bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing artificial consciousness
Authors: Dung Leonard , Kersten Luke
Published: November 2024

Implementationalism maintains that conventional, silicon‐based artificial systems are not conscious because they fail to satisfy certain substantive constraints on computational implementation. In this article, we argue that several recently proposed substantive constraints are implausible, or at least are not well‐supported, insofar as they conflate intuitions about computational implementation generally and consciousness specifically. We argue instead that the mechanistic account of computation can explain several of the intuitions driving implementationalism and non‐computationalism in a manner which is consistent with artificial consciousness. Our argument provides indirect support for computationalism about consciousness and the view that conventional artificial systems can be conscious.
Functional characterization reveals the importance of Arabidopsis ECA4 and EPSIN3 in clathrin mediated endocytosis and wall structure in apical growing cells
Authors: Teixeira Rita Teresa , Marchese Dario , Duckney Patrick J. , Dias Fernando Vaz , Carapeto Ana P. , Louro Mariana , Silva Marta Sousa , Cordeiro Carlos , Rodrigues Mário S. , Malhó Rui
Published: November 2024

Localized clathrin mediated endocytosis is vital for secretion and wall deposition in apical growing plant cells. Adaptor and signalling proteins, along with phosphoinositides, are known to play a regulatory, yet poorly defined role in this process. Here we investigated the function of Arabidopsis ECA4 and EPSIN3, putative mediators of the process, in pollen tubes and root hairs.

Homozygous eca4 and epsin3 plants exhibited altered pollen tube morphology (in vitro) and self‐pollination led to fewer seeds and shorter siliques. These effects were augmented in eca4/epsin3 double mutant and quantitative polymerase chain reaction data revealed changes in phosphoinositide metabolism and flowering genes suggestive of a synergistic action. No visible changes were observed in root morphology, but atomic force microscopy in mutant root hairs showed altered structural stiffness.

Imaging and FRET‐FLIM analysis of ECA4 and EPSIN3 X‐FP constructs revealed that both proteins interact at the plasma membrane but exhibit slightly different intracellular localization. FT‐ICR‐MS metabolomic analysis of mutant cells showed changes in lipids, amino acids and carbohydrate composition consistent with a role in secretion and growth.

Characterization of double mutants of eca4 and epsin3 with phospholipase C genes (plc5, plc7) indicates that phosphoinositides (e.g. PtdIns(4,5)P2) are fundamental for a combined and complementary role of ECA4‐EPSIN3 in cell secretion.
Thermal tolerance and sociality explain the interactive role of bees in a pollination network
Authors: Ratoni Brenda , Pinilla Cruz Carlos , Guevara Roger , González‐Tokman Daniel , Ayala Ricardo , Baena Fernanda , Dáttilo Wesley
Published: November 2024

Numerous studies have explored the organization of pollination networks and the factors influencing these interactions at various spatial and temporal scales. Within these networks, species vary in their significance and influence on one another (i.e. their interactive roles), and understanding which factors determine this significance enables us to better comprehend the interconnected relationships that drive the resilience and diversity of ecosystems. Nevertheless, despite the ectothermic nature of bees and the potential impact of social behaviour on bee foraging patterns on plants, the amount of theoretical and empirical information available regarding how bee thermal tolerance limits and sociality affect their interactive roles within pollination networks remains relatively scarce. In this study, we assess how sociality and physiological (thermal tolerance) traits shape the interactive role of bees within a pollination network in a coastal environment of the Gulf of Mexico, Mexico. For sociality, we classified bees as eusocial, subsocial, and solitary while for the limits of thermal tolerance, we used both warmest (i.e. critical thermal maximum, CTmax) and coldest (i.e. critical thermal minimum, CTmin) temperature. In general, we found that bees' sociality and thermal tolerance limits explain the interactive role of bees within the pollination network studied. Specifically, eusocial bees had a greater interactive role than subsocial and solitary bees. Moreover, we observed that bees with lower CTmax and higher CTmin (i.e. less heat and cold tolerant) had greater interactive role. Our findings suggest that traits inherent to the life history of bees are valuable for predicting the interactive roles of bees within pollination networks and may have implications for various ecological, functional and evolutionary processes within ecosystems, including potential impacts resulting from climate change.
Classification of accommodative insufficiency by monocular subjective push‐up test is poorly predictive of monocular objective amplitudes in children and young adults
Authors: Anderson Heather A. , Parks Sidney M. , Kulp Marjean T. , Mitchell G. Lynn
Published: November 2024

Introduction

To determine whether classification of accommodative insufficiency (AI) based on the subjective push‐up test is indicative of reduced amplitude measured objectively.

Methods

Monocular subjective accommodative amplitude was measured in participants 7–24 years of age with the push‐up test; a 0.9 mm letter was moved towards the eye until first sustained blur occurred. Monocular objective amplitude was measured with the same target and an autorefractor for demands from 2.5 to 30 D. The maximum response was termed the amplitude. Near point of convergence (NPC) was measured in a subset of participants. Participants were classified into groups using subjective amplitude: normal amplitude or AI (amplitude < ((15 – 0.25 × age) – 2)). Objective amplitude was plotted by age for each group and one‐way ANCOVA used to evaluate differences while controlling for age. For NPC measures, a t‐test compared the magnitude of the break between those with and without AI.

