bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Real-Time Gaze Sharing Help Team Collaboration? A Preliminary Examination of its Effectiveness with Pairs
Authors: Atweh Jad A. , Hazimeh Rana , Riggs Sara L.
Published: October 2023

Complex and dynamic domains rely on operators to collaborate on multiple tasks and cope with changes in task demands. Gaze sharing is a means of communication used to exchange visual information by allowing teammates to view each other’s gaze points on their displays. Existing work on gaze sharing focuses on relatively simple task-specific domains and no work-to-date addresses how to use gaze sharing in data-rich environments. For this study, nine pairs of participants completed a UAV search and rescue command-and-control task with three visualization techniques: no gaze sharing, gaze sharing using the real-time dot, and gaze sharing using the real-time fixation trail. Our preliminary results show that performance scores using the real-time fixation trail were statistically significantly higher than when no gaze sharing was present. This suggests that the real-time fixation trail is a promising tool to better understand operators’ strategies and could form the basis of an adaptive display.
Looking at Participant Engagement for Product Design Through a Critical Lens
Authors: Harris Maurita T. , Harrington Christina N. , Oduor Kenya , Montague Enid , Roscoe Rod D. , Stonewall Jacklin , Statler Marie Campbell
Published: October 2023

Human factors focus on taking the users’ capabilities, limitations, and environment into consideration when developing products. Thus, it is essential to have diverse perspectives and voices when designing products to be used by a variety of users. However, this is not always done and can be a missed opportunity in developing inclusive products. In this panel, we bring together researchers from different sectors to discuss challenges and strategies to engage a diverse research population at different stages in the product design process. Topics include research planning and the design process; data collection methods; and community- and participant-level recruitment. We hope that by sharing our experiences, we can prepare others to have the conversations needed that will allow them to successfully approach these topics.
Cognitive Systems Engineering at 40, Part II: Applying Theory to Practice
Authors: Rayo Michael F. , Elm William C. , Endsley Mica R. , Militello Laura , Nemeth Christopher , Roth Emilie M.
Published: October 2023

This expert panel is the second of a two-panel series marking the 40th anniversary of “Cognitive Systems Engineering: New Wine in New Bottles” by Hollnagel and Woods (1983) and, arguably, the beginning of Cognitive Systems Engineering (CSE). These experts were there at (or near) the beginning. They wrestled with the daunting issues of how to apply new CSE findings, many of which they themselves discovered, into workable solutions that actually improved systems performance in high-uncertainty, high-stakes settings. Their work has been implemented in a number of fields, including aviation, healthcare, power generation, and defense. They will each answer the question, “What ideas and perspectives are important about Cognitive Systems Engineering, and why?”
Narratives of Ageing, Narratives of Nation-building: Manjul and the Poetics of Dissidence in Nepal
Authors: Shakya Mallika
Published: October 2023

This article reads the work of a publicly engaged poet from Nepal, Manjul, to explore how revolutions age along with humans and nations. His recent work is juxtaposed against his earlier political activism leading a radical movement ‘Ralpha’ which had spearheaded literary activism against the Panchayati dictatorship. Earlier known for his subversive lifestyle and rebellious literary repertoire, Manjul later turned self-reflective, not only pondering on the ironies of everyday living and the poetics of dissidence but also inching towards a more humanised outlook on the ideals of the nation and the state. Clearly, there are paradoxes in the way the intimate and the public, the accordant and the disruptive, and the conformist and the subversive are played off against one another by those in power. In a poetic tribute dedicated to his forebearer poet Siddhicharan, Manjul contemplates how political slogans may inspire and even serve as cornerstones for certain strands of poetry. However, he emphasises how these slogans are only one of the many dimensions of society and nation. The flame of revolutionary spirit still burns within Manjul even in his advanced years. Yet, it seamlessly blends into the broader tapestry of life embracing the sanctity of thought, expression and action. The article situates this corpus within the anthropological debates on the epistemologies of writing culture.
Shrinking homes? The geographies of small domestic properties in London, 2010–2021
Authors: Hubbard Phil , Reades Jon , Walter Hendrik , Preston Catrin
Published: October 2023

In the last decade, the UK’s media have highlighted an apparent rise in the number of homes below the recommended Nationally Described Space Standard for a one-person, one-bed home. However, evidence for the growth of ‘micro-apartments’ is mixed, with existing data making it difficult to map the geographies of sub-standard homes below the Local Authority scale. Focussing on London, this paper uses Energy Performance Certificates (EPCs) as a source of floorspace data, matching this to the Land Registry’s Price Paid Data (PPD) and information from the London Planning Database. It quantifies the number of sub-standard homes in London registered for an EPC 2010–21, maps their location at the MSOA (neighbourhood) level, and compares property prices for small and larger homes. Focusing on newly-built homes, it shows that the numbers of small homes doubled across this period with growth in select outer London ‘hotspots’ accounting for much of this. It also demonstrates the overall numbers of small homes rose despite the formal incorporation of NDSS in the London Plan 2016, with the by-passing of space standards in property conversions under Permitted Development Rights, 2013–21 appearing relatively insignificant in explaining these temporal and spatial trends. Finally, it shows that the price per square metre of small homes often far exceeds that of much larger homes in the same area. While recognising the limitations of EPC data, our findings point to the need for further exploration of the enforcement of space standards, not least because it is often assumed that building more, smaller homes in the capital will create more affordable homes for Londoners.
Iyotheethasariyam—A Historiography of the Marginalized People
Authors: Varusakkani K.
Published: October 2023

