bluuebunny/crossref_metadata_2025 huggingface dataset:
Facts, Interests, and Values
Authors: Deconinck Koen
Published: October 2023

Facts, interests, and values are three major areas of disagreement over food systems policies. This chapter shows how understanding the role of facts, interests, and values can also point the way to more effective approaches to policymaking. For some issues, there are major evidence gaps to be resolved. In others, the main obstacle is that interest groups try to influence the policy process. In still others, there might also be a lack of societal consensus on what the relative priorities should be since people differ in the values they emphasize. To complicate matters, trouble in one area can spill over to other areas, such as when people become unwilling to consider facts that go against their interests. The chapter identifies several good practices that can help overcome disagreements over facts, interests, and values.
The Political Economy of Reforming Agricultural Support Policies
Authors: Vos Rob , Martin Will , Resnick Danielle
Published: October 2023

Agricultural support policies amounted to about US$817 billion per year worldwide in the 2019–2021 period. Although some agricultural support policies have boosted global food production, there are serious concerns about their impacts on achieving sustainable, healthy, and inclusive food systems. This chapter first demonstrates how repurposing agricultural subsidies toward investments such as agricultural research and development and rural infrastructure has the potential to improve both dietary and planetary health. Since such reforms are contingent on political economy considerations, the chapter subsequently presents a framework for analyzing how interests, institutions, information, and policy characteristics intersect to facilitate or stymie reform efforts. Case studies of attempted reforms from China, the European Union, India, and the United States, are presented that highlight the relevance of the framework. The chapter concludes by summarizing some potentially enabling political economy conditions for repurposing agricultural support policies.
Tracking Progress and Generating Accountability for Global Food System Commitments
Authors: Nordhagen Stella , Fanzo Jessica
Published: October 2023

Commitments and plans for food system transformation will have no impact if not followed by concrete action, including by governments and the private sector. It is thus essential to ensure accountability mechanisms are in place to follow-up on commitments and track progress. While reports and tracking mechanisms exist for various sub-aspects and outcomes of food systems, none of these are comprehensive and coherently connected in addressing all the diverse outcomes of food systems—including not only health but also environmental sustainability and livelihood and equity indicators, as well as governance aspects. They also lack mechanisms to actually hold decision-makers to account. A more comprehensive, multi-disciplinary, and inclusive approach is needed. This chapter describes the importance of tracking commitments and outcomes of food systems, examines prior related tracking efforts and the gaps they leave to be filled, and details progress and plans for improved tracking mechanisms now and into the future.
Introduction: UN peace operations, global policing, and social order
Authors: Pingeot Lou
Published: October 2023

This chapter introduces the main questions raised by Police Peacekeeping and presents the book’s aims and core contributions. The book argues that intervening in (post)conflict situations through the lens of policing leads to the depoliticization of conflict and the criminalization of the ‘intervened upon’. It locates these dynamics within the field of global policing. Peace operations act as transnational points of cross-fertilization for the creation and transmission of policing practices, not only allowing existing discourses and practices to circulate, but also generating new experiences of intervention that can travel out. The chapter identifies four mechanisms through which policing within UN peace operations can circulate outside of these missions. It introduces the case of UN intervention in Haiti and concludes with an overview of the succeeding chapters.
L’École des maris
Authors: Lyons John D.
Published: October 2023

Molière’s The School for Husbands is less well known than the very similar subsequent comedy, The School for Wives. In this earlier comedy, two brothers each raise an orphan with the hope of marrying her. One brother is kind to his ward and will allow her to choose her husband freely. The other, despite the quasi-incestuous nature of the situation, plans to force his ward to marry him, but she improvises several ways to communicate with a younger suitor, and even manages to make her guardian transmit and facilitate messages to her suitor. Her methods involve the ironic form known as preterition and sometimes resemble the form of code known as steganography, in which a code appears as a perfectly innocuous message.
Le Misanthrope
Authors: Lyons John D.
Published: October 2023

The Misanthr ope, often considered Molière’s greatest comedy, takes place in a Parisian salon. The privileged position of the male and female protagonists (the fact that both are free to choose a spouse without parental intervention) makes the play, despite its urban setting, resemble the very popular contemporary genre of the dramatic pastoral. In the pastoral, as in the Misanthrope, the strictures of Church and state concerning marriage are nowhere in evidence, and characters engage in free courtship. There is a long critical tradition of describing the male protagonist of this play, Alceste, as a champion of truth, and to see his beloved, Célimène, as a deceitful ‘coquette’. But this traditional vision of the comedy neglects Alceste’s dream of controlling Célimène and of isolating her from society. Célimène is actually more truthful than Alceste, once we make the crucial distinction between truth and sincerity.
Organizational and Individual Change
Authors: Rouse William B.
Published: October 2023

Overcoming Common Hurdles focuses on organizational and individual change. Learning and growth are central, but require reflection and absorption. This has to be pursued while responding to natural and human-made challenges, including those associated with markets, competitors, organizations, technologies, execution, stakeholders, and leaders. This chapter provides practical guidance on how to sense, understand, and respond to such obstacles, drawing upon a wide range of vignettes from industry, government, and academia. The keys are recognizing the strategic situation actually being faced, avoiding delusions about available resources and competitive positions, and committed leadership. Many of the vignettes illustrate the unfortunate consequences of these key enablers being absent.
Some Asian Journeys
Authors: Mohan Rajat
Published: October 2023

