bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends and outcomes of heart transplantation in adults with congenital heart disease
Authors: Alsoufi Bahaaldin , Kozik Deborah , Perrotta Melissa , Wilkens Sarah , Lambert Andrea Nicole , Deshpande Shriprasad , Slaughter Mark , Trivedi Jaimin
Published: March 2024

OBJECTIVES

Heart transplantation for adult congenital heart disease is complicated and associated with challenging pretransplant support, long waiting and high early post-transplant mortality. We explored if surgical and medical advances and allocation system changes have affected outcomes.

METHODS

From United Network for Organ Sharing database, adults with congenital heart disease listed for heart transplantation were queried. To explore practice and outcome trends, patients were divided into 4 eras (eras 1–3: nearly 3 equal periods from 1992 to 2018, era 4: after 2018, corresponding with new allocation system). Univariate and multivariable analysis was performed to evaluate outcomes.

RESULTS

A total of 2737 patients were listed. There was gradual increase in listed and transplanted patients, along with significant increase in use of mechanical support, simultaneous kidney and liver transplantation. While proportion of transplanted remained constant, there was decrease in proportion delisted/died after listing (P = 0.01) and waiting list duration (P = 0.01), especially in era 4. Thirty-day post-transplant mortality remains high; however, it has significantly improved starting era 3 (P = 0.01). Current survival at 1-year and 5-years is 85% and 65%, with improvement mainly related to decreased early death. On multivariable analysis, factors associated with survival were lower glomerular filtration rate (hazard ratio = 0.99, P = 0.042), bilirubin (hazard ratio = 1.17, P<0.001) and mechanical ventilation (hazard ratio = 2.3, P=0.004)

CONCLUSIONS

Heart transplantation in adults with congenital heart disease is increasing, along with added complexity, higher usage of pretransplant mechanical support and simultaneous organ transplantation. Despite that, more complex patients do not experience worse outcomes. Early mortality improved but remains high. New donor allocation system allowed shorter waiting time and higher proportion transplanted without altering early mortality.
An insight into healthcare professionals’ perspectives on discussing implantable cardioverter defibrillator deactivation
Authors: Hill Loreena , Cassidy Lorna , Dixon Lana , Fitzsimons Donna , Thylen Ingela , Jaarsma Tiny
Published: March 2024

Aims

International studies have examined patients’ views concerning the discussion of deactivating an implantable cardioverter defibrillator (ICD). Findings reported that many patients were either not informed about the subject or were informed late in their illness trajectory. This study aimed to explore healthcare professionals’ perspectives on discussing ICD deactivation and identify priorities for clinical practice and future research.

Methods and results

Eleven interviews were conducted, involving heart failure nurses, physicians, and an allied professional. All were responsible for the care of patients with an ICD, from the UK or Sweden. A semi-structured guide was used. All interviews were audio-recorded, transcribed, translated (as applicable), and analysed independently by experienced researchers, using framework analysis. Findings were presented, along with published work at a stakeholder meeting, and a consensus agreement was reached on priorities for clinical practice and future research. Four themes emerged from the exploratory interviews. Healthcare professionals described the discussion about deactivation as challenging, requiring compassion and involvement of family members. They agreed that the topic should be initiated prior to, or shortly after, device implantation. This was reflected in the priorities to improve communication, through the increased availability and implementation of prompts and tools, as well as the provision of tailored information to patients and family members. Stakeholders recognized the future potential of digital technology in device education.

Conclusion

Discussing deactivation remains challenging. Healthcare professionals recognized the need to initiate the discussion early, with compassion and involvement of family members. Priorities were agreed by stakeholders, which require clinical implementation and further research.
Exceptions to the rule: When does resistance evolution not undermine antibiotic therapy in human bacterial infections?
Authors: Bhattacharya Amrita , Aluquin Anton , Kennedy David A
Published: March 2024

The use of antibiotics to treat bacterial infections often imposes strong selection for antibiotic resistance. However, the prevalence of antibiotic resistance varies greatly across different combinations of pathogens and drugs. What underlies this variation? Systematic reviews, meta-analyses, and literature surveys capable of integrating data across many studies have tried to answer this question, but the vast majority of these studies have focused only on cases where resistance is common or problematic. Yet much could presumably be learned from the cases where resistance is infrequent or absent. Here we conducted a literature survey and a systematic review to study the evolution of antibiotic resistance across a wide range of pathogen-by-drug combinations (57 pathogens and 53 antibiotics from 15 drug classes). Using Akaike information criterion-based model selection and model-averaged parameter estimation we explored 14 different factors posited to be associated with resistance evolution. We find that the most robust predictors of high resistance are nosocomial transmission (i.e., hospital-acquired pathogens) and indirect transmission (e.g., vector-, water-, air-, or vehicle-borne pathogens). While the former was to be expected based on prior studies, the positive correlation between high resistance frequencies and indirect transmission is, to our knowledge, a novel insight. The most robust predictor of low resistance is zoonosis from wild animal reservoirs. We also found partial support that resistance was associated with pathogen type, horizontal gene transfer, commensalism, and human-to-human transmission. We did not find support for correlations between resistance and environmental reservoirs, mechanisms of drug action, and global drug use. This work explores the relative explanatory power of various pathogen and drug factors on resistance evolution, which is necessary to identify priority targets of stewardship efforts to slow the spread of drug-resistant pathogens.
Mining the microbiome of Lake Afdera to gain insights into microbial diversity and biosynthetic potential
Authors: Balcha Ermias Sissay , Macey Michael C , Gemeda Mesfin Tafesse , Cavalazzi Barbara , Woldesemayat Adugna Abdi
Published: March 2024

