bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CRISPR base editing approach for the functional assessment of telomere biology disorder-related genes in human health and aging
Authors: Borges Gustavo , Benslimane Yahya , Harrington Lea 
Published: February 2024

AbstractTelomere Biology Disorders (TBDs) are a group of rare diseases characterized by the presence of short and/or dysfunctional telomeres. They comprise a group of bone marrow failure syndromes, idiopathic pulmonary fibrosis, and liver disease, among other diseases. Genetic alterations (variants) in the genes responsible for telomere homeostasis have been linked to TBDs. Despite the number of variants already identified as pathogenic, an even more significant number must be better understood. The study of TBDs is challenging since identifying these variants is difficult due to their rareness, it is hard to predict their impact on the disease onset, and there are not enough samples to study. Most of our knowledge about pathogenic variants comes from assessing telomerase activity from patients and their relatives affected by a TBD. However, we still lack a cell-based model to identify new variants and to study the long-term impact of such variants on the genes involved in TBDs. Herein, we present a cell-based model using CRISPR base editing to mutagenize the endogenous alleles of 21 genes involved in telomere biology. We identified key residues in the genes encoding 17 different proteins impacting cell growth. We provide functional evidence for variants of uncertain significance in patients with TBDs. We also identified variants resistant to telomerase inhibition that, similar to cells expressing wild-type telomerase, exhibited increased tumorigenic potential using an in vitro tumour growth assay. We believe that such cell-based approaches will significantly advance our understanding of the biology of TBDs and may contribute to the development of new therapies for this group of diseases.
Cumulative effects of offshore wind farms on common guillemots (Uria aalge) in the southern North Sea - climate versus biodiversity?
Authors: Peschko Verena , Schwemmer Henriette , Mercker Moritz , Markones Nele , Borkenhagen Kai , Garthe Stefan 
Published: February 2024

AbstractGovernments are under increasing pressure to reduce greenhouse gas emissions, and large-scale wind farms are being developed in marine environments worldwide. However, top predators are strongly affected by environmental change and anthropogenic activities. Common guillemots (Uria aalge, hereafter guillemots), as one of the world’s most numerous seabird species, are prone to interference with offshore wind farms (OWFs). This study assessed the cumulative impacts of all operating OWFs on guillemots in the German North Sea. These estimates were applied to quantify the possible conflicts between guillemot occurrence and current German government plans to implement large-scale OWFs. If OWFs were implemented according to the current maritime spatial plan for the German Exclusive Economic zone, they would cover 13% of the German North Sea. Guillemot numbers peak during autumn, with German North Sea offshore waters hosting approximately 90,000 individuals. Guillemot density in autumn was significantly reduced within a radius of 19.5 km around operating OWFs. Applying this disturbance distance to current installation plans, about 70% of the German North Sea would be affected, and an estimated 68% of guillemots in the German North Sea would experience habitat loss. This highlights the possible threat to guillemots in the southern North Sea if the current German government plans are implemented. The current estimates are highly relevant to decisions regarding marine spatial planning and management recommendations. Such evaluations are essential for developing sustainable scenarios including reducing the human CO2 footprint, whilst also conserving biodiversity.
A Novel Similarity Approach for Describing the Bulk Shear in the Atmospheric Surface Layer
Authors: Urbancic G. H. , Stiperski I. , Holtslag A. A. M. , Mosso S. , Vihma T. 
Published: February 2024

