bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell multiomics reveal divergent effects of DNMT3A- and TET2-mutant clonal hematopoiesis in inflammatory response
Authors: Mohammed Ismail Wazim , Fernandez Jenna A. , Binder Moritz , Lasho Terra L. , Kim Minsuk , Geyer Susan M. , Mazzone Amelia , Finke Christy M. , Mangaonkar Abhishek A. , Lee Jeong-Heon , Wang Liguo , Kim Kwan Hyun , Simon Vernadette A. , Rakhshan Rohakthar Fariborz , Munankarmy Amik , Byeon Seul Kee , Schwager Susan M. , Harrington Jonathan J. , Snyder Melissa R. , Robertson Keith D. , Pandey Akhilesh , Wieben Eric D. , Chia Nicholas , Gaspar-Maia Alexandre , Patnaik Mrinal M. 
Published: December 2024

Abstract
DNMT3A and TET2 are epigenetic regulator genes commonly mutated in age-related clonal hematopoiesis (CH). Despite having opposed epigenetic functions, these mutations are associated with increased all-cause mortality and a low risk for progression to hematologic neoplasms. Although individual impacts on the epigenome have been described using different model systems, the phenotypic complexity in humans remains to be elucidated. Here, we make use of a natural inflammatory response occurring during coronavirus disease 2019 (COVID-19), to understand the association of these mutations with inflammatory morbidity (acute respiratory distress syndrome [ARDS]) and mortality. We demonstrate the age-independent, negative impact of DNMT3A mutant (DNMT3Amt) CH on COVID-19–related ARDS and mortality. Using single-cell proteogenomics we show that DNMT3A mutations involve myeloid and lymphoid lineage cells. Using single-cell multiomics sequencing, we identify cell-specific gene expression changes associated with DNMT3A mutations, along with significant epigenomic deregulation affecting enhancer accessibility, resulting in overexpression of interleukin-32 (IL-32), a proinflammatory cytokine that can result in inflammasome activation in monocytes and macrophages. Finally, we show with single-cell resolution that the loss of function of DNMT3A is directly associated with increased chromatin accessibility in mutant cells. Hence, we demonstrate the negative prognostic impact of DNMT3Amt CH on COVID-19–related ARDS and mortality. DNMT3Amt CH in the context of COVID-19, was associated with inflammatory transcriptional priming, resulting in overexpression of IL32. This overexpression was secondary to increased chromatic accessibility, specific to DNMT3Amt CH cells. DNMT3Amt CH can thus serve as a potential biomarker for adverse outcomes in COVID-19.
Choroidal vasculitis as a biomarker of inflammation of the choroid. Indocyanine Green Angiography (ICGA) spearheading for diagnosis and follow-up, an imaging tutorial
Authors: Papasavvas Ioannis , Tucker William R. , Mantovani Alessandro , Fabozzi Lorenzo , Herbort Carl P. 
Published: December 2024

Abstract
Background
Indocyanine green angiography (ICGA) is the gold standard to diagnose, evaluate and follow up choroidal inflammation. It allows clinicians to precisely determine the type and extension of choroidal vasculitis in the two main choroidal structures, the choriocapillaris and the choroidal stroma. The presence of choroidal vasculitis is often overlooked by the physician who often does not include ICGA in the investigation of posterior uveitis.

Purpose
To describe choroidal vasculitis by analysing its ICGA signs in order to investigate and follow choroiditis and determine the pathophysiological mechanisms of inflammation of choroidal vessels.

Methods
The tutorial is presenting the normal findings in a non-inflamed choroid and the semiology of diverse choroidal vasculitis conditions, followed by practical illustrations using typical cases.

Results
The two identified patterns of choroidal vasculitis corresponded on one side to choriocapillaritis appearing as areas of hypofluorescence depicting the involvement and extension of choriocapillaris inflammatory non-perfusion. The vasculitis of the choriocapillaris goes from limited and reversible when distal endcapillary vessels are involved such as in Multiple Evanescent White Dot Syndrome (MEWDS) to more severe involvement in Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE), Multifocal Choroiditis (MFC) or Serpiginous Choroiditis (SC) with more pronounced non-perfusion causing scars if not treated diligently. On the other side, stromal choroidal vasculitis is characterised by leaking hyperfluorescent vessels that appear fuzzy and at the origin of late diffuse choroidal hyperfluorescence.