Pandit C. Iyothee Thass, better known as Iyothee Thass Pandithar (1845–1914), was a social thinker who lived in Tamil Nadu and has now become a part of the social academic discourse of contemporary times. He is well-read in various disciplines like sociology, politics, religion, culture, medicine and journalism. His way of thinking is known as Iyotheethasariyam. Instead of the traditional Vedic history that focused on Brahmins and Hinduism, he created an alternative history named ‘Indra Desa Sarithiram’ by focusing on Buddhism and the oppressed people, which is considered the first subaltern history written in Tamil from the perspective of the oppressed. The article discusses the inadequacies of traditional histories and the need for alternative histories. Furthermore, it enquires about the importance of oral data in reconstructing the histories of the oppressed and neglected people by the ruling class, the methods of writing alternative histories, and the historiographical strategies that help the oppressed communities to reconstruct their histories through the thoughts of Iyothee Thass.
Regulatory effects of silicon nanoparticles on the growth and photosynthesis of cotton seedlings under salt and low-temperature dual stress
Authors: Liang Yueping , Liu Hao , Fu Yuanyuan , Li Penghui , Li Shuang , Gao Yang
Published: October 2023

Background

Silicon nanoparticles (SiO2-NPs) play a crucial role in plants mitigating abiotic stress. However, the regulatory mechanism of SiO2-NPs in response to multiple stress remains unclear. The objectives of this study were to reveal the regulatory mechanism of SiO2-NPs on the growth and photosynthesis in cotton seedlings under salt and low-temperature dual stress. It will provide a theoretical basis for perfecting the mechanism of crop resistance and developing the technology of cotton seedling preservation and stable yield in arid and high salt areas.

Results

The results showed that the salt and low-temperature dual stress markedly decreased the plant height, leaf area, and aboveground biomass of cotton seedlings by 9.58%, 15.76%, and 39.80%, respectively. While SiO2-NPs alleviated the damage of the dual stress to cotton seedling growth. In addition to reduced intercellular CO2 concentration, SiO2-NPs significantly improved the photosynthetic rate, stomatal conductance, and transpiration rate of cotton seedling leaves. Additionally, stomatal length, stomatal width, and stomatal density increased with the increase in SiO2-NPs concentration. Notably, SiO2-NPs not only enhanced chlorophyll a, chlorophyll b, and total chlorophyll content, but also slowed the decrease of maximum photochemical efficiency, actual photochemical efficiency, photochemical quenching of variable chlorophyll, and the increase in non-photochemical quenching. Moreover, SiO2-NPs enhanced the activities of ribulose-1,5-bisphosphate carboxylase/oxygenase and phosphoenolpyruvate carboxylase, improved leaf water potential, and decreased abscisic acid and malondialdehyde content. All the parameters obtained the optimal effects at a SiO2-NPs concentration of 100 mg L− 1, and significantly increased the plant height, leaf area, and aboveground biomass by 7.68%, 5.37%, and 43.00%, respectively. Furthermore, significant correlation relationships were observed between photosynthetic rate and stomatal conductance, stomatal length, stomatal width, stomatal density, chlorophyll content, maximum photochemical efficiency, actual photochemical efficiency, photochemical quenching of variable chlorophyll, and Rubisco activity.

Conclusion

The results suggested that the SiO2-NPs improved the growth and photosynthesis of cotton seedlings might mainly result from regulating the stomatal state, improving the light energy utilization efficiency and electron transport activity of PSII reaction center, and inducing the increase of Rubisco activity to enhance carbon assimilation under the salt and low-temperature dual stress.
Association of adiposity indices with cardiometabolic multimorbidity among 101,973 chinese adults: a cross-sectional study
Authors: Qin Xiaoru , Chen Chaolei , Wang Jiabin , Cai Anping , Feng Xiaoxuan , Jiang Xiaofei , Feng Yingqing
Published: October 2023

Background

Cardiometabolic multimorbidity (CMM) and obesity represent two major health problems. The relationship between adiposity indices and CMM, however, remains understudied. This study aimed to investigate the associations of body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), and conicity index (CI) with CMM among Chinese adults.

Methods

Data of 101,973 participants were collected from a population-based screening project in Southern China. CMM was defined as having two or more of the following diseases: coronary heart disease, stroke, hypertension, and diabetes. The relationship between the six adiposity indices and CMM was investigated by multivariate logistic regression and restricted cubic splines. Receiver operator characteristic curve, C-statistic and net reclassification index were used to estimate the discriminative and incremental values of adiposity indices on CMM.