Microorganisms inhabiting hypersaline environments have received significant attention due to their ability to thrive under poly-extreme conditions, including high salinity, elevated temperatures and heavy metal stress. They are believed to possess biosynthetic gene clusters (BGCs) that encode secondary metabolites as survival strategy and offer potential biotechnological applications. In this study, we mined BGCs in shotgun metagenomic sequences generated from Lake Afdera, a hypersaline lake in the Afar Depression, Ethiopia. The microbiome of Lake Afdera is predominantly bacterial, with Acinetobacter (18.6%) and Pseudomonas (11.8%) being ubiquitously detected. A total of 94 distinct BGCs were identified in the metagenomic data. These BGCs are found to encode secondary metabolites with two main categories of functions: (i) potential pharmaceutical applications (nonribosomal peptide synthase NRPs, polyketide synthase, others) and (ii) miscellaneous roles conferring adaptation to extreme environment (bacteriocins, ectoine, others). Notably, NRPs (20.6%) and bacteriocins (10.6%) were the most abundant. Furthermore, our metagenomic analysis predicted gene clusters that enable microbes to defend against a wide range of toxic metals, oxidative stress and osmotic stress. These findings suggest that Lake Afdera is a rich biological reservoir, with the predicted BGCs playing critical role in the survival and adaptation of extremophiles.
Informing Producers in a Nontraditional Maple Syrup Region: Red Maple and Sugar Maple Production Parameters in Kentucky
Authors: Hackworth Zachary J , Lhotka John M , Ochuodho Thomas O , Thomas William R
Published: March 2024

Maple syrup is an important nontimber forest product in the northern latitudes of North America but has regained popularity in more southerly regions, including Kentucky. We provide the first formal investigation of the relationships between tree attributes and sap production parameters for red maple (Acer rubrum) and sugar maple (Acer saccharum) in Kentucky. During the 2020 and 2021 maple syrup seasons, we monitored per-tap sap volume production and sugar content of seventy-five red maples and seventy-five sugar maples to understand regional trends in maple production. Positive interannual correlations (r = 0.69–0.71) for sap volume and sugar content indicated that individual-tree production was relatively consistent between years. Moderate to strong positive relationships between diameter at breast height (DBH) and both annual sap volume production and sugar content were identified for both species. Predictive equations for sap volume and sugar content based on dbh demonstrated satisfactory predictive power and probable generalizability to new data sets. Trends in sap volume production and sugar content during Kentucky’s maple syrup season indicated that maple syrup production is closely related to weather patterns and site and tree characteristics, and the tools developed in this study will aid regional practitioners with feasibility analyses, operational implementation, long-term planning, and sugarbush management.

Study Implications: Maple syrup production has become more popular in southern states in recent decades. Our study tracked yearly sap volume production and sugar content (the measures that control syrup yield) for red and sugar maples across two seasons in Kentucky. We found that both sap volume and sugar content increased with DBH and can be satisfactorily predicted by DBH. Trees in dominant and codominant crown classes yielded higher syrup volumes than intermediate and overtopped trees. The tools developed by this study will aid landowners and foresters in estimating the potential maple syrup yield of southern sugarbushes.
Ancient Loss of Catalytic Selenocysteine Spurred Convergent Adaptation in a Mammalian Oxidoreductase
Authors: Rees Jasmin , Sarangi Gaurab , Cheng Qing , Floor Martin , Andrés Aida M , Oliva Miguel Baldomero , Villà-Freixa Jordi , Arnér Elias S J , Castellano Sergi
Published: March 2024

Selenocysteine, the 21st amino acid specified by the genetic code, is a rare selenium-containing residue found in the catalytic site of selenoprotein oxidoreductases. Selenocysteine is analogous to the common cysteine amino acid, but its selenium atom offers physical–chemical properties not provided by the corresponding sulfur atom in cysteine. Catalytic sites with selenocysteine in selenoproteins of vertebrates are under strong purifying selection, but one enzyme, glutathione peroxidase 6 (GPX6), independently exchanged selenocysteine for cysteine <100 million years ago in several mammalian lineages. We reconstructed and assayed these ancient enzymes before and after selenocysteine was lost and up to today and found them to have lost their classic ability to reduce hydroperoxides using glutathione. This loss of function, however, was accompanied by additional amino acid changes in the catalytic domain, with protein sites concertedly changing under positive selection across distant lineages abandoning selenocysteine in glutathione peroxidase 6. This demonstrates a narrow evolutionary range in maintaining fitness when sulfur in cysteine impairs the catalytic activity of this protein, with pleiotropy and epistasis likely driving the observed convergent evolution. We propose that the mutations shared across distinct lineages may trigger enzymatic properties beyond those in classic glutathione peroxidases, rather than simply recovering catalytic rate. These findings are an unusual example of adaptive convergence across mammalian selenoproteins, with the evolutionary signatures possibly representing the evolution of novel oxidoreductase functions.
Age Differences in Experiences of Pandemic-Related Health and Economic Challenges Among Adults Aged 55 and Older
Authors: Wiemers Emily E , Lin I-Fen , Wiersma Strauss Anna , Chin Janecca , Hotz V Joseph , Seltzer Judith A
Published: March 2024

