bluuebunny/crossref_metadata_2025 huggingface dataset:
How to do (or not to do)… health resource allocations using constrained mathematical optimization
Authors: Stuart Robyn M , Fraser-Hurt Nicole , Shubber Zara , Vu Lung , Cheik Nejma , Kerr Cliff C , Wilson David P
Published: November 2022

Despite the push towards evidence-based health policy, decisions about how to allocate health resources are all too often made on the basis of political forces or a continuation of the status quo. This results in wastage in health systems and loss of potential population health. However, if health systems are to serve people best, then they must operate efficiently and equitably, and appropriate valuation methods are needed to determine how to do this. With the advances in computing power over the past few decades, advanced mathematical optimization algorithms can now be run on personal computers and can be used to provide comprehensive, evidence-based recommendations for policymakers on how to prioritize health spending considering policy objectives, interactions of interventions, real-world system constraints and budget envelopes. Such methods provide an invaluable complement to traditional or extended cost-effectiveness analyses or league tables. In this paper, we describe how such methods work, how policymakers and programme managers can access them and implement their recommendations and how they have changed health spending in the world to date.
Exploring how social inequalities in health have influenced the design of Mali’s SARS-CoV-2 testing policy: a qualitative study
Authors: Boivin Pauline , Gautier Lara , Coulibaly Abdourahmane , Zinszer Kate , Ridde Valéry
Published: November 2022

In the fight against infectious diseases, social inequalities in health (SIH) are generally forgotten. Mali, already weakened by security and political unrest, has not been spared by the COVID-19 pandemic. Although the country was unprepared, the authorities were quick to implement public health measures, including a SARS-CoV-2 testing programme. This study aimed to understand if and how social inequalities in health were addressed in the design and planning for the national COVID-19 testing policy in Mali. A qualitative survey was conducted between March and April 2021 in Bamako, the capital of Mali. A total of 26 interviews were conducted with key government actors and national and international partners. A document review of national reports and policy documents complemented this data collection. The results demonstrated that the concept of SIH was unclear to the participants and was not a priority. The authorities focused on a symptom-based testing strategy that was publicly available. Participants also mentioned some efforts to reduce inequalities across geographical territories. The reflection and consideration of SIH within COVID-19 interventions was difficult given the governance approach to response efforts. The urgency of the situation, the perceptions of COVID-19 and the country’s pre-existing fragility were factors limiting this reflection. Over time, little action has been taken to adapt to the specific needs of certain groups in the Malian population. This study (re)highlights the need to consider SIH in the planning stages of a public health intervention, to adapt its implementation and to limit the negative impact on SIH.
The role of the family in health promotion: a scoping review of models and mechanisms
Authors: Ho Yi-Ching Lynn , Mahirah Dhiya , Ho Clement Zhong-Hao , Thumboo Julian
Published: November 2022

The family is an important contributor to the cultural conditions that support health. Current challenges in family health promotion interventions include programme design that is not always guided by theory and change mechanisms. Multifaceted programmes also make it hard to examine what works for whom, given different family roles and the range of lifestyle behaviour and mechanisms examined within diverse conceptual frameworks and cultures. We performed a scoping review on the heterogeneous literature to map and categorize the models and mechanisms by which a family may promote health behaviours among its members. We searched five electronic databases and grey literature up to 2020. Publications were included if they examined health-promoting behaviours, influences at the family level, and outlined the behavioural mechanisms involved. Two hundred and forty studies were identified. Ecological systems theory, social cognitive theory, family systems theory and the theory of planned behaviour were the frameworks most widely used in explaining either study context and/or mechanism. The most frequently studied family mechanisms involved aspects of family support, supervision and modelling, while some studies also included individual-level mechanisms. Majority of the studies investigated parental influence on the child, while few studies assessed the elderly family member as a recipient or actor of the influences. Studies on African, Asian and Middle Eastern populations were also in the minority, highlighting room for further research. Improving the understanding of context and behavioural mechanisms for family health promotion will aid the development of public health policy and chronic disease prevention programmes, complementing efforts targeted at individuals.
Predicting non-response in patient-reported outcome measures: results from the Swiss quality assurance programme in cardiac inpatient rehabilitation
Authors: KÖhn Stefanie , Schlumbohm Anna , Marquardt Manuela , Scheel-Sailer Anke , Tobler Stephan , Vontobel Jan , Menzi Luise
Published: November 2022

Background

Quality assurance programmes measure and compare certain health outcomes to ensure high-quality care in the health-care sector. The outcome of health-related quality of life is typically measured by patient-reported outcome measures (PROMs). However, certain patient groups are less likely to respond to PROMs than others. This non-response bias can potentially distort results in quality assurance programmes.

Objective

Our study aims to identify relevant predictors of non-response during assessment using the PROM MacNew Heart Disease questionnaire in cardiac rehabilitation.

Methods

This is a cross-sectional study based on data from the Swiss external quality assurance programme. All patients aged 18 years or older who underwent inpatient cardiac rehabilitation in 16 Swiss rehabilitation clinics between 2016 and 2019 were included. Patients’ socio-demographic and basic medical data were analysed descriptively by comparing two groups: non-responders and responders. We used a random intercept logistic regression model to estimate the associations of patient characteristics and clinic differences with non-response.

