bluuebunny/crossref_metadata_2025 huggingface dataset:
The entomopathogenic nematodeSteinernema hermaphroditumis a self-fertilizing hermaphrodite and a genetically tractable system for the study of parasitic and mutualistic symbiosis
Authors: Cao Mengyi , Schwartz Hillel T , Tan Chieh-Hsiang , Sternberg Paul W
Published: October 2021

Entomopathogenic nematodes (EPNs), including Heterorhabditis and Steinernema, are parasitic to insects and contain mutualistically symbiotic bacteria in their intestines (Photorhabdus and Xenorhabdus, respectively) and therefore offer opportunities to study both mutualistic and parasitic symbiosis. The establishment of genetic tools in EPNs has been impeded by limited genetic tractability, inconsistent growth in vitro, variable cryopreservation, and low mating efficiency. We obtained the recently described Steinernema hermaphroditum strain CS34 and optimized its in vitro growth, with a rapid generation time on a lawn of its native symbiotic bacteria Xenorhabdus griffiniae. We developed a simple and efficient cryopreservation method. Previously, S. hermaphroditum isolated from insect hosts was described as producing hermaphrodites in the first generation. We discovered that CS34, when grown in vitro, produced consecutive generations of autonomously reproducing hermaphrodites accompanied by rare males. We performed mutagenesis screens in S. hermaphroditum that produced mutant lines with visible and heritable phenotypes. Genetic analysis of the mutants demonstrated that this species reproduces by self-fertilization rather than parthenogenesis and that its sex is determined chromosomally. Genetic mapping has thus far identified markers on the X chromosome and three of four autosomes. We report that S. hermaphroditum CS34 is the first consistently hermaphroditic EPN and is suitable for genetic model development to study naturally occurring mutualistic symbiosis and insect parasitism.
A data-based participatory approach for health equity and digital inclusion: prioritizing stakeholders
Authors: Fotopoulou Aristea , Barratt Harriet , Marandet Elodie
Published: October 2021

This article starts from the premise that projects informed by data science can address social concerns, beyond prioritizing the design of efficient products or services. How can we bring the stakeholders and their situated realities back into the picture? It is argued that data-based, participatory interventions can improve health equity and digital inclusion while avoiding the pitfalls of top-down, technocratic methods. A participatory framework puts users, patients and citizens as stakeholders at the centre of the process, and can offer complex, sustainable benefits, which go beyond simply the experience of participation or the development of an innovative design solution. A significant benefit for example is the development of skills, which should not be seen as a by-product of the participatory processes, but a central element of empowering marginalized or excluded communities to participate in public life. By drawing from different examples in various domains, the article discusses what can be learnt from implementations of schemes using data science for social good, human-centric design, arts and wellbeing, to argue for a data-centric, creative and participatory approach to address health equity and digital inclusion in tandem.
Compactness Within the Space of Complete, ConstantQ-Curvature Metrics on the Sphere with Isolated Singularities
Authors: Andrade João Henrique , do Ó João Marcos , Ratzkin Jesse
Published: October 2021

In this paper, we consider the moduli space of complete, conformally flat metrics on a sphere with $k$ punctures having constant positive $Q$-curvature and positive scalar curvature. Previous work has shown that such metrics admit an asymptotic expansion near each puncture, allowing one to define an asymptotic necksize of each singular point. We prove that any set in the moduli space such that the distances between distinct punctures and the asymptotic necksizes all remain bounded away from zero is sequentially compact, mirroring a theorem of D. Pollack about singular Yamabe metrics. Along the way, we define a radial Pohozaev invariant at each puncture and refine some a priori bounds of the conformal factor, which may be of independent interest.
The emergence of the ceftriaxone-resistantNeisseria gonorrhoeaeFC428 clone by transfer of resistance from an oralNeisseria subflavareservoir of resistance
Authors: Kanesaka Izumo , Ohno Akira , Katsuse Akiko Kanayama , Takahashi Hiroshi , Kobayashi Intetsu
Published: October 2021

Background

The ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone was first discovered in Japan in 2015.

Objectives

We investigated the possibility of horizontal gene transfer from Neisseria subflava harbouring the mosaic-like PBP-2 in the emergence of the FC428 clone. We also analysed whether there were fitness costs associated with the sustained international dissemination of the clone.

Methods

Sequencing of the penA gene in ceftriaxone-resistant N. subflava strains was performed. For transformation experiments between donor N. subflava and ciprofloxacin-resistant wild-type penA N. gonorrhoeae recipient, the full-length PCR amplification product of the penA gene, including DUS regions, was used as the donor DNA. Biological fitness of the transformants was measured by growth competition assays. The impact of QRDR and mtrR mutations, which have been reported as compensatory mutations, on fitness was also assessed.

Results

The penA mosaic allele of the FC428 clone showed 100%, 91.8%, and 89.8% homology, respectively, with penA genes of three ceftriaxone-resistant N. subflava strains, No. 30, No. 9 and No. 14. Results were consistent with homologous recombination with the donated penA mosaic allele. In co-cultures with the parent strain, transformants showed comparable growth indicating that a gyrA mutation compensates for the fitness cost of mosaic penA alleles.