Background and Objectives

The oldest adults faced the highest risk of death and hospitalization from coronavirus disease 2019 (COVID-19), but less is known about whether they also were the most likely to experience pandemic-related economic, healthcare, and mental health challenges. Guided by prior research on vulnerability versus resilience among older adults, the current study investigated age differences in economic hardship, delays in medical care, and mental health outcomes among adults aged 55 and older.

Research Design and Methods

Data were from the COVID-19 module and Leave Behind Questionnaire in the 2020 Health and Retirement Study (HRS). We estimated linear probability models to examine differences in experiences of pandemic-related economic and health challenges by age group (55–64, 65–74, 75+) with and without controls for preexisting sociodemographic, social program, health, and economic characteristics from the 2018 HRS. Models accounting for differential mortality also were estimated.

Results

Adults aged 65–74 and 75+ experienced fewer economic and mental health challenges and those aged 75+ were less likely to delay medical care than adults aged 55–64. Age gradients were consistent across a broad range of measures and were robust to including controls. For all age groups, economic challenges were less common than delays in medical care or experiences of loneliness, stress, or being emotionally overwhelmed.

Discussion and Implications

Even though the oldest adults were at the greatest risk of death and hospitalization from COVID-19, they experienced fewer secondary pandemic-related challenges. Future research should continue to explore the sources of this resilience for older adults.
TolDC Restores the Balance of Th17/Treg via Aryl Hydrocarbon Receptor to Attenuate Colitis
Authors: Wang Shu , Xu Ying , Wang Lu , Lin Junjie , Xu Chenjing , Zhao Xiaojing , Zhang Hongjie
Published: March 2024

Background

Tolerogenic dendritic cells (TolDCs) have been evidenced to trigger regulatory T cell’s (Treg’s) differentiation and be involved in the pathogenesis of Crohn’s disease (CD). Aryl hydrocarbon receptor (AhR) plays a crucial role in the differentiation of TolDCs, although the mechanism remains vague. This study aimed to evaluate the role of AhR in TolDCs formation, which may affect Th17/Treg balance in CD.

Methods

Colon biopsy specimens were obtained from healthy controls and patients with CD. Wild type (WT) and AhR-/- mice were induced colitis by drinking dextran sulphate sodium (DSS) with or without 6-formylindolo 3,2-b carbazole (FICZ) treatment. Wild type and AhR-/- bone marrow-derived cells (BMDCs) were cultured under TolDCs polarization condition. Ratios of DCs surface markers were determined by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was performed to quantify the levels of interleukin (IL)-1β, transforming growth factor (TGF)-β and IL-10. Tolerogenic dendritic cells differentiated from BMDCs of WT or AhR-/- mice were adoptively transferred to DSS-induced WT colitis mice.

Results

Patients with CD showed less AhR expression and activation in their inflamed colon regions. Compared with WT mice, AhR-/- mice experienced more severe colitis. Tolerogenic dendritic cells and Tregs were both decreased in the colon of AhR-/- colitis mice, while Th17 cells were upregulated. In vitro, compared with WT DCs, AhR-deficient DCs led to less TolDC formation. Furthermore, intestinal inflammation in WT colitis mice, which transferred with AhR-/- TolDCs, showed no obvious improvement compared with those transferred with WT TolDCs, as evidenced by no rescues of Th17/Treg balance.

Conclusions

Activation of AhR attenuates experimental colitis by modulating the balance of TolDCs and Th17/Treg. The AhR modulation of TolDCs may be a viable therapeutic approach for CD.
Gender and the legal academy
Authors: de Búrca Gráinne , Dixon Rosalind , Prieto Rudolphy Marcela
Published: March 2024

This Foreword examines what we describe as a “gender gap” in the legal academy. The gap can be seen most clearly in the significantly lower proportion of tenured women faculty members than of men faculty members in most parts of the world, but it is evident in many other aspects too, including the fact that women in academia are often clustered in a “pink ghetto” with lower pay, status, and job security. We begin by outlining the nature of the academic gender gap and some of the obstacles to its removal or reduction, before considering the reasons this gap should be a matter for concern. Two kinds of reasons for such concern are offered: consequences-based and justice-based. The Foreword concludes by suggesting a number of ways in which the gender gap might be addressed, arguing for attention to be paid to the risk of pursuing apparent solutions which may have the effect of entrenching or exacerbating aspects of the problem. Ultimately, we argue that what is needed is not just a larger proportion of women in law schools, but a more just and feminist legal academy along multiple intersecting dimensions.
Long-term outcome and cardiac function after anatomic repair of congenitally corrected transposition
Authors: Yokohama Fumi , Toh Norihisa , Kotani Yasuhiro , Takaya Yoichi , Kuroko Yosuke , Baba Kenji , Akagi Teiji , Kasahara Shingo , Ito Hiroshi
Published: March 2024

OBJECTIVES

There is limited information on long-term outcomes and trajectories of ventricular and valvular functions in patients with congenitally corrected transposition of the great arteries after anatomic repair according to the operative strategy with a median follow-up period of more than 10 years.

