bluuebunny/crossref_metadata_2025 huggingface dataset:
Requirements analysis for an AI-based clinical decision support system for general practitioners: a user-centered design process
Authors: Schütze Dania , Holtz Svea , Neff Michaela C. , Köhler Susanne M. , Schaaf Jannik , Frischen Lena S. , Sedlmayr Brita , Müller Beate S.
Published: July 2023

Background

As the first point of contact for patients with health issues, general practitioners (GPs) are frequently confronted with patients presenting with non-specific symptoms of unclear origin. This can result in delayed, prolonged or false diagnoses. To accelerate and improve the diagnosis of diseases, clinical decision support systems would appear to be an appropriate tool. The objective of the project ‘Smart physician portal for patients with unclear disease’ (SATURN) is to employ a user-centered design process based on the requirements analysis presented in this paper to develop an artificial Intelligence (AI)-based diagnosis support system that specifically addresses the needs of German GPs.

Methods

Requirements analysis for a GP-specific diagnosis support system was conducted in an iterative process with five GPs. First, interviews were conducted to analyze current workflows and the use of digital applications in cases of diagnostic uncertainty (as-is situation). Second, we focused on collecting and prioritizing tasks to be performed by an ideal smart physician portal (to-be situation) in a workshop. We then developed a task model with corresponding user requirements.

Results

Numerous GP-specific user requirements were identified concerning the tasks and subtasks: performing data entry (open system, enter patient data), reviewing results (receiving and evaluating results), discussing results (with patients and colleagues), scheduling further diagnostic procedures, referring to specialists (select, contact, make appointments), and case closure. Suggested features particularly concerned the process of screening and assessing results: e.g., the system should focus more on atypical patterns of common diseases than on rare diseases only, display probabilities of differential diagnoses, ensure sources and results are transparent, and mark diagnoses that have already been ruled out. Moreover, establishing a means of using the platform to communicate with colleagues and transferring patient data directly from electronic patient records to the system was strongly recommended.

Conclusions

Essential user requirements to be considered in the development and design of a diagnosis system for primary care could be derived from the analysis. They form the basis for mockup-development and system engineering.
Modes and models of care delivery in municipal long-term care services: a cross-sectional study from Norway
Authors: Rostad Hanne Marie , Skinner Marianne Sundlisæter , Wentzel-Larsen Tore , Hellesø Ragnhild , Sogstad Maren Kristine Raknes
Published: July 2023

Background

Numerous forces drive the evolution and need for transformation of long-term care services. Decision-makers across the globe are searching for models to redesign long-term care to become more responsive to changing health and care needs. Yet, knowledge of different care models unfolding in the long-term care service landscape is limited. The objective of this article is twofold: 1) to identify and characterise models of care in Norwegian municipal long-term care services based on four different modes of service delivery: Specialised municipal services, Assistive technology, Planning and coordination, and Health Promotion and Activity, and 2) to analyse whether the identified care models vary with regard to municipal characteristics, more specifically ‘population size’ and ‘income’.

Methods

We adopted a cross-sectional approach and used data from a web-based survey conducted in 2019 to identify and characterize models of care in Norwegian long-term care services, based on four modes of service delivery. The questionnaire was developed through a comprehensive review of national healthcare policy documents and previous research and amended in collaboration with a user panel. A set of questions from the questionnaire were used to create four modes of service delivery. Hierarchical cluster analysis was used to cluster the municipalities based on the mean scores of the modes to identify care models.

Results

In total, 277 municipalities (response rate 66%) completed the survey. The four modes made it possible to identify four care models that differ on the level of Specialised municipal services, Assistive technology, Planning and coordination, and Health Promotion and Activity. Additionally, the models differed regarding municipal population size (p < 0.001) and income (p = 0.006).

Conclusions

We put forward a theoretical description of the variety of ways long-term care services are provided, offering a way of simplifying complex information which can assist care providers and policymakers in analysing and monitoring their own service provision and making informed decisions. This is important to the development of services for current and future care needs.
Economic analysis of a new four-panel rapid screening test in antenatal care in Kenya, Rwanda, and Uganda
Authors: Shepard Donald S , Halasa-Rappel Yara A , Rowlands Katharine R , Kulchyckyj Maria , Basaza Robert K , Otieno Emmanuel D , Mutatina Boniface , Kariuki Simon , Musange Sabine F
Published: July 2023

Background

We performed an economic analysis of a new technology used in antenatal care (ANC) clinics, the ANC panel. Introduced in 2019–2020 in five Rwandan districts, the ANC panel screens for four infections [hepatitis B virus (HBV), human immunodeficiency virus (HIV), malaria, and syphilis] using blood from a single fingerstick. It increases the scope and sensitivity of screening over conventional testing.

Methods

We developed and applied an Excel-based economic and epidemiologic model to perform cost-effectiveness and cost-benefit analyses of this technology in Kenya, Rwanda, and Uganda. Costs include the ANC panel itself, its administration, and follow-up treatment. Effectiveness models predicted impacts on maternal and infant mortality and other outcomes. Key parameters are the baseline prevalence of each infection and the effectiveness of early treatment using observations from the Rwanda pilot, national and international literature, and expert opinion. For each parameter, we found the best estimate (with 95% confidence bound).