Results

Of 24 572 patients, there were 33.3% non-responders and 66.7% responders. The mean age was 70 years, and 31.0% were women. The regression model showed that being female was associated with non-response [odds ratio (OR) 1.22; 95% confidence interval (CI) 1.14–1.30], as well as having no supplementary health insurance (OR 1.49; 95% CI 1.39–1.59). Each additional year of age increased the chance of non-response by an OR of 1.02 (95% CI 1.02–1.02). Not being a first language speaker of German, French or Italian increased the chance of non-response by an OR of 6.94 (95% CI 6.03–7.99). Patients admitted directly from acute care had a higher chance of non-response (OR 1.23; 95% CI 1.10–1.38), as well as patients being discharged back into acute care after rehabilitation (OR 3.89; 95% CI 3.00–5.04). Each point on the cumulative illness rating scale total score increased the chance of non-response by an OR of 1.05 (95% CI 1.04–1.05). Certain diagnoses also influenced the chance of non-response. Even after adjustment for known confounders, response rates differed substantially between the 16 clinics.

Conclusion

We have found significant non-response bias among certain patient groups, as well as across different treatment facilities. Measures to improve response rates among patients with known barriers to participation, as well as among different treatment facilities, need to be considered, particularly when PROMs are being used for comparison of providers in quality assurance programmes or outcome evaluation.
Monkeypox Emergence and the Eradication of Smallpox: An Historical Review
Authors: Shulman Stanford T
Published: November 2022

Background

Human monkeypox infection was first identified in 1970 in African. Small rodents were the natural reservoir of this orthopoxvirus, with humans and primates as incidental hosts. Smallpox vaccination induces cross protection against monkeypox. In Africa monkeypox overlapped with the Global Smallpox Eradication Program (GSEP) six decades ago. The 2022 human monkeypox epidemic prompted literature review re potential impact of monkeypox upon GSEP efforts.

Methods

Literature review from 1960 to present related to GSEP launched in 1969 with particular focus on monkeypox epidemiology during planning of GSEP in the 1960’s through 1989 including surveillance years later.

Results

Establishing the lack of a non-human reservoir of smallpox was essential to assessing the GSEP because of the similarity of the two orthopoxviruses. It was found that a non-human smallpox reservoir was highly remote. Human monkeypox did not occur in smallpox-vaccinated humans and was limited to non-vaccinees. Surveillance in Democratic Republic of the Congo (DRC) until 1989 found monkeypox was very unlikely to persist in humans and unlikely to become a major public health problem. From 2005–2007, decades after cessation of smallpox vaccination, monkeypox surveillance in DRC revealed 20-fold higher incidence of human monkeypox correlated with much lower rates of prior smallpox vaccination.

Conclusions

Human monkeypox rates in DRC were 20-fold higher decades after cessation of smallpox vaccination compared to when smallpox vaccination was still used. The resultant decreased cross-protection against monkeypox contributed to the 2022 multinational outbreak of human monkeypox.
First Light And Reionization Epoch Simulations (FLARES) VII: The star formation and metal enrichment histories of galaxies in the early Universe
Authors: Wilkins Stephen M , Vijayan Aswin P , Lovell Christopher C , Roper William J , Zackrisson Erik , Irodotou Dimitrios , Seeyave Louise T C , Kuusisto Jussi K , Thomas Peter A , Caruana Joseph , Conselice Christopher J
Published: November 2022

The star formation and metal enrichment histories of galaxies – at any epoch – constitute one of the key properties of galaxies, and their measurement is a core aim of observational extragalactic astronomy. The lack of deep rest-frame optical coverage at high redshift has made robust constraints elusive, but this is now changing thanks to JWST. In preparation for the constraints provided by JWST, we explore the star formation and metal enrichment histories of galaxies at z = 5–13 using the First Light And Reionization Epoch Simulations (flares) suite. Built on the EAGLE model, the unique strategy of flares allows us to simulate galaxies with a wide range of stellar masses (and luminosities) and environments. While we predict significant redshift evolution of average ages and specific star formation rates, our core result is mostly a flat relationship of age and specific star formation rate with stellar mass. We also find that galaxies in this epoch predominantly have strongly rising star formation histories, albeit with the normalization dropping with redshift and stellar mass. In terms of chemical enrichment, we predict a strong stellar mass–metallicity relation present at z = 10 and beyond alongside significant α-enhancement. Finally, we find no large-scale environmental dependence of the relationship between age, specific star formation rate, or metallicity with stellar mass.
Morphological signatures of mergers in the TNG50 simulation and the Kilo-Degree Survey: the merger fraction from dwarfs to Milky Way-like galaxies
Authors: Guzmán-Ortega Alejandro , Rodriguez-Gomez Vicente , Snyder Gregory F , Chamberlain Katie , Hernquist Lars
Published: November 2022

