bluuebunny/crossref_metadata_2025 huggingface dataset:
The very possibility of contemplation: The dialectics of intellect and will in Schopenhauer's aesthetics
Authors: Sattar Alexander
Published: December 2023

In this article, I explore how Schopenhauer's theory of aesthetic experience—independently of his theory of arts—accommodates the possibility of contemplation. The standard reading of his aesthetics is that contemplation becomes possible because of a certain “surplus” of intellect and facilitating external occasions. I argue, however, that the “essential imperfections” of intellect and Schopenhauer's overall metaphysics are inconsistent with the very idea of will‐less cognition and, hence, of a free intellect. An alternative explanation of contemplation better fits with Schopenhauer's philosophy overall by stating that it is driven by the will itself. I analyze two approaches to elaborating such a theory. First, the “metaphysical” account, according to which the will as thing‐in‐itself brings forth the (surplus of) intellect needed for contemplation as a means of self‐cognition. Second, the “physiological” account, which presupposes a quasi‐evolutionary process that has aesthetic cognition as a byproduct of intellect. The two accounts complement each other and in tandem better explain the possibility of contemplation than postulating a will‐less intellect.
COVID‐19 responsibility and blame: How group identity and political ideology inform perceptions of responsibility, blame, and racial disparities
Authors: Wallace Lyndsey , Mikkelborg Anna , Gonzales Rubi , Hurd Kyneshawau , Romano Celina , Plaut Victoria
Published: December 2023

This study explored how racial group, racial identity centrality, and political ideology inform perceptions of responsibility, blame, and racial disparities in COVID‐19 outcomes. The findings revealed that highly identified members of non‐dominant racial groups were less likely to endorse items indicating individual blame, while being more inclined to attribute racial disparities to structural inequalities. Furthermore, conservative ideology was consistently linked to individual blame and responsibility, with those endorsing conservative ideology agreeing less with explanations of racial disparities based on structural inequalities and agreeing more with explanations for racial disparities based on personal blame and responsibility. Understanding perceptions of blame and responsibility for COVID‐19 may influence political discourse and subsequent health inequities, highlighting the importance of exploring how race, identity, and political ideology shape such perceptions.
An artificial neural network for digital image correlation dynamic subset selection based on speckle pattern quality metrics
Authors: Atkinson Devan James , van Rooyen Melody , Becker Thorsten Hermann
Published: December 2023

Precise and accurate digital image correlation computed displacement data requires sufficient noise suppression and spatial resolution, which improve and diminish, respectively, with increased subset size. Furthermore, spatially varying speckle pattern quality and displacement field complexity ideally necessitate a location‐specific optimal subset size to obtain a favourable compromise between noise suppression and spatial resolution. Although dynamic subset selection (DSS) methods have been proposed based on speckle pattern quality metrics (SPQMs), they do not ensure such a favourable compromise.

This work investigates using an artificial neural network (ANN) for DSS. An ANN is trained to predict the displacement error standard deviation of a subset from multiple SPQMs and the standard deviation of image noise, such that the smallest subset offering sufficient noise suppression, dictated by a displacement error standard deviation threshold, is appointed.

Validation, both within and outside the domain of the training images, shows that the smallest subset providing sufficient noise suppression offers a favourable compromise for up to moderate displacement gradients. Additionally, the proposed method is shown to perform with greater consistency and reliability relative to existing SPQM‐based DSS methods.

The novel proposition lies in utilising an ANN as an error prediction tool, based on multiple SPQMs, and hence, is an attractive alternative for DSS.
Reevaluation of the medical necessity of washed red blood cell transfusion in chronically transfused adults
Authors: Huso Tait , Buban Kristen , Van Denakker Tayler A. , Haddaway Kathy , Smetana Heather , Marshall Christi , Rai Herleen , Ness Paul M. , Bloch Evan M. , Tobian Aaron A. R. , Crowe Elizabeth P.
Published: December 2023

Background

Washing red blood cell (RBC) units mitigates severe allergic transfusion reactions. However, washing reduces the time to expiration and the effective dose. Automated washing is time‐ and labor‐intensive. A shortage of cell processor tubing sets prompted review of medical necessity for washed RBC for patients previously thought to require washing.

Study Design and Methods

A single‐center, retrospective study investigated discontinuing wash RBC protocols in chronically transfused adults. In select patients with prior requirements for washing, due to a history of allergic transfusion reactions, trials of unwashed transfusions were performed. Patient demographic, clinical, laboratory, and transfusion data were compiled. The per‐unit washing cost was the sum of the tubing set, saline, and technical labor costs.

Results

Fifteen patients (median age 34 years interquartile range [IQR] 23–53 years, 46.7% female) were evaluated. These patients had been transfused with a median of 531 washed RBC units (IQR 244–1066) per patient over 12 years (IQR 5–18 years), most commonly for recurrent, non‐severe allergic reactions. There were no transfusion reactions with unwashed RBCs aside from one patient with one episode of pruritus and another with recurrent pruritus, which was typical even with washed RBC. We decreased the mean number of washed RBC units per month by 72.9% (104 ± 10 vs. 28.2 ± 25.2; p < .0001) and saved US $100.25 per RBC unit.

