bluuebunny/crossref_metadata_2025_split huggingface dataset:
What matters to parents? A scoping review of parents’ service experiences and needs regarding genetic testing for rare diseases
Authors: Crellin Erin , Martyn Melissa , McClaren Belinda , Gaff Clara 
Published: June 2023

AbstractPatient care experiences are key to promoting better outcomes and are an essential consideration for successful implementation of genomics in paediatric care. To understand parents’ service experiences and needs regarding testing of their child for rare diseases, we conducted a scoping review. Five databases were searched (2000–2022), with 29 studies meeting the inclusion criteria. Experiences of care wholly delivered by genetic services were most commonly reported (n = 11). Results were synthesised by mapping extracted data to adapted Picker principles of person-centred care. Parents especially valued and emphasised the importance of feeling ‘cared for’, continuous relationships with clinicians, empathic communication, being kept informed while awaiting genetic test results, linkage with informational and psychosocial resources following results disclosure, and follow-up. Strategies were often proposed by authors to address long-standing unmet needs but evidence from the literature regarding their potential effectiveness was rarely provided. We conclude that ‘what matters’ to parents regarding genetic testing is not dissimilar to other aspects of care. Paediatric medical specialists have existing skill sets, trusted relationships and can apply familiar principles of ‘good’ care to enhance experiences of genetic testing. The lack of evidence for service improvement strategies highlights the pressing need to undertake rigorous design and testing of interventions alongside mainstreaming of genomics into paediatric care.
Collective excitations of a bound-in-the-continuum condensate
Authors: Grudinina Anna , Efthymiou-Tsironi Maria , Ardizzone Vincenzo , Riminucci Fabrizio , Giorgi Milena De , Trypogeorgos Dimitris , Baldwin Kirk , Pfeiffer Loren , Ballarini Dario , Sanvitto Daniele , Voronova Nina 
Published: June 2023

AbstractSpectra of low-lying elementary excitations are critical to characterize properties of bosonic quantum fluids. Usually these spectra are difficult to observe, due to low occupation of non-condensate states compared to the ground state. Recently, low-threshold Bose-Einstein condensation was realised in a symmetry-protected bound state in the continuum, at a saddle point, thanks to coupling of this electromagnetic resonance to semiconductor excitons. While it has opened the door to long-living polariton condensates, their intrinsic collective properties are still unexplored. Here we unveil the peculiar features of the Bogoliubov spectrum of excitations in this system. Thanks to the dark nature of the bound-in-the-continuum state, collective excitations lying directly above the condensate become observable in enhanced detail. We reveal interesting aspects, such as energy-flat parts of the dispersion characterized by two parallel stripes in photoluminescence pattern, pronounced linearization at non-zero momenta in one of the directions, and a strongly anisotropic velocity of sound.
Atomic model for core modifying region of human fatty acid synthase in complex with Denifanstat
Authors: Hasan S. M. Naimul , Lou Jennifer W. , Keszei Alexander F. A. , Dai David L. , Mazhab-Jafari Mohammad T. 
Published: June 2023

AbstractFatty acid synthase (FASN) catalyzes the de novo synthesis of palmitate, a 16-carbon chain fatty acid that is the primary precursor of lipid metabolism and an important intracellular signaling molecule. FASN is an attractive drug target in diabetes, cancer, fatty liver diseases, and viral infections. Here, we develop an engineered full-length human FASN (hFASN) that enables isolation of the condensing and modifying regions of the protein post-translation. The engineered protein enables electron cryo-microscopy (cryoEM) structure determination of the core modifying region of hFASN to 2.7 Å resolution. Examination of the dehydratase dimer within this region reveals that unlike its close homolog, porcine FASN, the catalytic cavity is close-ended and is accessible only through one opening in the vicinity of the active site. The core modifying region exhibits two major global conformational variabilities that describe long-range bending and twisting motions of the complex in solution. Finally, we solved the structure of this region bound to an anti-cancer drug, Denifanstat (i.e., TVB-2640), demonstrating the utility of our approach as a platform for structure guided design of future hFASN small molecule inhibitors.
A pilot metabolomic study of drug interaction with the immune response to seasonal influenza vaccination
Authors: Siddiqa Amnah , Wang Yating , Thapa Maheshwor , Martin Dominique E. , Cadar Andreia N. , Bartley Jenna M. , Li Shuzhao 
Published: June 2023

