bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological carry-over effects of variable precipitation are mediated by reproductive status in a long-lived ungulate
Authors: Hediger Joseph A , Spencer Bryan D , Rice Michaela F , Hopper Miranda L , DeYoung Randy W , Ortega-Santos J Alfonso , Fulbright Timothy E , Hewitt David G , Foley Aaron M , Schofield Landon R , Campbell Tyler A , Sheriff Michael J , Cherry Michael J
Published: July 2024

In the age of global climate change, extreme climatic events are expected to increase in frequency and severity. Animals will be forced to cope with these novel stressors in their environment. Glucocorticoids (i.e. ‘stress’ hormones) facilitate an animal’s ability to cope with their environment. To date, most studies involving glucocorticoids focus on the immediate physiological effects of an environmental stressor on an individual, few studies have investigated the long-term physiological impacts of such stressors. Here, we tested the hypothesis that previous exposure to an environmental stressor will impart lasting consequences to an individual’s glucocorticoid levels. In semi-arid environments, variable rainfall drives forage availability for herbivores. Reduced seasonal precipitation can present an extreme environmental stressor potentially imparting long-term impacts on an individual’s glucocorticoid levels. We examined the effects of rainfall and environmental characteristics (i.e. soil and vegetation attributes) during fawn-rearing (i.e. summer) on subsequent glucocorticoid levels of female white-tailed deer (Odocoileus virginianus) in autumn. We captured 124 adult (≥2.5-year-old) female deer via aerial net-gunning during autumn of 2015, 2016 and 2021 across four populations spanning a gradient of environmental characteristics and rainfall in the semi-arid environment of South Texas, USA. We found for every 1 cm decrease in summer rainfall, faecal glucocorticoid levels in autumn increased 6.9%, but only in lactating females. Glucocorticoid levels in non-lactating, female deer were relatively insensitive to environmental conditions. Our study demonstrates the long-lasting effects of environmental stressors on an individual’s glucocorticoid levels. A better understanding of the long-term effects stressors impart on an individual’s glucocorticoid levels will help to evaluate the totality of the cost of a stressor to an individual’s welfare and predict the consequences of future climate scenarios.
SpadaHC: a database to improve the classification of variants in hereditary cancer genes in the Spanish population
Authors: Moreno-Cabrera José M , Feliubadaló Lidia , Pineda Marta , Prada-Dacasa Patricia , Ramos-Muntada Mireia , Del Valle Jesús , Brunet Joan , Gel Bernat , Currás-Freixes María , Calsina Bruna , Salazar-Hidalgo Milton E , Rodríguez-Balada Marta , Roig Bàrbara , Fernández-Castillejo Sara , Durán Domínguez Mercedes , Arranz Ledo Mónica , Infante Sanz Mar , Castillejo Adela , Dámaso Estela , Soto José L , de Miguel Montserrat , Hidalgo Calero Beatriz , Sánchez-Zapardiel José M , Ramon Y Cajal Teresa , Lasa Adriana , Gisbert-Beamud Alexandra , López-Novo Anael , Ruiz-Ponte Clara , Potrony Miriam , Álvarez-Mora María I , Osorio Ana , Lorda-Sánchez Isabel , Robledo Mercedes , Cascón Alberto , Ruiz Anna , Spataro Nino , Hernan Imma , Borràs Emma , Moles-Fernández Alejandro , Earl Julie , Cadiñanos Juan , Sánchez-Heras Ana B , Bigas Anna , Capellá Gabriel , Lázaro Conxi
Published: July 2024

Accurate classification of genetic variants is crucial for clinical decision-making in hereditary cancer. In Spain, genetic diagnostic laboratories have traditionally approached this task independently due to the lack of a dedicated resource. Here we present SpadaHC, a web-based database for sharing variants in hereditary cancer genes in the Spanish population. SpadaHC is implemented using a three-tier architecture consisting of a relational database, a web tool and a bioinformatics pipeline. Contributing laboratories can share variant classifications and variants from individuals in Variant Calling Format (VCF) format. The platform supports open and restricted access, flexible dataset submissions, automatic pseudo-anonymization, VCF quality control, variant normalization and liftover between genome builds. Users can flexibly explore and search data, receive automatic discrepancy notifications and access SpadaHC population frequencies based on many criteria. In February 2024, SpadaHC included 18 laboratory members, storing 1.17 million variants from 4306 patients and 16 343 laboratory classifications. In the first analysis of the shared data, we identified 84 genetic variants with clinically relevant discrepancies in their classifications and addressed them through a three-phase resolution strategy. This work highlights the importance of data sharing to promote consistency in variant classifications among laboratories, so patients and family members can benefit from more accurate clinical management.

Database URL: https://spadahc.ciberisciii.es/
Socioeconomic status and cardiovascular mortality in over 170 000 cancer survivors
Authors: Jung Mi-Hyang , Choi Yun-Seok , Yi Sang-Wook , An Sang Joon , Yi Jee-Jeon , Ihm Sang-Hyun , Lee So-Young , Youn Jong-Chan , Chung Woo-Baek , Jung Hae Ok , Youn Ho-Joong
Published: July 2024

Aims

Cardiovascular health is acknowledged as a crucial concern among cancer survivors. Socioeconomic status (SES) is an essential but often neglected risk factor for cardiovascular disease (CVD). We conducted this study to identify the relationship between SES and CVD mortality in cancer survivors.