Results

The ANC panel averted 92 (69–115) disability-adjusted life years (DALYs) per 1,000 pregnant women in ANC in Kenya, 54 (52–57) in Rwanda, and 258 (156–360) in Uganda. Net healthcare costs per woman ranged from $0.53 ($0.02-$4.21) in Kenya, $1.77 ($1.23-$5.60) in Rwanda, and negative $5.01 (-$6.45 to $0.48) in Uganda. Incremental cost-effectiveness ratios (ICERs) in dollars per DALY averted were $5.76 (-$3.50-$11.13) in Kenya, $32.62 ($17.54-$46.70) in Rwanda, and negative $19.40 (-$24.18 to -$15.42) in Uganda. Benefit-cost ratios were $17.48 ($15.90-$23.71) in Kenya, $6.20 ($5.91-$6.45) in Rwanda, and $25.36 ($16.88-$33.14) in Uganda. All results appear very favorable and cost-saving in Uganda.

Conclusion

Though subject to uncertainty, even our lowest estimates were still favorable. By combining field data and literature, the ANC model could be applied to other countries.
Rehabilitation models that support transitions from hospital to home for people with acquired brain injury (ABI): a scoping review
Authors: Eliassen Marianne , Arntzen Cathrine , Nikolaisen Morten , Gramstad Astrid
Published: July 2023

Background

Research shows a lack of continuity in service provision during the transition from hospital to home for people with acquired brain injuries (ABI). There is a need to gather and synthesize knowledge about services that can support strategies for more standardized referral and services supporting this critical transition phase for patients with ABI. We aimed to identify how rehabilitation models that support the transition phase from hospital to home for these patients are described in the research literature and to discuss the content of these models.

Methods

We based our review on the “Arksey and O`Malley framework” for scoping reviews. The review considered all study designs, including qualitative and quantitative methodologies. We extracted data of service model descriptions and presented the results in a narrative summary.

Results

A total of 3975 studies were reviewed, and 73 were included. Five categories were identified: (1) multidisciplinary home-based teams, (2) key coordinators, (3) trained family caregivers or lay health workers, (4) predischarge planning, and (5) self-management programs. In general, the studies lack in-depth professional and contextual descriptions.

Conclusions

There is a wide variety of rehabilitation models that support the transition phase from hospital to home for people with ABI. The variety may indicate a lack of consensus of best practices. However, it may also reflect contextual adaptations. This study indicates that health care service research lacks robust and thorough descriptions of contextual features, which may limit the feasibility and transferability to diverse contexts.
Supervised smoking facility access, harm reduction practices, and substance use changes during the COVID-19 pandemic: a community-engaged cross-sectional study
Authors: van Draanen Jenna , Hamilton Jonah , Morgan Jeffrey , Maxwell Scott , Taylor Tara , Richardson Lindsey , Nolan Seonaid
Published: July 2023

Background

The potential public health benefits of supervised smoking facilities (SSFs) are considerable, and yet implementation of SSFs in North America has been slow. We conducted this study to respond to significant knowledge gaps surrounding SSF utilization and to characterize substance use, harm reduction practices, and service utilization following the onset of the COVID-19 pandemic.

Methods

A questionnaire was self-administered at a single site by 175 clients using an outdoor SSF in Vancouver, Canada, between October–December 2020. Questionnaire responses were summarized using descriptive statistics. Multinomial logistic regression techniques were used to examine factors associated with increased SSF utilization.

Results

Almost all respondents reported daily substance use (93% daily use of opioids; 74% stimulants). Most used opioids (85%) and/or methamphetamine (66%) on the day of their visit to the SSF. Respondents reported drug use practice changes at the onset of COVID-19 to reduce harm, including using supervised consumption sites, not sharing equipment, accessing medically prescribed alternatives, cleaning supplies and surfaces, and stocking up on harm reduction supplies. Importantly, 45% of SSF clients reported using the SSF more often since the start of COVID-19 with 65.2% reporting daily use of the site. Increased substance use was associated with increased use of the SSF, after controlling for covariates.

Conclusions

Clients of the SSF reported increasing not only their substance use, but also their SSF utilization and harm reduction practices following the onset of COVID-19. Increased scope and scale of SSF services to meet these needs are necessary.
A topology-marginal composite likelihood via a generalized phylogenetic pruning algorithm
Authors: Jun Seong-Hwan , Nasif Hassan , Jennings-Shaffer Chris , Rich David H , Kooperberg Anna , Fourment Mathieu , Zhang Cheng , Suchard Marc A , Matsen Frederick A
Published: July 2023

Bayesian phylogenetics is a computationally challenging inferential problem. Classical methods are based on random-walk Markov chain Monte Carlo (MCMC), where random proposals are made on the tree parameter and the continuous parameters simultaneously. Variational phylogenetics is a promising alternative to MCMC, in which one fits an approximating distribution to the unnormalized phylogenetic posterior. Previous work fit this variational approximation using stochastic gradient descent, which is the canonical way of fitting general variational approximations. However, phylogenetic trees are special structures, giving opportunities for efficient computation. In this paper we describe a new algorithm that directly generalizes the Felsenstein pruning algorithm (a.k.a. sum-product algorithm) to compute a composite-like likelihood by marginalizing out ancestral states and subtrees simultaneously. We show the utility of this algorithm by rapidly making point estimates for branch lengths of a multi-tree phylogenetic model. These estimates accord with a long MCMC run and with estimates obtained using a variational method, but are much faster to obtain. Thus, although generalized pruning does not lead to a variational algorithm as such, we believe that it will form a useful starting point for variational inference.
Changes in proprioception at different time points following anterior cruciate ligament injury or reconstruction
Authors: Zhao Yixuan , Chen Ze , Li Longfei , Wu Xipeng , Li Wei
Published: July 2023

Purpose

To investigate the changes in 30° and 60° position sense in patients with anterior cruciate ligament (ACL) injury at different time points after injury and reconstruction.