AbstractMany human diseases, including metabolic diseases, are intertwined with the immune system. The understanding of how the human immune system interacts with pharmaceutical drugs is still limited, and epidemiological studies only start to emerge. As the metabolomics technology matures, both drug metabolites and biological responses can be measured in the same global profiling data. Therefore, a new opportunity presents itself to study the interactions between pharmaceutical drugs and immune system in the high-resolution mass spectrometry data. We report here a double-blinded pilot study of seasonal influenza vaccination, where half of the participants received daily metformin administration. Global metabolomics was measured in the plasma samples at six timepoints. Metformin signatures were successfully identified in the metabolomics data. Statistically significant metabolite features were found both for the vaccination effect and for the drug-vaccine interactions. This study demonstrates the concept of using metabolomics to investigate drug interaction with the immune response in human samples directly at molecular levels.
Metal-dependent enzyme symmetry guides the biosynthetic flux of terpene precursors
Authors: Ecker Felix , Vattekkatte Abith , Boland Wilhelm , Groll Michael 
Published: June 2023

AbstractTerpenoids account for more than 60% of all natural products, and their carbon skeletons originate from common isoprenoid units of different lengths such as geranyl pyrophosphate and farnesyl pyrophosphate. Here we characterize a metal-dependent, bifunctional isoprenyl diphosphate synthase from the leaf beetle Phaedon cochleariae by structural and functional analyses. Inter- and intramolecular cooperative effects in the homodimer strongly depend on the provided metal ions and regulate the biosynthetic flux of terpene precursors to either biological defence or physiological development. Strikingly, a unique chain length determination domain adapts to form geranyl or farnesyl pyrophosphate by altering enzyme symmetry and ligand affinity between both subunits. In addition, we identify an allosteric geranyl-pyrophosphate-specific binding site that shares similarity with end-product inhibition in human farnesyl pyrophosphate synthase. Our combined findings elucidate a deeply intertwined reaction mechanism in the P. cochleariae isoprenyl diphosphate synthase that integrates substrate, product and metal-ion concentrations to harness its dynamic potential.
Leveraging rail-based mobile energy storage to increase grid reliability in the face of climate uncertainty
Authors: Moraski Jill W. , Popovich Natalie D. , Phadke Amol A. 
Published: June 2023

AbstractMaintaining reliability is increasingly challenging for electric grids as they endure more frequent extreme weather events and utilize more intermittent generation. Exploration of alternative reliability approaches is needed to effectively address these emerging issues. Here we examine the potential to use the US rail system as a nationwide backup transmission grid over which containerized batteries, or rail-based mobile energy storage (RMES), are shared among regions to meet demand peaks, relieve transmission congestion and increase resilience. We find that RMES is a feasible reliability solution for low-frequency, high-impact events and quantify its cost effectiveness relative to reliability-driven investments in transmission infrastructure and stationary capacity. Compared to new transmission lines and stationary battery capacity, deploying RMES for such events could save the power sector upwards of US$300 per kW-year and US$85 per kW-year, respectively. While no known technical barriers exclude RMES from grid participation, addressing interconnection challenges and revising regulatory frameworks is necessary for deployment at scale.
Mid-Proterozoic day length stalled by tidal resonance
Authors: Mitchell Ross N. , Kirscher Uwe 
Published: June 2023

AbstractWe present statistical analysis of a compilation of observational constraints on the Precambrian length of day and find that the day length stalled at about 19 h for about 1 billion years during the mid-Proterozoic. We suggest that the accelerative torque of atmospheric thermal tides from solar energy balanced the decelerative torque of lunar oceanic tides, temporarily stabilizing Earth’s rotation. This stalling coincides with a period of relatively limited biological evolution known as the boring billion.
Genome-wide association study of thoracic aortic aneurysm and dissection in the Million Veteran Program
Authors: Klarin Derek , Devineni Poornima , Sendamarai Anoop K. , Angueira Anthony R. , Graham Sarah E. , Shen Ying H. , Levin Michael G. , Pirruccello James P. , Surakka Ida , Karnam Purushotham R. , Roychowdhury Tanmoy , Li Yanming , Wang Minxian , Aragam Krishna G. , Paruchuri Kaavya , Zuber Verena , Shakt Gabrielle E. , Tsao Noah L. , Judy Renae L. , Vy Ha My T. , Verma Shefali S. , Rader Daniel J. , Do Ron , Bavaria Joseph E. , Nadkarni Girish N. , Ritchie Marylyn D. ,   VA Million Veteran Program, Burgess Stephen , Guo Dong-chuan , Ellinor Patrick T. , LeMaire Scott A. , Milewicz Dianna M. , Willer Cristen J. , Natarajan Pradeep , Tsao Philip S. , Pyarajan Saiju , Damrauer Scott M. 
Published: June 2023

