bluuebunny/crossref_metadata_2025 huggingface dataset:
An alternative method for estimating effective elastic thickness by the Vening Meinesz regional isostatic theory with application to continents
Authors: Zhang Xingyu , Kaban Mikhail K , Chen Chao , Liang Qing
Published: January 2023

Effective elastic thickness, ${T_\mathrm{ e}}$, is a measure of the lithosphere's mechanical strength, and describes the flexural response of the lithosphere to applied loads in the same way as a thin elastic plate. In this study, a new method for estimating ${T_\mathrm{ e}}$ in the spatial domain is presented based on the Veining Meinesz regional isostatic theory. By comparing the absolute values of the correlation coefficients between the observed Moho flexure model and different Veining Meinesz Moho flexure models, the optimal ${T_\mathrm{ e}}$ is determined. Also, the estimated correlation coefficients can be used to examine the effect of the unknown subsurface loads, which are usually difficult to evaluate in the spatial domain. This method is verified to be capable of recovering ${T_\mathrm{ e}}$ variations through synthetic tests for the models with predefined ${T_\mathrm{ e}}$ variations. Finally, the effective elastic thickness is globally determined for the continents using the topography data and recent seismically-derived Moho model. These results are compared with two published ${T_\mathrm{ e}}$ models obtained with different methods. For the areas with relatively small Moho uncertainties and high correlation coefficients, the estimated ${T_\mathrm{ e}}$ variations generally agree with previous results. The differences between three ${T_\mathrm{ e}}$ estimates could characterize the advantages of different methods in specific cases.
Comment on ‘Geophysical inversion and optimal transport’ by M. Sambridge, A. Jackson and A. P. Valentine
Authors: Okazaki Tomohisa , Ueda Naonori
Published: January 2023

A similarity measure between waveforms developed by Sambridge et al. realized an effective use of optimal transport as well as computational efficiency through the marginalization of a 2-D probability distribution obtained from a seismogram. We demonstrate that information loss due to marginalization could lead to significant non-uniqueness in the resulting measure and propose the use of the sliced Wasserstein distance as a potential solution. This formulation may enhance the robustness of the method developed by Sambridge et al. by maintaining its computational efficiency.
Benefits and challenges of consolidating public health functions into a National Public Health Institute: a policy analysis
Authors: Carnevale Caroline R , Woldetsadik Mahlet A , Shiver Arielle , Gutierrez Margaret , Chhea Chhorvann , Ilori Elsie , Jani Ilesh , MaCauley Jane , Mukonka Victor , Nsanzimana Sabin , Ospina Martha Lucia , Raji Tajudeen , Spotts Whitney Ellen A , Bratton Shelly
Published: January 2023

National Public Health Institutes (NPHIs) around the world vary in composition. Consolidated organizational models can bring together critical functions such as disease surveillance, emergency preparedness and response, public health research, workforce development and laboratory diagnosis within a single focal point. This can lead to enhanced coordination and management of resources and enable more efficient and effective public health operations. We explored stakeholders’ perceptions about the benefits and challenges of consolidating public health functions in an NPHI in seven countries where the US Centers for Disease Control and Prevention has supported NPHI establishment and strengthening. From August 2019 through January 2020, we interviewed a total of 96 stakeholders, including NPHI staff (N = 43), non-NPHI government staff (N = 29) and non-governmental and international organization staff (N = 24) in Cambodia, Colombia, Liberia, Mozambique, Nigeria, Rwanda and Zambia. We conducted a policy analysis using Tea Collins’s health policy analysis framework to assess various possible options for coordinating public health functions and their likely effectiveness. The findings can be used by policymakers as they consider public health infrastructure. We found that consolidating functions in an NPHI, to the extent politically and organizationally feasible, promotes efficiency, flexibility and coordination, as well as supports data-driven health recommendations to government decision makers. Countries pursuing NPHI establishment can weigh the potential challenges and benefits of consolidating functions when determining which public health functions will comprise the NPHI, including clarity of role, access to resources, influence over decisions and political viability.
Effectiveness of Workplace Health Promotion (WHP) interventions in university employees: a scoping review
Authors: Moroni Alessia , Degan Raffaella , Martin Barbara , Sciannameo Veronica , Berchialla Paola , Gilli Giorgio , Micheletti Cremasco Margherita
Published: January 2023

Workplace Health Promotion (WHP) interventions proved to be effective in several workplace contexts. Currently, the effectiveness of such interventions in the academic workplace is lacking, albeit evidence suggests similar patterns to those occurring in other workplace sectors. The aim of this study was to review WHP interventions in the university workplace that led to improve health- and work-related outcomes. Articles were selected using Pubmed, Web of Science, Scopus, Embase, PsycInfo, Cinhal and FSTA, using search strings focused on health- and/or work-related outcomes and involving University WHP interventions published between January 2010 and July 2021. The majority of the 12 studies selected reported positive results in their individuality, especially regarding health-related outcomes [biological such as weight loss, physical activity, mental health and lifestyle habits] and work-related outcomes concerning improvements either for the employee or for the working system. Studies on economic advantage and Return on Investment were limited and reported contrasting results. In conclusion, we have highlighted how the studies on effectiveness of WHP interventions in the university context are few and heterogeneous and need to be encouraged further research in order to build specific guidelines that are effective.
Considering social inequalities in health in COVID-19 response: insights from a French case study
Authors: Richard Zoé , Chabrol Fanny , Gautier Lara , Zinszer Kate , Ridde Valéry
Published: January 2023