Methods

Patients were divided into six groups according to time after ACL injury and reconstruction: group A (ACL injury 1.5–6 months), group B (ACL injury 6–12 months), group C (ACL injury > 12 months), group D (postoperative ACL reconstruction 1–6 months), group E (postoperative ACL reconstruction > 6 months), and group F consisting of 14 healthy adults (control group). The ability of the affected leg to reproduce the same joint position during knee flexion was tested using active joint position sense assays to assess proprioception in both the lower extremities of the patient or between groups.

Results

Proprioception decreased rapidly during the early stages of ACL injury. Significant difference in the affected side at 30° compared to the healthy side (Group A: 4.70 (4.78, 9.00) vs 4.15 (3.35, 6.13), P = 0.03; Group B: 2.90 (0.48, 4.56) vs 8.30 (4.18, 10.43), P = 0.001; Group E: 6.25 (2.55, 11.60) vs 9.60 (3.90, 12.73), P = 0.009). However, no significant differences were detected for a double lower limb contrast of 60° (Group A: 5.1 (1.00, 8.00) vs 3.00 (0.75, 3.55), P = 0.044). Finally, the affected side of patients in groups C, D and E had significant differences in position perception at 30° compared with healthy subjects (P < 0.01), and the affected side of patients in groups C and E had significant differences in position sense at 60° compared with healthy subjects (P < 0.01).

Conclusion

ACL injury had a greater impact on the patient's 30° position sense, with only a small impact for 60°. Further, the early and middle proprioception recovery stages after ACL injury were the best before surgery. Finally, proprioception recovery training should be performed soon after injury.
MicroRNA-185-5p targets tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta to regulate non-small cell lung cancer progression
Authors: Ma Jiangang , Bai Yan , Chen Fangyuan , Zhou Feng , Zhang Liyuan , Xue Peini , Wang Dong
Published: July 2023

Background

Lung cancer (LC) is one of the most frequent cancers worldwide, as well as the leading cause of cancer-related death. Non-small cell lung cancer (NSCLC, which accounts for 85% of occurrences) is the main type of LC. MiRNAs appear to play a role in the occurrence and progression of many malignancies, according to mounting data. The underlying mechanism of miRNAs in regulating NSCLC cell biological activity and progression, on the other hand, is still being investigated.

Methods

QRT-PCR were used to detect miR-185-5p expression and YWHAZ mRNA in NSCLC. The CCK-8 assay was used to determine the tumor cells’ ability to proliferate. Transwall assay was used to test the migratory and invasive properties of cells. Cell apoptosis was detected using flow cytometry. Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ), E-Cadherin, N-Cadherin and cleaved-caspase3 protein expression were assessed using Western Blot. The bioinformatics analysis software StarBase2.0 predicted miR-185-5p downstream targets. To confirm the target association between miR-185-5p and YWHAZ, a luciferase experiment was used. In addition, an NCl-H1299 xenograft model was created to assess the anti-tumor impact of miR-185-5p in vivo. The expression level of YWHAZ in tumor tissues of small xenograft tumor model was detected by immunohistochemistry assay.

Results

Decreased miR-185-5p expression levels were observed in NSCLC. In vitro, over-expressed miR-185-5p decreased cell viability, proliferation, invasion/migration, and induced cell apoptosis, while inhibiting tumor growth in vivo. Dual-luciferase gene experiments confirmed that YWHAZ binds to miR-185-5p. Overexpression of YWHAZ partially restored the inhibitory effects of miR-185-5p on cell behaviors.

Conclusion

MiR-185-5p was down-regulated in NSCLC, and that overexpressed miR-185-5p inhibited malignant behaviors of cells and tumor growth by negatively regulating YWHAZ.
A multidisciplinary approach to inherited retinal dystrophies from diagnosis to initial care: a narrative review with inputs from clinical practice
Authors: Murro Vittoria , Banfi Sandro , Testa Francesco , Iarossi Giancarlo , Falsini Benedetto , Sodi Andrea , Signorini Sabrina , Iolascon Achille , Russo Roberta , Mucciolo Dario Pasquale , Caputo Roberto , Bacci Giacomo Maria , Bargiacchi Sara , Turco Simona , Fortini Stefania , Simonelli Francesca
Published: July 2023

Background

Non-syndromic inherited retinal dystrophies (IRDs) such as retinitis pigmentosa or Leber congenital amaurosis generally manifest between early childhood and late adolescence, imposing profound long-term impacts as a result of vision impairment or blindness. IRDs are highly heterogeneous, with often overlapping symptoms among different IRDs, and achieving a definite diagnosis is challenging. This narrative review provides a clinical overview of the non-syndromic generalized photoreceptor dystrophies, particularly retinitis pigmentosa and Leber congenital amaurosis. The clinical investigations and genetic testing needed to establish a diagnosis are outlined, and current management approaches are discussed, focusing on the importance of the involvement of an interdisciplinary team from diagnosis and initial care to long-term follow-up and support.

