments: the Perceived Stress Scale, the Five-Facet Mindfulness Questionnaire-15, the Flourishing Scale, and the Brief Resilience Scale.

Results

Eighty-nine pharmacy students volunteered for the study. Sixty (67%) enrolled by completing the baseline survey. Of these, 28 (47%) completed the week 4 survey and 22 (37%) completed the week 12 survey. Participants experienced a reduction in perceived stress (P = 0.0005) and increases in resilience (P < 0.0001) and well-being (P = 0.0006). Increases in mindfulness were seen in 4 of the 5 subscales of the Five-Facet Mindfulness Questionnaire-15 (P ≤ 0.05). These benefits were noted at week 4 and maintained at week 12.

Conclusion

Pharmacy students who practiced mindful meditation through the Ten Percent Happier app for an average of 5 days a week for 4 weeks experienced reduced stress and improved mindfulness, well-being, and resilience. Benefits experienced during the intervention were maintained at the 8-week follow-up, despite app usage decreasing to an average of 4 days a week.
A biomedical knowledge graph-based method for drug–drug interactions prediction through combining local and global features with deep neural networks
Authors: Ren Zhong-Hao , You Zhu-Hong , Yu Chang-Qing , Li Li-Ping , Guan Yong-Jian , Guo Lu-Xiang , Pan Jie
Published: September 2022

Drug–drug interactions (DDIs) prediction is a challenging task in drug development and clinical application. Due to the extremely large complete set of all possible DDIs, computer-aided DDIs prediction methods are getting lots of attention in the pharmaceutical industry and academia. However, most existing computational methods only use single perspective information and few of them conduct the task based on the biomedical knowledge graph (BKG), which can provide more detailed and comprehensive drug lateral side information flow. To this end, a deep learning framework, namely DeepLGF, is proposed to fully exploit BKG fusing local–global information to improve the performance of DDIs prediction. More specifically, DeepLGF first obtains chemical local information on drug sequence semantics through a natural language processing algorithm. Then a model of BFGNN based on graph neural network is proposed to extract biological local information on drug through learning embedding vector from different biological functional spaces. The global feature information is extracted from the BKG by our knowledge graph embedding method. In DeepLGF, for fusing local–global features well, we designed four aggregating methods to explore the most suitable ones. Finally, the advanced fusing feature vectors are fed into deep neural network to train and predict. To evaluate the prediction performance of DeepLGF, we tested our method in three prediction tasks and compared it with state-of-the-art models. In addition, case studies of three cancer-related and COVID-19-related drugs further demonstrated DeepLGF’s superior ability for potential DDIs prediction. The webserver of the DeepLGF predictor is freely available at http://120.77.11.78/DeepLGF/.
GraphCDA: a hybrid graph representation learning framework based on GCN and GAT for predicting disease-associated circRNAs
Authors: Dai Qiguo , Liu Ziqiang , Wang Zhaowei , Duan Xiaodong , Guo Maozu
Published: September 2022

Motivation: CircularRNA (circRNA) is a class of noncoding RNA with high conservation and stability, which is considered as an important disease biomarker and drug target. Accumulating pieces of evidence have indicated that circRNA plays a crucial role in the pathogenesis and progression of many complex diseases. As the biological experiments are time-consuming and labor-intensive, developing an accurate computational prediction method has become indispensable to identify disease-related circRNAs. Results: We presented a hybrid graph representation learning framework, named GraphCDA, for predicting the potential circRNA–disease associations. Firstly, the circRNA–circRNA similarity network and disease–disease similarity network were constructed to characterize the relationships of circRNAs and diseases, respectively. Secondly, a hybrid graph embedding model combining Graph Convolutional Networks and Graph Attention Networks was introduced to learn the feature representations of circRNAs and diseases simultaneously. Finally, the learned representations were concatenated and employed to build the prediction model for identifying the circRNA–disease associations. A series of experimental results demonstrated that GraphCDA outperformed other state-of-the-art methods on several public databases. Moreover, GraphCDA could achieve good performance when only using a small number of known circRNA–disease associations as the training set. Besides, case studies conducted on several human diseases further confirmed the prediction capability of GraphCDA for predicting potential disease-related circRNAs. In conclusion, extensive experimental results indicated that GraphCDA could serve as a reliable tool for exploring the regulatory role of circRNAs in complex diseases.
Boosting single-cell gene regulatory network reconstruction via bulk-cell transcriptomic data
Authors: Shu Hantao , Ding Fan , Zhou Jingtian , Xue Yexiang , Zhao Dan , Zeng Jianyang , Ma Jianzhu
Published: September 2022