Though the long-lasting Tokugawa regime (1603–1868) had been deeply feudal, they had always placed significant emphasis on education, resulting in the country’s achieving high literacy levels, a professionalized merit-based bureaucracy, and impressive economic growth. The modernization of Japan began in earnest with the Meiji Restoration in 1868. Feudalism was abolished, social mobility allowed, and private property rights were recognized. Modern institutions, postal networks, and a banking system were established, economic institutions increasingly became inclusive, as did political institutions, with a new written constitution adopted in 1890. Increased plurality and inclusivity in both economic and political institutions laid the groundwork for Japan’s subsequent economic and social development. Unified Korea had suffered from extractive institutions through its long, culturally rich history. Land reforms were a high priority for both Koreas after the 1948 partition, and by the mid-1960s, South Korea had implemented a radical land-reform programme which fundamentally transformed its rural class structure. A growing sense of empowerment in the common citizen led to increased demands for better educational opportunities and meritocracy in the bureaucracy. The virtual elimination of the landed elite also reduced domination of the state by any section of society and limited the political clientelism. However, political institutions remained extractive till President Roh Tae-woo was democratically elected as the country’s president in 1987. Note that Japan’s and Korea’s economic development was principally driven by human-capability formation promoted by both public policy and a supportive cultural climate.
Enlightened Oxford
Authors: Aston Nigel
Published: October 2023

How far was the eighteenth-century University of Oxford, still often dismissed as a moribund and marginal institution, actually something of an ‘enlightened’ presence? This book offers some answers as it seeks to discern, establish, and clarify the multiplicity of connections between the University, its members, and the world outside; to offer readers a fresh, contextualised sense of the University’s role in the state, in society, in scholarly and cultural life between the Glorious Revolution and the first decade of the nineteenth century, the era loosely describable as England’s ancien régime. It looks at where Oxford fitted in to that wider polity, locates its importance in Church and state, and ponders its place as an institution that upheld confessional entitlement in an ever-shifting intellectual world where national and confessional boundaries were under scrutiny. Patronage, clientage, connection, and, at times, blatant jobbery, figure considerably, as they would in any study of an eighteenth-century institution. But, equally, ties of friendship, kinship, and moral obligation are emphasised, all of them having an Oxonian dimension with consequences in the conduct of public life. Oxford based academics and authors were nurturing ever closer connections with the commercial print world. Increasingly, they did not want to stand apart, to restrict consideration of what they wrote to an academic audience at home and abroad. It is a reminder that Oxford deserves treatment within the multiple contexts of Enlightenment Britain, and against versions of the Enlightenment found elsewhere in Europe.
Subjunctive
Authors: Potowski Kim , Torres Lourdes
Published: October 2023

This chapter examines subjunctive use across three generations of Spanish-English bilinguals with Mexican and Puerto Rican origin residing in Chicago. The goal of the chapter is to determine whether there are differences in subjunctive usage according to regional origin, generation, regional origin and generation, and level of Spanish proficiency and whether Spanish proficiency or generational group is more strongly connected to subjunctive use. The chapter begins with a review of studies of the subjunctive in U.S. Spanish and then describes the methodology. The chapter then presents subjunctive usage by regional origin, generation, regional origin and generation, and level of Spanish proficiency. Next, the chapter considers whether generational and/or dialectal differences emerge for subjunctive and indicative usage in obligatory and variable contexts separately by generation, regional origin and generation, and level of Spanish proficiency. Chapter findings are compared with other studies of subjunctive use in U.S. Spanish.
Conclusions
Authors: Potowski Kim , Torres Lourdes
Published: October 2023

This chapter summarizes the study’s findings and makes suggestions for the continued vitality of Spanish in Chicago and in the United States. It starts with a discussion of how to measure Spanish and support its vitality. The chapter then provides a summary of the study’s findings. It discusses conclusions about generation and proficiency, differences in regional groups, evidence of dialect leveling, and evidence of convergence for the five linguistic features analyzed: lexical familiarity, proportional use of so versus entonces, number of codeswitches and percentage of English use, production of subjunctive morphology in obligatory and variable contexts, and two phonological features, the weakening of coda /s/ and the velarization of /r̄/. For MexiRicans, it additionally discusses evidence of a “mother factor. The chapter closes with suggestions for areas of further research.
Pay-As-You-Go Insurance: Experimental Evidence on Consumer Demand and Behavior
Authors: Kluender Raymond
Published: October 2023

Pay-as-you-go contracts reduce minimum purchase requirements, which may increase market participation. This paper randomizes the introduction and price(s) of a novel pay-as-you-go contract to the California auto insurance market, where 17% of drivers are uninsured. The pay-as-you-go contract increases take-up by 10.8 p.p. (89%) and days with coverage by 4.6 days over the 3-month experiment (27%). Demand is relatively inelastic, and pay-as-you-go increases insurance coverage in part by relaxing liquidity requirements: most drivers’ purchasing behavior is consistent with a cost of credit in excess of payday lending rates, and 19% of drivers have a purchase rejected for insufficient funds.
The usefulness of ultrasound in predicting outcomes in patients with shoulder pain: a prospective observational study
Authors: Tran Gui , Hensor Elizabeth M A , Kingsbury Sarah R , O’Connor Philip , Cowling Paul , Conaghan Philip G
Published: October 2023

Objectives

Shoulder pain is common but current clinical classification has limited utility. We aimed to determine whether groups of ultrasound-based shoulder pathologies exist and to evaluate outcomes according to identified groups and individual pathologies.