Conclusions

Our findings support the hypothesis that the FC428 clone was generated by transformation of the mosaic penA allele from oropharyngeal N. subflava to N. gonorrhoeae. Furthermore, it suggests that mutations in the gyrA QRDR region compensate for fitness costs and contribute to the continued transmission of the FC428 clone.
Myostatin suppresses adipogenic differentiation and lipid accumulation by activating crosstalk between ERK1/2 and PKA signaling pathways in porcine subcutaneous preadipocytes
Authors: Pan Shifeng , Zhang Lin , Liu Zhuang , Xing Hua
Published: October 2021

The current study was undertaken to determine the effect of myostatin (MSTN) on lipid accumulation in porcine subcutaneous preadipocytes (PSPAs) and to further explore the potential molecular mechanisms. PSPAs isolated from Meishan weaned piglets were added with various concentrations of MSTN recombinant protein during the entire period of adipogenic differentiation process. Results showed that MSTN treatment significantly reduced the lipid accumulation, intracellular triglyceride (TG) content, glucose consumption, and glycerol phosphate dehydrogenase activity, while increased glycerol and free fatty acid release. Consistent with above results, the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway was obviously activated and thus key adipogenic transcription factors peroxisome proliferator-activated receptor-gamma (PPAR-γ), CCAAT/enhancer-binding protein-alpha (C/EBP-α), and their downstream enzymes fatty acid synthase and acetyl-CoA carboxylase were all inhibited. However, chemical inhibition of ERK1/2 signaling pathway by PD98059 markedly reversed the decreased TG content by increasing PPAR-γ expression. In addition, MSTN activated the cyclic AMP/protein kinase A (cAMP/PKA) pathway and stimulated lipolysis by reducing the expression of antilipolytic gene perilipin, thus elevated key lipolytic enzymes adipose triglyceride lipase and hormone-sensitive lipase (HSL) expression and enzyme activity. On the contrary, pretreatment with PKA inhibitor H89 significantly reversed TG accumulation by increasing PPAR-γ expression and thus inhibiting ERK1/2, perilipin, and HSL phosphorylation, supporting the crosstalk between PKA and ERK1/2 pathways in both the anti-adipogenic and pro-lipolytic effects. In summary, our results suggested that MSTN suppressed adipogenesis and stimulated lipolysis, which was mainly mediated by activating crosstalk of ERK1/2 and PKA signaling pathways, and consequently decreased lipid accumulation in PSPAs, our findings may provide novel insights for further exploring MSTN as a potent inhibitor of porcine subcutaneous lipid accumulation.
The Future of Brands and Branding: An Essay on Multiplicity, Heterogeneity, and Integration
Authors: Keller Kevin Lane
Published: October 2021

Brands come in many forms and perform multiple roles and functions for a variety of different types of individuals and organizations. Focusing on companies or non-profits marketing to consumers, this essay speculates on the future of branding in five main areas: brand elements, brand drivers, brand meaning, consumer heterogeneity, and consumer insights. Across these five areas, the main theme that emerges is that branding is increasingly being defined both by multiplicity, in terms of what marketers can do, and by heterogeneity, in terms of the consumers being marketed to. Successful brand marketers going forward will be those who can find integrative branding solutions that balance and blend multiplicity and heterogeneity.
The Wenceslaus Hollar collection of Sidney T. Fisher, and catalogue by Richard Pennington
Authors: Turner Simon
Published: October 2021

The comprehensive collection of prints by Wenceslaus Hollar (1607–1677) donated by Sidney T. Fisher to the Thomas Fisher Rare Book Library of the University of Toronto ranks alongside the collections in London, Prague and Windsor. Based on the extensive unpublished correspondence between Sidney Fisher and Richard Pennington preserved in Toronto, this article describes the formation of Fisher’s Hollar collection and Pennington’s work towards ‘A Descriptive Catalogue of the Etched Work of Wenceslaus Hollar, 1607–1677’ (Cambridge, 1982). The activities of Pennington as an agent for Fisher and his dealings with Cambridge University Press are also detailed.
Diversity of Culicoides (Diptera: Ceratopogonidae) in Rural Settlements and Degraded Seasonal Deciduous Forests
Authors: da Conceição Abreu Bandeira Maria , Cerqueira Allane Barros , Luiz Pinto Moraes Jorge , Brazil Reginaldo Peçanha , Rebêlo José Manuel Macário
Published: October 2021

Biting midges are widespread in Brazilian natural ecosystems. However, deforestation and other activities that impact the environment are reducing natural habitats where biting midges proliferate. The objective of this study was to verify whether there is variation in the composition, richness, abundance, and seasonality of biting midges between wild and rural environments, in a forest area with intense deforestation. Biting midges were captured using 6 traps installed at an average height of 1.5 m in the peridomicile, intradomicile, and deciduous seasonal forests, once a month from May 2012 to April 2013. In total, 2,182 specimens of 13 species of the genus Culicoides were captured. Species richness was similar in the intradomicile (13 species), forest (12), and peridomicile (11), but species diversity was greater in the peridomicile (H’ = 0.803) compared with the intradomicile (H’ = 0.717) and forest (H’ = 0.687). The order of species dominance varied between the forest (Culicoides paucienfuscatus Barbosa > Culicoides leopodoi Ortiz > Culicoides foxi Ortiz > Culicoides ignacioi Forattini) and peridomicile + intradomicile habitats (C. paucienfuscatus > C. foxi > C. filariferus Hoffman > C. ignacioi). The activity of these dipterans was strongly influenced by meteorological variables, as biting midges are predominant in the rainy season (80.7% of specimens), when higher rainfall, relative humidity, and lower temperatures prevail. The abundance of biting midges was higher in the peridomicile + intradomicile (83.7% of specimens) compared with the degraded forest (16.3%), a result that reflects the loss of forest habitat due to intense and progressive deforestation.
Place and Pain: Association Between Neighborhood SES and Quantitative Sensory Testing Responses in Youth With Functional Abdominal Pain
Authors: Morris Matthew C , Bruehl Stephen , Stone Amanda L , Garber Judy , Smith Craig , Palermo Tonya M , Walker Lynn S
Published: October 2021

