bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiratory Syncytial Virus Bronchiolitis Before and After COVID-19 Pandemic: Has the Immunity Debt Been Paid Off?
Authors: Nenna Raffaella , Pierangeli Alessandra , Matera Luigi , Petrarca Laura , Conti Maria Giulia , Mancino Enrica , di Mattia Greta , La Regina Domenico Paolo , Virgili Fabrizio , Papoff Paola , Bonci Enea , Midulla Fabio 
Published: March 2024

Background:
Our aim was to hypothesize that the COVID-19 pandemic influenced the characteristics of viral bronchiolitis by comparing the last 3 epidemics with 3 pre-COVID-19 epidemics in infants hospitalized with bronchiolitis.

Methods:
We prospectively enrolled 637 consecutive infants (median age 3.0 ± 2.1 months, 58.5% males), hospitalized for bronchiolitis during 6 consecutive annual epidemic seasons from 2017 to 2023. All parents of the children were given a structured anamnestic questionnaire. A nasopharyngeal aspirate was tested for 15 respiratory viruses. As measures of severity, we evaluated the O2 supplementation and the admission at the pediatric intensive care unit.

Results:
A total of 166 were hospitalized with bronchiolitis in 2017–2018, 97 in 2018–2019, 69 in 2019–2020, 0 in 2020–2021, 129 in 2021–2022 and 176 in 2022–2023. Taking together the 332 bronchiolitis cases hospitalized during the 3 prepandemic seasons, they peaked between December and January; after the flat curve in 2020–2021, the cases of bronchiolitis peaked in November 2021 and in December 2022. While the 2021–2022 season registered a less severe clinical presentation, O2 supplementation and pediatric intensive care unit admissions increased in 2022–2023 with respect to the prepandemic seasons (P < 0.001).

Conclusions:
This study represents an important scientific demonstration of the impact of primary prevention measures on the epidemiology of viral infections; their fluctuations were related to the intensity of restrictive measures and to the changing trend of respiratory viruses. It is essential to predict the real temporal trend of bronchiolitis not to leave high-risk children uncovered and to guide hospitals to maintain a high level of readiness.
The association of breast surgery ASPIRE: breast pain pathway rapid evaluation project – study protocol
Authors: Hubbard Thomas J. E. , Isaac Anna T. , Cui Alice , Cutress Ramsey I. , Dave Rajiv , Ellis Katy , Fields Jo , Halliday Suzanne , Hu Jennifer , Potter Shelley , Chagla Leena , Cox Karina , Holcombe Christopher 
Published: March 2024

Background:
Breast pain accounts for 20–40% of new referrals to breast units in the UK and these patients have a very low risk of breast cancer. Patients have previously been assessed in resource-intensive, cancer-exclusion, one stop clinics, which are now failing to meet government targets due to excessive demand. UK Breast units are increasingly piloting Breast Pain-only Pathways (BPP) to assess these patients, and there is no consensus for the optimal pathway. The aim of this prospective multicentre study is to assess the safety and patient satisfaction of different BPPs to inform future BPP design and implementation.

Methods:
All UK breast units will be invited to join the ASPIRE study between January 2023 and December 2023. Units with a BPP are invited to submit their pathway for evaluation; and those without a BPP who see patients with breast pain-only in a one stop clinics setting are also invited to join the study to evaluate the traditional pathway model concurrently. Patient satisfaction assessments will be collected after their initial consultation and patient outcomes, including subsequent cancer diagnosis, will be followed up at 12 months to determine if they have cancer diagnosis after discharge to assess pathway safety.
Human spinal cord activation during filling and emptying of the bladder
Authors: Agyeman K. A. , Lee D.J. , Abedi A. , Sakellaridi S. , Kreydin E.I. , Russin J. , Lo Y.T. , Wu K. , Choi W. , Edgerton V.R. , Liu C. , Christopoulos V.N. 
Published: March 2024