Results

Fifty‐five of 185 participants were classified as having AI. Objective amplitude decreased with age (0.20 D/year) and there was no significant difference in the age‐adjusted mean amplitudes for the two groups (AI: 7.62 D, CI = 7.19, 8.04; Normal: 7.86 D, CI = 7.58, 8.15; p = 0.11). For the subset with NPC measures, participants classified as having AI had significantly more receded break values than those without AI (7.7 ± 5 vs. 3.7 ± 3 cm, p < 0.001).

Conclusions

Factors other than accommodative ability may be contributing to lower subjective amplitude findings in individuals meeting the criterion for AI.
Childhood PUFA levels in relation to allergic sensitization and rhinitis up to young adulthood
Authors: Ekström Sandra , Sdona Emmanouela , Klevebro Susanna , Westman Marit , van Hage Marianne , Georgelis Antonios , Kull Inger , Melén Erik , Risérus Ulf , Bergström Anna
Published: November 2024

Background

Very long‐chain (VLC) polyunsaturated fatty acids (PUFA) have been hypothesized to influence the risk of allergic disease. The aim of the study was to investigate the role of plasma levels of omega‐3 (n‐3) and omega‐6 (n‐6) PUFA in childhood and adolescence, for the development of rhinitis and allergic sensitization up to young adulthood.

Methods

The study included n = 933 participants from the BAMSE cohort. Proportions of n‐3 and n‐6 PUFA in plasma phospholipids were analyzed at 8 and 16 years using gas chromatography. Associations between PUFA and rhinitis as well as allergic sensitization, analyzed by IgE reactivity against airborne allergens, up to age 24 years were analyzed by generalized estimating equations and logistic regression models.

Results

High plasma levels of VLC n‐3 PUFA as well as the n‐6 PUFA arachidonic acid (AA) at 8 years were inversely associated with rhinitis (overall OR up to 24 years: 0.72, 95% CI 0.55, 0.0.93 and 0.69 [0.53, 0.89], respectively) and aeroallergen sensitization (0.64 [0.49, 0.83] and 0.71 [0.54, 0.92], respectively). However, excluding prevalent cases at 8 years attenuated the associations.

Conclusion

Plasma levels of n‐3 and certain n‐6 PUFA in childhood were inversely associated with allergic sensitization and allergic rhinitis up to young adulthood. The association may to some extent be explained by persistent childhood disease, rather than new incident cases in adolescence and young adulthood. To what extent these associations are driven by dietary PUFA intake versus metabolism remains to be clarified for the prevention of rhinitis and allergic sensitization.
Internalizing symptoms and affective vulnerability among heterosexual and sexual minority young adults
Authors: McLeish Alison C. , Hartson Kimberly R. , Hart Joy L. , Walker Kandi L.
Published: November 2024

Objectives

Sexual minority young adults report higher rates of anxiety and depression, and affective vulnerability factors (i.e. anxiety sensitivity, distress tolerance, emotion dysregulation) may help explain these mental health disparities.

Design

The current cross‐sectional study examined differences between sexual minority and heterosexual college students (n = 465; Mage = 19.84, SD = 3.51; 76.3% female) in anxiety, depression and affective vulnerability and whether affective vulnerability served as an explanatory mechanism in these associations.

Methods

Participants completed self‐report measures for course credit.

Results

Sexual minority young adults reported greater anxiety, depression, anxiety sensitivity, emotion regulation difficulties and lower distress tolerance. There were also significant indirect effects for all three affective vulnerability variables for anxiety symptoms and for emotion regulation difficulties for depression symptoms.

Conclusions

Affective vulnerability, particularly emotion regulation difficulties, appears to serve as a mechanism through which sexual minority status is associated with anxiety and depression. Improving emotion regulation skills may help to reduce mental health disparities in this population.
Some Like It Hot: Differential Photosynthetic Performance and Recovery of English Walnut Accessions Under Emerging California Heat Waves
Authors: Momayyezi Mina , Williams Troy , Tolentino Peter , Hammermeister Abby , Kluepfel Daniel A. , Forrestel Elisabeth J. , McElrone Andrew J.
Published: November 2024

Heat waves (HWs) pose a significant threat to California agriculture, with potential adverse effects on crop photosynthetic capacity, quality and yield, all of which contribute to significant economic loss. Lack of heat‐resilient cultivars puts perennial crop production under severe threat due to increasing HW frequency, duration and intensity. Currently, available walnut cultivars are highly sensitive to abiotic stress, and germplasm collections provide potential solutions via genotypes native to varied climates. We screened nine English walnut accessions (Juglans regia) for physiological heat stress resilience and recovery in the USDA‐ARS National Clonal Germplasm over 2‐years, and identified accessions with superior resilience to heat stress. Heat stress impacted photosynthetic capacity in most accessions, as evidenced by reductions in net (An) and maximum (Amax) assimilation rates, quantum efficiency of PSII, and changes in stomatal conductance (gs). However, two accessions exhibited either higher or complete recovery post‐irrigation. This aligns with the established practice of using irrigation to mitigate heat stress, as it improved recovery for several accessions, with A3 and A5 demonstrating the most resilience. One of these two superior accessions is native to one of the hottest and driest habitats of all studied accessions. These same accessions exhibited the highest An under non‐stressed conditions and at higher temperatures of 35° to 45°C. Higher performance for A3 and A5 under HWs was associated with greater carboxylation rates, electron transport rates, and Amax. All accessions suffered significant declines in photosynthetic performance at 45°C, which were the ambient leaf temperatures approached during record‐setting heat waves in California during September 2022.
The effects of different doses of single‐ and dual‐wavelength whole‐body photobiomodulation on metabolic parameters in obese mice
Authors: Rocha Maíra da Silva Almeida , de Oliveira Lucas Renan Sena , Xavier Diêgo Mendes , Ottone Natielle Cecília dos Santos , Ferreira Pedro Paulo Ribeiro , Paulino Kaio Augusto Oliveira , Costa Juliana Sales Rodrigues , Fonseca Graciene Fernandes Araújo Campos , Silva Gabriela , Silva Patrick Almeida , da Silva Saulo Soares , Almeida João Paulo de Paula , Coimbra Cândido Celso , Esteves Elizabethe Adriana , Ferraresi Cleber , de Castro Magalhaes Flavio
Published: November 2024