Objective

Neighborhood socioeconomic status (SES) is linked to self-reported pain severity and disability but its association with evoked pain responsiveness in individuals with chronic pain remains unclear. The present study examined relations between neighborhood SES, assessed through the area deprivation index (ADI), and static and dynamic pain response indices. It was hypothesized that youth with functional abdominal pain (FAP) living in lower SES neighborhoods would exhibit lower pain threshold, lower pain tolerance, and reduced conditioned pain modulation (CPM) compared to youth living in higher SES neighborhoods.

Methods

Participants were 183 youth with FAP and their parents. Youth completed a quantitative sensory testing protocol. Family addresses were used to compute ADI scores. Thermal stimuli for pain threshold and tolerance were delivered to participants’ forearms using thermodes. CPM, an index of descending pain inhibition, was determined using a thermode as test stimulus and a hot water bath as conditioning stimulus.

Results

As hypothesized, youth with FAP living in lower SES neighborhoods exhibited weaker CPM. Contrary to hypotheses, lower neighborhood SES was associated with neither pain thresholds nor with pain tolerance.

Conclusions

These findings demonstrated the independent contribution of place of residence—an often neglected component of the biopsychosocial model—to efficiency of descending pain inhibition. Understanding the mechanisms that account for such associations between place and pain could guide the development of public health and policy initiatives designed to mitigate chronic pain risk in underserved and economically marginalized communities.
Submillimetre compactness as a critical dimension to understand the main sequence of star-forming galaxies
Authors: Puglisi Annagrazia , Daddi Emanuele , Valentino Francesco , Magdis Georgios , Liu Daizhong , Kokorev Vasily , Circosta Chiara , Elbaz David , Bournaud Frederic , Gomez-Guijarro Carlos , Jin Shuowen , Madden Suzanne , Sargent Mark T , Swinbank Mark
Published: October 2021

We study the interstellar medium (ISM) properties as a function of the molecular gas size for 77 infrared-selected galaxies at z ∼ 1.3, having stellar masses 109.4 ≲ M⋆ ≲ 1012.0 M⊙ and star formation rates 12 ≲ SFRFIR ≲ 1000 M⊙ yr−1. Molecular gas sizes are measured on ALMA images that combine CO(2-1), CO(5-4), and underlying continuum observations, and include CO(4-3), CO(7-6) + [CI](3P2 − 3P1), [CI](3P1 − 3P0) observations for a subset of the sample. The $\gtrsim $46 per cent of our galaxies have a compact molecular gas reservoir, and lie below the optical discs mass–size relation. Compact galaxies on and above the main sequence have higher CO excitation and star formation efficiency than galaxies with extended molecular gas reservoirs, as traced by CO(5-4)/CO(2-1) and CO(2-1)/LIR, SF ratios. Average CO + [CI] spectral line energy distributions indicate higher excitation in compacts relative to extended sources. Using CO(2-1) and dust masses as molecular gas mass tracers, and conversion factors tailored to their ISM conditions, we measure lower gas fractions in compact main-sequence galaxies compared to extended sources. We suggest that the submillimetre compactness, defined as the ratio between the molecular gas and the stellar size, is an unavoidable information to be used with the main sequence offset to describe the ISM properties of galaxies, at least above M⋆ ≥ 1010.6 M⊙, where our observations fully probe the main sequence scatter. Our results are consistent with mergers driving the gas in the nuclear regions, enhancing the CO excitation and star formation efficiency. Compact main-sequence galaxies are consistent with being an early post-starburst population following a merger-driven starburst episode, stressing the important role of mergers in the evolution of massive galaxies.
Dynamics of relativistic radio jets in asymmetric environments
Authors: Yates-Jones Patrick M , Shabala Stanislav S , Krause Martin G H
Published: October 2021

We have carried out relativistic three-dimensional simulations of high-power radio sources propagating i,nto asymmetric cluster environments. We offset the environment by 0 or 1 core radii (equal to 144 kpc), and incline the jets by 0, 15, or 45° away from the environment centre. The different environment encountered by each radio lobe provides a unique opportunity to study the effect of environment on otherwise identical jets. We find that the jets become unstable towards the end of the simulations, even with a Lorentz factor of 5; they nevertheless develop typical Fanaroff–Riley class II radio morphology. The jets propagating into denser environments have consistently shorter lobe lengths and brighter hotspots, while the axial ratio of the two lobes is similar. We reproduce the recently reported observational anticorrelation between lobe length asymmetry and environment asymmetry, corroborating the notion that observed large-scale radio lobe asymmetry can be driven by differences in the underlying environment.
Two striking head–tail galaxies in the galaxy cluster IIZW108: insights into transition to turbulence, magnetic fields, and particle re-acceleration
Authors: Müller Ancla , Pfrommer Christoph , Ignesti Alessandro , Moretti Alessia , Lourenço Ana , Paladino Rosita , Jaffé Yara , Gitti Myriam , Venturi Tiziana , Gullieuszik Marco , Poggianti Bianca , Vulcani Benedetta , Biviano Andrea , Adebahr Björn , Dettmar Ralf-Jürgen
Published: October 2021

