bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful Treatment of Acquired Thrombotic Thrombocytopenic Purpura With Caplacizumab Combined With Plasma Exchanges and Immune Suppression in 3 Children
Authors: Kalinina Irina I. , Antonova Khristina S. , Avdonin Pavel V. , Klebanova Elizaveta E. , Kotskaya Natalia N. , Kurnikova Elena E. , Shutova Alexandra D. , Matveev Victor E. , Maschan Alexey A.
Published: March 2024

Acquired thrombotic thrombocytopenic (aTTP) purpura is a life-threatening condition that can lead to devastating thromboembolic events. Recently, caplacizumab has been shown to rapidly restore platelet numbers and reduce the risk of severe end-organ damage when added to plasma exchanges (PEXs) and immunosuppression (IST). Here, we report the outcomes in 3 children with aTTP who were treated with caplacizumab in combination with PEXs and IST. In all 3 patients, platelet count increased to >15,000/mm3 in 24 h and normalized on day 4, whereas normalization of ADAMTS13 activity >50% and elimination of the inhibitor was achieved after 18 to 89 days. Epistaxis was observed in 2 patients and was the only side effect related to caplacizumab. Caplacizumab is a promising agent for first-line treatment of children with aTTP.
Bartonella henselae Infection and Lymphadenopathy in a Patient With T Cell Acute Lymphoblastic Leukemia
Authors: Sadanand Arhanti , Patel Pratik , Riedesel Erica , Berkowitz Frank , Keller Frank G.
Published: March 2024

Patients undergoing therapy for T cell acute lymphoblastic leukemia are at risk of infections during their treatment course. Cat scratch disease caused by Bartonella hensalae can masquerade as leukemic relapse and cause systemic infection. Obtaining a thorough exposure history may aid clinicians in making the diagnosis.
Healthcare Burden and Resource Utilization After Pediatric Acute Respiratory Distress Syndrome: A Secondary Analysis of the Collaborative Pediatric Critical Care Research Network Acute Respiratory Distress Syndrome Study
Authors: Ames Stefanie G. , Maddux Aline B. , Burgunder Lauren , Meeks Huong , Fink Erica L. , Meert Kathleen L. , Zinter Matt S. , Mourani Peter M. , Carcillo Joseph A. , Carpenter Todd , Pollack Murray M. , Mareboina Manvita , Notterman Daniel A. , Sapru Anil ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN)
Published: March 2024

OBJECTIVES:

To describe family healthcare burden and health resource utilization in pediatric survivors of acute respiratory distress syndrome (ARDS) at 3 and 9 months.

DESIGN:

Secondary analysis of a prospective multisite cohort study.

SETTING:

Eight academic PICUs in the United States (2019–2020).

PATIENTS:

Critically ill children with ARDS and follow-up survey data collected at 3 and/or 9 months after the event.

INTERVENTIONS:

None.

METHODS AND MEASUREMENT:

We evaluated family healthcare burden, a measure of healthcare provided by families at home, and child health resource use including medication use and emergency department (ED) and hospital readmissions during the initial 3- and 9-month post-ARDS using proxy-report. Using multivariable logistic regression, we evaluated patient characteristics associated with family healthcare burden at 3 months.

MAIN RESULTS:

Of 109 eligible patients, 74 (68%) and 63 patients (58%) had follow-up at 3- and 9-month post-ARDS. At 3 months, 46 families (62%) reported healthcare burden including (22%) with unmet care coordination needs. At 9 months, 33 families (52%) reported healthcare burden including 10 families (16%) with unmet care coordination needs. At month 3, 61 patients (82%) required prescription medications, 13 patients (18%) had ED visits and 16 patients (22%) required hospital readmission. At month 9, 41 patients (65%) required prescription medications, 19 patients (30%) had ED visits, and 16 (25%) required hospital readmission were reported. Medication use was associated with family healthcare burden at both 3 and 9 months. In a multivariable analysis, preillness functional status and chronic conditions were associated with healthcare burden at month 3 but illness characteristics were not.

CONCLUSIONS:

Pediatric ARDS survivors report high rates of healthcare burden and health resource utilization at 3- and 9-month post-ARDS. Future studies should assess the impact of improved care coordination to simplify care (e.g., medication management) and improve family burden.
MSCT 3D Analysis of Nasopharyngeal Airway After Le Fort I Maxillary Setback Surgeries
Authors: Zou Yiwen , Yang Ruicong , Yeweng San-jie , Wu Zhongxing
Published: March 2024