Using the TNG50 cosmological simulation and observations from the Kilo-Degree Survey (KiDS), we investigate the connection between galaxy mergers and optical morphology in the local Universe over a wide range of galaxy stellar masses (8.5 ≤ log (M*/M⊙) ≤ 11). To this end, we have generated over 16 000 synthetic images of TNG50 galaxies designed to match KiDS observations, including the effects of dust attenuation and scattering, and used the statmorph code to measure various image-based morphological diagnostics in the r-band for both data sets. Such measurements include the Gini–M20 and concentration–asymmetry–smoothness statistics. Overall, we find good agreement between the optical morphologies of TNG50 and KiDS galaxies, although the former are slightly more concentrated and asymmetric than their observational counterparts. Afterwards, we trained a random forest classifier to identify merging galaxies in the simulation (including major and minor mergers) using the morphological diagnostics as the model features, along with merger statistics from the merger trees as the ground truth. We find that the asymmetry statistic exhibits the highest feature importance of all the morphological parameters considered. Thus, the performance of our algorithm is comparable to that of the more traditional method of selecting highly asymmetric galaxies. Finally, using our trained model, we estimate the galaxy merger fraction in both our synthetic and observational galaxy samples, finding in both cases that the galaxy merger fraction increases steadily as a function of stellar mass.
SuperNatural 3.0—a database of natural products and natural product-based derivatives
Authors: Gallo Kathleen , Kemmler Emanuel , Goede Andrean , Becker Finnja , Dunkel Mathias , Preissner Robert , Banerjee Priyanka
Published: November 2022

Natural products (NPs) are single chemical compounds, substances or mixtures produced by a living organism - found in nature. Evolutionarily, NPs have been used as healing agents since thousands of years and still today continue to be the most important source of new potential therapeutic preparations. Natural products have played a key role in modern drug discovery for several diseases. Furthermore, following consumers’ increasing demand for natural food ingredients, many efforts have been made to discover natural low-calorie sweeteners in recent years. SuperNatural 3.0 is a freely available database of natural products and derivatives. The updated version contains 449 058 natural compounds along with their structural and physicochemical information. Additionally, information on pathways, mechanism of action, toxicity, vendor information if available, drug-like chemical space prediction for several diseases as antiviral, antibacterial, antimalarial, anticancer, and target specific cells like the central nervous system (CNS) are also provided for the natural compounds. The updated version of the database also provides a valuable pool of natural compounds in which potential highly sweet compounds are expected to be found. The possible taste profile of the natural compounds was predicted using our published VirtualTaste models. The SuperNatural 3.0 database is freely available via http://bioinf-applied.charite.de/supernatural_3, without any login or registration.
GPCRdb in 2023: state-specific structure models using AlphaFold2 and new ligand resources
Authors: Pándy-Szekeres Gáspár , Caroli Jimmy , Mamyrbekov Alibek , Kermani Ali A , Keserű György M , Kooistra Albert J , Gloriam David E
Published: November 2022

G protein-coupled receptors (GPCRs) are physiologically abundant signaling hubs routing hundreds of extracellular signal substances and drugs into intracellular pathways. The GPCR database, GPCRdb supports >5000 interdisciplinary researchers every month with reference data, analysis, visualization, experiment design and dissemination. Here, we present our fifth major GPCRdb release setting out with an overview of the many resources for receptor sequences, structures, and ligands. This includes recently published additions of class D generic residue numbers, a comparative structure analysis tool to identify functional determinants, trees clustering GPCR structures by 3D conformation, and mutations stabilizing inactive/active states. We provide new state-specific structure models of all human non-olfactory GPCRs built using AlphaFold2-MultiState. We also provide a new resource of endogenous ligands along with a larger number of surrogate ligands with bioactivity, vendor, and physiochemical descriptor data. The one-stop-shop ligand resources integrate ligands/data from the ChEMBL, Guide to Pharmacology, PDSP Ki and PubChem database. The GPCRdb is available at https://gpcrdb.org.
PDCM Finder: an open global research platform for patient-derived cancer models
Authors: Perova Zinaida , Martinez Mauricio , Mandloi Tushar , Gomez Federico Lopez , Halmagyi Csaba , Follette Alex , Mason Jeremy , Newhauser Steven , Begley Dale A , Krupke Debra M , Bult Carol , Parkinson Helen , Groza Tudor
Published: November 2022

PDCM Finder (www.cancermodels.org) is a cancer research platform that aggregates clinical, genomic and functional data from patient-derived xenografts, organoids and cell lines. It was launched in April 2022 as a successor of the PDX Finder portal, which focused solely on patient-derived xenograft models. Currently the portal has over 6200 models across 13 cancer types, including rare paediatric models (17%) and models from minority ethnic backgrounds (33%), making it the largest free to consumer and open access resource of this kind. The PDCM Finder standardises, harmonises and integrates the complex and diverse data associated with PDCMs for the cancer community and displays over 90 million data points across a variety of data types (clinical metadata, molecular and treatment-based). PDCM data is FAIR and underpins the generation and testing of new hypotheses in cancer mechanisms and personalised medicine development.
METTL3-mediated m6A modification stabilizes TERRA and maintains telomere stability
Authors: Chen Liping , Zhang Canfeng , Ma Wenbin , Huang Junjiu , Zhao Yong , Liu Haiying
Published: November 2022

