bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simple mathematical model and physical device to estimate a woman-specific probability of skilled birth assistance and associated benefit of maternity waiting home stay
Authors: Gallien Jérémie , Chen George , Zhang Yi , Du Yuhang , Lori Jody , Sieka Joseph , Tehoungue Bentoe 
Published: April 2024

AbstractThis paper presents a simple mathematical model and an associated physical device to predict (i) the risk that a woman’s active labor will begin without a skilled birth attendant based on her parity and anticipated time to access skilled care; and (ii) the extent to which that risk may be reduced by moving to a maternity waiting home some time before her expected due date. This tool is designed to facilitate more systematic discussions and better-informed decisions about labour care access arrangements during antenatal consultations.
Scalable Risk Stratification for Heart Failure Using Artificial Intelligence applied to 12-lead Electrocardiographic Images: A Multinational Study
Authors: Dhingra Lovedeep S , Aminorroaya Arya , Sangha Veer , Camargos Aline Pedroso , Asselbergs Folkert W , Brant Luisa CC , Barreto Sandhi M , Ribeiro Antonio Luiz P , Krumholz Harlan M , Oikonomou Evangelos K , Khera Rohan 
Published: April 2024

ABSTRACTBackgroundCurrent risk stratification strategies for heart failure (HF) risk require either specific blood-based biomarkers or comprehensive clinical evaluation. In this study, we evaluated the use of artificial intelligence (AI) applied to images of electrocardiograms (ECGs) to predict HF risk.MethodsAcross multinational longitudinal cohorts in the integrated Yale New Haven Health System (YNHHS) and in population-based UK Biobank (UKB) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we identified individuals without HF at baseline. Incident HF was defined based on the first occurrence of an HF hospitalization. We evaluated an AI-ECG model that defines the cross-sectional probability of left ventricular dysfunction from a single image of a 12-lead ECG and its association with incident HF. We accounted for the competing risk of death using the Fine-Gray subdistribution model and evaluated the discrimination using Harrel’s c-statistic. The pooled cohort equations to prevent HF (PCP-HF) were used as a comparator for estimating incident HF risk.ResultsAmong 231,285 individuals at YNHHS, 4472 had a primary HF hospitalization over 4.5 years (IQR 2.5-6.6) of follow-up. In UKB and ELSA-Brasil, among 42,741 and 13,454 people, 46 and 31 developed HF over a follow-up of 3.1 (2.1-4.5) and 4.2 (3.7-4.5) years, respectively. A positive AI-ECG screen portended a 4-fold higher risk of incident HF among YNHHS patients (age-, sex-adjusted HR [aHR] 3.88 [95% CI, 3.63-4.14]). In UKB and ELSA-Brasil, a positive-screen ECG portended 13- and 24-fold higher hazard of incident HF, respectively (aHR: UKBB, 12.85 [6.87-24.02]; ELSA-Brasil, 23.50 [11.09-49.81]). The association was consistent after accounting for comorbidities and the competing risk of death. Higher model output probabilities were progressively associated with a higher risk for HF. The model’s discrimination for incident HF was 0.718 in YNHHS, 0.769 in UKB, and 0.810 in ELSA-Brasil. Across cohorts, incorporating model probability with PCP-HF yielded a significant improvement in discrimination over PCP-HF alone.ConclusionsAn AI model applied to images of 12-lead ECGs can identify those at elevated risk of HF across multinational cohorts. As a digital biomarker of HF risk that requires just an ECG image, this AI-ECG approach can enable scalable and efficient screening for HF risk.
Cryo-EM insight into hydrogen positions and water networks in photosystem II
Authors: Hussein Rana , Graça André , Forsman Jack , Aydin A. Orkun , Hall Michael , Gaetcke Julia , Chernev Petko , Wendler Petra , Dobbek Holger , Messinger Johannes , Zouni Athina , Schröder Wolfgang P. 
Published: April 2024