METHODS

Twenty-nine patients who underwent anatomic repair in Okayama University Hospital between January 1994 and December 2020 were reviewed. Outcomes were compared between patients who underwent a double switch operation (DS group) and patients with an atrial switch with a Rastelli operation (Rastelli–Senning/Mustard group).

RESULTS

Fifteen (52%) were in the DS group and 14 (48%) were in the Rastelli–Senning/Mustard group. The median follow-up period after anatomic repair was 12.7 (interquartile range 4.2–18.8) years. There were 3 (10%) early deaths and 3 (10%) late deaths. Survival rates for the entire cohort at 10 and 20 years were 86% and 71%, respectively, and were not different between the 2 groups. Using competing risk analysis, risks of heart failure, cardiac rhythm device implantation and atrial arrhythmia showed no significant differences between the 2 groups, whereas risk of reoperation was higher in the Rastelli–Senning/Mustard group than that in the DS group. Four patients after a DS operation and 1 patient after a Rastelli technique developed more than moderate aortic regurgitation.

CONCLUSIONS

During a median follow-up period of more than 10 years, mortality rate and ventricular and valvular functions after anatomic repair were acceptable, though the incidences of late complications were relatively high, especially in the Rastelli–Senning/Mustard group.
Mitral valve replacement in children: balancing durability and risk with mechanical and bioprosthetic valves
Authors: Van Puyvelde Joeri , Meyns Bart , Rega Filip , Gewillig Marc , Eyskens Benedicte , Heying Ruth , Cools Bjorn , Salaets Thomas , Hellings Peter-William , Meuris Bart
Published: March 2024

OBJECTIVES

To investigate if there is still a place for bioprosthetic mitral valve replacement in children by comparing the prosthetic durability and transplant-free survival after bioprosthetic and mechanical mitral valve replacement.

METHODS

We reviewed all mitral valve replacements in children between 1981 and 2020. Bioprosthetic mitral valve replacement cases were individually matched to mechanical mitral valve replacement cases. The incidence rate of a 2nd replacement was calculated using the cumulative incidence function that considered death or transplantation as a competing risk.

RESULTS

The median age at implantation was 3.6 years (interquartile range 0.8–7.9) for the bioprosthetic valve cohort (n = 28) and 3 years (interquartile range 1.3–7.8) for the mechanical valve cohort (n = 28). Seven years after bioprosthetic mitral valve replacement, the cumulative incidence of death or transplantation was 17.9% [95% confidence interval (CI) 6.3–34.1] and the cumulative incidence of a 2nd replacement was 63.6% (95% CI 39.9–80.1). Seven years after mechanical mitral valve replacement, the cumulative incidence of death or transplantation was 28.6% (95% CI 13.3–46) and the cumulative incidence of a 2nd replacement was 10.7% (95% CI 2.6–25.5). Fifteen years after mechanical mitral valve replacement, the cumulative incidence of death or transplantation was 33.6% (95% CI 16.2–52.1) and the cumulative incidence of a 2nd replacement was 41.1% (95% CI 18.4–62.7). The cumulative incidence curves for bioprosthetic and mechanical mitral valve replacement were statistically different for a 2nd valve replacement (P < 0.001) but not for death or transplantation (P = 0.33).

CONCLUSIONS

There is no difference in transplant-free survival after bioprosthetic and mechanical mitral valve replacement in children. The lifespan of bioprosthetic mitral valves remains limited in children because of structural valve failure due to calcification. After 15 years, 40% of mechanical valves were replaced, primarily because of patient–prosthesis mismatch related to somatic growth.
Research and application of safety monitoring technology of distribution automation based on SOM neural network
Authors: Han Yinfeng , Li Peng , Xu Chongyou , Ye Xiaming , Xie Yuzhe
Published: March 2024

For automatic situation monitoring in power distribution safety monitoring, data features are mainly extracted by single hidden layer neural network, which makes the standard error of monitoring results larger. Therefore, the research and application of power distribution automation safety monitoring technology based on SOM neural network are proposed. Preprocess the power grid, collect distribution operation data, set multi-dimensional monitoring nodes according to the collected data, build a distribution operation status monitoring model and analyze the data fusion technology of distribution automation safety monitoring according to the model. On this basis, the distribution automation safety monitoring system is defined, the output node correction weight and the reverse output node correction weight are calculated, the SOM neural network identification model is constructed and the research and application of the distribution automation safety monitoring technology are completed under the action of the gravitational function between individuals within the target time. The experimental results show that the change curve of the number of vulnerabilities and the actual number of false positives is consistent, the number of vulnerabilities is small and the monitoring results are more accurate; The state of the safety monitoring equipment of distribution automation is normal. After applying the method in this paper, the change curve is consistent with the actual value, and the delay time is less than 15 ms.
Spreading potential and spatial layout of circulating fluidized bed in China under the background of low-carbon development
Authors: Chen Haidong , Qiao Ning , Zhang Chao , Li Qiang , Zhang Jisheng , Tian Hongjie , Jing Hua
Published: March 2024