Telomeric repeat-containing RNA (TERRA) is a type of long non-coding RNA transcribed from telomeres, and it forms R-loops by invasion into telomeric DNA. Since either an excessive or inadequate number of R-loops leads to telomere instability, the TERRA levels need to be delicately modulated. In this study, we found that m6A modification presents on the subtelomeric regions of TERRA and stabilizes it, and the loss of METTL3 impacts telomere stability. Mechanically, the m6A modification on TERRA is catalyzed by METTL3, recognized and stabilized by the m6A reader YTHDC1. Knockdown of either METTL3 or YTHDC1 enhances TERRA degradation. The m6A-modified TERRA forms R-loops and promotes homologous recombination which is essential for the alternative lengthening of telomeres (ALT) pathway in cancer cells. METTL3 depletion leads to R-loop reduction, telomere shortening and instability. Altogether, these findings reveal that METTL3 protects telomeres by catalyzing m6A modification on TERRA, indicating that inhibition or deletion of METTL3 is potentially a new avenue for ALT cancer therapy.
Glucocorticoids unmask silent non-coding genetic risk variants for common diseases
Authors: Nguyen Thanh Thanh L , Gao Huanyao , Liu Duan , Philips Trudy Janice , Ye Zhenqing , Lee Jeong-Heon , Shi Geng-xian , Copenhaver Kaleigh , Zhang Lingxin , Wei Lixuan , Yu Jia , Zhang Huan , Barath Abhijeet , Luong Maggie , Zhang Cheng , Gaspar-Maia Alexandre , Li Hu , Wang Liewei , Ordog Tamas , Weinshilboum Richard M
Published: November 2022

Understanding the function of non-coding genomic sequence variants represents a challenge for biomedicine. Many diseases are products of gene-by-environment interactions with complex mechanisms. This study addresses these themes by mechanistic characterization of non-coding variants that influence gene expression only after drug or hormone exposure. Using glucocorticoid signaling as a model system, we integrated genomic, transcriptomic, and epigenomic approaches to unravel mechanisms by which variant function could be revealed by hormones or drugs. Specifically, we identified cis-regulatory elements and 3D interactions underlying ligand-dependent associations between variants and gene expression. One-quarter of the glucocorticoid-modulated variants that we identified had already been associated with clinical phenotypes. However, their affected genes were ‘unmasked’ only after glucocorticoid exposure and often with function relevant to the disease phenotypes. These diseases involved glucocorticoids as risk factors or therapeutic agents and included autoimmunity, metabolic and mood disorders, osteoporosis and cancer. For example, we identified a novel breast cancer risk gene, MAST4, with expression that was repressed by glucocorticoids in cells carrying the risk genotype, repression that correlated with MAST4 expression in breast cancer and treatment outcomes. These observations provide a mechanistic framework for understanding non-coding genetic variant-chemical environment interactions and their role in disease risk and drug response.
IntroVerse: a comprehensive database of introns across human tissues
Authors: García-Ruiz Sonia , Gustavsson Emil K , Zhang David , Reynolds Regina H , Chen Zhongbo , Fairbrother-Browne Aine , Gil-Martínez Ana Luisa , Botia Juan A , Collado-Torres Leonardo , Ryten Mina
Published: November 2022

Dysregulation of RNA splicing contributes to both rare and complex diseases. RNA-sequencing data from human tissues has shown that this process can be inaccurate, resulting in the presence of novel introns detected at low frequency across samples and within an individual. To enable the full spectrum of intron use to be explored, we have developed IntroVerse, which offers an extensive catalogue on the splicing of 332,571 annotated introns and a linked set of 4,679,474 novel junctions covering 32,669 different genes. This dataset has been generated through the analysis of 17,510 human control RNA samples from 54 tissues provided by the Genotype-Tissue Expression Consortium. IntroVerse has two unique features: (i) it provides a complete catalogue of novel junctions and (ii) each novel junction has been assigned to a specific annotated intron. This unique, hierarchical structure offers multiple uses, including the identification of novel transcripts from known genes and their tissue-specific usage, and the assessment of background splicing noise for introns thought to be mis-spliced in disease states. IntroVerse provides a user-friendly web interface and is freely available at https://rytenlab.com/browser/app/introverse.
ChIPBase v3.0: the encyclopedia of transcriptional regulations of non-coding RNAs and protein-coding genes
Authors: Huang Junhong , Zheng Wujian , Zhang Ping , Lin Qiao , Chen Zhirong , Xuan Jiajia , Liu Chang , Wu Di , Huang Qiaojuan , Zheng Lingling , Liu Shurong , Zhou Keren , Qu Lianghu , Li Bin , Yang Jianhua
Published: November 2022

Non-coding RNAs (ncRNAs) are emerging as key regulators of various biological processes. Although thousands of ncRNAs have been discovered, the transcriptional mechanisms and networks of the majority of ncRNAs have not been fully investigated. In this study, we updated ChIPBase to version 3.0 (https://rnasysu.com/chipbase3/) to provide the most comprehensive transcriptional regulation atlas of ncRNAs and protein-coding genes (PCGs). ChIPBase has identified ∼151 187 000 regulatory relationships between ∼171 600 genes and ∼3000 regulators by analyzing ∼55 000 ChIP-seq datasets, which represent a 30-fold expansion. Moreover, we de novo identified ∼29 000 motif matrices of transcription factors. In addition, we constructed a novel ‘Enhancer’ module to predict ∼1 837 200 regulation regions functioning as poised, active or super enhancers under ∼1300 conditions. Importantly, we constructed exhaustive coexpression maps between regulators and their target genes by integrating expression profiles of ∼65 000 normal and ∼15 000 tumor samples. We built a ‘Disease’ module to obtain an atlas of the disease-associated variations in the regulation regions of genes. We also constructed an ‘EpiInter’ module to explore potential interactions between epitranscriptome and epigenome. Finally, we designed ‘Network’ module to provide extensive and gene-centred regulatory networks. ChIPBase will serve as a useful resource to facilitate integrative explorations and expand our understanding of transcriptional regulation.
ViLoN—a multi-layer network approach to data integration demonstrated for patient stratification
Authors: Kańduła Maciej M , Aldoshin Alexander D , Singh Swati , Kolaczyk Eric D , Kreil David P
Published: November 2022

