bluuebunny/crossref_metadata_2025 huggingface dataset:
Resource sharing of an infant gut microbiota synthetic community in combinations of human milk oligosaccharides
Authors: Ioannou Athanasia , Berkhout Maryse D , Scott William T , Blijenberg Bernadet , Boeren Sjef , Mank Marko , Knol Jan , Belzer Clara
Published: October 2024

Quickly after birth, the gut microbiota is shaped via species acquisition and resource pressure. Breastmilk, and more specifically, human milk oligosaccharides are a determining factor in the formation of microbial communities and the interactions between bacteria. Prominent human milk oligosaccharide degraders have been rigorously characterized, but it is not known how the gut microbiota is shaped as a complex community. Here, we designed BIG-Syc, a synthetic community of 13 strains from the gut of vaginally born, breastfed infants. BIG-Syc replicated key compositional, metabolic, and proteomic characteristics of the gut microbiota of infants. Upon fermentation of a four and five human milk oligosaccharide mix, BIG-Syc demonstrated different compositional and proteomic profiles, with Bifidobacterium infantis and Bifidobacterium bifidum suppressing one another. The mix of five human milk oligosaccharides resulted in a more diverse composition with dominance of B. bifidum, whereas that with four human milk oligosaccharides supported the dominance of B. infantis, in four of six replicates. Reintroduction of bifidobacteria to BIG-Syc led to their engraftment and establishment of their niche. Based on proteomics and genome-scale metabolic models, we reconstructed the carbon source utilization and metabolite and gas production per strain. BIG-Syc demonstrated teamwork as cross-feeders utilized simpler carbohydrates, organic acids, and gases released from human milk oligosaccharide degraders. Collectively, our results showed that human milk oligosaccharides prompt resource-sharing for their complete degradation while leading to a different compositional and functional profile in the community. At the same time, BIG-Syc proved to be an accurate model for the representation of intra-microbe interactions.
Genomic characterization of MRSA recovered from people with cystic fibrosis during two Spanish multicentre studies (2013 and 2021)
Authors: Maruri-Aransolo Ainhize , Hernandez-García Marta , Barbero Raquel , Michelena Malkoa , Pastor-Vivero María Dolores , Mondejar-Lopez Pedro , Solé Amparo , Cantón Rafael , Caballero-Pérez Juan de Dios ,   GEIFQ study group, Maruri-Aransolo Ainhize , de Dios-Caballero Juan , Cantón Rafael , Michelena-González Malkoa , Máiz Luis , Vicente Saioa , Quintana Esther , Pastor-Vivero María Dolores , Álvarez Antonio , Alarcón Rosa Girón, Teresa , Luna-Paredes Carmen , de Valbuena Marta Ruiz , Prados María Concepción , Castillo-Corullón Silvia , Selma María José , Solé Amparo , Cols-Roig Maria , Mondéjar-López Pedro , Ruiz Estela Pérez , Olveira Casilda , Aguilera Pilar Caro , Ruiz Pilar Bermúdez , Causapé Carla López , Figuerola Joan , Oliver Antonio , Asensio Oscar
Published: October 2024

Background

Chronic bronchopulmonary infection due to MRSA in people with cystic fibrosis (pwCF) has been associated with accelerated decline in lung function, increased hospitalizations and increased mortality.

Material and methods

We studied microbiological and genomic characteristics of MRSA isolates recovered from pwCF in two Spanish multicentre studies (2013, 2021). Antimicrobial susceptibility was performed. WGS was carried out to determine population structure [MLST, spa-typing, staphylococcal cassette chromosome mec (SCCmec)], resistome and virulome. Clinical charts of MRSA-infected and MRSA-non-infected pwCF were also reviewed.

Results

MRSA infection prevalence decreased between 2013 (29/341, 8.5%) and 2021 (21/326, 6.4%) (P = 0.378). Differences in lung function were observed between infected and non-infected patients (P < 0.005). A higher prevalence of hospital-acquired (HA) clones was found compared with community-acquired (CA) clones (2013: 67% versus 33%; and 2021: 71% versus 29%). Overall, we noted clustering of isolates based on year of sampling, type of acquisition and clonal complex (CC). HA-MRSA population was dominated by CC5, with ST125-MRSA-IVc-t067 the most prevalent lineage (37%). A higher clonal diversity was detected among CA-MRSA. One Panton–Valentine leucocidin (PVL)-positive strain (ST8-MRSA-IV) and three strains of porcine origin (two ST398-MRSA-V-t011, one ST398-MRSA-V-t8567) were found. Additionally, acquired resistance genes (n = 24) were detected, including the cfr gene conferring linezolid resistance. A higher gentamicin resistance was found in 2021 (42%) compared with 2013 (7%) (P = 0.046), associated with the aac(6′)-aph(2″) gene.

Conclusions

Despite a decrease in MRSA prevalence, we showed its potential impact on CF severity and progression. Moreover, we observed great genotypic and phenotypic diversity in MRSA isolates from pwCF as well as an MDR trait.
Asaia spp. accelerate development of the yellow fever mosquito, Aedes aegypti, via interactions with the vertically transmitted larval microbiome
Authors: Roman Alessandro , Koenraadt Constantianus Johanna Maria , Raymond Ben
Published: October 2024

Aims

A wide range of vector control programmes rely on the efficient production and release of male mosquito. Asaia bacteria are described as potential symbionts of several mosquito species but their relationship with Aedes aegypti has never been rigorously tested. Here, we aimed to quantify the benefits of three Asaia species on host development in Ae. aegypti, and the ability of these bacteria to form a stable symbiotic association with growing larvae.