Photobiomodulation (PBM) shows beneficial effects on obesity‐related alterations. It is not known if dual‐ is more beneficial than single‐wavelength, nor the dose–response effect of such treatments. The effects of different doses of single‐ and dual‐wavelength whole‐body PBM on metabolic parameters in obese mice were evaluated. Male Swiss albino mice were fed with standard (Chow) or a cafeteria (CAF) diet and allocated into Sham (lights off), and PBM (whole‐body blanket (140 cm2) composed of 20 LED clusters, 2.14 mW/cm2/cluster, for 67 or 133 s: 1 or 2 J per cluster; 20 and 40 J total energy; and 0.143 and 0.286 J/cm2) with 660 nm (660), 850 (850) nm, or 660 nm + 850 nm (660/850). CAF induced insulin resistance that was inhibited in 660–1, 660–2, 850–1, and 660/850–2. CAF increased serum total cholesterol that was inhibited in 660–1, 660–2, 850–1, 660/850–1, and 660/850–2. There were no PBM‐induced changes in other variables assessed. The effects of whole‐body PBM in metabolic paraments in obese mice were wavelength and dose dependent: increasing the dose for 660 did not affect the outcomes; increasing the dose for 850 negatively affected the outcomes, and increasing the dose for 660/850 was mostly beneficial on the outcomes.
Exposure Practices to Animal‐Origin Influenza A Virus at the Animal–Human Interface in Poultry and Swine Backyard Farms
Authors: Baumberger Cecilia , Anríquez Gustavo , Galdames Pablo , Palma Tamara , Gonzalez María Antonieta , Orozco Katherinne , Oyarzun Cristobal , Rojas Camila , Marambio Victor , Ruiz Soledad , Di Pillo Francisca , Schultz‐Cherry Stacey , Jimenez‐Bluhm Pedro , Rushton Jonathan , Hamilton‐West Christopher
Published: November 2024

Aim

Backyard production systems (BPS) represent an interface of contact between people, domestic and wild animals. Studies conducted in Chile during the last decade have provided extensive evidence of influenza A virus (IAV) circulation in backyard poultry and swine. The aim of this study was to investigate exposure practices of humans to animal‐origin IAV within backyards.

Methods and Results

Backyard farmers and household members of a total of 101 BPS in the proximity of wetlands located throughout Chile were interviewed between 2021 and 2022. Data were collected on the nature of human–animal contacts through participation in productive activities conducted within backyards, which was used to estimate participants' exposure risk to animal‐origin IAV. Additionally, RT‐qPCR and serologic IAV active surveillance was carried out in backyard animals. Multilinear regression was used to identify factors associated with exposure risk. Overall, IAV prevalence was 10.1% (95% CI: 4.7%–15.5%) and seroprevalence was 43.5% (95% CI: 29.7%–54.2%), both at the BPS level. Of 180 interviewees, 86% reported participating regularly in poultry or swine exposure activities within the backyard. A greater participation of male participants was observed when evaluating swine exposure activities, while female participation was greater for some activities related to poultry handling. Handwashing was a very extended hygiene practice; however, the use of personal protective equipment was uncommon. Different factors related to participants, households and backyards were associated with an increased exposure risk of participants to animal‐origin IAV: (i) older age, (ii) less years of education, (iii) no off‐farm work, (iv) greater backyard production value and (v) greater household consumption of backyard products.

Conclusion

These results indicate the circulation of IAV in BPS and the frequent human–animal contact at this interface, highlighting the need for awareness campaigns and educational programmes aimed at backyard farmers on prevention and biosecurity measures in the management of backyard animals.
Improving Surface Finish of Laser Additively Manufactured Curvilinear Surfaces Via Electropolishing and Electroless Coating
Authors: Praharaj Amit Kumar , Kambikath Nisha Vayalachery , Suvin Parayantayyathu Somarajan , Bontha Srikanth
Published: November 2024

Laser-directed energy deposition (LDED) is a very useful additive manufacturing technique for repairing and manufacturing complex-shaped parts compared to traditional manufacturing techniques. However, the inadequate surface quality of the LDED fabricated components limits their direct utilization in different sectors. In addition, improving the surface finish of the curvilinear surfaces (useful for cooling channels and fuel nozzles) is also challenging. Hence, the current study focuses on surface modification of LDED fabricated SS 316L hollow cylindrical samples by combining electropolishing and electroless coating. We have performed electropolishing (two different currents, 8 A and 15 A) on the as-deposited (AD) sample with and without the application of the grinding process. The electropolishing reduced the roughness of the AD sample from 3.2 µm to 0.85 µm and 0.74 µm for 8 A and 15 A, respectively. The reduction in roughness was more at a higher current value due to the rapid anodic dissolution of the surface peaks. A further reduction in roughness was observed when grinding was performed before electropolishing. However, grinding resulted in higher material removal from the deposited surfaces and reduction in roughness was also minimal. Hence, only the electropolishing sample was selected for the next step, in which Ni-P electroless coating was performed on the surface to form a protective layer. After electroless coating, the coefficient of friction and wear-rate were reduced by 9.5% and 25.6% compared to the AD sample. Delamination and severe plastic deformation were the major wear mechanisms for the AD sample, whereas abrasion was dominant for the coated sample. The current work proposes a combined surface modification approach of electropolishing and electroless coating for the LDED processed components with curvilinear surfaces.
Mitigating Low-Speed Crawling and Jitter in Telescopic Hydraulic Cylinders Through Stick-Slip Dynamics Analysis and Friction Reduction Strategies
Authors: Ma Zeyu , Huang Demin , Lu Shan , Zhang Evan , Wu Yuhao , Huang Xiaodong , Qin Liguo , Li Jun , Yin Hong
Published: November 2024