AbstractThe Monin–Obukhov Similarity Theory (MOST) is a cornerstone of boundary layer meteorology and the basis of most parameterizations of the atmospheric surface layer. Due to its significance for observations and modelling, we generalize the dimensional analysis of MOST by considering the bulk gradient directly, enabling the study of any sublayer of the atmospheric surface layer. This results in a family of similarity relations describing all gradients from the local gradient to the full-layer bulk gradient. By applying the profiles derived from the law-of-the-wall and MOST, we are able to derive analytic expressions for this family of similarity relations. Under stable conditions, we discover that the log-linear profile of Businger–Dyer generalizes from the local to the bulk shear where the slope is dependent on the choice of the layer. The simplicity of the general log-linear relation allows for estimating the influence of stability on the non-dimensional gradients. It is shown that bulk gradients are less sensitive to stability than the local gradient. By correctly filtering cases where the full-layer bulk gradient is influenced by stability, we demonstrate that MOST is compatible with the Hockey-Stick Transition. For unstable conditions, the Kader and Yaglom (J Fluid Mech 212(151):637-662, 1990) model represents the local gradient well but was not successful in representing the bulk gradient, demonstrating the need for further analysis of scaling relations for the unstable atmospheric surface layer.
Real-world treatment patterns and clinical outcomes in patients treated with eribulin after prior phosphoinositide 3-Kinase inhibitor treatment for metastatic breast cancer
Authors: Goyal Ravi K. , Zhang Jingchuan , Davis Keith L. , Sluga-O’Callaghan Martina , Kaufman Peter A. 
Published: February 2024

Abstract
Purpose
In 2010, the US Food and Drug Administration approved eribulin for the treatment of metastatic breast cancer (MBC). Since then, the treatment landscape has evolved with many new therapy classes, a more recent one being the small molecule inhibitors of phosphoinositide 3 kinase (PI3K). We sought to characterize the treatment patterns and clinical outcomes of patients with MBC who received eribulin following prior treatment with a PI3K inhibitor.

Methods
A retrospective cohort study based on medical record review included MBC patients who initiated eribulin between March 2019 and September 2020 following prior treatment with a PI3K inhibitor was conducted. Patient demographics, treatment characteristics, and clinical outcomes were analyzed descriptively. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated from the initiation of eribulin therapy using Kaplan-Meier analyses.

Results
82 eligible patients were included. Patients’ median age at eribulin initiation was 62 years; 86.5% had hormone receptor–positive, human epidermal growth factor receptor 2–negative tumors. Eribulin was most often administered in the second or third line (82.9%) in the metastatic setting. Best overall response on eribulin was reported as complete or partial response in 72% of the patients. The median rwPFS was 18.9 months (95% confidence interval [CI], 12.4-not estimable); median OS was not reached. The estimated rwPFS and OS rates at 12 months were 63.3% (95% CI, 50.5–73.7) and 82.6% (95% CI, 72.4–89.3), respectively.

Conclusion
Our real-world study suggests that eribulin may be a potential treatment option for MBC patients who fail a prior PI3K inhibitor.
The Association of Quality of Life with Psychosocial Factors in Adolescents with Tourette Syndrome
Authors: Watson Kelly H. , Eckland Michelle , Schwartzman Jessica M. , Molnar Andrew , Boon Whitney , Hiller Matthew , Scholer Seth , Mace Rachel , Rothman Alice , Claassen Daniel O. , Riordan Heather R. , Isaacs David A. 
Published: February 2024

AbstractIndividuals with Tourette syndrome (TS) have poorer quality of life (QoL) than their peers, yet factors contributing to poor QoL in this population remain unclear. Research to date has predominantly focused on the impact of tics and psychiatric symptoms on QoL in TS samples. The aim of this cross-sectional, multi-informant study was to identify psychosocial variables that may impact adolescent QoL in TS. Thirty-eight adolescents aged 13 to 17 with TS and 28 age-matched controls participated with a caregiver. No group differences were found on QoL, although the TS group reported reduced QoL compared to population normative data. In the TS group, reduced QoL was associated with lower self-esteem, poorer family functioning, higher stress, and greater depression and anxiety; QoL was unrelated to tic severity. In regression analyses, after adjusting for covariates, family functioning was the strongest predictor of QoL. These results emphasize the need to further explore the influence of psychosocial factors, particularly family functioning, on QoL in adolescents with TS.
What is a mathematician doing…in a chemistry class?
Authors: Estrada Ernesto 
Published: February 2024