Circulating fluidized bed (CFB) technology plays a pivotal role as a clean thermal power generation technology in China. This paper delves into the prospective development potential and strategic deployment of CFB technology within the country. Initially, an integrated intelligent algorithm is devised to forecast future coal consumption. Leveraging the projected scope of existing CFB installations and the estimated volume of waste products from coal production, the development capacity of China’s CFB sector is quantitatively assessed. Subsequently, the regional deployment of CFB technology is examined. The projections indicate that coal production will likely range from 0.79 to 1.44 billion tons by 2030 and 1.23 to 2.30 billion tons by 2040. Furthermore, the ‘waste’ output from coal is anticipated to reach 700 to 900 million tons in 2020, escalating to 900 million to 1.2 billion tons by 2030. CFB technology exhibits a robust capacity for waste consumption, currently accounting for approximately 20% to 25% of the actual coal production. Spatially, North China presents the greatest development potential, while Northeast China shows the least, and South China experiences a declining demand. In the future spatial distribution, both coal-producing regions and environmental conservation considerations must be given due attention.
Patient information leaflets and package inserts of ibuprofen provided in the UK and Thailand: a comparative assessment
Authors: Nualdaisri Pitchaya , Corlett Sarah A , Krska Janet
Published: March 2024

Objectives

Written medicine information (WMI) is important for ensuring patients understand and use their medicines optimally, but relatively little research has assessed the quality of available WMI. This study assessed the quality of WMI using a sample of leaflets for ibuprofen in the UK and Thailand.

Methods

Leaflets were obtained by purchasing a product from retail outlets or community pharmacies, 18 from each country. In the UK, these were patient information leaflets (PILs); in Thailand, they were package inserts PIs not specifically designed for patients. Leaflets were assessed for content, layout, and readability using standard methods and compared to relevant guidelines.

Key findings

The UK PILs were uniform and conformed to EU regulatory requirements for content, whereas Thai PIs varied considerably, many failing to include important information required by Thai regulations. Several forms of Thai PIs were found, including some very short leaflets, containing minimal information. The readability of both was rated as poor, all used small font size and had less than desirable white space. Fewer Thai PIs than UK PILs met the Keystone Criteria for ibuprofen.

Conclusions

The extent of variation in format and content of Thai WMI could potentially cause confusion and reduce willingness to read it. PILs, conforming to Thai regulatory guidelines, should be provided with medicines instead. Leaflets in both countries would benefit from improved readability and layout.
Global existence and boundedness in a two-species chemotaxis-fluid system with indirect pursuit–evasion interaction
Authors: Liu Chao , Liu Bin
Published: March 2024

This paper investigates a two-species chemotaxis-fluid system with indirect pursuit–evasion interaction in a bounded domain with smooth boundary. Under suitably regular initial data and no-flux/no-flux/no-flux/no-flux/Dirichlet boundary conditions, we prove that the system possesses a global bounded classical solution in the two-dimensional and three-dimensional cases. Our results extend the result obtained in previously known ones and partly result is new.
Coordinated transcriptional response to environmental stress by a Synechococcus virus
Authors: Rihtman Branko , Torcello-Requena Alberto , Mikhaylina Alevtina , Puxty Richard J , Clokie Martha R J , Millard Andrew D , Scanlan David J
Published: March 2024

Viruses are a major control on populations of microbes. Often, their virulence is examined in controlled laboratory conditions. Yet, in nature, environmental conditions lead to changes in host physiology and fitness that may impart both costs and benefits on viral success. Phosphorus (P) is a major abiotic control on the marine cyanobacterium Synechococcus. Some viruses infecting Synechococcus have acquired, from their host, a gene encoding a P substrate binding protein (PstS), thought to improve virus replication under phosphate starvation. Yet, pstS is uncommon among cyanobacterial viruses. Thus, we asked how infections with viruses lacking PstS are affected by P scarcity. We show that the production of infectious virus particles of such viruses is reduced in low P conditions. However, this reduction in progeny is not caused by impaired phage genome replication, thought to be a major sink for cellular phosphate. Instead, transcriptomic analysis showed that under low P conditions, a PstS-lacking cyanophage increased the expression of a specific gene set that included mazG, hli2, and gp43 encoding a pyrophosphatase, a high-light inducible protein and DNA polymerase, respectively. Moreover, several of the upregulated genes were controlled by the host’s phoBR two-component system. We hypothesize that recycling and polymerization of nucleotides liberates free phosphate and thus allows viral morphogenesis, albeit at lower rates than when phosphate is replete or when phages encode pstS. Altogether, our data show how phage genomes, lacking obvious P-stress–related genes, have evolved to exploit their host’s environmental sensing mechanisms to coordinate their own gene expression in response to resource limitation.
Carbapenem- and cefiderocol-resistant Enterobacterales in surface water in Kumasi, Ashanti Region, Ghana
Authors: Eger Elias , Homeier-Bachmann Timo , Adade Eugene , Dreyer Sylvia , Heiden Stefan E , Lübcke Phillip , Tawiah Patrick O , Sylverken Augustina A , Knauf Sascha , Schaufler Katharina
Published: March 2024

Background

MDR pathogens including ESBL- and/or carbapenemase-producing Enterobacterales (ESBL-PE and CPE) increasingly occur worldwide in the One Health context.

