bluuebunny/crossref_metadata_2025 huggingface dataset:
Progress towards permanent respiratory support
Authors: Shin Suji , Nasim Umar , O’Connor Hassana , Hong Yeahwa
Published: July 2024

Purpose of review

Although lung transplantation stands as the gold standard curative therapy option for end-stage lung disease, the scarcity of available organs poses a significant challenge in meeting the escalating demand. This review provides an overview of recent advancements in ambulatory respiratory assist systems, selective anticoagulation therapies that target the intrinsic pathway, and innovative surface coatings to enable permanent respiratory support as a viable alternative to lung transplantation.

Recent findings

Several emerging ambulatory respiratory assist systems have shown promise in both preclinical and clinical trials. These systems aim to create more biocompatible, compact, and portable forms of extracorporeal membrane oxygenation that can provide long-term respiratory support. Additionally, innovative selective anticoagulation strategies, currently in various stages of preclinical or clinical development, present a promising alternative to currently utilized nonselective anticoagulants. Moreover, novel surface coatings hold the potential to locally prevent artificial surface-induced thrombosis and minimize bleeding risks.

This review of recent advancements toward permanent respiratory support summarizes the development of ambulatory respiratory assist systems, selective anticoagulation therapies, and novel surface coatings. The integration of these evolving device technologies with targeted anticoagulation strategies may allow a safe and effective mode of permanent respiratory support for patients with chronic lung disease.
Acute Care Use Among Patients with Multiple Chronic Conditions Receiving Care from Nurse Practitioner Practices in Health Professional Shortage Areas
Authors: McMenamin Amy , Turi Eleanor , Dixon Justinna , Liu Jianfang , Martsolf Grant , Poghosyan Lusine
Published: July 2024

Background

Patients with multiple chronic conditions often have many care plans, polypharmacy, and unrelieved symptoms that contribute to high emergency department and hospital use. High-quality primary care delivered in practices that employ nurse practitioners can help prevent the need for such acute care services. However, such practices located in primary care health professional shortage areas face challenges caring for these patients due to higher workloads and fewer resources.

Objective

We examined differences in hospitalization and emergency department use among patients with multiple chronic conditions who receive care from practices that employ nurse practitioners in health professional shortage areas compared to practices that employ nurse practitioners in non-health professional shortage areas.

Methods

We performed an analysis of Medicare claims, merged with Health Resources and Services Administration data on health professional shortage area status in five states. Our sample included 394,424 community-dwelling Medicare beneficiaries aged ≥65 with at least two of 15 common chronic conditions who received care in 779 practices that employ nurse practitioners. We used logistic regression to assess the relationship between health professional shortage area status and emergency department visits or hospitalizations.

Results

We found a higher likelihood of emergency department visits among patients in health professional shortage areas compared to those in non-health professional shortage areas, and no difference in the likelihood of hospitalization.

Discussion

Emergency department use differences exist among older adults with multiple chronic conditions receiving care in practices that employ nurse practitioners in health professional shortage areas, compared to those in non-health professional shortage areas. To address this disparity, the health professional shortage area program should invest in recruiting and retaining nurse practitioners to health professional shortage areas to ease workforce shortages.
Using Civic Service Design Methods to Redevelop a Data Communication Website With a Health Literacy Lens
Authors: Montesano Matthew , Porter Michael , Olson Carolyn , Gettings Chris , Torem Emily , Pezeshki Grant
Published: July 2024

Context:

Public health agencies routinely publish data in hopes that data influence public health policy and practice. However, data websites can often be difficult to use, posing barriers to people trying to access, understand, and use data. Working to make data websites easier to use can add value to public health data communication work.

Program:

The New York City Department of Health and Mental Hygiene (DOHMH) redesigned its Environment and Health Data Portal, a website used to communicate environmental health data, with the goal of making data more accessible and understandable to a broader audience. The DOHMH used Civic Service Design methods to establish priorities and strategies for the redesign work, to build a data communication website that emphasizes a high level of usability, and content that explains data.

Implementation:

By following a Civic Service Design process, the DOHMH synthesized findings from health communications, data visualization and communication, and web usability to create an easy-to-use website with explanations of data and findings alongside datasets. On the new site, automated dataset visualizations are supplemented with narrative content, explanatory content, and custom interactive applications designed to explain data and findings.

Evaluation:

Web analytics showed that, in its first year of operation, the site’s web traffic grew substantially, with the last 12 weeks recording weekly page views 150% higher than the first 12 weeks of operation (7185 average weekly page views compared with 2866 average weekly page views). Two-thirds (66.3%) of page views include recorded user engagement. Additional evaluations to measure specific aspects of usability compared with the previous version of the site are planned.

