bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractMicroglia, 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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