AbstractThe way of thinking of mathematicians and chemists in their respective disciplines seems to have very different levels of abstractions. While the firsts are involved in the most abstract of all sciences, the seconds are engaged in a practical, mainly experimental discipline. Therefore, it is surprising that many luminaries of the mathematics universe have studied chemistry as their main subject. Others have started studying chemistry before swapping to mathematics or have declared some admiration and even love for this discipline. Here I reveal some of these mathematicians who were involved in chemistry from a biographical perspective. Then, I analyze what these remarkable mathematicians and statisticians could have learned while studying chemical subjects. I found analogies between code-breaking and molecular structure elucidation, inspiration for statistics in quantitative analytical chemistry, and on the role of topology in the study of some organic molecules. I also analyze some parallelisms between the way of thinking of organic chemists and mathematicians in terms of the use of backward analysis, search for patterns, and use of pictures in their respective researches.
Leaf extracts of eight selected southern African medicinal plants modulate pro-inflammatory cytokine secretion in LPS-stimulated RAW 264.7 macrophages
Authors: Khumalo Gugulethu P. , Loa-Kum-Cheung Wendy , Van Wyk Ben-Erik , Feng Yunjiang , Cock Ian E. 
Published: February 2024

AbstractThis study investigates the anti-inflammatory properties of extracts prepared from the leaves of eight southern African medicinal plants used traditionally to treat inflammation and pain. The inhibitory effect of aqueous and ethanol extracts on the release of pro-inflammatory cytokines was determined in lipopolysaccharide (LPS) stimulated and unstimulated RAW 264.7 murine macrophage cells. The levels of interleukin (IL)-1β, IL-6, tumour necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein (MIP)-2 release were determined using cytokine multiplex-bead assays. The ethanol extracts of Melianthus comosus Vahl (commonly known as honey flower), Tetradenia riparia (Hochst.) Codd (misty plume bush) and Warburgia salutaris (G. Bertol.) Chiov. (pepper-bark tree), demonstrated the most significant inhibitory activity, with over 50-fold inhibition of IL-1β, IL-6 and TNF-α levels in LPS-stimulated RAW 264.7 macrophages. The aqueous extract of M. comosus also significantly inhibited the secretion of all the tested cytokines and chemokines. Phytochemical investigation of M. comosus ethanol leaf extract using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) led to the detection of crassolide, deoxylimonoic acid D-ring-lactone, 2-hydroxynonanoic acid and 5-noniloxytryptamine. To the best of our knowledge, the cytokine inhibition properties of most of the medicinal plants screened in this study are reported for the first time. Our results support the use of southern African medicinal plants as anti-inflammatory remedies and provide an insight into the immunomodulatory mechanisms of action.
Suspension electrospinning of SBR latex combined with photo-induced crosslinking: control of nanofiber composition, morphology, and properties
Authors: Kianfar Parnian , Bakry Ahmed , Dalle Vacche Sara , Bongiovanni Roberta , Vitale Alessandra 
Published: February 2024

AbstractSuspension electrospinning of a styrene-butadiene rubber (SBR) latex coupled with photo-induced crosslinking in ambient conditions is proposed as a rapid method to prepare ultrafine shape-stable rubber fibrous membranes. Polyethylene oxide (PEO) is used as template polymer and can eventually be removed from the nanostructured membrane by a simple water treatment. A multifunctional thiol crosslinker and an appropriate photo-initiating system are added to the latex to allow the fast and efficient photo-induced crosslinking of the nanofibers, based on thiol addition to the SBR double bonds, as demonstrated by real-time Infrared spectroscopy analyses. It is proved that by varying the PEO template polymer and the thiol crosslinker content, a fine control of the chemical composition, morphology, water solubility, and thermal properties of the nanofibrous membranes is ensured. Moreover, comparable mechanical properties to those of fibrous membranes produced by conventional electrospinning of organic solvent-based solutions are obtained, clearly showing the attractiveness of the present method, especially in terms of process sustainability.
Graphical abstract
A novel adaptive filter with a heart-rate-based reference signal for esophageal pressure signal denoising
Authors: Qin Yu , Huang Zhiwen , Zhou Xiaoyong , Gui Shuiqing , Xiong Lihong , Liu Ling , Liu Jinglei 
Published: February 2024

