bluuebunny/crossref_metadata_2025_split huggingface dataset:
An assessment of cryptocurrencies as a global commercial determinant of health
Authors: Davies Nathan 
Published: December 2024

Abstract
Through the commercial determinants of health framework, gambling has been identified as a powerful threat to health. This research critically examines cryptocurrency, which is promoted and sold as a highly gamblified product. Using the commercial determinants of health framework, the multifaceted ways in which cryptocurrency firm operations may impact health outcomes are highlighted. Political influence is exerted through substantial donations, with high-profile cases illustrating the sector’s attempts to sway policy, whilst cryptocurrencies often operate in unregulated markets. Marketing strategies mirror those of traditional harmful industries, deploying immense advertising budgets and celebrity endorsements to promote highly speculative and risky financial products. Cryptocurrency mining, demanding considerable energy consumption, causes significant environmental damage. Financial practices include hundreds of outright frauds targeting low- and middle-income countries. Cryptocurrency investment, with 24/7 access and promises of huge wealth, mirrors gambling and is likely to result in public health harms through the same mechanisms as other forms of gambling. Despite the supposed potential of blockchain technology for improving payment and contract systems, the lack of realization of these benefits contrasts sharply with the immediate and growing costs associated with cryptocurrency speculation. Cryptoassets are a case study for the need for health promotion professionals to critically evaluate new technologies and advocate for regulatory measures to protect public health in the face of novel, high-risk products that overlap gambling and finance.
Imipenem Pharmacokinetics/Pharmacodynamics in Preclinical Hollow Fiber Model, Dose Finding in Virtual Patients, and Clinical Evidence of Efficacy for Mycobacterium abscessus Lung Disease
Authors: Singh Sanjay , Gumbo Tawanda , Wang Jann-Yuan , Boorgula Gunavanthi D , Burke Andrew , Huang Hung-Ling , McShane Pamela J , Amaro-Galvez Rodolfo , Gross Jane E , Aryal Santosh , Heysell Scott K , Srivastava Shashikant 
Published: December 2024

ABSTRACT

Background
Guideline-based therapy (GBT) for Mycobacterium abscessus (Mab) lung disease achieves sputum culture conversion (SCC) rates of 35%. This poor GBT efficacy is mirrored in the hollow fiber system model of Mab (HFS-Mab). While imipenem is part of GBT, its biologic effect, with or without β-lactamase inhibitors, is unproven.

Methods
We performed imipenem-relebactam minimum inhibitory concentration (MIC) in 122 Mab isolates, and an exposure-response study in the HFS-Mab using human intrapulmonary pharmacokinetics. The percentage of time that concentration persisted above the MIC (TMIC), mediating maximal effect in the HFS-Mab, was used as the exposure target for dose finding in a Monte Carlo experiment including 10 000 virtual patients. For real-world evidence, we performed a patient, intervention (imipenem), comparison (no β-lactam), and outcome (SCC) (PICO) analysis.

Results
Imipenem killed 1.32 log10 colony-forming units/mL below the day 0 level in HFS-Mab. The average target exposure for imipenem was a TMIC of 47.9% (SD, 9.77%). Infusion of 1 g every 6 hours achieved the target in &gt;90% of virtual patients in Monte Carlo experiments. The pharmacokinetic-pharmacodynamic MIC break point was 1 mg/L. In PICO analyses, the median time to SCC was 470 days in comparators, 311 days for imipenem added on to a failing regimen, and 37 days in newly treated patients (P = .049). The odds ratio for SCC when imipenem was part of the initial regimen, versus comparators, was 12.5 (95% confidence interval, 1.47­–84.55). No patients receiving imipenem experienced treatment-limiting adverse events, compared with 2 of 7 comparators (P = .046). Middlebrook 7H9 broth MIC distribution, read at 24 hours, was better correlated with patient responses than cation-adjusted Mueller-Hinton broth.

Conclusions
Imipenem demonstrated biologic effect in the HFS-Mab and in patients. Imipenem-relebactam doses of 1 g every 6 hours are recommended.
Phylodynamics for Human Immunodeficiency Virus Prevention: A Miami-Dade County Case Study
Authors: Mehta Sanjay R , Wells Alan B , Cohen Colby , Campbell Angela , Truong Michelle , Little Susan J , Chaillon Antoine 
Published: December 2024

Abstract

Background
To date, human immunodeficiency virus (HIV) molecular epidemiology has been primarily used to identify clusters of related infections (cluster detection and response) and then address interventions to these clusters. Community groups have raised concern regarding cluster detection and response related to privacy and ethical concerns. Here we demonstrate how an alternative approach to HIV molecular epidemiology can provide public health benefit.