In recent years, maxillary Le Fort I osteotomy setback has been widely applied in correcting maxilla prognathism. In the meantime, airway considerations have attracted more and more attention. The aim of this research was to observe the alteration of nasopharyngeal airway indexes after maxilla setback and offer evidence for the effectiveness and safety of maxillary Le Fort I setback surgeries. As for a retrospective cross-sectional study, 40 patients diagnosed with maxilla prognathism and undergoing maxillary setback surgeries were enrolled. They were grouped by the type of maxillary setback operations as group A (integral maxillary setback, n=19) and group B (segmental maxillary setback, n=21). Multislice computed tomography data were collected 1 week before (T0) and more than 3 months (T1) after surgery. 3D reconstruction and evaluation of the pharyngeal airway were conducted to analyze nasopharyngeal airway index variation before and after surgery and the difference between group A and group B. Preoperative and postoperative nasopharyngeal airway volume showed no statistical significance in group A (P=0.872) and group B (P=0.169) as well as other indexes of the nasopharynx. The comparison of postoperative airway changes between group A and group B also showed no significant difference. Both integral and segmental maxillary Le Fort I osteotomy setbacks have slight impact on nasopharyngeal airway dimensions and are safe within a specific setback range.
Role of seasonal importation and genetic drift on selection for drug-resistant genotypes of
Plasmodium falciparum
in high-transmission settings
Authors: Zupko Robert J. , Servadio Joseph L. , Nguyen Tran Dang , Tran Thu Nguyen-Anh , Tran Kien Trung , Somé Anyirékun Fabrice , Boni Maciej F.
Published: March 2024

Historically
Plasmodium falciparum
has followed a pattern of drug resistance first appearing in low-transmission settings before spreading to high-transmission settings. Several features of low-transmission regions are hypothesized as explanations: higher chance of symptoms and treatment seeking, better treatment access, less within-host competition among clones and lower rates of recombination. Here, we test whether importation of drug-resistant parasites is more likely to lead to successful emergence and establishment in low-transmission or high-transmission periods of the same epidemiological setting, using a spatial, individual-based stochastic model of malaria and drug-resistance evolution calibrated for Burkina Faso. Upon controlling for the timing of importation of drug-resistant genotypes and examination of key model variables, we found that drug-resistant genotypes imported during the low-transmission season were (i) more susceptible to stochastic extinction due to the action of genetic drift, and (ii) more likely to lead to establishment of drug resistance when parasites are able to survive early stochastic loss due to drift. This implies that rare importation events are more likely to lead to establishment if they occur during a high-transmission season, but that constant importation (e.g. neighbouring countries with high levels of resistance) may produce a greater risk during low-transmission periods.
Himalayan lichen biomass for green synthesis of silver nanocolloids: growth kinetics, effect of pH and metal sensing
Authors: Sharma Nirmala , Gautam Surendra Kumar , Adhikari Achyut , Bhakta Neupane Bhanu
Published: March 2024

Lichen is one of the most abundant non-vascular biomasses; however, a systematic study on the application of biomass in nanomaterial synthesis is very limited. In this study, an aqueous lichen extract was obtained from
Hypotrachyna cirrhata
, one of the most abundant Himalayan lichen biomasses, using a simple cold percolation method. The effects of extract-to-silver nitrate mixing ratio, pH and waiting time on the growth and stability of nanoparticles were systematically explored. The rate constant for bio-reduction was found to be 5.3 × 10
−3
min
−1
. Transmission electron microscopy showed a narrow particle size distribution with a mean particle size of 11.1 ± 3.6 nm (
n
= 200). The X-ray diffraction and selected area electron diffraction techniques confirmed the formation of cubic crystals. The synthesized colloidal solution showed excellent response to Hg
2+
and Cu
2+
ions in spiked water samples. The limit of detection and calibration sensitivity for Hg
2+
and Cu
2+
ions were found to be 1 and 5 mg l
−1
and 2.9 × 10
−3
and 1.6 × 10
−3
units ppm
−1
, respectively. These findings suggested that spherical silver nanoparticles with a narrow particle size distribution can be synthesized on a laboratory scale using an aqueous
H. cirrhata
lichen extract, and the colloidal solution can be used for the detection of selected heavy metals in water samples.
Targeting fin whale conservation in the North-Western Mediterranean Sea: insights on movements and behaviour from biologging and habitat modelling
Authors: Panigada Viola , Bodey Thomas W. , Friedlaender Ari , Druon Jean-Noël , Huckstädt Luis A. , Pierantonio Nino , Degollada Eduard , Tort Beatriu , Panigada Simone
Published: March 2024

Biologging and habitat modelling are key tools supporting the development of conservation measures and mitigating the effects of anthropogenic pressures on marine species. Here, we analysed satellite telemetry data and foraging habitat preferences in relation to chlorophyll-a productivity fronts to understand the movements and behaviour of endangered Mediterranean fin whales (
Balaenoptera physalus)
during their spring–summer feeding aggregation in the North-Western Mediterranean Sea. Eleven individuals were equipped with Argos satellite transmitters across 3 years, with transmissions averaging 23.5 ± 11.3 days. Hidden Markov Models were used to identify foraging behaviour, revealing how individuals showed consistency in their use of seasonal core feeding grounds; this was supported by the distribution of potential foraging habitat. Importantly, tracked whales spent most of their time in areas with no explicit protected status within the study region. This highlights the need for enhanced time- and place-based conservation actions to mitigate the effects of anthropogenic impacts for this species, notably ship strike risk and noise disturbance in an area of exceptionally high maritime traffic levels. These findings strengthen the need to further assess critical habitats and Important Marine Mammal Areas that are crucial for focused conservation, management and mitigation efforts.
Complex systems in ecology: a guided tour with large Lotka–Volterra models and random matrices
Authors: Akjouj Imane , Barbier Matthieu , Clenet Maxime , Hachem Walid , Maïda Mylène , Massol François , Najim Jamal , Tran Viet Chi
Published: March 2024