Results

Logistic regression models showed the six adiposity indices were all significantly associated with the odds of CMM with non-linear relationships. For per SD increment, WC (Odds ratio [OR]: 1.66; 95% confidence interval (CI): 1.62–1.70) and WHtR (OR, 1.61; 95% CI, 1.58–1.65) were more significantly associated with a higher prevalence of CMM than BMI (OR, 1.55; 95% CI, 1.52–1.58) (all P < 0.05). In addition, WC, WHtR, and BRI displayed significantly better performance in detecting CMM compared with BMI (all P < 0.05). Their respective area under the curve (AUC) values were 0.675 (95% CI: 0.670–0.680), 0.679 (95% CI: 0.675–0.684), and 0.679 (95% CI: 0.675–0.684), while BMI yielded an AUC of 0.637 (95% CI: 0.632–0.643). These findings hold true across all subgroups based on sex and age. When Adding WC, WHtR, or BRI to a base model, they all provided larger incremental values for the discrimination of CMM compared with BMI (all P < 0.05).

Conclusions

Adiposity indices were closely associated with the odds of CMM, with WC and WHtR demonstrating stronger associations than BMI. WC, WHtR, and BRI were superior to BMI in discriminative ability for CMM. Avoidance of obesity (especially abdominal obesity) may be the preferred primary prevention strategy for CMM while controlling for other major CMM risk factors.
Prevalence and factors associated with pre-hospital delay among acute stroke patients at Mulago and Kiruddu national referral hospitals, Kampala: a cross-sectional study
Authors: Kakame Keith Twirire , Nakibuuka Jane , Mukiza Nelson , Andia-Biraro Irene , Kaddumukasa Mark , Burant Chris , Katabira Elly , Sajatovic Martha
Published: October 2023

Background

Despite advancements in acute stroke care, acute stroke patients present late for care resulting in high mortality and poor functional outcomes. This study determined the prevalence of pre-hospital delay and associated factors among adult acute stroke patients in Uganda.

Methods

In a hospital based, cross-sectional study, one hundred and forty-three study participants with confirmed acute stroke presenting to the emergency units of Mulago and Kiruddu national referral hospitals were enrolled. Using an interviewer-administered questionnaire, details on sociodemographics, onset of stroke, arrival at the tertiary facility, health system and clinical factors were collected. Descriptive statistics and modified Poisson regression analyses were performed to determine factors associated with prehospital delay.

Results

Among the 143 study participants, nearly two-thirds (79/146) had ischemic stroke while a third (59/143) had haemorrhagic stroke. The mean age was 59 years (SD 16) and 51.7% of acute stroke patients were males. Ninety one percent (130/143) presented to the emergency unit after 3 hours. The majority (124/143) reported visiting lower-level facilities prior to referral to the tertiary facility. Staying outside Kampala district (PR: 1.28 (1.22–1.34),p < 0.001), and using hired or government ambulance for transport to tertiary facility (PR: 1.17 (1.13–1.20),p < 0.001) were associated with pre-hospital delay.

Conclusions

Prevalence of pre-hospital delay among acute stroke patients presenting to public tertiary hospitals in Uganda is very high. The causes of pre hospital delay should be further explored qualitatively. Efforts to reduce prehospital delay should include improving pre-hospital transport systems for stroke patients.
Evaluation of occupational stress and job performance in Iranian nurses: the mediating effect of moral and emotional intelligence
Authors: Alinejad Vahid , Parizad Naser , Almasi Laleh , Cheraghi Rozita , Piran Mehri
Published: October 2023

Background

Nurses’ Job performance could be affected by occupational stress. Previous studies reported contradictory results in this regard. Factors such as moral and emotional intelligence could impact occupational stress. However, the extent of any mediating effect is unclear. Thus, this study aimed to determine the effect of occupational stress on nurses’ Job performance and the mediating impact of moral and emotional intelligence.

Methods

This cross-sectional study was conducted in Urmia teaching hospitals (Imam Khomeini, Motahari, Taleghani, Kosar, and Seyed al-Shohada Hospitals). Six hundred twenty-one nurses were selected using quota sampling from February 2022 to April 2022. Data were collected using demographic questionnaires, the Nursing Stress Scale, Paterson’s Job Performance Questionnaire, Siberia Schering’s Emotional Intelligence Standard Questionnaire, and Lennik and Keil’s Moral Intelligence Questionnaire. Data were analyzed using SPSS ver. 23 and SmartPLS ver. 2.

Results

Occupational stress had a positive, direct, and minor effect on nurses’ job performance (β = 0.088, t-value = 2.245, p < 0.01). Occupational stress had a positive and direct impact on moral intelligence (β = 0.161, t-value = 2.945, p < 0.01) and a negative and direct effect on emotional intelligence (β = -0.351, t-value = 7.484, p < 0.01). Occupational stress negatively and indirectly affected job performance through moral intelligence (β =—0.560, t-value = 14.773, p < 0.01). Occupational stress also positively and indirectly impacted job performance through emotional intelligence (β = 0.098, t-value = 2.177, p < 0.01).