Methods and results

Using the National Health Insurance Service-National Health Examinee database, we identified cancer survivors diagnosed and surviving beyond 5 years post-diagnosis. SES was assessed based on insurance premiums and classified into five groups. The primary outcome was overall CVD mortality. This study analysed 170 555 individuals (mean age 60.7 ± 11.9 years, 57.8% female). A gradual increase in risk was observed across SES groups: adjusted hazard ratios (95% confidence intervals) for overall CVD mortality were 1.15 (1.04–1.26), 1.28 (1.15–1.44), 1.31 (1.18–1.46), and 2.13 (1.30–3.49) for the second, third, and fourth quartile, and medical aid group (the lowest SES group) compared to the highest SES group, respectively (P for trend < 0.001). The lowest SES group with hypertension exhibited a 3.4-fold higher risk of CVD mortality compared to the highest SES group without hypertension. Interaction analyses revealed that low SES synergistically interacts with hypertension, heightening the risk of CVD mortality (synergy index 1.62).

Conclusion

This study demonstrates a significant correlation between low SES and increased CVD mortality among cancer survivors. Particularly, the lowest SES group, when combined with hypertension, significantly escalates CVD mortality. Our findings underscore the critical importance of recognizing SES as a significant risk factor for CVD mortality in this population of cancer survivors.

Lay Summary

Our population-based cohort study, involving over 170 000 cancer survivors, demonstrates a significant association between socioeconomic status (SES) and cardiovascular disease (CVD) mortality.
The pectus care guidelines: best practice consensus guidelines from the joint specialist societies SCTS/MF/CWIG/BOA/BAPS for the treatment of patients with pectus abnormalities
Authors: Dunning Joel , Burdett Clare , Child Anne , Davies Carl , Eastwood Deborah , Goodacre Tim , Haecker Frank-Martin , Kendall Simon , Kolvekar Shyam , MacMahon Lisa , Marven Sean , Murray Sarah , Naidu Babu , Pandya Bejal , Redmond Karen , Coonar Aman
Published: July 2024

EXECUTIVE SUMMARY

Pectus defects are a group of congenital conditions found in approximately 1 in 250 people, where the sternum is depressed back towards the spine (excavatum), protrudes forwards (carinatum) or more rarely is a mixture of both (arcuatum or mixed defects). For the majority of patients, it is well tolerated, but some patients are affected psychologically, physiologically or both.

The deformity becomes apparent at a young age due to the growth of the ribs and the cartilage that links them to the sternum. The majority of defects are mild and are well tolerated, i.e. they do not affect activity and do not cause psychological harm. However, some young people develop lower self-esteem and depression, causing them to withdraw from activities (such as swimming, dancing) and from interactions that might ‘expose’ them (such as sleepovers, dating, going to the beach and wearing fashionable clothes). This psychological harm occurs at a crucial time during their physical and social development. A small number of patients have more extreme depression of their sternum that impedes their physiological reserve, which can occur when engaging in strenuous exercise (such as running) but can also limit moderate activity such as walking and climbing stairs. The effects can be so extreme that symptoms occur at rest or cause life-threatening compression of the major blood vessels and organs. The group of patients with physiological impairment usually also suffer from low self-esteem and depression.

This paper summarizes the current evidence for the different treatment strategies for this condition, including supportive care, psychological support and non-surgical techniques including bracing and vacuum bell therapy. We also consider surgical techniques including the Ravitch procedure, the Nuss procedure (minimally invasive repair of pectus excavatum), pectus implants and other rare procedures such as Pectus Up.

For the majority of patients, supportive care is sufficient, but for a minority, a combination of the other techniques may be considered.

This paper also outlines best practice guidance for the delivery of such therapies, including standardized assessment, consent to treatment, audit, quality assurance and long-term support.

All the interventions have risks and benefits that the patient, parents and clinicians need to carefully consider and discuss when deciding on the most appropriate course. We hope this evidence review of ‘Best Practice for Pectus’ will make a significant contribution to those considerations and help all involved, from patients to national policy makers, to deliver the best possible care.
A Learners’ Dictionary Versus ChatGPT in Receptive and Productive Lexical Tasks
Authors: Ptasznik Bartosz , Wolfer Sascha , Lew Robert
Published: July 2024

This study assesses the effectiveness of ChatGPT versus the Longman Dictionary of Contemporary English (LDOCE) in supporting English language learners in lexically challenging receptive and productive lexical tasks. With a sample of 223 university students at B2 to C1 proficiency levels, this research investigates whether a leading AI-driven chatbot or a high-quality learners’ dictionary better assists learners in accurately understanding and producing English. The results reveal ChatGPT’s superior performance in both task types. Efficiency, in terms of consultation speed, also favoured ChatGPT, though only in the production task. This study advocates for an integrated approach that leverages both AI, with its interactive and immediate feedback, and more traditional lexicographic tools that may foster learner autonomy and linguistic proficiency.
Perceptions and experiences of community pharmacists with off-label prescribing in the pediatric population
Authors: Noga Fabiola , Hoti Ela , Ibrahimi Eliana , Toma Diana , Malaj Ledjan
Published: July 2024

Objectives

This study aimed to investigate and provide insight into the prevalence and patterns of off-label drug use in the pediatric population from the perspective of community pharmacists, addressing the existing data gap in a developing setting.