The COVID-19 pandemic highlighted the impact of social inequalities in health (SIH). Various studies have shown significant inequalities in mortality and morbidity associated with COVID-19 and the influence of social determinants of health. The objective of this qualitative case study was to analyze the consideration of SIH in the design of two key COVID-19 prevention and control interventions in France: testing and contact tracing. Interviews were conducted with 36 key informants involved in the design of the intervention and/or the government response to the pandemic as well as relevant documents (n = 15) were reviewed. We applied data triangulation and a hybrid deductive and inductive analysis to analyze the data. Findings revealed the divergent understandings and perspectives about SIH, as well as the challenges associated with consideration for these at the beginning stages of the pandemic. Despite a shared concern for SIH between the participants, an epidemiological frame of reference dominated the design of the intervention. It resulted in a model in which consideration for SIH appeared as a complement, with a clinical goal of the intervention: breaking the chain of COVID-19 transmission. Although the COVID-19 health crisis highlighted the importance of SIH, it did not appear to be an opportunity to further their consideration in response efforts. This article provides original insights into consideration for SIH in the design of testing and contact-tracing interventions based upon a qualitative investigation.
Walking and perception of green space among older adults in Japan: subgroup analysis based self-efficacy
Authors: Encho Haruhi , Uchida Kazuaki , Horibe Kana , Nakatsuka Kiyomasa , Ono Rei
Published: January 2023

Self-efficacy is the key factor for promoting physical activity. Older adults with low self-efficacy tend to be physical inactive than those with high self-efficacy, and an approach is needed to promote physical activity. Among several approaches, increasing the perception of green space may be an effective approach for low self-efficacy not high self-efficacy, but no study has investigated. This study investigated the association between walking and perception of green space among older adults with high and low self-efficacy, respectively. We conducted a cross-sectional study among 204 community-dwelling older adults (mean age = 78.3 years, 62.3% females). Using the median split, the participants were divided into high and low self-efficacy groups based on the median score of 12. Walking was measured using the International Physical Activity Questionnaire and ‘more walking’ was defined as ≥150 min of walking time per week. Perception of green space was measured using an 8-item questionnaire. We performed logistic regression analysis to investigate the association between walking and perception of green space adjusted for age, gender, years of education, living with someone and income level. For all participants, 94 participants (46.1%) fell under low self-efficacy. After adjustment, higher perception of green space is associated with more walking among older adults with low self-efficacy [adjusted odds ratio (aOR) = 1.07, 95% confidence interval (CI) = 1.00–1.15], but not among those with high self-efficacy (aOR = 1.09, 95% CI= 0.99–1.20). To increase perception of green space, experts should design/improve green spaces considering beneficiaries’ characteristics.
Women, alcohol consumption and health promotion: the value of a critical realist approach
Authors: Kersey Kate , Hutton Fiona , Lyons Antonia C
Published: January 2023

Research on women’s drinking occurs in largely disparate disciplines—including public health, health promotion, psychology, sociology, and cultural studies—and draws on differing philosophical understandings and theoretical frameworks. Tensions between the aims and paradigmatic underpinnings of this research (across and within disciplines) have meant that knowledge and insight can be frequently disciplinary-specific and somewhat siloed. However, in line with the social and economic determinants of the health model, alcohol research needs approaches that can explore how multiple gender-related factors—biological, psycho-social, material, and socio-cultural—combine to produce certain drinking behaviours, pleasures and potential harms. We argue that critical realism as a philosophical underpinning to research can accommodate this broader conceptualization, enabling researchers to draw on multiple perspectives to better understand women’s drinking. We illustrate the benefit of this approach by presenting a critical realist theoretical framework for understanding women’s drinking that outlines interrelationships between the psychoactive properties of alcohol, the role of embodied individual characteristics and the material, institutional and socio-cultural contexts in which women live. This approach can underpin and foster inter-disciplinary research collaboration to inform more nuanced health promotion practices and policies to reduce alcohol-related harm in a wide range of women across societies.
G3BP1-dependent mechanism suppressing protein aggregation in Huntington’s models and its demise upon stress granule assembly
Authors: Gutiérrez-Garcia Ricardo , Koyuncu Seda , Hommen Franziska , Bilican Saygın , Lee Hyun Ju , Fatima Azra , Vilchez David
Published: January 2023

Stress granules are membrane-less ribonucleoprotein organelles that assemble upon exposure to stress conditions, but rapidly disassemble upon removal of stress. However, chronic stress can lead to persistent stress granules, a feature of distinct age-related neurodegenerative disorders. Among them, Huntington’s disease (HD), which is caused by mutant expansion of the polyglutamine (polyQ) repeats of huntingtin protein (HTT), leading to its aggregation. To identify modulators of mutant HTT aggregation, we define its interactome in striatal neurons differentiated from patient-derived induced pluripotent stem cells (HD-iPSCs). We find that HTT interacts with G3BP1, a characteristic component of stress granules. Knockdown of G3BP1 increases mutant HTT protein levels and abolishes the ability of iPSCs as well as their differentiated neural counterparts to suppress mutant HTT aggregation. Moreover, loss of G3BP1 hastens polyQ-expanded aggregation and toxicity in the neurons of HD C. elegans models. Likewise, the assembly of G3BP1 into stress granules upon distinct stress conditions also reduces its interaction with HTT in human cells, promoting mutant HTT aggregation. Notably, enhancing the levels of G3BP1 is sufficient to induce proteasomal degradation of mutant HTT and prevent its aggregation, whereas the formation of stress granules blocks these ameliorative effects. In contrast, a mutant G3BP1 variant that cannot accumulate into granules retains its capacity to prevent mutant HTT aggregation even when the cells assemble stress granules. Thus, our findings indicate a direct role of G3BP1 and stress granule assembly in mutant HTT aggregation that may have implications for HD.
High-quality haplotype-resolved genome assembly of cultivated octoploid strawberry
Authors: Mao Jianxin , Wang Yan , Wang Baotian , Li Jiqi , Zhang Chao , Zhang Wenshuo , Li Xue , Li Jie , Zhang Junxiang , Li He , Zhang Zhihong
Published: January 2023