Ecosystems represent archetypal complex dynamical systems, often modelled by coupled differential equations of the formdxidt=xiϕi(x1,…,xN),whereNrepresents the number of species andxi, the abundance of speciesi. Among these families of coupled differential equations, Lotka–Volterra (LV) equations, corresponding toϕi(x1,…,xN)=ri−xi+(Γx)i,play a privileged role, as the LV model represents an acceptable trade-off between complexity and tractability. Here,riis the intrinsic growth of speciesiandΓstands for the interaction matrix:Γijrepresents the effect of speciesjover speciesi. For largeN, estimating matrixΓis often an overwhelming task and an alternative is to drawΓat random, parameterizing its statistical distribution by a limited number of model features. Dealing with large random matrices, we naturally rely on random matrix theory (RMT). The aim of this review article is to present an overview of the work at the junction of theoretical ecology and large RMT. It is intended to an interdisciplinary audience spanning theoretical ecology, complex systems, statistical physics and mathematical biology.
Asymptotic numerical method for hyperelasticity and elastoplasticity: a review
Authors: Potier-Ferry Michel
Published: March 2024

The literature about the asymptotic numerical method (ANM) is reviewed in this paper as well as its application to hyperelasticity and elastoplasticity. ANM is a generic continuation method based on the computation of Taylor series for solving nonlinear partial differential equations. Modern techniques of high-order differentiation provide simple tools for computing these power series, the corresponding algorithms for finite strain elasticity and elastoplasticity being summarized here. Taylor series is not only a computation tool, but it contains also useful information about the structure of the considered solution curve. The paper ends with a short historical account about the development of this numerical method.
Axisymmetric vibration and stability of dielectric-elastic tubular bilayer system
Authors: Almamo Ahmad , Su Yipin , Chen Weiqiu , Wang Huiming
Published: March 2024

Modern transducers and actuators may have functional layers with multi-field coupling and some elastic layers. This paper considers a tubular bilayer system consisting of a thin dielectric tube coated with a thick elastic layer. We study the nonlinear electromechanical response and the linear axisymmetric vibration of the system subject to different applied voltages and inner/outer pressures within the framework of the general nonlinear theory of electro-elasticity, the related linear incremental theory, and by considering the continuity conditions at the interface. We investigate instability behaviour using the same basic formulae. The state-space method provides efficient and accurate free vibration analysis, considering the dynamic response at the lowest frequencies, so we can neglect the viscous and damping effects, which is well suited to this problem. New results indicate that the bilayer system improves its frequency capability and stability compared to the monolayer dielectric tube. The thick outer elastic layer stiffens the bilayer system against axisymmetric bifurcation, bulging and necking instabilities. It also performs better in front of axisymmetric instability, increasing the system’s capability to receive or produce higher voltages, especially for long waves.This work thoroughly explains bilayer functional systems’ behaviour when exposed to extreme environments such as high voltage or pressure.
Predators control pests and increase yield across crop types and climates: a meta-analysis
Authors: Boldorini Gabriel X. , Mccary Matthew A. , Romero Gustavo Q. , Mills Kirby L. , Sanders Nathan J. , Reich Peter B. , Michalko Radek , Gonçalves-Souza Thiago
Published: March 2024

Pesticides have well-documented negative consequences to control crop pests, and natural predators are alternatives and can provide an ecosystem service as biological control agents. However, there remains considerable uncertainty regarding whether such biological control can be a widely applicable solution, especially given ongoing climatic variation and climate change. Here, we performed a meta-analysis focused on field studies with natural predators to explore broadly whether and how predators might control pests and in turn increase yield. We also contrasted across studies pest suppression by a single and multiple predators and how climate influence biological control. Predators reduced pest populations by 73% on average, and increased crop yield by 25% on average. Surprisingly, the impact of predators did not depend on whether there were many or a single predator species. Precipitation seasonality was a key climatic influence on biological control: as seasonality increased, the impact of predators on pest populations increased. Taken together, the positive contribution of predators in controlling pests and increasing yield, and the consistency of such responses in the face of precipitation variability, suggest that biocontrol has the potential to be an important part of pest management and increasing food supplies as the planet precipitation patterns become increasingly variable.
Energy input, habitat heterogeneity and host specificity drive avian haemosporidian diversity at continental scales
Authors: Darío Hernandes Córdoba Oscar , Torres-Romero Erik Joaquín , Villalobos Fabricio , Chapa-Vargas Leonardo , Santiago-Alarcon Diego
Published: March 2024