Results

The effective management of IRDs requires a multidisciplinary, and ideally interdisciplinary, team of experts knowledgeable about IRDs, with experienced professionals from fields as diverse as ophthalmology, neuropsychiatry, psychology, neurology, genetics, orthoptics, developmental therapy, typhlology, occupational therapy, otolaryngology, and orientation and mobility specialties. Accurate clinical diagnosis encompasses a range of objective and subjective assessments as a prerequisite for the genetic testing essential in establishing an accurate diagnosis necessary for the effective management of IRDs, particularly in the era of gene therapies. Improvements in genome sequencing techniques, such as next-generation sequencing, have greatly facilitated the complex process of determining IRD-causing gene variants and establishing a molecular diagnosis. Genetic counseling is essential to help the individual and their family understand the condition, the potential risk for offspring, and the implications of a diagnosis on visual prognosis and treatment options. Psychological support for patients and caregivers is important at all stages of diagnosis, care, and rehabilitation and is an essential part of the multidisciplinary approach to managing IRDs. Effective communication throughout is essential, and the patient and caregivers’ needs and expectations must be acknowledged and discussed.

Conclusion

As IRDs can present at an early age, clinicians need to be aware of the clinical signs suggesting visual impairment and follow up with multidisciplinary support for timely diagnoses to facilitate appropriate therapeutic or rehabilitation intervention to minimize vision loss.
Engineering Saccharomyces cerevisiae for improved biofilm formation and ethanol production in continuous fermentation
Authors: Wang Zhenyu , Xu Weikai , Gao Yixuan , Zha Mingwei , Zhang Di , Peng Xiwei , Zhang Huifang , Wang Cheng , Xu Chenchen , Zhou Tingqiu , Liu Dong , Niu Huanqing , Liu Qingguo , Chen Yong , Zhu Chenjie , Guo Ting , Ying Hanjie
Published: July 2023

Background

Biofilm-immobilized continuous fermentation has the potential to enhance cellular environmental tolerance, maintain cell activity and improve production efficiency.

Results

In this study, different biofilm-forming genes (FLO5, FLO8 and FLO10) were integrated into the genome of S. cerevisiae for overexpression, while FLO5 and FLO10 gave the best results. The biofilm formation of the engineered strains 1308-FLO5 and 1308-FLO10 was improved by 31.3% and 58.7% compared to that of the WT strain, respectively. The counts of cells adhering onto the biofilm carrier were increased. Compared to free-cell fermentation, the average ethanol production of 1308, 1308-FLO5 and 1308-FLO10 was increased by 17.4%, 20.8% and 19.1% in the biofilm-immobilized continuous fermentation, respectively. Due to good adhering ability, the fermentation broth turbidity of 1308-FLO5 and 1308-FLO10 was decreased by 22.3% and 59.1% in the biofilm-immobilized fermentation, respectively. Subsequently, for biofilm-immobilized fermentation coupled with membrane separation, the engineered strain significantly reduced the pollution of cells onto the membrane and the membrane separation flux was increased by 36.3%.

Conclusions

In conclusion, enhanced biofilm-forming capability of S. cerevisiae could offer multiple benefits in ethanol fermentation.

Graphical Abstract
Effects of the cascading translocations of larch (Larix decidua Mill.) on canker disease due to Lachnellula willkommii (R. Hartig) Dennis
Authors: Robin Cécile , Wagner Stefanie , Baubet Olivier , Ehrenmann François , Castagneyrol Bastien , Capdevielle Xavier , Fabreguettes Olivier , Petit Rémy J. , Piou Dominique
Published: July 2023

Key message

Appropriate silvicultural practices combined with the use of resistant Central European provenances can reduce the prevalence of larch canker caused by Lachnellula willkommii (R. Hartig) Dennis, a major disease affecting larch plantations in France. However, cascading translocations have resulted in frequent admixture in European larch (Larix decidua Mill.) and subsequent certification errors regarding the origin of plant material. Our study highlights the urgent need to improve the certification process of seed orchards.

Context

The recent history of European larch has been marked by translocations of plant stock within and beyond its native range. In order to increase stand resistance to larch canker disease, it is strongly recommended by French authorities to plant Central European provenances. However, a recent disease outbreak questioned the resistance of Central European provenances and the origin of the forest material used in these plantations.

Aims

Our goal was to assess the effects of cascading translocations and mixing between larch gene pools on genetic composition of plantations and on their vulnerability to the disease.

Methods

In the outbreak area, we checked the genetic origin of the trees and we estimated the percentage of Central European trees, disease prevalence and severity.

Results

Intra-site genetic diversity was high. Genetic composition did not match with geographic origin certificates. A high proportion of trees could not be assigned to either the Alpine or Central European gene pools. These admixed trees were as resistant as Central European trees. Geographic origin turned out to be one of the main drivers of canker prevalence, along with abiotic factors.