Discussion:

By following a Civic Service Design process, the DOHMH redesigned a vital data communication platform to increase its usability and saw significant increase in engagement in its first year of operations. By designing data material with usability in mind, public health departments have the potential to improve public health data communication work.
The impact of Mpox virus incidence and Mpox virus first-dose vaccination on recent HIV testing
Authors: Linfield Rebecca Y. , Slusky David J.G. , Moskatel Leon S.
Published: July 2024

Understanding the impact of Mpox incidence and Mpox first dose vaccination on recent HIV testing is critical to better address both epidemics. We conducted a regression analysis of Mpox incidence and Mpox first dose vaccinations with recent HIV testing during the 2022 Mpox epidemic. We found that increased Mpox first dose vaccination was associated with a decrease in recent HIV testing in men but not women. Mpox incidence was not associated with changes in HIV testing.
The bidirectional interaction between antidepressants and the gut microbiota: are there implications for treatment response?
Authors: Borgiani Gianluca , Possidente Chiara , Fabbri Chiara , Oliva Vincenzo , Bloemendaal Mirjam , Arias Vasquez Alejandro , Dinan Ted G. , Vieta Eduard , Menchetti Marco , De Ronchi Diana , Serretti Alessandro , Fanelli Giuseppe
Published: July 2024

This review synthesizes the evidence on associations between antidepressant use and gut microbiota composition and function, exploring the microbiota’s possible role in modulating antidepressant treatment outcomes. Antidepressants exert an influence on measures of gut microbial diversity. The most consistently reported differences were in β-diversity between those exposed to antidepressants and those not exposed, with longitudinal studies supporting a potential causal association. Compositional alterations in antidepressant users include an increase in the Bacteroidetes phylum, Christensenellaceae family, and Bacteroides and Clostridium genera, while a decrease was found in the Firmicutes phylum, Ruminococcaceae family, and Ruminococcus genus. In addition, antidepressants attenuate gut microbial differences between depressed and healthy individuals, modulate microbial serotonin transport, and influence microbiota’s metabolic functions. These include lyxose degradation, peptidoglycan maturation, membrane transport, and methylerythritol phosphate pathways, alongside gamma-aminobutyric acid metabolism. Importantly, baseline increased α-diversity and abundance of the Roseburia and Faecalibacterium genera, in the Firmicutes phylum, are associated with antidepressant response, emerging as promising biomarkers. This review highlights the potential for gut microbiota as a predictor of treatment response and emphasizes the need for further research to elucidate the mechanisms underlying antidepressant-microbiota interactions. More homogeneous studies and standardized techniques are required to confirm these initial findings.
Ventricular lymphatic vessel density correlates with mild cardiac remodelling and preserved heart function in moderate murine aortic valve stenosis
Authors: Becker Katrin
Published: July 2024

Aortic valve stenosis (AS) is one of the most frequent heart valve diseases in the western world, but aortic valve replacement (AVR) remains the only therapeutic option. While one of the most common complications of AS is heart failure, the early disease phase is asymptomatic with preserved cardiac function. Increased ventricular lymphatic vessel density is part of myocardial remodelling upon cardiac pressure overload and an important adaptation mechanism to maintain heart function after myocardial infarction, while in heart failure patients, circulating lymphatic growth factor levels and ventricular lymphatic vessel numbers are altered. Lymphangiogenesis is enhanced in endocardium of human stenotic aortic valves, however, ventricular lymphatic vessels have not been investigated in AS, yet.

Therefore, aim of this study was to in a well-characterized mouse model of moderate AS analyse the link between density of ventricular lymphatic vessels, cardiac remodelling and function.
Objective Markers of Sustained Attention Fluctuate Independently of Mind-Wandering Reports
Authors: Chidharom Matthieu , Bonnefond Anne , Vogel Edward K. , Rosenberg Monica D.
Published: July 2024

Sustained attention fluctuates between periods of good and poor attentional performance. Two major methodologies exist to study these fluctuations: an objective approach that identifies "in-the-zone" states of consistent response times (RTs) and "out-of-the-zone" states of erratic RTs and a subjective approach that asks participants whether they are on-task or mind wandering. Although both approaches effectively predict attentional lapses, it remains unclear whether they capture the same or distinct attentional fluctuations. We combined both approaches within a single sustained attention task requiring frequent responses and response inhibition to rare targets to explore their consistency (N=40). Behaviorally, both objective out-of-the-zone and subjective mind-wandering states were associated with more attentional lapses. However, the percentage of time spent out-of-the-zone did not differ between on-task and mind-wandering periods and both objective and subjective states independently predicted error-proneness, suggesting that the two methods do not capture the same type of attention fluctuations. Whereas attentional preparation before correct inhibitions was greater during out-of-the-zone compared to in-the-zone periods, preparation did not differ by subjective state. In contrast, post-error slowing differed by both objective and subjective states, but in opposite directions: slowing was observed when participants were objectively out-of-the-zone or subjectively on-task. Overall, our results provide evidence that objective and subjective approaches capture distinct attention fluctuations during sustained attention tasks. Integrating both objective and subjective measures is crucial for fully understanding the mechanisms underlying our ability to remain focused.
GATA6 regulates WNT and BMP programs to pattern precardiac mesoderm during the earliest stages of human cardiogenesis
Authors: Bisson Joseph A. , Gordillo Miriam , Kumar Ritu , de Silva Neranjan , Yang Ellen , Banks Kelly M. , Shi Zhong-Dong , Lee Kihyun , Yang Dapeng , Chung Wendy K. , Huangfu Danwei , Evans Todd
Published: July 2024

