bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased AID results in mutations at the CRLF2 locus implicated in Latin American ALL health disparities
Authors: Rangel Valeria , Sterrenberg Jason N. , Garawi Aya , Mezcord Vyanka , Folkerts Melissa L. , Calderon Sabrina E. , Garcia Yadhira E. , Wang Jinglong , Soyfer Eli M. , Eng Oliver S. , Valerin Jennifer B. , Tanjasiri Sora Park , Quintero-Rivera Fabiola , Seldin Marcus M. , Masri Selma , Frock Richard L. , Fleischman Angela G. , Pannunzio Nicholas R. 
Published: July 2024

AbstractActivation-induced cytidine deaminase (AID) is a B cell-specific mutator required for antibody diversification. However, it is also implicated in the etiology of several B cell malignancies. Evaluating the AID-induced mutation load in patients at-risk for certain blood cancers is critical in assessing disease severity and treatment options. We have developed a digital PCR (dPCR) assay that allows us to quantify mutations resulting from AID modification or DNA double-strand break (DSB) formation and repair at sites known to be prone to DSBs. Implementation of this assay shows that increased AID levels in immature B cells increase genome instability at loci linked to chromosomal translocation formation. This includes the CRLF2 locus that is often involved in translocations associated with a subtype of acute lymphoblastic leukemia (ALL) that disproportionately affects Hispanics, particularly those with Latin American ancestry. Using dPCR, we characterize the CRLF2 locus in B cell-derived genomic DNA from both Hispanic ALL patients and healthy Hispanic donors and found increased mutations in both, suggesting that vulnerability to DNA damage at CRLF2 may be driving this health disparity. Our ability to detect and quantify these mutations will potentiate future risk identification, early detection of cancers, and reduction of associated cancer health disparities.
Designed 2D protein crystals as dynamic molecular gatekeepers for a solid-state device
Authors: Vijayakumar Sanahan , Alberstein Robert G. , Zhang Zhiyin , Lu Yi-Sheng , Chan Adriano , Wahl Charlotte E. , Ha James S. , Hunka Deborah E. , Boss Gerry R. , Sailor Michael J. , Tezcan F. Akif 
Published: July 2024

AbstractThe sensitivity and responsiveness of living cells to environmental changes are enabled by dynamic protein structures, inspiring efforts to construct artificial supramolecular protein assemblies. However, despite their sophisticated structures, designed protein assemblies have yet to be incorporated into macroscale devices for real-life applications. We report a 2D crystalline protein assembly of C98/E57/E66L-rhamnulose-1-phosphate aldolase (CEERhuA) that selectively blocks or passes molecular species when exposed to a chemical trigger. CEERhuA crystals are engineered via cobalt(II) coordination bonds to undergo a coherent conformational change from a closed state (pore dimensions <1 nm) to an ajar state (pore dimensions ~4 nm) when exposed to an HCN(g) trigger. When layered onto a mesoporous silicon (pSi) photonic crystal optical sensor configured to detect HCN(g), the 2D CEERhuA crystal layer effectively blocks interferents that would otherwise result in a false positive signal. The 2D CEERhuA crystal layer opens in selective response to low-ppm levels of HCN(g), allowing analyte penetration into the pSi sensor layer for detection. These findings illustrate that designed protein assemblies can function as dynamic components of solid-state devices in non-aqueous environments.
Global regulation via modulation of ribosome pausing by the ABC-F protein EttA
Authors: Ousalem Farès , Ngo Saravuth , Oïffer Thomas , Omairi-Nasser Amin , Hamon Marion , Monlezun Laura , Boël Grégory 
Published: July 2024