Objectives

This proof-of-principle study investigated the occurrence of ESBL-PE in surface water in the Ashanti Region in Ghana, sub-Saharan Africa (SSA), and investigated their additional genotypic and phenotypic antimicrobial resistance features as part of the Surveillance Outbreak Response Management and Analysis System (SORMAS).

Methods

From 75 water samples overall, from nine small to medium-sized river streams and one pond spatially connected to a channelled water stream in the greater area of Kumasi (capital of the Ashanti Region in Ghana) in 2021, we isolated 121 putative ESBL-PE that were subsequently subjected to in-depth genotypic and phenotypic analysis.

Results

Of all 121 isolates, Escherichia coli (70.25%) and Klebsiella pneumoniae (23.14%) were the most prevalent bacterial species. In addition to ESBL enzyme-production of mostly the CTX-M-15 type, one-fifth of the isolates carried carbapenemase genes including blaNDM-5. More importantly, susceptibility testing not only confirmed phenotypic carbapenem resistance, but also revealed two isolates resistant to the just recently approved last-resort antibiotic cefiderocol. In addition, we detected several genes associated with heavy metal resistance.

Conclusions

ESBL-PE and CPE occur in surface water sources in and around Kumasi in Ghana. Further surveillance and research are needed to not only improve our understanding of their exact prevalence and the reservoir function of water sources in SSA but should include the investigation of cefiderocol-resistant isolates.
Enterococcal endocarditis management and relapses
Authors: Garofoli Nina , Joly Véronique , Le Pluart Diane , Hobson Claire Amaris , Beaumont Anne-Lise , Lariven Sylvie , Grall Nathalie , Para Marylou , Yazdanpanah Yazdan , Lescure François-Xavier , Peiffer-Smadja Nathan , Deconinck Laurène , Thy Michael
Published: March 2024

Introduction

Enterococcus faecalis is the third micro-organism causing endocarditis and is associated with a significant relapse rate. The objective of this study was to describe the management of patients with Enterococcus faecalis endocarditis (EE) and its implication for relapses.

Methods

We conducted a monocentric, retrospective analysis of all patients hospitalized for EE including endocarditis or infection of cardiac implantable electronic device defined by the modified ESC 2015 Duke criteria in a referral centre in Paris, France.

Results

Between October 2016, and September 2022, 54 patients with EE were included, mostly men (n = 40, 74%) with a median age of 75 [68–80] years. A high risk for infective endocarditis (IE) was found in 42 patients (78%), including 14 (26%) previous histories of IE, and 32 (59%) histories of valvular cardiac surgery. The aortic valve was the most frequently affected (n = 36, 67%). Combination therapy was mainly amoxicillin-ceftriaxone during all the curative antibiotic therapy duration (n = 31, 57%). Surgery was indicated for 40 patients (74%), but only 27 (50%) were operated on, mainly due to their frailty. Among the 17 deaths (32%), six (11%) happened during the first hospitalization for EE. A suppressive antibiotic treatment was initiated in 15 (29%) patients, mostly because of not performing surgery. During the 6-year study period an EE relapse occurred in three (6%) patients.

Conclusions

EE is a worrying disease associated with a high risk of relapse and significant mortality. Suppressive antibiotic therapy could be a key treatment to limit the occurrence of relapses.
Sociotechnical feasibility of natural language processing-driven tools in clinical trial eligibility prescreening for Alzheimer’s disease and related dementias
Authors: Idnay Betina , Liu Jianfang , Fang Yilu , Hernandez Alex , Kaw Shivani , Etwaru Alicia , Juarez Padilla Janeth , Ramírez Sergio Ozoria , Marder Karen , Weng Chunhua , Schnall Rebecca
Published: March 2024

Background

Alzheimer’s disease and related dementias (ADRD) affect over 55 million globally. Current clinical trials suffer from low recruitment rates, a challenge potentially addressable via natural language processing (NLP) technologies for researchers to effectively identify eligible clinical trial participants.

Objective

This study investigates the sociotechnical feasibility of NLP-driven tools for ADRD research prescreening and analyzes the tools’ cognitive complexity's effect on usability to identify cognitive support strategies.

Methods

A randomized experiment was conducted with 60 clinical research staff using three prescreening tools (Criteria2Query, Informatics for Integrating Biology and the Bedside [i2b2], and Leaf). Cognitive task analysis was employed to analyze the usability of each tool using the Health Information Technology Usability Evaluation Scale. Data analysis involved calculating descriptive statistics, interrater agreement via intraclass correlation coefficient, cognitive complexity, and Generalized Estimating Equations models.