Conclusion
Choroidal vasculitis is present in almost all patients with inflammatory choroidal involvement, occlusive in case of choriocapillaritis and leaky in stromal choroiditis causing vessel hyperfluorescence, fuzziness of the choroidal vessels and late diffuse stromal hyperfluorescence on ICGA. Systemic vasculitis entities produce occlusive vasculitis of large choroidal vessels.
Role of turnover, downsizing, overtime and night shifts on workplace violence against healthcare workers: a seven-year ecological study
Authors: Giusti Emanuele M. , Veronesi Giovanni , Forest Hannah , Ghelli Monica , Persechino Benedetta , Borchini Rossana , Magnavita Nicola , Ferrario Marco Mario 
Published: December 2024

Abstract
Background
About one-third of workers identify organisational factors as contributors to workplace violence (WPV), but the associations between these factors and WPV have primarily been explored retrospectively and with measures of perceived organisational constraints, hence providing limited information for prevention. Therefore, we assessed whether objectively measured ward-level indicators of turnover, downsizing, overtime, and night shifts are associated with the occurrence of WPV and whether these associations vary by ward type.

Methods
We conducted an ecological study at a university hospital in northern Italy from 2016 to 2022, using wards as statistical unit (average: 230 wards per year). Active surveillance of WPV was based on an in-hospital incident reporting procedure, updated in November 2021 based on Health Regional Administration guidelines; 2021 was therefore excluded as a transition year. Individual-level administrative data were used to compute ward-level yearly indicators of turnover, downsizing, overtime and night shifts per active worker. Using generalised linear models, we estimated rate ratios (RRs) for yearly WPV counts per 1 SD increase in the indicators, controlling for study period, ward type (emergency department [ED], psychiatric ward, other) and ward sociodemographic composition.

Results
A total of 337 WPV episodes occurred in the 1381 ward-year observations. The WPV rates per 100 active workers per year increased from 1.40 (95%CI: 1.23–1.60) during 2016–2020 to 3.48 (2.90–4.17) in 2022. Higher turnover (RR, 95%CI: 1.47, 1.23–1.75) and downsizing (1.12, 1.00-1.24) were associated with a greater occurrence of WPV across all wards; these associations were consistent across the study periods. In wards with night shift scheduling, turnover (1.64, 1.40–1.92), downsizing (1.21, 1.04–1.40) and the mean number of night shifts (2.50, 1.37–4.56) were associated with WPV. The association between night shifts and WPV was greater in psychiatric wards (RR = 8.73; interaction p-value = 0.02), whereas the role of downsizing was greater in EDs (RR = 1.42, interaction p-value = 0.09) and the role of turnover was greater in the other wards (RR = 1.34, interaction p-value = 0.16).

Conclusion
Work organisational factors are associated with the occurrence of WPV episodes against healthcare workers. Ward type-tailored priorities should be given to minimising turnover and downsizing and promoting a fairer allocation of night shifts to decrease WPV occurrence.
Incorporating clinical and demographic data into the Elixhauser Comorbidity Model: deriving and validating an enhanced model in a tertiary hospital’s internal medicine department
Authors: Leibner Gideon , Katz David E. , Esayag Yaakov , Kaufman Nechama , Brammli-Greenberg Shuli , Rose Adam J. 
Published: December 2024

Abstract
Background and objectives
The Elixhauser Comorbidity Model is a prominent, freely-available risk adjustment model which performs well in predicting outcomes of inpatient care. However, because it relies solely on diagnosis codes, it may not capture the full extent of patient complexity. Our objective was to enhance and validatethe Elixhauser Model by incorporating additional clinical and demographic data to improve the accuracy of outcome prediction.

Methods
This retrospective observational cohort study included 55,945 admissions to the internal medicine service of a large tertiary care hospital in Jerusalem. A model was derived and validated to predict four primary outcomes. The four primary outcomes measured were length of stay (LOS), in-hospital mortality, readmission within 30 days, and increased care.