AbstractHaving multiple rounds of translation of the same mRNA creates dynamic complexities along with opportunities for regulation related to ribosome pausing and stalling at specific sequences. Yet, mechanisms controlling these critical processes and the principles guiding their evolution remain poorly understood. Through genetic, genomic, physiological, and biochemical approaches, we demonstrate that regulating ribosome pausing at specific amino acid sequences can produce ~2-fold changes in protein expression levels which strongly influence cell growth and therefore evolutionary fitness. We demonstrate, both in vivo and in vitro, that the ABC-F protein EttA directly controls the translation of mRNAs coding for a subset of enzymes in the tricarboxylic acid (TCA) cycle and its glyoxylate shunt, which modulates growth in some chemical environments. EttA also modulates expression of specific proteins involved in metabolically related physiological and stress-response pathways. These regulatory activities are mediated by EttA rescuing ribosomes paused at specific patterns of negatively charged residues within the first 30 amino acids of nascent proteins. We thus establish a unique global regulatory paradigm based on sequence-specific modulation of translational pausing.
Growth and mineralization of fetal mouse long bones under microgravity and daily 1 g gravity exposure
Authors: van Loon Jack J. W. A. , Berezovska Olga P. , Bervoets Theodorus J. M. , Montufar-Solis Dina , Semeins Cor M. , Zandieh-Doulabi Behrouz , Rodionova P. Natalia V. , Duke Jackie , Veldhuijzen J. Paul 
Published: July 2024

AbstractIn a previous Space Shuttle/Spacelab experiment (STS-42), we observed direct responses of isolated fetal mouse long bones to near weightlessness. This paper aimed to verify those results and study the effects of daily 1×g exposure during microgravity on the growth and mineralization of these bones. Two experiments were conducted: one on an American Space Shuttle mission (IML-2 on STS-65) and another on a Russian Bio-Cosmos flight (Bion-10 on Cosmos-2229). Despite differences in hardware, both used 17-day-old fetal mouse metatarsals cultured for 4 days. Results showed reduced proteoglycan content under microgravity compared to 1×g conditions, with no main differences in other cellular structures. While the overall metatarsal length was unaffected, the length increase of the mineralized diaphysis was significantly reduced under microgravity. Daily 1×g exposure for at least 6 h abolished the microgravity-induced reduction in cartilage mineralization, indicating the need for long-duration exposure to 1×g as an in-flight countermeasure using artificial gravity.
Characterizing a complex CT-rich haplotype in intron 4 of SNCA using large-scale targeted amplicon long-read sequencing
Authors: Alvarez Jerez Pilar , Daida Kensuke , Grenn Francis P. , Malik Laksh , Miano-Burkhardt Abigail , Makarious Mary B. , Ding Jinhui , Gibbs J. Raphael , Moore Anni , Reed Xylena , Nalls Mike A. , Shah Syed , Mahmoud Medhat , Sedlazeck Fritz J. , Dolzhenko Egor , Park Morgan , Iwaki Hirotaka , Casey Bradford , Ryten Mina , Blauwendraat Cornelis , Singleton Andrew B. , Billingsley Kimberley J. 
Published: July 2024

AbstractParkinson’s disease (PD) is a common neurodegenerative disorder with a significant risk proportion driven by genetics. While much progress has been made, most of the heritability remains unknown. This is in-part because previous genetic studies have focused on the contribution of single nucleotide variants. More complex forms of variation, such as structural variants and tandem repeats, are already associated with several synucleinopathies. However, because more sophisticated sequencing methods are usually required to detect these regions, little is understood regarding their contribution to PD. One example is a polymorphic CT-rich region in intron 4 of the SNCA gene. This haplotype has been suggested to be associated with risk of Lewy Body (LB) pathology in Alzheimer’s Disease and SNCA gene expression, but is yet to be investigated in PD. Here, we attempt to resolve this CT-rich haplotype and investigate its role in PD. We performed targeted PacBio HiFi sequencing of the region in 1375 PD cases and 959 controls. We replicate the previously reported associations and a novel association between two PD risk SNVs (rs356182 and rs5019538) and haplotype 4, the largest haplotype. Through quantitative trait locus analyzes we identify a significant haplotype 4 association with alternative CAGE transcriptional start site usage, not leading to significant differential SNCA gene expression in post-mortem frontal cortex brain tissue. Therefore, disease association in this locus might not be biologically driven by this CT-rich repeat region. Our data demonstrates the complexity of this SNCA region and highlights that further follow up functional studies are warranted.
In-Situ Characterization of Cathode Catalyst Degradation in PEM Fuel Cells
Authors: Schneider Patrick , Scherzer Anne-Christine , Ney Linda , Kwon Ha-Kyung , Storey Brian D. , Gerteisen Dietmar , Zamel Nada 
Published: July 2024