Methods and results

In order to disentangle direct and indirect effects of Asaia inoculation on host development, experiments used insects with an intact microbiome and those reared in near-aseptic conditions, while we characterized bacterial communities and Asaia densities with culture dependent and independent methods (16S rRNA amplicon sequencing). Neonate larvae were inoculated with Asaia spp. for 24 h, or left as uninoculated controls, all were reared on sterile food. Aseptic larvae were produced by surface sterilization of eggs. Although all Asaia were transient members of the gut community, two species accelerated larval development relative to controls. The two mutualistic species had lasting impacts on the larval microbiome, largely by altering the relative abundance of dominant bacteria, namely Klebsiella and Pseudomonas. Axenic larvae were dominated by Asaia when inoculated with this species but showed slower development than conventionally reared insects, indicating that Asaia alone could not restore normal development.

Conclusions

Our results reveal Asaia as a poor mutualist for Ae. aegypti, but with a species-specific positive effect on improving host performance mediated by interactions with other bacteria.
Biofilms and microbiome profiles in chronic wounds: links to antibiotic use and wound severity in a Sri Lankan cohort
Authors: Dilhari Ayomi , Campbell Paul M , Munasinghe Anuradha , Brown Hannah , Kaluarachchi Thilini D J , Gunasekara Chinthika , Pathirage Sujatha , Fernando Neluka , Weerasekara Deepaka , Humphreys Gavin J , McBain Andrew J , Weerasekera Manjula
Published: October 2024

Aims

We have characterized the microbiome of infected chronic diabetic wounds (CDWs), exploring associations with antibiotic use and wound severity in a Sri Lankan cohort.

Methods and results

Fifty CDW patients were enrolled, 38 of whom received antibiotics. Tissue biopsies were analysed by microbiome profiling, and wounds were graded using the University of Texas Wound Grading System. Biofilm presence was assessed in 20 wounds. The microbiome was largely dominated by Enterobacteriaceae, Pseudomonadaceae, Streptococcaceae, and Corynebacteriaceae. Proteobacteria levels were significantly higher in antibiotic-treated wounds (P = .019), with increased Pseudomonas abundance. Wounds were categorized as grade 1 (10), grade 2 (29), and grade 3 (11). Alpha diversity varied by wound grade (P = .015), with grade 2 wounds showing the highest diversity and grade 3 the lowest. All 20 tested wounds were biofilm-positive, and community composition varied more in antibiotic-treated wounds (P = .004).

Conclusions

CDW microbiomes were dominated by Enterobacteriaceae and Pseudomonadaceae, with elevated Proteobacteria in antibiotic-treated wounds. Alpha diversity correlated with wound severity, peaking in grade 2 wounds. The high prevalence of biofilms in wounds underscores the need for management of CDWs that address microbial complexity.
Resistance to carbapenems in the urban soil isolate Cupriavidus taiwanensis S2-1-W is associated with OXA-1206, a newly discovered carbapenemase
Authors: Lopez Nicolas V , Ruiz Cristian
Published: October 2024

Aims

Cupriavidus isolates are found in environmental and clinical samples and are often resistant to carbapenems, which are last-resort antibiotics. However, their carbapenem-resistance molecular mechanisms remain unknown. This study aimed to (i) characterize and sequence the carbapenem-resistant soil isolate Cupriavidus taiwanensis S2-1-W to uncover its antibiotic resistance determinants; and (ii) clone and characterize a putative novel carbapenemase gene identified in this isolate.

Methods and results

Antibiotic susceptibility testing of C. taiwanensis S2-1-W revealed that it was resistant to most carbapenems, other β-lactams, and aminoglycosides tested. Genome sequencing of this isolate revealed a complex chromosomal resistome that included multidrug efflux pump genes, one aminoglycoside transferase gene, and three β-lactamase genes. Among them, we identified a novel putative class D β-lactamase gene (blaOXA-1206) that is highly conserved among other sequenced C. taiwanensis isolates. Cloning and characterization of blaOXA-1206 confirmed that it encodes for a newly discovered carbapenemase (OXA-1206) that confers resistance to carbapenems and other β-lactams.

Conclusion

Carbapenem-resistance in C. taiwanensis S2-1-W is associated with a newly discovered carbapenemase, OXA-1206.
CALIFRAME: a proposed method of calibrating reporting guidelines with FAIR principles to foster reproducibility of AI research in medicine
Authors: Shiferaw Kirubel Biruk , Balaur Irina , Welter Danielle , Waltemath Dagmar , Zeleke Atinkut Alamirrew
Published: October 2024

Background

Procedural and reporting guidelines are crucial in framing scientific practices and communications among researchers and the broader community. These guidelines aim to ensure transparency, reproducibility, and reliability in scientific research. Despite several methodological frameworks proposed by various initiatives to foster reproducibility, challenges such as data leakage and reproducibility remain prevalent. Recent studies have highlighted the transformative potential of incorporating the FAIR (Findable, Accessible, Interoperable, and Reusable) principles into workflows, particularly in contexts like software and machine learning model development, to promote open science.

Objective

This study aims to introduce a comprehensive framework, designed to calibrate existing reporting guidelines against the FAIR principles. The goal is to enhance reproducibility and promote open science by integrating these principles into the scientific reporting process.

Methods

We employed the “Best fit” framework synthesis approach which involves systematically reviewing and synthesizing existing frameworks and guidelines to identify best practices and gaps. We then proposed a series of defined workflows to align reporting guidelines with FAIR principles. A use case was developed to demonstrate the practical application of the framework.