Methods
A limited data set for Miami-Dade County provided by the Florida Department of Health was curated and annotated by neighborhood health district (NBHD) and genetic linkage (using a genetic distance threshold of ≤0.5%) and phylodynamic analyses were performed. Phylodynamic analyses were used to infer viral transmissions into Miami-Dade County and between NBHDs within the county.

Results
A total of 7274 HIV sequences from unique persons collected between 1 January 2015 and 31 December 2021 were analyzed, including 50% of the 7894 new diagnoses during this period. The proportion of sequences in local clusters increased over time. Higher ratios of local introductions, compared to viral egress (ie, source of local clusters in other NBHDs) were observed in 3 NBHDs in North Miami (range, 1.9–2.5), suggesting earlier diagnosis, but high numbers of susceptible persons not receiving preexposure prophylaxis. South Dade/Homestead had a low ratio (0.3) of local introductions compared with egress, suggesting later diagnosis and less durable suppression.

Conclusions
Phylodynamic and genetic linkage analyses can highlight populations and geographic regions that might benefit more from particular types of HIV prevention interventions. These findings will need to be explored by evaluating the impact of scaling up interventions informed by these analyses.
Islands, Enclaves, and the Offshoring of Clerical Sexual Abuse
Authors: O’Neill Kevin Lewis 
Published: December 2024

Abstract
Between 1952 and 1968, a Roman Catholic religious order known as the Servants of the Paraclete sought, bought, and finally sold several small islands in the Caribbean for priests said to be unable to stop “sin[ning] repeatedly with little children.” This article, in response, details the Servants of the Paraclete’s mid-twentieth-century efforts at offshoring sexually abusive priests in and then beyond the Caribbean. It is an historical account that pushes scholars of clerical sexual abuse to engage the interstitial spaces that Church leaders have long sought for its perpetrators while at the same time flagging for students of sovereignty and the nation-state that mid-century practices of offshoring shaped not only the history of capitalism but also the history of the Roman Catholic Church.
Intrinsic cues guiding changes in division orientation in the Arabidopsis root meristem: a formative experience
Authors: Konstantinova Nataliia , von der Mark Claudia , De Rybel Bert 
Published: December 2024

Abstract
The orientation of cell division is crucial for normal development of all plant organs throughout their life cycle. Despite the importance of understanding the intricate molecular mechanisms guiding this process, relatively few pathways have been characterized to date. Here we want to outline what is known about the molecular regulation guiding changes in division orientation in the root apical meristem of the model plant Arabidopsis thaliana, from the upstream transcriptional modules to the downstream executors that lead to division plane establishment. We specifically focus on the gaps in our knowledge about this highly coordinated process and propose that a new approach should be taken to characterize how changes in division orientation are controlled in more holistic detail.
Perceptions of Children and Young People in England on the Smokefree Generation Policy: A Focus Group Study
Authors: Davies Nathan P , Murray Rachael L , Langley Tessa , Morling Joanne R , Bains Manpreet 
Published: December 2024

Abstract

Background
Modeling shows smokefree generation (SFG) policies could effectively reduce smoking rates by banning tobacco sales to those born after a specific year. Little is known about how young people perceive the legitimacy and impact of the planned SFG policy in England.

Methods
We conducted seven semi-structured focus groups with 36 participants aged 12–21 (mean = 15) in England over video call and in person. Twenty-one participants were female and 15 male. Participants were purposively sampled to include those from areas of greater deprivation and for use of tobacco or e-cigarettes. Data was analyzed using the framework approach.

Results
Participants expressed broadly negative perceptions toward tobacco and its manufacturers. Most participants supported SFG policy goals and its focus on freedom from addiction and harm; some believed it should also encompass electronic cigarettes. Many believed the law would only be successful if it included stringent enforcement, accompanying tobacco licensing, and input from young people. A minority raised concerns about the loss of freedom to purchase tobacco.

Conclusions
Communication of the freedom-giving nature of SFG is likely to resonate with many young people. Enforcement, communication, and involvement of young people in SFG should be considered carefully to maximize policy impact.