This study investigates the mechanisms of jittering in telescopic cylinders and proposes effective mitigation strategies. The focus is on the dynamic behavior of hydraulic cylinders under low-speed conditions, particularly the stick-slip phenomenon. Through finite element analysis using abaqus and tribological tests, the impact of various factors on the friction and wear properties of cylinder components is examined. Findings reveal that optimizing the average friction coefficient, stick-slip amplitude, and stick-slip time can significantly reduce jitter and creep in hydraulic cylinders. The results provide valuable insights for improving the performance and longevity of hydraulic systems in engineering machinery.
Li2B4O7 XPS using monochromatic Al Kα x rays
Authors: Zahra Khadisha M. , Moulton Benjamin J. A. , Soomary Liam A. J. , Counsell Jonathan D. P.
Published: November 2024

XPS spectra of lithium tetraborate (Li2B4O7) were obtained using an Al Kα (1486.6 eV) source and a quartz (1010) crystal monochromator through first-order diffraction. Irradiation occurs on the sample at 54.7° to the surface normal. Spectra of the principal lines include O 1s, C 1s, B 1s, and Li 1s. Spectra of O KLL and O 2s and valence band were also acquired.
Structural evolution and mechanical properties of Cr coatings deposited by magnetron sputtering on PCrNi1MoA steel
Authors: Wan Zirui , Shi Wanyu , Geng Xuehao , Xia Yu , Xu Zhigang , Peng Jian , Shen Qiang , Li Wenjun , Wang Chuanbin
Published: November 2024

Cr coatings were prepared by direct current magnetron sputtering on PCrNi1MoA steel, a substrate that has received limited attention in previous studies. The influence of deposition temperature on the microstructure and mechanical properties of Cr coatings was clarified. A comparative analysis was also performed to assess their performance relative to Cr coatings on the stainless steel substrate. All coatings on PCrNi1MoA steel exhibited densely packed fibrous grains in the cross section and a faceted triangular pyramid shape on the surface. Generally, increasing the deposition temperature led to enhanced mechanical properties, primarily due to the reduction of flaws and microporosity, facilitated by the increased mobility of adatoms at higher temperatures. The maximum values of hardness (H), elastic modulus (E), ratios of H/E and H3/E2, and adhesion strength are 4.1 GPa, 117.8 GPa, 0.43, 0.45 GPa, and 27 N, respectively. Compared to the Cr coatings on stainless steel, those on PCrNi1MoA steel exhibited a higher (110) texture coefficient, more uniform grain structures at high deposition temperatures, smoother surfaces, and better adhesion to the substrate.
Line spectrum tracking method in transformed signal space for underwater moving targets in low signal-to-noise ratio environment
Authors: Shi Yunjia , Piao Shengchun , Guo Junyuan
Published: November 2024

Line spectrum tracking is an essential signal-processing method for underwater passive detection. However, its performance is often seriously degraded due to signal fluctuation, especially in low signal-to-noise ratio scenarios. In this paper, based on signal space transformation and hidden Markov model, a signal trajectory tracking method is proposed for underwater moving target detection and parameter estimation. With this method, tracking the varying line spectrum trajectory in three-dimensional frequency-azimuth-time signal space is constrained onto a two-dimensional plane in the transformed signal space. Not only is the computation complexity reduced, but the ability to track weak line spectrums and estimate target parameters is improved. The performance of this method is verified with numerical simulations and experimental data processing.
Direct articulatory observation reveals phoneme recognition performance characteristics of a self-supervised speech model
Authors: Shi Xuan , Feng Tiantian , Huang Kevin , Kadiri Sudarsana Reddy , Lee Jihwan , Lu Yijing , Zhang Yubin , Goldstein Louis , Narayanan Shrikanth
Published: November 2024

Variability in speech pronunciation is widely observed across different linguistic backgrounds, which impacts modern automatic speech recognition performance. Here, we evaluate the performance of a self-supervised speech model in phoneme recognition using direct articulatory evidence. Findings indicate significant differences in phoneme recognition, especially in front vowels, between American English and Indian English speakers. To gain a deeper understanding of these differences, we conduct real-time MRI-based articulatory analysis, revealing distinct velar region patterns during the production of specific front vowels. This underscores the need to deepen the scientific understanding of self-supervised speech model variances to advance robust and inclusive speech technology.
Probing the past: historical case study analysis to inform more just and sustainable global health partnerships in education
Authors: Vorobej Lucy , Wondimagegn Dawit , Baheretibebe Yonas , Bizuneh Belete , Hodges Brian , Petros Adane , Jobin Stephane , Whitehead Cynthia Ruth
Published: November 2024

Introduction

Disparities of power between high-income (HICs) and low- and middle-income countries (LMICs) have long characterised the structures of global health, including knowledge production and training. Historical case study analysis is an often-overlooked tool to improve our understanding of how to mitigate inequalities.