Cultivated strawberry (Fragaria × ananassa), a perennial herb belonging to the family Rosaceae, is a complex octoploid with high heterozygosity at most loci. However, there is no research on the haplotype of the octoploid strawberry genome. Here we aimed to obtain a high-quality genome of the cultivated strawberry cultivar, “Yanli”, using single molecule real-time sequencing and high-throughput chromosome conformation capture technology. The “Yanli” genome was 823 Mb in size, with a long terminal repeat assembly index of 14.99. The genome was phased into two haplotypes, Hap1 (825 Mb with contig N50 of 26.70 Mb) and Hap2 (808 Mb with contig N50 of 27.51 Mb). Using the combination of Hap1 and Hap2, we obtained for the first time a haplotype-resolved genome with 56 chromosomes for the cultivated octoploid strawberry. We identified a ~ 10 Mb inversion and translocation on chromosome 2-1. 104 957 and 102 356 protein-coding genes were annotated in Hap1 and Hap2, respectively. Analysis of the genes related to the anthocyanin biosynthesis pathway revealed the structural diversity and complexity in the expression of the alleles in the octoploid F. × ananassa genome. In summary, we obtained a high-quality haplotype-resolved genome assembly of F. × ananassa, which will provide the foundation for investigating gene function and evolution of the genome of cultivated octoploid strawberry.
Histones of Neutrophil Extracellular Traps Directly Disrupt the Permeability and Integrity of the Intestinal Epithelial Barrier
Authors: Lai Hsuan-Ju , Doan Ha T , Lin Elliot Y , Chiu Yi-Ling , Cheng Yuan-Kai , Lin Yi-He , Chiang Hao-Sen
Published: January 2023

Background

Increased neutrophil extracellular trap (NET) formation and abundant NET-associated proteins are frequently found in the inflamed colon of patients with inflammatory bowel disease. Peptidyl arginine deiminase 4 (PAD4) activation is essential for the generation of NET and NET-mediated pathogenesis. However, the role of PAD4-dependent NET formation in murine inflammatory bowel disease models and the molecular mechanisms responsible for the altered gut barrier function are unknown.

Methods

Wild-type and Pad4 knockout (Pad4-/-) mice were administrated 3% dextran sulfate sodium (DSS) in their drinking water. Caco-2 monolayers were used to test the effect of NETs on intestinal barrier function and cytotoxicity. Histones were intrarectally administrated to wild-type mice to determine their effects on intestinal barrier function and cytotoxicity in vivo.

Results

PAD4 deficiency reduced the severity of DSS-induced colitis with decreased intestinal NET formation and enhanced gut barrier function and integrity in mice. NETs disrupted the barrier function in intestinal epithelial Caco-2 monolayers through their protein, rather than DNA, components. Pretreatment of NETs with histone inhibitors abrogated the effects on epithelial permeability. Consistent with these observations, adding purified histone proteins to Caco-2 monolayers significantly damaged epithelial barrier function, which was associated with the abnormal distribution and integrity of tight junctions as well as with increased cell death. Furthermore, intrarectal administration of histones damaged the intestinal barrier integrity and induced cytotoxicity in the mouse colon epithelium.

Conclusions

PAD4-mediated NET formation has a detrimental role in acute colitis. NET-associated histones directly inhibit intestinal barrier function, resulting in cytotoxicity in vitro and in vivo.
Influence of HLADQA1*05 Genotype in Adults With Inflammatory Bowel Disease and Anti-TNF Treatment With Proactive Therapeutic Drug Monitoring: A Retrospective Cohort Study
Authors: Fuentes-Valenzuela Esteban , García-Alonso Francisco Javier , Maroto-Martín Carlos , Juan Casamayor Laura , Garrote José Antonio , Almendros Muñoz Rosendo , De Prado Ángel , Vara Castrodeza Alejando , Marinero María Ángeles , Calleja Carbajosa Raquel , Barrio Jesús
Published: January 2023

Background

Carriers of the human leucocyte antigen variant HLADQA1*05 (rs2097432) are at risk of developing antibodies against infliximab and adalimumab with reduced tumor necrosis factor (TNF) antagonist persistence. The impact of proactive therapeutic drug monitoring (PTDM) on this association has been barely assessed.

Methods

We conducted a retrospective single-center cohort study including patients with inflammatory bowel disease starting anti-TNF therapy between January 2017 and March 2021. Proactive therapeutic drug monitoring was defined as periodic drug level measurement (≥2 determinations during the first year of treatment and ≥1/annual determination during the following years), regardless of clinical condition, followed by dose optimization. Variables associated with treatment persistence were assessed with multivariable Cox regression analysis.