The correct identification of variables affecting parasite diversity and assemblage composition at different spatial scales is crucial for understanding how pathogen distribution responds to anthropogenic disturbance and climate change. Here, we used a database of avian haemosporidian parasites to test how the taxonomic and phylogenetic diversity and phylogenetic structure of the genera
Plasmodium
,
Haemoproteus
and
Leucocytozoon
from three zoogeographic regions are related to surrogate variables of Earth's energy input, habitat heterogeneity (climatic diversity, landscape heterogeneity, host richness and human disturbance) and ecological interactions (resource use), which was measured by a novel assemblage-level metric related to parasite niche overlap (degree of generalism). We found that different components of energy input explained variation in richness for each genus. We found that human disturbance influences the phylogenetic structure of
Haemoproteus
while the degree of generalism explained richness and phylogenetic structure of
Plasmodium
and
Leucocytozoon
genera. Furthermore, landscape attributes related to human disturbance (human footprint) can filter
Haemoproteus
assemblages by their phylogenetic relatedness. Finally, assembly processes related to resource use within parasite assemblages modify species richness and phylogenetic structure of
Plasmodium
and
Leucocytozoon
assemblages. Overall, our study highlighted the genus-specific patterns with the different components of Earth's energy budget, human disturbances and degree of generalism.
Integration of genomic and ecological methods inform management of an undescribed, yet highly exploited, sardine species
Authors: Coelho Jéssica Fernanda Ramos , Mendes Liana de Figueiredo , Di Dario Fabio , Carvalho Pedro Hollanda , Dias Ricardo Marques , Lima Sergio Maia Queiroz , Verba Julia Tovar , Pereira Ricardo J.
Published: March 2024

Assessing genetic diversity within species is key for conservation strategies in the context of human-induced biotic changes. This is important in marine systems, where many species remain undescribed while being overfished, and conflicts between resource-users and conservation agencies are common. Combining niche modelling with population genomics can contribute to resolving those conflicts by identifying management units and understanding how past climatic cycles resulted in current patterns of genetic diversity. We addressed these issues on an undescribed but already overexploited species of sardine of the genus
Harengula
. We find that the species distribution is determined by salinity and depth, with a continuous distribution along the Brazilian mainland and two disconnected oceanic archipelagos. Genomic data indicate that such biogeographic barriers are associated with two divergent intraspecific lineages. Changes in habitat availability during the last glacial cycle led to different demographic histories among stocks. One coastal population experienced a 3.6-fold expansion, whereas an island-associated population contracted 3-fold, relative to the size of the ancestral population. Our results indicate that the island population should be managed separately from the coastal population, and that a Marine Protected Area covering part of the island population distribution can support the viability of this lineage.
Hospital admissions for acute respiratory tract infections among infants from Nunavut and the burden of respiratory syncytial virus: a 10-year review in regional and tertiary hospitals
Authors: Kinshella Mai-Lei Woo , Allen Jean , Pawa Jasmine , Papenburg Jesse , Jetty Radha , Dwilow Rachel , Embree Joanne , Robinson Joan , Arbour Laura , Sadarangani Manish , Shen Ye , Bone Jeffrey N. , Walker Celia , Kayda Iryna , Sheffield Holden , Scott Darcy , Miners Amber , Goldfarb David M.
Published: March 2024

Background

Nunavut is a northern Canadian territory in Inuit Nunangat (Inuit homeland in Canada). Approximately 85% of the population identifies as Inuit. A high proportion of infants in Nunavut are admitted to hospital with acute respiratory tract infection (ARI) but previous studies have been limited in regional and/or short duration of coverage. This study aimed to estimate the incidence rate, microbiology and outcomes of ARI hospitalizations in Nunavut infants.

Methods

We conducted chart reviews with a retrospective cohort of infants aged <1 year from Nunavut at six Canadian hospitals, including two regional and four tertiary pediatric hospitals January 1, 2010, to June 30, 2020. Descriptive statistics and multivariable logistic regression were performed.

Results

We identified 1189 ARI admissions of infants during the study period, with an incidence rate of 133.9 per 1000 infants per year (95% confidence interval (CI): 126.8, 141.3). Of these admissions, 56.0% (n=666) were to regional hospitals alone, 72.3% (n=860) involved hospitalization outside of Nunavut, 15.6% (n=185) were admitted into intensive care, and 9.2% (n=109) underwent mechanical ventilation. Of the 730 admissions with a pathogen identified, 45.8% had respiratory syncytial virus (RSV; n=334), for a yearly incidence rate of 37.8 hospitalizations per 1000 infants (95% CI: 33.9, 42.1). Among RSV hospitalizations, 41.1% (n=138) were infants 0-2 months of age and 32.1% (n=108) were > 6months.

Interpretation

Understanding the high burden of ARI among Nunavut infants can inform health policy and serve as a baseline for assessing the impact of any new interventions targeting infant ARIs.
Vividness of Visual Imagery Supported by Intrinsic Structural-Functional Brain Network Dynamics
Authors: Kvamme Timo L. , Lumaca Massimo , Zana Blanka , Paunovic Dunja , Silvanto Juha , Sandberg Kristian
Published: March 2024