Methods

This was a prospective study of a community-based cohort with shoulder pain referred for their first ultrasound scan at a single radiology unit, with subsequent routine clinical care. Patient-reported outcomes were collected at baseline, 2 weeks and 6 months; standardized ultrasound reporting was employed. Latent class analysis (LCA) identified ultrasound pathology–based groups. Multiple linear regression analysis explored associations between baseline pathologies, subsequent treatment and Shoulder Pain and Disability Index (SPADI). Short-term response to corticosteroid injections was investigated.

Results

Of 500 participants (mean age 53.6 years; 52% female), 330 completed follow-up. LCA identified four groups: bursitis with (33%) or without (27%) acromioclavicular joint degeneration, rotator cuff tear (21%) and no bursitis/tear (19%). Total SPADI was higher at baseline for cuff tears (mean 55.1 vs 49.7–51.3; overall P = 0.005), but accounting for this, groups did not differ at 6 months (43.5 vs 38.5–40.5; P = 0.379). Baseline SPADI was the only predictor of 6-month SPADI retained by penalized modelling; neither LCA-derived ultrasound groups nor individual pathologies were selected. Response to baseline injection at week 2 did not differ between groups (mean SPADI 40.1–43.8; P = 0.423).

Conclusion

Ultrasound-based classification (groups or individual pathologies) of shoulder pain did not predict medium-term outcomes using current treatments. The role of routine diagnostic ultrasound for shoulder pain needs consideration; it may be useful to establish evidence-based therapies for specific pathologies.
Gerontocracy, labor market bottlenecks, and generational crises in modern science
Authors: Siler Kyle
Published: October 2023

Many early career researchers (ECRs) currently face long odds of attaining a full-time or tenure-track research position. Populations of graduate and postdoctoral researchers have continually increased, without concomitant increases in tenure-track jobs or stable research careers. The current hypercompetitive academic labor market is societally inefficient and often inhumane to ECRs, commonly characterized by precarious, exploitative, and/or uncertain employment terms. Compounding generational disadvantages endured by many ECRs at work, analysis of worldwide data on housing rental costs reveals that escalating costs of living are an especially acute problem for ECRs, since major research universities tend to be located in expensive cities. The unfavorable plight of today’s ECRs can be partly attributed to the disproportionate zero-sum distribution of resources to senior academics, particularly of the baby boomer generation. The uncertainty, precariousness, and hypercompetitiveness of ECR academic labor markets undermine the quantity and quality of scientific innovations, both in the present and in the future.
Using intervention mapping to design and implement a multicomponent intervention to improve antibiotic and NSAID prescribing
Authors: Reese Thomas J , Mixon Amanda S , Matheny Michael E , Flatt Christina N , Rubenstein Melissa , Han Jin H , Wrenn Jesse , Dagostino Chloe , Bonnet Kemberlee , Anders Shilo , Schlundt David , Ward Michael J
Published: October 2023

Successfully changing prescribing behavior to reduce inappropriate antibiotic and nonsteroidal anti-inflammatory drug (NSAID) prescriptions often requires combining components into a multicomponent intervention. However, multicomponent interventions often fail because of development and implementation complexity. To increase the likelihood of successfully changing prescribing behavior, we applied a systematic process to design and implement a multicomponent intervention. We used Intervention Mapping to create a roadmap for a multicomponent intervention in unscheduled outpatient care settings in the Veterans Health Administration. Intervention Mapping is a systematic process consisting of six steps that we grouped into three phases: (i) understand behavioral determinants and barriers to implementation, (ii) develop the intervention, and (iii) define evaluation plan and implementation strategies. A targeted literature review, combined with 25 prescriber and 25 stakeholder interviews, helped identify key behavioral determinants to inappropriate prescribing (e.g. perceived social pressure from patients to prescribe). We targeted three desired prescriber behaviors: (i) review guideline-concordant prescribing and patient outcomes, (ii) manage diagnostic and treatment uncertainty, and (iii) educate patients and caregivers. The intervention consisted of components for academic detailing, prescribing feedback, and alternative prescription order sets. Implementation strategies consisted of preparing clinical champions, conducting readiness assessments, and incentivizing use of the intervention. We chose a mixed-method study design with a commonly used evaluation framework to assess effectiveness and implementation outcomes in a subsequent trial. This study furthers knowledge about causes of inappropriate antibiotic and NSAID prescribing and demonstrates how theoretical, empirical, and practical information can be systematically applied to develop a multicomponent intervention to help address these causes.
Quantitative Trait Locus Mapping for Fire Blight Resistance in an F2 Population of Malus fusca MAL0045 Uncovers Novel Resistance Loci
Authors: Emeriewen Ofere Francis , Richter Klaus , Flachowsky Henryk , Peil Andreas
Published: October 2023