Conclusion

Washing of RBCs may be safely reconsidered in chronically transfused patients without a history of anaphylaxis. Washing should be implemented judiciously due to potential lack of necessity and logistical/operational challenges.
Computed tomographic findings in a canine ovarian teratoma
Authors: Radtke Alexandra V. , Jorge Kelsey M. , Townsend Adam M. , Hardie Robert J. , Jones Kaitlin , Yap Seng Wai
Published: December 2023

A 2‐year‐old, intact female, Labrador Retriever was referred for progressive abdominal distension, assessed by emergency clinicians as being extrauterine in origin on AFAST. Abdominal radiographs and ultrasound identified a large, lobulated, partially mineralized, soft tissue, mid‐abdominal mass and gravid uterus. Contrast‐enhanced CT identified a mixed fat to soft tissue attenuating mass with a complex internal mineralized matrix, heterogeneous contrast enhancement, receiving blood from the left ovarian artery. Histology confirmed a left ovarian teratoma, diffuse endometrial hyperplasia, and fetal implantation. The patient had a good post‐operative outcome for 2 years, but was later diagnosed with primary cranial mediastinal neuroendocrine carcinoma.
Radiographic and CT features of metallosis in a lame dog after total hip replacement: the cloud sign
Authors: Lucaci Felix Daniel , Battiato Pierantonio , Bassi Jessica , Zani Davide Danilo , De Zani Donatella , Vezzoni Aldo , Stranieri Angelica , Longo Maurizio
Published: December 2023

A 2‐year‐old female American Akita was referred for CT of the pelvis and hindlimbs due to a left hindlimb lameness after a left total hip replacement. Referral radiographs and CT images demonstrated amorphous soft‐tissue and mineral opacities surrounding the proximal femur and the prosthetic stem, consistent with the “cloud sign” reported as a characteristic of metallosis in humans. Dorsomedial displacement of the prosthetic head, multiple foci of geographic osteolysis alongside the “cloud sign”, presumed pseudotumor lesions, and medial iliac lymphadenopathy were also identified with CT. Metallosis was confirmed based on ultrasound‐guided cytology, revision surgery, and histopathology.
Key management practices to reduce the risk of the occurrence of Rumex obtusifolius in productive grasslands
Authors: Klötzli Julie , Suter Matthias , Beaumont Deborah , Kolmanič Aleš , Leskovšek Robert , Schaffner Urs , Storkey Jonathan , Lüscher Andreas
Published: December 2023

Rumex obtusifolius (broad‐leaved dock) is a problematic weed that reduces yield and nutritional value of forage in grasslands of temperate regions worldwide. We conducted an on‐farm study to identify management practices and environmental factors that influence the risk of the occurrence of R. obtusifolius in high densities in permanent, productive grasslands used for forage production. Following a common protocol, a paired case–control design was implemented in Switzerland (CH), Slovenia (SI), and United Kingdom (UK) to compare parcels with high densities of R. obtusifolius (cases, ≥1 plant m−2) with nearby parcels free of or with very low densities of the species (controls, ≤4 plants 100 m−2). A total of 40, 20, and 18 pairs were recorded in CH, SI, and UK respectively. Parameters measured included data about management practices and history, vegetation cover and composition, and soil nutrients and texture. Across countries, increased vegetation cover reduced the relative risk of R. obtusifolius occurrence. By contrast, increased soil phosphorus and potassium and high soil bulk density raised the relative risk. These effects were consistent across countries, as no interactions between country and any of the factors were observed. The two indicator species for case parcels, Plantago major and Poa annua, were typical species of disturbed areas and fertile soils, while indicators for control parcels were characteristic of grasslands under medium to high management intensity (e.g., Festuca rubra, Cynosorus cristatus, Anthoxantum odoratum). We conclude that the risk for grassland infestation with R. obtusifolius can be significantly affected by management practices. Prevention measures should target phosphorus and potassium fertilisation to the forage plants' requirements, minimise soil compaction, and maintain dense swards.
Effects of electron irradiation on graphene drums
Authors: Ojo Ibikunle , Hathaway Evan , Li Jianchao , Gonzalez Roberto , Jiang Yan , Cui Jingbiao , Perez Jose
Published: December 2023

Using a scanning electron microscope, we irradiate graphene drums with electrons at an energy of 20 keV and a dosage of about 1.58 × 1017 electrons/cm2. The drums consist of graphene exfoliated in ambient air over holes having a diameter of 4.6 μm and etched into an SiO2 substrate. After irradiation, we observe that the drum’s suspended monolayer (ML) region has a ratio of the Raman D peak height, ID, to the Raman G peak height, IG, as high as 6.3. In contrast, the supported ML on the SiO2 substrate has an ID/IG ratio of 0.49. Previous studies have shown that graphene drums containing air can leak in a vacuum at a low rate. We attribute the high ID/IG ratio of the suspended ML to the air that may be in the drums. We propose that the air produces much adsorbed water on the ML, resulting in a high average defect density during irradiation. We present Raman maps of the full-width-at-half maximum, position, and height of the G, 2D, D, and D’ peaks before and after irradiation and maps of ID/IG and ID/ID’. We anneal the drums at temperatures from 50 to 215 °C and find that ID/IG significantly reduces to 0.42. The annealing data are analyzed using an Arrhenius plot. We also find that ID/ID’ depends on annealing temperature and has values ≥8, in the range expected for sp3 defects, for ID/IG ≤ 3.9. This irradiation method may help achieve high average defect densities in ML graphene, imparting novel and potentially valuable properties.
High power pulsed magnetron sputtering tailored low temperature CrAlN + MoWS coatings for dry tribological contacts
Authors: Bobzin K. , Kalscheuer C. , Möbius M. P. , Schulze C. , Miranda Marti M.
Published: December 2023