Haploinsufficiency forGATA6is associated with congenital heart disease (CHD) with variable comorbidity of pancreatic or diaphragm defects, although the etiology of disease is not well understood. Here, we used cardiac directed differentiation from human embryonic stem cells (hESCs) as a platform to study GATA6 function during early cardiogenesis. GATA6 loss-of-function hESCs had a profound impairment in cardiac progenitor cell (CPC) specification and cardiomyocyte (CM) generation due to early defects during the mesendoderm and lateral mesoderm patterning stages. Profiling by RNA-seq and CUT&RUN identified genes of the WNT and BMP programs regulated by GATA6 during early mesoderm patterning. Furthermore, interactome analysis detected GATA6 binding with developmental transcription factors and chromatin remodelers suggesting cooperative regulation of cardiac lineage gene accessibility. We show that modulating WNT and BMP inputs during the first 48 hours of cardiac differentiation is sufficient to partially rescue CPC and CM defects inGATA6heterozygous and homozygous mutant hESCs. This study provides evidence of the regulatory functions for GATA6 directing human precardiac mesoderm patterning during the earliest stages of cardiogenesis to further our understanding of haploinsufficiency causing CHD and the co-occurrence of cardiac and other organ defects caused by humanGATA6mutations.
Genetics identifies obesity as a shared risk factor for co-occurring multiple long-term conditions
Authors: Mounier Ninon , Voller Bethany , Masoli Jane AH , Delgado João , Dudbridge Frank , Pilling Luke C , Frayling Timothy M , Bowden Jack
Published: July 2024

Background

Multimorbidity, the co-occurrence of multiple long-term conditions (LTCs), is an increasingly important clinical problem, but often little is known about the underlying causes. Observational studies are highly susceptible to confounding and bias, and patients with multiple LTCs are usually excluded from randomised controlled trials. We investigate the role of a potentially critical multimorbidity risk factor, obesity, as measured by body mass index (BMI), in explaining shared genetics amongst 71 common LTCs.

Methods and Findings

In a population of northern Europeans, we estimated unadjusted pairwisegenetic correlation,, between LTCs and partial genetic correlations after adjustment for the genetics of BMI,. We compared these correlations using a bespoke block-jackknife approach to assess whether differences between the estimates were statistically meaningful. We then used multiple causal inference methods to confirm that BMI causally affects not only individual LTCs, but also their co-occurrence. Finally, we attempted to quantify the population-level impact of intervening and lowering BMI on the prevalence of 15 key common multimorbid LTC pairs. Our results showed evidence that BMI partially explains some of the shared genetics for 740 LTC-pairs (30% of all pairs considered). For a further 161 LTC-pairs, the genetic similarity between the LTCs was entirely accounted for by BMI genetics. This list included diabetes and osteoarthritis:, as well as those involving LTCs from the same broad family, or ‘domain’, such as gout and osteoarthritis:. Causal inference methods confirmed that higher BMI acts as a common risk factor for a subset of these pairs, and therefore BMI-lowering interventions would reduce the prevalence of these pairs of LTCs. For example, we estimated that a 1 standard deviation or 4.5 unit decrease in BMI would result in 17 fewer people with both chronic kidney disease and osteoarthritis per 1000 who currently have both LTCs.

Conclusions

Our genetics-centred approach shows that obesity is an important mechanistic cause of many shared long-term conditions. We identify LTC pairs for which obesity is the predominating shared risk factor, and cases where it is one of the several shared risk factors involved. Our method for calculating full and partial genetic correlations is published as an R package{partialLDSC}for use by the research community.
Mapping brain lesions to conduction delays: the next step for personalized brain models in Multiple Sclerosis
Authors: Mazzara C. , Ziaeemehr A. , Troisi E. Lopez , Cipriano L. , Angiolelli M. , Sparaco M. , Quarantelli M. , Granata C. , Sorrentino G. , Hashemi M. , Jirsa V. , Sorrentino P.
Published: July 2024

Multiple sclerosis (MS) is a clinically heterogeneous, multifactorial autoimmune disorder affecting the central nervous system. Structural damage to the myelin sheath, resulting in the consequent slowing of the conduction velocities, is a key pathophysiological mechanism. In fact, the conduction velocities are closely related to the degree of myelination, with thicker myelin sheaths associated to higher conduction velocities. However, how the intensity of the structural lesions of the myelin translates to slowing of nerve conduction delays is not known. In this work, we use large-scale brain models and Bayesian model inversion to estimate how myelin lesions translate to longer conduction delays across the damaged tracts. A cohort of 38 subjects (20 healthy and 18 with MS) underwent MEG and MRI acquisitions, with detailed white matter tractography analysis. We observed that MS patients consistently showed decreased power within the alpha frequency band (8-13Hz) as compared to the healthy group. We also derived a lesion matrix indicating the percentage of lesions for each tract in every patient. Using large-scale brain modeling, the neural activity of each region was represented as a Stuart-Landau oscillator operating in a regime showing damped oscillations, and the regions were coupled according to subject-specific connectomes. We propose a linear formulation to the relationship between the conduction delays and the amount of structural damage in each white matter tract. Dependent upon the parameterγ, this function translates lesions into edge-specific conduction delays (leading to shifts in the power spectra). Using deep neural density estimators, we found that the estimation ofγshowed a strong correlation with the alpha peak in MEG recordings. The most probable inferredγfor each subject is inversely proportional to the observed peaks, while power peaks themselves do not correlate with total lesion volume. Furthermore, the estimated parameters were predictive (cross-sectionally) of individual clinical disability. This study represents the initial exploration showcasing the location-specific impact of myelin lesions on conduction delays, thereby enhancing the customization of models for individuals with multiple sclerosis.
Acceptability of a community health worker- led health literacy intervention on lifestyle modification among hypertensive and diabetes patients in the City of Harare, Zimbabwe
Authors: Katena Nyaradzai Arster , Shamu Shepherd , Fana Golden Tafadzwa , Dewa Evans , Dombojena Admire , Rusakaniko Simbarashe
Published: July 2024