AbstractRecording neural activity from the spinal cord is crucial for gaining insights into how it functions. However, the neural activity of the human spinal cord is notoriously difficult to measure. The bony and fascial enclosures combined with the relatively small anatomic size of the spinal cord make it an unfavorable target for traditional functional neuroimaging techniques. Functional ultrasound imaging (fUSI) is an emerging neuroimaging technology that represents a new platform for studying large-scale neural dynamics with high sensitivity, spatial coverage and spatiotemporal resolution. Although it was originally developed for studying brain function, fUSI was recently extended for imaging the spinal cord in animals and humans. While these studies are significant, their primary focus is on the neuroactivation of the spinal cord in response to external sensory stimulations. Here, we combined fUSI with urodynamically-controlled bladder filling and emptying to characterize the hemodynamic response of the human spinal cord during the micturition cycle. Our findings provide the first practical evidence of the existence of bladder pressure-responsive regions, whose hemodynamic signal is strongly correlated with the bladder pressure.
Monosynaptically-interconnected Network Module (MNM) Approach for High-Resolution Brain Sub-Network Analysis
Authors: Kim Sunwhi , Kim Yong-Eun , Ujihara Yusuke , Kim Il Hwan 
Published: March 2024

AbstractWe introduce the Monosynaptically-interconnected Network Module (MNM) approach, an innovative method designed for efficiently analyzing the anatomical structure and functional dynamics of specific brain network modulesin vivo. Utilizing an Intein-mediated split-Cre system combined with bidirectional adeno-associated viruses, this technique precisely targets and manipulates monosynaptically interconnected modular subnetworks in freely moving animals. We demonstrate its utility through anatomical and functional mapping of a specific MNM encompassing the prefrontal cortex (PFC), basolateral amygdala (BLA), and intermediary hub regions. Specifically, the MNM approach with Cre-reporter mice visualizes detailed network architecture and enables the tracing of axonal connections among the nodes in the network. Furthermore, integration of the MNM approach with Cre-dependent Ca2+indicator and multi-fiber photometry in freely moving mice reveals enhanced correlative network activities in social contexts. This versatile technique offers significant potential for advancing our understanding of network functions that underlie complex behaviors, providing a modular network perspective.
Graspable foods and tools elicit similar responses in visual cortex
Authors: Ritchie J. Brendan , Andrews Spencer , Vaziri-Pashkam Maryam , Baker Christopher I. 
Published: March 2024

AbstractExtrastriatal visual cortex is known to exhibit distinct response profiles to complex stimuli of varying ecological importance (e.g., faces, scenes, and tools). The dominant interpretation of these effects is that they reflect activation of distinct “category-selective” brain regions specialized to represent these and other stimulus categories. We sought to explore an alternative perspective: that the response to these stimuli is determined less by whether they form distinct categories, and more by their relevance to different forms of natural behavior. In this regard, food is an interesting test case, since it is primarily distinguished from other objects by its edibility, not its appearance, and there is evidence of food-selectivity in human visual cortex. Food is also associated with a common behavior, eating, and food consumption typically also involves the manipulation of food, often with the hands. In this context, food items share many properties in common with tools: they are graspable objects that we manipulate in self-directed and stereotyped forms of action. Thus, food items may be preferentially represented in extrastriatal visual cortex in part because of these shared affordance properties, rather than because they reflect a wholly distinct kind of category. We conducted fMRI and behavioral experiments to test this hypothesis. We found that behaviorally graspable food items and tools were judged to be similar in their action-related properties, and that the location, magnitude, and patterns of neural responses for images of graspable food items were similar in profile to the responses for tool stimuli. Our findings suggest that food-selectivity may reflect the behavioral affordances of food items rather than a distinct form of category-selectivity.
Expansion microscopy reveals unique ultrastructural features of pathogenic budding yeast species
Authors: Reza Md. Hashim , Dutta Srijana , Goyal Rohit , Shah Hiral , Dey Gautam , Sanyal Kaustuv 
Published: March 2024