Gears are used in a variety of applications, for example, in automotive and aerospace industries. In these applications, gears are exposed to harsh conditions such as high Hertzian pressures. In many cases, lubricants are used to achieve a reduction in the coefficient of friction and, thus, in the wear of the components. Nevertheless, in some applications, the use of a lubricant is difficult, for example, in vacuum environments. One promising approach is the application of solid lubricants by using triboactive elements. The present study shows the potential of a process combining high power pulsed magnetron sputtering (HPPMS) and direct current magnetron sputtering (dcMS) for the deposition of CrAlN + MoWS coatings. In HPPMS/dcMS processes, especially, the share of HPPMS leads to higher ionization of the coating plasma and, therefore, to higher coating thicknesses on the teeth of gears. One major challenge in coating processes is the adjustment of the deposition temperature, since steels used for gear applications are temperature sensitive. Therefore, starting from an established coating process with a high coating temperature, the coating process was adjusted by reducing the number of used cathodes. By reducing the count of used dcMS cathodes, the share of HPPMS cathodes within the coating process was increased. Furthermore, segments of gears were coated in order to determine the coating thickness at different distances from the head of the gear tooth. A sufficient coating thickness distribution on the flank of the gear tooth is crucial for friction reduction and wear protection when used in gearboxes. The reduction of used cathodes led to a decrease in the coating temperature from a maximum coating temperature of Tmax = 281 °C to Tmax = 214 and 197 °C. It was shown by nanoindentation measurements that the effect of soft annealing was eliminated by reducing the coating temperature. At the same time, coatings deposited with increased HPPMS fraction led to a reduced coefficient of friction as well as lower wear volumes for pin-on-disk measurements in a dry tribological contact with an uncoated 100Cr6 counterpart. Moreover, these processes exhibited a good coatability of the gear tooth with a relatively high coating thickness even near the gear tooth root. The present study shows the potential of increasing the share of HPPMS during the deposition of coatings for dry-running applications. By increasing the HPPMS content, the tribological behavior as well as the coating thickness distribution on gears can be significantly improved.
Psychology of Ultrarunning: Evaluating Validation, Social Identity, and Disharmony in the Long-Distance Experience
Authors: Mueller Thomas S.
Published: December 2023

This study (N = 394) investigated motivators and detractors in ultrarunners. Latent factors Validation, Social Identity, and Disharmony were identified. Network analysis supported Social Identity through the hub node “ultra tells a lot about me” associated with “glimpse of who I am” with “can tell a lot about the person.” The regression “upset if unable to participate,” F(5, 365) = 16.90, p < .001, R2 = .019, view Cognitive Involvement (t = 4.54, p < .001), Disharmony (t = 2.96, p = .003), and Social Identity (t = 2.41, p = .016) as significant predictors. “Lone Wolf” isolationist runners were highly masculine and motivated by emotional involvement. Back and middle of the pack runners viewed Disharmony differently than front of the pack runners. Text analysis sentiment “Affect Friends and Family” supports the Disharmony factor. Event promoters and product marketers should acknowledge ultrarunning motivators and detractors, and promote wellness among competitors.
Patterns and Correlates of Participation in a Weekly Mass Participation Physical Activity Event, parkrun, in Australia, 2011–2020
Authors: Grunseit Anne C. , Huang Bo-Huei , Merom Dafna , Bauman Adrian , Cranney Leonie , Rogers Kris
Published: December 2023

Background: Studying effective interventions already operating at scale is critical to improving physical activity intervention research translation. The free, weekly, timed 5-km run or walk parkrun represents a unique opportunity to examine successful organic dissemination. We conducted an ecological analysis to identify patterns of growth in Australian parkrun participation and their correlates from 2011 to 2020. Method: Outcome variables were (1) weekly counts of walkers/runners and (2) monthly number of new parkrun registrants. We used latent class analysis to characterize growth trajectories followed by logistic regression on class membership. Covariates included parkrun course characteristics (eg, surface type and route), site-level aggregate participant profile (eg, proportion women and mean age), and surrounding area characteristics (eg, population density and physical activity norm). Results: Three hundred and sixty-three parkruns were included (n = 8,388,695 participation instances). Sixty-nine percent followed a low-growth and 31% a high-growth participation pattern. High growth was associated with greater participation by women, concrete/bitumen surface type, lower area socioeconomic status, and greater volunteer heterogeneity. Odds of being in the slow-growth class were higher if the course contained >1 km of repetition, higher average age of participants, better average parkrun performance, and higher running group membership. Two patterns of new registration were identified: high start followed by steep decline; and low start, slow decline with similar correlates to participation. Conclusions: Parkruns with a less competitive social milieu may have more rapid dissemination. As a free and regular event, parkruns in low socioeconomic areas have the potential to improve the activity levels of those with fewer resources.
Omadacycline pharmacokinetics/pharmacodynamics and efficacy against multidrug-resistant
Mycobacterium tuberculosis
in the hollow fiber system model
Authors: Singh Sanjay , Gumbo Tawanda , Boorgula Gunavanthi D. , Thomas Tania A. , Philley Julie V. , Srivastava Shashikant
Published: December 2023