Deploying community health workers (CHWs) is a vital strategy to improve health at a community level in low- and middle-income countries. Whilst there is substantial evidence on the effectiveness of CHWs interventions, there is a need for more research on the mechanisms through which these interventions work. Understanding the acceptability of these interventions is one way of assessing the mechanisms through which they work. This article examines the acceptability of a community health worker-led health literacy intervention on lifestyle modification among hypertensive and diabetes patients based on the perspectives of the CHWs, community nurses and diabetes and hypertensive patients. A qualitative study was imbedded within a cluster randomized trial to assess the effectiveness community health worker-led health literacy intervention on lifestyle modification among hypertensive and diabetes patients in the City of Harare, Zimbabwe. Data were gathered through semi-structured interviews with 3 community health nurses and 15 diabetes and hypertension patients as well as 2 focus group discussions with CHWs. Data were analyzed manually using the thematic analysis method. There was consensus that the intervention had many benefits amongst CHWs and community nurses. However, among patients, there were mixed perceptions regarding the benefits of the intervention. The main challenges that were mentioned by CHWs include resistance to advice by patients, insufficient resources, and lack of acceptance at some of the patient’s homes. All participants believed the intervention was acceptable. Our study provides vital information that should be considered in upscaling CHW led interventions.
New-onset chronic musculoskeletal pain following COVID-19 infection fulfil the Fibromyalgia clinical syndrome criteria
Authors: Khoja Omar , Mulvey Matthew , Astill Sarah , Tan Ai Lyn , Sivan Manoj
Published: July 2024

Background

New-onset chronic musculoskeletal (MSK) pain (> 3 months duration) is one of the commonest persistent symptoms of Post-COVID syndrome (PCS). There is emerging evidence that the chronic MSK pain and associated symptoms in PCS have similarities to Fibromyalgia Syndrome (FMS). This study aimed to characterise PCS related new-onset chronic MSK pain and its overlap with Fibromyalgia Syndrome (FMS).

Methods

Patients with new-onset chronic MSK pain following COVID-19 infection were enrolled and the nature of pain and associated symptoms captured using the C19-YRS (Yorkshire Rehabilitation Scale). FMS assessment was conducted as part of standard clinical examination using the American College of Rheumatology (ACR) 2010 criteria. Diagnosis of FMS was made when they meet the standard criteria of (1) Widespread Pain Index (WPI) ≥ 7 and Symptoms Severity (SS) score ≥ 5, or WPI is 3-6 and SS score ≥ 9, (2) symptoms have been present at a similar level for at least 3 months, and (3) the patient does not have a disorder that would otherwise explain the symptoms.

Results

Eighteen patients, twelve of whom were female, with an average age of 49.6 (SD 11.8) years and a Body Mass Index of 31.7 (SD 8.6) were enrolled. The average duration of symptoms from COVID-19 infection to assessment was 27.9 (SD 6.97) months. The new-onset chronic pain was widespread, primarily manifesting as muscle pain. Thirteen (72.2%) patients met the diagnostic criteria for FMS, with an average WPI score of 8.8 and an average SS score of 8.2, indicating a high level of pain and significant adverse impact on their quality of life.

Conclusion

The study found that 72.2% of the patients with new-onset chronic MSK pain following COVID-19 infection met the criteria for FMS. These findings support the hypothesis that FMS may develop as a long-term sequela of a viral infection, underscoring the need for further research into post-viral long-term conditions.
Infectious Complications Following CD30 Chimeric Antigen Receptor T-Cell Therapy in Adults
Authors: Cao Felicia , Xiu Yueling , Mohnasky Michael , Serody Jonathan S. , Armistead Paul , Dotti Gianpietro , Smith Melody , Huggins Jonathan , Messina Julia , Ramachandran Bhanu , Saullo Jennifer , Stromberg Joseph , Saha Manish K. , Walsh Megan , Savoldo Barbara , Grover Natalie , Henderson Heather I. , Andermann Tessa M.
Published: July 2024