Results

The integration of FAIR principles with established reporting guidelines through the framework effectively bridges the gap between FAIR metrics and traditional reporting standards. The framework provides a structured approach to enhance the findability, accessibility, interoperability, and reusability of scientific data and outputs. The use case demonstrated the practical benefits of the framework, showing improved data management and reporting practices.

Discussion

The framework addresses critical challenges in scientific research, such as data leakage and reproducibility issues. By embedding FAIR principles into reporting guidelines, the framework ensures that scientific outputs are more transparent, reliable, and reusable. This integration not only benefits researchers by improving data management practices but also enhances the overall scientific process by promoting open science and collaboration.

Conclusion

The proposed framework successfully combines FAIR principles with reporting guidelines, offering a robust solution to enhance reproducibility and open science. This framework can be applied across various contexts, including software and machine learning model development stages, to foster a more transparent and collaborative scientific environment.
Artificial intelligence-generated feedback on social signals in patient–provider communication: technical performance, feedback usability, and impact
Authors: Bedmutha Manas Satish , Bascom Emily , Sladek Kimberly R , Tobar Kelly , Casanova-Perez Reggie , Andreiu Alexandra , Bhat Amrit , Mangal Sabrina , Wood Brian R , Sabin Janice , Pratt Wanda , Weibel Nadir , Hartzler Andrea L
Published: October 2024

Objectives

Implicit bias perpetuates health care inequities and manifests in patient–provider interactions, particularly nonverbal social cues like dominance. We investigated the use of artificial intelligence (AI) for automated communication assessment and feedback during primary care visits to raise clinician awareness of bias in patient interactions.

Materials and Methods

(1) Assessed the technical performance of our AI models by building a machine-learning pipeline that automatically detects social signals in patient–provider interactions from 145 primary care visits. (2) Engaged 24 clinicians to design usable AI-generated communication feedback for their workflow. (3) Evaluated the impact of our AI-based approach in a prospective cohort of 108 primary care visits.

Results

Findings demonstrate the feasibility of AI models to identify social signals, such as dominance, warmth, engagement, and interactivity, in nonverbal patient–provider communication. Although engaged clinicians preferred feedback delivered in personalized dashboards, they found nonverbal cues difficult to interpret, motivating social signals as an alternative feedback mechanism. Impact evaluation demonstrated fairness in all AI models with better generalizability of provider dominance, provider engagement, and patient warmth. Stronger clinician implicit race bias was associated with less provider dominance and warmth. Although clinicians expressed overall interest in our AI approach, they recommended improvements to enhance acceptability, feasibility, and implementation in telehealth and medical education contexts.

Discussion and Conclusion

Findings demonstrate promise for AI-driven communication assessment and feedback systems focused on social signals. Future work should improve the performance of this approach, personalize models, and contextualize feedback, and investigate system implementation in educational workflows. This work exemplifies a systematic, multistage approach for evaluating AI tools designed to raise clinician awareness of implicit bias and promote patient-centered, equitable health care interactions.
HR-pQCT reveals marked trabecular and cortical structural deficits in women with pregnancy and lactation-associated osteoporosis (PLO)
Authors: Agarwal Sanchita , El-Najjar Dany , Kondapalli Ananya , Kil Nayoung , Kamanda-Kosseh Mafo , Bucovsky Mariana , Colon Ivelisse , Lappe Joan M , Stubby Julie , Recker Robert R , Guo X Edward , Shane Elizabeth , Cohen Adi
Published: October 2024

Pregnancy and lactation-associated osteoporosis (PLO) is a rare presentation of early-onset osteoporosis characterized by low trauma and spontaneous fractures during late pregnancy/lactation. Herein, we report areal BMD (aBMD) by DXA and volumetric BMD (vBMD), microarchitecture, and strength at the distal radius and tibia by HR-pQCT in 59 women with PLO—in comparison to both healthy premenopausal controls (n = 28) and premenopausal women with idiopathic osteoporotic fractures not associated with pregnancy/lactation (non-PLO IOP; n = 50). Women with PLO (aged 34 ± 6 yr) had a more severe clinical presentation than non-PLO IOP: 80% had vertebral and 92% had multiple fractures (p<.001). They had lower DXA aBMD at all sites vs Controls (all p<.001) and non-PLO IOP (all p<.05). By HR-pQCT, PLO had deficits in all radial/tibial density and most microarchitecture parameters and lower bone strength than controls (all p<.001). Compared to non-PLO IOP, PLO had lower total and trabecular density at radius and tibia (all p ≤ .01) and significant deficits in trabecular microstructure and cortical thickness at the radius only. We studied PLO subgroups with clinical factors potentially related to bone physiology: Within PLO, women with vertebral fractures had lower spine aBMD and higher tibial cortical porosity but were otherwise structurally similar to the nonvertebral group. Those with prior heparin exposure had larger bone size and trabecular area, and those with renal stones had smaller bone size and lower 1/3 radius aBMD. We also compared groups based on postpartum timing: Recent PLO (n = 25) evaluated ≤12 M postpartum, before expected recovery of pregnancy/lactation bone loss, had significantly lower aBMD than distant PLO (n = 34) evaluated >12 M postpartum. However, radial/tibial HR-pQCT measures did not differ, suggesting pre-existing and/or persistent structural deficits. This structural study increases our mechanistic understanding of the severe bone fragility presentation that characterizes PLO and also highlights areas of potential mechanistic heterogeneity that require additional investigation.
An enhanced slime mould algorithm with triple strategy for engineering design optimization
Authors: Wang Shuai , Zhang Junxing , Li Shaobo , Wu Fengbin , Li Shaoyang
Published: October 2024