We present deep Jansky Very Large Array observations at 1.4 and 2.7 GHz (full polarization), as well as optical OmegaWINGS/WINGS and X-ray observations of two extended radio galaxies in the IIZW108 galaxy cluster at z = 0.04889. They show a bent tail morphology in agreement with a radio lobed galaxy falling into the cluster potential. Both galaxies are found to possess properties comparable with narrow-angle tail galaxies in the literature even though they are part of a low mass cluster. We find a spectral index steepening and an increase in fractional polarization through the galaxy jets and an ordered magnetic field component mostly aligned with the jet direction. This is likely caused by either shear due to the velocity difference of the intracluster medium and the jet fluid and/or magnetic draping of the intracluster medium across the galaxy jets. We find clear evidence that one source is showing two active galactic nuclei (AGN) outbursts from which we expect the AGN has never turned off completely. We show that pure standard electron cooling cannot explain the jet length. We demonstrate therefore that these galaxies can be used as a laboratory to study gentle re-acceleration of relativistic electrons in galaxy jets via transition from laminar to turbulent motion.
The effects of magnetic fields on observational signatures of atmospheric escape in exoplanets: Double tail structures
Authors: Carolan S , Vidotto A A , Hazra G , Villarreal D’Angelo C , Kubyshkina D
Published: October 2021

Using 3D radiative MHD simulations and Lyman-α transit calculations, we investigate the effect of magnetic fields on the observational signatures of atmospheric escape in exoplanets. Using the same stellar wind, we vary the planet’s dipole field strength (Bp) from 0 to 10G. For Bp < 3G, the structure of the escaping atmosphere begins to break away from a comet-like tail following the planet (Bp = 0), as we see more absorbing material above and below the orbital plane. For Bp ≥ 3G, we find a ‘dead-zone’ around the equator, where low velocity material is trapped in the closed magnetic field lines. The dead-zone separates two polar outflows where absorbing material escapes along open field lines, leading to a double tail structure, above and below the orbital plane. We demonstrate that atmospheric escape in magnetized planets occurs through polar outflows, as opposed to the predominantly night-side escape in non-magnetized models. We find a small increase in escape rate with Bp, though this should not affect the time-scale of atmospheric loss. As the size of the dead-zone increases with Bp, so does the line centre absorption in Lyman-α, as more low-velocity neutral hydrogen covers the stellar disc during transit. For Bp < 3G the absorption in the blue wing decreases, as the escaping atmosphere is less funnelled along the line of sight by the stellar wind. In the red wing (and for Bp > 3G in the blue wing) the absorption increases caused by the growing volume of the magnetosphere. Finally we show that transits below and above the mid-disc differ caused by the asymmetry of the double tail structure.
Impacting the Treatment of Highly Eloquent Supratentorial Cerebral Cavernous Malformations by Noninvasive Functional Mapping—An Observational Cohort Study
Authors: Ille Sebastian , Schroeder Axel , Hostettler Isabel C , Wostrack Maria , Meyer Bernhard , Krieg Sandro M
Published: October 2021

BACKGROUND

Cerebral cavernous malformations (CCM) may cause cavernoma-related epilepsy (CRE) and intracranial hemorrhage (ICH). Functional mapping has shown its usefulness during the resection of eloquent lesions including the treatment of brain arteriovenous malformations.

OBJECTIVE

To evaluate the impact of noninvasive functional mapping on decision-making and resection of eloquently located CCM.

METHODS

Of 126 patients with intracranial cavernomas, we prospectively included 40 consecutive patients (31.7%) with highly eloquent CCM between 2012 and 2020. We performed functional mapping via navigated transcranial magnetic stimulation (nTMS) motor mapping in 30 cases and nTMS language mapping in 20 cases. Twenty patients suffered from CRE. CCM caused ICH in 18 cases.

RESULTS

We used functional mapping data including function-based tractography in all cases. Indication toward (31 cases) or against (9 cases) CCM resection was influenced by noninvasive functional mapping in 36 cases (90%). We resected CCMs in 24 cases, and 7 patients refused the recommendation for surgery. In 19 and 4 cases, we used additional intraoperative neuromonitoring and awake craniotomy, respectively. Patients suffered from transient postoperative motor or language deficits in 2 and 2 cases, respectively. No patient suffered from permanent deficits. After 1 yr of follow-up, anti-epileptic drugs could be discontinued in all patients who underwent surgery but 1 patient.