Conclusion

We need a precise knowledge of the origin of material used in seed orchards to mitigate canker disease and adapt forests through assisted migration.
Variation in herbivore space use: comparing two savanna ecosystems with different anthrax outbreak patterns in southern Africa
Authors: Huang Yen-Hua , Owen-Smith Norman , Henley Michelle D. , Kilian J. Werner , Kamath Pauline L. , Ochai Sunday O. , van Heerden Henriette , Mfune John K. E. , Getz Wayne M. , Turner Wendy C.
Published: July 2023

Background

The distribution of resources can affect animal range sizes, which in turn may alter infectious disease dynamics in heterogenous environments. The risk of pathogen exposure or the spatial extent of outbreaks may vary with host range size. This study examined the range sizes of herbivorous anthrax host species in two ecosystems and relationships between spatial movement behavior and patterns of disease outbreaks for a multi-host environmentally transmitted pathogen.

Methods

We examined range sizes for seven host species and the spatial extent of anthrax outbreaks in Etosha National Park, Namibia and Kruger National Park, South Africa, where the main host species and outbreak sizes differ. We evaluated host range sizes using the local convex hull method at different temporal scales, within-individual temporal range overlap, and relationships between ranging behavior and species contributions to anthrax cases in each park. We estimated the spatial extent of annual anthrax mortalities and evaluated whether the extent was correlated with case numbers of a given host species.

Results

Range size differences among species were not linearly related to anthrax case numbers. In Kruger the main host species had small range sizes and high range overlap, which may heighten exposure when outbreaks occur within their ranges. However, different patterns were observed in Etosha, where the main host species had large range sizes and relatively little overlap. The spatial extent of anthrax mortalities was similar between parks but less variable in Etosha than Kruger. In Kruger outbreaks varied from small local clusters to large areas and the spatial extent correlated with case numbers and species affected. Secondary host species contributed relatively few cases to outbreaks; however, for these species with large range sizes, case numbers positively correlated with outbreak extent.

Conclusions

Our results provide new information on the spatiotemporal structuring of ranging movements of anthrax host species in two ecosystems. The results linking anthrax dynamics to host space use are correlative, yet suggest that, though partial and proximate, host range size and overlap may be contributing factors in outbreak characteristics for environmentally transmitted pathogens.
Women Veterans’ experiences discussing household firearms with their intimate partners: collaborative, devalued, and deferential relational types
Authors: Polzer Evan R. , Rohs Carly M. , Thomas Suzanne M. , Holliday Ryan , Miller Christin N. , Simonetti Joseph A. , Iverson Katherine M. , Brenner Lisa A. , Monteith Lindsey L.
Published: July 2023

Background

Rates of firearm suicide have increased among women Veterans. Discussing firearm access and reducing access to lethal means of suicide when suicide risk is heightened are central tenets of suicide prevention, as is tailoring suicide prevention strategies to specific populations. While research has begun to explore how to optimize firearm lethal means safety counseling with women Veterans, there is limited knowledge of women Veterans' perspectives on including their intimate partners in such efforts. This gap is notable since many women Veterans have access to firearms owned by other household members. Understanding women Veterans’ experiences and perspectives regarding including their partners in firearm lethal means safety conversations can provide important information for tailoring firearm lethal means safety counseling for women Veterans.

Methods

Qualitative interviews were conducted with 40 women Veterans with current or prior household firearm access. Interview questions focused on the roles of women Veterans’ partners in household firearm access and storage, as well as women Veterans’ perspectives regarding including intimate partners in firearm lethal means safety counseling. Inductive thematic analysis was performed.

Results

Three relational types characterized how household firearms were discussed between women Veterans and their partners: collaborative, devalued, and deferential. These types were distinguished via women Veterans’ agency in decision-making related to household firearms, partners’ receptivity to women Veterans’ mental health or trauma histories, and willingness (or lack thereof) of partners to change household firearm access and storage considering such histories. Intimate partner violence was common in the devalued relational subtype.

Conclusions

Findings extend knowledge regarding the context of women Veterans’ household firearm access, including relational dynamics between women Veterans and their partners. The acceptability, feasibility, challenges, and facilitators of including women Veterans’ partners in firearm lethal means safety efforts likely vary for each relational type. For example, in dyads with a collaborative dynamic, incorporating partners may create opportunities for increased firearm safety, whereas including partners in devalued dynamics may present unique challenges. Research is warranted to determine optimal methods of navigating firearm lethal means safety counseling in the presence of each relational dynamic.
Weaning assessment of veno-arteriovenous (V-AV) extracorporeal membrane oxygenation (ECMO)
Authors: Heymer Johannes , Hein Anna , Ott Matthias , Schilling Tobias , Räpple Daniel
Published: July 2023

Currently, there is a lack of methods for simultaneous assessment of readiness for decannulation of the veno-venous (V-V) and veno-arterial (V-A) components during veno-arteriovenous (V-AV) extracorporal membrane oxygenation (ECMO) support. We describe a novel approach using a simultaneous off-sweep and controlled backflow test to assess readiness for decannulation from V-AV ECMO. This method needs testing in future clinical trials.
Bureaucratic configuration and discretion in asylum case processing: the case of the EUAA in Greece
Authors: Ekstedt Johan
Published: July 2023