Several fire blight resistance loci in Malus genotypes map on different linkage groups (LGs) representing chromosomes of the domesticated apple. Prior genetics studies primarily focused on F1 populations. A strong resistance quantitative trait locus (QTL) explained up to 66% of phenotypic variance in an F1 progeny derived from crossing the highly resistant wild apple genotype Malus fusca MAL0045 and the highly susceptible apple cultivar ‘Idared’, which was previously mapped on LG10 ( Mfu10) of MAL0045. Strains of the causative bacterial pathogen Erwinia amylovora, notably those that show a single nucleotide polymorphism in the avrRpt2EA effector protein sequence at position 156 (e.g., Ea3049), are more virulent and overcome some known fire blight resistance donors and their QTLs. However, MAL0045 is resistant to Ea3049 and Mfu10 is not overcome, but most of the F1 progeny were highly susceptible to this strain. This phenomenon led to the assumption that other putative resistance factors not segregating in the F1 progeny might be present in the genome of MAL0045. Here, we crossed F1 progeny together to obtain 135 F2 individuals. Facilitated by genotyping-by-sequencing and phenotypic assessments, we identified and mapped two novel resistance QTLs in these F2 individuals on LGs 4 and 15, which were not identified in the F1. To our knowledge, these are the first resistance QTLs mapped in F2 progeny in Malus. In addition, we report that neither MAL0045 nor Mfu10 is broken down by a highly aggressive U.S. strain, LA635, after analyses in the original F1 individuals.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Multigenic Hairpin Transgenes in Tomato Confer Resistance to Multiple Orthotospoviruses Including Sw-5 Resistance-Breaking Tomato Spotted Wilt Virus
Authors: Oliver Jonathan E. , Rotenberg Dorith , Agosto-Shaw Karolyn , McInnes Holly A. , Lahre Kirsten A. , Mulot Michaël , Adkins Scott , Whitfield Anna E.
Published: October 2023

Tomato spotted wilt virus (TSWV) and related thrips-borne orthotospoviruses are a threat to food and ornamental crops. Orthotospoviruses have the capacity for rapid genetic change by genome segment reassortment and mutation. Genetic resistance is one of the most effective strategies for managing orthotospoviruses, but there are multiple examples of resistance gene breakdown. Our goal was to develop effective multigenic, broad-spectrum resistance to TSWV and other orthotospoviruses. The most conserved sequences for each open reading frame (ORF) of the TSWV genome were identified, and comparison with other orthotospoviruses revealed sequence conservation within virus clades; some overlapped with domains with well-documented biological functions. We made six hairpin constructs, each of which incorporated sequences matching portions of all five ORFs. Tomato plants expressing the hairpin transgene were challenged with TSWV by thrips and leaf-rub inoculation, and four constructs provided strong protection against TSWV in foliage and fruit. To determine if the hairpin constructs provided protection against other emerging orthotospoviruses, we challenged the plants with tomato chlorotic spot virus and resistance-breaking TSWV and found that the same constructs also provided resistance to these related viruses. Antiviral hairpin constructs are an effective way to protect plants from multiple orthotospoviruses and are an important strategy in the fight against resistance-breaking TSWV and emerging viruses. Targeting of all five viral ORFs is expected to increase the durability of resistance, and combining them with other resistance genes could further extend the utility of this disease control strategy.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Complete Genome Sequence of Sclerotinia sclerotiorum (S1), One of the Pathogens Causing Sclerotinosis in Mulberry Fruit
Authors: Peng Fangfang , Li Xunlan , Wei Zhaoxin , Han Guohui
Published: October 2023

Sclerotinia sclerotiorum is a fungal pathogen that infects an extremely wide range of hosts and can cause diseases in over 600 plant species. In this study, Sclerotinia sclerotiorum (strain S1), which causes sclerotinosis in mulberry fruits, was isolated from the mulberry orchard at the Chongqing Academy of Agricultural Sciences, China, and its complete genome was sequenced using PacBio Sequel II. The assembly consists of 24 contigs with an estimated genome size of 38.91 Mbp and is predicted to encode 9,920 protein-coding genes. This is the first genomic information for Sclerotinia sclerotiorum isolated from diseased mulberry fruit and represents a valuable resource for a comprehensive understanding of Sclerotinia spp.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Effect of Topical Antibiotic Powder Application in the Emergency Department on Deep Fracture Related Infection in Type III Open Lower Extremity Fractures
Authors: Taylor Shea , John Mitchell P , Grayson Whisper , Mir Hassan R.
Published: October 2023

Objective:

Despite advances in management, open fractures are at an elevated risk for deep fracture related infection (FRI). Time to systemic antibiotic (ABX) administration and intraoperative topical administration of ABX powder have been utilized to decrease FRI risk. The purpose of this study was to determine if topical application of antibiotic powder to type III open lower extremity fractures immediately upon presentation to the emergency department (ED) reduces the rate of FRI.