Methods

A questionnaire-based cross-sectional study was conducted on Albanian community pharmacists in June 2021. The online administered survey explored the participants’ demographic details, perceptions, and experiences with off-label prescriptions in pediatric patients. The statistical analysis conducted on the survey data comprised the construction of frequency tables and the application of the chi-square test for independence.

Key findings

Three hundred and thirty-six community pharmacists nationwide completed the survey, out of which 186 (55.3%) were practiced in Tirana, the capital of Albania. Over 80% of surveyed pharmacists (n = 275) had encountered off-label drug prescriptions in pediatric patients, yet only 40% of participants reported dispensing medicines for off-label use. Community pharmacists reported that general pediatricians tended to prescribe off-label medications more frequently than pediatric subspecialists or general practitioners. It was found that off-label prescriptions were more frequently observed among children aged between 2 and 11 years. Antibiotics were the most reported medicines for off-label use in this study mentioned in almost all off-label categories.

Conclusions

Prescribing medicines for unapproved uses for the treatment of pediatric patients is present in community settings in Albania. This indicates the need for further data collection and analysis to understand off-label practices in our country’s pediatric population comprehensively.
A Conjugate System for Twisted Araki–Woods von Neumann Algebras of Finite Dimensional Spaces
Authors: Yang Zhiyuan
Published: July 2024

We compute the conjugate system of twisted Araki–Woods von Neumann algebras $ \mathcal{L}_{T}(H) $ introduced in [ 7] for a compatible braided crossing symmetric twist $T$ on a finite dimensional Hilbert space $ {{\mathcal{H}}} $ with norm $ \|T\| <1$. This implies that those algebras have finite non-microstates free Fisher information and therefore are always factors of type $\text{III}_{\lambda }$ ($0<\lambda \leq 1$) or $ \text{II}_{1} $. Moreover, using the (nontracial) free monotone transport [ 19], we show that $ \mathcal{L}_{T}(H) $ is isomorphic to the free Araki–Woods algebra $ \mathcal{L}_{0}(H) $ when $ \|T\|=q $ is small enough.
Damage constitutive model of rock and application based on strength theory
Authors: Feng Tianxin , Yu Xinglan , Cheng Guoqiang
Published: July 2024

Extending the one-dimensional damage constitutive model of rock materials to 3 dimensions using classical methods fails to capture the significant differences in tensile, compressive, and shear strengths exhibited by the rock materials. Consequently, it is necessary to revise the existing damage constitutive model to describe the damage evolution law and constitutive relationship of rock materials more accurately and provide a theoretical basis for the safety and stability analysis of underground engineering more scientifically, thus ensuring the sustainable development of underground engineering. By introducing the Weibull distribution function and building upon strength theory, a correction function was established. This correction function adjusted the equivalent strain, enabling the development of a 3-dimensional damage constitutive model that accounted for the varying tensile, compressive, and shear strengths of rock materials. The impact of various parameters on the model's fitting effectiveness was evaluated, and a comparative analysis was conducted against pertinent experimental results. Using the theory of neutral axis deviation, the relationship between bending moment and damage variables in a purely bending rock beam was derived. The study revealed that all parameters of the damage constitutive model could be derived from the uniaxial stress-strain curve, and its theoretical findings exhibited strong agreement with experimental results obtained from rock and rock-like materials under uniaxial tension, compression and triaxial compression. Based on the examined cases, it was concluded that, when considering both tensile and compressive damage, the ultimate bending moment of a rock beam was approximately one-third of its elastic limit bending moment in an undamaged state. The results have verified the feasibility of the damage constitutive model.
Interactive effects of soils, local environmental conditions and herbivores on secondary chemicals in tallow tree
Authors: Xiao Li , Huang Wei , Carrillo Juli , Ding Jianqing , Siemann Evan
Published: July 2024

Plants produce secondary chemicals that may vary along with latitude due to changing abiotic and biotic stress gradients and local environmental conditions. Teasing apart the individual and combined effects of these different abiotic, such as soil nutrients, and biotic factors, such as soil biota and herbivores, on secondary chemicals is critical for understanding plant responses to changing environments. We conducted an experiment at different latitudes in China, using tallow tree (Triadica sebifera) seedlings sourced from a population at 31° N. These seedlings were cultivated in gardens located at low, middle and high latitudes, with either local soil or soil from the original seed collection site (origin soil). The seedlings were exposed to natural levels of aboveground herbivores or had them excluded. Plant secondary chemicals (both foliar and root), aboveground herbivores and soil characteristics were measured. Results showed that most leaf and root secondary metabolites depended on the interaction of the experimental site and soil type. Leaf and root phenolic and tannin concentrations were higher at the middle latitude site, especially in the origin soil. Root and foliar flavonoid concentrations increased when aboveground herbivores were excluded. Microbial communities depended strongly on soil treatment. The different responses of tannins versus flavonoids suggest that these two chemical classes differ in their responses to the varying abiotic and biotic factors in these sites along latitudes. Taken together, our results emphasize the importance of considering the interactive effects of local environmental conditions, soil properties and herbivory in regulating plant chemical defenses.
Surrogates’, intended parents’, and professionals’ perspectives on ways to improve access to surrogacy in Australia
Authors: Kneebone Ezra , Hammarberg Karin , Beilby Kiri
Published: July 2024