This paper introduces an enhanced slime mould algorithm (EESMA) designed to address critical challenges in engineering design optimization. The EESMA integrates three novel strategies: the Laplace logistic sine map technique, the adaptive t-distribution elite mutation mechanism, and the ranking-based dynamic learning strategy. These enhancements collectively improve the algorithm’s search efficiency, mitigate convergence to local optima, and bolster robustness in complex optimization tasks. The proposed EESMA demonstrates significant advantages over many conventional optimization algorithms and performs on par with, or even surpasses, several advanced algorithms in benchmark tests. Its superior performance is validated through extensive evaluations on diverse test sets, including IEEE CEC2014, IEEE CEC2020, and IEEE CEC2022, and its successful application in six distinct engineering problems. Notably, EESMA excels in solving economic load dispatch problems, highlighting its capability to tackle challenging optimization scenarios. The results affirm that EESMA is a competitive and effective tool for addressing complex optimization issues, showcasing its potential for widespread application in engineering and beyond.
The Contrast Pressures on Consumer-Level Food Waste During a Pandemic: The Impact of Infection Salience Versus Lockdown Salience
Authors: Gao Huachao
Published: October 2024

Consumer food waste, with its extensive social, economic, and environmental implications, gained heightened attention during the COVID-19 pandemic, which disrupted food supply chains and exacerbated food insecurity. Amidst conflicting reports on the pandemic’s influences on consumer-level food waste, this research differentiates between the infection and lockdown facets of a pandemic. Specifically, we demonstrate that infection salience amplifies safety–health concerns, leading to increased consumer food waste, while lockdown salience raises concerns over resource scarcity, resulting in reduced consumer food waste. Considering that most pandemics or infectious diseases primarily increase infection salience without inducing lockdowns, we propose a safety–health intervention to mitigate the rise in consumer food waste driven by infection salience and the associated safety–health concerns. Through a large-scale field s tudy, a lab experiment measuring real food waste, a country-level secondary dataset, and three supplementary experiments, we provide converging supports for our theory. These studies also showcase various implementations of the safety–health intervention, such as table tents, napkins, and to-go boxes. This research reconciles divergent perspectives on the pandemic’s impact on consumer-level food waste, enriches the understanding of pandemics and associated food waste dynamics, and offers actionable strategies for businesses and policymakers to address consumer food waste during pandemics.
The bifurcation challenge at the Unified Patent Court
Authors: Dani Martina
Published: October 2024

Among the issues that have been examined during the preparatory phase for establishing the Unified Patent Court (UPC), bifurcation is one of the most discussed and criticized. In this article, the trends towards bifurcation developed during the first year of the UPC operations will be examined, thus offering valuable insights into what we can expect to see in the near future.
MerTK signaling in human primary T cells modulates memory potential and improves recall response
Authors: Rahbech Anne , Kurzay Annina , Fresnillo Saló Sara , Seremet Tina , Debets Reno , Met Özcan , Peeters Marlies J W , thor Straten Per
Published: October 2024

Immune therapy using checkpoint inhibitors or adoptive cell transfer has revolutionized the treatment of several types of cancers. However, response to treatment is currently limited to a fraction of patients. Elucidation of immune modulatory mechanisms might optimize patient selection and present ways to modify anti-cancer immune responses. We recently discovered the expression and an important costimulatory role of TAM receptor MerTK signaling on activated human primary CD8+ T cells. Here we extend our study of the costimulatory role of MerTK expression in human CD8+ T cells. We uncover a clear link between MerTK expression and less differentiated Central Memory T cells based on an increased expression of CCR7, CD45RO, CD28, CD62L, and an altered metabolic profile. In addition, we observe an improved proliferative capacity and elevated expression of effector molecule IFNγ upon recall responses of MerTK-expressing cells in vitro. Finally, using gp100TCR-transduced T cells, we demonstrate how PROS1 treatment results in improved cytotoxicity and killing of tumors. Our findings describe a role of MerTK expression in T cells, which could be exploited in the search for improving immunotherapeutic approaches.
RE: The first living cervid species described in the 21st century and revalidation of Pudella (Artiodactyla)
Authors: Zijlstra Jelle S
Published: October 2024

The correct name combination for the Northern Pudu, which was recently assigned to the revalidated genus Pudella, is Pudella mephistophiles (de Winton, 1896). There has been confusion over the number of its holotype specimen; the correct specimen number of the holotype is BMNH 1896.1.28.6.
Cognitive and affective links between childhood adversity and psychological adjustment in emerging adults with chronic medical conditions
Authors: DeLone Alexandra M , Basile Nathan L , Chaney John M , Mullins Larry L , Sharkey Christina M
Published: October 2024

Objective

Childhood adversity has been linked to poor psychological adjustment and decreased emotion regulation (ER) abilities. The extended process model of ER outlines the pivotal role of cognitive appraisals in the generation and expression of emotion as well as the pursuit of ER. The aim of the current study is to examine whether illness-related cognitive appraisals (i.e., illness uncertainty and illness intrusiveness) and emotion dysregulation serially mediate the relationship between childhood adversity and psychological adjustment for emerging adults with chronic medical conditions (CMCs).

Methods

Participants included 557 undergraduate college students (Mage= 19.53 years, SD = 1.34) enrolled in a Midwestern public university with self-reported CMCs. Participants completed measures of adverse childhood experiences (ACEs), illness uncertainty, illness intrusiveness, emotion dysregulation, anxious symptoms, and depressive symptoms. A path analysis was conducted examining ACEs → cognitive appraisals (i.e., illness uncertainty, illness intrusiveness) → emotion dysregulation → depressive and anxious symptoms.