This article takes an in-depth look at caseworkers at the European Union Asylum Agency in Greece. The agency’s increased role in asylum case processing and the emergence of the called “integrated European administration” is an unusual but nevertheless critical case to study for scholars of European asylum bureaucracies. Previous research into member state’s national migration authorities has shown that discretionary decision-making is widely deployed by asylum caseworkers. Generally, street-level bureaucrats tend to ‘reinterpret’ policy and creatively make use of the legal framework of the Common European Asylum System in order to make their day-to-day operations run more smoothly and resolve ethical dilemmas. However, this article finds that in the case of the European Union Asylum Agency, the compartmentalized institutional arrangement and short-term contracts removes both the incentive and ability for caseworkers to creatively reinterpret policy and deploy discretionary practices. It is therefore argued that scholars of asylum bureaucracy in Europe must pay increased attention to how the bureaucratic configuration of migration authorities.
An integrated approach for knowledge extraction and analysis in collaborative knowledge construction
Authors: Zhang Ning , Ouyang Fan
Published: July 2023

Collaborative knowledge construction (CKC) involved students’ sharing of information, improvement of ideas, and construction of collective knowledge. In this process, knowledge extraction and analysis can provide valuable insights into students’ knowledge capacities, depths, and levels in order to improve the CKC quality. However, existing studies tended to extract and analyze knowledge from a single perspective (e.g., the number of certain knowledge types and knowledge structures), which failed to demonstrate the complexity and dynamics of knowledge construction and advancement. To fill this gap, this research designed a series of computer-supported collaborative concept mapping (CSCCM) activities to facilitate students’ CKC process and then used an integrated approach (i.e., semantic knowledge analysis combined with learning analytics) to extract, analyze, and understand students’ knowledge characteristics and evolutionary trends. Results demonstrated that compared to the low-performing pairs, the high-performing pairs mainly discussed knowledge related to the course content, and their knowledge evolution trend was relatively stable. Based on the results, this research provided analytical implications to extract, analyze, and understand students’ knowledge and pedagogical implications to promote students’ knowledge construction and advancement.
Mesenchymal stem cells modulate IL-17 and IL-9 production induced by Th17-inducing cytokine conditions in autoimmune arthritis: an explorative analysis
Authors: Riekert Maximilian , Almanzar Giovanni , Schmalzing Marc , Schütze Norbert , Jakob Franz , Prelog Martina
Published: July 2023

Background

The importance of proinflammatory T-cells and their cytokine production in patients with autoimmune arthritis has been widely described. Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have come into focus as a potential therapeutic concept. The aim of this study was to investigate the influence of MSCs on the phenotype, cytokine profile, and functionality of naive and non-naive CD4+ T-cells from healthy donors (HD) and patients with autoimmune arthritis under Th17-cytokine polarizing conditions in an explorative way using a transwell system prohibiting any cell–cell-contact.

Methods

Magnetically isolated naive and non-naive CD4+ T-cells were stimulated under Th17-polarizing proinflammatory cytokine conditions in presence and absence of bone marrow derived mesenchymal stromal cells (MSCs). After an incubation period of 6 days, the proportions of the T-cell subpopulations TEMRA (CD45RA+CD27−), memory (CD45RA−CD27+), effector (CD45RA−CD27−) and naive cells (CD45RA+CD27+) were determined. Quantitative immunofluorescence intensity was used as a measure for IL-9, IL-17 and IFN-γ production in each subpopulation.

Results

In isolated naive CD4+ T-cells from HD and patients, MSCs suppressed the differentiation of naive towards an effector phenotype while memory and naive cells showed higher percentages in culture with MSCs. In patients, MSCs significantly decreased the proportion of IL-9 and IL-17 producing effector T-cells. MSCs also reduced IFN-γ production in the naive and memory phenotype from HD.

Conclusion

The results of the study indicate significant immunomodulatory properties of MSCs, as under Th17-polarizing conditions MSCs are still able to control T-cell differentiation and proinflammatory cytokine production in both HD and patients with autoimmune arthritis.
Analysis of clinical risk factors of failed electrical cardioversion in patients with persistent atrial fibrillation or atrial flutter
Authors: Kim Ki-Hun , Choi Ha-Young , Park Jino , Song Yeo-Jeong , Kim Seunghwan , Kim Dong-Kie , Seol Sang-Hoon , Kim Doo-Il , Yang Pil-Sung , Lim Hong Euy , Park Junbeum , Shim Jae-Min , Ahn Jinhee , Lee Sung Ho , Im Sung Il , Kim Ju Youn
Published: July 2023

Background

Although rhythm control could be the best for symptomatic atrial fibrillation (AF), some patients fail to achieve sinus rhythm (SR). This study aimed to identify clinical risk factors of failed electrical cardioversion (ECV).

Methods

A total of 248 patients who received ECV for persistent AF or atrial flutter (AFL) were retrospectively reviewed. Patients were divided into three groups: Group 1 maintained SR for > 1 year, group 2 maintained SR ≤ 1 year after ECV, and group 3 failed ECV. SR maintenance was assessed using regular electrocardiography or Holter monitoring.

Results

Patients were divided into group 1 (73, 29%), group 2 (146, 59%), and group 3 (29, 12%). The mean age of patients was 60 ± 10 years, and 197 (79%) were male. Age, sex, and baseline characteristics were similar among groups. However, increased cardiac size, digoxin use, heart failure (HF), and decreased left ventricular ejection fraction (LVEF) were more common in group 3. Univariate analysis of clinical risk factors for failed ECV was increased cardiac size [hazard ratio (HR) 2.14 (95% confidence interval [CI], 1.06–4.34, p = 0.030)], digoxin use [HR 2.66 (95% CI, 1.15–6.14), p = 0.027], HF [HR 2.60 (95% CI, 1.32–5.09), p = 0.005], LVEF < 40% [HR 3.45 (95% CI, 1.00–11.85), p = 0.038], and decreased LVEF [HR 2.49 (95% CI, 1.18–5.25), p = 0.012]. Among them, HF showed clinical significance only by multivariate analysis [HR 3.01 (95% CI, 1.13–7.99), p = 0.027].