While altruistic surrogacy arrangements are permitted in Australia, commercial ones are not. Regardless of this, most intended parents undertake commercial arrangements by bypassing domestic laws and engaging with foreign surrogates. Considering the welfare risks and ethical concerns associated with international surrogacy, developing a more accessible model of surrogacy in Australia has been proposed as a harm minimization approach. This study aims to describe how Australians who have navigated or facilitated surrogacy believe access to arrangements could be improved. Australian surrogates, intended parents, parents through surrogacy, and surrogacy professionals were interviewed, and interview transcripts were analysed thematically. The themes identified were ‘improve public awareness’, ‘develop policies to guide healthcare practitioners’, ‘establish agencies’, and ‘reform the law’. ‘Reform the law’ had four sub-themes: ‘harmonise laws across the states and territories’; ‘grant intended parents legal parenthood at birth’; ‘legalise commercial surrogacy and gamete donation’; and ‘fair surrogate compensation’. Findings indicate that improving access to surrogacy in Australia will require an overhaul of the legislative environment relating to surrogacy and gamete donation, policies to guide healthcare practitioners, and public awareness campaigns.
Integration of chromosome locations and functional aspects of enhancers and topologically associating domains in knowledge graphs enables versatile queries about gene regulation
Authors: Mulero-Hernández Juan , Mironov Vladimir , Miñarro-Giménez José Antonio , Kuiper Martin , Fernández-Breis Jesualdo Tomás
Published: July 2024

Knowledge about transcription factor binding and regulation, target genes, cis-regulatory modules and topologically associating domains is not only defined by functional associations like biological processes or diseases but also has a determinative genome location aspect. Here, we exploit these location and functional aspects together to develop new strategies to enable advanced data querying. Many databases have been developed to provide information about enhancers, but a schema that allows the standardized representation of data, securing interoperability between resources, has been lacking. In this work, we use knowledge graphs for the standardized representation of enhancers and topologically associating domains, together with data about their target genes, transcription factors, location on the human genome, and functional data about diseases and gene ontology annotations. We used this schema to integrate twenty-five enhancer datasets and two domain datasets, creating the most powerful integrative resource in this field to date. The knowledge graphs have been implemented using the Resource Description Framework and integrated within the open-access BioGateway knowledge network, generating a resource that contains an interoperable set of knowledge graphs (enhancers, TADs, genes, proteins, diseases, GO terms, and interactions between domains). We show how advanced queries, which combine functional and location restrictions, can be used to develop new hypotheses about functional aspects of gene expression regulation.
Asymmetric bulges within hairpin RNA transgenes influence small RNA size, secondary siRNA production and viral defence
Authors: Zhang Daai , Jue Dengwei , Smith Neil , Zhong Chengcheng , Finnegan E Jean , de Feyter Robert , Wang Ming-Bo , Greaves Ian
Published: July 2024

Small RNAs (sRNAs) are essential for normal plant development and range in size classes of 21–24 nucleotides. The 22nt small interfering RNAs (siRNAs) and miRNAs are processed by Dicer-like 2 (DCL2) and DCL1 respectively and can initiate secondary siRNA production from the target transcript. 22nt siRNAs are under-represented due to competition between DCL2 and DCL4, while only a small number of 22nt miRNAs exist. Here we produce abundant 22nt siRNAs and other siRNA size classes using long hairpin RNA (hpRNA) transgenes. By introducing asymmetric bulges into the antisense strand of hpRNA, we shifted the dominant siRNA size class from 21nt of the traditional hpRNA to 22, 23 and 24nt of the asymmetric hpRNAs. The asymmetric hpRNAs effectively silenced a β-glucuronidase (GUS) reporter transgene and the endogenous ethylene insensitive-2 (EIN2) and chalcone synthase (CHS) genes. Furthermore, plants containing the asymmetric hpRNA transgenes showed increased amounts of 21nt siRNAs downstream of the hpRNA target site compared to plants with the traditional hpRNA transgenes. This indicates that these asymmetric hpRNAs are more effective at inducing secondary siRNA production to amplify silencing signals. The 22nt asymmetric hpRNA constructs enhanced virus resistance in plants compared to the traditional hpRNA constructs.
The TOPOVIBL meiotic DSB formation protein: new insights from its biochemical and structural characterization
Authors: Diagouraga Boubou , Tambones Izabella , Carivenc Coralie , Bechara Chérine , Nadal Marc , de Massy Bernard , le Maire Albane , Robert Thomas
Published: July 2024