Results

The overall model was significant and predicted 63.5% of the variability in anxious symptoms and 60.2% of the variability in depressive symptoms. All anticipated direct and indirect paths were significant.

Conclusions

The current study indicates that greater childhood adversity is indeed associated with negative appraisals of one’s CMC, such as greater perceived uncertainty and intrusiveness. Negative illness-related cognitive appraisals thus may limit one’s ability to effectively employ adaptive strategies to regulate emotions, which could contribute to greater depressive and anxious symptoms.
Potential for an Electronic Clinical Decision Support Tool to Support Appropriate Antibiotic Use for Pediatric Diarrhea Among Village Doctors in Bangladesh
Authors: Khan Isthtiakul I , Hanson Olivia R , Khan Zahid Hasan , Amin Mohammad Ashraful , Biswas Debashish , Das Jyoti Bhushan , Munim Mohammad Saeed , Shihab Ridwan Mostafa , Islam Md Taufiqul , Mangadu Aparna , Nelson Eric J , Ahmed Sharia M , Qadri Firdausi , Watt Melissa H , Leung Daniel T , Khan Ashraful I
Published: October 2024

Village doctors in Bangladesh expressed broad interest in clinical decision support tools for pediatric diarrheal disease management and described their willingness to alter their antibiotic dispensing practices if guided by one. Future research should evaluate the tool’s impact on appropriate antibiotic use and patient outcomes.
High-throughput, low-cost FLASH: irradiation of Drosophila melanogaster with low-energy X-rays using time structures spanning conventional and ultrahigh dose rates
Authors: Hart Alexander , Dudzic Jan P , Clarke Jameson W , Eby Jonathan , Perlman Steve J , Bazalova-Carter Magdalena
Published: October 2024

FLASH radiotherapy is an emerging technique in radiation oncology that may improve clinical outcomes by reducing normal tissue toxicities. The physical radiation characteristics needed to induce the radiobiological benefits of FLASH are still an active area of investigation. To determine the dose rate, range of doses and delivery time structure necessary to trigger the FLASH effect, Drosophila melanogaster were exposed to ultrahigh dose rate (UHDR) or conventional radiotherapy dose rate (CONV) 120-kVp X-rays. A conventional X-ray tube outfitted with a shutter system was used to deliver 17- to 44-Gy doses to third-instar D. melanogaster larvae at both UHDR (210 Gy/s) and CONV (0.2–0.4 Gy/s) dose rates. The larvae were then tracked through development to adulthood and scored for eclosion and lifespan. Larvae exposed to UHDR eclosed at higher rates and had longer median survival as adults compared to those treated with CONV at the same doses. Eclosion rates at 24 Gy were 68% higher for the UHDR group (P < 0.05). Median survival from 22 Gy was >22 days for UHDR and 17 days for CONV (P < 0.01). Two normal tissue-sparing effects were observed for D. melanogaster irradiated with UHDR 120-kVp X-rays. The effects appeared only at intermediate doses and may be useful in establishing the dose range over which the benefits of FLASH can be obtained. This work also demonstrates the usefulness of a high-throughput fruit fly model and a low-cost X-ray tube system for radiobiological FLASH research.
High-fidelity Image Restoration of Large 3D Electron Microscopy Volume
Authors: Kreinin Yuri , Gunn Pat , Chklovskii Dmitri , Wu Jingpeng
Published: October 2024

Volume electron microscopy (VEM) is an essential tool for studying biological structures. Due to the challenges of sample preparation and continuous volumetric imaging, image artifacts are almost inevitable. Such image artifacts complicate further processing both for automated computer vision methods and human experts. Unfortunately, the widely used contrast limited adaptive histogram equalization (CLAHE) can alter the essential relative contrast information about some biological structures. We developed an image-processing pipeline to remove the artifacts and enhance the images without CLAHE. We apply our method to VEM datasets of a Microwasp head. We demonstrate that our method restores the images with high fidelity while preserving the original relative contrast. This pipeline is adaptable to other VEM datasets.
Intravital Microscopy With an Airy Beam Light Sheet Microscope Improves Temporal Resolution and Reduces Surgical Trauma
Authors: Stegmeyer Rebekka I , Stasch Malte , Olesker Daniel , Taylor Jonathan M , Mitchell Thomas J , Hosny Neveen A , Kirschnick Nils , Spickermann Gunnar , Vestweber Dietmar , Volkery Stefan
Published: October 2024

Intravital microscopy has emerged as a powerful imaging tool, which allows the visualization and precise understanding of rapid physiological processes at sites of inflammation in vivo, such as vascular permeability and leukocyte migration. Leukocyte interactions with the vascular endothelium can be characterized in the living organism in the murine cremaster muscle. Here, we present a microscopy technique using an Airy Beam Light Sheet microscope that has significant advantages over our previously used confocal microscopy systems. In comparison, the light sheet microscope offers near isotropic optical resolution and faster acquisition speed, while imaging a larger field of view. With less invasive surgery we can significantly reduce side effects such as bleeding, muscle twitching, and surgical inflammation. However, the increased acquisition speed requires exceptional tissue stability to avoid imaging artefacts. Since respiratory motion is transmitted to the tissue under investigation, we have developed a relocation algorithm that removes motion artefacts from our intravital microscopy images. Using these techniques, we are now able to obtain more detailed 3D time-lapse images of the cremaster vascular microcirculation, which allow us to observe the process of leukocyte emigration into the surrounding tissue with increased temporal resolution in comparison to our previous confocal approach.
Clinical importance of cerebrospinal fluid protein levels in HIV-associated cryptococcal meningitis: Insights from a prospective cohort study in Uganda
Authors: Kasibante John , Irfanullah Eesha , Wele Abduljewad , Okafor Elizabeth C , Ssebambulidde Kenneth , Okurut Samuel , Kagimu Enock , Gakuru Jane , Rutakingirwa Morris K , Mugabi Timothy , Nuwagira Edwin , Jjunju Samuel , Mpoza Edward , Tugume Lillian , Nsangi Laura , Musibire Abdu K , Muzoora Conrad , Rhein Joshua , Meya David B , Boulware David R , Abassi Mahsa
Published: October 2024