Methods:

Design:

Prospective cohort compared to retrospective historical control

Setting:

Level I trauma center

Intervention:

Application of 1g vancomycin and 1.2g tobramycin powder directly to open fracture wounds on presentation to the ED.

Patient Selection Criteria:

Patients with type III open lower extremity fractures treated from July 1, 2019 to September 17, 2022 who received topical ABX powder in the ED were compared to patients from a 4-year historical cohort from July 1, 2015 to June 30, 2019 who were treated without topical ABX powder.

Outcome Measures and Comparisons:

Development of a FRI within 6 months of follow up. Patient demographics, injury characteristics, and postoperative data were analyzed as risk factors for FRI.

Results:

Sixty-six patients received topical ABX powder in the ED and were compared to 129 patients who were treated without topical ABX powder.

The rate of FRI in the trial group was 6/66 (9.09%) versus 22/129 (17.05%) in the control cohort (p=.133). Multivariate analysis demonstrated higher BMI as a risk factor for development of FRI (p=0.036).

Conclusion:

No statistically significant difference in rates of FRI in open lower extremity fractures treated with immediate topical ABX administration in the ED versus standard of care treatment without topical ABX were found. These findings may have been limited by insufficient power. Further large-scale study is warranted to determine the significance of topical antibiotic powder application in the ED.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Successful Outcomes with Nonoperative Treatment and Immediate Weightbearing Despite Stress-Positive Radiographs in Isolated Distal Fibula (OTA/AO 44B) Fractures
Authors: Stockwell Erin , Thomas Phillip , Grossman Leonid , Lyden Elizabeth , Mormino Matthew , Siebler Justin , Putnam Sara
Published: October 2023

Objectives: To determine if a nonoperative management protocol results in equivalent outcomes in isolated OTA/AO 44B (Weber B) fractures without initial medial clear space (MCS) widening regardless of stress radiography findings

Design: Prospective cohort

Setting: Level 1 academic trauma center

Patients/Participants: Sixty-nine patients with isolated OTA/AO 44B fractures and MCS ≤ 4 mm on initial non-weightbearing injury radiographs over a 4-year period

Intervention: nonoperative management of isolated OTA/AO 44B fractures without initial MCS widening > 4 mm

Main Outcome Measurements: MCS measurements on weightbearing radiographs at first follow up, six weeks, 12 weeks, and six months post-injury; American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores

Results: None of the 38/69 (55%) patients with widening on gravity stress radiographs demonstrated persistent widening with weightbearing radiographs at any time point. Mean MCS measurement differences between the two cohorts were statistically significant for all time points (p=0.012), however with a model adjusted mean MCS value of 2.7 mm for the non-widening cohort and 2.9 mm for the widening cohort, these are not clinically significant. There was no statistically significant difference in overall final AOFAS scores between the two groups (p=0.451). Additionally, statistical equivalence using Schuirmann’s two one-sided tests was achieved between the two groups. Both cohorts had mean AOFAS scores representing excellent outcomes at final follow up.

Conclusions: Isolated OTA/AO 44B fractures without MCS widening on initial injury radiographs have equivalent outcomes regardless of gravity stress radiography findings when treated nonoperatively. Weightbearing radiographs at initial follow-up are a reliable assessment of ankle stability in these injuries and are an appropriate alternative to painful and time-consuming stress radiography.

Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Multistudy Research Operations in the ICU: An Interprofessional Pandemic-Informed Approach
Authors: Cook Deborah J. , Duan Erick H. , Clarke France J. , Matic Karlo , Culgin Sarah , Kelly Laurel , Nelson Katlynne S. , Wallace Christine V. , Soth Mark D. , Lewis Kimberley A. , Rudkowski Jill C. , Perri Dan , Ligori Tania L. , Jaeschke Roman Z. , Chagla Zain , Chaudhuri Dipayan , Wright Angela E. , Fu Zoe Y. , Reeve Brenda K. , Lee Hilary M. , Overington Jeffrey D. , Rozenberg Anna , Bloomfield Kimberly A. , Love Katryn , Gain Jennifer L. , Zytaruk Nicole L. , Cheung Jason H. , Thabane Lehana , Kho Michelle E. ,   for the Department of Critical Care Research Operations Committee
Published: October 2023

OBJECTIVES:

Proliferation of COVID-19 research underscored the need for improved awareness among investigators, research staff and bedside clinicians of the operational details of clinical studies. The objective was to describe the genesis, goals, participation, procedures, and outcomes of two research operations committees in an academic ICU during the COVID-19 pandemic.

DESIGN:

Two-phase, single-center multistudy cohort.

SETTING:

University-affiliated ICU in Hamilton, ON, Canada.