Results

A total of 112 patients were included, 52 (46.4%) HLA-DQA1*05 carriers, with a median follow-up of 73.9 (interquartile range, 35.4-133.1) weeks. Combination therapy with thiopurines was more frequent among HLA-DQA1*05 noncarriers (28 [46.7%] vs 12 [23.1%]; P = .01). Clinical remission rates at week 14 (77.9% vs 73.9%; P = .69) and 56 (73.2% vs 68.4%; P = .64) were similar between HLA-DQA1*05 noncarriers and carriers. Drug persistence was higher among HLA-DQA1*05 carriers (hazard ratio [HR], 0.32; 95% confidence interval, 0.14-0.71; P = .01). Multivariable Cox regression analysis identified systemic steroids at anti-TNF initiation (HR, 4; 95% confidence interval, 1.7-9.7) as a risk factor and HLA-DQA1*05 carriers (HR, 0.31; 95% confidence interval, 0.12–0.81) as a protective factor of treatment cessation.

Conclusion

In adult patients with PTDM, a positive HLA-DQA1*05 genotype does not associate a higher risk of treatment cessation nor worse clinical outcomes.
Estimated Glomerular Filtration Rate and the Risk of Inflammatory Bowel Disease in Adults: A Swedish Population-Based Study
Authors: Yang Yuanhang , Ludvigsson Jonas F , Olén Ola , Sjölander Arvid , Carrero Juan J
Published: January 2023

Background

Kidney complications are common in patients with long-standing inflammatory bowel disease (IBD). Whether kidney complications, defined as low estimated glomerular filtration rate (eGFR), may predispose to later IBD is unknown.

Methods

We analyzed the association between eGFR and the risk of being subsequently diagnosed with IBD among 1 612 160 adults from Stockholm. The exposure was categories of eGFR, with 90 to 104 mL/min/1.73 m2 as the reference. Cox regression models were used to investigate the association between eGFR, IBD, and IBD subtypes. Subgroup analyses included age strata, sex, education, and comorbidities. To explore the possibility of detection bias or reverse causation, we estimated IBD hazard ratios (HRs) after excluding cases and individuals censored during early years of follow-up.

Results

During a median of 9 years of follow-up, we detected 9663 cases of IBD (3299 Crohn’s disease, 5072 ulcerative colitis, 1292 IBD unclassified). Lower eGFR levels were associated with higher IBD risk (for eGFR 30-59 mL/min/1.73 m2: adjusted HR, 1.15; 95% confidence interval [CI], 1.01-1.33; and for eGFR <30 mL/min/1.73 m2: adjusted HR, 1.65; 95% CI, 1.16-2.37). This association was stronger in magnitude for Crohn’s disease (for eGFR 30-59 mL/min/1.73 m2: HR, 1.33, 95% CI, 1.04-1.72; and for eGFR <30 mL/min/1.73 m2: HR, 2.25; 95% CI, 1.26-3.99). Results were consistent across strata of age, comorbidities, and attained education but suggested the association between eGFR and IBD to be stronger in women (P for interaction <.05). Results attenuated but were robust to exclusion of early IBD cases.

Conclusions

We observed an association between reduced eGFR and the risk of developing IBD, which was stronger in magnitude for Crohn’s disease.
Mixed-stock analysis of Atlantic herring (Clupea harengus): a tool for identifying management units and complex migration dynamics
Authors: Bekkevold Dorte , Berg Florian , Polte Patrick , Bartolino Valerio , Ojaveer Henn , Mosegaard Henrik , Farrell Edward D , Fedotova Jelena , Hemmer-Hansen Jakob , Huwer Bastian , Trijoulet Vanessa , Albertsen Christoffer Moesgaard , Fuentes-Pardo Angela P , Gröhsler Tomas , Pettersson Mats , Jansen Teunis , Folkvord Arild , Andersson Leif
Published: January 2023

We developed and validated a mixed-stock analysis (MSA) method with 59 single-nucleotide polymorphisms selected from genome-wide data to assign individuals to populations in mixed-stock samples of Atlantic herring from the North and Baltic seas. We analysed 3734 herring from spawning locations and scientific catches of mixed feeding stocks to demonstrate a “one-fits-all” tool with unprecedented accuracy for monitoring spatio-temporal dynamics throughout a large geographical range with complex stock mixing. We re-analysed time-series data (2002–2021) and compared inferences about stock composition with estimates from morphological data. We show that contributions from the western Baltic spring-spawning stock complex, which is under management concern, have likely been overestimated. We also show that a genetically distinctive population of western Baltic autumn spawners, ascribed low fisheries importance, contributes non-negligible and potentially temporally increasing proportions to mixed-stock aggregations, calling for a re-evaluation of stock definitions. MSA data can be implemented in stock assessment and in a variety of applications, including marine ecosystem description, impact assessment of specific fleets, and stock-rebuilding plans.
Incorporating distribution shifts and spatio-temporal variation when estimating weight-at-age for stock assessments: a case study involving the Bering Sea pollock (Gadus chalcogrammus)
Authors: Indivero Julia , Essington Timothy E , Ianelli James N , Thorson James T
Published: January 2023