AbstractPhotosystem II starts the photosynthetic electron transport chain that converts solar energy into chemical energy and thereby sustains life on Earth. It catalyzes two chemical reactions, plastoquinone reduction and water oxidation to molecular oxygen, which both are performed at sequestered sites. While it is known that proton-coupled electron transfer is crucial for these processes, the molecular details have remained speculative due to incomplete structural data. Thus, we collected high-resolution cryo-EM data of photosystem II fromThermosynechococcus vestitus. The advanced structure (1.71 Å) reveals several previously unditected occupied water binding sites and more than half of the hydrogen and proton positions of the protein. This unprecedented insight into the structure of photosystem II significantly enhances our understanding of its intricate protein-water-cofactor interactions enabling solar-driven catalysis.One sentence summaryCryo-EM structure of PSII at 1.71 Å resolution reveals over 50% of hydrogen and proton sites and additional water binding sites, aiding catalytic insight.
Functional recruitment and connectivity of the cerebellum supports the emergence of Theory of Mind in early childhood
Authors: Manoli Aikaterina , Van Overwalle Frank , Grosse Wiesmann Charlotte , Valk Sofie L. 
Published: April 2024

AbstractThere is accumulating evidence that the human cerebellum is heavily implicated in adult social cognition. Yet, its involvement in the development of Theory of Mind (ToM), a hallmark of social cognition, remains elusive. In a functional MRI study involving children with emerging ToM abilities (N=41, age range: 3-12 years) and adults (N=78), we showed that children with ToM abilities activated cerebellar Crus I-II in response to ToM events during a movie-watching task, similar to adults. This activation was absent in children lacking ToM abilities. Functional connectivity profiles between cerebellar and cerebral ToM regions differed as a function of children’s ToM abilities. Notably, task-driven connectivity shifted from upstream to downstream connections between cerebellar and cerebral ToM regions from childhood to adulthood. Greater dependence on connections emerging from the cerebellum early in life suggests an important role of the cerebellum in establishing the cognitive processes underlying ToM in childhood and thus for the undisrupted development of social cognition.
Potassium rhythms couple the circadian clock to the cell cycle
Authors: Gil Rodríguez Sergio , Crosby Priya , Hansen Louise L. , Grünewald Ellen , Beale Andrew D. , Spangler Rebecca K. , Rabbitts Beverley M. , Partch Carrie L. , Stangherlin Alessandra , O’Neill John S. , van Ooijen Gerben 
Published: April 2024

AbstractCircadian (∼24 h) rhythms are a fundamental feature of life, and their disruption increases the risk of infectious diseases, metabolic disorders, and cancer1–6. Circadian rhythms couple to the cell cycle across eukaryotes7,8but the underlying mechanism is unknown. We previously identified an evolutionarily conserved circadian oscillation in intracellular potassium concentration, [K+]i9,10. As critical events in the cell cycle are regulated by intracellular potassium11,12, an enticing hypothesis is that circadian rhythms in [K+]iform the basis of this coupling. We used a minimal model cell, the algaOstreococcus tauri,to uncover the role of potassium in linking these two cycles. We found direct reciprocal feedback between [K+]iand circadian gene expression. Inhibition of proliferation by manipulating potassium rhythms was dependent on the phase of the circadian cycle. Furthermore, we observed a total inhibition of cell proliferation when circadian gene expression is inhibited. Strikingly, under these conditions a sudden enforced gradient of extracellular potassium was sufficient to induce a round of cell division. Finally, we provide evidence that interactions between potassium and circadian rhythms also influence proliferation in mammalian cells. These results establish circadian regulation of intracellular potassium levels as a primary factor coupling the cell- and circadian cycles across diverse organisms.
LASSO Based Analysis for Prediction of Prognostic Signature Genes Associated with Breast Cancer
Authors: Guha Souvik 
Published: April 2024