AbstractThe composition and morphology of the cathode catalyst layer (CCL) have a significant impact on the performance and stability of polymer electrolyte membrane fuel cells (PEMFC). Understanding the primary degradation mechanism of the CCL and its influencing factors is crucial for optimizing PEMFC performance and durability. Within this work, we present comprehensive in-situ characterization data focused on cathode catalyst degradation. The dataset consists of 36 unique durability tests with over 4000 testing hours, including variations in the cathode ionomer to carbon ratio, platinum on carbon ratio, ionomer equivalent weight, and carbon support type. The applied accelerated stress tests were conducted with different upper potential limits and relative humidities. Characterization techniques including IV-curves, limiting current measurements, electrochemical impedance spectroscopy, and cyclic voltammetry were employed to analyse changes in performance, charge and mass transfer, and electrochemically active surface area of the catalyst. The aim of the dataset is to improve the understanding of catalyst degradation by allowing comparisons across material variations and provide practical information for other researchers in the field.
Intelligence Assessment of Children & Youth Benefiting from Psychological-Educational Support System in Poland
Authors: Olech Michał , Jurek Paweł , Radtke Bartosz M. , Sajewicz-Radtke Urszula , Łada-Maśko Ariadna 
Published: July 2024

AbstractThis article presents a unique dataset comprising 419,135 intelligence assessment results. The study utilised the Polish adaptation of the Stanford-Binet Intelligence Scale 5 during individual diagnostic sessions conducted under natural conditions. The research included children aged 3;0–18;11 of both genders who had been referred to support institutions (psychological-educational counselling centres, post-hospital clinics, hospital departments) by preschools or schools, or voluntarily requested by parents with their consent. The data collection spanned the entire country of Poland from 2018 to 2023. In addition to comprehensive intelligence assessment results, the dataset contains valuable demographic information, enabling in-depth analyses. The dataset’s uniqueness lies in its impressive sample size, encompassing over four hundred thousand observations as well as the utilisation of time-consuming and thorough intelligence assessment procedures in settings that mimic the real world. Moreover, the context of the study is noteworthy, as the participants are individuals benefiting from the publicly - available Polish psychological support system.
Research on one-dimensional phase change heat transfer characteristics based on instrument compartment structure
Authors: Zhao Jiabin , Liu Longbin , Li Mingkun 
Published: July 2024

AbstractTo address the issue of electronic equipment failure inside the instrument compartment due to aerodynamic heating during high-speed flight. Combining the heat transfer characteristics of phase change materials, a new instrument compartment structure was proposed as the research subject based on phase change materials. While studying the heat transfer characteristics of this structure, one-dimensional phase change heat transfer theoretical model was constructed based on the Lightfoot integral equation method, and the corresponding analytical solution was obtained. To explore the temperature change law of the instrument compartment structure and verify the rationality of the theoretical model, the new thermal experiment was carried out for the instrument compartment structure. Compared with the aluminum alloy instrument compartment structure, the experimental results show that the instrument compartment structure design based on phase change materials could effectively reduce the temperature of the structure itself, and the experimental data are in good agreement with the theoretical calculation results, which verified the rationality of the theoretical model and provided a scientific basis for the practical application of phase change materials in instrument compartment structures.
E-Health-based, trans-sectoral, geriatric health service – Geriatric Network (GerNe)
Authors: Mohr Michael , Büttner Matthias , Deuster Oliver , Heckmann Jochen , Huwer Frank , Krämer Irene , Lippold Cornelia , Siegrist Bettina , Singer Susanne , Veith Marina , Zinke Ariane , Hardt Roland 
Published: July 2024