Seventy-five years ago, first-generation tetracyclines demonstrated limited efficacy in the treatment of tuberculosis but were more toxic than efficacious. We performed a series of pharmacokinetic/pharmacodynamic (PK/PD) experiments with a potentially safer third-generation tetracycline, omadacycline, for the treatment of multidrug-resistant tuberculosis (MDR-TB).
Mycobacterium tuberculosis
(
Mtb
) H37Rv and an MDR-TB clinical strain (16D) were used in the minimum inhibitory concentration (MIC) and static concentration-response studies in test tubes, followed by a PK/PD study using the hollow fiber system model of TB (HFS-TB) that examined six human-like omadacycline doses. The inhibitory sigmoid maximal effect (
E
max
) model and Monte Carlo experiments (MCEs) were used for data analysis and clinical dose-finding, respectively. The omadacycline MIC for both
Mtb
H37Rv and MDR-TB clinical strain was 16 mg/L but dropped to 4 mg/L with daily drug supplementation to account for omadacycline degradation. The Mycobacteria Growth Indicator Tube MIC was 2 mg/L. In the test tubes, omadacycline killed 4.39 log
10
CFU/mL in 7 days. On Day 28 of the HFS-TB study, the
E
max
was 4.64 log
10
CFU/mL, while exposure mediating 50% of
E
max
(EC
50
) was an area under the concentration-time curve to MIC (AUC
0–24
/MIC) ratio of 22.86. This translates to PK/PD optimal exposure or EC
80
as AUC
0–24
/MIC of 26.93. The target attainment probability of the 300-mg daily oral dose was 90% but fell at MIC ≧4 mg/L. Omadacycline demonstrated efficacy and potency against both drug-susceptible and MDR-TB. Further studies are needed to identify the omadacycline effect in combination therapy for the treatment of both drug-susceptible and MDR-TB.
Metabolic engineering of
Caldicellulosiruptor bescii
for 2,3-butanediol production from unpretreated lignocellulosic biomass and metabolic strategies for improving yields and titers
Authors: Tanwee Tania N. N. , Lipscomb Gina L. , Vailionis Jason L. , Zhang Ke , Bing Ryan G. , O'Quinn Hailey C. , Poole Farris L. , Zhang Ying , Kelly Robert M. , Adams Michael W. W.
Published: December 2023

The platform chemical 2,3-butanediol (2,3-BDO) is used to derive products, such as 1,3-butadiene and methyl ethyl ketone, for the chemical and fuel production industries. Efficient microbial 2,3-BDO production at industrial scales has not been achieved yet for various reasons, including product inhibition to host organisms, mixed stereospecificity in product formation, and dependence on expensive substrates (i.e., glucose). In this study, we explore engineering of a 2,3-BDO pathway in
Caldicellulosiruptor bescii
, an extremely thermophilic (optimal growth temperature = 78°C) and anaerobic bacterium that can break down crystalline cellulose and hemicellulose into fermentable C
5
and C
6
sugars. In addition
, C. bescii
grows on unpretreated plant biomass, such as switchgrass. Biosynthesis of 2,3-BDO involves three steps: two molecules of pyruvate are condensed into acetolactate; acetolactate is decarboxylated to acetoin, and finally, acetoin is reduced to 2,3-BDO.
C. bescii
natively produces acetoin; therefore, in order to complete the 2,3-BDO biosynthetic pathway,
C. bescii
was engineered to produce a secondary alcohol dehydrogenase (sADH) to catalyze the final step. Two previously characterized, thermostable sADH enzymes with high affinity for acetoin, one from a bacterium and one from an archaeon, were tested independently. When either sADH was present in
C. bescii,
the recombinant strains were able to produce up to 2.5-mM 2,3-BDO from crystalline cellulose and xylan and 0.2-mM 2,3-BDO directly from unpretreated switchgrass. This serves as the basis for higher yields and productivities, and to this end, limiting factors and potential genetic targets for further optimization were assessed using the genome-scale metabolic model of
C. bescii
.

IMPORTANCE

Lignocellulosic plant biomass as the substrate for microbial synthesis of 2,3-butanediol is one of the major keys toward cost-effective bio-based production of this chemical at an industrial scale. However, deconstruction of biomass to release the sugars for microbial growth currently requires expensive thermochemical and enzymatic pretreatments. In this study, the thermo-cellulolytic bacterium
Caldicellulosiruptor bescii
was successfully engineered to produce 2,3-butanediol from cellulose, xylan, and directly from unpretreated switchgrass. Genome-scale metabolic modeling of
C. bescii
was applied to adjust carbon and redox fluxes to maximize productivity of 2,3-butanediol, thereby revealing bottlenecks that require genetic modifications.
Research on phage λ: a lucky choice
Authors: Lewis Dale E. A. , Adhya Sankar
Published: December 2023

Bacteriophage λ is a paradigm in the field of gene regulation and one of the best-understood systems in genetic regulatory biology. A so-called Genetic Switch determines the mechanisms by which λ transitions to its dual lifestyles—lytic or lysogenic. When λ initiates the lysogenic lifestyle, the phage-encoded CI repressor binds cooperatively to multi-partite operators in a defined pattern that autoregulates repression of phage lytic promoters as well as activation of the lysogenic promoter. The study of this genetic switch and related earlier research on phage λ revealed the main principles of gene expression and regulation in molecular biology. This article describes the underlying molecular details of λ lysogeny, as it is currently understood.
Retrospective evaluation of clinical decision support for within-laboratory optimization of SARS-CoV-2 NAAT workflow
Authors: Durant Thomas J. S. , Peaper David R.
Published: December 2023

We describe a novel approach to clinical decision support (CDS) for triaging specimens within the clinical laboratory for severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) nucleic acid amplification tests (NAAT). The use of our CDS tool could help clinical laboratories prioritize and process specimens efficiently, especially during times of high demand. There were significant differences in the turnaround time for specimens differentiated by icons on specimen labels. Further studies are needed to evaluate the impact of our CDS tool on overall laboratory efficiency and patient outcomes.
Early and exclusive enteral nutrition in infants born very preterm
Authors: Razzaghy Jacqueline , Shukla Vivek V , Gunawan Emily , Reeves Audrey , Nguyen Kelly , Salas Ariel A
Published: December 2023

Objective

To characterise the effects of early and exclusive enteral nutrition with either maternal or donor milk in infants born very preterm (280/7–326/7weeks of gestation).