The TOPOVIL complex catalyzes the formation of DNA double strand breaks (DSB) that initiate meiotic homologous recombination, an essential step for chromosome segregation and genetic diversity during gamete production. TOPOVIL is composed of two subunits (SPO11 and TOPOVIBL) and is evolutionarily related to the archaeal TopoVI topoisomerase complex. SPO11 is the TopoVIA subunit orthologue and carries the DSB formation catalytic activity. TOPOVIBL shares homology with the TopoVIB ATPase subunit. TOPOVIBL is essential for meiotic DSB formation, but its molecular function remains elusive, partly due to the lack of biochemical studies. Here, we purified TOPOVIBLΔC25 and characterized its structure and mode of action in vitro. Our structural analysis revealed that TOPOVIBLΔC25 adopts a dynamic conformation in solution and our biochemical study showed that the protein remains monomeric upon incubation with ATP, which correlates with the absence of ATP binding. Moreover, TOPOVIBLΔC25 interacted with DNA, with a preference for some geometries, suggesting that TOPOVIBL senses specific DNA architectures. Altogether, our study identified specific TOPOVIBL features that might help to explain how TOPOVIL function evolved toward a DSB formation activity in meiosis.
O-105 HOW HEALTHY IS YOUR WORKPLACE? OCCUPATIONAL HEALTH PROGRAMS IN GERMAN COMPANIES – CREATION AND VALIDATION OF EFFECTIVE MEASURES*
Authors: Afrahi Jasmin
Published: July 2024

Introduction

Companies are struggling with the costs of absenteeism due to their employees’ physical and increasing psychological illnesses. At the same time, employers should recognize the value of healthy employees in terms of greater productivity and the development of positive organizational attitudes. Many organizations have implemented workplace health promotion (WHP) programs; however, we still have limited knowledge about the effectiveness of various measures. The present study examines 18 WHP activities and their effect on employees’ perceived health support and actual absence rates.

Methods

I organized 112 German companies into four groups based on their subjective (employee perception of health promotion) and objective (absence rate) performance. Applying multinomial regression analysis, I assessed a company’s likelihood of falling into one of the four clusters if a specific measure is not implemented in it.

Results

Five measures were identified that significantly differ between company clusters: healthy food offerings, sports offerings, having fitness rooms, systematically evaluating WHP programs, and smoking cessation courses.

Discussion

Sports courses and fitness rooms not only give employees the chance to improve their physical and mental health but also fulfill social needs by enabling contact with other colleagues. Companies should inform their employees about health topics and make them aware of their own health behavior. Moreover, health managers should carefully implement interventions and follow strategies not only to ensure high participation rates but also to evaluate the interventions systematically.

Conclusion

Investing in occupational health management can be a strategic asset for organizations. It shows that employers can enhance employee well-being by using simple WHP activities. *The full article will be published in the International Journal of Workplace Health Management, DOI 10.1108/IJWHM-08-2023-0118.
P-516 WORKING IN THE TIME OF COVID-19: HOW COVID-19 PUBLIC HEALTH POLICIES AFFECT THE EXPERIENCE OF BULLYING AND HARASSMENT AMONG RESTAURANT WORKERS
Authors: McLeod Christopher , Deering Kathleen , Aguiar Luis , Skourtes Stephanie , Frank Billie
Published: July 2024

Introduction

This study explored how COVID-19 public health policies affected experiences of bullying and harassment among workers in the restaurant industry and the impact of these policies on the health and safety of workers.

Methods

Qualitative interviews were conducted with 47 restaurant workers in the Canadian province of British Columbia. Participants worked in various roles at any kind of restaurant during the first two years of the COVID-19 pandemic. Ethics approval was obtained from the UBC Research Ethics Board. Inductive coding was applied towards the development of themes.

Results

COVID-19 public health restrictions in restaurants contributed to bullying and harassment of workers. A lack of managerial support and implementation guidelines from public health officials led to workers having to enforce restrictions on their own, which resulted in workers routinely experiencing verbal violence and harassment by customers. Workers described unsafe work conditions that put them at risk for contracting COVID-19 as well for bullying and harassment from management, which was exacerbated for women, gender-diverse, and racialized workers. In workplaces with a supportive organizational culture, workers reported feeling safer and buffered from incidents of bullying and harassment from customers.“

Discussion

The COVID-19 pandemic exacerbated existing structural dynamics in the restaurant industry that enabled bullying and harassment of workers, including the hierarchical dynamic of restaurant work as well as discrimination in the industry.

Conclusion

While supportive workplace policies and practices mitigated some of the bullying and harassment experienced by restaurant workers working during the COVID-19 pandemic, broader equity-focused organizational and structural change is needed to protect workers.
Perspectives on U.S. University research reactor policy
Authors: Nienow Sara , Walsh Amanda C , Merker Jonathan
Published: July 2024

Widely promoted by the Atomic Energy Commission in the 1950s and 1960s, university research reactors allowed faculty to experiment with neutron scattering, advancing our understanding of organic and inorganic materials. These advances led to innovations in commercial products, including automobiles, computers, medicine, and batteries. However, since the 1980s, more than half of all the university research reactors have been decommissioned and remaining reactors are ill-suited for modern needs. RTI International assembled a team of economists, neutron scientists, and policy analysts to examine the history of university research reactor policy in the USA, assess barriers to greater usage, and consider how US policy differs from those in other countries. We present three policy options to enhance the role of university research reactors in federal research and the national science infrastructure landscape.
Sustainable application of biocides to promote hygiene and minimize antimicrobial resistance
Authors: Willmott Thomas , Jadaan Layali , Humphreys Gavin J , Lu Jian R , McBain Andrew J , Chapman John
Published: July 2024