AbstractBackgroundCancer is a genetic disease, where gene alterations play a significant role in the disease onset and pathogenesis. Analysis of the underlying gene interaction pathways could reveal new biomarkers and could also potentially help in the development of targeted drugs for therapeutics. Microarray techniques have emerged as powerful tools capable of simultaneously measuring the expression levels of thousands of genes, making them invaluable in cancer biology research. However, the processing of the resultant datasets poses significant challenges due to their high dimensionality. Also, feature extraction becomes essential to discern the crucial features within these extensive datasets. To mitigate these difficulties advanced computational techniques like Machine Learning (ML) could be instrumental. LASSO-regression-based classification is an advanced ML technique that can help in feature selection by evaluating individual parameters like genes.MethodsThis study focuses on uncovering key prognostic genes for breast cancer using a combination of LASSO regression-based classifier and statistical bioinformatics models. Differentially expressed genes (DEGs) were identified using the “Limma” package in R, and significant genes were further filtered using the LASSO-based classifier significance coefficient. Genes common to both methods were considered as the focus of this study. Additionally, Protein-Protein Interaction (PPI) networks of these key genes were constructed using STRING, and hub genes, significant modules, and associated genes were identified using Cytoscape.ResultsThis study identified CCR8, CXCL11, CCL23, CCL24, CCL28, and CCL21 as signature prognostic genes for breast cancer, revealing a strong association between chemokines and breast cancer pathogenesis. Extensive literature searches were conducted to validate and confirm their prognostic significance in the disease.ConclusionThese findings are pivotal for enhancing our comprehension of the pathways involved in breast cancer. Additionally, they hold promise as novel biomarkers for diagnostic purposes and may also reveal significant therapeutic targets for the management of breast cancer.
BEAN and HABAS: Polyphyletic insertions in RNAP that point to deep-time evolutionary divergence of bacteria
Authors: Alvarez-Carreño Claudia , Huynh Angela T. , Petrov Anton S. , Orengo Christine , Williams Loren Dean 
Published: April 2024

AbstractThe β and β’ subunits of the RNA polymerase (RNAP) are large proteins with complex multi-domain architectures that include several insertional domains. Here, we analyze the multi-domain organizations of bacterial RNAP-β and RNAP-β’ using sequence, experimentally determined structures and AlphaFold structure predictions. We observe that bacterial lineage-specific domains in RNAP-β belong to a group of domains that we call BEAN (Broadly Embedded ANnex) and that in RNAP-β’, bacterial lineage-specific domains are HAmmerhead/BArrel-Sandwich Hybrid (HABAS) domains. The BEAN domain has a characteristic three-dimensional structure composed of two square bracket-like elements that are antiparallel relative to each other. The HABAS domain contains a four-stranded open β-sheet with a GD-box-like motif in one of the β-strands and the adjoining loop. The BEAN domain is identified not only in the bacterial RNAP-β’, but also in the archaeal version of universal ribosomal protein L10. The HABAS domain is observed as an insertional domain in several metabolic proteins. The phylogenetic distributions of bacterial lineage-specific insertional domains of β and β’ subunits of RNAP follow the Tree of Life. The presence of insertional domains can help establish a relative timeline of events in the evolution of a protein because insertion is inferred to post-date the base domain. We discuss mechanisms that might account for the discovery of homologous insertional domains in non-equivalent locations in bacteria and archaea.
Proteomic Assessment of SKBR3/HER2+ Breast Cancer Cellular Response to Lapatinib and Investigational Ipatasertib Kinase Inhibitors
Authors: Karcini Arba , Mercier Nicole R. , Lazar Iulia M. 
Published: April 2024

AbstractModern cancer treatment approaches aim at achieving cancer remission by using targeted and personalized therapies, as well as harnessing the power of the immune system to recognize and eliminate the cancer cells. To overcome a relatively short-lived response due to the development of resistance to the administered drugs, combination therapies have been pursued, as well. To expand the outlook of combination therapies, the objective of this study was to use high-throughput data generation technologies such as mass spectrometry and proteomics to investigate the response of HER2+ breast cancer cells to a mixture of two kinase inhibitors that has not been adopted yet as a standard treatment regime. The broader landscape of biological processes that are affected by inhibiting two major pathways that sustain the growth and survival of cancer cells, i.e., EGFR and PI3K/AKT, was investigated by treating SKBR3/HER2+ breast cancer cells with Lapatinib or a mixture of Lapatinib/Ipatasertib small molecule drugs. Changes in protein expression and/or activity in response to the drug treatments were assessed by using two complementary quantitative proteomic approaches based on peak area and peptide spectrum match measurements. Over 900 proteins matched by three unique peptide sequences (FDR<0.05) were affected by the exposure of cells to the drugs. The work corroborated the anti-proliferative activity of Lapatinib and Ipatasertib, and, in addition to cell cycle and growth arrest processes enabled the identification of several multi-functional proteins with roles in cancer-supportive hallmark processes. Among these, immune response, adhesion and migration emerged as particularly relevant to the ability to effectively suppress the proliferation and dissemination of cancer cells. The supplementation of Lapatinib with Ipatasertib further affected the expression or activity of additional transcription factors and proteins involved in gene expression, trafficking, DNA repair, and development of multidrug resistance. Furthermore, over fifty of the affected proteins represented approved or investigational targets in the DrugBank database, which through their protein-protein interaction networks can inform the selection of effective therapeutic partners. Altogether, our findings exposed a broad plethora of yet untapped opportunities that can be further explored for enhancing the anti-cancer effects of each drug as well as of many other multi-drug therapies that target the EGFR/ERBB2 and PI3K/AKT pathways. The data are available via ProteomeXchange with identifier PXD051094.
Molecular Identification ofEchinococcusspp. and other Taeniid Tapeworms Using Next Generation Sequence Analysis of PCR Amplified 18s rRNA gene
Authors: Abu-Helu Rasmi , Kokaly George , Nojoum Sajeda , Matouk Imad , Ibrahim Murad , Abbasi Ibrahim 
Published: April 2024