Design

Parallel-group, unmasked randomised controlled trial.

Setting

Regional, tertiary neonatal intensive care unit.

Participants

102 infants born very preterm between 2021 and 2022 (51 in each group).

Intervention

Infants randomised to the intervention group received 60–80 mL/kg/day within the first 36 hours after birth. Infants randomised to the control group received 20–30 mL/kg/day (standard trophic feeding volumes).

Main outcome measures

The primary outcome was the number of full enteral feeding days (>150 mL/kg/day) in the first 28 days after birth. Secondary outcomes included growth and body composition at the end of the first two postnatal weeks, and length of hospitalisation.

Results

The mean birth weight was 1477 g (SD: 334). Half of the infants were male, and 44% were black. Early and exclusive enteral nutrition increased the number of full enteral feeding days (+2; 0–2 days; p=0.004), the fat-free mass-for-age z-scores at postnatal day 14 (+0.5; 0.1–1.0; p=0.02) and the length-for-age z-scores at the time of hospital discharge (+0.6; 0.2–1.0; p=0.002). Hospitalisation costs differed between groups (mean difference favouring the intervention group: −$28 754; −$647 to −$56 861; p=0.04).

Conclusions

In infants born very preterm, early and exclusive enteral nutrition increases the number of full enteral feeding days. This feeding practice may also improve fat-free mass accretion, increase length and reduce hospitalisation costs.

Trial registration number

NCT04337710.
Relationship of close contact settings with transmission and infection during the SARS-CoV-2 Omicron BA.2 epidemic in Shanghai
Authors: Zhu Wenlong , Yuan Shiying , Mao Shenghua , Chen Jian , Zheng Yaxu , Jiang Xianjin , Yu Xiao , Jiang Chenyan , Fang Qiwen , Wang Weibing , Yuan Zheng'an , Yao Ye
Published: December 2023

Introduction

We analysed case-contact clusters during the Omicron BA.2 epidemic in Shanghai to assess the risk of infection of contacts in different settings and to evaluate the effect of demographic factors on the association of infectivity and susceptibility to the Omicron variant.

Methods

Data on the settings and frequency of contact, demographic characteristics and comorbidities of index cases, contacts and secondary cases were analysed. Independent effect of multiple variables on the risk for transmission and infection was evaluated using generalised estimating equations.

Results

From 1 March to 1 June 2022, we identified 450 770 close contacts of 90 885 index cases. The risk for infection was greater for contacts in farmers’ markets (fixed locations where farmers gather to sell products, adjusted OR (aOR): 3.62; 95% CI 2.87 to 4.55) and households (aOR: 2.68; 95% CI 2.15 to 3.35). Children (0–4 years) and elderly adults (60 years and above) had higher risk for infection and transmission. During the course of the epidemic, the risk for infection and transmission in different age groups initially increased, and then decreased on about 21 April (17th day of citywide home quarantine). Compared with medical workers (reference, aOR: 1.00), unemployed contacts (aOR: 1.77; 95% CI 1.53 to 2.04) and preschoolers (aOR: 1.61; 95% CI 1.26 to 2.05) had the highest risk for infection; delivery workers (aOR: 1.90, 95% CI 1.51 to 2.40) and public service workers (aOR: 1.85; 95% CI 1.64 to 2.10) had the highest risk for transmission. Contacts who had comorbidities (aOR: 1.10; 95% CI 1.09 to 1.12) had a higher risk for infection, particularly those with lung diseases or immune deficiency.

Conclusion

Farmers’ markets and households were the main setting for transmission of Omicron. Children, the elderly, delivery workers and public service workers had the highest risk for transmission and infection. These findings should be considered when implementing targeted interventions.
Real-world evaluation of smartphone-based artificial intelligence to screen for diabetic retinopathy in Dominica: a clinical validation study
Authors: Kemp Oliver , Bascaran Covadonga , Cartwright Edyta , McQuillan Lauren , Matthew Nanda , Shillingford-Ricketts Hazel , Zondervan Marcia , Foster Allen , Burton Matthew
Published: December 2023

Objective

Several artificial intelligence (AI) systems for diabetic retinopathy screening have been validated but there is limited evidence on their performance in real-world settings. This study aimed to assess the performance of an AI software deployed within the diabetic retinopathy screening programme in Dominica.

Methods and analysis

We conducted a prospective, cross-sectional clinical validation study. Patients with diabetes aged 18 years and above attending the diabetic retinopathy screening in primary care facilities in Dominica from 5 June to 3 July 2021 were enrolled.

Grading was done at the point of care by the field grader, followed by counselling and referral to the eye clinic. Images were then graded by an AI system. Sensitivity, specificity with 95% CIs and area under the curve (AUC) were calculated for comparing the AI to field grader as gold standard.