Infections are increasingly recognized as a common complication of chimeric antigen receptor (CAR) T-cell therapy. The incidence of clinically-defined infection after CD19.CAR T-cell therapy for relapsed/refractory lymphoma ranges from 60-90% in the first year after CAR T-cell therapy and is the most common cause for non-relapse mortality. However, infectious risk after CAR T-cell therapy targeting other malignancies is not well understood. Herein, we report for the first time, infectious complications after CD30.CAR T-cell treatment for patients with Hodgkin’s lymphoma and peripheral T-cell lymphoma. Since CD30 is only expressed on a subset of activated T and B-cells, we hypothesized that CD30.CAR T-cell patients would have reduced incidence and severity of infections after infusion compared to CD19.CAR T-cell patients. We retrospectively evaluated all 64 patients who received CD30.CAR T-cells at a single institution between 2016-2021, and assessed infections within one year after cell infusion, comparing these data to a contemporary cohort of 50 patients who received CD19.CAR T-cells at the same institution between 2018-2021. 23 CD30.CAR T-cell patients (36%) and 18 CD19.CAR T-cell patients (36%) developed a microbiologically confirmed infection. Infection severity and bacterial infections were higher in the CD19.CAR T-cell group compared to CD30.CAR T-cell recipients who more commonly had grade 1 respiratory viral infections. Our data reflect expected outcomes for severity and infection type in CD19.CAR T-cell patients and provide a benchmark for comparison with the novel CD30.CAR T-cell product. Although our findings require replication in a larger cohort, they have implications for antimicrobial prophylaxis guidelines after CD30.CAR T-cell therapy.

KEY POINTS

1) The incidence of infections within the first year after CD30.CAR T-cell therapy was equivalent to that following CD19.CAR T-cell therapy

2) Viral infections were more common after CD30.CAR T-cell therapy but bacterial infections predominated after CD19.CAR T-cell therapy.
Dynamics of bacterial biofilm development imaged using light sheet fluorescence microscopy
Authors: Šmerdová Lenka , Füzik Tibor , Valentová Lucie , Bárdy Pavol , Procházková Michaela , Pařenicová Martina , Plevka Pavel
Published: July 2024

Biofilm formation exacerbates bacterial infections and interferes with industrial processes. However, the dynamics of biofilm development is not entirely understood. Here, we present a microfluidic cultivation system that enables continuous imaging of biofilm growth using light sheet fluorescence microscopy (LSFM). We studied the development of biofilms of the human pathogensStaphylococcus aureusandPseudomonas aeruginosa. Due to the low phototoxicity of LSFM, biofilms can be continuously imaged without adverse effects on their development. WhereasS. aureusforms 50-70-μm-thick mushroom-like structures, aP. aeruginosabiofilm is 10-15 μm thick with cell clusters 25 μm in diameter. A combined biofilm, inoculated with an equal OD600ratio ofS. aureusandP. aeruginosa, resulted in the formation of large mushroom-like clusters ofS. aureuscells that were subsequently dispersed by invadingP. aeruginosa.A higher inoculation ratio favoringP. aeruginosaresulted in the formation of small and stableS. aureusclusters overgrown withP. aeruginosacells. Applying conditioned media fromS. aureusandP. aeruginosacoculture to a single-speciesS. aureusbiofilm induced its dispersion. Integrating a microfluidic system into LSFM enables the visualization of biofilm formation dynamics and the effects of compounds on biofilm development.
Importin α inhibitors act against the differentiated stages of apicomplexan parasitesPlasmodium falciparumandToxoplasma gondii
Authors: Bhambid Manasi , Walunj Sujata , C. A. Anupama , Jain Shilpi , Mehta Diksha , Wagstaff Kylie , Panda Ashutosh , Jans David A. , Mohmmed Asif , Patankar Swati
Published: July 2024

Protozoan parasites of the phylum Apicomplexa, includingPlasmodium falciparumandToxoplasma gondii, cause widespread disease in humans. New drugs and protein targets are required for the treatment of these diseases, particularly therapies targeting multiple stages of the parasite life cycles. Nuclear import, carried out by the transporter’s importin (IMP) α and β subunits, is a valid target for the discovery of lead compounds against these protozoan parasites: small molecules were identified that inhibit interactions between IMPα and nuclear localisation signalsin vitroand also inhibit the growth of the rapidly-dividing stages ofP. falciparumandT. gondii(asexual stages and tachyzoites) in culture. In this report, we add another small molecule (Bay 11-7082) to the panel of inhibitors of IMPα and test the ability of these inhibitors to first, inhibit nuclear transport in the rapidly dividing stages and, next, the maturation of differentiated stages of both parasites. We show that GW5074 and CAPE inhibit nuclear transport in theP. falciparumblood stages, while Bay 11-7085 inhibits nuclear transport inT. gondiitachyzoites. Interestingly, CAPE strongly inhibits gametocyte maturation, the sexual stages ofP. falciparum, and Bay 11-7085 weakly inhibits bradyzoite differentiation, the latent stages ofT. gondii. As differentiation of both these stages is dependent on activation of gene expression, triggered by the nuclear translocation of transcription factors, our work provides a “proof of concept” that targeting nuclear import is a viable strategy for the development of therapeutics against multiple stages of apicomplexan parasites, some of them recalcitrant to existing drugs.
Proton-pump inhibitors increaseC. difficileinfection risk by altering pH rather than by affecting the gut microbiome based on a bioreactor model
Authors: Schumacher Julia , Müller Patrick , Sulzer Johannes , Faber Franziska , Molitor Bastian , Maier Lisa
Published: July 2024

Clostridioides difficileinfections often occur after antibiotic use, but they have also been linked to proton-pump inhibitor (PPI) therapy. The underlying mechanism—whether infection risk is due to a direct effect of PPIs on the gut microbiome or changes in gastrointestinal pH—has remained unclear.