Results
Initially, the Elixhauser Model was applied using standard Elixhauser definitions based on diagnosis codes. Subsequently, clinical variables such as laboratory test results, vital signs, and demographic information were added to the model. The expanded models demonstrated improved prediction compared to the baseline model. For example, the R2 for log LOS improved from 0.101 to 0.281 and the c-statistic to predict in-hospital mortality improved from 0.711 to 0.879.

Conclusions
Adding readily available clinical and demographic data to the base Elixhauser model improves outcome prediction by a considerable margin. This enhanced model provides a more comprehensive representation of patients’ health status. It could be utilized to support decisions regarding admission and to what setting, determine suitability for home hospitalization, and facilitate differential payment adjustments based on patient complexity.
Estrogen administration enhances the adverse effects of cigarette smoking on the heart in cycling female mice
Authors: Abidi Emna , Diab Reine , Zahreddine Rana , Amin Ghadir , Kaplan Abdullah , Booz George W. , Zouein Fouad A. 
Published: December 2024

AbstractSmoking, particularly chronic smoking (CS), is a threat to global health, contributing to increased mortality and morbidity associated with cardiovascular disease (CVD). CS induces oxidative stress and endothelial dysfunction, which has a profound impact on cardiac structure and function. While the protective effects of estrogen, particularly 17β-estradiol (E2), on cardiovascular health are well-documented in premenopausal women, the interaction between estrogen and CS remains poorly understood. The aim of this study is to investigate the impact of chronic cigarette smoking on cardiac health in relation to ethinylestradiol (EE) oral contraceptive (OC) usage in premenopausal females. Female mice were exposed to chronic cigarette smoke and co-administered EE. Cardiac structural and functional parameters were assessed alongside inflammatory markers, oxidative stress indicators, and histological changes. Results revealed that the combination of EE and CS led to adverse cardiac remodeling characterized by increased left ventricular end-diastolic volume and elevated left ventricular mass. In addition, an inflammatory state was evident, marked by increased expression of IL-4, IL-1β, IL-13, IL-10, and PARP-1, as well as increased interstitial collagen deposition. These findings suggest a progression towards adverse cardiac remodeling resembling dilated cardiomyopathy. Furthermore, our observations highlight the complexity of the inflammatory response triggered by smoking, potentially exacerbated by estrogen supplementation. The main finding of this study is that the combination of CS and EE enhanced adverse cardiac remodeling, which was shown structurally, histologically, and biochemically.
How is the concept of charisma used in the academic literature about biodiversity conservation? A systematic map protocol
Authors: Isaac Maxim , Fukushima Caroline S. , Macura Biljana , Di Minin Enrico , Correia Ricardo A. 
Published: December 2024

Abstract
Background
The extinction of species is a multifaceted phenomenon shaped by the complex interplay between biological and socio-cultural factors. Public and academic preferences for different species often play a direct or indirect role in influencing the conservation outlook of these species. The “charisma” of species and other components of biodiversity is often mentioned as an important factor in shaping human preferences, determining both the scope of scientific studies and justifications for such scope. Here, we present a protocol for systematically mapping the use of the concept of “charisma” in relation to biodiversity peer-reviewed academic literature focused on biodiversity conservation.

Methods
The search targeting academic peer-reviewed research articles and reviews will be conducted in three publication databases, The Lens, Scopus and Web of Science (Core Collection and SciELO), and will be supplemented by search engine results from Google Scholar. Broad-scope searches will be performed in 3 different languages (English, Portuguese, and Spanish) and article screening will be performed at two stages to ensure the relevance of each entry and consistency amongst reviewers in their use of the defined inclusion criteria. The resulting systematic map of the literature will be summarised by employing a narrative synthesis approach, and through descriptive statistics and analysis of temporal trends.
The 1,7-malaria reactive community-based testing and response (1,7-mRCTR) approach in Tanzania: a cost-effectiveness analysis
Authors: Tampi Radhika Pradip , Wang Duoquan , Abdulla Salim , Mahende Muhidin Kassim , Gavana Tegemeo , Msuya Hajirani M. , Kuwawenaruwa Augustine , Mihayo Michael , Brown Felix , Masanja Honorati , Anthony Wilbald , Bruxvoort Katia , Kihwele Fadhila , Chila Godlove , Chang Wei , Castro Marcia , Ning Xiao , Chaki Prosper P. , Mlacha Yeromin P. , Cohen Jessica , Menzies Nicolas A. 
Published: December 2024

Abstract
Background
Reactive case detection (RACD) for malaria control has been found effective in low transmission settings, but its impact and cost-effectiveness in moderate-to-high transmission settings are unknown. We conducted an economic evaluation alongside an empirical trial of a modified RACD strategy (1,7-mRCTR) in three moderate-to-high malaria transmission districts in Tanzania.