AbstractThe current understanding of the genetic determinants of thoracic aortic aneurysms and dissections (TAAD) has largely been informed through studies of rare, Mendelian forms of disease. Here, we conducted a genome-wide association study (GWAS) of TAAD, testing ~25 million DNA sequence variants in 8,626 participants with and 453,043 participants without TAAD in the Million Veteran Program, with replication in an independent sample of 4,459 individuals with and 512,463 without TAAD from six cohorts. We identified 21 TAAD risk loci, 17 of which have not been previously reported. We leverage multiple downstream analytic methods to identify causal TAAD risk genes and cell types and provide human genetic evidence that TAAD is a non-atherosclerotic aortic disorder distinct from other forms of vascular disease. Our results demonstrate that the genetic architecture of TAAD mirrors that of other complex traits and that it is not solely inherited through protein-altering variants of large effect size.
Direct stimulation of de novo nucleotide synthesis by O-GlcNAcylation
Authors: Chen Lulu , Zhou Qi , Zhang Pingfeng , Tan Wei , Li Yingge , Xu Ziwen , Ma Junfeng , Kupfer Gary M. , Pei Yanxin , Song Qibin , Pei Huadong 
Published: June 2023

AbstractO-linked β-N-acetyl glucosamine (O-GlcNAc) is at the crossroads of cellular metabolism, including glucose and glutamine; its dysregulation leads to molecular and pathological alterations that cause diseases. Here we report thatO-GlcNAc directly regulates de novo nucleotide synthesis and nicotinamide adenine dinucleotide (NAD) production upon abnormal metabolic states. Phosphoribosyl pyrophosphate synthetase 1 (PRPS1), the key enzyme of the de novo nucleotide synthesis pathway, isO-GlcNAcylated byO-GlcNAc transferase (OGT), which triggers PRPS1 hexamer formation and relieves nucleotide product-mediated feedback inhibition, thereby boosting PRPS1 activity. PRPS1O-GlcNAcylation blocked AMPK binding and inhibited AMPK-mediated PRPS1 phosphorylation. OGT still regulates PRPS1 activity in AMPK-deficient cells. Elevated PRPS1O-GlcNAcylation promotes tumorigenesis and confers resistance to chemoradiotherapy in lung cancer. Furthermore, Arts-syndrome-associated PRPS1 R196W mutant exhibits decreased PRPS1O-GlcNAcylation and activity. Together, our findings establish a direct connection amongO-GlcNAc signals, de novo nucleotide synthesis and human diseases, including cancer and Arts syndrome.
H4K16ac activates the transcription of transposable elements and contributes to their cis-regulatory function
Authors: Pal Debosree , Patel Manthan , Boulet Fanny , Sundarraj Jayakumar , Grant Olivia A. , Branco Miguel R. , Basu Srinjan , Santos Silvia D. M. , Zabet Nicolae Radu , Scaffidi Paola , Pradeepa Madapura M. 
Published: June 2023