Computational recovery of gene regulatory network (GRN) has recently undergone a great shift from bulk-cell towards designing algorithms targeting single-cell data. In this work, we investigate whether the widely available bulk-cell data could be leveraged to assist the GRN predictions for single cells. We infer cell-type-specific GRNs from both the single-cell RNA sequencing data and the generic GRN derived from the bulk cells by constructing a weakly supervised learning framework based on the axial transformer. We verify our assumption that the bulk-cell transcriptomic data are a valuable resource, which could improve the prediction of single-cell GRN by conducting extensive experiments. Our GRN-transformer achieves the state-of-the-art prediction accuracy in comparison to existing supervised and unsupervised approaches. In addition, we show that our method can identify important transcription factors and potential regulations for Alzheimer’s disease risk genes by using the predicted GRN. Availability: The implementation of GRN-transformer is available at https://github.com/HantaoShu/GRN-Transformer.
Icolos: a workflow manager for structure-based post-processing of de novo generated small molecules
Authors: Moore J Harry , Bauer Matthias R , Guo Jeff , Patronov Atanas , Engkvist Ola , Margreitter Christian
Published: September 2022

We present Icolos, a workflow manager written in Python as a tool for automating complex structure-based workflows for drug design. Icolos can be used as a standalone tool, for example in virtual screening campaigns, or can be used in conjunction with deep learning-based molecular generation facilitated for example by REINVENT, a previously published molecular de novo design package. In this publication, we focus on the internal structure and general capabilities of Icolos, using molecular docking experiments as an illustrative example.

Availability and implementation

The source code is freely available at https://github.com/MolecularAI/Icolos under the Apache 2.0 license. Tutorial notebooks containing minimal working examples can be found at https://github.com/MolecularAI/IcolosCommunity.

Supplementary information

Supplementary data are available at Bioinformatics online.
dsMTL: a computational framework for privacy-preserving, distributed multi-task machine learning
Authors: Cao Han , Zhang Youcheng , Baumbach Jan , Burton Paul R , Dwyer Dominic , Koutsouleris Nikolaos , Matschinske Julian , Marcon Yannick , Rajan Sivanesan , Rieg Thilo , Ryser-Welch Patricia , Späth Julian ,   The COMMITMENT Consortium, Herrmann Carl , Schwarz Emanuel
Published: September 2022

Motivation

In multi-cohort machine learning studies, it is critical to differentiate between effects that are reproducible across cohorts and those that are cohort-specific. Multi-task learning (MTL) is a machine learning approach that facilitates this differentiation through the simultaneous learning of prediction tasks across cohorts. Since multi-cohort data can often not be combined into a single storage solution, there would be the substantial utility of an MTL application for geographically distributed data sources.

Results

Here, we describe the development of ‘dsMTL’, a computational framework for privacy-preserving, distributed multi-task machine learning that includes three supervised and one unsupervised algorithms. First, we derive the theoretical properties of these methods and the relevant machine learning workflows to ensure the validity of the software implementation. Second, we implement dsMTL as a library for the R programming language, building on the DataSHIELD platform that supports the federated analysis of sensitive individual-level data. Third, we demonstrate the applicability of dsMTL for comorbidity modeling in distributed data. We show that comorbidity modeling using dsMTL outperformed conventional, federated machine learning, as well as the aggregation of multiple models built on the distributed datasets individually. The application of dsMTL was computationally efficient and highly scalable when applied to moderate-size (n < 500), real expression data given the actual network latency.

Availability and implementation

dsMTL is freely available at https://github.com/transbioZI/dsMTLBase (server-side package) and https://github.com/transbioZI/dsMTLClient (client-side package).