AbstractCandida albicansis the most prevalent fungal pathogen isolated from patients with candidemia. As is the case for many other fungi, the complex life cycle ofC. albicanshas been challenging to study with high-resolution microscopy techniques due to its small size. We employed ultrastructure expansion microscopy (U-ExM) to directly visualise sub-cellular structures at high resolution in theC. albicansyeast and during its transition to hyphal growth. NHS-ester pan-labelling in combination with immunofluorescence (IF) provided the first comprehensive map of nucleolar and mitochondrial dynamics through theC. albicanscell cycle. Analysis of microtubules (MTs) and spindle pole bodies (SPBs) stained with marker proteins suggests that contrary to the pole-to-pole arrangement observed inSaccharomyces cerevisiae, C. albicansyeast cells display a unique side-by-side arrangement of SPBs with a short mitotic spindle and longer astral MTs (aMTs) at the pre-anaphase stage. Modifications to the established U-ExM protocol enabled the expansion of several medically relevant human fungal pathogens, revealing that the side-by-side SPB configuration is a plausible conserved feature shared by many fungal species. We highlight the power of U-ExM to investigate sub-cellular organisation and organellar dynamics at high resolution and low cost in poorly studied, medically relevant microbial pathogens.
ACE1 knockout in neurons selectively dysregulates the hippocampal renin angiotensin system and causes vascular loss
Authors: Jeon Sohee , Salvo Miranda A. , Alia Alia O. , Popovic Jelena , Zagardo Mitchell , Chandra Sidhanth , Nassan Malik , Gate David , Vassar Robert , Cuddy Leah K. 
Published: March 2024

AbstractAngiotensin I converting enzyme (ACE1) maintains blood pressure homeostasis by converting angiotensin I (angI) into angiotensin II (angII) in the renin-angiotensin system (RAS). ACE1 is expressed in the brain, where an intrinsic RAS regulates complex cognitive functions including learning and memory. ACE1 has been implicated in neurodegenerative disorders including Alzheimer’s disease (AD) and Parkinson’s disease (PD), but the mechanisms remain incompletely understood. Here, we performed single-nucleus RNA sequencing to characterize the expression RAS genes in the hippocampus and discovered thatAceis mostly expressed in CA region excitatory neurons. To gain a deeper understanding of the function of neuronal ACE1, we generated ACE1 conditional knockout (cKO) mice lacking ACE1 expression specifically in hippocampal and cortical excitatory neurons. Interestingly, ACE1 cKO mice exhibited hippocampus-dependent memory impairment in the Morris water maze, y-maze, and fear conditioning tests, but exhibited normal motor skills in rotarod. Total ACE1 level was significantly reduced in the cortex and hippocampus of ACE1 cKO mice showing that excitatory neurons are the predominant cell type expressing ACE1 in the forebrain. Despite similar reductions in total ACE1 level in both the hippocampus and cortex, the RAS pathway was dysregulated in the hippocampus only. Importantly, ACE cKO mice exhibited exacerbated age-related capillary loss selectively in the hippocampus. Here, we show selective vulnerability of the hippocampal microvasculature and RAS pathway to neuronal ACE1 knockout. Our results provide important insights into the function of ACE1 in the brain and demonstrate a connection between neuronal ACE and cerebrovascular function in the hippocampus.
Probing Phosphorylation-Induced Vibrational Couplings in CFTR by 2D IR Spectra Simulations
Authors: Zhu Jing , Chen Tunan , Zhao Yu , Ji Guangfu 
Published: March 2024

AbstractPhosphorylation of the regulator (R) domain underlies the basis for gating in the human cystic fibrosis transmembrane conductance regulator (CFTR), malfunction or down regulation of CFTR leads to defective apical chloride transport. The biophysical mechanism that underlies the regulatory effect of R domain is still unclear. Here, we utilize a combination of molecular dynamics simulations and theoretically calculated two-dimensional infrared (2D IR) spectra to probe both the structure and spectral signature of phosphorylated and unphosphorylated CFTR. We uncover an ATP-independent asymptotic movement of nucleotide binding domains (NBDs) driven by phosphorylated R domain. Utilizing non-rephasing cross ground-state bleach infrared (GB IR) spectra simulation, we overcome the interpretation hurdle caused by overlaps of multiple vibrational modes, and find distinct vibrational couplings induced by phosphorylation. By calculating exciton eigenfrequencies, we pinpoint specific vibrational couplings to individual amide I modes (carbonyl stretches), unveiling a critical role of serine residues in modulating the coupling state of neighboring amino acids. Our findings offer a bond-specific perspective on how intramolecular interactions within the R domain translate into its broader regulatory function.
Introducing ARTiMiS: A low-cost flow imaging microscope for phytoplankton monitoring in engineered and natural environments
Authors: Gincley Benjamin , Khan Farhan , Hartnett Elaine , Fisher Autumn , Pinto Ameet J. 
Published: March 2024