With more and more data being collected, modern network representations exploit the complementary nature of different data sources as well as similarities across patients. We here introduce the Variation of information fused Layers of Networks algorithm (ViLoN), a novel network-based approach for the integration of multiple molecular profiles. As a key innovation, it directly incorporates prior functional knowledge (KEGG, GO). In the constructed network of patients, patients are represented by networks of pathways, comprising genes that are linked by common functions and joint regulation in the disease. Patient stratification remains a key challenge both in the clinic and for research on disease mechanisms and treatments. We thus validated ViLoN for patient stratification on multiple data type combinations (gene expression, methylation, copy number), showing substantial improvements and consistently competitive performance for all. Notably, the incorporation of prior functional knowledge was critical for good results in the smaller cohorts (rectum adenocarcinoma: 90, esophageal carcinoma: 180), where alternative methods failed.
Roxadustat (FG-4592) protects against ischaemia-induced acute kidney injury via improving CD73 and decreasing AIM2 inflammasome activation
Authors: Yang Huan , Wu Yong , Cheng Ming , Zhang Ming , Qiu Xiaoyan , Liu Shaojun , Zhang Minmin
Published: November 2022

Background

Hypoxia-mediated inflammation plays a crucial role in renal ischaemia–reperfusion (IR)-induced acute kidney injury (AKI) and may influence renal graft survival, with no available pharmacological treatments. Here we investigate the protective effects and mechanism of roxadustat (FG-4592), a hypoxia-inducible factor stabilizer, against renal IR injury.

Methods

The protein expression levels of CD73 and AIM2 inflammasome complex were examined in kidney biopsy specimens of AKI and post-renal transplantation (PRT) patients. The effects of FG-4592 on CD73 and absent in melanoma 2 (AIM2) inflammasome components were examined in IR mice (right nephrectomy, followed by 30 min of unilateral renal ischaemia and reperfusion for 24 h), and some of the model mice received intraperitoneal administrations of adenosine 5′-(α,β-methylene)diphosphate sodium salt, which is an inhibitor of CD73. The function of FG-4592 was also investigated in vitro with HK-2 cells.

Results

In the AKI and PRT patients, the protein expression of AIM2 complex [AIM2–apoptosis-associated speck-like protein (ASC)–cleaved caspase-1) increased and the activation of CD73 signalling pathway was detected as well. The pretreatment of FG-4592 improved the creatinine elevation and renal tubular injuries induced by ischaemia. What's more, the administration of FG-4592 significantly enhanced CD73 synthesis in mouse kidney but suppressed the activation of the AIM2 inflammasome [decreased AIM2, ASC, caspase-1, interleukin (IL)-1β and IL-18 levels]. Notably, the renoprotection of FG-4592 and the inhibition of AIM2 were abolished by the CD73 inhibitor.

Conclusion

FG-4592-conveyed protection against AKI might be mediated by the induction of CD73 and the suppression of the AIM2 inflammasome, which may provide a novel therapeutic method for the treatment of AKI.
VrMYB90Functions Synergistically withVrbHLHAandVrMYB3to Regulate Anthocyanin Biosynthesis in Mung Bean
Authors: Chen Jiahui , Zhan Junyi , Wang Haixia , Zhao Yingdi , Zhang Derui , Chen Xin , Su Nana , Cui Jin
Published: November 2022

Mung bean is an important grain-legume crop and its sprout is an economical and nutrient vegetable for the public, but the genetic regulation of anthocyanin production, which is an antioxidant in mung bean, remains elusive. In our study, we characterized a subgroup (SG) 6 R2R3-MYB anthocyanin activator VrMYB90 and a SG 4 R2R3-MYB anthocyanin repressor VrMYB3, which synergistically function in regulating anthocyanin synthesis with VrbHLHA transcription factor. The overexpressed VrMYB90 protein activates the expression of VrMYB3 and VrbHLHA in mung bean hair roots, and also promotes VrDFR and VrANS transcript levels by directly binding to the corresponding promoters at specific motifs (CAACTG and CCGTTG). VrMYB90 interacts with VrbHLHA to enhance its regulatory activities on VrDFR and VrANS. Furthermore, the interaction between VrMYB3 with VrMYB90 and VrbHLHA could result in the restriction of anthocyanin synthesis to prevent excessive anthocyanin accumulation. Our results demonstrate that the VrMYB90 protein, in conjunction with VrMYB3 and VrbHLHA, forms a key regulatory module to fine-tune anthocyanin synthesis in mung bean.
UV-B-Induced CPD Photolyase Gene Expression is Regulated by UVR8-Dependent and -Independent Pathways in Arabidopsis
Authors: Li Nan , Teranishi Mika , Yamaguchi Hiroko , Matsushita Tomonao , Watahiki Masaaki K , Tsuge Tomohiko , Li Shao-Shan , Hidema Jun
Published: November 2022