Supplementary information

Supplementary data are available at Bioinformatics online.
Is Active Learning Enough? The Contributions of Misconception-Focused Instruction and Active-Learning Dosage on Student Learning of Evolution
Authors: Nehm Ross H , Finch Stephen J , Sbeglia Gena C
Published: September 2022

abstract

Prior studies of active learning (AL) efficacy have typically lacked dosage designs (e.g., varying intensities rather than simple presence or absence) or specification of whether misconceptions were part of the instructional treatments. In this study, we examine the extent to which different doses of AL (approximately 10%, 15%, 20%, 36% of unit time), doses of misconception-focused instruction (MFI; approximately 0%, 8%, 11%, 13%), and their intersections affect evolution learning. A quantitative, quasiexperimental study (N > 1500 undergraduates) was conducted using a pretest, posttest, delayed posttest design with multiple validated measures of evolution understanding. The student background variables (e.g., binary sex, race or ethnicity), evolution acceptance, and prior coursework were controlled. The results of hierarchical linear and logistic models indicated that higher doses of AL and MFI were associated with significantly larger knowledge and abstract reasoning gains and misconception declines. MFI produced significant learning above and beyond AL. Explicit misconception treatments, coupled with AL, should be explored in more areas of life science education.
Visit-to-visit variability in blood pressure and kidney disease progression in IgA nephropathy
Authors: Tang Chen , Zhang Xiao-Yan , Lv Ji-Cheng , Shi Su-Fang , Zhou Xu-Jie , Liu Li-Jun , Zhang Hong
Published: September 2022

Background

The visit-to-visit variability (VVV) in blood pressure (BP) is an important risk factor for stroke and coronary heart disease and may also be associated with kidney damage and the development of chronic kidney disease (CKD). Data on the association between VVV in BP and the risk of CKD progression among patients with immunoglobulin A nephropathy (IgAN) are limited. We aimed to evaluate the relationships of VVV in BP with the progression of IgAN.

Methods

We assessed 1376 patients with IgAN at Peking University First Hospital. The main VVV in BP was expressed as the standard deviation (SD), coefficient of variation (CV) and average real variability (ARV). The associations of variability in BP with composite kidney disease progression events, defined as a 50% decline in estimated glomerular filtration rate (eGFR) and kidney failure, were examined using Cox models.

Results

During a median follow-up of 44.1 months (interquartile range 23.0–76.7), 247 (18.0%) patients experienced composite kidney disease progression events. With a higher SD in systolic BP (SBP) values, the risk of kidney disease progression events increased {hazard ratio [HR] 1.07 [95% confidence interval (CI) 1.03–1.11]; P < .001} after maximal adjustment, including baseline SBP and mean SBP during the first 12-month period. Using the first quartile of SD SBP values as the reference, the risk of composite kidney disease progression events was higher among patients with higher SD SBP values; the HR was 2.12 (95% CI 1.31–3.44) in the highest quartile (P for trend < .001). A similar trend could be observed when analysing the SD of diastolic BP, but the risk was not significantly increased. The associations were similar when analysed with the CV and ARV.

Conclusion

SBP variability was significantly associated with kidney disease progression in IgAN.
CarrotOmics: a genetics and comparative genomics database for carrot (Daucus carota)
Authors: Rolling William R , Senalik Douglas , Iorizzo Massimo , Ellison Shelby , Van Deynze Allen , Simon Philipp W
Published: September 2022

CarrotOmics (https://carrotomics.org/) is a comprehensive database for carrot (Daucus carota L.) breeding and research. CarrotOmics was developed using resources available at the MainLab Bioinformatics core (https://www.bioinfo.wsu.edu/) and is implemented using Tripal with Drupal modules. The database delivers access to download or visualize the carrot reference genome with gene predictions, gene annotations and sequence assembly. Other genomic resources include information for 11 224 genetic markers from 73 linkage maps or genotyping-by-sequencing and descriptions of 371 mapped loci. There are records for 1601 Apiales species (or subspecies) and descriptions of 9408 accessions from 11 germplasm collections representing more than 600 of these species. Additionally, 204 Apiales species have phenotypic information, totaling 28 517 observations from 10 041 biological samples. Resources on CarrotOmics are freely available, search functions are provided to find data of interest and video tutorials are available to describe the search functions and genomic tools. CarrotOmics is a timely resource for the Apiaceae research community and for carrot geneticists developing improved cultivars with novel traits addressing challenges including an expanding acreage in tropical climates, an evolving consumer interested in sustainably grown vegetables and a dynamic environment due to climate change. Data from CarrotOmics can be applied in genomic-assisted selection and genetic research to improve basic research and carrot breeding efficiency.