To disentangle both possibilities, we studied the impact of the proton-pump inhibitor omeprazole and pH changes on key members of the human gut microbiome and stool-derived microbial communities from different donorsin vitro. We then developed a custom multiple-bioreactor system to grow a model human microbiome community in chemostat mode and tested the effects of omeprazole exposure, pH changes, and their combination onC. difficilegrowth within this community.

Our findings show that changes in pH significantly affect the gut microbial community’s biomass and the abundances of different strains, leading to increasedC. difficilegrowth within the community. However, omeprazole treatment alone did not result in such effects. These findings imply that the higher risk ofC. difficileinfection following proton-pump inhibitor therapy is probably because of alterations in gastrointestinal pH rather than a direct interaction between the drug and the microbiome. This understanding paves the way for reducing infection risks in proton-pump inhibitor therapy.
Pleiotropic regulation of bacterial toxin production and Allee effect govern microbial predator–prey interactions
Authors: Suma Harikumar R. , Stallforth Pierre
Published: July 2024

Bacteria are social organisms, which are constantly exposed to predation by nematodes or amoebae. To counteract these predation pressures, bacteria have evolved a variety of potent antipredator strategies. Bacteria of the genusPseudomonas, for instance, evade amoebal predation by the secretion of amoebicidal natural products. The soil bacteriumPseudomonas fluorescensHKI0770 produces pyreudione alkaloids that can kill amoebae. Even though the mode of action of the pyreudiones has been elucidated, the spatiotemporal dynamics underlying this predator–prey interaction remain unknown. Using a combination of microscopic and analytical techniques, we elucidated the intricate relationship of this predator−prey association. We used the chromatic bacteria toolbox for intraspecific differentiation of the amoebicide-producing wildtype and the non-producing mutant within microcosms. These allow for variations in nutrient availability and the emergence of predation-evasion strategies of interacting microorganisms. Imaging of the co-cultures revealed that the amoebae initially ingest both the non-producer as well as the toxin-producer cells. The outcomes of predator–prey interactions are governed by the population size and fitness of the interacting partners. We identified that changes in the cell density coupled with alterations in nutrient availability led to a strong Allee effect resulting in the diminished production of pyreudione A. The loss of defence capabilities rendersP. fluorescensHKI0770 palatable to amoebae. Such a multifaceted regulation provides the basis for a model by which predator–prey populations are being regulated in specific niches. Our results demonstrate how the spatiotemporal regulation of bacterial toxin production alters the feeding behaviour of amoebae.
Structural constraints and drivers of molecular evolution in a macromolecular complex; the kinetochore
Authors: Pare Hannah K. , Nguyen Alexandra L. , Pankey M. Sabrina , Cheeseman Iain M. , Plachetzki David C.
Published: July 2024

Evolutionary theory suggests that critical cellular structures should be subject to strong purifying selection as protein changes would result in inviability. However, how this evolutionary principle relates to multi-subunit complexes remains incompletely explored. For example, the macromolecular kinetochore complex, which mediates the faithful segregation of DNA during cell division, violates the expectation of purifying selection as subsets of kinetochore proteins exhibit rapid evolution despite its critical role. Here, we developed a multi-level approach to investigate the evolutionary dynamics of the kinetochore as a model for understanding how an essential multi-protein structure can experience high rates of diversifying selection while maintaining function. Our comprehensive approach analyzed 57 kinetochore genes for signatures of purifying and diversifying selection across 70 mammalian species. Intraspecies comparisons of kinetochore gene evolution showed that members of the order Afrotheria experience higher rates of diversifying selection than other mammalian orders. Among individual loci, genes that serve regulatory functions, such as the mitotic checkpoint genes, are conserved under strong purifying selection. In contrast, the proteins that serve as the structural base of the kinetochore, including the inner and outer kinetochore, evolve rapidly across species. We also demonstrated that diversifying selection is targeted to protein regions that lack clear structural predictions. Finally, we identified sites that exhibit corresponding trends in evolution across different genes, potentially providing evidence of compensatory evolution in this complex. Together, our study of the kinetochore reveals a potential avenue by which selection can alter the genes that comprise an essential cellular complex without compromising its function.
2D Transfer Learning for ECG Classification using Continuous Wavelet Transform
Authors: Zhang Wei
Published: July 2024