AbstractCurrently, exchange of information between the geriatric clinic and the attending general practitioner (GP) occurs primarily through the doctor's letter after discharging from the clinic. The aim of our study was to reduce readmissions of multimorbid, geriatric patients to the clinic by establishing a new form of care via an electronic case file (ECF) and a consultation service (CS). The discharging geriatric clinic filled out an online ECF. The patient's GP should document quarterly follow-ups in the ECF. The case file was monitored by the discharging clinic due to a consultation service. The primary efficacy endpoint was the rehospitalization rate within one year. The hospitalization rate for patients managed in the project was 83.1/100 person years (PY), while the control group from insurance data had a rate of 69.0/100 PY. The primary endpoint did not show a statistically significant difference (p = 0.15). A total of 195 contacts were documented via CS for 171 participants, mostly initiated by the clinics. The clinical queries primarily concerned drug therapy. The Covid pandemic had an overall impact on hospitalizations. There are many approaches to reducing hospital readmissions after discharge of older patients. Supporting the transition from inpatient to outpatient care by different professional groups or care systems has been shown to have a positive effect. Furthermore, the utilisation of an ECF can also be beneficial in this regard.
Skeleton density and ellipsoid zone loss are prognostic for progression in Macular Telangiectasia Type 2
Authors: Goerdt Lukas , Berger Moritz , Jungblut Julie , Rodriguez Garcia Jose Luis , Pfau Kristina , Herrmann Philipp , Holz Frank G. , Wintergerst Maximilian W. M. 
Published: July 2024

AbstractMacular Telangiectasia Type 2 (MacTel) is a chronic, progressive disease of the central retina characterized by vascular and neurodegenerative changes. As there is currently no treatment for non-neovascular MacTel, there is a dearth for biomarkers identifying eyes with an increased risk for disease progression for patient counseling and clinical trial recruitment. Eyes were classified to be stable or progressive, defined by the fundus photography-based grading system by Gass and Blodi. First, structural differences between these two groups were assessed, employing optical coherence tomography (OCT) and OCT-angiography. Univariate regression analyses revealed evidence towards a lower superficial retinal layer (SRL) vessel density (VD), skeleton density (SD) and deep retinal layer (DRL) SD in progressing compared to stable eyes (p = 0.05, p = 0.05, p = 0.07). Second, a multivariable predictive model was employed to examine the predictive value of structural and functional parameters for disease progression. Baseline best corrected visual acuity (BCVA) and SRL SD are prognostic for disease progression (p < 0.001, p = 0.05). The presence of ellipsoid zone (EZ) loss is prognostic for future central retinal thickness (p < 0.01). We propose SRL SD, BCVA, and EZ loss as prognostic biomarkers and as possible outcome measures in future interventional studies in MacTel.
Simulation-based prior knowledge elicitation for parametric Bayesian models
Authors: Bockting Florence , Radev Stefan T. , Bürkner Paul-Christian 
Published: July 2024

AbstractA central characteristic of Bayesian statistics is the ability to consistently incorporate prior knowledge into various modeling processes. In this paper, we focus on translating domain expert knowledge into corresponding prior distributions over model parameters, a process known as prior elicitation. Expert knowledge can manifest itself in diverse formats, including information about raw data, summary statistics, or model parameters. A major challenge for existing elicitation methods is how to effectively utilize all of these different formats in order to formulate prior distributions that align with the expert’s expectations, regardless of the model structure. To address these challenges, we develop a simulation-based elicitation method that can learn the hyperparameters of potentially any parametric prior distribution from a wide spectrum of expert knowledge using stochastic gradient descent. We validate the effectiveness and robustness of our elicitation method in four representative simulation studies covering linear models, generalized linear models, and hierarchical models. Our results support the claim that our method is largely independent of the underlying model structure and adaptable to various elicitation techniques, including quantile-based, moment-based, and histogram-based methods.
Identification of kinase inhibitors as potential host-directed therapies for intracellular bacteria
Authors: van den Biggelaar Robin H. G. A. , Walburg Kimberley V. , van den Eeden Susan J. F. , van Doorn Cassandra L. R. , Meiler Eugenia , de Ries Alex S. , Fusco M. Chiara , Meijer Annemarie H. , Ottenhoff Tom H. M. , Saris Anno 
Published: July 2024