Database URL

https://carrotomics.org/
Opportunistic Infections in Patients with Inflammatory Bowel Disease Treated with Advanced Therapies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Olivera Pablo A , Lasa Juan S , Zubiaurre Ignacio , Jairath Vipul , Abreu Maria T , Rubin David T , Reinisch Walter , Magro Fernando , Rahier Jean-François , Danese Silvio , Rabaud Christian , Peyrin-Biroulet Laurent
Published: September 2022

Background and Aims

Advanced therapies for inflammatory bowel disease [IBD] could potentially lead to a state of immunosuppression with an increased risk of opportunistic infections [OIs]. We aimed to provide an update on the incidence of OIs among adult IBD patients in randomized controlled trials [RCTs] of approved biologics and small-molecule drugs [SMDs]. Also, we aimed to describe OI definitions utilized in RCTs, to ultimately propose a standardized definition.

Methods

Electronic databases were searched from January 1, 1990, until April 16, 2022. Our primary outcome was incidence rate of overall OIs among IBD patients exposed and unexposed to biologics or SMDs. We also describe specific OIs reported in included trials, as well as definitions of OIs within studies when provided.

Results

Ninety studies were included. The incidence rates of reported OIs were 0.42 and 0.21 per 100 person-years in patients exposed to advanced therapies and placebo, respectively. This was highest for anti-tumour necrosis factors [0.83 per 100 person-years] and Janus kinase inhibitors [0.55 per 100 person-years] and lowest for anti-integrins and ozanimod. On meta-analysis, no increased risk of OIs was observed. None of the studies provided a detailed definition of OIs, or a comprehensive list of infections considered as OIs.

Conclusion

Different mechanisms of action may have specific OI profiles. In the absence of a uniform definition of OIs, these estimates are less reliable. We propose a definition to be used in future studies to help provide standardized reporting. When using this definition, we saw significant differences in incidence rates of OIs across mechanisms of action.
European Society of Cardiology quality indicators for the cardiovascular pre-operative assessment and management of patients considered for non-cardiac surgery. Developed in collaboration with the European Society of Anaesthesiology and Intensive Care
Authors: Gencer Baris , Gale Chris P , Aktaa Suleman , Halvorsen Sigrun , Beska Ben , Abdelhamid Magdy , Mueller Christian , Tutarel Oktay , McGreavy Paul , Schirmer Henrik , Geissler Tobias , Sillesen Henrik , Niessner Alexander , Zacharowski Kai , Mehilli Julinda , Potpara Tatjana
Published: September 2022

Aims

To establish a set of quality indicators (QIs) for the cardiovascular (CV) assessment and management of patients undergoing non-cardiac surgery (NCS).

Methods and results

The Quality Indicator Committee of the European Society of Cardiology (ESC) and European Society of Anaesthesiology and Intensive Care (ESAIC) in collaboration with Task Force members of the 2022 ESC Guidelines on CV assessment and management of patients undergoing NCS followed the ESC methodology for QI development. This included (1) identification, by constructing a conceptual framework of care, of domains of the CV assessment, and management of patients with risk factors or established cardiovascular disease (CVD) who are considered for or undergoing NCS, (2) development of candidate QIs following a systematic literature review, (3) selection of the final set of QIs using a modified Delphi method, and (4) evaluation of the feasibility of the developed QIs. In total, eight main and nine secondary QIs were selected across six domains: (1) structural framework (written policy), (2) patient education and quality of life (CV risk discussion), (3) peri-operative risk assessment (indication for diagnostic tests), (4) peri-operative risk mitigation (use of hospital therapies), (5) follow-up (post-discharge assessment), and (6) outcomes (major CV events).