CONCLUSION

Surgery-related deficit rates are low even for highly eloquent CCM and seizure outcome is excellent. The present results show that noninvasive functional mapping and function-based tractography is a useful tool for the decision-making process and during microsurgical resection of eloquently located CCM.
Versatile Use of Intraoperative Ultrasound Guidance for Brain Puncture
Authors: Unal Tugrul Cem , Gulsever Cafer Ikbal , Sahin Duran , Dagdeviren Huseyin Emre , Dolas Ilyas , Sabanci Pulat Akin , Aras Yavuz , Sencer Altay , Aydoseli Aydin
Published: October 2021

BACKGROUND

Intraoperative ultrasound (iUS) is an effective guidance and imaging system commonly used in neuro-oncological surgery. Despite the versatility of iUS, its utility for single burr hole puncture guidance remains fairly underappreciated.

OBJECTIVE

To highlight the simplicity, versatility, and effectiveness of iUS guidance in brain puncture by presenting the current case series and technical note collection.

METHODS

We present 4 novel uses of iUS guidance for single burr hole brain puncture: cannulation of normal-sized ventricles, endoscopic third ventriculostomy (ETV) guidance, evacuation of interhemispheric empyema, and stereotactic biopsy assistance.

RESULTS

All techniques were performed successfully in a total of 16 patients. Normal-sized ventricles were cannulated in 7 patients, among whom 5 underwent Ommaya reservoir placement and 2 underwent ventriculoperitoneal shunt placement for idiopathic intracranial hypertension. No more than 1 attempt was needed for cannulation. All ventricular tip positions were optimal as shown by postoperative imaging. iUS guidance was used in 5 ETV procedures. The working cannula was successfully introduced to the lateral ventricle, providing the optimal trajectory to the third ventricular floor in these cases. Interhemispheric subdural empyema was aspirated with iUS guidance in 1 patient. Volume reduction was clearly visible, allowing near-total evacuation of the empyema. iUS guidance was used for assistive purposes during stereotactic biopsy in 3 patients. No major perioperative complications were observed throughout this series.

CONCLUSION

iUS is an effective and versatile guidance system that allows for real-time imaging and can be easily and safely employed for various brain puncture procedures.
Forbidden Fruits: The Political Economy of Science, Religion, and Growth
Authors: Bénabou Roland , Ticchi Davide , Vindigni Andrea
Published: October 2021

We study the co-evolution of religion, science, and politics. We first uncover, in international and U.S. data, a robust negative relationship between religiosity and patents per capita. The model then combines: (1) scientific discoveries that raise productivity but sometimes erode religious beliefs; (2) a government that allows innovations to diffuse, or blocks them; (3) religious institutions that can invest in doctrinal reform. Three long-term outcomes emerge. The “Western-European Secularization” regime has declining religiosity, unimpeded science, and high taxes and transfers. The “Theocratic” regime involves knowledge stagnation, unquestioned dogma, and high religious-public-goods spending. The “American” regime combines scientific progress and stable religiosity through doctrinal adaptations, with low taxes and some fiscal-legal advantages for religious activities. Rising income inequality can, however, empower a Religious-Right alliance that starts blocking belief-eroding ideas.
Refinement of Nonantibiotic Spray Programs for Fire Blight Control in Organic Pome Fruit
Authors: Johnson Kenneth B. , Temple Todd N. , KC Achala , Elkins Rachel B.
Published: October 2021

Fire blight-susceptible, certified organic pome fruit is produced on 9,000 ha in the Pacific Northwest region of the United States with acreage continuing to expand despite a 2014 prohibition on antibiotics as allowable materials for infection suppression. Nonantibiotic practices for fire blight pathogen suppression mirror conventional management, but the full-bloom-to-petal-fall period when antibiotics are typically sprayed for fire blight control continues to receive research scrutiny owing to drawbacks and weaknesses of alternative materials. As solitary treatments, effective nonantibiotic materials (e.g., a yeast biocontrol, soluble coppers, and potassium aluminum sulfate) raise the risk of a crop-value–reducing, phytotoxic response termed “fruit russeting.” Conversely, materials with less russeting risk (e.g., Bacillus-based biorationals) are less effective for fire blight control. Spray programs using a sequence of materials applied from midbloom to petal fall have the potential to provide high levels of protection with reduced russeting risk. In orchard trials, the effects of nonantibiotic spray programs on the epiphytic population size of Erwinia amylovora in flowers, yeast biocontrol population size, floral pH, infection suppression, and fruit russeting revealed strategies for sequencing sprays of nonantibiotic materials. The yeast biocontrol, Blossom Protect (Aureobasidium pullulans), sprayed at 70% bloom, was an important contributor to fire blight pathogen suppression as was the soluble copper material, Previsto, when applied at full bloom. Choice of material for the petal-fall spray timing was important to fruit russeting risk but apparently less important to overall infection incidence. Consequently, treatment programs of Blossom Protect at 70% bloom, a soluble copper at full bloom, and a Bacillus-based biorational at petal fall, best balance the quality of infection suppression with the risk of fruit russeting.
Investigating Chemical and Biological Control Applications for Pythium Root Rot Prevention and Impacts on Creeping Bentgrass Putting Green Rhizosphere Bacterial Communities
Authors: Doherty Joseph R. , Roberts Joseph A.
Published: October 2021