Conclusions

Occupational stress slightly affects nurses’ job performance, and emotional and moral intelligence mediates the impact of occupational stress and improves nurses’ job performance. Low occupational stress improves nurses’ job performance, but too much occupational stress could harm nurses’ job performance. Healthcare administrators should work to help reduce nurses’ occupational stress and improve their job performance by adopting practical strategies to help nurses manage and control their stress. Holding stress reduction classes, eliminating the nursing shortage, reducing working hours, reducing workload, and providing financial and spiritual support to nurses would be recommended. It is also recommended to provide theoretical and practical emotional and moral intelligence-oriented courses for nursing students and hold training workshops for nurses to improve their emotional and moral intelligence.
Network pharmacology-based strategy to investigate the effect and mechanism of α-solanine against glioma
Authors: Wang ChunPeng , Liu XiaoHui , Guo ShiWen
Published: October 2023

Background

An anti-tumour activity has been demonstrated for α-solanine, a bioactive compound extracted from the traditional Chinese herbSolanum nigrum L. However, its efficacy in the treatment of gliomas and the underlying mechanisms remain unclear. The aim of this study was to investigate the inhibitory effects of α-solanine on glioma and elucidate its mechanisms and targets using network pharmacology, molecular docking, and molecular biology experiments.

Methods

Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was utilized to predict the potential targets of α-solanine. GeneCards was used to gather glioma-related targets, and the STRING online database was used to analyze protein–protein interaction (PPI) networks for the shared targets. Hub genes were identified from the resulting PPI network and further investigated using Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Additionally, prognostic and gene set enrichment analyses (GSEA) were carried out to identify potential therapeutic targets and their underlying mechanisms of action in relation to the prognosis of gliomas. In vitro experiments were conducted to verify the findings from the network pharmacology analysis.

Results

A total of 289 α-solanine targets and 1149 glioma-related targets were screened, of which 78 were common targets. 11 hub genes were obtained, including SRC, HRAS, HSP90AA1, IGF1, MAPK1, MAPK14, KDR, STAT1, JAK2, MAP2K1, and IGF1R. The GO and KEGG pathway analyses unveiled that α-solanine was strongly associated with several signaling pathways, including positive regulation of MAP kinase activity and PI3K-Akt. Moreover, α-solanine (10 µM and 15 µM) inhibited the proliferation and migration but promoted the apoptosis of glioma cells. Finally, STAT1 was identified as a potential mediator of the effect of α-solanine on glioma prognosis.

Conclusion

α-Solanine can inhibit the proliferation and migration of gliomas by regulating multiple targets and signalling pathways. These findings lay the foundation for the creation of innovative clinical anti-glioma agents.
The informal way to success or failure? Findings from a comparative case study on video consultation training and implementation in two Danish hospitals
Authors: Eriksen Susanne , Dahler Anne Marie , Øye Christine
Published: October 2023

Background

This study evaluated an attempt to implement video consultations through a novel education intervention in telehealth training and implementation in two middle-sized hospitals in Denmark. Three units tested the education intervention along with a regional decision to strengthen multidisciplinary and cross-sectoral collaboration through technology to improve service delivery by making the process more coherent and saving time and resources. This study aims to identify what contextual factors enable workplace learning, skills acquisition, and utilization of new digital skills to use and routinize video consultations in workplace practice.

Methods

This qualitative case study draws on the principles of the realist evaluation framework using cross-case comparisons to test and refine program theories by exploring the complex and dynamic interaction among context, mechanism, and outcome. The methods in this study include participant observations, document analysis, semi-structured individual interviews, and focus groups. We performed an interpretive cross-case analysis, which explored the context-mechanism-outcome relationship using the guiding question, “What works, for whom, under what circumstances, and why?”.

Results

Two broad mechanisms appeared to enable skills acquisition and routinization of video consultations: informal workplace learning and adjusting video consultations to professional judgment. The three units had different approaches to the implementation and training and, as such, had different outcomes. First, the skills acquired in the units differed; therefore, how and with whom they used video consultations varied. Second, video consultation use was more likely to be adjusted to workflows if unit managers were responsive to staff’s professional judgments regarding patients, as was evident in all three units.

Conclusion

Our study shows that a formal training course alone is insufficient to provide healthcare professionals with the skills needed to use video consultations in workplace practice. Informal workplace learning with support on the spot and continuous follow-up seems to equip healthcare professionals with the skills to use video consultations. Video consultations are more likely to be used confidently if novel workflows are adjusted to health care professionals' knowledge, skills, and judgment and their concerns regarding patient soundness.
Familial co-aggregation and shared genetics of cardiometabolic disorders and traits: data from the multi-generational Lifelines Cohort Study
Authors: Triatin Rima D. , Chen Zekai , Ani Alireza , Wang Rujia , Hartman Catharina A. , Nolte Ilja M. , Thio Chris H. L. , Snieder Harold
Published: October 2023

Background

It is unclear to what extent genetics explain the familial clustering and the co-occurrence of distinct cardiometabolic disorders in the general population. We therefore aimed to quantify the familial (co-)aggregation of various cardiometabolic disorders and to estimate the heritability of cardiometabolic traits and their genetic correlations using the large, multi-generational Lifelines Cohort Study.