Conclusion

We present the 2022 ESC/ESAIC QIs for the CV assessment and management of patients with risk factors or established CVD who are considered for or are undergoing NCS y. These indicators are supported by evidence from the literature, underpinned by expert consensus, and align with the 2022 ESC Guidelines on CV assessment and management of patients undergoing NCS.
An Adaptable Physiological Model of Endocytic Megalin Trafficking in Opossum Kidney Cells and Mouse Kidney Proximal Tubule
Authors: Shipman Katherine E , Long Kimberly R , Cowan Isabella A , Rbaibi Youssef , Baty Catherine J , Weisz Ora A
Published: September 2022

The cells that comprise the proximal tubule (PT) are specialized for high-capacity apical endocytosis necessary to maintain a protein-free urine. Filtered proteins are reclaimed via receptor-mediated endocytosis facilitated by the multiligand receptors megalin and cubilin. Despite the importance of this pathway, we lack a detailed understanding of megalin trafficking kinetics and how they are regulated. Here, we utilized biochemical and quantitative imaging methods in a highly differentiated model of opossum kidney (OK) cells and in mouse kidney in vivo to develop mathematical models of megalin traffic. A preliminary model based on biochemically quantified kinetic parameters was refined by colocalization of megalin with individual apical endocytic compartment markers. Our model predicts that megalin is rapidly internalized, resulting in primarily intracellular distribution of the receptor at steady state. Moreover, our data show that early endosomes mature rapidly in PT cells and suggest that Rab11 is the primary mediator of apical recycling of megalin from maturing endocytic compartments. Apical recycling represents the rate-limiting component of endocytic traffic, suggesting that this step has the largest impact in determining the endocytic capacity of PT cells. Adaptation of our model to the S1 segment of mouse PT using colocalization data obtained in kidney sections confirms basic aspects of our model and suggests that our OK cell model largely recapitulates in vivo membrane trafficking kinetics. We provide a downloadable application that can be used to adapt our working parameters to further study how endocytic capacity of PT cells may be altered under normal and disease conditions.
Motivational Drivers of Temporal Dynamics in Postretirement Work
Authors: Hansson Isabelle , Henkens Kène , van Solinge Hanna
Published: September 2022

Objectives

Many retirees continue to work in retirement, but the temporal dynamics of this process are not well understood. This article examined the extent to which retirees increase, decrease, and exit their work engagement over time. We hypothesized that different motives for postretirement work—financial, social, personal, and organizational—have differential affects on changes in work extent.

Methods

We analyzed 7 waves of the HEalth, Aging and Retirement Transitions in Sweden study (n = 3,123). Postretirement work was defined as working for pay while receiving pension benefits. Changes in work extent were estimated with multistate models and examined in relation to the 4 motives.

Results

Results showed a gradual decrease in work extent following retirement. Financial motives increased the likelihood to take up more work and decreased the likelihood to reduce work hours. Social motives increased the likelihood to reduce and exit work, while personal motives decreased the likelihood for those same pathways. Organizational (demand-driven) motives increased the likelihood to stop working.

Discussion

Our findings suggest that financial motives constitute an important driver for taking up more work in retirement, while motives related to the personal meaning of work explain why retirees maintain their level of engagement over time. The social function of work, on the other hand, may be gradually replaced by social activities outside of work, resulting in a gradual disengagement from work. Finally, demand-driven motives appear insufficient to remain in the labor force, highlighting the need to acknowledge the diversity of motives for continuing to work.
Racial Capitalism in Voltaire’s Enlightenment
Authors: Giovannetti-Singh Gianamar
Published: September 2022

This essay argues that the concept of ‘racial capitalism’ can help us understand the connections between seemingly disparate parts of Voltaire’s extensive corpus of work. It contends that even though the Enlightenment’s racial politics abounded with contradictions and ambivalences, Voltaire stood out from his contemporaries. While the connections between his polygenism – the theory that humans of different races were created separately – and material investments in colonial commerce have long been debated by radical historians, this essay suggests that Voltaire’s views about race’s relationship to labour were transformed by France’s colonial losses during the Seven Years’ War.
Decreasing the Interval Wait Times for Screening Mammogram Results Using the “Reflex Testing” Algorithm
Authors: Alvarenga Julio , Moran Jay , Bulgaru Anca , Moran Meena S
Published: September 2022

Objective

The purpose of this analysis was to determine whether our “reflex testing” (RefT) intervention, implemented to address barriers in scheduling, communication, and diagnostic order placement for resolving BI-RADS 0 screening mammograms, resulted in decreased interval wait times (IWT) for patients with abnormal screening mammograms (abSM).