Methods

Drawing from the contemporary experience of collaborators from Canada and Ethiopia, we chose to examine the historical relationship between Ethiopian Emperor Haile Selassie and Canadian Jesuit Lucien Matte as a case study for international collaborations based on the model of an ‘invited guest’. We used critical historical context and qualitative content analysis methodologies to assess written correspondence between them from the 1940s to the 1970s and drew from postcolonial theory to situate this case study in a broader context.

Results

The respectful and responsive relationship that developed between Emperor Haile Selassie and Lucien Matte reveals important characteristics needed for meaningful collaborations in global health education. Matte came to Ethiopia fully cognizant of the imperial context of his work and prepared to take on the position of invited guest. As a result, many of both Matte and Haile Selassie’s goals were achieved. At the same time, however, this case study also revealed how problematic constructions of authoritative power can arise even when productive partnerships among individuals occur. Matte and Haile Selassie’s collaboration reinscribed belief in the superiority of western theories of intellectual and social development. In addition, their prescriptive vision for education in Ethiopia repeatedly dismissed competing local positions.

Conclusion

As international partnerships in global health education continue to exist and form, historical case studies offer valuable insights to guide such work. Among the most crucial arenas of knowledge is the need to understand powerful dynamics that have and continue to shape HIC-LMIC interaction. The historical case study of Matte and Haile Selassie reveals how problematic power differentials can be reinforced or mitigated.
Effects of using wearable devices on reducing sedentary time and prolonged sitting in healthy adults: a network meta-analysis
Authors: He Zihao , Zhao Guanggao , Li Chao , Xing Yachen , Xu Anjie , Yang Junchao , Wang Ronghui
Published: November 2024

Objectives

This study aimed to compare the effectiveness of different wearable intervention strategies in reducing sedentary time (ST) and prolonged sitting (PS) on healthy adults.

Design

A network meta-analysis (NMA).

Data sources

PubMed, Web of Science, SPORTDiscus, ProQuest, Opengrey, Medline and Cochrane Central Register of Controlled Trials were searched up to 1 June 2024.

Eligibility criteria for selecting studies

Randomised controlled trials (RCTs) that examined the effect of wearable device interventions on ST and PS among healthy adults were included.

Data extraction and synthesis

Two independent reviewers used standardised methods to search, screen and code included studies. Bias risks were assessed using Cochrane tools (Risk of Bias 2.0). Data were analysed using a frequentist framework NMA to directly and indirectly compare the effects of the five different intervention strategies (comparators). The results were reported as standardised mean differences (SMDs) with 95% CI and surface under cumulative ranking curve (SUCRA) was used to rank the best interventions. The five comparators were as follows: (1) wearable-only intervention (only using wearable devices for self-monitoring); (2) wearable combined with online intervention (ie, online coaching and social media support); (3) wearable combined with offline intervention (ie, face-to-face seminars and courses); (4) comparison group (ie, traditional, non-wearable interventions); (5) control group (ie, maintaining daily routine, waitlist).

Results

12 RCTs with a total of 2957 participants were included. Results of NMA showed that the ‘wearable+online’ has significantly better effects in reducing ST compared with control group, comparison group and ‘wearable only’, with moderate to large effect sizes (SMD=0.96, 95% CI 0.65 to 1.27; SMD=0.87, 95% CI 0.21 to 1.53; SMD=0.78, 95% CI 0.14 to 1.42, respectively). However, no significant differences were identified between the groups in reducing PS. The SUCRA values were ranked as wearable+online (98.1%), wearable+offline (64.4%,), ‘wearable only’ (40.5%), comparison group (25.9%) and control group (21.1%) for ST reduction. Similar rankings were observed for PS reduction, with probabilities of 69.9%, 61.1%, 59.7%, 37.1% and 22.1%, respectively.

Conclusions

Wearable+online is the best intervention strategy for reducing ST in healthy adults. Additionally, none of the wearable-based interventions effectively reduced PS in healthy adults, but as there is little research on PS, it should receive more attention in the future.

PROSPERO registration number:CRD42021290017.
Post-COVID in healthcare workers and its consequences on quality of life, activities, participation, need for rehabilitation and care experiences: protocol of a cohort study
Authors: Luedtke Laura , Haller-Wolf Julia , Kriston Levente , Koch Uwe , Nienhaus Albert , Härter Martin
Published: November 2024

Introduction

Healthcare workers (HCWs) have been of particular relevance for overcoming the SARS-CoV-2 pandemic. At the same time they have been affected by SARS-CoV-2 infections with above average probability. Around 6.5% of the overall infected persons are likely to develop persistent symptoms resulting from the infection, known as long-COVID or post-COVID syndrome (PCS). The aim of this study is (1) to investigate the prevalence, course and characteristics of PCS in German HCWs, (2) to examine its effects on psychosocial variables, (3) to identify rehabilitation and healthcare needs and (4) to analyse treatment experiences.

Methods and analysis

In a cohort study with a randomised selection of participants (N=20 000) from the Employer’s Liability Insurance Association for Health and Welfare Care, the health status of HCWs, who had COVID-19 in their professional context will be examined. There will be two measurement points: baseline (T1) and a 12-month follow-up (T2). The outcome measures are the health status with a particular focus on persistent or newly occurring symptoms after a SARS-CoV-2 infection, health-related quality of life, functional capacity, the subjective need for and utilisation of healthcare services. Pre-existing conditions, the course of the acute infection and sociodemographic factors are considered as predictors. An advisory board made up of affected HCWs supports the study by contributing to the surveys’ contents.