Methods
The costs and cost savings associated with the intervention relative to passive case detection alone were estimated in the study sites of Kilwa, Kibiti, and Rufiji districts in Tanzania from 2019–2021. Empirical cost data were collected using household surveys. The incremental costs of the intervention were calculated from under a societal perspective. Costs are reported in 2022 US dollars.
Trial data and malaria registers from health facilities were used to calculate the number of malaria cases detected. We simulated unobserved and distal health effects of the intervention to assess cost-effectiveness in terms of incremental cost-effectiveness ratios (ICERs).
Propagated uncertainty was assessed via second-order Monte Carlo simulation, including bootstrapping of empirical data distributions. Incremental costs per disability-adjusted life year (DALY) averted were compared to a willingness-to-pay threshold based on estimated opportunity costs of healthcare spending in Tanzania.

Results
The programmatic cost of the 1,7-mRCTR intervention was 5327 United States Dollars (USD) per 1000 population. The combination of reactive and passive case detection in the intervention arm resulted in an additional 445 malaria cases detected per 1000 compared to passive detection alone, yielding an incremental cost per additional case detected of 12.0 USD. Based on modelling results, for every percentage point decline in malaria prevalence, the intervention averted 95.2 cases and 0.04 deaths per 1000 population. On average, the 1,7-mRCTR intervention averted 19.1 DALYs per 1000 population. Compared to passive malaria detection, the ICERs for the 1,7-mRCTR intervention were 7.3 USD per case averted, 16,884 USD per death averted, and 163 USD per DALY averted.

Conclusions
Our analysis demonstrates that the 1,7-mRCTR intervention appears to be cost-effective under a willingness-to-pay threshold of 417 USD per DALY averted, showing that modified RACD strategies can provide value for money in moderate-to-high transmission settings.

Graphical Abstract
Trajectory, interactions, and predictors of higher symptom burden during induction therapy for multiple myeloma
Authors: Kamal Mona , Shi Qiuling , Shen Shu-En , Cleeland Charles , Wang Xin Shelley 
Published: December 2024

Abstract
Background
Patients with multiple myeloma (MM) experience disabling symptoms that are difficult to manage and may persist after induction therapy. Monitoring disease-related and induction therapy–induced symptoms and identifying patients at greater risk for high symptom burden are unmet clinical needs. The objective of this study was to examine the trajectories of symptom severity over time and identify predictors of high symptom burden during MM induction therapy.

Methodology
Eligible patients with MM rated their symptoms by completing the MD Anderson Symptom Inventory MM module repeatedly during 16 weeks of induction therapy. Group-based trajectory modeling identified patient groups with persistently high-severity (versus low-severity) symptom trajectories over time. Quality of life (QOL) and affective and physical functioning status were assessed. Predictors of high symptom burden were examined by regression analysis.

Results
Sixty-four MM patients participated. Most patients (89%) received bortezomib-based therapy. The five most-severe symptom trajectory groups were pain (59%), muscle weakness (46%), numbness (42%), disturbed sleep (41%), and fatigue (31%). Patients in the high-severity trajectory group for the five most-severe symptoms (31% of the sample) were more likely to have high-severity cognitive and affective symptoms. Patients in the high-severity trajectory groups for fatigue, muscle weakness, disturbed sleep, and bone aches were more likely to have high pain scores (all p < 0.05). Significant increases over time were observed in scores for pain (estimate: 0.026), numbness (0.051), muscle weakness (0.020), physical items (0.028), and affective items (0.014) (all p < 0.05). A higher baseline composite score of the five most-severe symptoms predicted worse QOL (− 6.24), and poor affective (0.80) and physical (1.10) statuses (all p < 0.01). Female sex predicted higher risk for being in the high-severity trajectory group for muscle weakness.