Vividness of visual imagery is subject to individual variability, a phenomenon with largely unexplored neurobiological underpinnings. By analyzing data from 273 participants we explored the link between the structural-functional organization of brain connectomes and the reported intensity of visual imagery (measured with VVIQ-2). Employing graph theory analyses we investigated both the structural (DTI) and functional (rs-fMRI) connectomes within a network of regions often implicated in visual imagery. Our results indicate a relationship between increased local efficiency and clustering coefficients in the structural connectome in individuals who experience more vivid visual imagery. Increased local efficiency and clustering coefficients were mirrored in the functional connectome with increases in left inferior temporal regions, a region frequently identified as a critical hub in the visual imagery literature. Furthermore, individuals with more vivid imagery were found to have lower levels of global efficiency in their functional connectome. We propose that the clarity and intensity of visual imagery are optimized by a network organization characterized by heightened localized information transfer and interconnectedness. Conversely, an excessively globally integrated network might dilute the specific neural activity crucial for generating vivid visual images, leading to less locally concentrated resource allocation in key regions involved in visual imagery vividness.
Development of a Bipyrimidineamide based α-Helix Mimetic Lead Compound for efficient Targeting of MDM2 in Triple-Negative Breast Cancer
Authors: On Jasmin Linh , Woloschin Vitalij , Gier Franziska , Tu Jia-Wey , Bhatia Sanil , Lenz Thomas , Kulik Andrea , Stühler Kai , Niederacher Dieter , Neubauer Hans , Fehm Tanja , Kurz Thomas , Esser Knud
Published: March 2024

Abstract Figure

Triple-negative breast cancer (TNBC) represents the most aggressive form among breast carcinoma subtypes. Due to limited therapy options, identification of novel active pharmacological compounds is an urgent medical need. A promising approach in cancer treatment is the pharmacological inhibition of murine double minutes 2 (MDM2)-p53/p73 interactions inducing apoptosis in tumors. We here describe a novel bipyrimidineamide based α-helix mimetic9(VWK603) which was designed as a lead candidate to target MDM2.9(VWK603) potently induced cell death in the TNBC cell lines MDA-MB-231, MDA-MB-436 and MDA-MB-468 with IC50values ranging between 3.7 µM and 6.6 µM. The anti-tumor activity was about four more potent higher than determined for the MDM2-specific inhibitor Nutlin-3a. Mechanistic analysis revealed induction of cellular apoptosis as the underlying mode of action of9(VWK603) anti-tumor activity. Since toxicity was observed to be reduced in non-cancerous breast cells, these studies make9(VWK603) a promising candidate for further preclinical MDM2 inhibitor development.
DUAL: deep unsupervised simultaneous simulation and denoising for cryo-electron tomography
Authors: Zeng Xiangrui , Ding Yizhe , Zhang Yueqian , Uddin Mostofa Rafid , Dabouei Ali , Xu Min
Published: March 2024

Recent biotechnological developments in cryo-electron tomography allow direct visualization of native sub-cellular structures with unprecedented details and provide essential information on protein functions/dysfunctions. Denoising can enhance the visualization of protein structures and distributions. Automatic annotation via data simulation can ameliorate the time-consuming manual labeling of large-scale datasets. Here, we combine the two major cryo-ET tasks together in DUAL, by a specific cyclic generative adversarial network with novel noise disentanglement. This enables end-to-end unsupervised learning that requires no labeled data for training. The denoising branch outperforms existing works and substantially improves downstream particle picking accuracy on benchmark datasets. The simulation branch provides learning-based cryo-ET simulation for the first time and generates synthetic tomograms indistinguishable from experimental ones. Through comprehensive evaluations, we showcase the effectiveness of DUAL in detecting macromolecular complexes across a wide range of molecular weights in experimental datasets. The versatility of DUAL is expected to empower cryo-ET researchers by improving visual interpretability, enhancing structural detection accuracy, expediting annotation processes, facilitating cross-domain model adaptability, and compensating for missing wedge artifacts. Our work represents a significant advancement in the unsupervised mining of protein structures in cryo-ET, offering a multifaceted tool that facilitates cryo-ET research.
Adult Neurogenesis Reconciles Flexibility and Stability of Olfactory Perceptual Memory
Authors: Sakelaris Bennet , Riecke Hermann
Published: March 2024

In brain regions featuring ongoing plasticity, the task of quickly encoding new information without overwriting old memories presents a significant challenge. In the rodent olfactory bulb, which is renowned for substantial structural plasticity driven by adult neurogenesis and persistent turnover of dendritic spines, we show that by synergistically combining both types of plasticity this flexibility-stability dilemma can be overcome. To do so, we develop a computational model for structural plasticity in the olfactory bulb and show that it is the maturation process of adult-born neurons that enables the bulb to learn quickly and forget slowly. Particularly important are the transient enhancement of the plasticity, excitability, and susceptibility to apoptosis that characterizes young neurons. The model captures many experimental observations and makes a number of testable predictions. Overall, it identifies memory consolidation as an important role of adult neurogenesis in olfaction and exemplifies how the brain can maintain stable memories despite ongoing extensive neurogenesis and synaptic plasticity.
Prevalent fast evolution of genes involved in heterochromatin functions
Authors: Lin Leila , Huang Yuheng , McIntyre Jennifer , Chang Ching-Ho , Colmenares Serafin , Lee Yuh Chwen G.
Published: March 2024