Cerebrospinal fluid (CSF) protein levels exhibit high variability in HIV-associated cryptococcal meningitis; however, its clinical implications remain unclear. We analyzed data from 890 adults with HIV-associated cryptococcal meningitis randomized into two clinical trials in Uganda between 2015 and 2021. CSF protein was grouped into < 100 mg/dl (72%, n = 641) and ≥ 100 mg/dl (28%, n = 249). We described baseline clinical variables and 18-week mortality by CSF protein groups. Those with CSF protein ≥ 100 mg/dl were more likely to present with Glasgow coma scale score < 15 (P < .01), self-reported seizures at baseline (P = .02), higher CD4 T-cell count (P < .001), and higher CSF white blood cells (P < .001). Moreover, those with a baseline CSF protein ≥ 100 mg/dl also had a lower baseline CSF fungal burden (P < .001) and a higher percentage of sterile CSF cultures at day 14 (P = .02). Individuals with CSF protein ≥ 100 mg/dl demonstrated a more pronounced immune response consisting of upregulation of immune effector molecules, pro-inflammatory cytokines, T-helper cell type 1 and 17 cytokines, and immune-exhaustion marker (P < .05). 18-week mortality risk in individuals with a CSF protein < 100 mg/dl was 34% higher (unadjusted Hazard Ratio 1.34; 95% Confidence Interval, 1.05–1.70; P = .02) than those with CSF protein ≥ 100 mg/dl. In HIV-associated cryptococcal meningitis, individuals with baseline CSF protein ≥ 100 mg/dl more frequently presented with neurological symptoms, higher CSF inflammatory cytokines, reduced fungal burden, and lower mortality risk. The findings underscore the prognostic significance of baseline CSF protein levels in predicting disease severity and mortality risk in cryptococcal meningitis.
A correlation between sunspot observations and solar Ca ii H&K activity proxies
Authors: Ferreira R R , Gonçalves B F O , do Nascimento J -D , Castro M
Published: October 2024

The magnetic phenomena on the solar surface have been the subject of several investigations over the last 400 yr. An early indicator of solar magnetic activity was sunspot counting. Currently, the main sunspot indicators are the international sunspot number, the sunspot group number, the total sunspot area, and the photometric sunspot index. Several improvements in observational techniques have allowed magnetic activity to be measured using solar/stellar spectra. Standard spectroscopic activity indicators are the $S_{\rm MW}$ index, based on the Ca ii H&K emission lines, and the chromospheric component $R^{\prime }_{\rm HK}$ index. In this context, we present a correlation between sunspot observations and solar Ca ii H&K activity proxies. We present our comparisons between the spectroscopic chromospheric activity proxies ($S_{\rm MW}$ and $R^{\prime }_{\rm HK}$) and the sunspot indicators over the last decades, using solar measurements (spectroscopic and spot proxy) performed on the same day. In general, our results indicate a linear fit between the chromospheric proxies and sunspot indicators. In addition, using the long-term sunspot group number records, we estimate an average spectroscopic proxy along the solar Maunder minimum (MM) phase, corresponding to $\mathinner {\langle {S_{\rm MW}}\rangle } = 0.167 \pm 0.013$ and $\mathinner {\log \langle {R^{\prime }_{\rm HK}}\rangle } = -4.913 \pm 0.363$. The estimated variability is $\sigma _{S_{\rm MW}} = 1.137 \times 10^{-7}$ and $\sigma _{\log R^{\prime }_{\rm HK}} = 2.704 \times 10^{-6}$. Our linear regression analysis, applied annually, suggests that the variability level of the chromospheric activity in the MM phase is significantly lower than in the normal period of activity and that this could be the result of linear regression on annually averaged data, combined with minimal sunspot activity during the solar MM phase. Further observations of MM analogues will be needed to test this hypothesis.
scTWAS Atlas: an integrative knowledgebase of single-cell transcriptome-wide association studies
Authors: Mai Jialin , Qian Qiheng , Gao Hao , Fan Zhuojing , Zeng Jingyao , Xiao Jingfa
Published: October 2024