Results

A total of 587 participants were screened. The AI had a sensitivity and specificity for detecting referable diabetic retinopathy of 77.5% and 91.5% compared with the grader, for all participants, including ungradable images. The AUC was 0.8455. Excluding 52 participants deemed ungradable by the grader, the AI had a sensitivity and specificity of 81.4% and 91.5%, with an AUC of 0.9648.

Conclusion

This study provides evidence that AI has the potential to be deployed to assist a diabetic screening programme in a middle-income real-world setting and perform with reasonable accuracy compared with a specialist grader.
Incident glaucoma and ocular hypertension after periocular and intravitreal steroid injections: a claims-based analysis
Authors: Polski Ashley , Liu Katy C , Gupta Divakar , Grewal Dilraj S , Horns Joshua , Wirostko Barbara M , Stagg Brian C
Published: December 2023

Background/aims

This study aims to determine the incidence and risk of open-angle glaucoma or ocular hypertension (OHT) following ocular steroid injections using healthcare claims data.

Methods

We retrospectively reviewed deidentified insurance claims data from the IBM MarketScan Database to identify 19 156 adult patients with no prior history of glaucoma who received ocular steroid injections between 2011 and 2020. Patient demographics and steroid treatment characteristics were collected. Postinjection glaucoma/OHT development was defined as a new diagnosis of glaucoma/OHT, initiation of glaucoma drops, and/or surgical or laser glaucoma treatment. Cox proportional hazards models were used to determine the risk of glaucoma/OHT development within 5 years after first steroid injection.

Results

Overall, 3932 (20.5%) patients were diagnosed with new glaucoma/OHT, 3345 (17.5%) started glaucoma drops and 435 (2.27%) required a laser or surgical glaucoma procedure within 5 years of first steroid injection. Triamcinolone subconjunctival injections were associated with a lower risk of glaucoma/OHT development than retrobulbar or intravitreal steroid injections (p<0.001, HR 0.68, 95% CI 0.59 to 0.79), whereas the 0.59 mg fluocinolone acetonide intravitreal implant had the highest risk of glaucoma/OHT development (p=0.001, HR 2.01, 95% CI 1.34 to 3.02). The risk of glaucoma/OHT development was also higher for patients receiving multiple steroid injections (p<0.001), with the largest increase in risk occurring after three total steroid injections.

Conclusion

Patients receiving ocular steroid injections are at risk of developing glaucoma/OHT, even with no prior glaucoma/OHT diagnosis or treatment. Patients should be closely monitored for the development of glaucoma following ocular steroid injections, particularly in the setting of intravitreal and/or repeated steroid administration.
Examining adaptive models of care implemented in hospital ICUs during the COVID-19 pandemic: a qualitative study
Authors: McGillis Hall Linda , Reali Vanessa , Canzian Sonya , Johnston Linda , Hatcher Carol , Hayward-Murray Kathryn , Layton Mikki , Merkley Jane , Richards Joy , Taggar Ru , Woollard Susan
Published: December 2023

Background

The emergence of the COVID-19 pandemic led to an increased demand for hospital beds, which in turn led to unique changes to both the organisation and delivery of patient care, including the adoption of adaptive models of care. Our objective was to understand staff perspectives on adaptive models of care employed in intensive care units (ICUs) during the pandemic.

Methods

We interviewed 77 participants representing direct care staff (registered nurses) and members of the nursing management team (nurse managers, clinical educators and nurse practitioners) from 12 different ICUs. Thematic analysis was used to code and analyse the data.

Results

Our findings highlight effective elements of adaptive models of care, including appreciation for redeployed staff, organising aspects of team-based models and ICU culture. Challenges experienced with the pandemic models of care were heightened workload, the influence of experience, the disparity between model and practice and missed care. Finally, debriefing, advanced planning and preparation, the redeployment process and management support and communication were important areas to consider in implementing future adaptive care models.

Conclusion

The implementation of adaptive models of care in ICUs during the COVID-19 pandemic provided a rapid solution for staffing during the surge in critical care patients. Findings from this study highlight some of the challenges of implementing redeployment as a staffing strategy, including how role clarity and accountability can influence the adoption of care delivery models, lead to workarounds and contribute to adverse patient and nurse outcomes.
Reduced tidal volume-inflection point and elevated operating lung volumes during exercise in females with well-controlled asthma
Authors: Brotto Andrew R , Phillips Devin B , Rowland Samira D , Moore Linn E , Wong Eric , Stickland Michael K
Published: December 2023

Introduction

Individuals with asthma breathe at higher operating lung volumes during exercise compared with healthy individuals, which contributes to increased exertional dyspnoea. In health, females are more likely to develop exertional dyspnoea than males at a given workload or ventilation, and therefore, it is possible that females with asthma may develop disproportional dyspnoea on exertion. The purpose of this study was to compare operating lung volume and dyspnoea responses during exercise in females with and without asthma.

Methods

Sixteen female controls and 16 females with asthma were recruited for the study along with 16 male controls and 16 males with asthma as a comparison group. Asthma was confirmed using American Thoracic Society criteria. Participants completed a cycle ergometry cardiopulmonary exercise test to volitional exhaustion. Inspiratory capacity manoeuvres were performed to estimate inspiratory reserve volume (IRV) and dyspnoea was evaluated using the Modified Borg Scale.