Heterochromatin is a gene-poor and repeat-rich genomic compartment universally found in eukaryotes. Despite its low transcriptional activity, heterochromatin plays important roles in maintaining genome stability, organizing chromosomes, and suppressing transposable elements (TEs). Given the importance of these functions, it is expected that the genes involved in heterochromatin regulation would be highly conserved. Yet, a handful of these genes were found to evolve rapidly. To investigate whether these previous findings are anecdotal or general to genes modulating heterochromatin, we compile an exhaustive list of 106 candidate genes involved in heterochromatin functions and investigate their evolution over short and long evolutionary time scales inDrosophila.Our analyses find that these genes exhibit significantly more frequent evolutionary changes, both in the forms of amino acid substitutions and gene copy number change, when compared to genes involved in Polycomb-based repressive chromatin. While positive selection drives amino acid changes within both structured domains with diverse functions and intrinsically disordered regions (IDRs), purifying selection may have maintained the proportions of IDRs of these proteins. Together with the observed negative associations between evolutionary rates of these genes and genomic TE abundance, we propose an evolutionary model where the fast evolution of genes involved in heterochromatin functions is an inevitable outcome of the unique functional roles of heterochromatin, while the rapid evolution of TEs may be an effect rather than cause. Our study provides an important global view of the evolution of genes involved in this critical cellular domain and provides insights into the factors driving the distinctive evolution of heterochromatin.
GDOP: A graph convolutional network-based drug “on-target” pathway prediction algorithm
Authors: Wu Xiaolong , Zhang Lehan , Zheng Mingyue
Published: March 2024

Since most compounds do not induce changes in the transcriptomic levels of their target proteins in vivo, traditional gene set enrichment analysis methods can only retrieve downstream differentially expressed genes, which offer little hints to their targets. To address this problem, we proposed a graph convolutional network-based drug “on-target” pathway prediction algorithm, GDOP, which can predict small pathways that contain target gene through the power of deep learning algorithms. Our model receives as input structural information and biological characteristics (gene expression profiles) of molecules. After being trained on the publicly available LINCS data set, GDOP showed better generalization ability, reaching an AUC-ROC of 0.89 and an averaged Top10 accuracy of 0.63 on the test set. Besides, demonstrated that GDOP was able to use RNA-Seq data as input and achieved accuracy prediction results.
Does What You Eat Affect How You Mate? Disentangling the Interactions Between Diet-Induced Phenotypic Plasticity and Adult Reproductive Strategies in Black Soldier Flies
Authors: Zhang Qi-Hui , Ng Keng Hee , Chin Wells Shijian , Tang Yong Jen , Lin Jielin , Puniamoorthy Nalini
Published: March 2024

Phenotypic plasticity enables organisms to response to environmental variations by generating a range of phenotypes from a single genotype. In holometabolous insects, traits that influence larval plasticity may hold relevance for adult life history strategies. We present a comprehensive investigation into phenotypic plasticity in black soldier flies, a species known for its efficient waste-to-biomass conversion in the larval stage. Here, we document adult sex-specific plastic responses and reproductive strategies shaped by larval diets. We examined traits including adult body size, reproductive organ development, sperm length, mating behaviours, egg production and other life history parameters across different treatments. Our findings reveal notable sex-specific differences in phenotypic plasticity, with females showing increased plasticity in reproductive investment. Furthermore, males and females differed starkly in allometric growth and weight ratio of reproductive organs. Diets that facilitated longer male lifespans also prompted earlier male emergence suggesting an interplay between lifespan and degree of protandry. This maximizes the overlap of male and female lifespans, thereby enhancing mating success in diverse environmental conditions. Our results reveal plastic responses in mating behaviours, where diets producing smaller adults, smaller reproductive organs, and shorter sperm correlated with significantly enhanced mating effort and performance. This study highlights the complex interactions between nutrition, development, and reproductive strategies, and has significant implications for the insect bioconversion industries.
Learning from the COVID-19 pandemic: a systematic review of mathematical vaccine prioritization models
Authors: Gonzalez-Parra Gilberto , Mahmud Md Shahriar , Kadelka Claus
Published: March 2024

As the world becomes ever more connected, the chance of pandemics increases as well. The recent COVID-19 pandemic and the concurrent global mass vaccine roll-out provides an ideal setting to learn from and refine our understanding of infectious disease models for better future preparedness. In this review, we systematically analyze and categorize mathematical models that have been developed to design optimal vaccine prioritization strategies of an initially limited vaccine. As older individuals are disproportionately affected by COVID-19, the focus is on models that take age explicitly into account. The lower mobility and activity level of older individuals gives rise to non-trivial trade-offs. Secondary research questions concern the optimal time interval between vaccine doses and spatial vaccine distribution. This review showcases the effect of various modeling assumptions on model outcomes. A solid understanding of these relationships yields better infectious disease models and thus public health decisions during the next pandemic.
Impact of Multimodal Prompt Elements on Diagnostic Performance of GPT-4(V) in Challenging Brain MRI Cases
Authors: Schramm Severin , Preis Silas , Metz Marie-Christin , Jung Kirsten , Schmitz-Koep Benita , Zimmer Claus , Wiestler Benedikt , Hedderich Dennis M. , Kim Su Hwan
Published: March 2024

Background

Recent studies have explored the application of multimodal large language models (LLMs) in radiological differential diagnosis. Yet, how different multimodal input combinations affect diagnostic performance is not well understood.

Purpose

To evaluate the impact of varying multimodal input elements on the accuracy of GPT-4(V)-based brain MRI differential diagnosis.