Biocidal (microbicidal) products play a critical role in controlling microorganisms in healthcare, industrial, community, and home environments. There is, however, concern that their use and misuse might contribute to the evolution of antimicrobial resistance (AMR). When evaluating the risk associated with biocides, it is important to adopt an objective approach towards the evidence regarding both the benefits of their appropriate deployment as well as potential contribution to AMR. Biocide use should be restricted to applications where there are tangible benefits but also not unnecessarily restricted where genuine benefits can be demonstrated. From the perspective of sustainability, such benefits include the control and prevention of infections in clinical settings with associated reductions in antibiotic use, preservation of a range of products and materials, substantial reduction in infection risk for consumers, hygiene in the community (e.g. in public swimming baths), and microbial control in many facets of industry. Here, we will provide a critical assessment of the contribution of biocides to sustainability based on a critical evaluation of the literature, followed by offering our views on the future management of biocide use across the globe.
Dynamic changes of gut microbiota in mouse models of metabolic dysfunction‐associated steatohepatitis and its transition to hepatocellular carcinoma
Authors: Wang Yu‐Li , Liu Chang , Yang Yong‐Yu , Zhang Li , Guo Xiao , Niu Chen , Zhang Ning‐Ping , Ding Jia , Wu Jian
Published: July 2024

Dysbiosis of gut microbiota may account for pathobiology in simple fatty liver (SFL), metabolic dysfunction‐associated steatohepatitis (MASH), fibrotic progression, and transformation to MASH‐associated hepatocellular carcinoma (MASH‐HCC). The aim of the present study is to investigate gut dysbiosis in this progression. Fecal microbial rRNA‐16S sequencing, absolute quantification, histopathologic, and biochemical tests were performed in mice fed high fat/calorie diet plus high fructose and glucose in drinking water (HFCD‐HF/G) or control diet (CD) for 2, 16 weeks, or 14 months. Histopathologic examination verified an early stage of SFL, MASH, fibrotic, or MASH‐HCC progression with disturbance of lipid metabolism, liver injury, and impaired gut mucosal barrier as indicated by loss of occludin in ileum mucosa. Gut dysbiosis occurred as early as 2 weeks with reduced α diversity, expansion of Kineothrix, Lactococcus, Akkermansia; and shrinkage in Bifidobacterium, Lactobacillus, etc., at a genus level. Dysbiosis was found as early as MAHS initiation, and was much more profound through the MASH‐fibrotic and oncogenic progression. Moreover, the expansion of specific species, such as Lactobacillus johnsonii and Kineothrix alysoides, was confirmed by an optimized method for absolute quantification. Dynamic alterations of gut microbiota were characterized in three stages of early SFL, MASH, and its HCC transformation. The findings suggest that the extent of dysbiosis was accompanied with MASH progression and its transformation to HCC, and the shrinking or emerging of specific microbial species may account at least in part for pathologic, metabolic, and immunologic alterations in fibrogenic progression and malignant transition in the liver.
Toward Reliable Symptom Coding in Electronic Health Records for Symptom Assessment and Research
Authors: Cao Tru , Brady Veronica , Whisenant Meagan , Wang Xueying , Gu Yuxuan , Wu Hulin
Published: July 2024

To date, symptom documentation has mostly relied on clinical notes in electronic health records or patient-reported outcomes using disease-specific symptom inventories. To provide a common and precise language for symptom recording, assessment, and research, a comprehensive list of symptom codes is needed. The International Classification of Diseases, Ninth Revision or its clinical modification (International Classification of Diseases, Ninth Revision, Clinical Modification) has a range of codes designated for symptoms, but it does not contain codes for all possible symptoms, and not all codes in that range are symptom related. This study aimed to identify and categorize the first list of International Classification of Diseases, Ninth Revision, Clinical Modification symptom codes for a general population and demonstrate their use to characterize symptoms of patients with type 2 diabetes mellitus in the Cerner database. A list of potential symptom codes was automatically extracted from the Unified Medical Language System Metathesaurus. Two clinical experts in symptom science and diabetes manually reviewed this list to identify and categorize codes as symptoms. A total of 1888 International Classification of Diseases, Ninth Revision, Clinical Modification symptom codes were identified and categorized into 65 categories. The symptom characterization using the newly obtained symptom codes and categories was found to be more reasonable than that using the previous symptom codes and categories on the same Cerner diabetes cohort.
Overcoming Data Gaps in Life Course Epidemiology by Matching Across Cohorts
Authors: Kezios Katrina L. , Zimmerman Scott C. , Buto Peter T. , Rudolph Kara E. , Calonico Sebastian , Zeki Al Hazzouri Adina , Glymour M. Maria
Published: July 2024

Life course epidemiology is hampered by the absence of large studies with exposures and outcomes measured at different life stages in the same individuals. We describe when the effect of an exposure (A) on an outcome (Y) in a target population is identifiable in a combined (“synthetic”) cohort created by pooling an early-life cohort including measures of A with a late-life cohort including measures of Y. We enumerate causal assumptions needed for unbiased effect estimation in the synthetic cohort and illustrate by simulating target populations under four causal models. From each target population, we randomly sampled early- and late-life cohorts and created a synthetic cohort by matching individuals from the two cohorts based on mediators and confounders. We estimated the effect of A on Y in the synthetic cohort, varying matching variables, the match ratio, and the strength of association between matching variables and A. Finally, we compared bias in the synthetic cohort estimates when matching variables did not d-separate A and Y to the bias expected in the original cohort. When the set of matching variables includes all variables d-connecting exposure and outcome (i.e., variables blocking all backdoor and front-door pathways), the synthetic cohort yields unbiased effect estimates. Even when matching variables did not fully account for confounders, the synthetic cohort estimate was sometimes less biased than comparable estimates in the original cohort. Methods based on merging cohorts may hasten the evaluation of early- and mid-life determinants of late-life health but rely on available measures of both confounders and mediators.
Association Among Vitamin D Supplementation, Serum 25(OH)D Concentrations, and Mortality Risk: A Prospective Cohort Study Using NHANES 2007–2018 Data
Authors: Liu Hong , Bai Yu
Published: July 2024