Results

Females with asthma exhibited elevated dyspnoea during submaximal exercise compared with female controls (p<0.05). Females with asthma obtained a similar IRV and dyspnoea at peak exercise compared with healthy females despite lower ventilatory demand, suggesting mechanical constraint to tidal volume (VT) expansion. VT-inflection point was observed at significantly lower ventilation andV̇O2in females with asthma compared with female controls. Forced expired volume in 1 s was significantly associated with VT-inflection point in females with asthma (R2=0.401; p<0.01) but not female controls (R2=0.002; p=0.88).

Conclusion

These results suggest that females with asthma are more prone to experience exertional dyspnoea, secondary to dynamic mechanical constraints during submaximal exercise when compared with females without asthma.
Does mixing inhaler devices lead to unchecked inhaler technique errors in patients with COPD? Findings from the cross-sectional observational MISMATCH study
Authors: Dijk Lars , Kerkhof Marjan , Driessen Merijn , Gerritsma Yoran H , Bosnic-Anticevich Sinthia , Correia-de-Sousa Jaime , Dekhuijzen P N Richard , Leving Marika , Price David B , Tsiligianni Ioanna , Usmani Omar , Kerstjens Huib A M , Kocks Janwillem W H
Published: December 2023

Background

Patients with chronic obstructive pulmonary disease (COPD) may be prescribed multiple inhalers that require different techniques for optimal performance. Mixing devices has been associated with poorer COPD outcomes suggesting that it leads to inappropriate inhaler technique. However, empirical evidence is lacking.

Aims

Compare the nature and frequency of dry powder inhaler (DPI) technique errors in patients with COPD using (1) a single DPI or (2) mixed-devices (a DPI and pressurised metered dose inhaler (pMDI)).

Methods

Data from the PIFotal study—a cross-sectional study on Peak Inspiratory Flow in patients with COPD using a DPI as maintenance therapy, capturing data from 1434 patients on demographic characteristics, COPD health status and inhaler technique—were used to select 291 patients using mixed-devices. Frequency matching based on country of residence and DPI device type was used to select 291 patients using a DPI-only for comparison. Predetermined checklists were used for the evaluation of DPI video recordings and complemented with additional errors that were observed in ≥10%. Error proportions were calculated for the (1) individual and total number of errors, (2) number of critical errors and (3) number of pMDI-related errors.

Results

The study sample contained 582 patients (mean (SD) age 69.6 (9.4) years, 47.1% female). DPI technique errors were common, but not significantly different between the groups. The majority of patients made at least one critical error (DPI-only: 90.7% vs mixed-devices: 92.8%). Proportions of total, ‘pMDI-related’ and critical errors did not significantly differ between the groups.

Conclusion

The nature and frequency of inhaler technique errors did not substantially differ between patients prescribed with a single DPI and mixed-devices. Currently, ‘pMDI-related errors’ in DPI use are not accounted for in existing checklists.

Trial registration number

ENCEPP/EUPAS48776.
Identification of pan-cancer/testis genes and validation of therapeutic targeting in triple-negative breast cancer: Lin28a-based and Siglece-based vaccination induces antitumor immunity and inhibits metastasis
Authors: Carter Jason A , Matta Bharati , Battaglia Jenna , Somerville Carter , Harris Benjamin D , LaPan Margaret , Atwal Gurinder S , Barnes Betsy J
Published: December 2023

Background

Cancer–testis (CT) genes are targets for tumor antigen-specific immunotherapy given that their expression is normally restricted to the immune-privileged testis in healthy individuals with aberrant expression in tumor tissues. While they represent targetable germ tissue antigens and play important functional roles in tumorigenesis, there is currently no standardized approach for identifying clinically relevant CT genes. Optimized algorithms and validated methods for accurate prediction of reliable CT antigens (CTAs) with high immunogenicity are also lacking.

Methods

Sequencing data from the Genotype-Tissue Expression (GTEx) and The Genomic Data Commons (GDC) databases was used for the development of a bioinformatic pipeline to identify CT exclusive genes. A CT germness score was calculated based on the number of CT genes expressed within a tumor type and their degree of expression. The impact of tumor germness on clinical outcome was evaluated using healthy GTEx and GDC tumor samples. We then used a triple-negative breast cancer mouse model to develop and test an algorithm that predicts epitope immunogenicity based on the identification of germline sequences with strong major histocompatibility complex class I (MHCI) and MHCII binding affinities. Germline sequences for CT genes were synthesized as long synthetic peptide vaccines and tested in the 4T1 triple-negative model of invasive breast cancer with Poly(I:C) adjuvant. Vaccine immunogenicity was determined by flow cytometric analysis of in vitro and in vivo T-cell responses. Primary tumor growth and lung metastasis was evaluated by histopathology, flow cytometry and colony formation assay.

Results

We developed a new bioinformatic pipeline to reliably identify CT exclusive genes as immunogenic targets for immunotherapy. We identified CT genes that are exclusively expressed within the testis, lack detectable thymic expression, and are significantly expressed in multiple tumor types. High tumor germness correlated with tumor progression but not with tumor mutation burden, supporting CTAs as appealing targets in low mutation burden tumors. Importantly, tumor germness also correlated with markers of antitumor immunity. Vaccination of 4T1 tumor-bearing mice with Siglece and Lin28a antigens resulted in increased T-cell antitumor immunity and reduced primary tumor growth and lung metastases.