Implications
The smokefree generation (SFG) policy’s potential to offer freedom from addiction and disease can resonate with young people. Its effectiveness could be maximized through targeted enforcement in areas with high youth smoking rates and low adherence to age-of-sale laws, and through the introduction of additional policies that offer restrictive licensing of tobacco retailers. A phased approach to SFG, initially covering tobacco and later incorporating e-cigarettes as smoking prevalence declines, could balance reducing youth vaping and harm reduction; future research could investigate optimal policy conditions for this approach.
Identification and characterization of PpUGT91BP1 as a trillin synthase from Paris polyphylla
Authors: Li Shuyu , Chen Sa , Fu Chunjin , Zhang Jingjing , Xing Jiale , Chai Xin , Zhang Qian , Zhou Jie , Lyu Haining , Xu Chengchao , Liao Jingjing 
Published: December 2024

Abstract
Polyphyllins are the active ingredients of the medicinal plant Paris polyphylla. The biosynthesis of different types of polyphyllins all requires the catalysis of glycosyltransferases. Even though significant efforts have been made to identify PpUGTs capable of catalyzing the initial glycosylation reaction, the specific glycosyltransferases responsible for the synthesis of trillin have not been reported in P. polyphylla. Here, we identified a new trillin synthase, named PpUGT91BP1, which was highly expressed in the rhizome. Importantly, PpUGT91BP1 could specifically glycosylate diosgenin but not pennogenin. To improve its catalytic efficiency, we introduced random mutations through error-prone PCR and conducted an activity-based screening. Three mutants with significantly enhanced trillin synthase activity were identified. Finally, we successfully reconstituted trillin biosynthesis in Nicotiana benthamiana, achieving a yield of 3.69 mg/g of plant dry weight using the mutant PpUGT91BP1. Taken together, our results deepen the understanding of the PpUGT91 family’s role in polyphyllin biosynthesis in P. polyphylla, facilitating rational selection of better P. polyphylla cultivars and guiding future studies in the metabolic engineering of polyphllins.
Nutrient limitation determines biological interactions between a mixotrophic Chrysophyte and toxin-producing Microcystis
Authors: Princiotta Sarah D , Hiripitiyage Yasawantha , Holen Dale , Kellogg Joshua J , Sturm Belinda , Harris Ted D 
Published: December 2024

Abstract
Blooms of toxigenic cyanobacteria pose a mounting risk to aquatic ecosystems. Relative to abiotic drivers of cyanobacteria success, biotic processes have received less attention. Mixotrophic nanoflagellates that combine heterotrophic ingestion of particulate prey with photoautotrophy are among the eukaryotes that can resist cyanotoxins. We used laboratory experiments in culture to integrate top-down (herbivory) and bottom-up (nitrogen and phosphorus limitation) controls on the growth and production of microcystin-LR, including biodegradation products, of Microcystis by Ochromonas (mixotroph) and Spumella (heterotroph). A notable reduction in the growth rate of toxic Microcystis was evident in co-culture with either Ochromonas or Spumella under P-limitation. Under P-limitation, the co-culture of toxic Microcystis with Ochromonas also led to a reduction in concentration of microcystin-LR (MC-LR and an increase in biodegradation products. Grazing rates up to 31 and 50 cell−1 day−1 on toxic Microcystis were recorded for Ochromonas and Spumella, respectively. The highest grazing rates by Ochromonas were observed on toxic Microcystis under N-limitation. Hence, it is likely that Ochromonas is an herbivore of toxic Microcystis under N-limitation and a competitor for nutrients under P-limitation. Collectively, these results suggest a role of eukaryotic nanoflagellates in decreasing the biomass and toxicity associated with cyanobacteria blooms that vary with nutrient availability.
Integrating dynamical modeling and phylogeographic inference to characterize global influenza circulation
Authors: Parino Francesco , Gustani-Buss Emanuele , Bedford Trevor , Suchard Marc A , Trovão Nídia S , Rambaut Andrew , Colizza Vittoria , Poletto Chiara , Lemey Philippe 
Published: December 2024