Environmental conditions can create spatial and temporal variability in growth and distribution processes, yet contemporary stock assessment methods often do not explicitly address the consequences of these patterns. For example, stock assessments often assume that body weight-at-age (i.e. size) is constant across the stocks’ range, and may thereby miss important spatio-temporal patterns. This is becoming increasingly relevant given climate-driven distributional shifts, because samples for estimating size-at-age can be spatially unbalanced and lead to biases when extrapolating into unsampled areas. Here, we jointly analysed data on the local abundance and size of walleye pollock (Gadus chalcogrammus) in the Bering Sea, to demonstrate a tractable first step in expanding spatially unbalanced size-at-age samples, while incorporating fine-scale spatial and temporal variation for inclusion in stock assessments. The data come from NOAA’s bottom trawl survey data and were evaluated using a multivariate spatio-temporal statistical model. We found extensive variation in size-at-age at fine spatial scales, though specific patterns differed between age classes. In addition to persistent spatial patterns, we also documented year-to-year differences in the spatial patterning of size-at-age. Intra-annual variation in the population-level size-at-age (used to generate the size-at-age matrix in the stock assessment) was largely driven by localized changes in fish size, while shifts in species distribution had a smaller effect. The spatio-temporal size-at-age matrix led to marginal improvement in the stock assessment fit to the survey biomass index. Results from our case study suggest that accounting for spatially unbalanced sampling improved stock assessment consistency. Additionally, it improved our understanding on the dynamics of how local and population-level demographic processes interact. As climate change affects fish distribution and growth, integrating spatiotemporally explicit size-at-age processes with anticipated environmental conditions may improve stock-assessment forecasts used to set annual harvest limits.
China’s Foreign Policies and Attitudes toward Chinese Diaspora: A Direct Link?
Authors: Sumaktoyo Nathanael Gratias , Muhtadi Burhanuddin
Published: January 2023

Do China’s foreign policies and actions as a state directly influence public opinion toward Chinese diaspora? Notwithstanding the multitude of studies and commentaries on the rise of China and its consequences on the regional and global orders, evidence, and insights on the topic have been lacking. We answer this question through two original, nationally representative survey experiments in Indonesia and by leveraging both contemporary dynamics related to China’s growing influence in Southeast Asia and historical discrimination against ethnic Chinese minorities in the country. We examine whether information about a positive (negative) international issue related to China as a state leads to more positive (negative) attitudes toward Chinese Indonesians. Our findings, consistently replicated in the two surveys, show that information about positive or negative international issues concerning China has only little impacts on attitudes toward ethnic Chinese. To the extent that these issues matter, they mostly affect perceptions toward China itself, not toward ethnic Chinese.
Characterizing the Spectrum of LatentMycobacterium tuberculosisin the Cynomolgus Macaque Model: Clinical, Immunologic, and Imaging Features of Evolution
Authors: Medrano Jessica Marie , Maiello Pauline , Rutledge Tara , Tomko Jaime , Rodgers Mark A , Fillmore Daniel , Frye L James , Janssen Christopher , Klein Edwin , Flynn JoAnne L , Lin Philana Ling
Published: January 2023

Mycobacterium tuberculosis infection outcomes have been described as active tuberculosis or latent infection but a spectrum of outcomes is now recognized. We used a nonhuman primate model, which recapitulates human infection, to characterize the clinical, microbiologic, and radiographic patterns associated with developing latent M. tuberculosis infection. Four patterns were identified. “Controllers” had normal erythrocyte sedimentation rate (ESR) without M. tuberculosis growth in bronchoalveolar lavage or gastric aspirate (BAL/GA). “Early subclinicals” showed transient ESR elevation and/or M. tuberculosis growth on BAL/GA for 60 days postinfection, “mid subclinicals” were positive for 90 days, and “late subclinicals” were positive intermittently, despite the absence of clinical disease. Variability was noted regarding granuloma formation, lung/lymph node metabolic activity, lung/lymph node bacterial burden, gross pathology, and extrapulmonary disease. Like human M. tuberculosis infection, this highlights the heterogeneity associated with the establishment of latent infection, underscoring the need to understand the clinical spectrum and risk factors associated with severe disease.
Development of a Corticosteroid-Immunosuppressed Mouse Model to Study the Pathogenesis and Therapy of Influenza-Associated Pulmonary Aspergillosis
Authors: Wurster Sebastian , Pantaleón García Jezreel , Albert Nathaniel D , Jiang Ying , Bhoda Keerthi , Kulkarni Vikram V , Wang Yongxing , Walsh Thomas J , Evans Scott , Kontoyiannis Dimitrios P
Published: January 2023

Influenza-associated pulmonary aspergillosis (IAPA) is a feared complication in patients with influenza tracheobronchitis, especially those receiving corticosteroids. Herein, we established a novel IAPA mouse model with low-inoculum Aspergillus infection and compared outcomes in mice with and without cortisone acetate (CA) immunosuppression. CA was an independent predictor of increased morbidity/mortality in mice with IAPA. Early antifungal treatment with liposomal amphotericin B was pivotal to improve IAPA outcomes in CA-immunosuppressed mice, even after prior antiviral therapy with oseltamivir. In summary, our model recapitulates key clinical features of IAPA and provides a robust preclinical platform to study the pathogenesis and treatment of IAPA.
Aesthetic Cognitivism and Serialized Television Fiction
Authors: Vidmar Jovanović Iris
Published: January 2023