AbstractThe emergence of antimicrobial resistance has created an urgent need for alternative treatments against bacterial pathogens. Here, we investigated kinase inhibitors as potential host-directed therapies (HDTs) against intracellular bacteria, specifically Salmonella Typhimurium (Stm) and Mycobacterium tuberculosis (Mtb). We screened 827 ATP-competitive kinase inhibitors with known target profiles from two Published Kinase Inhibitor Sets (PKIS1 and PKIS2) using intracellular infection models for Stm and Mtb, based on human cell lines and primary macrophages. Additionally, the in vivo safety and efficacy of the compounds were assessed using zebrafish embryo infection models. Our screen identified 11 hit compounds for Stm and 17 hit compounds for Mtb that were effective against intracellular bacteria and non-toxic for host cells. Further experiments were conducted to prioritize Stm hit compounds that were able to clear the intracellular infection in primary human macrophages. From these, two structurally related Stm hit compounds, GSK1379738A and GSK1379760A, exhibited significant activity against Stm in infected zebrafish embryos. In addition, we identified compounds that were active against intracellular Mtb, including morpholino-imidazo/triazolo-pyrimidinones that target PIK3CB, as well as 2-aminobenzimidazoles targeting ABL1. Overall, this study provided insights into kinase targets acting at the host–pathogen interface and identified several kinase inhibitors as potential HDTs.
Neurobiological modulation with REAC technology: enhancing pain, depression, anxiety, stress, and quality of life in post-polio syndrome subjects
Authors: André Nogueira Jeyce Adrielly , Souza Bulle Oliveira Acary , Pereira Motta Monalisa , Vieira de Souza Moscardi Alcione Aparecida , Manchim Favaro Vanessa , Munhoz Teixeira Claudete , Orasmo Simcsik Amanda , Patrizi Maria Clara , Conde Maria Salete , Rinaldi Arianna , Fontani Vania , Rinaldi Salvatore 
Published: July 2024

AbstractPost-polio syndrome (PPS) brings new challenges for polio survivors, including muscle decline, pain, depression, and diminished quality of life. This study explored the potential of REAC neuromodulatory treatments to ease pain, improve mood, and enhance quality of life in PPS patients. 17 individuals with PPS (average age 54.8) received three REAC treatments: Neuro Postural Optimization, Neuro Psycho Physical Optimization, and Neuro Psycho Physical Optimization-Cervico Brachial. Pain, depression, anxiety, stress, and quality of life were assessed before and after using established scales. REAC treatments significantly reduced pain across various dimensions, along with depression, anxiety, and stress levels. Additionally, patients reported improved physical and psychological quality of life. This study suggests REAC neuromodulatory treatments as a promising non-invasive option to improve pain, emotional well-being, and quality of life in individuals with PPS.
Optimal design of fractional-order proportional integral derivative controllers for structural vibration suppression
Authors: Khodadoost Saeed , Saraee Meysam , Talatahari Siamak , Sareh Pooya 
Published: July 2024

AbstractIn designing control systems, it is known that fractional-order proportional integral derivative (FOPID) controllers often provide greater flexibility than conventional proportional integral derivative (PID) controllers. This higher level of flexibility has proven to be extremely valuable for various applications such as vibration suppression in structural engineering. In this paper, we study the optimization of FOPID controllers using twelve well-established algorithms to minimize structural responses under seismic excitations. The algorithms include crystal structure algorithm (CryStAl), stochastic paint optimizer, particle swarm optimization, krill herd, harmony search, ant colony optimization, genetic algorithm, grey wolf optimizer, Harris hawks optimization, sparrow search algorithm, hippopotamus optimization algorithm, and duck swarm algorithm. In addition to highlighting the benefits of fractional calculus in structural control, this study provides a detailed analysis of FOPID controllers as well as a brief description of the algorithms used to optimize them. To evaluate the efficiency of the proposed techniques, two building models with different numbers of stories are examined. FOPID controllers are designed based on oustaloup’s approximation and the El Centro earthquake data. Using five well-known metrics, the performances of the developed methods are evaluated against five earthquake scenarios, including the recent earthquake in Turkey. A non-parametric (Friedman) test is also employed to compare the algorithms based on their corresponding vibration reduction. The findings of this analysis show that CryStAl consistently performs better than the other algorithms for both building models, thus resulting in superior vibration suppression.