AbstractCystic echinococcosis (CE) is a prevalent zoonotic disease caused by Echinococcus granulosus, with cosmopolitan distribution. The parasite is transmitted cyclically between canines and numerous intermediate herbivorous livestock animals. Also other taeniid tapeworm could infect domestic dogs and they pose significant veterinary and public health concerns worldwide. This study aimed to develop a sensitive molecular method for detecting Echinococcus spp. DNA in dog fecal samples using next-generation sequencing (NGS). A set of PCR primers targeting conserved regions of Taeniid tapeworms’ 18s rRNA genes was designed and tested for amplifying genomic DNA from various tapeworm species. The PCR system demonstrated high sensitivity, amplifying DNA from all tested tapeworm species, with differences observed in amplified band sizes. The primers were adapted for NGS analysis by adding forward and reverse adapters, enabling sequencing of amplified DNA fragments. Application of the developed PCR system to dog fecal samples collected from Yatta town, Palestine, revealed the presence ofE. granulosusDNA in five out of 50 samples. NGS analysis confirmed the specificity of the amplified DNA fragments, showing 98-99% similarity with the 18s rDNA gene ofE. granulosus. This study demonstrates the utility of NGS-based molecular methods for accurate and sensitive detection of Echinococcus spp. in dog fecal samples, providing valuable insights for epidemiological surveillance and control programs of echinococcosis in endemic regions.Author SummaryCystic echinococcosis, or hydatidosis, is a serious and chronic zoonotic disease in humans caused by the dog tapewormEchinococcus granulosus. The disease is transmitted cyclically between canines and numerous herbivorous livestock animals. DeterminingE. granulosusinfection in dogs is crucial for assessing infection risk and identifying new foci of active infections. The infection rate in dogs is also necessary for evaluating transmission dynamics and assessing the efficacy of control programs. In this study, we present a PCR system based on amplification of the 18S rDNA. New primers were designed following an alignment of various taeniid tapeworms’ 18S rDNA sequences. The current PCR system was adapted to be used in amplicon sequencing utilizing next-generation sequencing technology. This strategy enables accurate detection of tapeworm DNA extracted from dogs’ fecal samples and provides quantitative measurement of taeniid infection in dogs.
A large-scale and long-term experiment to identify effectiveness of ecosystem restoration
Authors: Elo Merja , Kareksela Santtu , Ovaskainen Otso , Abrego Nerea , Niku Jenni , Taskinen Sara , Aapala Kaisu , Kotiaho Janne S. 
Published: April 2024

ABSTRACTEcosystem restoration will increase following the ambitious international targets, which calls for a rigorous evaluation of restoration effectiveness. Studies addressing restoration effectiveness across ecosystems have thus far shown varying and unpredictable patterns. A rigorous assessment of the factors influencing restoration effectiveness is best done with large-scale and long-term experimental data. Here, we present results from a well replicated long-term before-after control-impact experiment on restoration of forestry-drained boreal peatland ecosystems. Our data comprise 151 sites, representing six ecosystem types. Vegetation sampling has been conducted to the species level before restoration and two, five and ten years after restoration. We show that, on average, restoration stops and reverses the trend of further degradation. The variation in restoration outcomes largely arises from ecosystem types: restoration of nutrient-poor ecosystems has higher probability of failure. Our experiment provides clear evidence that restoration can be effective in halting the biodiversity loss of degraded ecosystems, although ecosystem attributes can affect the restoration outcome. These findings underlie the need for evidence-based prioritization of restoration efforts across ecosystems.
Time-based shifts in xylem vulnerability curves of angiosperms based on the flow-centrifuge method
Authors: Silva Luciano M. , Pfaff Jonas , Pereira Luciano , Miranda Marcela T. , Jansen Steven 
Published: April 2024