Ethics and dissemination

The study has been approved by the Local Ethics Committee of the Center for Psychosocial Medicine at the University Hospital Hamburg-Eppendorf (LPEK-0518). For dissemination, the results will be published in peer-reviewed journals, presented at conferences and communicated to relevant stakeholders in general and rehabilitation medicine.

Trail registration number

https://drks.de/search/de/trial/DRKS00029314
Behavioural economics to improve and motivate vaccination in primary care using nudges through the electronic health record: rationale and design of the BE IMMUNE randomised clinical trial
Authors: Waddell Kimberly , Mehta Shivan J , Navathe Amol , Linn Kristin , Park Sae-Hwan , White Andrew , Staloff Jonathan , Rhodes Corinne , Couzens Chaylin , Goel Keshav , McDonald Caitlin , Reitz Catherine , Williams Keyirah , Liao Joshua M
Published: November 2024

Introduction

Annual influenza vaccination reduces disease burden but vaccination rates are suboptimal, with persistent disparities among subpopulations. The purpose of this trial is to evaluate multicomponent behavioural economic nudge interventions to clinicians and patients to increase influenza vaccination. This trial also includes an intensification nudge to reduce disparities in vaccination among older adult, primary care patients.

Methods

This is a two-part, multisite cluster randomised, pragmatic clinical trial. In the first part, a multicomponent nudge intervention will be tested over approximately 6 months (September 2023–February 2024). The second part consists of a replication trial conducted at an additional site during the following influenza season (September 2024–February 2025). Primary care clinics will be randomised to the nudge intervention or usual care. Eligible clinicians and patients at intervention clinics will receive the intervention, and patients deemed high risk for not receiving a vaccine will be further randomised to receive an intensification nudge. The primary outcome is vaccine completion during the eligible visit and the secondary outcome is vaccine completion within 3 months of the eligible visit.

Analysis

The effect of the clinic-level nudge intervention on the primary and secondary outcomes will be evaluated using generalised estimating equations (GEEs) with a clinic-level exchangeable working correlation to account for clustering of observations within the clinic. GEE models with an independent working correlation will be used to evaluate the impact of the additional intensification nudge on the primary and secondary outcomes.

Ethics and dissemination

The University of Pennsylvania Institutional Review Board (IRB) approved this trial and serves as the single IRB of record (IRB #851838). Results will be disseminated via peer-reviewed publication and conference presentations.

Trial registration number

NCT06057727.
Extended-duration work shifts among care workers: a scoping review protocol
Authors: Xu Mengjiao , Song Yuting , Lan Caifeng , Xu Yong , Liu Xueying , Dong Sihan , Weeks Lori E
Published: November 2024

Introduction

The available literature reviews of shift work among care workers are almost exclusively focused on 8-hour shifts and 12-hour shifts or 24-hour on-call shifts for physicians. We do not yet know the scope of evidence regarding extended-duration work shifts (defined as on-duty shifts of 16 or more hours per shift) in diverse healthcare settings, such as the impact on care workers and recipients of care. In this proposed scoping review, we aim to provide an overview of the current research regarding extended-duration work shifts among care workers in various healthcare settings.

Methods and analysis

We will conduct this scoping review in accordance with the Joanna Briggs Institute scoping review methodology. Comprehensive searches will be conducted in PubMed, Embase, MEDLINE, Web of Science and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases and grey literature sources. We will include empirical studies that focus on extended-duration work shifts among care workers working in different healthcare settings, including home care, community, acute care settings, long-term care homes and assisted living facilities. We will not apply language restrictions. We will conduct searches in August 2024, followed by screening of records. We will exclude research on on-call work shifts and investigations that solely focus on interns. The included literature will be screened independently by pairs of reviewers at the title and abstract review phase, followed by a full-text review for relevant literature. Any disagreement will be resolved by consensus or discussion with a third reviewer. The results will be extracted and summarised in the final report in tabular form, when possible, along with narrative synthesis.

Ethics and dissemination

All data for this study will come from published literature, so an ethics review is not necessary. The findings will be disseminated through conference presentations and publication in peer-reviewed journals, with the expectation that they will guide future research and inform future management of work shifts in care workers.
Risk factors for incidence of interstitial lung disease in patients with rheumatoid arthritis: a systematic review and meta-analysis
Authors: Yu Chen , Zhang Yupei , Jin Shangyi , Wang Yanhong , Wang Qian , Li Mengtao , Zeng Xiaofeng , Tian Xinping , Jiang Nan
Published: November 2024

Objectives

This study aimed at identifying risk factors for the incidence of interstitial lung disease in patients with rheumatoid arthritis (RA-ILD) by a systematic review and meta-analysis.

Methods

Information sources: studies published by March 2021 were searched in PubMed, Web of Science, MEDLINE, EMBASE, Cochrane Library and Scopus databases.Eligibility criteria: cohort studies or nested case-control studies that reported OR or HR of risk factors for RA-ILD were included. Two researchers independently screened the studies and extracted data.Synthesis of results: the relative risks (RRs) were introduced to measure the association across studies.Risk bias: quality assessments of included studies were performed using the Newcastle-Ottawa Scale. Based on the result of heterogeneity, the random-effects model or fixed-effects model was chosen in the meta-analysis. Furthermore, a sensitivity analysis was conducted to identify the origins of heterogeneity, and publication bias was evaluated for the factors with no less than five included studies by funnel plots and Egger’s test.