Methods

All BI-RADS 0 cases over two six-month periods (pre-RefT and post-RefT) were analyzed. Timelines were generated for each BI-RADS 0 case. Elapsed days were computed from date of BI-RADS 0 report to the date of biopsy, additional diagnostic testing, and final resolution. The means of each endpoint within the pre-RefT and post-RefT cohorts were statistically analyzed using Pearson chi-square analysis to assess whether IWT differed significantly after RefT implementation.

Results

The analytic cohort consisted of 1523 BI-RADS 0 cases (n(pre-RefT) = 647, n(post-RefT) = 876). Reflex testing decreased the overall mean IWT from 23.5 to 8.2 days (P < 0.001). For patients not requiring biopsy (1190/1523, 78.1%), the mean IWT from the BI-RADS 0 designation to first diagnostic test or resolution decreased from 29.7 to 10.8 days (P < 0.010). For patients who had biopsy (333/1523, 21.9%), RefT significantly decreased the IWT from BI-RADS 0 to first diagnostic test from 31.4 to 7.7 days (P < 0.001) and also significantly decreased the IWT from first diagnostic test to biopsy (20.9 to 17.7 days; P < 0.013).

Conclusion

Reflex testing intervention streamlines the workflow and significantly decreases IWT for resolving BI-RADS 0 abSM. The RefT intervention could be considered to improve efficiency at other breast centers.
Using the Medical Audit to Improve Practice Performance
Authors: Friedewald Sarah M , Schacht David V , Houshmand Golbahar , Nishikawa Robert M , Linver Michael N
Published: September 2022

Feedback to physicians on their clinical performance is critical to continuous learning and maintenance of skills as well as maintaining patient safety. However, it is fraught with challenges around both implementation and acceptance. Additionally, rewarding of performance improvement is not often done, putting into question the efficacy of the process. Physician audit and feedback have been studied extensively and shown to be beneficial in many fields of medicine. Documenting physician performance and sharing individual and group data have been positively linked to changing physician behavior, ultimately leading to improved patient outcomes. Although casual review of one’s own performance is often the easiest approach, it is frequently over- or underestimated by self-evaluation. Objective measures are therefore important to provide concrete data on which physicians can act. A fundamental question remains in mammography: Is reporting the information to the physician and accreditation bodies enough, or should there be consequences for the radiologist and/or facility if there is outlier behavior?
Identification and observations of parasitic isopod larvae (Isopoda: Epicaridea) from the northeastern Pacific: pelagic distribution and association with copepod intermediate hosts
Authors: Williams Jason D , Escalante Monique , Shanks Alan L
Published: September 2022