AbstractCentrifuges provide a fast and standard approach to quantify embolism resistance of xylem in vulnerability curves (VCs). Traditionally, embolism formation in centrifuge experiments is assumingly driven by centrifuge speed, and thus pressure, but unaffected by spin time. Here, we explore to what extent embolism resistance is not only pressure but also spin time dependent, and hypothesise that time-stable hydraulic conductivity (Kh) values could shift VCs. We quantified time-based shifts in flow- centrifuge VCs and their parameter estimations for six angiosperm species by measuring Khat regular intervals over 15 minutes of spinning at a particular speed before a higher speed was applied to the same sample. We compared various VCs per sample based on cumulative spin time, and modelled the relationship between Kh, xylem water potential (Ψ), and spin time. Time-based changes of Khshowed considerable increases and decreases at low and high centrifuge speeds, respectively, which generally shifted VCs towards more positive Ψ values. Values corresponding to 50% loss of hydraulic conductivity (P50) increased up to 0.72 MPa inAcer pseudoplatanus, and on average by 8.5% for all six species compared to VCs that did not consider spin time. By employing an asymptotic exponential model, we estimated time-stable Kh, which improved the statistical significance of VCs in 5 of the 6 species studied. This model also revealed the instability of VCs at short spin times, and showed that embolism formation in flow-centrifuges followed a saturating exponential growth curve. Although pressure remains the major determinant of embolism formation, spin time should be considered in flow- centrifuge VCs to avoid overestimation of embolism resistance. This spin-time artefact is species- specific, and likely based on relatively slow gas diffusion associated with embolism spreading. It can be minimized by determining time-stable Khvalues for each centrifuge speed, without considerably extending the experimental time to construct VCs.
Mid-infrared photoacoustic brain imaging enabled by cascaded gas-filled hollow-core fiber lasers
Authors: Zhang Cuiling , Sui Kunyang , Meneghetti Marcello , Antonio-Lopez Jose Enrique , Dasa Manoj K. , Berg Rune W. , Amezcua-Correa Rodrigo , Wang Yazhou , Markos Christos 
Published: April 2024

AbstractSignificanceExtending the photoacoustic microscopy (PAM) into the mid-infrared (MIR) molecular fingerprint region constitutes a promising route towards label-free imaging of biological molecular structures. Realizing this objective requires a high-energy nano-second MIR laser source. However, existing MIR laser technologies are limited to either low pulse energy or free-space structure which is sensitive to environmental conditions. Fiber lasers are promising technologies for PAM for their potential of offering both high pulse energy and robust performance against environmental conditions. However, MIR high energy fiber laser has not yet been used for PAM because it is still at the infant research stage.AimWe aim to employ the emerging gas-filled anti-resonant hollow-core fiber (ARHCF) laser technology for MIR-PAM for the purpose of imaging myelin-rich regions in a mouse brain.ApproachThis laser source is developed with a ∼2.75 μJ high-pulse-energy nano-second laser at 3.4 μm, targeting the main absorption band of myelin sheaths, the primary chemical component of axons in the central nervous system. The laser mechanism relies on two-orders gas-induced vibrational stimulated Raman scattering (SRS) for nonlinear wavelength conversion, starting from a 1060 nm pump laser to 1409 nm through the 1storder Stokes generation in the nitrogen-filled 1ststage ARHCF, then, from 1409 nm to 3.4 μm through the 2ndstage hydrogen-filled ARHCF.ResultsThe developed Raman laser was used for the first time for transmission-mode MIR-PAM of mouse brain regions containing rich myelin structures.ConclusionsThis work pioneers the potential use of high-energy and nano-second gas-filled ARHCF laser source to MIR-PAM, with a first attempt to report this kind of fiber laser source for PAM of lipid-rich myelin regions in a mouse brain. The proposed ARHCF laser technology is also expected to generate high-energy pulses at the ultraviolet (UV) region, which can significantly improve the lateral resolution of the PAM.