Plants have evolved various mechanisms that protect against the harmful effects of UV-B radiation (280–315 nm) on growth and development. Cyclobutane pyrimidine dimer (CPD) photolyase, the repair enzyme for UV-B-induced CPDs, is essential for protecting cells from UV-B radiation. Expression of the CPD photolyase gene (PHR) is controlled by light with various wavelengths including UV-B, but the mechanisms of this regulation remain poorly understood. In this study, we investigated the regulation of PHR expression by light with various wavelengths, in particular low-fluence UV-B radiation (280 nm, 0.2 µmol m–2 s –1), in Arabidopsis thaliana seedlings grown under light–dark cycles for 7 d and then adapted to the dark for 3 d. Low-fluence UV-B radiation induced CPDs but not reactive oxygen species. AtPHR expression was effectively induced by UV-B, UV-A (375 nm) and blue light. Expression induced by UV-A and blue light was predominantly regulated by the cryptochrome-dependent pathway, whereas phytochromes A and B played a minor but noticeable role. Expression induced by UV-B was predominantly regulated by the UVR8-dependent pathway. AtPHR expression was also mediated by a UVR8-independent pathway, which is correlated with CPD accumulation induced by UV-B radiation. These results indicate that Arabidopsis has evolved diverse mechanisms to regulate CPD photolyase expression by multiple photoreceptor signaling pathways, including UVR8-dependent and -independent pathways, as protection against harmful effects of UV-B radiation.
Attributing Increases in Ozone to Accelerated Oxidation of Volatile Organic Compounds at Reduced Nitrogen Oxides Concentrations
Authors: Zhang Zekun , Jiang Jiakui , Lu Bingqing , Meng Xue , Herrmann Hartmut , Chen Jianmin , Li Xiang
Published: November 2022

Surface ozone (O3) is an important secondary pollutant affecting climate change and air quality in the atmosphere. Observations during the COVID-19 lockdown in urban China show that the co-abatement of nitrogen oxides (NOx) and volatile organic compounds (VOCs) caused winter ground-level O3 increases, but the chemical mechanisms involved are unclear. Here we report field observations in the Shanghai lockdown that reveals increasing photochemical formation of O3 from VOC oxidation with decreasing NOx. Analyses of the VOC profiles and NO/NO2 indicate that the O3 increases by the NOx reduction counteracted the O3 decreases through the VOC emission reduction in the VOC-limited region, and this may have been the main mechanism for this net O3 increase. The mechanism may have involved accelerated OH–HO2–RO2 radical cycling. The NOx reductions for increasing O3 production could explain why O3 increased from 2014 to 2020 in response to NOx emission reduction even as VOC emissions have essentially remained unchanged. Model simulations suggest that aggressive VOC abatement, particularly for alkenes and aromatics, should help reverse the long-term O3 increase under current NOx abatement conditions.
The Hierarchy of Care Work: How Immigrants Influence the Gender-Segregated Labor Market
Authors: Østbakken Kjersti Misje , Orupabo Julia , Nadim Marjan
Published: November 2022

The devaluation of care work is regarded as a main explanation for the dominance of women in care work. However, less attention has been paid to how such devaluation affects not only the gender balance of jobs but also their ethnic and racial composition. This article examines patterns of gender and ethnic segregation and inequality within different types of care work. Using high-quality linked administrative register data covering the period 2004–2017, the analysis shows that although the strong female dominance in care work is relatively stable, a shift in the composition of workers has occurred. While native women are leaving the most devalued types of care work, they are replaced by immigrants—both women and men. The findings underscore how patterns of gender segregation are influenced by immigration, and that not all men benefit from being men in female-dominated occupations.
The Puzzle of Lionel Robbins: How a Neoliberal Economist Expanded Public University Education in 1960s Britain
Authors: Patel Josh
Published: November 2022

Lionel Robbins (1898–1984) has been identified as one of the leading ‘neoliberal’ economists of his day. However, his name remains irrevocably linked with the massive state-funded ‘social democratic’ expansion of higher education recommended by the Robbins Report (1963). This article explores this paradox. Examining Robbins’s writings on higher education in the context of his economic thought shows how he blended the liberalism of Adam Smith and J. S. Mill, neoliberal economics, and growing demands for personal choice. For Robbins, the atrocities of the Nazi and Soviet regimes demonstrated how the state armed with new modern technologies could endanger freedom and prosperity. But the ‘good society’ might wield technology to secure conditions of freedom and choice. Robbins advocated a system of state-subsidized universities based on ‘student demand’ and which generated social and individual returns. This system would perpetuate what Robbins called the ‘creed of freedom’: a reimagined interdisciplinary liberal education through which students would understand the importance of their specialism to liberal capitalism. His thought on higher education indicates something of the dynamism of post-war British liberalism and the range of support for higher education expansion. It further counters the impression of the British universities as sites of a static and conservative liberal education.
A Nitrate-Sensing Domain-Containing Chemoreceptor Is Required for Successful Entry and Virulence ofDickeya dadantii3937 in Potato Plants
Authors: Gálvez-Roldán Clara , Cerna-Vargas Jean Paul , Rodríguez-Herva José Juan , Krell Tino , Santamaría-Hernando Saray , López-Solanilla Emilia
Published: November 2022