Single-cell transcriptome-wide association studies (scTWAS) is a new method for conducting TWAS analysis at the cellular level to identify gene-trait associations with higher precision. This approach helps overcome the challenge of interpreting cell-type heterogeneity in traditional TWAS results. As the field of scTWAS rapidly advances, there is a growing need for additional database platforms to integrate this wealth of data and knowledge effectively. To address this gap, we present scTWAS Atlas (https://ngdc.cncb.ac.cn/sctwas/), a comprehensive database of scTWAS information integrating literature curation and data analysis. The current version of scTWAS Atlas amasses 2,765,211 associations encompassing 34 traits, 30 cell types, 9 cell conditions and 16,470 genes. The database features visualization tools, including an interactive knowledge graph that integrates single-cell expression quantitative trait loci (sc-eQTL) and scTWAS associations to build a multi-omics level regulatory network at the cellular level. Additionally, scTWAS Atlas facilitates cross-cell-type analysis, highlighting cell-type-specific and shared TWAS genes. The database is designed with user-friendly interfaces and allows for easy browsing, searching, and downloading of relevant information. Overall, scTWAS Atlas is instrumental in exploring the genetic regulatory mechanisms at the cellular level and shedding light on the role of various cell types in biological processes, offering novel insights for human health research.
Magnesium and boron isotope evidence for the generation of arc magma through serpentinite-mélange melting
Authors: Qiao Xin-Yue , Xiong Jia-Wei , Chen Yi-Xiang , De Hoog Jan C M , Pearce Julian , Huang Fang , Zhao Zi-Fu , Chen Kun
Published: October 2024

Serpentinites play a crucial role in mass transport and volatile recycling in subduction zones, yet the mechanism for their contribution to the formation of arc magma remains elusive. Here, we investigate this issue by examining the magnesium (Mg) and boron (B) isotope compositions of volcanic rocks and forearc serpentinites from the South Sandwich Island arc. The volcanic rocks display δ26Mg values ranging from −0.25‰ to −0.06‰ and δ11B values ranging from +9.6‰ to +16.5‰, while the forearc serpentinites exhibit δ26Mg values of −0.21‰ to −0.02‰ and δ11B values of +5.2‰ to +9.8‰. Given the substantial contrast in both Mg and B contents between mantle rocks and fluids, the combined heavy Mg–B isotope compositions of volcanic rocks pose a challenge to traditional arc formation models, i.e. flux melting of depleted subarc mantle metasomatized by slab-derived fluids. Although an alternative model involving flux melting of dehydrated serpentinites can partly account for the heavy Mg isotope compositions of arc magmas, it is difficult to simultaneously explain the B isotope and trace-element compositions. Instead, these distinct compositions can be adequately explained by partial melting of a serpentinite-dominated mélange beneath the volcanic arc. Given that arc magmas exhibiting coupled heavy Mg–B isotope compositions are increasingly reported, we propose that serpentinite-mélange melting represents an effective and geochemically self-consistent mechanism for transferring signatures of subducted slabs to the overlying mantle source. This process can be significant in subduction zones with prominent forearc mantle erosion or those involving considerable amounts of slab-hosted serpentinite.
Real-world outcomes in patients with brain metastases secondary to HR+/HER2− MBC treated with abemaciclib and local intracranial therapy
Authors: Gathirua-Mwangi Wambui , Martin Holly , He Dan , Zheng Shen , Sheffield Kristin M , John Jincy , Yamazawa Erika , Rybowski Sarah , Brastianos Priscilla K
Published: October 2024

Background

Real-world data are limited for patients with brain metastases secondary to metastatic breast cancer (MBC) and treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). This study describes real-world outcomes in patients with hormone receptor-positive, human epidermal growth factor 2-negative (HR+/HER2−) MBC with brain metastases diagnosis before abemaciclib initiation.

Patients and Methods

A nationwide electronic health record-derived de-identified MBC database (January 2011-December 2021) was assessed retrospectively. Patients with HR+/HER2− MBC who were treated with abemaciclib (monotherapy or in combination) following diagnosis of brain metastases were included. Real-world best response reflected clinician-documented response assessment of the brain imaging (intracranial) and change in disease burden following radiographic imaging (extracranial); these were reported descriptively. Time to treatment discontinuation (TTD), real-world progression-free survival (rwPFS), and overall survival (rwOS) were assessed using Kaplan-Meier methods from abemaciclib initiation (index date).

Results

Among 82 included patients (mean age 57.0 years; 98.8% female), 22.0% and 19.5% received CDK4/6i and chemotherapy before abemaciclib initiation, respectively, and the majority (80.5%) received radiation/local surgery to the brain before abemaciclib initiation. Patients mostly received abemaciclib as monotherapy (n = 6) or in combination with endocrine therapy (n = 68). Median TTD was 7.1 (95% CI 4.6-11.3) months, rwPFS was 9.2 (95% CI 6.0-11.6) months, and rwOS was 20.8 (95% CI 13.9-26.0) months. Intracranial and extracranial objective response rates, as determined by treating physicians, were 45.1% (n = 23/51) and 56.7% (n = 34/60), respectively. Intracranial and extracranial clinical benefit rates were 62.7% (n = 32/51) and 70.0% (n = 42/60), respectively.

Conclusion

In this real-world study of patients diagnosed with brain metastases and initiating abemaciclib, most patients received radiation/local surgery to the brain before abemaciclib initiation. Although the outcomes in this real-world study are encouraging, it is unclear if the benefit was due to local therapy, abemaciclib, or the combination, and causality cannot be inferred. Further prospective clinical studies are needed to confirm the clinical benefit of this approach.
The effect of π-spacer on D-A'-π-a system organic dyes for dye-sensitized solar cells (DSSCs) technology: a computational approach”
Authors: Sanama Michael Kennedy , Abubakari Ismail , Numbury Surendra Babu
Published: October 2024