Conclusions

Increased cardiac size, digoxin use, HF, LVEF < 40%, and decreased LVEF were related to failed ECV for persistent AF or AFL. Among these, HF was the most important risk factor. Further multi-center studies including greater number of participants are planned.
Duo-decapolar catheter entrapment in the Chiari network: successful extraction with the snare catheter
Authors: Lee Kyung-Yeon , Rhee Tae-Min , Lee So-Ryoung , Choi Eue-Keun , Oh Seil
Published: July 2023

Background

The Chiari network (CN) is the net-like embryonic remnants of the right valve of the sinus venosus. Catheter entrapment by CN is a not uncommon complication during catheter manipulation inside the right atrium (RA).

Case presentation

A 49-year-old man with atrial fibrillation was admitted for cryoablation. Transesophageal echocardiography revealed a prominent CN in the RA. Through the sheath placed in the right femoral vein, a diagnostic electrophysiologic duo-decapolar (DD) catheter (Livewire, St Jude Medical, St Paul, MN) was advanced. The catheter tip was knotted after multiple rotations in the RA to properly locate the DD catheter at the RA wall and coronary sinus (CS). Initial attempts to disentangle the folded catheter tip by traction and rotation maneuvers were unsuccessful. We inserted the large-bore sheath (Sentrant; Medtronic, 20 Fr) into the patient’s left femoral vein and then, captured the folded catheter tip with the 20-mm circular snare catheter (Snare Kit, Medtronic, Minneapolis, MN). Then, we cut the proximal portion of the DD catheter externally and removed it retrogradely through the Flexcath sheath. We found that the catheter tip was entrapped by the fibrous tissue of the CN. After a successful retrieval, cryoablation was conducted as planned. Follow-up echocardiography did not reveal any peri-procedural complications.

Conclusions

The electrophysiological procedure that exists at the RA entails a potential risk of catheter entrapment manipulating the catheter at the RA. If catheter entrapment occurs during the procedure, the entrapped catheter may be removed via a large-bore sheath using a snare catheter.
Modeling roadway temperatures for wildfire evacuation and assessment of pavement damage
Authors: Barzegar Mohammadreza , Wen Haifang
Published: July 2023

Wildfires can cause enormous loss of assets and human lives, and thus, timely evacuation from the wildfire zone is critical to saving lives. Understanding evacuation route conditions, including traffic and temperature data, is imperative for safe evacuation. This study modeled the temperature conditions of an evacuation roadway within a wildfire zone, using the 2018 Camp Fire in Butte County, California as an experiment. The numerical modeling program, FlamMap, was used in this study to analyze the temperature conditions of an evacuation route. The results show that the temperature of the evacuation roadway increased quickly in a matter of a few hours. The change of roadways temperatures ranged from 3°C to 297°C within five hours after ignition, depending on the specific location along the roadway and other conditions. The results from this study can be used to understand temperature conditions for effective evacuation and to estimate roadway damage as well.
Outcomes After Preoperative Chemoradiation With or Without Pazopanib in Non-Rhabdomyosarcoma Soft Tissue Sarcoma: A Report From Children's Oncology Group and NRG Oncology
Authors: Weiss Aaron R. , Chen Yen-Lin , Scharschmidt Thomas J. , Xue Wei , Gao Zhengya , Black Jennifer O. , Choy Edwin , Davis Jessica L. , Fanburg-Smith Julie C. , Kao Simon C. , Kayton Mark L. , Kessel Sandy , Lim Ruth , Million Lynn , Okuno Scott H. , Ostrenga Andrew , Parisi Marguerite T. , Pryma Daniel A. , Randall R. Lor , Rosen Mark A. , Shulkin Barry L. , Terezakis Stephanie , Venkatramani Rajkumar , Zambrano Eduardo , Wang Dian , Hawkins Douglas S. , Spunt Sheri L.
Published: July 2023

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

ARST1321 was a phase II study designed to compare the near complete pathologic response rate after preoperative chemoradiation with/without pazopanib in children and adults with intermediate-/high-risk chemotherapy-sensitive body wall/extremity non-Rhabdomyosarcoma Soft Tissue Sarcoma (ClinicalTrials.gov identifier: NCT02180867 ). Enrollment was stopped early following a predetermined interim analysis that found the rate of near complete pathologic response to be significantly greater with the addition of pazopanib. As a planned secondary aim of the study, the outcome data for this cohort were analyzed. Eight-five eligible patients were randomly assigned to receive (regimen A) or not receive (regimen B) pazopanib in combination with ifosfamide and doxorubicin + preoperative radiotherapy followed by primary resection at week 13 and then further chemotherapy at week 25. As of December 31, 2021, at a median survivor follow-up of 3.3 years (range, 0.1-5.8 years), the 3-year event-free survival for all patients in the intent-to-treat analysis was 52.5% (95% CI, 34.8 to 70.2) for regimen A and 50.6% (95% CI, 32 to 69.2) for regimen B ( P = .8677, log-rank test); the 3-year overall survival was 75.7% (95% CI, 59.7 to 91.7) for regimen A and 65.4% (95% CI, 48.1 to 82.7) for regimen B ( P = .1919, log-rank test). Although the rate of near complete pathologic response was significantly greater with the addition of pazopanib, outcomes were not statistically significantly different between the two regimens.
Non-perturbative stabilization of two Kähler moduli in type-IIB/F theory and the inflaton potential
Authors: Let Abhijit , Sarkar Arunoday , Sarkar Chitrak , Ghosh Buddhadeb
Published: July 2023