Results

Leaf scored highest for usability followed by Criteria2Query and i2b2. Cognitive complexity was found to be affected by age, computer literacy, and number of criteria, but was not significantly associated with usability.

Discussion

Adopting NLP for ADRD prescreening demands careful task delegation, comprehensive training, precise translation of eligibility criteria, and increased research accessibility. The study highlights the relevance of these factors in enhancing NLP-driven tools’ usability and efficacy in clinical research prescreening.

Conclusion

User-modifiable NLP-driven prescreening tools were favorably received, with system type, evaluation sequence, and user's computer literacy influencing usability more than cognitive complexity. The study emphasizes NLP's potential in improving recruitment for clinical trials, endorsing a mixed-methods approach for future system evaluation and enhancements.
Empowering personalized pharmacogenomics with generative AI solutions
Authors: Murugan Mullai , Yuan Bo , Venner Eric , Ballantyne Christie M , Robinson Katherine M , Coons James C , Wang Liwen , Empey Philip E , Gibbs Richard A
Published: March 2024

Objective

This study evaluates an AI assistant developed using OpenAI’s GPT-4 for interpreting pharmacogenomic (PGx) testing results, aiming to improve decision-making and knowledge sharing in clinical genetics and to enhance patient care with equitable access.

Materials and Methods

The AI assistant employs retrieval-augmented generation (RAG), which combines retrieval and generative techniques, by harnessing a knowledge base (KB) that comprises data from the Clinical Pharmacogenetics Implementation Consortium (CPIC). It uses context-aware GPT-4 to generate tailored responses to user queries from this KB, further refined through prompt engineering and guardrails.

Results

Evaluated against a specialized PGx question catalog, the AI assistant showed high efficacy in addressing user queries. Compared with OpenAI’s ChatGPT 3.5, it demonstrated better performance, especially in provider-specific queries requiring specialized data and citations. Key areas for improvement include enhancing accuracy, relevancy, and representative language in responses.

Discussion

The integration of context-aware GPT-4 with RAG significantly enhanced the AI assistant’s utility. RAG’s ability to incorporate domain-specific CPIC data, including recent literature, proved beneficial. Challenges persist, such as the need for specialized genetic/PGx models to improve accuracy and relevancy and addressing ethical, regulatory, and safety concerns.

Conclusion

This study underscores generative AI’s potential for transforming healthcare provider support and patient accessibility to complex pharmacogenomic information. While careful implementation of large language models like GPT-4 is necessary, it is clear that they can substantially improve understanding of pharmacogenomic data. With further development, these tools could augment healthcare expertise, provider productivity, and the delivery of equitable, patient-centered healthcare services.
A comparative analysis of gastrointestinal tract barrier function and immune markers in gilt vs. sow progeny at birth and weaning
Authors: Wijesiriwardana Udani A , Pluske John R , Craig Jessica R , Furness John B , Ringuet Mitchell , Fothergill Linda J , Dunshea Frank R , Cottrell Jeremy J
Published: March 2024

Progeny born to primiparous sows (gilt progeny; GP) have lower birth, weaning and slaughter weights than sow progeny (SP). GP also have reduced gastrointestinal tract (GIT) development, as evidenced by lower organ weights. Therefore, the aim of this experiment was to quantify changes in GIT barrier function that occur in birth and weaning, representing two major challenges to the young piglet. The effects of parity (GP vs. SP) in GIT barrier integrity function were quantified at four timepoints: birth (~0 h), 24 h after birth (24 h), 1-d preweaning (PrW), and 1-d postweaning (PoW) in commercially reared piglets. Due to inherent differences between newborn and weanling pigs, the results were analyzed in two cohorts, birth (0 vs. 24 h, n = 31) and weaning (PrW vs. PoW, n = 40). Samples of the stomach, jejunum, ileum, and colon were excised after euthanasia and barrier integrity was quantified by measuring transepithelial resistance (TER), macromolecular permeability, the abundance of inflammatory proteins (IL-8, IL-1β, and TNF-α) and tight junction proteins (claudin-2 and -3). Papp was characterized using a dual tracer approach comprising 4 KDa fluorescein isothiocyanate (FD4) and 150 kDa tetramethyl rhodamine isothiocyanate (T150)-labeled dextrans. Characteristic effects of the initiation of feeding and weaning were observed on the GIT with the initiation of feeding, such as increasing TER and reducing Papp at 24 h, consistent with mucosal growth (P = 0.058) This was accompanied by increased cytokine abundance as evidenced by elevations in TNF-α and IL-1β. However, GP had increased IL-8 abundance (P = 0.011 and 0.063 for jejunum and ileum respectively) at birth than 24 h overall. In the weaning cohort, jejunal and ileal permeability to FD4 was higher in GP (P = 0.05 and 0.022, respectively) while only higher ileal T150 was observed in GP (P = 0.032). Ileal claudin-2 abundance tended to be higher in SP overall (P = 0.063), but GP ileal claudin-2 expression was upregulated weaning while no change was observed in SP (P = 0.043). Finally, other than a higher jejunal TNF-α abundance observed in SP (P = 0.016), no other effect of parity was observed on inflammatory markers in the weaning cohort. The results from this study indicate that the GIT of GP have poorer adaptation to early life events, with the response to weaning, being more challenging which is likely to contribute to poorer postweaning growth.
Freedom to Operate analysis as competitive necessity—the Selden automobile patent case revisited
Authors: Howells John , Katznelson Ron D
Published: March 2024