Nitrate metabolism plays an important role in bacterial physiology. During the interaction of plant-pathogenic bacteria with their hosts, bacteria face variable conditions with respect to nitrate availability. Perception mechanisms through the chemosensory pathway drive the entry and control the colonization of the plant host in phytopathogenic bacteria. In this work, the identification and characterization of the nitrate- and nitrite-sensing (NIT) domain-containing chemoreceptor of Dickeya dadantii 3937 ( Dd3937) allowed us to unveil the key role of nitrate sensing not only for the entry into the plant apoplast through wounds but also for infection success. We determined the specificity of this chemoreceptor to bind nitrate and nitrite, with a slight ligand preference for nitrate. Gene expression analysis showed that nitrate perception controls not only the expression of nitrate reductase genes involved in respiratory and assimilatory metabolic processes but also the expression of gyrA, hrpN, and bgxA, three well-known virulence determinants in Dd3937.
Strategies for successfully completing a DNP final project
Authors: Reid Kimone Racquel Yolanda , DeGennaro Regina
Published: November 2022

Completion of a final project is an essential component of Doctor of Nursing Practice programs. Strategies for successful project planning, implementation, and evaluation are outlined, from identifying an evidence-based practice or quality improvement project, advisor, and practice mentor through completion, presentation, and dissemination of your work.
Evidence-based updates to the 2021 Surviving Sepsis Campaign guidelines Part 2
Authors: Lehman Karen D.
Published: November 2022

NPs should be prepared to screen for sepsis, initiate treatment, and optimize care for sepsis survivors. The 2021 Surviving Sepsis Campaign guidelines offer best practices for identification and management of sepsis and septic shock. This article, second in a 2-part series, presents evidence updates and discusses implications for NPs.
Predictive Models for Length of Stay and Discharge Disposition in Elective Spine Surgery: Development, Validation, and Comparison to the ACS NSQIP Risk Calculator
Authors: Arora Ayush , Lituiev Dmytro , Jain Deeptee , Hadley Dexter , Butte Atul J. , Berven Sigurd , Peterson Thomas A.
Published: November 2022

Study Design.

A retrospective study at a single academic institution.

Objective.

The purpose of this study is to utilize machine learning to predict hospital length of stay (LOS) and discharge disposition following adult elective spine surgery, and to compare performance metrics of machine learning models to the American College of Surgeon’s National Surgical Quality Improvement Program’s (ACS NSQIP) prediction calculator.

Summary of Background Data.

A total of 3678 adult patients undergoing elective spine surgery between 2014 and 2019, acquired from the electronic health record.

Methods.

Patients were divided into three stratified cohorts: cervical degenerative, lumbar degenerative, and adult spinal deformity groups. Predictive variables included demographics, body mass index, surgical region, surgical invasiveness, surgical approach, and comorbidities. Regression, classification trees, and least absolute shrinkage and selection operator (LASSO) were used to build predictive models. Validation of the models was conducted on 16% of patients (N=587), using area under the receiver operator curve (AUROC), sensitivity, specificity, and correlation. Patient data were manually entered into the ACS NSQIP online risk calculator to compare performance. Outcome variables were discharge disposition (home vs. rehabilitation) and LOS (days).

Results.

Of 3678 patients analyzed, 51.4% were male (n=1890) and 48.6% were female (n=1788). The average LOS was 3.66 days. In all, 78% were discharged home and 22% discharged to rehabilitation. Compared with NSQIP (Pearson R
2=0.16), the predictions of poisson regression (R
2=0.29) and LASSO (R
2=0.29) models were significantly more correlated with observed LOS (P=0.025 and 0.004, respectively). Of the models generated to predict discharge location, logistic regression yielded an AUROC of 0.79, which was statistically equivalent to the AUROC of 0.75 for NSQIP (P=0.135).

Conclusion.

The predictive models developed in this study can enable accurate preoperative estimation of LOS and risk of rehabilitation discharge for adult patients undergoing elective spine surgery. The demonstrated models exhibited better performance than NSQIP for prediction of LOS and equivalent performance to NSQIP for prediction of discharge location.
Rilonacept and Other Interleukin-1 Inhibitors in the Treatment of Recurrent Pericarditis
Authors: Goel Akshay , Bandyopadhyay Dhrubajyoti , Malik Aaqib H , Gupta Rahul , Frishman William H , Aronow Wilbert S
Published: November 2022

Pericarditis is the commonest form of pericardial disease. Unfortunately, despite optimal treatment, approximately 15–30% of patients with acute pericarditis have recurrence. Many of these patients are refractory to colchicine, and become corticosteroid-dependent. Recurrent pericarditis severely impairs quality of life, and is associated with significant morbidity. Inflammasome formation and overproduction of interleukin (IL)-1 have been found to drive the systemic inflammatory response in recurrent autoinflammatory pericarditis. Several IL-1 inhibitors have been evaluated for their usefulness as therapeutic options. Rilonacept is a dimeric fusion protein that functions as a soluble decoy receptor that binds to both IL-1α and IL-1β, thereby inhibiting the IL-1 pathway. It is safe and efficacious in the treatment of recurrent pericarditis in the RHAPSODY II and III trials. Anakinra is a recombinant IL-1 receptor antagonist that blocks the action of circulating IL-1α and IL-1β. It has also been shown to be safe and efficacious in the AIRTRIP and IRAP studies. Canakinumab is a selective human monoclonal antibody against IL-1β, and data on its use in recurrent pericarditis is scarce. Several questions regarding IL-1 inhibitor therapy, such as the duration of treatment and the recommended tapering protocols, as well as their use in special populations like pregnant or lactating women, remain unanswered and need to be addressed in future studies.
The Surgical Management of Ileal Pouch Strictures
Authors: Aviran Eyal , Zaghiyan Karen , Fleshner Phillip
Published: November 2022

BACKGROUND:

Total proctocolectomy with IPAA reconstruction is the surgical approach of choice in ulcerative colitis, indeterminate colitis, familial adenomatous polyposis, and selected patients with Crohn’s disease. Pouch stricture is a common complication after IPAA.