In this article, I defend the cognitive value of certain generic television series. Unlike media and television scholars, who have been appreciative of the informative capacity of television fiction, philosophers have been less willing to acknowledge the way in which these works contribute to our understanding of our social reality. My aim here is to provide one such account, grounded in aesthetic cognitivism, that is, the view that fiction is a source of knowledge. Focusing on crime and courtroom dramas, I start by offering some examples of the cognitive benefits available in some of these series and I argue that the more beneficial cases establish superior mimetic relations with reality, enhancing their capacity to present ethically challenging issues. I then examine whether the fictional dimension of these works presents an obstacle to their informative potential and I conclude that it does not. A central aspect of my account is the claim that the degree of cognitive benefit depends on the underlying narrative strategy of the series. Specifically, there are clues in any given show, including the treatment of ongoing characters, which signal the extent to which it can be taken as mimetically reliable and thus, cognitively valuable. I complete my account by addressing anti-cognitivists’ arguments which call to doubt the informative aspect of television series and their capacity to address ethical concerns.
Big Tent Aesthetics
Authors: Lopes Dominic McIver
Published: January 2023

Theoretical work on aesthetic value has taken off in the past 5 or 10 years. Since work on artistic value dates at least as far back as the first debates about the interaction between artistic and other values, aesthetic value presumably differs from artistic value. Unlike artistic value, aesthetic value is found in art, but also in nature, design, and intellectual material, even philosophy (Lopes 2022a). Indeed, continued use of “aesthetic” as a synonym for “artistic” has held up work on aesthetic value, as has the hegemony of aesthetic hedonism (Van der Berg 2020). Now a raft of new ideas are on offer, and each has something going for it. We should not be too quick to winnow: we can build a tent that is big enough to house them all.
Effect of sulfadoxine-pyrimethamine chemoprophylaxis in pregnant women on selection of the newP. falciparum dhpsquintuple mutant carrying the I431V mutation
Authors: Cohen Olivia , Guemas Emilie , Menard Sandie , Tsague Kenfack Martial , Talom Ngassa Carine , Iriart Xavier , Bidzogo Lebobo Marlise , Ondobo Ekae Celestin , Eboumbou Carole , Tiyou Kenmeni Calvin , Berry Antoine
Published: January 2023

Background

A new mutation in the Plasmodium falciparum dihydropteroate synthetase gene (pfdhps), I431V, has been identified in several countries of Central and West Africa. This mutation is mostly found in association with four other SNPs on pfdhps (S436A, A437G, A581G and A613S), forming a quintuple mutant (vagKgs) and almost always associated with the Plasmodium falciparum dihydrofolate reductase gene (pfdhfr) CirnI (C50R, N51I, S108N) triple mutant. To date, nothing is known about the impact of this new pfdhps genotype on sulfadoxine-pyrimethamine (SP) resistance.

Objectives

We sought to assess the prevalence of this pfdhps vagKgs quintuple mutant in two groups of pregnant women with malaria, one that took intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and one that did not.

Methods

The pfdhfr and pfdhps genes from Plasmodium falciparum isolates collected in Yaoundé (Cameroon) from pregnant women with symptomatic malaria under IPTp-SP or not, were sequenced.

Results

Of 159 patients evaluated, 70 had already taken SP during pregnancy and 89 had never taken SP. Only the vagKgs allele was significantly overrepresented in the SP+ group (21.4% versus 3.4%; P < 0.001), whereas the ISgKAA mutant, widely distributed in this area and known to be less susceptible to SP, tended to be less abundant in this group (48.6% versus 64.0%; P = 0.0503).

Conclusions

We found a strong overrepresentation of the CirnI/vagKgs haplotype in the IPTp-SP pregnant group, suggesting a high level of resistance of this mutant to SP. This could compromise not only the effectiveness of IPTp-SP but also the seasonal malaria chemoprevention of young children, now widely implemented.
Evaluation of publication bias for 12 clinical trials of molnupiravir to treat SARS-CoV-2 infection in 13 694 patients with meta-analysis
Authors: Lawrence Jack M , Mirchandani Manya , Hill Andrew
Published: January 2023

In response to the COVID-19 pandemic, Merck Sharp & Dohme (MSD) acquired the global licensing rights for the antiviral molnupiravir, promising affordable access via licensing deals. Numerous Indian pharmaceutical companies subsequently conducted trials of the drug. Registered trials of molnupiravir were searched on the Clinical Trials Registry–India (CTRI) and efforts made to detect resulting public data. Per the CTRI, 12 randomized trials of molnupiravir were conducted in 13 694 Indian patients, from mid-2021. By August 2022, only a preprint and medical conference presentation had resulted. Additionally, two trials were mentioned in press releases suggesting failure of treatment. The available data contain unexplained results that differ significantly from both the PANORAMIC and MSD MOVe-OUT trials. Approximately one-third of the global data on molnupiravir remain unpublished. We conducted a meta-analysis with four studies that provided results and observed that molnupiravir does not have a significant benefit for hospitalizations.
Utility of the BioFire® FilmArray® Pneumonia Panel plus assay for syndromic testing of lower respiratory tract infections in a low/middle-income setting
Authors: Van Der Westhuyzen M , Samodien N , Brink A J , Moodley C
Published: January 2023

Background

Determining lower respiratory tract infection (LRTI) aetiology is complex. Culture-based methods are laborious with poor sensitivity. Molecular assays improve detection of potential pathogens, but incorrect interpretation of results may lead to inappropriate antimicrobial therapy.