PATIENTS:

Adult patients in the ICU, medical stepdown unit, or COVID-19 ward.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

An interprofessional COVID Collaborative was convened at the pandemic onset within our department, to proactively coordinate studies, help navigate multiple authentic consent encounters by different research staff, and determine which studies would be suitable for coenrollment. From March 2020 to May 2021, five non-COVID trials continued, two were paused then restarted, and five were launched. Over 15 months, 161 patients were involved in 215 trial enrollments, 110 (51.1%) of which were into a COVID treatment trial. The overall informed consent rate (proportion agreed of those eligible and approached including a priori and deferred consent models) was 83% (215/259). The informed consent rate was lower for COVID-19 trials (110/142, 77.5%) than other trials (105/117, 89.7%; p = 0.01). Patients with COVID-19 were significantly more likely to be coenrolled in two or more studies (29/77, 37.7%) compared with other patients (13/84, 15.5%; p = 0.002). Review items for each new study were collated, refined, and evolved into a modifiable checklist template to set up each study for success. The COVID Collaborative expanded to a more formal Department of Critical Care Research Operations Committee in June 2021, supporting sustainable research operations during and beyond the pandemic.

CONCLUSIONS:

Structured coordination and increased communication about research operations among diverse research stakeholders cultivated a sense of shared purpose and enhanced the integrity of clinical research operations.
Elevated Driving Pressure and Elastance Does Not Increase In-Hospital Mortality Among Obese and Severely Obese Patients With Ventilator Dependent Respiratory Failure
Authors: Terry Charles , Brinton Daniel , Simpson Annie N. , Kirchoff Katie , Files D. Clark , Carter George , Ford Dee W. , Goodwin Andrew J.
Published: October 2023

Importance:

Existing recommendations for mechanical ventilation are based on studies that under-sampled or excluded obese and severely obese individuals.

Objective:

To determine if driving pressure (DP) and total respiratory system elastance (Ers) differ among normal/overweight (body mass index [BMI] < 30 kg/m2), obese, and severely obese ventilator-dependent respiratory failure (VDRF) patients and if there any associations with clinical outcomes.

Design, Setting, and Participants:

Retrospective observational cohort study during 2016–2018 at two tertiary care academic medical centers using electronic health record data from the first 2 full days of mechanical ventilation. The cohort was stratified by BMI classes to measure median DP, time-weighted mean tidal volume, plateau pressure, and Ers for each BMI class.

Setting and Participants:

Mechanically ventilated patients in medical and surgical ICUs.

Main Outcomes and Measures:

Primary outcome and effect measures included relative risk of in-hospital mortality, ventilator-free days, ICU length of stay, and hospital length of stay with multivariable adjustment.

Results:

The cohort included 3,204 patients with 976 (30.4%) and 382 (11.9%) obese and severely obese patients, respectively. Severe obesity was associated with a DP greater than or equal to 15 cm H2O (relative risk [RR], 1.51 [95% CI, 1.26–1.82]) and Ers greater than or equal to 2 cm H2O/(mL/kg) (RR, 1.31 [95% CI, 1.14–1.49]). Despite elevated DP and Ers, there were no differences in in-hospital mortality, ventilator-free days, or ICU length of stay among all three groups.

Conclusions and Relevance:

Despite higher DP and ERS among obese and severely obese VDRF patients, there were no differences in in-hospital mortality or duration of mechanical ventilation, suggesting that DP has less prognostic value in obese and severely obese VDRF patients.
Concussion in Kids
Authors: Shank Bettina , Rice Eve
Published: October 2023

The incidence of concussions in kids has increased over the past decade. Concussions occur from blunt force trauma and are often caused by sports-related head injuries. Clinical presentation varies by individual, and symptoms typically resolve within a couple of weeks from the injury. Key domains for diagnosis, clinical presentation, and clinical management include somatic, cognitive, emotional, and sleep-related disturbances. Patient education is an essential component of care for concussion prevention and recovery. Pediatric nurses play a pivotal role in patient education and optimizing care for kids suffering from a concussion and associated complications. Most concussions resolve without complications over time, but with continued education and research, a mild traumatic brain injury will become less problematic through continued prevention methods and early diagnosis.
Indications of Effective Hyperbaric Oxygen Therapy Combined With Steroid Therapy for Sudden Hearing Loss
Authors: Ohira Shinya , Komori Manabu , Tsuna Yukari , Nakamura Mitsuto , Yamaguchi Yusei , Matsuura Kentaro , Osafune Hiroshi , Wada Kota
Published: October 2023

Objective

This study evaluated the therapeutic effect of hyperbaric oxygen therapy (HBOT) combined with steroid therapy to treat sudden hearing loss and examined the index associated with excellent therapeutic effect.

Methods

We included 109 patients with sudden hearing loss. Patients were divided into the HBOT combination group (59 sides) treated with HBOT and steroid therapy and HBOT noncombination group (50 sides) involving steroid therapy only. The recovery rate of each group was compared according to the severity of hearing loss. Blood samples were evaluated and inflammatory markers, such as neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR), were calculated and compared by severity. We evaluated the usefulness of inflammatory markers for predicting recovery rate, and calculated cutoff values were also evaluated.

Results

The HBOT combination group exhibited a higher overall recovery rate than the HBOT noncombination group, particularly in severe cases. However, there was no significant difference in the severity of hearing loss based on various inflammatory markers. NLR and PLR are useful for predicting the effect in patients treated with concomitant HBOT. By setting 2.43 and 146.67 as cutoff values for NLR and PLR, respectively, we observed that lower values resulted in better recovery rates.