Methods

Thirty brain MRI cases with a challenging yet verified diagnosis were selected. Seven prompt groups with variations of four input elements (image, image annotation, medical history, image description) were defined. For each MRI case and prompt group, three identical queries were performed using an LLM-based search engine (© PerplexityAI, powered by GPT-4(V)). Accuracy of LLM-generated differential diagnoses was rated using a binary and a numeric scoring system and analyzed using a chi-square test and a Kruskal-Wallis test. Results were corrected for false discovery rate employing the Benjamini-Hochberg procedure. Regression analyses were performed to determine the contribution of each individual input element to diagnostic performance.

Results

The prompt group containing an annotated image, medical history, and image description as input exhibited the highest diagnostic accuracy (67.8% correct responses). Significant differences were observed between prompt groups, especially between groups that contained the image description among their inputs, and those that did not. Regression analyses confirmed a large positive effect of the image description on diagnostic accuracy (p ≪ 0.001), as well as a moderate positive effect of the medical history (p < 0.001). The presence of unannotated or annotated images had only minor or insignificant effects on diagnostic accuracy.

Conclusion

The textual description of radiological image findings was identified as the strongest contributor to performance of GPT-4(V) in brain MRI differential diagnosis, followed by the medical history. The unannotated or annotated image alone yielded very low diagnostic performance. These findings offer guidance on the effective utilization of multimodal LLMs in clinical practice.
Re-irradiation to the Prostate using stereotactic body radiotherapy (SBRT) after initial definitive Radiotherapy – A systematic review and Meta-analysis of recent trials
Authors: Schröder Christina , Tang Hongjian , Buchali André , Zwahlen Daniel Rudolf , Förster Robert , Windisch Paul
Published: March 2024

Background

There is increasing data on re-irradiation to the prostate using stereotactic body radiotherapy (SBRT) after definite radiotherapy for prostate cancer. There has been increasing evidence on prostate re-irradiation using a C-arm LINAC or a MR LINAC in the last years. We therefore conducted this systematic review and meta-analysis on prostate re-irradiation including studies published from 2020-2023 to serve as an update on existing meta-analysis.

Methods

We searched the Pubmed and Embase databases in October 2023 with queries including combinations of “repeat”, “radiotherapy”, “prostate”, “re-irradiation”, “reirradiation”, “re treatment”, “SBRT”, “retreatment”. Publication date was set to be from 2020 to 2023. There was no limitation regarding language. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. After data extraction, heterogeneity testing using I2. Afterwards a random effects model with a restricted maximum likelihood estimator was used for estimating the combined effect. Funnel plot asymmetry was assessed visually and using Eggers test to estimate the presence of publication and/or small study bias.

Results

14 publications were included in the systematic review. The rates of acute ≥ grade 2 (G2) GU and GI toxicities reported in the included studies range from 0.0-30.0% and 0.0-25.0% respectively. For late ≥G2 GU and GI toxicity, those values are 4.0-51.8% and 0.0-25.0%. The pooled rate of acute GU and GI toxicity ≥G2 were 13% (95% CI: 7-18%) and 2% (95% CI: 0-4%). For late GU and GI toxicity ≥G2 the pooled rates were 25% (95% CI: 14-35%) and 5% (95% CI: 1-9%). The pooled 2-year biochemical recurrence-free survival was 72% (95% CI: 64-92%).

Conclusions

SBRT in the re-irradiation of radiorecurrent prostate cancer is overall safe and effective also when applied with a C-arm Linac or an MR Linac. Further prospective data are warranted.
Perceived acceptability of self-administered topical therapy for cervical precancer treatment among women undergoing cervical cancer screening in Kenya
Authors: Mungo Chemtai , Ellis Grace K , Rop Mercy , Zou Yating , Omoto Jackton , Rahangdale Lisa
Published: March 2024

Purpose

Innovative strategies are urgently needed to meet the World Health Organization’s 2030 target of treating 90% of women with precancerous cervical lesions, especially in countries most affected by cervical cancer. We assessed the acceptability of self-administered intravaginal therapies for treating cervical precancer in women undergoing cervical cancer screening and precancer treatment in Kenya.

Methods

We conducted a cross-sectional study among women aged 18 to 65 years undergoing cervical cancer screening or precancer treatment between January and October 2023 in Kisumu County, Kenya. Participants completed a questionnaire about their perceptions and perceived acceptability of self- or provider-administered topical therapies for cervical precancer treatment. Quantitative data were summarized using descriptive statistics.

Results

A total of 379 questionnaires were completed. The median age of participants was 35 years (IQR 25-62), 62% had a primary education or less, and 71% earned $5 or less daily. All participants had been screened for cervical cancer, and 191 (51%) had received precancer treatment, primarily thermal ablation. Ninety-eight percent of participants were willing to use a self-administered intravaginal therapy for cervical precancer, if available. The majority, 91%, believed their male partner would support their use. Given a choice, 63% preferred self-admiration at home compared to provider-administration of a topical therapy in the clinic, citing time and cost savings. In multivariate analysis, married women were more likely to expect partner support for self-administration than single women. Participants preferred a therapy used less frequently but for a longer duration, compared to daily use therapy with a shorter duration of use.