Abstract

Advanced deep neural networks, when trained on extensive datasets, can outperform cardiologists in diagnosing cardiac arrhythmias. However, the availability of large-scale training data is often impractical. This study explores the use of transfer learning to identify and classify three ECG patterns. It applies knowledge gained from 2D image classification tasks to the domain of 1D time-series ECG signal classification. The research leverages various deep learning models to classify continuous wavelet transform (2D representations) of ECG signals. The effectiveness of these transferred deep learning models in classifying ECG time-series data is then evaluated.
Gravitational Wave Symphony from Oscillating Spectator Scalar Fields
Authors: Cui Yanou , Saha Pankaj , Sfakianakis Evangelos I.
Published: July 2024

We investigate a generic source of stochastic gravitational wave background due to the parametric resonance of oscillating scalar fields in the early Universe. By systematically analyzing benchmark models through lattice simulations and considering a wide range of parameters, we demonstrate that such a scenario can lead to detectable signals in gravitational wave detectors over a broad frequency range and potentially address the recent findings by pulsar timing array experiments. Furthermore, these models naturally yield ultralight dark matter candidates or dark radiation detectable by cosmic microwave background observatories.

Published by the American Physical Society
2024
Enhanced Quantum Metric due to Vacancies in Graphene
Authors: Marsal Quentin , Black-Schaffer Annica M.
Published: July 2024

Random vacancies in a graphene monolayer induce defect states that are known to form a narrow impurity band centered around zero energy at half filling. We use a space-resolved formulation of the quantum metric and establish a strong enhancement of the electronic correlations in this impurity band. The enhancement is primarily due to strong correlations between pairs of vacancies situated on different sublattices at anomalously large spatial distances. We trace the strong enhancement to both the multifractal vacancy wave functions, which ties the system exactly at the Anderson insulator transition for all defect concentrations, and preserving the chiral symmetry.

Published by the American Physical Society
2024
Effect of noise in the direction of motion over the spatial distribution and proliferation of migrating cell collectives
Authors: Dawson Jonathan E. , Malmi-Kakkada Abdul N.
Published: July 2024

A variety of living and nonliving systems exhibit collective motion. From swarm robotics to bacterial swarms, and tissue wound healing to human crowds, examples of collective motion are highly diverse but all of them share the common necessary ingredient of moving and interacting agents. While collective motion has been extensively studied in nonproliferating systems, how the proliferation of constituent agents affects their collective behavior is not well understood. Here, we focus on growing active agents as a model for cells and study how the interplay between noise in their direction of movement and proliferation determines the overall spatial pattern of collective motion. In this agent-based model, motile cells possess the ability to adhere to each other through cell-cell adhesion, grow in size, and divide. Cell-cell interactions influence not only the direction of cell movement but also cell growth through a force-dependent mechanical feedback process. We show that noise in the direction of a cell's motion has striking effects on both the emergent spatial distribution of cell collectives and proliferation. While higher noise strength leads to a random spatial distribution of cells, we also observe increased cell proliferation. On the other hand, low noise strength leads to a ringlike spatial distribution of cell collectives together with lower proliferation. Our findings provide insight into how noisy cell motion determines the local spatial organization of cells with consequent mechanical feedback on cell division impacting cell proliferation due to the formation of cell clusters.

Published by the American Physical Society
2024
Simulating
(2+1)D
SU(2) Yang-Mills lattice gauge theory at finite density with tensor networks
Authors: Cataldi Giovanni , Magnifico Giuseppe , Silvi Pietro , Montangero Simone
Published: July 2024

We numerically simulate a non-Abelian lattice gauge theory in two spatial dimensions, with tensor networks (TN), up to intermediate sizes (>30 matter sites) well beyond exact diagonalization. We focus on the SU(2) Yang-Mills model in Hamiltonian formulation, with dynamical matter and minimally truncated gauge field (hardcore gluon). Thanks to the TN sign-problem-free approach, we characterize the phase diagram of the model at zero and finite baryon number as a function of the quark bare mass and color charge. At intermediate system sizes, we detect a liquid phase of quark-pair bound-state quasiparticles (baryons), whose mass is finite towards the continuum limit. Interesting phenomena arise at the transition boundary where color-electric and color-magnetic terms are maximally frustrated: For low quark masses, we see traces of potential deconfinement, while for high masses, signatures of a possible topological order.

Published by the American Physical Society
2024
Fractional skyrme lines in ferroelectric barium titanate
Authors: Halcrow Chris , Babaev Egor
Published: July 2024

We predict a topological defect in perfectly screened ferroelectric barium titanate which we call a skyrme line. These are linelike objects characterized by skyrmionic topological charge. As well as configurations with integer topological charge, the charge density can split into well-localized parts carrying a localized fraction of topological charge. We show that under certain conditions the fractional skyrme lines are stable. We discuss a mechanism to create fractional topological charge objects and investigate their stability.