Abstract
Global seasonal influenza circulation involves a complex interplay between local (seasonality, demography, host immunity) and global factors (international mobility) shaping recurrent epidemic patterns. No studies so far have reconciled the two spatial levels, evaluating the coupling between national epidemics, considering heterogeneous coverage of epidemiological, and virological data, integrating different data sources. We propose a novel-combined approach based on a dynamical model of global influenza spread (GLEAM), integrating high-resolution demographic, and mobility data, and a generalized linear model of phylogeographic diffusion that accounts for time-varying migration rates. Seasonal migration fluxes across countries simulated with GLEAM are tested as phylogeographic predictors to provide model validation and calibration based on genetic data. Seasonal fluxes obtained with a specific transmissibility peak time and recurrent travel outperformed the raw air-transportation predictor, previously considered as optimal indicator of global influenza migration. Influenza A subtypes supported autumn–winter reproductive number as high as 2.25 and an average immunity duration of 2 years. Similar dynamics were preferred by influenza B lineages, with a lower autumn–winter reproductive number. Comparing simulated epidemic profiles against FluNet data offered comparatively limited resolution power. The multiscale approach enables model selection yielding a novel computational framework for describing global influenza dynamics at different scales—local transmission and national epidemics vs. international coupling through mobility and imported cases. Our findings have important implications to improve preparedness against seasonal influenza epidemics. The approach can be generalized to other epidemic contexts, such as emerging disease outbreaks to improve the flexibility and predictive power of modeling.
Comorbidity in incident rheumatoid arthritis—a nationwide case-control study with bidirectional follow-up
Authors: Batko Bogdan , Szeląg Mateusz , Krajewska-Włodarczyk Magdalena , Żuber Zbigniew , Orleański Michał , Podwójcic Krzysztof , Sowiński Jakub , Świderek Maria , Maluchnik Michał , Batko Krzysztof , Śmiglewska Agata , Brzosko Marek , Stajszczyk Marcin , Kwiatkowska Brygida 
Published: December 2024

Abstract

Objectives
To investigate the association between risk of different co-morbidities and diagnosis of rheumatoid arthritis (RA) using a temporal approach.

Methods
Retrospective, case-control study. Data were extracted from all healthcare claims for Poland between 2011-2021. Prevalent RA(n = 262 265) patients were examined to evaluate morbidity patterns. Incident RA(n = 15 879) and age-, sex- and region-matched controls were sampled 1:10 from the general population (GP). Exposure was new-onset RA identified by interspaced, repeat claims and prescription. Follow-up was performed in a bidirectional, five-year timeframe from RA diagnosis(Dx).

Results
RA is associated with enhanced risk of multiple organ system disorders both pre- and post-Dx, especially hematologic (IRR 1.80, 95% CI 1.58, 2.05), pulmonary (IRR 1.57, 95% CI 1.53, 1.62), gastrointestinal (IRR 1.53, 95% CI 1.46, 1.60), and cardiovascular (IRR 1.25, 95% CI 1.22, 1.27) conditions. RA appears strongly associated with interstitial lung disease (pre-Dx IRR 2.97, 95% CI 2.20, 4.02; post-Dx IRR 4.66, 95% CI 3.91, 5.56) and inflammatory bowel disease (pre-Dx IRR 1.61, 95% CI 1.25, 2.07; post-Dx IRR 2.12, 95% CI 1.70, 2.63). Enhanced post-Dx risk of thyroid cancer (IRR 1.29, 95% CI 1.00, 1.66) and lymphoma (IRR 1.50, 95% CI 1.20, 1.88) was observed, in contrast to reduced risk of colon cancer (IRR 0.77, 95% CI 0.62, 0.94).

Conclusion
Enhanced risk of multiple comorbidities was observed both pre- and post-RA Dx, with varying patterns across different organ systems. These data highlight the multisystem nature of RA and warrant research into causal, bidirectional relationships.
Biomechanics of venom delivery in South America’s first toxungen-spraying scorpion
Authors: Laborieux Léo 
Published: December 2024

Abstract
Venom is a metabolically expensive secretion used sparingly in a variety of ecological contexts, most notably predation and defence. Accordingly, few animals employ their toxins from a distance, and venom-squirting behaviour is only known from select taxa. In scorpions, species belonging to two genera are known to spray venom when threatened, and previous work in Parabuthus transvaalicus shows that venom delivery depends on perceived levels of threat. Here, I describe Tityus (Tityus) achilles sp. nov., a new species of buthid scorpion from Cundinamarca, Colombia. Remarkably, this species is capable of venom spraying, a first for both the genus and the South American continent. Using frame-by-frame video analysis and ballistic equations, I show that T. (Tityus) achilles sp. nov. employs not one, but two types of airborne defences with dramatic differences in reach and venom expenditure. Further, the new species uses an unusually large reserve of prevenom-like secretion for spraying, as opposed to the costly venom used by other spraying scorpions. In light of these key specializations, I propose that toxungen spraying convergently evolved in response to different selection pressures, laying the groundwork for future investigation.
Validity Evidence for Using Virtual, Interactive Patient Encounters to Teach and Assess Clinical Reasoning for First-Year Medical Students
Authors: Roberts John K. , Weigle Nancy , Fox James W. , Natesan Sreeja , Gordon David , Chudgar Saumil M. 
Published: December 2024