Methods

We used baseline data of 162,416 participants from Lifelines. Cardiometabolic disorders including type 2 diabetes (T2D), cardiovascular diseases, hypertension, obesity, hypercholesterolemia, and metabolic syndrome (MetS), were defined in adult participants. Fifteen additional cardiometabolic traits indexing obesity, blood pressure, inflammation, glucose regulation, and lipid levels were measured in all included participants. Recurrence risk ratios (λR) for first-degree relatives (FDR) indexed familial (co-)aggregation of cardiometabolic disorders using modified conditional Cox proportional hazards models and were compared to those of spouses. Heritability (h2), shared environment, and genetic correlation (rg) were estimated using restricted maximum likelihood variance decomposition methods, adjusted for age, age2, and sex.

Results

Individuals with a first-degree relative with a cardiometabolic disorder had a higher risk of the same disorder, ranging from λFDR of 1.23 (95% CI 1.20–1.25) for hypertension to λFDR of 2.48 (95% CI 2.15–2.86) for T2D. Most of these were higher than in spouses (λSpouses < λFDR), except for obesity which was slightly higher in spouses. We found moderate heritability for cardiometabolic traits (from h2CRP: 0.26 to h2HDL: 0.50). Cardiometabolic disorders showed positive familial co-aggregation, particularly between T2D, MetS, and obesity (from λFDR obesity-MetS: 1.28 (95% CI 1.24–1.32) to λFDR MetS-T2D: 1.61 (95% CI 1.52–1.70)), consistent with the genetic correlations between continuous intermediate traits (ranging from rg HDL-Triglycerides: − 0.53 to rg LDL-Apolipoprotein B: 0.94).

Conclusions

There is positive familial (co-)aggregation of cardiometabolic disorder, moderate heritability of intermediate traits, and moderate genetic correlations between traits. These results indicate that shared genetics and common genetic architecture contribute to cardiometabolic disease.
Identification of a novel family B DNA polymerase from Enterococcus phage IME199 and its overproduction in Escherichia coli BL21(DE3)
Authors: Han Pengjun , Fan Huahao , Tong Yigang
Published: October 2023

Background

Identification and characterization of novel, faithful and processive DNA polymerases is a driving force in the development of DNA amplification methods. Purification of proteins from natural phages is often time-consuming, cumbersome and low yielding. Escherichia coli is a host bacterium widely used for the production of recombinant proteins, is the cell factory of choice for in vitro studies of phage protein function.

Results

We expressed the gene encoding Enterococcus faecium phage IME199 DNA polymerase (IME199 DNAP) in Escherichia coli BL21(DE3), and characterized protein function. IME199 DNAP has 3′-5′ exonuclease activity, but does not have 5′-3′ exonuclease activity. In addition, IME199 DNAP has dNTP-dependent 5′-3′ polymerase activity and can amplify DNA at 15–35 °C and a pH range of 5.5–9.5. The amino acid residues Asp30, Glu32, Asp112 and Asp251 are the 3′-5′ exonuclease active sites of IME199 DNAP, while residues Asp596 and Tyr639 are essential for DNA synthesis by IME199 DNAP. More importantly, the IME199 DNAP has strand displacement and processive synthesis capabilities, and can perform rolling circle amplification and multiple displacement amplification with very low error rates (approximately 3.67 × 10–6).

Conclusions

A novel family B DNA polymerase was successfully overproduced in Escherichia coli BL21(DE3). Based on the characterized properties, IME199 DNAP is expected to be developed as a high-fidelity polymerase for DNA amplification at room temperature.
Adolescent and caregiver preferences for juvenile idiopathic arthritis treatment: a discrete-choice experiment
Authors: McErlane Flora , Boeri Marco , Bussberg Cooper , Cappelleri Joseph C. , Germino Rebecca , Stockert Lori , Vass Caroline , Huber Adam M.
Published: October 2023

Background

This study aimed to elicit and quantify preferences for treatments for juvenile idiopathic arthritis (JIA).

Methods

We conducted a discrete-choice experiment among adolescents with JIA in the United States (US) (n = 197) and United Kingdom (UK) (n = 100) and caregivers of children with JIA in the US (n = 207) and UK (n = 200). In a series of questions, respondents chose between experimentally designed profiles for hypothetical JIA treatments that varied in efficacy (symptom control; time until next flare-up), side effects (stomachache, nausea, and vomiting; headaches), mode and frequency of administration, and the need for combination therapy. Using a random-parameters logit model, we estimated preference weights for these attributes, from which we derived their conditional relative importance.

Results

On average, respondents preferred greater symptom control; greater time until the next flare-up; less stomachache, nausea, and vomiting; and fewer headaches. However, adolescents and caregivers in the US were generally indifferent across varying modes and frequencies of administration. UK adolescents and caregivers preferred tablets, syrup, or injections to intravenous infusions. US and UK adolescents were indifferent between treatment with monotherapy or combination therapy; caregivers in the UK preferred treatment with combination therapy to monotherapy. Subgroup analysis showed preference heterogeneity across characteristics including gender, treatment experience, and symptom experience in both adolescents and caregivers.