Pythium root rot (PRR) is a disease that can rapidly devastate large swaths of golf course putting greens, with little recourse once symptoms appear. Golf courses routinely apply preventive fungicides for root diseases, which may alter the rhizosphere microbiome, leading to unintended effects on plant health. A multiyear field trial was initiated on a ‘T-1’ creeping bentgrass (Agrostis stolonifera L. cultivar T-1) putting green in College Park, Maryland to evaluate preventive PRR management for disease suppression and effects on rhizosphere bacterial communities. Fungicides commonly used to prevent PRR and a biological fungicide were repeatedly applied to experimental plots throughout the growing season. Rhizosphere samples were collected twice annually from each plot for evaluation of rhizosphere bacterial communities through amplicon sequencing and monitoring of biological control organism populations via quantitative PCR. Cyazofamid was the only treatment to suppress PRR in both years compared with the control. Fosetyl-Al on a 14-day interval and Bacillus subtilis QST713 also reduced PRR severity in 2019 compared with the nontreated control. Treatments did not significantly affect bacterial diversity or relative abundances of bacterial classes; however, seasonal environmental changes did. Repeated rhizosphere-targeted applications of B. subtilis QST713 appear to have established the bacterium into the rhizosphere, as populations increased between samples, even after applications stopped. These findings suggest that QST713 may reduce pathogen pressure when repeatedly applied and can reduce fungicide usage during periods of low PRR pressure.
Transforming an Orthopaedic Unit Into an “Age-Friendly” Unit Through Implementation of the American Geriatrics Society's CoCare: Ortho Program
Authors: Shen Jenny Y. , Mendelson Daniel Ari , Lang Valerie J.
Published: October 2021

Objective:

To transform an inpatient orthopaedic unit into an age-friendly unit for geriatric fracture center (GFC) patients.

Design:

Pragmatic dissemination study of a continuous quality improvement intervention with episodic data review.

Setting:

Large quaternary care university hospital with no on-site geriatrics program and no dedicated geriatric inpatient unit.

Participants:

Individuals 60 years of age and older with fragility fracture of the native proximal femur hospitalized from July 2017 to June 2020.

Intervention:

A hospital medicine-orthopaedics comanagement model for a GFC was developed using processes, tools, and education provided by the American Geriatrics Society's AGS CoCare: Ortho program to support the age-friendly 4Ms principles: mentation, mobility, medications, and what matters. Delirium reduction strategies included minimizing sleep interruption through changes in blood draw times, order sets for pain management, and nursing education. Mobility specialists were incorporated to improve early mobilization on the orthopaedic unit.

Main Outcome Measurements:

Frequency of weight-bearing on postoperative day 1 and frequency of delirium among GFC patients on the orthopaedic unit were compared with those among concurrent GFC patients on other units.

Results:

Frequency of delirium was 26% among patients on the orthopaedic unit versus 35% among those on other units (P = 0.055). Frequency of weight-bearing on post-operative day 1 was 84% among patients on the orthopaedic unit versus 72% among those on other units (P = 0.003).

Conclusions:

AGS CoCare: Ortho is an effective dissemination program for establishing a hospital medicine-orthopaedics comanagement program and making an orthopaedic unit age-friendly in a hospital without onsite geriatricians or a dedicated geriatrics unit.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Validation and Clinical Application of a Liquid Chromatography–Ultraviolet Detection Method to Quantify Dolutegravir in Dried Blood Spots
Authors: Akinloye Abdulafeez , Eniayewu Oluwasegun , Adeagbo Babatunde , Bolaji Oluseye , Olagunju Adeniyi
Published: October 2021

Background:

Dolutegravir is currently the preferred component of first-line antiretroviral therapy. To facilitate clinical pharmacology studies in key populations, quantitative analytical methods compatible with microsampling and adaptable to resource-limited settings are desirable. The authors developed and validated a liquid chromatography–ultraviolet detection method to quantify dolutegravir in dried blood spots (DBS).

Methods:

Calibration standards and quality control samples were prepared by spotting 50 μL of dolutegravir-spiked whole blood on each circle of DBS cards. Three spots (two 6-mm punches/spot) were extracted with methanol. Chromatographic separation was achieved with gradient elution of acetonitrile/potassium phosphate monobasic buffer (pH 5) on a reverse-phase C18 column (flow rate, 1 mL/min) using pioglitazone as the internal standard. UV detection was performed at 260 nm. In the clinical pharmacokinetic study, DBS from finger prick was collected from participants (n = 10) at 8 time points over 12 hours postdosing, with paired plasma at 1 and 12 hours. The method was used to quantify dolutegravir, estimating pharmacokinetic parameters. Agreement between DBS and plasma concentrations was evaluated using linearity and Bland–Altman plots.

Results:

The method was validated over the concentration range of 0.4–10 mcg/mL, accuracy was 102.4%–114.8%, and precision was 3.4%–14.7%. The mean recovery was 42.3% (%CV: 8.3). The mean (±SD) dolutegravir concentration in DBS was 37.5% (±3.8%) lower than that in the plasma. DBS-derived and measured plasma concentrations showed strong correlation with linearity (R2 = 0.9804) and Bland–Altman plots. Means (%CV) of area under curve, Cmax, and C24 from the DBS-derived plasma concentration were 37.8 (23.2) mcg·h/mL, 2.7 (24.7) mcg/mL, and 1.34 (31.6) mcg/mL, respectively.

Conclusions:

The application of this simple, accurate, and precise method will expand opportunities for clinical assessment of dolutegravir in resource-limited settings.
Immunization-Associated Corneal Transplantation Rejection: A Review
Authors: Lee Edward H. , Li Jennifer Y.
Published: October 2021

Purpose:

The purpose of this review was to examine and characterize the available literature regarding immunization-associated corneal graft rejection.