Abstract

Purpose
Despite universal agreement on the importance of clinical reasoning skills, inadequate curricular attention to these skills remains a problem. To facilitate integration of clinical reasoning instruction and assessment into the preclerkship phase, the authors created a clinical reasoning curriculum using technology-enhanced patient simulations.

Method
In 2023, first-year medical students at Duke University School of Medicine were enrolled in a biomedical science course using diagnostic reasoning sessions and 16 virtual, interactive patient (VIP) encounters to teach and assess clinical reasoning. The encounters were enhanced with interactive pop-in windows that assessed multiple clinical reasoning domains. Student responses were independently evaluated by faculty. Cumulative VIP clinical reasoning composite (CRC) scores were calculated, and growth mixture modeling was used to define students by growth trajectory. Clinical reasoning was assessed in a summative objective structured clinical examination (OSCE).

Results
Of the 118 students who participated in the curriculum, 1 was excluded from analysis for inadequate participation in the VIP encounters, leaving 117 students. The aggregate VIP encounter response rate was 95% (1,783 of 1,872 assessments completed). Clinical reasoning was assessed through cumulative performance across multiple domains. The mean (SD) scores were 58 (13) for information gathering, 46 (13) for illness script identification, 64 (14) for hypothesis generation, 59 (12) for differential diagnosis, and 77 (21) for management and plan. To identify latent classes of growth in cumulative VIP-CRC scores, growth mixture modeling was performed for 1-, 2-, and 3-class models. The 2-class model showed the best fit due to having the lowest bayesian information criterion (11,765.17) and Akaike information criteria (11,737.55).

Conclusions
Integrated clinical reasoning instruction and deliberate, formative practice through authentic simulations were effective at teaching and assessing clinical reasoning in the preclerkship phase. VIP and OSCE can be used to identify students at risk of low performance in the clerkship year.
Anaesthesia practice in Europe
Authors: Pinelli Fulvio , Romagnoli Stefano , Singh Sweta , Albaladejo Pierre , Nau Carla , Bilotta Federico 
Published: December 2024

BACKGROUND
Similar to other continents, Europe is experiencing a shortage of anaesthesia workforce, which profoundly impacts the national healthcare systems of affected countries.

OBJECTIVE
To assess the current landscape of the anaesthesia workforce, organisational practices, rules and responsibilities of anaesthesiologists and other anaesthesia providers in operating rooms.

DESIGN
Survey.

SETTING
Thirty-nine out of 41 European countries were surveyed between April 2022 and April 2023.

PARTICIPANTS
Delegates of the National Anaesthesiologists Societies Committee (NASC) of the European Society of Anaesthesiology and Intensive Care (ESAIC).

INTERVENTION
A faculty of experts from France, Germany and Italy, selected by the Chair of NASC, developed a survey consisting of 16 questions, which was sent to the NASC delegates of all European countries.

MAIN OUTCOME MEASURES
Responses from the NASC delegates.

RESULTS
The anaesthesia workforce, composition, roles and duties of anaesthesia teams vary significantly among European countries. The majority of respondents reported a workforce shortage, with variable trends, exacerbated in some cases by an increased loss of anaesthesiologists following the COVID-19 pandemic. Significant differences in anaesthesiologists’ salaries exist across countries. A one-to-one anaesthesiologist-to-patient ratio during general anaesthesia maintenance, neuraxial and peripheral blocks is the most common; however, in a notable number of cases, this ratio decreases to one-to-two or even less. In such instances, residents or nonphysician anaesthesia personnel (NPAs) play a crucial role, enabling anaesthesiologists to supervise more than one patient simultaneously. Differences in the training of anaesthesia team members, as well as rules regulating anaesthesia team composition and the autonomy of its members, were also evident.

CONCLUSION
The survey provides data on the current anaesthesia practice in Europe. The availability, composition and organisation of anaesthesia team members differ among European countries. The study highlights areas for further focus in operating room organisation and anaesthesia team composition, particularly regarding safety, efficacy and cost-effectiveness.