Methods

The utility of the BioFire® FilmArray® Pneumonia Panel plus (FA-PP) to detect LRTI pathogens, and the potential impact on antimicrobial stewardship in a low-resource setting, were assessed. Routine LRT samples were included from adult patients with clinically suspected LRTI or with a concomitant blood culture at Groote Schuur Hospital and referring facilities. Culture and FA-PP results were compared, and pharmacy data analysed to determine appropriateness of antibiotic therapy.

Results

There was an 80% correlation between cultured LRTI pathogens and the FA-PP bin ≥107 results. Compared with culture, the FA-PP detected substantially more pathogens (86.6% versus 17.9%) and produced a combined 100% positive percent agreement, and 88% negative percent agreement. The FA-PP detected bacterial/viral coinfections in 27% of samples. Correlation of FA-PP results with pharmacy data (n = 69) indicated a potential antibiotic change in 75% of cases, but this is difficult to accurately characterize without a ‘gold standard’ for treatment or complete clinical data.

Conclusions

The FA-PP increased the number of positive samples with typical bacteria, but the semi-quantitative reporting algorithm does not describe the correlation between the different bin values and colonization versus infection. This complicates result interpretation and may lead to inappropriate antimicrobial treatment. This study highlights the potential positive impact of rapid molecular assays for routine care in lower-income settings, but also underscores the interpretive challenges associated with these tests.
Point prevalence survey of antibiotic use among hospitalized patients across 41 hospitals in Thailand
Authors: Anugulruengkitt Suvaporn , Charoenpong Lantharita , Kulthanmanusorn Anond , Thienthong Varaporn , Usayaporn Sang , Kaewkhankhaeng Wanwisa , Rueangna Oranat , Sophonphan Jiratchaya , Moolasart Visal , Manosuthi Weerawat , Tangcharoensathien Viroj
Published: January 2023

Objectives

To describe the antibiotic use among hospitalized patients in Thailand.

Methods

A standardized cross-sectional point prevalence survey (PPS) modified from the WHO PPS protocol was conducted in 41 selected hospitals in Thailand. All inpatients who received an antibiotic at 9 a.m. on the survey date were enrolled. The total number of inpatients on that day was the denominator.

Results

Between March and May 2021, a total of 8958 inpatients were enumerated; 4745 inpatients received antibiotics on the day of the survey and there were 6619 prescriptions of antibiotics. The prevalence of antibiotic use was 53.0% (95% CI 51.1%–54.0%), ranging from 14.3% to 73.4%. The antibiotic use was highest among adults aged >65 years (57.1%; 95% CI 55.3%–58.9%). From 6619 antibiotics prescribed, 68.6% were used to treat infection, 26.7% for prophylaxis and 4.7% for other or unknown indications. Overall, the top three commonly used antibiotics were third-generation cephalosporins (1993; 30.1%), followed by first-generation cephalosporins (737; 11.1%) and carbapenems (703; 10.6%). The most frequently used antibiotics for community-acquired infections were third-generation cephalosporins (36.8%), followed by β-lactam/β-lactamase inhibitors (11.8%) and carbapenems (11.3%) whereas for the patients with hospital-acquired infections, the most common antibiotics used were carbapenems (32.7%), followed by β-lactam/β-lactamase inhibitors (15.7%), third-generation cephalosporins (11.7%) and colistin (11.7%). The first-generation cephalosporins were the most commonly used antibiotics (37.7%) for surgical prophylaxis. Seventy percent of the patients received surgical prophylaxis for more than 1 day post surgery.

Conclusions

The prevalence of antibiotic use among hospitalized patients in Thailand is high and one-quarter of these antibiotics were used for prophylaxis. The majority of surgical prophylaxis was inappropriately used for a long duration post operation. Therefore, it is recommended that local guidelines should be developed and implemented.
Firm Size Distribution in African Manufacturing Firms: Revisiting the ‘Missing Middle’
Authors: Tsaedu Kahsay G , Chen Zhihong , Azmete Hana W
Published: January 2023

There has been a widespread view that firm size distribution (FSD) in developing countries has been characterised as having a ‘missing middle’. We have investigated this question using evidence from the entire population of Ethiopian manufacturing firms, including small informal firms. Based on the analysis, we have documented the following four facts. First, there is no evidence of a bimodal distribution in the FSD. Second, small firms overwhelmingly, and increasingly, dominate the distribution. Third, the distribution of the average product of factor input is neither bimodal nor an inverted U-shaped. Fourth, we have investigated the potential regulatory notches of employment sizes of the sort often thought to discourage firm growth and have found no unusual bunching of firms near the notch points. More recently it has been argued by Tybout that instead of looking at the actual FSD to capture a ‘missing middle’, the actual should be compared with an undistorted one, which could be characterised as Paretian. We show, using this approach, that there is a ‘missing middle’ when using employment shares. However, when we look at firm share, by size category, over time large firms have been missing as well.
Potential Impact of Pharmacogenomic Single Nucleotide Variants in a Rural Caucasian Population
Authors: Williams Grace R , Tsongalis Gregory J , Lewis Lionel D , Barney Rachael E , Cook Leanne J , Aaron Geno K , Nerenz Robert D
Published: January 2023

Background

In the US adverse drug reactions (ADRs) are estimated to cause 100 000 fatalities and cost over $136 billion annually. A patient’s genes play a significant role in their response to a drug. Pharmacogenomics aims to optimize drug choice and dose for individual patients by characterizing patients’ pharmacologically relevant genes to identify variants of known impact.