Methods:

A Literature search was conducted using PubMed keywords relevant to corneal transplantation, graft rejection, and immunization to find relevant publications through July 2021. Nine studies were included in this review. Data including patient demographics, type of transplant, chronology of disease, type of immunization, treatment, and outcomes were evaluated.

Results:

Twenty-three cases of corneal graft rejection associated temporally with immunizations have been described in the literature. Most of these patients were female, and most commonly had received the influenza vaccine before the rejection episode. Most episodes resulted in graft preservation with intensive corticosteroid therapy.

Conclusions:

Immunization-associated corneal graft rejection is a rare but likely underreported phenomenon. Patients and surgeons should be aware of this possible risk, although the evidence is inconclusive. Conclusions are limited because of the small sample size and the retrospective nature of all existing literature on this subject. Surgeons should be encouraged to document and report these episodes.
IgA nephropathy in IgG kappa multiple myeloma
Authors: Couto Maria Eduarda , Sousa Domingos , Ferreira Hugo , Tavares Alda , Oliveira Isabel , Domingues Nelson , Paiva Ana , Chuva Teresa , Maximino José , Henrique Rui Manuel Ferreira , Mariz José Mário
Published: October 2021

Multiple myeloma (MM) frequently affects kidney function through multiple mechanisms. Nonetheless, some patients develop kidney injury due to other causes. A 54-year-old woman was diagnosed with IgG kappa MM developed IgA nephropathy without cast nephropathy. Further studies did not show criteria for MM progression or other causes. This case highlights the need for further investigation of kidney injury in MM patients (such as toxicity of previous drugs, infectious events, or immune-mediated disorders).
Severe ocular involvement in hereditary gelsolin amyloidosis
Authors: da Silva Nisa Filipa Pinho , Beirão João Nuno Melo
Published: October 2021

Hereditary gelsolin amyloidosis is a rare subtype of hereditary systemic amyloidosis. An old male presented with the characteristic triad of symptoms, including bilateral facial palsy, cutis laxa, and corneal lattice amyloidosis. The diagnosis was confirmed by the detection of the mutation in gelsolin gene located on chromosome 9. Although the presenting symptoms were highly suggestive of the disease, reports of severe ocular involvement are scarce in the literature.
Estimation of Utility Values for Computing Quality-adjusted Life Years Associated With Homelessness
Authors: Rajan Suja S. , Tsai Jack
Published: October 2021

Background:

There is a lack of data-driven evidence about the burden of homelessness, and lack of a holistic measure of effectiveness for evaluating interventions targeting homelessness. Quality-adjusted life years (QALYs) can help holistically capture the burden of homelessness, and facilitate the valuation and comparison of interventions designed to address homelessness.

Objective:

This study estimated utility values required to compute the QALYs associated with homelessness, and also examined individual-level characteristics that affect these values.

Research Design:

The study is cross-sectional and derived from a large national survey conducted during the coronavirus disease 2019 pandemic.

Subjects:

A sample of 6607 middle- and low-income adults in the United States.

Measures:

A self-completion standard gamble survey was used to estimate utility values associated with homelessness. Linear regression was used to analyze the association between individual-level characteristics and these utility values.

Results:

The study estimated the average utility value associated with homelessness as 43.4% among the study participants. This implies that 1 year of life as a homeless individual is perceived to be equivalent to less than half a year of life as a stably housed individual in good health. The study also found that individuals who have experienced homelessness and financial distress value life as a homeless person considerably less than those who have not had these experiences.

Conclusions:

The method developed in this study can be used to estimate QALYs in studies evaluating homelessness interventions, thereby establishing the societal value of these interventions and informing policy and budgetary decision-making. Future studies estimating the utility values associated with homelessness in the general population, as well as specific homeless groups, are required to provide more generalizable evidence.
A Risk Prediction Model for Long-term Prescription Opioid Use
Authors: Tseregounis Iraklis E. , Tancredi Daniel J. , Stewart Susan L. , Shev Aaron B. , Crawford Andrew , Gasper James J. , Wintemute Garen , Marshall Brandon D.L. , Cerdá Magdalena , Henry Stephen G.
Published: October 2021

Background:

Tools are needed to aid clinicians in estimating their patients’ risk of transitioning to long-term opioid use and to inform prescribing decisions.

Objective:

The objective of this study was to develop and validate a model that predicts previously opioid-naive patients’ risk of transitioning to long-term use.

Research Design:

This was a statewide population-based prognostic study.

Subjects:

Opioid-naive (no prescriptions in previous 2 y) patients aged 12 years old and above who received a pill-form opioid analgesic in 2016–2018 and whose prescriptions were registered in the California Prescription Drug Monitoring Program (PDMP).

Measures:

A multiple logistic regression approach was used to construct a prediction model with long-term (ie, >90 d) opioid use as the outcome. Models were developed using 2016–2017 data and validated using 2018 data. Discrimination (c-statistic), calibration (calibration slope, intercept, and visual inspection of calibration plots), and clinical utility (decision curve analysis) were evaluated to assess performance.