Background:

To determine the associations among self-reported vitamin D (VD) supplementation, measured serum 25-hydroxyvitamin D (25[OH]D) concentrations, and all-cause and cause-specific mortality risks.

Methods:

Self-reported VD supplementation, serum 25(OH)D concentration, and all-cause and cause-specific mortality data from the National Health and Nutrition Examination Survey 2007–2018 were examined for 10,793 adults ≥20 years from the United States. VD dosage was categorized as <800 or ≥800 IU/d. The mortality status and causes of mortality up to 2019 were determined using the National Death Index. The relationships among VD, 25(OH)D levels, and mortality were analyzed using Cox regression before and after propensity score matching (PSM).

Results:

Over a median of 6.6 years, 915 deaths were recorded, 230 because of cardiovascular disease (CVD), 240 because of cancer, and 445 because of other specific causes. Mortality risk did not differ between VD <800 IU/d and ≥800 IU/d before or after PSM. However, serum 25(OH)D concentrations were statistically different before and after PSM. The upper 2 quartiles of 25(OH)D levels were associated with lower all-cause mortality, and the fourth quartile was associated with reduced other-specific mortality before and after PSM. No correlation was found between the 25(OH)D concentration and CVD- or cancer-specific mortality after PSM. The inverse 25(OH)D–mortality relationship was consistent across subgroups.

Conclusions:

Based on this large cohort study, higher 25(OH)D levels are robustly associated with reduced all-cause and other specific mortality but not CVD- or cancer-specific mortality. These findings support the benefits of maintaining adequate VD status for longevity. Further research is required to elucidate these mechanisms and define the optimal VD concentration to reduce mortality. These results underscore the importance of public health strategies for preventing VD deficiency.
Using Microeconomic Spending Traits to Inform Trends in Utilization of Cosmetic Procedures by Race and Ethnicity
Authors: Rhee Ben S. , Pham John , Tanzer Joshua R. , Charvis Jodi S. , Roussel Lauren O.
Published: July 2024

Background:

Cosmetic plastic surgery in the United States is underutilized by African American and Hispanic populations compared with their White and Asian counterparts. This study evaluated whether microeconomic spending traits as a representation of financial stability can inform trends in cosmetic procedure volumes by racial group.

Methods:

Annual volumes for the top five cosmetic surgical and cosmetic minimally invasive procedures by racial/ethnic group from 2012 to 2020 were collected from the American Society of Plastic Surgeons’ annual reports. Factor analysis was used to calculate inflexible and flexible consumer spending by racial/ethnic groupings from the US Bureau of Labor Statistics’ consumer expenditure data. All four factors were calculated across US Bureau of Labor Statistics–defined racial/ethnic groupings and standardized so they could be interpreted relative to each other.

Results:

Compared with the other groupings, the White/Asian/other grouping spent significantly more on average for inflexible consumer spending (P = 0.0097), flexible consumer spending (P < 0.0001), cosmetic surgical procedures (P < 0.0001), and cosmetic minimally invasive procedures (P = 0.0006). In contrast, African American people spent significantly less on average for all four factors (all P < 0.01). For Hispanic people, values were significantly less on average for flexible consumer spending (P = 0.0023), cosmetic surgical procedures (P < 0.0001), and cosmetic minimally invasive procedures (P = 0.0002).

Conclusions:

This study demonstrates that inflexible and flexible consumer spending follow trends in utilization of cosmetic surgical and minimally invasive procedures by racial/ethnic groups. These microeconomic spending inequities may help further contextualize the racial/ethnic variation in access to cosmetic surgery.
COVID-19 in Pregnancy: An Update for Clinicians
Authors: Packer Claire H. , Prabhu Malavika
Published: July 2024

In this review, we will discuss the risks of COVID-19 on maternal, obstetric, and neonatal outcomes. We will also review the safety of COVID-19 vaccination in pregnancy, as well as review the management of COVID-19 in pregnancy.
Whole-exome sequencing reveals novel cancer genes and actionable targets in biliary tract cancers in primary sclerosing cholangitis
Authors: Grimsrud Marit M. , Forster Michael , Goeppert Benjamin , Hemmrich-Stanisak Georg , Sax Irmi , Grzyb Krzysztof , Braadland Peder R. , Charbel Alphonse , Metzger Carmen , Albrecht Thomas , Steiert Tim Alexander , Schlesner Matthias , Manns Michael P. , Vogel Arndt , Yaqub Sheraz , Karlsen Tom H. , Schirmacher Peter , Boberg Kirsten M. , Franke Andre , Roessler Stephanie , Folseraas Trine
Published: July 2024

Background:

People with primary sclerosing cholangitis (PSC) have a 20% lifetime risk of biliary tract cancer (BTC). Using whole-exome sequencing, we characterized genomic alterations in tissue samples from BTC with underlying PSC.