Conclusion

Our results present a novel strategy for the identification of highly immunogenic CTAs for the development of targeted vaccines that induce antitumor immunity and inhibit metastasis.
Association of indicators of extensive disease and rifampin-resistant tuberculosis treatment outcomes: an individual participant data meta-analysis
Authors: Campbell Jonathon R , Brode Sarah K , Barry Pennan , Bastos Mayara Lisboa , Bonnet Maryline , Guglielmetti Lorenzo , Kempker Russell , Klimuk Dzmitry , Laborín Rafael Laniado , Milanov Vladimir , Singla Rupak , Skrahina Alena , Trajman Anete , van der Werf Tjip S , Viiklepp Piret , Menzies Dick
Published: December 2023

Background

Indicators of extensive disease—acid fast bacilli (AFB) smear positivity and lung cavitation—have been inconsistently associated with clinical rifampin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) outcomes. We evaluated the association of these indicators with end-of-treatment outcomes.

Methods

We did an individual participant data meta-analysis of people treated for RR/MDR-TB with longer regimens with documented AFB smear and chest radiography findings. We compared people AFB smear-negative without cavities to people: (1) smear-negative with lung cavities; (2) smear-positive without lung cavities and (3) AFB smear-positive with lung cavities. Using multivariable logistic regression accounting for demographic, treatment and clinical factors, we calculated adjusted ORs (aOR) for any unfavourable outcome (death, lost to follow-up, failure/recurrence), and mortality and treatment failure/recurrence alone.

Results

We included 5596 participants; included participants significantly differed from excluded participants. Overall, 774 (13.8%) were AFB smear-negative without cavities, 647 (11.6%) only had cavities, 1424 (25.4%) were AFB smear-positive alone and 2751 (49.2%) were AFB smear-positive with cavities. The median age was 37 years (IQR: 28–47), 3580 (64%) were male and 686 (12.5%) had HIV. Compared with participants AFB smear-negative without cavities, aOR (95% CI) for any unfavourable outcome was 1.0 (0.8 to 1.4) for participants smear-negative with lung cavities, 1.2 (0.9 to 1.5) if smear-positive without cavities and 1.6 (1.3 to 2.0) if AFB smear-positive with lung cavities. Odds were only significantly increased for mortality (1.5, 95% CI 1.1 to 2.1) and failure/recurrence (2.2, 95% CI 1.5 to 3.3) among participants AFB smear-positive with lung cavities.

Conclusion

Only the combination of AFB smear-positivity and lung cavitation was associated with unfavourable outcomes, suggesting they may benefit from stronger regimens.
Evaluation of survival estimates generated from tracking downstream migrating juvenile sea lamprey (Petromyzon marinus) with a miniature acoustic telemetry tag
Authors: Haas Taylor F. , Brenden Travis O. , Deng Zhiqun D. , Wagner C. Michael
Published: December 2023

Fish that undertake juvenile migration pass through habitats that vary in mortality risk. The ability to identify regions of persistently low survival would improve fishery management. We conducted a field study combined with predictive modeling of survival in downstream migrating juvenile sea lamprey using a new micro-acoustic telemetry tag designed for implantation into small, slender-bodied fishes. Detection data were collected from eight receivers placed across a coastal riverine–wetland–lake complex. Juvenile sea lamprey initiated downstream movement near nautical twilight, stopped frequently, and were more likely to move during high river discharge. Estimated survival was highest in the riverine reach, declined through the river–wetland complex, and dropped precipitously in the drowned rivermouth lake. However, the high transmission rate and resulting short battery life of the microtransmitters (as configured) likely resulted in missed detections in the lower reaches. Simulation analyses suggested survival estimation could be improved by increasing the number of tagged lamprey and staggering release locations. We offer practical recommendations for the use of this new transmitter in field studies with small anguilliform fish.
Enterococcus faecium inhibits NF-κB/NLRP3/Caspase-1 signaling pathway to antagonize enterotoxigenic Escherichia coli-mediated inflammatory response
Authors: Zheng Huibin , Pu Sicheng , Liu Jiahao , Yang Falong , Chen Dechun
Published: December 2023

Enterotoxigenic Escherichia coli (ETEC) can cause intestinal inflammation and diarrhea in yaks, which has a negative impact on their economic value. In recent years, probiotics have gained increasing attention as a pure, natural, nontoxic, harmless, and residue-free additive. However, the underlying mechanisms by which probiotics safeguard against ETEC are not completely elucidated. This study aimed to investigate the protective effect of Enterococcus faecium ( E. faecium) against ETEC infection in mice through oral gavage. Morphological changes were examined through light microscopy. The expressions of inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-10, NF-κB, and NLRP3), tight junction protein (ZO-1, Claudin-1), and pyroptosis (Caspase-1, Caspase-4, and gasdermin D (GSDMD)) were detected using immunohistochemistry and quantitative real-time PCR. The results indicate that ETEC infection triggers the activation of inflammation-related pathways (NF-κB) and NLRP3 inflammasome, leading to the expression of a large number of inflammatory cytokines. Additionally, the activation of NLRP3 leads to the release of GSDMD activation through Caspase-1, ultimately resulting in inflammatory injury and pyroptosis. Feeding mice E. faecium early resulted in an increase in the expression of tight junction protein, a reduction in inflammatory cytokines, and alleviation of inflammatory injury and pyroptosis in intestinal tissues. Our research indicates that E. faecium has the ability to antagonize ETEC and provide protection to the gastrointestinal mucosa in mice.