Results

Among 3075 identified articles, 12 studies met the inclusion criteria. 17 risk factors were included in the meta-analysis. Male (RR 1.94, 95% CI 1.33 to 2.85, p<0.001), elder age (>60 years, RR 1.42, 95% CI 1.05 to 1.94, p=0.02), older RA onset age (RR 1.05, 95% CI 1.01 to 1.10, p=0.02), smoking (RR 1.37, 95% CI 1.09 to 1.71, p=0.006), lung complications (RR 2.72, 95% CI 1.24 to 5.95, p=0.01), rheumatoid nodule (RR 1.85, 95% CI 1.36 to 2.51, p<0.001), leflunomide usage (RR 1.41, 95% CI 1.02 to 1.96, p=0.04) were identified as risk factors of RA-ILD.

Conclusion

Physicians should be aware that patients with RA with the above risk factors are likely to develop RA-ILD, and perform close ILD screening during follow-ups so that the patients can be early diagnosed and treated, and achieve improved prognosis.
Phase I study of a recombinant attenuated oncolytic virus, MEDI5395 (NDV–GM-CSF), administered systemically in combination with durvalumab in patients with advanced solid tumors
Authors: Davar Diwakar , Carneiro Benedito A , Dy Grace K , Sheth Siddharth , Borad Mitesh J , Harrington Kevin J , Patel Sandip P , Galanis Evanthia , Samson Adel , Agrawal Sonia , Chen Zhongying , Fan Chunling , Gong Maozhen , Burton Jenny , Tu Eric , Durham Nicholas , Laubscher Kevin , Arnaldez Fernanda , Zamarin Dmitriy
Published: November 2024

Background

MEDI5395 is a recombinant attenuated Newcastle disease virus engineered to express a human granulocyte-macrophage colony-stimulating factor transgene. Preclinically, MEDI5395 demonstrated broad oncolytic activity, augmented by concomitant programmed cell death-1/programmed cell death ligand-1 (PD-L1) axis blockade. Durvalumab is an anti-PD-L1 immune checkpoint inhibitor approved for the treatment of various solid tumors. We describe the results of the first-in-human study combining intravenous MEDI5395 with durvalumab in patients with advanced solid tumors.

Methods

This phase I, open-label, multicenter, dose-escalation, dose-expansion study recruited adult patients with advanced solid tumors, who had relapsed or were refractory or intolerant to ≥1 prior line of standard treatment. MEDI5395 was administered intravenously as six doses over 15–18 days. The dose-escalation phase assessed four-dose levels (108, 109, 1010, 1011focus forming units (FFU)) of MEDI5395, with sequential or delayed durvalumab. Durvalumab 1500 mg was administered intravenously every 4 weeks up to 2 years. The dose-expansion phase was not initiated. The primary objectives were to evaluate safety and tolerability, dose-limiting toxicities (DLTs) and the dose and schedule of MEDI5395 plus durvalumab administration. Secondary objectives included the assessment of the efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of MEDI5395.

Results

39 patients were treated with MEDI5395; 36 patients also received durvalumab. All 39 patients experienced ≥1 treatment-emergent adverse event (TEAE), most commonly fatigue (61.5%), nausea (53.8%) and chills (51.3%). Grade 3–4 TEAEs occurred in 27 (69.2%) patients; these were deemed MEDI5395-related in 12 (30.8%) patients. Two patients experienced a DLT, and the maximum tolerated dose of MEDI5395 with sequential and delayed durvalumab at study termination was 1011and 1010FFU, respectively. Four patients (10.3%) achieved a partial response (PR). Patients with PR or stable disease tended to have higher baseline PD-L1 and CD8+ levels in their tumor tissue. A tendency to dose-dependent pharmacokinetics of the viral genome was observed in whole blood and a tendency to dose-dependent viral shedding was observed in saliva and urine. Neutralizing antibodies were observed in all patients but did not appear to impact efficacy negatively.

Conclusion

This study demonstrates the feasibility, safety and preliminary efficacy of MEDI5395 with durvalumab in patients with advanced solid tumors.

Trial registration number

NCT03889275
Comparison of CAR T-cell and bispecific antibody as third-line or later-line treatments for multiple myeloma: a meta-analysis
Authors: Liang Xiaojie , Wang Yufan , Luo Baiwei , Lin Bingyu , Lu WeiXiang , Tian Shengyu , Liu Dan , Wang Liang
Published: November 2024

Background

CAR-T-cell therapy and bispecific antibody have revolutionized the treatment landscape for multiple myeloma. However, there is currently a lack of studies comparing the efficacy and safety of these two approaches. This meta-analysis assesses the efficacy and safety of B-cell maturation antigen (BCMA)-directed CAR-T-cell therapies and BCMA×CD3 bispecific antibodies as third-line or later interventions for relapsed/refractory multiple myeloma (RRMM).

Methods

We searched PubMed, Embase, Web of Science, and Cochrane databases up to May 31, 2024, identifying 11 eligible studies encompassing 1269 participants. Random-effects models evaluated the primary (complete response (CR) rate) and secondary (overall response rate (ORR)) outcomes, while meta-regression analyses adjusted for relevant covariates.