AbstractMammalian genomes harbor abundant transposable elements (TEs) and their remnants, with numerous epigenetic repression mechanisms enacted to silence TE transcription. However, TEs are upregulated during early development, neuronal lineage, and cancers, although the epigenetic factors contributing to the transcription of TEs have yet to be fully elucidated. Here, we demonstrate that the male-specific lethal (MSL)-complex-mediated histone H4 acetylation at lysine 16 (H4K16ac) is enriched at TEs in human embryonic stem cells (hESCs) and cancer cells. This in turn activates transcription of subsets of full-length long interspersed nuclear elements (LINE1s, L1s) and endogenous retrovirus (ERV) long terminal repeats (LTRs). Furthermore, we show that the H4K16ac-marked L1 and LTR subfamilies display enhancer-like functions and are enriched in genomic locations with chromatin features associated with active enhancers. Importantly, such regions often reside at boundaries of topologically associated domains and loop with genes. CRISPR-based epigenetic perturbation and genetic deletion of L1s reveal that H4K16ac-marked L1s and LTRs regulate the expression of genes in cis. Overall, TEs enriched with H4K16ac contribute to the cis-regulatory landscape at specific genomic locations by maintaining an active chromatin landscape at TEs.
Hantzsch reaction using copper nitrate hydroxide-containing mesoporous silica nanoparticle with C3N4 framework as a novel powerful and reusable catalyst
Authors: Rahmati Ensiyeh , Rafiee Zahra 
Published: June 2023

AbstractCopper nitrate hydroxide (CNH)-containing mesoporous silica nanoparticle (MSN) with g-C3N4 framework (MSN/C3N4/CNH) was fabricated via a four-step hydrothermal synthesis method. Functionalized MSN-based C3N4 was prepared, decorated with CNH, and identified by different physicochemical techniques such as FT-IR, XRD, SEM, EDX, and STA analyses. Then, MSN/C3N4/CNH composite was utilized as a robust catalyst for the fast fabrication of biologically active polyhydroquinoline derivatives with high yields between 88 and 97% via Hantzsch reaction under mild reaction conditions and short reaction time (within 15 min) owing to synergistic influence of Lewis acid and base sites. Moreover, MSN/C3N4/CNH can be straightforwardly recovered and used up to six reaction cycles without a conspicuous decrease in efficiency.
T cell repertoire breadth is associated with the number of acute respiratory infections in the LoewenKIDS birth cohort
Authors: Paschold Lisa , Gottschick Cornelia , Langer Susan , Klee Bianca , Diexer Sophie , Aksentijevich Ivona , Schultheiß Christoph , Purschke Oliver , Riese Peggy , Trittel Stephanie , Haase Roland , Dressler Frank , Eberl Wolfgang , Hübner Johannes , Strowig Till , Guzman Carlos A. , Mikolajczyk Rafael , Binder Mascha 
Published: June 2023

AbstractWe set out to gain insight into peripheral blood B and T cell repertoires from 120 infants of the LoewenKIDS birth cohort to investigate potential determinants of early life respiratory infections. Low antigen-dependent somatic hypermutation of B cell repertoires, as well as low T and B cell repertoire clonality, high diversity, and high richness especially in public T cell clonotypes reflected the immunological naivety at 12 months of age when high thymic and bone marrow output are associated with relatively few prior antigen encounters. Infants with inadequately low T cell repertoire diversity or high clonality showed higher numbers of acute respiratory infections over the first 4 years of life. No correlation of T or B cell repertoire metrics with other parameters such as sex, birth mode, older siblings, pets, the onset of daycare, or duration of breast feeding was noted. Together, this study supports that—regardless of T cell functionality—the breadth of the T cell repertoire is associated with the number of acute respiratory infections in the first 4 years of life. Moreover, this study provides a valuable resource of millions of T and B cell receptor sequences from infants with available metadata for researchers in the field.
Prognostic value of central blood pressure on the outcomes of embolic stroke of undetermined source
Authors: Han Minho , Heo JoonNyung , Lee Il Hyung , Kim Joon Ho , Lee Hyungwoo , Jung Jae Wook , Lim In Hwan , Hong Soon-Ho , Kim Young Dae , Nam Hyo Suk 
Published: June 2023