Conclusions

Improved symptom control, prolonged time to next flare-up, and avoidance of adverse events such as headache, stomachache, nausea, and vomiting are desirable characteristics of treatment regimens for adolescents with JIA and their caregivers.
Distinguishing the effects of systemic CSF1R inhibition by PLX3397 on microglia and peripheral immune cells
Authors: Okojie Akhabue K. , Uweru Joseph O. , Coburn Morgan A. , Li Sihan , Cao-Dao Vivian D. , Eyo Ukpong B.
Published: October 2023

Microglia, the primary immune cells of the central nervous system (CNS), are derived from the yolk sac and populate the brain during development. Once microglia migrate to the CNS, they are self-renewing and require CSF1R signaling for their maintenance. Pexidartinib (PLX3397, PLX), a small molecule inhibitor of the CSF1R, has been shown to effectively deplete microglia since microglial maintenance is CSF1R-dependent. There have, however, been several conflicting reports that have shown the potential off-target effects of PLX on peripheral immune cells particularly those of lymphoid origin. Given this controversy in the use of the PLX family of drugs, it has become important to ascertain to what extent PLX affects the peripheral immune profile in lymphoid (spleen, and bone marrow) and non-lymphoid (kidney, lungs, and heart) organs. PLX3397 chow treatment at 660 mg/kg for 7 days significantly reduced CD45+ macrophages, CX3CR1-GFP cells, CD11b+CD45intermediate cells, and P2RY12 expression in the brain. However, there were minimal effects on peripheral immune cells from both lymphoid and non-lymphoid organs except in the heart where there was a significant decrease in CD3+ cells, inflammatory and patrolling monocytes, and CD11b+Ly6G+ neutrophils. We then stimulated the immune system with 1 mg/kg of LPS which resulted in a significant reduction in the number of innate immune cells. In this context, PLX did not alter the cytokine profile in the serum and the brain of naïve mice but did so in the LPS-stimulated group resulting in a significant reduction in TNFα, IL-1α, IFN-γ and IL-1β. Furthermore, PLX did not alter locomotor activity in the open field test suggesting that microglia do not contribute to LPS-induced sickness behavior. Our results provide an assessment of immune cell populations with PLX3397 treatment on brain, lymphoid and non-lymphoid organs without and during LPS treatment that can serve as a resource for understanding consequences of such approaches.
Keeping reptiles as pets in Brazil: keepers’ motivations and husbandry practices
Authors: De la Fuente María Fernanda , de Araújo Bruna Monielly Carvalho , da Silva Policarpo Iamara , Pereira Heliene Mota , Borges Anna Karolina Martins , Vieira Washington Luiz Silva , Pereira Filho Gentil Alves , Alves Rômulo Romeu Nóbrega
Published: October 2023

Background

Reptiles are considered one of the most popular pets in the world and are often associated with an incorrect belief that they are simple, highly adaptable, and easy to keep animals when compared with other pets, such as dogs and cats. However, keeping reptiles as pets can pose several challenges in meeting their needs in a domestic setting, requiring specific conditions and effort to maintain their health, well-being, and survival.

Methods

During 2015, using online semi-structured questionnaires applied to 719 Brazilian pet reptile keepers who participated in online groups of reptile breeders on the social network Facebook, this study aimed to identify Brazilian keepers’ motivations for maintaining reptiles as pets, investigate their monthly expenses, and the husbandry practices for the maintenance, such as housing and feeding conditions, handling of the animal, health issues, and treatment provided.

Results

We found multiple motivations for keeping reptiles as pets (mostly snakes, lizards, and chelonians), the main motivation being emotional reasons, followed by entertainment and convenience reasons. The great majority of keepers (69%) declared to spend less than or up to US$30 per month in maintaining their reptiles. Most reptiles were kept alone in terrarium/aquarium enclosures, with basic environmental complexity in terms of physical elements. Lizards and chelonians were fed with a few insect species, cultivated fruits and vegetables, while snakes were fed mainly with domestic rodents, rabbits, or birds. Keepers declared frequent cleaning of the enclosure, but inappropriately handled their animals directly with their hands, which might result in potential threats to human and reptile health and safety. Several diseases or injuries were mentioned and 55.6% of the keepers declared taking the reptile to the vet for treatment.

Conclusions

Overall, our findings revealed several challenges that reptiles face when kept in domestic environments, including issues related to housing, nutrition, and healthcare. Even though keepers demonstrated positive feelings toward their pets, suggesting a positive relationship and a willingness to provide them with proper care, it seems that without the proper knowledge and awareness, reptiles may unintentionally be kept with poor husbandry. Addressing these challenges on husbandry practices is essential for improving reptiles’ welfare and promoting a responsible pet ownership.
Prevalence and predictors of shared decision-making in goals-of-care clinician-family meetings for critically ill neurologic patients: a multi-center mixed-methods study
Authors: Fleming Victoria , Prasad Abhinav , Ge Connie , Crawford Sybil , Meraj Shazeb , Hough Catherine L. , Lo Bernard , Carson Shannon S. , Steingrub Jay , White Douglas B. , Muehlschlegel Susanne
Published: October 2023

Background

Shared decision-making is a joint process where patients, or their surrogates, and clinicians make health choices based on evidence and preferences. We aimed to determine the extent and predictors of shared decision-making for goals-of-care discussions for critically ill neurological patients, which is crucial for patient-goal-concordant care but currently unknown.