Zooplankton samples from the northeastern Pacific, USA were analyzed to identify and determine the abundance and distribution of parasitic isopod larvae and copepod hosts. Vertically stratified samples were collected at stations spanning the continental shelf off Oregon, USA. Two species of epicarideans were identified: Hemioniscus balaniBuchholz, 1866 (endoparasite of barnacles) and Argeia pugettensisDana, 1853 (ectoparasite of shrimps). Cryptoniscus larvae of these species can be distinguished based on the antennae (four basal and five flagellar articles in H. balani, four basal and four flagellar articles in A. pugettensis), tooth-like structures on the antennules and coxal teeth (present in H. balani, lacking in A. pugettensis), and pereopods (1, 2 gnathopodal and 5, 6 ambulatory in H. balani, all gnathopodal in A. pugettensis). Epicaridean larvae were rare in zooplankton samples with concentrations up to 10 m–3. Larvae were often found within 10 km of shore, with highest concentrations below the Ekman layer at 20–50 m depth near the bottom and between the 8 and 10°C isotherms. Likely as a result of dislodgment, only 26 copepods with epicaridium or microniscus larvae attached were confirmed. Larvae were mostly (78%) found attached to two species of Acartia, suggesting they were the preferred host, but five other genera of copepods were documented as hosts. The concentration of copepods and larvae exhibited a significant positive correlation when the analysis was limited to stations where both larvae and copepods were caught. The distribution of host copepods was significantly shallower than epicaridean larvae and generally closer to shore. The planktonic phase of the life cycle of epicarideans remains a black box for most of the +860 known species. Future work should include molecular data to link their larval and adult life cycle stages and connect the parasites with their intermediate hosts.
Phosphorylation of CENP-R by Aurora B regulates kinetochore–microtubule attachment for accurate chromosome segregation
Authors: Sedzro Divine Mensah , Yuan Xiao , Mullen McKay , Ejaz Umer , Yang Tongtong , Liu Xu , Song Xiaoyu , Tang Yun-Chi , Pan Weijun , Zou Peng , Gao Xinjiao , Wang Dongmei , Wang Zhikai , Dou Zhen , Liu Xing , Yao Xuebiao
Published: September 2022

Error-free mitosis depends on accurate chromosome attachment to spindle microtubules via a fine structure called the centromere that is epigenetically specified by the enrichment of CENP-A nucleosomes. Centromere maintenance during mitosis requires CENP-A-mediated deposition of constitutive centromere-associated network that establishes the inner kinetochore and connects centromeric chromatin to spindle microtubules during mitosis. Although previously proposed to be an adaptor of retinoic acid receptor, here, we show that CENP-R synergizes with CENP-OPQU to regulate kinetochore–microtubule attachment stability and ensure accurate chromosome segregation in mitosis. We found that a phospho-mimicking mutation of CENP-R weakened its localization to the kinetochore, suggesting that phosphorylation may regulate its localization. Perturbation of CENP-R phosphorylation is shown to prevent proper kinetochore–microtubule attachment at metaphase. Mechanistically, CENP-R phosphorylation disrupts its binding with CENP-U. Thus, we speculate that Aurora B-mediated CENP-R phosphorylation promotes the correction of improper kinetochore–microtubule attachment in mitosis. As CENP-R is absent from yeast, we reasoned that metazoan evolved an elaborate chromosome stability control machinery to ensure faithful chromosome segregation in mitosis.
Drugs, Drugs, Drugs: Current Treatment Paradigms in Cystic Fibrosis Airway Infections
Authors: Cogen Jonathan D , Nichols David P , Goss Christopher H , Somayaji Ranjani
Published: September 2022

Airway infections have remained a prominent feature in persons living with cystic fibrosis (CF) despite the dramatic improvements in survival in the past decades. Antimicrobials are a cornerstone of infection management for both acute and chronic maintenance indications. Historic clinical trials of antimicrobials in CF have led to the adoption of consensus guidelines for their use in clinical care. More recently, however, there are efforts to re-think the optimal use of antimicrobials for care with the advent of novel and highly effective CF transmembrane conductance regulator modulator therapies. Encouragingly, however, drug development has remained active concurrently in this space. Our review focuses on the evidence for and perspectives regarding antimicrobial use in both acute and maintenance settings in persons with CF. The therapeutic innovations in CF and how this may affect antimicrobial approaches are also discussed.
Italian Jewish Identity and Zionism: From the Emancipation to Postwar Italy (1848–1948)
Authors: Bettin Cristina
Published: September 2022

Throughout the centuries, Italian Jews have been both accepted by and outside of Italian society, and several forces and events have shaped their concept of Jewish identity and their approach toward Zionism, both of which have changed over time. Among these events, the Emancipation, the Racial Legislation Laws of 1938, and the Holocaust all played a crucial role in transforming the way Jews perceived and identified themselves with Judaism. This article aims to show the impact of these forces on Italian Jews after World War II in their perception of their own Jewish identity, as well as Italian identity and Zionism, and particularly the role played by the Jewish Palestinian soldiers in the reconstruction of the Italian Jewish communities and the rebirth of Jewish identity.