AbstractManual microscopy is the gold standard for phytoplankton monitoring in diverse engineered and natural environments. However, it is both labor-intensive and requires specialized training for accuracy and consistency, and therefore difficult to implement on a routine basis without significant time investment. Automation can reduce this burden by simplifying the measurement to a single indicator (e.g., chlorophyll fluorescence) measurable by a probe, or by processing samples on an automated cytometer for more granular information. The cost of commercially available flow imaging cytometers, however, poses a steep financial barrier to adoption. To overcome these labor and cost barriers, we developed ARTiMiS: the Autonomous Real-Time Microbial ‘Scope. The ARTiMiS is a low-cost flow imaging microscopy-based platform with onboard software capable of providing species-level quantitation of phytoplankton communities in real-time. ARTiMiS leverages novel multi-modal imaging and onboard machine learning-based data processing that is currently optimized for a curated and expandable database of industrially relevant microalgae. We demonstrate its operational limits, performance in identification of laboratory-cultivated microalgae, and potential for continuous monitoring of complex microalgal communities in full-scale cultivation systems.SynopsisWe introduce a platform for low-cost real-time imaging monitoring of phytoplankton and demonstrate its utility in real-time monitoring of laboratory- and full-scale microalgal cultivation systems.
Early-stage lung adenocarcinoma is driven by an injury-associated, plastic cell state dependent on a KRAS-ITGA3-SRC axis
Authors: Moye Aaron L. , Dost Antonella F. M. , Ietswaart Robert , Sengupta Shreoshi , Ya VanNashlee , Aluya Chrystal , Fahey Caroline G. , Louie Sharon M. , Paschini Margherita , Kim Carla F. 
Published: March 2024

AbstractGlycine 12 mutations in the GTPase KRAS (KRASG12) are a known initiating event for lung adenocarcinoma (LUAD) with broad clinical relevance. KRASG12mutations promote cell-intrinsic rewiring of the lung alveolar type II progenitor (AT2) cells, but to what extent such changes interplay with pathways essential for lung homeostasis and cell fate is unclear. We used single-cell RNA-seq (scRNA-seq) from AT2-mesenchyme organoid co-cultures, mouse models, and stage IA LUAD patient samples to identify conserved regulators of AT2 cell transcriptional dynamics and the impact of KRASG12Dwith temporal resolution. In AT2WTorganoids, a transient injury/plasticity state preceded AT2 self-renewal and AT1 differentiation. Early-stage AT2KRAScells exhibited perturbed gene expression dynamics most noted by retention of the injury/plasticity state. At later time points in tumorigenesis, AT2KRAScells consisted of heterogeneous populations that could be defined by either the injury state or high expression of an AT2 cell signature. The injury state in AT2KRAScells of LUAD in patients, mice, and organoids was distinguishable from AT2WTstates by altered receptor expression, including co-expression of ITGA3 and SRC. The combination of clinically relevant KRASG12Dand SRC inhibitors to target the oncogenic injury cell state impaired AT2KRASorganoid growth. Thus, an injury/plasticity signature characterized as an essential step in lung repair is used during alveolar cell self-renewal and during initiation and progression of LUAD. Early-stage lung cancer may be susceptible to intervention by targeting the oncogenic-specific nature of this cell state.
Evolution Under Thermal Stress AffectsEscherichia coli’s Resistance to Antibiotics
Authors: Bullivant Austin , Lozano-Huntelman Natalie , Tabibian Kevin , Leung Vivien , Armstrong Dylan , Dudley Henry , Savage Van M. , Rodríguez-Verdugo Alejandra , Yeh Pamela J 
Published: March 2024