Results

CAR-T-cell therapy achieved significantly higher pooled CR rate (0.54 (95% CI 0.42–0.69) vs bispecific antibodies 0.35 (0.30–0.41), p<0.01) and pooled ORR (0.83 (0.76–0.90) vs 0.65 (0.59–0.71), p<0.01). However, CAR-T therapy had a higher incidence of adverse events, particularly cytokine release syndrome (CRS 0.83 (0.70–0.97) vs bispecific antibodies 0.59 (0.43–0.74), p<0.05). Severe CRS (grade ≥3) occurred at a rate of 0.07 (0.03–0.14) in the CAR-T cell group, contrasting with a negligible rate of 0.01 (0.00–0.02) in the bispecific antibody group (p<0.01). Hematologic adverse events, including neutropenia (grade ≥3; 0.88 (0.81–0.95) vs 0.48 (0.30–0.67), p<0.01) and anemia (grade≥3; 0.55 (0.47–0.62) vs 0.34 (0.28 to 0.40), p<0.01), were also more frequent in the CAR-T-cell group. Furthermore, differences in efficacy were observed among various CAR-T products, with ciltacabtagene autoleucel showing greater efficacy in CR rate (0.77 (0.71–0.84) vs 0.37 (0.32–0.41), p<0.01) and ORR (0.91 (0.83–0.99) vs 0.73 (0.68–0.77), p<0.01) compared with idecabtagene vicleucel.

Conclusion

CAR-T-cell therapy demonstrated superior CR rates compared with bispecific antibodies, although with an increase in severe adverse events.
YAP enhances mitochondrial OXPHOS in tumor-infiltrating Treg through upregulating Lars2 on stiff matrix
Authors: Bai Jingchao , Yan Meinan , Xu Yihan , Wang Youhui , Yao Yuan , Jin Peng , Zhang Yuhan , Qu Yang , Niu Liling , Li Hui
Published: November 2024

Background

Tumor-infiltrating regulatory T cells (TI-Tregs) are well-adapted to thrive in the challenging tumor microenvironment (TME) by undergoing metabolic reprogramming, notably shifting from glycolysis to mitochondrial oxidative phosphorylation (OXPHOS) for energy production. The extracellular matrix is an important component of the TME, contributing to the regulation of both tumor and immune cell metabolism patterns by activating mechanosensors such as YAP. Whether YAP plays a part in regulating TI-Treg mitochondrial function and the underlying mechanisms are yet to be elucidated.

Methods

To gain insights into the effect of matrix stiffness on YAP activation in Tregs, alterations in stiffness were performed bothin vitroandin vivo. YAP conditional knockout mice were used to determine the role of YAP in TI-Tregs. RNA-seq, quantitative PCR, flow cytometry, lentivirus infection and mitochondrial function assay were employed to uncover the mechanism of YAP modulating mitochondrial function in TI-Tregs. A YAP inhibitor and a low leucine diet were applied to tumor-bearing mice to seek the potential antitumor strategy.

Results

In this study, we found that YAP, as a mechanotransducer, was activated by matrix stiffness in TI-Tregs. A deficiency in YAP significantly hindered the immunosuppressive capability of TI-Tregs by disrupting mitochondrial function. Mechanically, YAP enhanced mitochondrial OXPHOS by upregulating the transcription ofLars2(Leucyl-tRNA synthetase 2, mitochondrial), which was essential for mitochondrial protein translation in TI-Tregs. Since Lars2 relied much on its substrate amino acid, leucine, the combination of a low leucine diet and YAP inhibitor synergistically induced mitochondrial dysfunction in TI-Tregs, ultimately restraining tumor growth.

Conclusions

This finding uncovered a new understanding of how YAP shapes mitochondrial function in TI-Tregs in response to mechanical signals within the TME, making the combined strategy of traditional medicine and diet adjustment a promising approach for tumor therapy.
Enhancing variant of uncertain significance (VUS) interpretation in neurogenetics: collaborative experiences from a tertiary care centre
Authors: Horowitz Kayla , Fotopoulos Nellie H , Mistry Alana J , Simo Justin , Medeiros Miranda , Bucco Isabela D , Ginsberg Mia , Dwosh Emily , La Piana Roberta , Rouleau Guy A , Dilliott Allison A , Farhan Sali M K
Published: November 2024

Background

The findings of variants of uncertain significance (VUS) on a clinical genetic testing report pose a challenge for attending healthcare professionals (HCPs) in patient care. Here, we describe the outcomes of multidisciplinary VUS Rounds, implemented at a neurological disease tertiary care centre, which aid in interpreting and communicating VUS identified in our neurogenetics patient population.

Methods

VUS Rounds brought together genetic counsellors, molecular geneticists and scientists to evaluate VUS against genomic and phenotypic evidence and assign an internal temperature classification of ‘VUS Hot’, ‘True VUS’ or ‘VUS Cold’, corresponding to potential pathogenicity. Biweekly meetings were held among the committee to deliberate variant classifications, determine additional clinical management actions and discuss nuances of VUS result communication.

Results

In total, 143 VUS identified in 72 individuals with neurological disease were curated between October 2022 and December 2023. Of these, 12.6% were classified as VUS Hot, carried by 22.2% of the individuals, allowing for prioritisation of additional evaluation to determine potential pathogenicity of the variants, such as clinical follow-up or segregation analysis. In contrast, 45.4% of VUS were Cold and could be eliminated from further consideration in the carrier’s care. We thoroughly evaluated the various evidence that contributed to our VUS classifications and resulting clinical actions.

Conclusions

The assessment of VUS leveraging multidisciplinary collaboration allowed us to delineate required follow-up analyses for our neurology patient population. Integration of VUS Rounds into healthcare practices ensures equitable knowledge dissemination among HCPs and effective incorporation of uncertain genetic results into patient care.