We consider a combination of perturbative and non-perturbative corrections in Kähler moduli stabilizations in the configuration of three magnetised intersecting D7 branes in the type-IIB/F theory, compactified on the 6d

orbifold of Calabi-Yau three-fold (CY3). Two of the Kähler moduli are stabilized non-perturbatively, out of the three which get perturbative corrections up to one-loop–order multi-graviton scattering amplitudes in the large volume scenario. In this framework, the dS vacua are achieved through all Kähler moduli stabilizations by considering the D-term. We obtain inflaton potentials of slow-roll plateau type, which are expected by recent cosmological observations. Calculations of cosmological parameters with the potentials yield experimentally favoured values.
The October Revolt in Chile: From “Now That We Have Found Each Other We Won't Let Go” to “Not with My Money!,” or Generalized Fear of the Other
Authors: Espinosa Jaime Donoso
Published: July 2023

This article seeks to describe the process of a form of relationality of the images that, at least in their glimmer, are seen in the immanence of the October 2019 revolt in Chile, which is expressed as an affective response to the promise opened by the revolt, in contrast to separation and distrust, which interrupts friendship. This reverse is expressed as a threat that interrupts the time to come of the revolt; it is also an interruption in the temporality of the images, which are now expressed in a more urgent and oppressive way and which, in their absolute presence, flood any type of common destiny.
Preferential killing of melanoma cells by a p16-related peptide
Authors: Soo Julia K. , Castle Joanna T. , Bennett Dorothy C.
Published: July 2023

We report the identification of a synthetic, cell-penetrating peptide able to kill human melanoma cells efficiently and selectively, while being less toxic to normal human melanocytes and nontoxic to human fibroblasts. The peptide is based on the target-binding site of the melanoma suppressor and senescence effector p16 (also known as INK4A or CDKN2A), coupled to a cell-penetrating moiety. The killing is by apoptosis and appears to act by a route other than the canonical downstream target of p16 and CDK4, the retinoblastoma (RB) protein family, as it is also effective in HeLa cells and a melanocyte line expressing HPV E7 oncogenes, which both lack any active RB. There was varying toxicity to other types of cancer cell lines, such as glioblastoma. Melanoma cell killing by a p16-derived peptide was reported once before but only at a higher concentration, while selectivity and generality were not previously tested.
Induction of kidney-related gene programs through co-option of SALL1 in mole ovotestes
Authors: Schindler Magdalena , Osterwalder Marco , Harabula Izabela , Wittler Lars , Tzika Athanasia C. , Dechmann Dina K. N. , Vingron Martin , Visel Axel , Haas Stefan A. , Real Francisca M.
Published: July 2023

Changes in gene expression represent an important source of phenotypic innovation. Yet how such changes emerge and impact the evolution of traits remains elusive. Here, we explore the molecular mechanisms associated with the development of masculinizing ovotestes in female moles. By performing integrative analyses of epigenetic and transcriptional data in mole and mouse, we identified the co-option of SALL1 expression in mole ovotestes formation. Chromosome conformation capture analyses highlight a striking conservation of the 3D organization at the SALL1 locus, but an evolutionary divergence of enhancer activity. Interspecies reporter assays support the capability of mole-specific enhancers to activate transcription in urogenital tissues. Through overexpression experiments in transgenic mice, we further demonstrate the capability of SALL1 to induce kidney-related gene programs, which are a signature of mole ovotestes. Our results highlight the co-option of gene expression, through changes in enhancer activity, as a plausible mechanism for the evolution of traits.
Neurogenesis redirects β-catenin from adherens junctions to the nucleus to promote axonal growth
Authors: Herrera Antonio , Menendez Anghara , Ochoa Andrea , Bardia Lídia , Colombelli Julien , Pons Sebastian
Published: July 2023

Here, we show that, in the developing spinal cord, after the early Wnt-mediated Tcf transcription activation that confers dorsal identity to neural stem cells, neurogenesis redirects β-catenin from the adherens junctions to the nucleus to stimulate Tcf-dependent transcription in a Wnt-independent manner. This new β-catenin activity regulates genes implicated in several aspects of contralateral axon growth, including axon guidance and adhesion. Using live imaging of ex-vivo chick neural tube, we showed that the nuclear accumulation of β-catenin and the rise in Tcf-dependent transcription both initiate before the dismantling of the adherens junctions and remain during the axon elongation process. Notably, we demonstrated that β-catenin activity in post-mitotic cells depends on TCF7L2 and is central to spinal commissural axon growth. Together, our results reveal Wnt-independent Tcf/β-catenin regulation of genes that control the growth and guidance of commissural axons in chick spinal cord.