Methods

We analyzed 72 audio-recorded routine clinician-family meetings during which goals-of-care were discussed from seven US hospitals. These occurred for 67 patients with 72 surrogates and 29 clinicians; one hospital provided 49/72 (68%) of the recordings. Using a previously validated 10-element shared decision-making instrument, we quantified the extent of shared decision-making in each meeting. We measured clinicians’ and surrogates’ characteristics and prognostic estimates for the patient’s hospital survival and 6-month independent function using post-meeting questionnaires. We calculated clinician-family prognostic discordance, defined as ≥ 20% absolute difference between the clinician’s and surrogate’s estimates. We applied mixed-effects regression to identify independent associations with greater shared decision-making.

Results

The median shared decision-making score was 7 (IQR 5–8). Only 6% of meetings contained all 10 shared decision-making elements. The most common elements were “discussing uncertainty”(89%) and “assessing family understanding”(86%); least frequent elements were “assessing the need for input from others”(36%) and “eliciting the context of the decision”(33%). Clinician-family prognostic discordance was present in 60% for hospital survival and 45% for 6-month independent function. Univariate analyses indicated associations between greater shared decision-making and younger clinician age, fewer years in practice, specialty (medical-surgical critical care > internal medicine > neurocritical care > other > trauma surgery), and higher clinician-family prognostic discordance for hospital survival. After adjustment, only higher clinician-family prognostic discordance for hospital survival remained independently associated with greater shared decision-making (p = 0.029).

Conclusion

Fewer than 1 in 10 goals-of-care clinician-family meetings for critically ill neurological patients contained all shared decision-making elements. Our findings highlight gaps in shared decision-making. Interventions promoting shared decision-making for high-stakes decisions in these patients may increase patient-value congruent care; future studies should also examine whether they will affect decision quality and surrogates’ health outcomes.
LPMO-supported saccharification of biomass: effects of continuous aeration of reaction mixtures with variable fractions of water-insoluble solids and cellulolytic enzymes
Authors: Tang Chaojun , Gandla Madhavi Latha , Jönsson Leif J.
Published: October 2023

Background

High substrate concentrations and high sugar yields are important aspects of enzymatic saccharification of lignocellulosic substrates. The benefit of supporting the catalytic action of lytic polysaccharide monooxygenase (LPMO) through continuous aeration of slurries of pretreated softwood was weighed against problems associated with increasing substrate content (quantitated as WIS, water-insoluble solids, in the range 12.5–17.5%), and was compared to the beneficial effect on the saccharification reaction achieved by increasing the enzyme preparation (Cellic CTec3) loadings. Aerated reactions were compared to reactions supplied with N2 to assess the contribution of LPMO to the saccharification reactions. Analysis using 13C NMR spectroscopy, XRD, Simons’ staining, BET analysis, and SEM analysis was used to gain further insights into the effects of the cellulolytic enzymes on the substrate under different reaction conditions.

Results

Although glucose production after 72 h was higher at 17.5% WIS than at 12.5% WIS, glucan conversion decreased with 24% (air) and 17% (N2). Compared to reactions with N2, the average increases in glucose production for aerated reactions were 91% (12.5% WIS), 70% (15.0% WIS), and 67% (17.5% WIS). Improvements in glucan conversion through aeration were larger (55–86%) than the negative effects of increasing WIS content. For reactions with 12.5% WIS, increased enzyme dosage with 50% improved glucan conversion with 25–30% for air and N2, whereas improvements with double enzyme dosage were 30% (N2) and 39% (air). Structural analyses of the solid fractions revealed that the enzymatic reaction, particularly with aeration, created increased surface area (BET analysis), increased disorder (SEM analysis), decreased crystallinity (XRD), and increased dye adsorption based on the cellulose content (Simons' staining).

Conclusions

The gains in glucan conversion with aeration were larger than the decreases observed due to increased substrate content, resulting in higher glucan conversion when using aeration at the highest WIS value than when using N2 at the lowest WIS value. The increase in glucan conversion with double enzyme preparation dosage was smaller than the increase achieved with aeration. The results demonstrate the potential in using proper aeration to exploit the inherent capacity of LPMO in enzymatic saccharification of lignocellulosic substrates and provide detailed information about the characteristics of the substrate after interaction with cellulolytic enzymes.
Differences in malaria vector biting behavior and changing vulnerability to malaria transmission in contrasting ecosystems of western Kenya
Authors: Nzioki Irene , Machani Maxwell G. , Onyango Shirley A. , Kabui Kevin K. , Githeko Andrew K. , Ochomo Eric , Yan Guiyun , Afrane Yaw A.
Published: October 2023

Background

Designing, implementing, and upscaling of effective malaria vector control strategies necessitates an understanding of when and where transmission occurs. This study assessed the biting patterns of potentially infectious malaria vectors at various hours, locations, and associated human behaviors in different ecological settings in western Kenya.