Conclusions

Self-administered intravaginal therapies for cervical precancer treatment are highly acceptable among women undergoing screening and precancer treatment in Kenya.
MUSCLE ENDURANCE, NEUROMUSCULAR FATIGABILITY AND COGNITIVE CONTROL DURING PROLONGED DUAL-TASK IN PEOPLE WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A CASE-CONTROL STUDY
Authors: Chatain Cyril , Vallier Jean-Marc , Paleiron Nicolas , Cucchietti Waltz Fanny , Ramdani Sofiane , Gruet Mathieu
Published: March 2024

Recent studies suggest that, compared to healthy individuals, people with chronic obstructive pulmonary disease (pwCOPD) present a reduced capacity to perform cognitive-motor dual-task (CMDT). However, these studies were focused on short-duration CMDT offering limited insight to prolonged CMDT inducing fatigue, which can be encountered in daily life. The present study aimed to explore the effect of adding a cognitive task during repeated muscle contractions on muscle endurance, neuromuscular fatigability and cognitive control in pwCOPD compared to healthy participants Thirteen pwCOPD and thirteen age- and sex-matched healthy participants performed submaximal isometric contractions of the knee extensors until exhaustion in two experimental sessions: (1) without cognitive task and (2) with a concurrent working memory task (i.e., 1-back task). Neuromuscular fatigability (as well as central and peripheral components measured by peripheral magnetic stimulation), cognitive performance and perceived muscle fatigue were assessed throughout the fatiguing tasks. Independently to the experimental condition, pwCOPD exhibited lower muscle endurance compared to healthy participants (p=0.039), mainly explained by earlier peripheral fatigue and faster attainment of higher perceived muscle fatigue (p<0.05). However, neither effect of cognitive task (p=0.223) nor interaction effect (group × condition; p=0.136) was revealed for muscle endurance. Interestingly, cognitive control was significantly reduced only in pwCOPD at the end of CMDT (p<0.015), suggesting greater difficulty for patients with dual-tasking under fatigue. These findings provide novel insights into how and why fatigue develops in COPD in dual-task context, offering a rationale for including such tasks in rehabilitation programs.
A complete mitochondrial genome of a Roman-eraPlasmodium falciparum
Authors: Llanos-Lizcano Alejandro , Hämmerle Michelle , Sperduti Alessandra , Sawyer Susanna , Zagorc Brina , Özdoğan Kadir Toykan , Guellil Meriam , Cheronet Olivia , Kuhlwilm Martin , Pinhasi Ron , Gelabert Pere
Published: March 2024

Malaria has historically been one of the leading infection-related causes of death in human populations. To this day, it continues to pose a significant public health threat in African countries, particularly among children. Humans are affected by fivePlasmodiumspecies, withPlasmodium falciparumbeing the most lethal. The study of pathogenic DNA from ancient human remains has been vital in understanding the origin, evolution, and virulence of human-infecting pathogens. However, there have been no complete pre-20th century mitochondrial DNA (mtDNA) or genomic sequences ofPlasmodium falciparumreported to date. This gap in knowledge makes it difficult to understand the genetic dynamics of this pathogen in the past. The difficulty in identifying ancient malaria cases through bioarchaeology and the infrequent presence ofPlasmodiumDNA in ancient bones contribute to these limitations. Here, we present the first complete mtDNA genome ofP. falciparumrecovered from an archaeological skeleton (a 2ndcentury CE Roman individual from Italy). The study of the 43-fold mtDNA genome supports the hypothesis of an Indian origin forP. falciparumin Europe and provides evidence for the genetic continuity of this lineage over the past 2,000 years. Additionally, our research highlights that extensive sampling may be necessary for malaria screening to gain insights into the evolution of this vector-borne disease from archaeological samples.
Step-wise evolution of azole resistance through copy number variation followed byKSR1loss of heterozygosity inCandida albicans
Authors: Zande Pétra Vande , Gautier Cécile , Kawar Nora , Maufrais Corinne , Metzner Katura , Wash Elizabeth , Beach Annette , Bracken Ryan , Maciel Eli Isael , Fernandes Caroline Mota , Solis Norma V. , Del Poeta Maurizio , Filler Scott G. , Berman Judith , Ene Iuliana V. , Selmecki Anna
Published: March 2024

Antimicrobial drug resistance poses a global health threat, requiring a deeper understanding of the evolutionary processes that lead to its emergence in pathogens. Complex evolutionary dynamics involve multiple mutations that can result in cooperative or competitive (clonal interference) effects.Candida albicans, a major fungal pathogen, displays high rates of copy number variation (CNV) and loss of heterozygosity (LOH). CNV and LOH events involve large numbers of genes and could synergize during evolutionary adaptation. Understanding the contributions of CNV and LOH to antifungal drug adaptation is challenging, especially in the context of whole-population genome sequencing. Here, we document the sequential evolution of fluconazole tolerance and then resistance in aC. albicansisolate involving an initial CNV on chromosome 4, followed by an LOH on chromosome R that involvesKSR1. Similar LOH events involvingKSR1,which encodes a reductase involved in sphingolipid biosynthesis, were also detected in independently evolved fluconazole resistant isolates. We dissect the specificKSR1codons that affect fluconazole resistance and tolerance. The combination of the chromosome 4 CNV andKSR1LOH results in a >500-fold increase in azole resistance, illustrating a compelling example of rapid, yet step-wise, interplay between CNV and LOH in drug resistance evolution.