AbstractWe investigated the prognostic impact of central blood pressure (BP) on outcomes in patients with embolic stroke of undetermined source (ESUS). The prognostic value of central BP according to ESUS subtype was also evaluated. We recruited patients with ESUS and data on their central BP parameters (central systolic BP [SBP], central diastolic BP [DBP], central pulse pressure [PP], augmentation pressure [AP], and augmentation index [AIx]) during admission. ESUS subtype classification was arteriogenic embolism, minor cardioembolism, two or more causes, and no cause. Major adverse cardiovascular event (MACE) was defined as recurrent stroke, acute coronary syndrome, hospitalization for heart failure, or death. Over a median of 45.8 months, 746 patients with ESUS were enrolled and followed up. Patients had a mean age of 62.8 years, and 62.2% were male. Multivariable Cox regression analysis showed that central SBP and PP were associated with MACE. All-cause mortality was independently associated with AIx. In patients with no cause ESUS, central SBP and PP, AP, and AIx were independently associated with MACE. AP and AIx were independently associated with all-cause mortality (all p < 0.05). We demonstrated that central BP can predict poor long-term prognosis in patients with ESUS, especially those with the no cause ESUS subtype.
NISNet3D: three-dimensional nuclear synthesis and instance segmentation for fluorescence microscopy images
Authors: Wu Liming , Chen Alain , Salama Paul , Winfree Seth , Dunn Kenneth W. , Delp Edward J. 
Published: June 2023

AbstractThe primary step in tissue cytometry is the automated distinction of individual cells (segmentation). Since cell borders are seldom labeled, cells are generally segmented by their nuclei. While tools have been developed for segmenting nuclei in two dimensions, segmentation of nuclei in three-dimensional volumes remains a challenging task. The lack of effective methods for three-dimensional segmentation represents a bottleneck in the realization of the potential of tissue cytometry, particularly as methods of tissue clearing present the opportunity to characterize entire organs. Methods based on deep learning have shown enormous promise, but their implementation is hampered by the need for large amounts of manually annotated training data. In this paper, we describe 3D Nuclei Instance Segmentation Network (NISNet3D) that directly segments 3D volumes through the use of a modified 3D U-Net, 3D marker-controlled watershed transform, and a nuclei instance segmentation system for separating touching nuclei. NISNet3D is unique in that it provides accurate segmentation of even challenging image volumes using a network trained on large amounts of synthetic nuclei derived from relatively few annotated volumes, or on synthetic data obtained without annotated volumes. We present a quantitative comparison of results obtained from NISNet3D with results obtained from a variety of existing nuclei segmentation techniques. We also examine the performance of the methods when no ground truth is available and only synthetic volumes were used for training.
Improving efficiency of semitransparent organic solar cells by constructing semitransparent microcavity
Authors: Annabi Milani Elmira , Piralaee Mina , Asgari Asghar 
Published: June 2023

AbstractSemitransparent organic solar cells have become attractive recently because of their photon harvesting in the near-infrared and ultraviolet range and passing in the visible light region. Semitransparent organic solar cells with Glass/MoO3/Ag/MoO3/PBDB-T:ITIC/TiO2/Ag/PML/1DPCs structure have been studied in this work and the effects microcavity with 1-dimensional photonic crystals (1DPCs) on the solar cell performance such as the power conversion efficiency, the average visible transmittance, Light utilization efficiency (LUE), the color coordinates in the CIE color space, and CIE LAB are investigated. The analytical calculation including the density of exactions and their displacement is used to model the devices. The model shows that the presence of microcavity can improve the power conversion efficiency by about %17 in comparison with the absence of microcavity. Although the transmission is decreasing slightly, microcavity does not change the color coordinates much. The device can transmit high-quality light with a near-white sensation to the human eye.
Designing Ising machines with higher order spin interactions and their application in solving combinatorial optimization
Authors: Bashar Mohammad Khairul , Shukla Nikhil 
Published: June 2023

AbstractThe Ising model provides a natural mapping for many computationally hard combinatorial optimization problems (COPs). Consequently, dynamical system-inspired computing models and hardware platforms that minimize the Ising Hamiltonian, have recently been proposed as a potential candidate for solving COPs, with the promise of significant performance benefit. However, prior work on designing dynamical systems as Ising machines has primarily considered quadratic interactions among the nodes. Dynamical systems and models considering higher order interactions among the Ising spins remain largely unexplored, particularly for applications in computing. Therefore, in this work, we propose Ising spin-based dynamical systems that consider higher order (> 2) interactions among the Ising spins, which subsequently, enables us to develop computational models to directly solve many COPs that entail such higher order interactions (i.e., COPs on hypergraphs). Specifically, we demonstrate our approach by developing dynamical systems to compute the solution for the Boolean NAE-K-SAT (K ≥ 4) problem as well as solve the Max-K-Cut of a hypergraph. Our work advances the potential of the physics-inspired ‘toolbox’ for solving COPs.