Conclusion

The use of HBOT is effective for severe cases and early blood flow disorders with low NLR and PLR and less inflammation. When determining treatment, not only should the severity of hearing loss be considered, but also the NLR and PLR should be evaluated and examined based on the cutoff values.
Predictive Factors for Subjective Vertigo Following Cochlear Implantation: A Regional Multicenter Cohort Study of 395 Patients
Authors: Ludbrook Isabella , Mair Manish , Phung Daniel , Corlette Toby , Huang Johnson , Kong (Worimi) Kelvin , Eisenberg Robert
Published: October 2023

Introduction

Cochlear implantation (CI) is generally accepted as having a low rate of postoperative complications, but between 9.3% and 13% of cases experience vertigo postoperatively. This study aimed to examine patient, surgical, and device factors contributing toward the risk of postoperative vertigo.

Methodology

A retrospective review was conducted of adult patients who underwent cochlear implant in a regional area of New South Wales from 2007 to 2018. A total of 395 cochlear implant cases were included in the final study.

Results

The overall incidence of vertigo at 3 months of follow-up was 7.1% (n = 28/395). No difference was identified in this study between rates of postoperative vertigo between device factors, including implant make (Cochlear vs. Med-El), electrode shape (perimodiolar vs. straight), and electrode model. No significant difference was found also for surgical factors such as the number of electrode rings inserted, side of implantation, or surgical approach of tympanic ramp (round window insertion vs. cochleostomy).

A higher percentage of patients with preoperative vertigo experienced vertigo postoperatively (18.4%, n = 7/38), compared with the population without preoperative vertigo (6.0%, n = 21/352) (p = 0.005). Patients with previous mastoid surgery also reported a higher rate of postoperative vertigo (20%, n = 9/45) compared with those who had not had mastoid surgery (5.43%, n = 19/350) (p = 0.006). The mean age of patients experiencing postoperative vertigo was higher than the population without postoperative symptoms (67 vs. 63).

Conclusion

This study of a large multicenter population outlines that patient factors are more critical than surgical or device factors when considering risk factors for vertigo post-cochlear implant.
AF2BIND: Predicting ligand-binding sites using the pair representation of AlphaFold2
Authors: Gazizov Artem , Lian Anna , Goverde Casper , Ovchinnikov Sergey , Polizzi Nicholas F.
Published: October 2023

Predicting ligand-binding sites, particularly in the absence of previously resolved homologous structures, presents a significant challenge in structural biology. Here, we leverage the internal pairwise representation of AlphaFold2 (AF2) to train a model, AF2BIND, to accurately predict small-molecule-binding residues given only a target protein. AF2BIND uses 20 “bait” amino acids to optimally extract the binding signal in the absence of a small-molecule ligand. We find that the AF2 pair representation outperforms other neural-network representations for binding-site prediction. Moreover, unique combinations of the 20 bait amino acids are correlated with chemical properties of the ligand.
Accurate identification of cancer cells in complex pre-clinical models using deep-learning: a transfection-free approach
Authors: Cortesi Marilisa , Liu Dongli , Powell Elyse , Barlow Ellen , Warton Kristina , Ford Caroline E.
Published: October 2023

3D co-cultures are key tools forin vitrobiomedical research as they recapitulate more closely thein vivoenvironment, while allowing control of the density and type of cells included in the analysis, as well as the experimental conditions in which they are maintained. More widespread application of these models is hampered however by the limited technologies available for their analysis. The separation of the contribution of the different cell types, in particular, is a fundamental challenge.

In this work, we present ORACLE, a deep neural network trained to distinguish between ovarian cancer and healthy cells based on the shape of their nucleus. The extensive validation that we have conducted includes multiple cell lines and patient derived cultures to characterise the effect of all the major potential confounding factors. High accuracy and reliability were maintained throughout the analysis demonstrating ORACLE effectiveness with this detection and classification task.

ORACLE is freely available (https://github.com/MarilisaCortesi/ORACLE/tree/main) and can be used to recognise both ovarian cancer cell lines and primary patient-derived cells. This feature sets ORACLE apart from currently available analysis methods and opens the possibility of analysingin vitroco-cultures comprised solely of patient-derived cells.
Mutualist-Provided Resources Increase Susceptibility to Parasites
Authors: Yi Eunnuri , Meng Nova , Wood Corlett Wolfe
Published: October 2023

Mutualistic microbes often increase the susceptibility of their host to parasite infection, but the mechanism underlying this pattern remains unknown. We tested two competing hypotheses to identify the cause of this phenomenon. First, mutualist-provided resources could attract antagonists by making hosts more resource-rich. Second, mutualism establishment itself might increase host vulnerability to antagonists. To test which mechanism underlies increased parasite susceptibility, we experimentally decoupled mutualism establishment and mutualist-provided resources in the legume-rhizobia mutualism. We measured parasite load on Medicago truncatula plants infected with root-knot nematodes in a full-factorial design, in which we independently manipulated rhizobia nodulation (mutualism establishment) and nitrogen availability (mutualist-provided resources). We found little effect of mutualism establishment on susceptibility, as nodulation without nitrogen fixation did not significantly increase parasite infection. By contrast, nitrogen did increase parasite infection. However, its effect was non-linear and was not explained by nitrogen assimilation into plant tissues, indicating that this effect is not driven by parasite attraction to resource-rich hosts. Our results suggest that mutualist-provided resources are an important driver of indirect ecological costs of mutualism, although the mechanism linking mutualist-provided resources and susceptibility to infection remains unknown.
ChEC-seq2: an improved Chromatin Endogenous Cleavage sequencing method and bioinformatic analysis pipeline for mappingin vivoprotein-DNA interactions
Authors: VanBelzen Jake , Duan Chengzhe , Brickner Donna Garvey , Brickner Jason H.
Published: October 2023