The globe is consuming more energy as a result of population growth and economic development. One of the most important forms of renewable energy for human usage is solar energy. By modifying the π-spacers, four D-A'-π-A of novel organic dye molecules (D1–D4) have been created in this study. To evaluate the optoelectronic capabilities and photovoltaic qualities of four D-A'-π-A new organic dyes created molecules, density functional theory (DFT) and time-dependent DFT (TD-DFT) theory methodologies through the B3LYP and 6-311G basis set have been employed. To ascertain the effect of developed π-spacer on enhancing intramolecular charge transfer (ICT) and enhancing light-absorbing capacities, a number of crucial factors, including molecular geometry, energy bandgap and light-harvesting efficiency (LHE), have been studied. Based on the available data, D4 outperforms the other four developed organic dye molecules, with energy bandgap of 1.4896 and 1.4253 eV for gas and solvent phase, respectively, regeneration driving forces (ΔGreg) of 0.0469 and 0.0300 eV for the gas phase and solvent phase, respectively, and open-circuit voltages (Voc) of 0.6427 and 0.5953 eV for the gas phase and solvent phase, respectively. Additionally, the maximum absorption wavelengths (λmax) for the gas phase and solvent phase are 932.03 and 1013.81 nm, respectively. Consequently, it was found that the D4 dye molecule was a more promising option for the use of dye-sensitized solar cells (DSSCs) technology hence advised for more practical research to provide efficient advancements in the D-A'-π-A system organic dye for the production of sustainable energy.
Impaired sleep-dependent memory consolidation in pediatric narcolepsy type 1
Authors: Maski Kiran , Heckler Gillian , Worhach Jennifer , Mylonas Dimitrios , Wang Grace , Szilagyi Klara , Zhang Bo , Diniz Behn Cecilia , Scammell Thomas E , Stickgold Robert
Published: October 2024

Study Objectives

Disrupted nighttime sleep is common in pediatric narcolepsy type 1, yet its cognitive impact is unknown. As N2 sleep spindles are necessary for sleep-dependent memory consolidation, we hypothesized that narcolepsy type 1 impairs memory consolidation via N2 sleep fragmentation and N2 sleep spindle alterations.

Methods

We trained 28 pediatric narcolepsy type 1 participants and 27 healthy controls (HCs) on a spatial declarative memory task before a nocturnal in-lab polysomnogram and then gave them a cued recall test upon awakening in the morning. We extracted wake and sleep stage bout numbers and N2 spindle characteristics from the polysomnogram and conducted mixed model analysis of sleep-dependent memory consolidation to identify group differences.

Results

Narcolepsy type 1 participants had shorter N2 bout durations and associated shorter N2 spindles versus HC, but other N2 spindle features were similar. Narcolepsy type 1 participants had worse memory performance postsleep than HCs after adjusting for age and gender (mean memory consolidation HC: −3.1% ± 18.7, NT1: −15.6 ± 24.8, main effect group × time of testing F = 5.3, p = .03). We did not find significant relationships between sleep-dependent memory consolidation and N2 spindle characteristics. Notably, increased N1% was associated with worse sleep-dependent memory consolidation with results driven by the narcolepsy type 1 group.

Conclusions

Sleep-dependent memory consolidation is mildly impaired in youth with narcolepsy type 1 and findings may be attributed to increases in N1 sleep. Further studies are needed to determine if these findings are generalizable and reversible with sleep-based therapies.
A systematic review of pelvic infective osteomyelitis in children: current state of evidence
Authors: Kumar Vishal , Barik Sitanshu , Garg Varun , Raj Vikash , Arora Shobha S
Published: October 2024

Musculoskeletal infection of pelvis can be confused with septic arthritis of the hip, irritable hip, sacroiliitis, and spondylodiscitis in the initial period. This study aimed to present the complete clinical picture of pelvic infective osteomyelitis (PIO) in children along with its natural course. Two researchers independently used PubMed and Scopus electronic databases for the literature review. This review includes all studies reporting PIO in the pediatric age group. The final inclusion of 11 eligible studies was done. A total of 277 patients were analyzed from the included studies with the majority of males (158/242, 65.2%). Hip and groin pain (147/195, 75.3%) and limp (155/249, 62.2%) were the common presenting symptoms. Increased systemic temperature (83/103, 80.5%) and localized tenderness at the hip joint area (90/121, 74.3%) were among the commonest signs. Magnetic resonance imaging was an investigation of choice for diagnosis (89/93, 95.6%). Blood culture showed growth in 47.6% (119/250) patients with Staphylococcus aureus (83/102, 81.3%) being the most common isolated organism. Treatment with sensitive antibiotics was the mainstay of management with surgery for debridement or biopsy being required in only 16.1% (23/142) of the patients. PIO in children is a rare condition mimicking several other disease processes affecting the neighboring tissues the diagnosis of which gets limited in low-resource settings. Further prospective clinical studies are the need of the hour to validate the guideline proposed. Explorative studies to define a clinical scoring system to differentiate septic arthritis of the hip from PIO may be considered.
From Workfare to Economic and Sociopolitical Stability? Evidence from a Randomized Trial in Eastern Congo
Authors: Brandily Paul , Mvukiyehe Eric , Smets Lodewijk , van der Windt Peter , Verpoorten Marijke
Published: October 2024

Did a workfare program in Eastern Congo have a lasting impact on economic and sociopolitical outcomes? Men and women in Eastern Congo were randomly assigned to 2,674 four-month job offers, or to the job offer plus a savings incentive, hard-skills training, or both. Eighteen months after the program, labor market and savings outcomes have improved, but there is no change across 12 other economic and sociopolitical outcome families. Regarding labor market outcomes, the most intensive treatment—the job offer plus the savings incentive and hard-skills training—outperforms treatments with only one add-on. This indicates that the savings incentive and hard-skills training, when combined, can create a synergistic impact greater than the sum of their individual effects. The results are mainly driven by female beneficiaries, who start at much lower levels of labor market participation and earnings than men.