OBJECTIVE:

This study aims to identify surgical management options for pouch stricture and offer a treatment algorithm.

DATA SOURCES:

A computer-assisted search of the online bibliographic databases MEDLINE and Embase from 1990 to 2021 was performed.

STUDY SELECTION:

Randomized controlled trials, cohort studies, observational studies, and case reports were considered.

INTERVENTIONS:

Mechanical dilation, strictureplasty, stapler resection, pouch advancement, bypass, and repeat IPAA were included.

MAIN OUTCOMES:

Twenty-three articles were considered eligible. Overall incidence of strictures varied from 5% to 38%. Strictures were categorized into 3 areas: pouch inlet (with a reported incidence of 9% to 56%), mid-pouch (with a reported incidence of 2%), and pouch-anal anastomosis (with a reported incidence of 43% to 87%). Pouch-anal strictures were initially managed using bougie or Hegar dilation, with various surgical procedures advocated when initial dilation failed. Mid-pouch strictures are relatively unstudied with scant data. Pouch inlet strictures can be surgically managed by various transabdominal techniques‚ including resection and reconnection, strictureplasty, or bypass.

RESULTS:

Pouch-anal strictures should be managed in a step-up strategy as conservative procedures are associated with acceptable success rates. Initial mechanical dilation using bougie or Hegar dilation has a success rate of >80%, although it is likely to require repeat dilations. When these measures fail, transanal surgical approaches using strictureplasty, stapler resection‚ or pouch advancement should be offered. Transabdominal pouch revision should be offered to patients refractory to a transanal approach. In mid-pouch strictures, the treatment of choice is pouch revision and reanastomosis. Pouch inlet strictures can be managed by resection, strictureplasty, or bypass depending on the location and length of the stricture and surgeon experience.

LIMITATIONS:

Studies were often small and retrospectively analyzed. There were no randomized controlled trials or comparison between different treatment options.
Computer-aided Surgical Planning and Osteosynthesis Plates for Bimaxillary Orthognathic Surgery: A Study of 14 Consecutive Patients
Authors: Shakoori Pasha , Yang Robin , Nah Hyun-Duck , Scott Michelle , Swanson Jordan W. , Taylor Jesse A. , Bartlett Scott P.
Published: November 2022

Background:

Computer-aided surgical planning has become popular for planning orthognathic surgery (OS) as it saves surgeons’ time and effort. A recent advancement has been the utilization of patient-specific cutting guides and osteosynthesis. The purpose of this study is to report the postoperative bimaxillary position utilizing custom plates for both jaws versus custom plates used in the maxilla only in 23 consecutive patients.

Methods:

All patients who underwent bimaxillary OS in 2017–2018 with preoperative computed tomography (CT) scan, postoperative day 1 CT scan, and at least 6 months follow-up were included in the study. Group 1 utilized maxillary preprinted plates (maxilla only). Group 2 utilized bimaxillary preprinted plates (maxillomandibular). Eight cephalometric landmarks to evaluate the movements were chosen. The ranges of the angle between the sella/nasion plane and the nasion/A plane (SNA), the angle between the sella/nasion plane and the nasion/B plane (SNB), and the angle created by the A point‚ nasion‚ and B point‚ which measures the relative position of maxilla to mandible, were analyzed to assess the angular change. Mean-squared displacement and the SD of the distances were used to assess movement in space.

Results:

Twenty-three patients (nine in group 1 and 14 in group 2) met the inclusion criteria. Results showed interarch relationships using custom plates for both jaws with ANB 0.4 compared to ANB 1.4 for maxillary custom plates only. Mandibular landmarks showed greater variation, and the t test study revealed the right mandibular first molar landmark showing the greatest variation (P = 0.03).

Conclusions:

Custom osteosynthesis plates for OS show good accuracy for the maxilla and higher variation in the mandible. Further studies will determine the margin of error that cannot be corrected with postoperative orthodontics.
Hypotensive unawareness in Parkinson's disease-related autonomic dysfunction
Authors: Slavescu Andreea , Byrne Lisa , Lavan Amanda , Briggs Robert
Published: November 2022

This case demonstrates how orthostatic hypotension in the absence of typical symptoms of light-headedness/dizziness when changing posture, can contribute to the burden of falls in Parkinson's disease. At least one-third of people with severe orthostatic hypotension do not report typical symptoms, and this figure appears to be higher in patients with Parkinson's disease. This is important clinically as it can increase the difficulty in ascribing falls to orthostatic hypotension, especially given the other competing reasons in Parkinson's disease and orthostatic hypotension symptoms can act as a prompt for the patient to act to prevent falls-related injuries. There is a clinical requirement, therefore, to screen for and manage orthostatic hypotension in patients with Parkinson's disease to prevent falls, even in those who do not report typical symptoms.