AbstractExposure to both antibiotics and temperature changes can induce similar physiological responses in bacteria. Thus, changes in growth temperature may affect antibiotic resistance. Previous studies have found that evolution under antibiotic stress causes shifts in the optimal growth temperature of bacteria. However, little is known about how evolution under thermal stress affects antibiotic resistance. We examined 100+ heat-evolved strains ofEscherichia colithat evolved under thermal stress. We asked whether evolution under thermal stress affects optimal growth temperature, if there are any correlations between evolving in high temperatures and antibiotic resistance, and if these strains’ antibiotic efficacy changes depending on the local environment’s temperature. We found that: (1) surprisingly, most of the heat-evolved strains displayed a decrease in optimal growth temperature and overall growth relative to the ancestor strain, (2) there were complex patterns of changes in antibiotic resistance when comparing the heat-evolved strains to the ancestor strain, and (3) there were few significant correlations among changes in antibiotic resistance, optimal growth temperature, and overall growth.ImportanceEscherichia coli, a bacteria species often found within the intestinal tract of warm-blooded organisms, can be harmful to humans. Like all species of bacteria,E. colican evolve, particularly in the presence of stressful conditions such as extreme temperatures or antibiotic treatments. Recent evidence suggests that when encountering one source of stress, an organism’s ability to deal with a different source of stress is also affected. With global climate change and the continued evolution of antibiotic-resistant bacteria, the need to further investigate how temperature and antibiotics interact is clear. The significance of our research is in identifying possible correlations between temperature and antibiotic stress, broadening our understanding of how stressors affect organisms, and allowing for insights into possible future evolutionary pathways.
PNAbind: Structure-based prediction of protein-nucleic acid binding using graph neural networks
Authors: Sagendorf Jared M. , Mitra Raktim , Huang Jiawei , Chen Xiaojiang S. , Rohs Remo 
Published: March 2024

AbstractThe recognition and binding of nucleic acids (NAs) by proteins depends upon complementary chemical, electrostatic and geometric properties of the protein-NA binding interface. Structural models of protein-NA complexes provide insights into these properties but are scarce relative to models of unbound proteins. We present a deep learning approach for predicting protein-NA binding given the apo structure of a protein (PNAbind). Our method utilizes graph neural networks to encode spatial distributions of physicochemical and geometric properties of the protein molecular surface that are predictive of NA binding. Using global physicochemical encodings, our models predict the overall binding function of a protein and can discriminate between specificity for DNA or RNA binding. We show that such predictions made on protein structures modeled with AlphaFold2 can be used to gain mechanistic understanding of chemical and structural features that determine NA recognition. Using local encodings, our models predict the location of NA binding sites at the level of individual binding residues. Binding site predictions were validated against benchmark datasets, achieving AUROC scores in the range of 0.92-0.95. We applied our models to the HIV-1 restriction factor APOBEC3G and show that our predictions are consistent with experimental RNA binding data.
Open Iris - An Open Source Framework for Video-Based Eye-Tracking Research and Development
Authors: Sadeghi Roksana , Ressmeyer Ryan , Yates Jacob , Otero-Millan Jorge 
Published: March 2024

ABSTRACTEye-tracking is an essential tool in many fields, yet existing solutions are often limited for customized applications due to cost or lack of flexibility. We present OpenIris, an adaptable and user-friendly open-source framework for video-based eye-tracking. OpenIris is developed in C# with modular design that allows further extension and customization through plugins for different hardware systems, tracking, and calibration pipelines. It can be remotely controlled via a network interface from other devices or programs. Eye movements can be recorded online from camera stream or offline post-processing recorded videos. Example plugins have been developed to track eye motion in 3-D, including torsion. Currently implemented binocular pupil tracking pipelines can achieve frame rates of more than 500Hz. With the OpenIris framework, we aim to fill a gap in the research tools available for high-precision and high-speed eye-tracking, especially in environments that require custom solutions that are not currently well-served by commercial eye-trackers.CCS CONCEPTSApplied computing→ Life and medical sciences.