Conclusion
Almost one-third of MM patients suffer from up to 5 moderate to severe symptoms persistently, including pain, muscle weakness, numbness, disturbed sleep, and fatigue. Importantly, these results identify a group of symptoms that should be monitored and managed as part of routine patient care during MM induction therapy and suggest that pre-therapy pain management is necessary for better symptom control.
Peltigera lichens as sources of uncharacterized cultured basidiomycete yeasts
Authors: Pérez Yosbany , Almendras Katerin , Millanes Ana M. , Serey Nayla , Yurkov Andrey , Lizana Natalia , Nesci Andrea , Fessia Aluminé , Orlando Julieta 
Published: December 2024

AbstractLichens represent one of the most successful examples of symbiosis. They are constituted by the association between a dominant fungus (i.e., the mycobiont), one or more photosynthetic partners (algae or cyanobacteria), and harbor an array of associated microorganisms, including bacteria and fungi. The associated fungal communities in lichens, known as the “lichen mycobiome”, are composed of both ascomycetes and basidiomycetes, including filamentous and yeast taxa. Recently, basidiomycete yeasts have received considerable attention as a much-overlooked source of diversity within the lichen mycobiome, with hypothesized roles in lichen symbiosis. This study surveyed the diversity of cultivable basidiomycete yeasts associated with Peltigera lichens across southern Chile. A phylogenetic study based on sequences of 179 yeast isolates allowed the identification of 29 taxa from 13 genera in the classes Agaricostilbomycetes, Cystobasidiomycetes, Microbotryomycetes, and Tremellomycetes, with the latter being the most represented. This research revealed several yeast species, including members of the genera Boekhoutia andGoffeauzyma, in lichens for the first time, thereby expanding our understanding of lichen-associated fungal diversity. In addition, four new cultivable species isolated from Peltigera are formally described. These are Boekhoutia peltigerae sp. nov., Cystobasidium chilense sp. nov., Genolevuria patagonica sp. nov. and Pseudotremella navarinensis sp. nov. These results highlight the role of lichens as reservoirs of uncharacterized basidiomycete yeasts.
Microbiological and physical-chemical characteristics of pollen and honey from stingless bees: a review
Authors: da Silva Raquel Nunes Almeida , Magalhães-Guedes Karina Teixeira , de Souza Carolina Oliveira , de Oliveira Alves Rogério Marcos , Umsza-Guez Marcelo Andrés 
Published: December 2024

AbstractThe physical, chemical and sensory characteristics of pollen and honey from stingless bees (SLB) are quite different when compared to those produced by Apis mellifera. Meliponine honey has a high moisture content (23–37.5%); reducing sugars (12.65–77.11%); and total acidity (11.23 to 124.2 mEq kg-1). Pollen also has fiber (0.87–13.65%); a high moisture content (23–53.93%); lipids (1.8–10.81%) and proteins (8–37.63%). The presence of yeasts, fungi and bacteria can be observed through fermentation (ethanolic and acid) that occurs during the maturation of pollen and honey from stingless bees. Among the microorganisms most associated with stingless bees are yeasts: Pichia, Zygosaccharomyces, Starmerella, Metschnikowia, Candida, Debaryomyces, Dekkera and Kloeckera; bacteria: Streptomyces, Bifidobacterium, Lactobacillus, Streptococcus, Neisseria, Bacillus, Ralstonia, Staphylococcus, Enterobacter, Lysinibacillus Pantoea, Fructobacillus Pseudomonas, and Clostridium; and fungal filaments Aspergillus, Talaromyces and Penicillium. This review corroborates the differences that exist in the physicochemical and microbiological characteristics of stingless bee products and honeybee (Apis melifera) products. These differences not only challenge established standards of quality and identity in apicultural products but also pave the way for new perspectives in biotechnology and nutrition, as well as for new bioactive compounds. The unique properties of pollen and honey from Meliponini, such as high moisture content, acidity, and microbial diversity, can be a distinguishing factor that enhances their applications in various technological fields. The valorization of these unique characteristics may stimulate the creation of specific standards for these products and promote the sustainable use of stingless bee biodiversity.

Graphical Abstract