Results:

Development and validation cohorts included 7,175,885 and 2,788,837 opioid-naive patients with outcome rates of 5.0% and 4.7%, respectively. The model showed high discrimination (c-statistic: 0.904 for development, 0.913 for validation), was well-calibrated after intercept adjustment (intercept, −0.006; 95% confidence interval, −0.016 to 0.004; slope, 1.049; 95% confidence interval, 1.045–1.053), and had a net benefit over a wide range of probability thresholds.

Conclusions:

A model for the transition from opioid-naive status to long-term use had high discrimination and was well-calibrated. Given its high predictive performance, this model shows promise for future integration into PDMPs to aid clinicians in formulating opioid prescribing decisions at the point of care.
Optic Disc Edema in Syphilis
Authors: Kabanovski Anna , Donaldson Laura , Jeeva-Patel Trishal , Margolin Edward A.
Published: October 2021

Background:

Syphilis is an uncommon cause of optic nerve head edema; however, differentiating syphilis from other etiologies of optic nerve head swelling may be challenging. We describe 4 cases of ocular syphilis presenting with swollen optic nerve head(s) without overt signs of intraocular inflammation to better define the phenotypic presentation of this condition to allow its early recognition and treatment and discuss potential pathophysiological mechanisms of syphilitic optic neuropathy.

Methods:

Retrospective case series of patients presenting to a tertiary neuro-ophthalmology practice with a swollen optic nerve head(s) but no overt signs of intraocular inflammation, which was eventually determined to be secondary to syphilis.

Results:

Four patients were included in the study. The mean age was 43 years, 2 were women and 2 had bilateral involvement. Two patients had a recent history of skin rash, and one patient was investigated for abdominal pain and elevated liver enzymes. Two patients presented with photopsias and preserved visual function, whereas 2 presented with vision loss. Although chorioretinitis was present in all cases, it was very subtle in all and was only appreciated on fundus autofluorescence (FA) in 3 of 4 cases. Three patients demonstrated evidence of optic perineuritis on neuro-imaging. All patients were treated with a course of intravenous penicillin with a variable degree of visual recovery.

Conclusions:

Systemic symptoms are common in patients with syphilic optic neuropathy. Optic disc edema as a manifestation of syphilis is usually accompanied by subtle chorioretinitis, which is best appreciated on FA. Optic perineuritis is common in patients with syphilitic optic neuropathy, with its pathophysiology likely similar to meningitis seen in neurosyphilis.
Locating disease spread: cholera to coronavirus and the art of the image
Authors: Barrett Katy , Belknap Geoffrey
Published: October 2021

This article considers the history of medical image-making to shed light on an aspect of the COVID-19 pandemic. Starting from a contemporary art commission in the Science Museum's ‘Medicine: The Wellcome Galleries’, we look at the role of image production and presentation in understanding the spread of disease. From the intertwined histories of art and scientific image-making, we explore five examples of iconic medical images, by John Snow, Florence Nightingale, Arthur Schuster, Donald Caspar and Aaron Klug, ending with a model of the coronavirus by the Cambridge University Laboratory of Molecular Biology. We trace how images have provided the means for discovery, for description and for diagnosis and outline the different ways in which diseases have been located in the history of the medical image: in the community, in the body, in the cell and on the image itself.
Miasmas, mental models and preventive public health: some philosophical reflections on science in the COVID-19 pandemic
Authors: Greenhalgh Trisha
Published: October 2021

When the history of the COVID-19 pandemic is written, it is likely to show that the mental models held by scientists sometimes facilitated their thinking, thereby leading to lives saved, and at other times constrained their thinking, thereby leading to lives lost. This paper explores some competing mental models of how infectious diseases spread and shows how these models influenced the scientific process and the kinds of facts that were generated, legitimized and used to support policy. A central theme in the paper is the relative weight given by dominant scientific voices to probabilistic arguments based on experimental measurements versus mechanistic arguments based on theory. Two examples are explored: the cholera epidemic in nineteenth century London—in which the story of John Snow and the Broad Street pump is retold—and the unfolding of the COVID-19 pandemic in 2020 and early 2021—in which the evidence-based medicine movement and its hierarchy of evidence features prominently. In each case, it is shown that prevailing mental models—which were assumed by some to transcend theory but were actually heavily theory-laden—powerfully shaped both science and policy, with fatal consequences for some.
How did we get here: what are droplets and aerosols and how far do they go? A historical perspective on the transmission of respiratory infectious diseases
Authors: Randall K. , Ewing E. T. , Marr L. C. , Jimenez J. L. , Bourouiba L.
Published: October 2021

The COVID-19 pandemic has exposed major gaps in our understanding of the transmission of viruses through the air. These gaps slowed recognition of airborne transmission of the disease, contributed to muddled public health policies and impeded clear messaging on how best to slow transmission of COVID-19. In particular, current recommendations have been based on four tenets: (i) respiratory disease transmission routes can be viewed mostly in a binary manner of ‘droplets’ versus ‘aerosols’; (ii) this dichotomy depends on droplet size alone; (iii) the cut-off size between these routes of transmission is 5 µm; and (iv) there is a dichotomy in the distance at which transmission by each route is relevant. Yet, a relationship between these assertions is not supported by current scientific knowledge. Here, we revisit the historical foundation of these notions, and how they became entangled from the 1800s to today, with a complex interplay among various fields of science and medicine. This journey into the past highlights potential solutions for better collaboration and integration of scientific results into practice for building a more resilient society with more sound, far-sighted and effective public health policies.