We contribute a unique empirical account of Freedom to Operate (FTO) analysis in respect to patent claims of others to avoid infringement liability. Over a century ago, the Selden automobile patent owners asserted that its scope encompassed early US automobiles. FTO analyses of the Selden patent claims demonstrated their narrow scope and hence their non-infringement. The legal opinion by patent attorney Parker on the Selden patent gave Ford Motor Company the confidence to publicly indemnify its customers from infringement liability and to publicly challenge the broad claim interpretation of the Selden patent. The asserted broad interpretation of Selden’s patent claims is sometimes alleged today to have retarded US automobile industry development but a review of commercial evidence of the development does not support this conjecture. That developers were undeterred is consistent with the FTO analyses conducted by Ford and others, and the patentee’s avoidance of a court challenge to the validity of the Selden patent on the merits. The Selden case should be known as the classic empirical example of how firms conduct FTO analysis to assess patent scope and validity to enable continued development. The prevalence of FTO practice today should be considered as a reason why such conjectured economic harms from ‘over-broad’ patents may not be realized today. Yet, we found a dearth of publicly available FTO analyses and lack of rigorous empirical studies demonstrating the actual extent of FTO analyses. Given continuing concerns over the harms from ‘over-broad’ patents, there is a need for research into the economics and behavioural influence of FTO analysis.
The post-emergence period for denning Polar Bears: phenology and influence on cub survival
Authors: Andersen Erik M , Wilson Ryan R , Rode Karyn D , Durner George M , Atwood Todd C , Gustine David D
Published: March 2024

Among polar bears (Ursus maritimus), only parturient females den for extended periods, emerging from maternal dens in spring after having substantially depleted their energy reserves during a fast that can exceed 8 months. Although den emergence coincides with a period of increasing prey availability, polar bears typically do not depart immediately to hunt, but instead remain at the den for up to a month. This delay suggests that there are likely adaptive advantages to remaining at the den between emergence and departure, but the influence of the timing and duration of this post-emergence period on cub survival has not been evaluated previously. We used temperature and location data from 70 denning bears collared within the Southern Beaufort Sea and Chukchi Sea subpopulations to estimate the phenology of the post-emergence period. We evaluated the influence of various spatial and temporal features on duration of the post-emergence period and evaluated the potential influence of post-emergence duration on litter survival early in the spring following denning. For dens that likely contained viable cubs at emergence (n = 56), mean den emergence occurred on 16 March (SE = 1.4 days) and mean departure on 24 March (SE = 1.6 days), with dates typically occurring later in the Chukchi Sea relative to Southern Beaufort Sea and on land relative to sea ice. Mean duration of the post-emergence period was 7.9 days (SE = 1.4) for bears that were observed with cubs later in the spring, which was over 4 times longer than duration of those observed without cubs (1.9 days). Litter survival in the spring following denning (n = 31 dens) increased from 0.5 to 0.9 when duration of the post-emergence period increased by ~4 days and other variables were held at mean values. Our limited sample size and inability to verify cub presence at emergence suggests that future research is merited to improve our understanding of this relationship. Nonetheless, our results highlight the importance of the post-emergence period in contributing to reproductive success and can assist managers in developing conservation and mitigation strategies in denning areas, which will be increasingly important as human activities expand in the Arctic.
Intra-professional collaboration and organization of work among teachers: How entangled institutional logics shape connectivity
Authors: Parding Karolina , Gavin Mihajla , Wilson Rachel , Fitzgerald Scott , Jakobsson Mats , McGrath-Champ Susan
Published: March 2024

Intra-professional collaboration is essential as it enables professionals to learn, develop, and define the terms of the profession in their own way. Yet conditions for collaboration are shaped by how work is organized and governed. This article examines how conditions for intra-professional collaboration, where work takes place with colleagues within the same profession in same or similar roles, are perceived by teachers, in relation to how work is organized, by drawing on empirical insights from a study on teachers working in education systems defined by market-driven reforms. Our findings nuance ideas of professional connectedness by showing how the organization of work, affected by ‘entangled institutional logics’ (Blomgren and Waks 2015; Alvehus and Andersson 2018) and market-based governance reforms, shapes intra-professional collaboration. Our contribution is thus to take departure from established understandings of connectivity, that is, ‘related to others and outsiders’ (Noordegraaf 2020) by examining connectivity within professions, showing how there continues to be a struggle between the profession, organization, and market which shapes conditions for intra-professional work within the teaching profession. Our analysis of intra-professional collaboration holds significance for emergent understandings of connectivity (see Adams et al. 2020a; Alvehus, Avoon and Oliver 2021: 201; Kanon and Andersson 2023) by underscoring how the contemporary organization and management of work shape the conditions that enable, or augment, inwards connectivity and the ability for professionals to collaborate in meaningful ways.