Methods:

We extracted DNA from formalin-fixed, paraffin-embedded tumor and paired nontumor tissue from 52 resection or biopsy specimens from patients with PSC and BTC and performed whole-exome sequencing. Following copy number analysis, variant calling, and filtering, putative PSC-BTC-associated genes were assessed by pathway analyses and annotated to targeted cancer therapies.

Results:

We identified 53 candidate cancer genes with a total of 123 nonsynonymous alterations passing filtering thresholds in 2 or more samples. Of the identified genes, 19% had not previously been implicated in BTC, including CNGA3, KRT28, and EFCAB5. Another subset comprised genes previously implicated in hepato-pancreato-biliary cancer, such as ARID2, ELF3, and PTPRD. Finally, we identified a subset of genes implicated in a wide range of cancers such as the tumor suppressor genes TP53, CDKN2A, SMAD4, and RNF43 and the oncogenes KRAS, ERBB2, and BRAF. Focal copy number variations were found in 51.9% of the samples. Alterations in potential actionable genes, including ERBB2, MDM2, and FGFR3 were identified and alterations in the RTK/RAS (p = 0.036), TP53 (p = 0.04), and PI3K (p = 0.043) pathways were significantly associated with reduced overall survival.

Conclusions:

In this exome-wide characterization of PSC-associated BTC, we delineated both PSC-specific and universal cancer genes. Our findings provide opportunities for a better understanding of the development of BTC in PSC and could be used as a platform to develop personalized treatment approaches.
A novel case of endophthalmitis secondary to Paenibacillus yonginensis after intravitreal injection of aflibercept
Authors: Ramirez Jose A. , Khurana Rahul N. , Wang Jay C.
Published: July 2024

Purpose:

To report a case of endophthalmitis after intravitreal injection due to Paenibacillus yonginensis.

Methods:

This is a retrospective case report.

Results:

An 87-year-old man with longstanding neovascular age-related macular degeneration (AMD) in his left eye presented with pain and loss of vision three days after intravitreal injection of aflibercept. Examination revealed a hypopyon and vitreous opacities. A diagnostic anterior chamber paracentesis and intravitreal injections of vancomycin and ceftazidime were performed. One month later, vitrectomy was performed for non-clearing vitreous opacities with a good final visual outcome. The causative bacterium, Paenibacillus yonginensis, was identified with polymerase chain reaction (PCR) sequencing from the aqueous specimen.

Conclusion:

We encountered a rare presentation of endophthalmitis caused by Paenibacillus yonginensis. Paenibacillus species have been implicated in human infection in recent years. DNA sequencing can allow for the identification of uncommon bacteria.
Hydroxyproline Concentration and Associated Factors of Preserved Small Incision Lenticule Extraction–Derived Corneal Stromal Lenticules
Authors: Han Xiaosong , Li Meiyan , Zhao Jing , Sun Bingqing , Zhang Xiaoyu , Xu Haipeng , Zhou Xingtao
Published: July 2024

Purpose:

To evaluate changes of hydroxyproline concentration and its influencing factors of small incision lenticule extraction (SMILE)-derived corneal stromal lenticules with different preservation methods.

Methods:

A total of 390 corneal stromal lenticules of 195 patients were derived from SMILE surgeries. Thirty of the lenticules were classified as the fresh (control) group, and the rest were randomly and evenly divided and stored in anhydrous glycerol, silicone oil, Optisol, and cryopreservation for 1 day, 1 week, or 1 month. A hydroxyproline assay kit (ab222941, Abcam) was used to measure the hydroxyproline concentration in each preservation method. Concentrations of MMP-2, TIMP-2, TNFα, TGFβ2, and reactive oxygen species were also evaluated.

Results:

In the anhydrous glycerol group, the concentration of hydroxyproline decreased within 1 week (fresh: 1 dΔ = 0.229, P < 0.001*; 1 d − 1 wΔ = 0.055, P < 0.001*) while that in the silicone oil group remained stable in 1 week (1 d − 1 wΔ = −0.005, P = 0.929) and decreased significantly in 1 m (1 m − 1 wΔ = −0.041, P = 0.003*). The sequence of hydroxyproline concentration in the Optisol group was 1 m > 1 day > 1 week. Hydroxyproline concentration in the cryopreservation group decreased within 1 m. Hydroxyproline concentration was highest in the Optisol group and lowest in the anhydrous glycerol group under the same preservation time. Hydroxyproline concentration was negatively correlated with MMP-2 (r = −0.16, P = 0.421) and TIMP-2 (r = −0.56, P = 0.002*) while MMP-2 and TNFα (r = 0.17, P = 0.242), TIMP-2 and TGFβ2 (r = 0.21, P = 0.207), and TNFα and reactive oxygen species (r = 0.52, P = 0.007*) were positively correlated.

Conclusions:

More collagen was retained in SMILE lenticules preserved in Optisol under the same preservation time. The mechanism of the changes of collagen in preserved SMILE-derived lenticules and oxidative stress requires additional investigation.