Defining thein vivoDNA binding specificity of transcription factors (TFs) has relied nearly exclusively on chromatin immunoprecipitation (ChIP). While ChIP reveals TF binding patterns, its resolution is low. Higher resolution methods employing nucleases such as ChIP-exo, chromatin endogenous cleavage (ChEC-seq) and CUT&RUN resolve both TF occupancy and binding site protection. ChEC-seq, in which an endogenous TF is fused to micrococcal nuclease, requires neither fixation nor antibodies. However, the specificity of DNA cleavage during ChEC has been suggested to be lower than the specificity of the peaks identified by ChIP or ChIP-exo, perhaps reflecting non-specific binding of transcription factors to DNA. We have simplified the ChEC-seq protocol to minimize nuclease digestion while increasing the yield of cleaved DNA. ChEC-seq2 cleavage patterns were highly reproducible between replicates and with published ChEC-seq data. Combined with DoubleChEC, a new bioinformatic pipeline that removes non-specific cleavage sites, ChEC-seq2 identified high-confidence cleavage sites for three different yeast TFs that are strongly enriched for their known binding sites and adjacent to known target genes.
Chromosomal DNA sequences of the Pacific saury genome: versatile resources for fishery science and comparative biology
Authors: Sato Mana , Fukuda Kazuya , Kadota Mitsutaka , Makino-Itou Hatsune , Tatsumi Kaori , Yamauchi Shinya , Kuraku Shigehiro
Published: October 2023

Pacific saury (Cololabis saira) is a commercially important small pelagic fish species in Asian. In this study, we conducted the first-ever whole genome sequencing of this species, with single molecule, real-time (SMRT) sequencing technology. The obtained high-fidelity (HiFi) long-read sequence data, which amount to approximately 30 folds of its haploid genome size that was measured with quantitative PCR (1.17 Gb), were assembled into contigs. Scaffolding with Hi-C reads yielded a whole genome assembly containing 24 chromosome-scale sequences, with a scaffold N50 length of 47.7 Mb. Screening of repetitive elements including telomeric repeats was performed to characterize possible factors that need to be resolved towards ‘telomere-to-telomere’ sequencing. The larger genome size than in medaka, a close relative in Beloniformes, is at least partly explained by larger repetitive element quantity, which is reflected in more abundant tRNAs, in the Pacific saury genome. Protein-coding regions was predicted using transcriptome data, which resulted in 22,274 components. Retrieval of Pacific saury homologs of aquaporin (AQP) genes known from other teleost fishes validated high completeness and continuity of the genome assembly. These resources are available athttps://treethinkers.nig.ac.jp/saira/and will assist various molecular-level studies in fishery science and comparative biology.
Defining metabolic flexibility in hair follicle stem cell induced squamous cell carcinoma
Authors: Galvan C , Flores A , Cerrillos V , Avila I , Murphy C , Zheng W , To TT , Christofk HR , Lowry WE
Published: October 2023

Among the numerous changes associated with the transformation to cancer, cellular metabolism is one of the first discovered and most prominent[1, 2]. However, despite the knowledge that nearly every cancer is associated with the strong upregulation of various metabolic pathways, there has yet to be much clinical progress on the treatment of cancer by targeting a single metabolic enzyme directly[3–6]. We previously showed that inhibition of glycolysis through lactate dehydrogenase (LDHA) deletion in cancer cells of origin had no effect on the initiation or progression of cutaneous squamous cell carcinoma[7], suggesting that these cancers are metabolically flexible enough to produce the necessary metabolites required for sustained growth in the absence of glycolysis. Here we focused on glutaminolysis, another metabolic pathway frequently implicated as important for tumorigenesis in correlative studies. We genetically blocked glutaminolysis through glutaminase (GLS) deletion in cancer cells of origin, and found that this had little effect on tumorigenesis, similar to what we previously showed for blocking glycolysis. Tumors with genetic deletion of glutaminolysis instead upregulated lactate consumption and utilization for the TCA cycle, providing further evidence of metabolic flexibility. We also found that the metabolic flexibility observed upon inhibition of glycolysis or glutaminolysis is due to post-transcriptional changes in the levels of plasma membrane lactate and glutamine transporters. To define the limits of metabolic flexibility in cancer initiating hair follicle stem cells, we genetically blocked both glycolysis and glutaminolysis simultaneously and found that frank carcinoma was not compatible with abrogation of both of these carbon utilization pathways. These data point towards metabolic flexibility mediated by regulation of nutrient consumption, and suggest that treatment of cancer through metabolic manipulation will require multiple interventions on distinct pathways.