Methods

DNA was extracted from randomly selected remnant whole blood samples from Caucasian patients with previously performed complete blood counts. Samples were genotyped by mass spectrometry using a customized pharmacogenomics panel. A third-party result interpretation service used genotypic results to predict likely individual responses to frequently prescribed drugs.

Results

Complete genotypic and phenotypic calls for all tested Cytochrome P450 isoenzymes and other genes were obtained from 152 DNA samples. Of these 152 unique genomic DNA samples, 140 had genetic variants suggesting dose adjustment for at least one drug. Cardiovascular and psychiatry drugs had the highest number of recommendations, which included United States Food and Drug Administration warnings for highly prescribed drugs metabolized by CYP2C19, CYP2C9, CYP2D6, HLA-A, and VKORC1.

Conclusions

Risk for each drug:gene pairing primarily depends upon the degree of predicted enzyme impairment or activation, width of the therapeutic window, and whether parent compound or metabolite is pharmacologically active. The resulting metabolic variations range from risk of toxicity to therapeutic failure. Pharmacogenomic profiling likely reduces ADR potential by allowing up front drug/dose selection to fit a patient’s unique drug-response profile.
Validation of the Reveal® 3-D for Gluten Assay for Detection of Gluten in Clean-in-Place Rinses and Stainless Steel Environmental Surfaces: AOAC Performance Tested MethodSM 122201
Authors: Le Quynh-Nhi , Beck Nancy , Schwingel Zack , Roman Brooke , Mozola Mark , Sperry Amanda , Almy Dave , Donofrio Robert
Published: January 2023

Background

Reveal® 3-D for Gluten is an immunochromatographic assay for the qualitative detection of gluten in environmental samples. The test uses monoclonal antibodies reactive to prolamins in wheat.

Objective

The objective of the study was to validate the Reveal 3-D test for detection of gluten in clean-in-place rinse and swabs from a stainless steel surface.

Methods

Elements of the study included food selectivity and interference testing, matrix testing, an assay robustness study, and reagent stability/lot-to-lot consistency testing. Wheat flour was used as the spiking material for all matrixes.

Results

In selectivity and interference testing, nine target matrixes all tested positive and 36 of 39 non-target matrixes tested negative. Almond flour, sesame flour, and cornstarch produced positive results as 100% commodities; reactivity can be eliminated with dilution or by testing without use of food extraction buffer, which is not a standard part of the environmental testing method. With a gluten spike at 9.3 mg/kg, chestnut flour, guar gum, and xanthan gum as 100% commodities inhibited the ability of the assay to detect gluten when tested without dilution. In quaternary ammonium clean-in-place rinse and swabs from stainless steel, 100% positive results were obtained at levels of 2.8 mg/kg and 4.7 µg/100 cm2, respectively. Results of independent laboratory testing of swabs from stainless steel supported those of internal trials. Robustness testing showed that introducing variations to three operating parameters simultaneously had no adverse effect on assay performance. In the reagent stability study, data supported kit expiration dating of 11 months.

Conclusion

Results of the current study show that the Reveal test is an accurate and reliable method for qualitative detection of gluten in select clean-in-place rinse and environmental samples.

Highlights

The Reveal test was able to detect gluten at levels of 2.8 ppm in clean-in-place rinse and 4.7 µg/100 cm2 in swabs from stainless steel.
Comparative Investigation Between Raw and Stir-Frying Processed Cuscutae Semen Based on HPLC Fingerprints Coupled With Chemometric Methods
Authors: Changli Xu , Yun Shi , Hua Xu , Guangrui Zhao , Shurui Niu , Jingchun Yao , Xun Gao , Weidong Li , Kunming Qin
Published: January 2023

Background

The curative effect of Cuscutae Semen (CS) could be adjusted after stir-frying, and it is difficult to distinguish between the raw CS and stir-fried processed Cuscutae Semen (SFCS) in clinical practice.

Objective

The paper aims to establish the fingerprints of raw and fried Cuscutae Semen products by high-performance liquid chromatography (HPLC) so that the compounds in raw and stir-fried products could be analyzed qualitatively and quantitatively. At the same time, the chemometrics method was used to evaluate the difference between CS and SFCS to provide reference for the research of traditional Chinese medicine (TCM) CS.

Method

The raw and SFCS products’ related substances were separated on a C18 column (250 mm × 4.6 mm, 5 µm) maintained at 30 °C (column temperature). The mobile phase comprised 0.1% formic acid aqueous solution (A) and acetonitrile (B), and a detection wavelength of 328 nm. The data were imported into statistical software for chemometric analysis.

Results

The developed HPLC method exhibits good linearity and has good systematic applicability. The content of these 12 compounds in the samples was further determined and the data analyzed by chemometrics. The results showed that the composition of CS changed on heating, and HCA showed that CS and SFCS could be clearly distinguished. PCA showed that six components caused differences, namely neochlorogenic acid, cryptophyllogenic acid, caffeic acid, quercetin, isorhamnetin, and kaempferol.

Conclusions

This study unequivocally establishes a chromatographic fingerprint method intended for the extensive analysis of raw and stir-fried processed CS, which could substantially enhance the quality control of CS and the rational development and utilization of TCM resources.

Highlights

This method for the simultaneous quantification of multiple compounds in CS and SFCS revealed the components responsible for the differences between raw and processed products. This will provide support for quality control of this herbal medicine.