Methods

Hourly indoor and outdoor catches of human-biting mosquitoes were sampled from 19:00 to 07:00 for four consecutive nights in four houses per village. The human behavior study was conducted via questionnaire surveys and observations. Species within the Anopheles gambiae complex and Anopheles funestus group were distinguished by polymerase chain reaction (PCR) and the presence of Plasmodium falciparum circumsporozoite proteins (CSP) determined by enzyme-linked immunosorbent assay (ELISA).

Results

Altogether, 2037 adult female anophelines were collected comprising the An. funestus group (76.7%), An. gambiae sensu lato (22.8%), and Anopheles coustani (0.5%). PCR results revealed that Anopheles arabiensis constituted 80.5% and 79% of the An. gambiae s.l. samples analyzed from the lowland sites (Ahero and Kisian, respectively). Anopheles gambiae sensu stricto (hereafter An. gambiae) (98.1%) was the dominant species in the highland site (Kimaeti). All the An. funestus s.l. analyzed belonged to An. funestus s.s. (hereafter An. funestus). Indoor biting densities of An. gambiae s.l. and An. funestus exceeded the outdoor biting densities in all sites. The peak biting occurred in early morning between 04:30 and 06:30 in the lowlands for An. funestus both indoors and outdoors. In the highlands, the peak biting of An. gambiae occurred between 01:00 and 02:00 indoors. Over 50% of the study population stayed outdoors from 18:00 to 22:00 and woke up at 05:00, coinciding with the times when the highest numbers of vectors were collected. The sporozoite rate was higher in vectors collected outdoors, with An. funestus being the main malaria vector in the lowlands and An. gambiae in the highlands.

Conclusion

This study shows heterogeneity of anopheline distribution, high outdoor malaria transmission, and early morning peak biting activity of An. funestus when humans are not protected by bednets in the lowland sites. Additional vector control efforts targeting the behaviors of these vectors, such as the use of non-pyrethroids for indoor residual spraying and spatial repellents outdoors, are needed.

Graphical Abstract
Functional integration of natural killer cells in a microfluidically perfused liver on-a-chip model
Authors: Fahrner René , Gröger Marko , Settmacher Utz , Mosig Alexander S.
Published: October 2023

Objective

The liver acts as an innate immunity-dominant organ and natural killer (NK) cells, are the main lymphocyte population in the human liver. NK cells are in close interaction with other immune cells, acting as the first line of defense against pathogens, infections, and injury.

A previously developed, three-dimensional, perfused liver-on-a-chip comprised of human cells was used to integrate NK cells, representing pivotal immune cells during liver injury and regeneration. The objective of this study was to integrate functional NK cells in an in vitro model of the human liver and assess utilization of the model for NK cell-dependent studies of liver inflammation.

Results

NK cells from human blood and liver specimen were isolated by Percoll separation with subsequent magnetic cell separation (MACS), yielding highly purified blood and liver derived NK cells. After stimulation with toll-like-receptor (TLR) agonists (lipopolysaccharides, Pam3CSK4), isolated NK cells showed increased interferon (IFN)-gamma secretion. To study the role of NK cells in a complex hepatic environment, these cells were integrated in the vascular compartment of a microfluidically supported liver-on-a-chip model in close interaction with endothelial and resident macrophages. Successful, functional integration of NK cells was verified by immunofluorescence staining (NKp46), flow cytometry analysis and TLR agonist-dependent secretion of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. Lastly, we observed that inflammatory activation of NK cells in the liver-on-a-chip led to a loss of vascular barrier integrity. Overall, our data shows the first successful, functional integration of NK cells in a liver-on-a-chip model that can be utilized to investigate NK cell-dependent effects on liver inflammation in vitro.
Late diagnosis of respiratory syncytial virus and influenza co-infection during coronavirus disease 2019 pandemic: a case report
Authors: Barahimi Elham , Azad Mehdi Hassani , Hesarooeyeh Zahra Ghaeini , Hafshejani Niloofar Hosseini , Defaee Sahar , Seddighi Narjes
Published: October 2023

Background

Respiratory syncytial virus (RSV)-induced disease is one of the important causes of flu-like illness in older adults and can cause serious disease in those who are at high-risk medical conditions. During coronavirus disease 2019 (COVID-19) pandemic, because of overlapping symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection with other respiratory infections, diagnosing diseases based on clinical and radiological findings was challenging and could cause misdiagnosis.

Case presentation

An 87-year-old Persian man was admitted to the hospital due to loss of consciousness, respiratory distress, tachypnea, and oliguria. He had previously hospitalized because of cough, fever, loss of appetite, and fatigue. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) test was performed which was negative; however, based on ground glass opacity on his chest computed tomography (CT) scan and being on the outbreak of COVID-19, he fulfilled case definition of COVID-19; therefore, he received protocol’s treatment (remdesivir) for COVID-19 and relatively recovered and discharged. In our center, we requested brain and chest CT scans, blood tests, and multiplex PCR. Multiplex PCR revealed co-infection of influenza virus and RSV. Although we had started pneumonia and sepsis treatment, old age, weak immune system and the delay in initiation of right antibiotic and antivirus therapy altogether led him to die.

Conclusion

As a takeaway lesson of this case report, it is necessary to pay attention to viruses that show similar symptoms during future specific virus pandemics, especially in patients with old age and weak immune systems.