Published by the American Physical Society
2024
Shepherding and herdability in complex multiagent systems
Authors: Lama Andrea , di Bernardo Mario
Published: July 2024

We study the shepherding control problem where a group of “herders” need to orchestrate their collective behavior in order to steer the dynamics of a group of “target” agents towards a desired goal. We relax the assumptions, often made in the existing literature, of targets showing cohesive collective behavior in the absence of the herders, and herders owning global sensing capabilities. We find scaling laws linking the number of targets with the minimum number of herders needed to shepherd them, and we unveil the existence of a critical threshold of the density of the targets, below which the number of herders needed for success significantly increases. We explain the existence of such a threshold in terms of the percolation of a suitably defined herdability graph and support our numerical evidence by analyzing a partial differential equation describing the herders dynamics in a simplified one-dimensional setting. Extensive numerical experiments validate our methodology.

Published by the American Physical Society
2024
Finite-Resource Performance of Small-Satellite-Based Quantum-Key-Distribution Missions
Authors: Islam Tanvirul , Sidhu Jasminder S. , Higgins Brendon L. , Brougham Thomas , Vergoossen Tom , Oi Daniel K.L. , Jennewein Thomas , Ling Alexander
Published: July 2024

In satellite-based quantum-key-distribution (QKD), the number of secret bits that can be generated in a single satellite pass over the ground station is severely restricted by the pass duration and the free-space optical channel loss. High channel loss may decrease the signal-to-noise ratio due to background noise, reduce the number of generated raw key bits, and increase the quantum bit error rate (QBER), all of which have detrimental effects on the output secret key length. Under finite-size security analysis, a higher QBER increases the minimum raw key length necessary for nonzero secret-key-length extraction due to less efficient reconciliation and postprocessing overheads. We show that recent developments in finite-key analysis allow three different small-satellite-based QKD projects, CQT-Sat, the United Kingdom QUARC-ROKS, and QEYSSat, to produce secret keys even under conditions of very high loss, improving on estimates based on previous finite-key bounds. This suggests that satellites in low Earth orbit can satisfy finite-size security requirements but that this remains challenging for satellites further from Earth. We analyze the performance of each mission to provide an informed route toward improving the performance of small-satellite QKD missions. We highlight the short- and long-term perspectives on the challenges and potential future developments in small-satellite-based QKD and quantum networks. In particular, we discuss some of the experimental and theoretical bottlenecks and the improvements necessary to achieve QKD and wider quantum networking capabilities in daylight and at different altitudes.

Published by the American Physical Society
2024
Enhancing the accuracy of stock return movement prediction in Indonesia through recent fundamental value incorporation in multilayer perceptron
Authors: Agusta Stiven , Rakhman Fuad , Mustakini Jogiyanto Hartono , Wijayana Singgih
Published: July 2024

Purpose

The study aims to explore how integrating recent fundamental values (RFVs) from conventional accounting studies enhances the accuracy of a machine learning (ML) model for predicting stock return movement in Indonesia.

Design/methodology/approach

The study uses multilayer perceptron (MLP) analysis, a deep learning model subset of the ML method. The model utilizes findings from conventional accounting studies from 2019 to 2021 and samples from 10 firms in the Indonesian stock market from September 2018 to August 2019.

Findings

Incorporating RFVs improves predictive accuracy in the MLP model, especially in long reporting data ranges. The accuracy of the RFVs is also higher than that of raw data and common accounting ratio inputs.

Research limitations/implications

The study uses Indonesian firms as its sample. We believe our findings apply to other emerging Asian markets and add to the existing ML literature on stock prediction. Nevertheless, expanding to different samples could strengthen the results of this study.

Practical implications

Governments can regulate RFV-based artificial intelligence (AI) applications for stock prediction to enhance decision-making about stock investment. Also, practitioners, analysts and investors can be inspired to develop RFV-based AI tools.

Originality/value

Studies in the literature on ML-based stock prediction find limited use for fundamental values and mainly apply technical indicators. However, this study demonstrates that including RFV in the ML model improves investors’ decision-making and minimizes unethical data use and artificial intelligence-based fraud.
Recognizing the importance of collaborative competencies and facilitative leadership in local government in the United States
Authors: Bukalova Dominika
Published: July 2024

Purpose

This article describes what department directors and chiefs of staff reported when asked about the competencies they need to be effective in addressing on-the-job challenges. The study analyzed the generated data in two different ways to both understand what participants said in their own terms and to determine whether there is a fit between participants’ responses and facilitative leadership theory.

Design/methodology/approach

Twenty-four semi-structured interviews were conducted with five department directors and seven chiefs of staff in a US city that had a mayor-council form of government. Responses were analyzed in two ways. Initially, coding categories were developed inductively in an effort to employ what anthropologists characterize as an emic or insider perspective. Then the data were recoded from an etic perspective using the theory of facilitative leadership as a conceptual framework.

Findings

Although participants identified a wide variety of competencies, all participants emphasized the importance of working collaboratively with others, including the members of their teams, the elected official they worked with (and for) and constituents.

Originality/value

While most studies of facilitative leadership have focused on mayors and city managers, i.e. those at the top of the city administration hierarchy, this study’s focus is on middle managers who are not necessarily thought of as leaders but who must in fact, exercise leadership at least at times. Another relatively unique feature of this paper is its focus on a city that employs a mayor-council form of governance, a type of governance structure that has been underdiscussed in the literature to date.