AbstractEsophageal pressure (Peso) is one of the most common and minimally invasive methods used to assess the respiratory and lung mechanics in patients receiving mechanical ventilation. However, the Peso measurement is contaminated by cardiogenic oscillations (CGOs), which cannot be easily eliminated in real-time. The field of study dealing with the elimination of CGO from Peso signals is still in the early stages of its development. In this study, we present an adaptive filtering-based method by constructing a reference signal based on the heart rate and sine function to remove CGOs in real-time. The proposed technique is tested using clinical data acquired from 20 patients admitted to the intensive care unit. Lung compliance ( QUOTE ) and esophageal pressure swings (△Pes) are used to evaluate the performance and efficiency of the proposed technique. The CGO can be efficiently suppressed when the constructional reference signal contains the fundamental, and second and third harmonic frequencies of the heart rate signal. The analysis of the data of 8 patients with controlled mechanical ventilation reveals that the standard deviation/mean of the QUOTE is reduced by 28.4–79.2% without changing the QUOTE and the △Pes measurement is more accurate, with the use of our proposed technique. The proposed technique can effectively eliminate the CGOs from the measured Peso signals in real-time without requiring additional equipment to collect the reference signal.
Financing Thresholds for Sustainability of Community Health Worker Programs for Patients Receiving Medicaid Across the United States
Authors: Basu Sanjay , Patel Sadiq Y. , Robinson Kiiera , Baum Aaron 
Published: February 2024

AbstractStates have turned to novel Medicaid financing to pay for community health worker (CHW) programs, often through fee-for-service or capitated payments. We sought to estimate Medicaid payment rates to ensure CHW program sustainability. A microsimulation model was constructed to estimate CHW salaries, equipment, transportation, space, and benefits costs across the U.S. Fee-for-service rates per 30-min CHW visit (code 98960) and capitated rates were calculated for financial sustainability. The mean CHW hourly wage was $23.51, varying from $15.90 in Puerto Rico to $31.61 in Rhode Island. Overhead per work hour averaged $43.65 nationwide, and was highest for transportation among other overhead categories (65.1% of overhead). The minimum fee-for-service rate for a 30-min visit was $53.24 (95% CI $24.80, $91.11), varying from $40.44 in South Dakota to $70.89 in Washington D.C. The minimum capitated rate was $140.18 per member per month (95% CI $105.94, $260.90), varying from $113.55 in South Dakota to $176.58 in Washington D.C. Rates varied minimally by metro status but more by panel size. Higher Medicaid fee-for-service and capitated rates than currently used may be needed to support financial viability of CHW programs. A revised payment estimation approach may help state officials, health systems and plans discussing CHW program sustainability.
Modeling Excitable Cells with the EMI Equations: Spectral Analysis and Iterative Solution Strategy
Authors: Benedusi Pietro , Ferrari Paola , Rognes Marie E. , Serra-Capizzano Stefano 
Published: February 2024

AbstractIn this work, we are interested in solving large linear systems stemming from the extra–membrane–intra model, which is employed for simulating excitable tissues at a cellular scale. After setting the related systems of partial differential equations equipped with proper boundary conditions, we provide its finite element discretization and focus on the resulting large linear systems. We first give a relatively complete spectral analysis using tools from the theory of Generalized Locally Toeplitz matrix sequences. The obtained spectral information is used for designing appropriate preconditioned Krylov solvers. Through numerical experiments, we show that the presented solution strategy is robust w.r.t. problem and discretization parameters, efficient and scalable.
Discrimination of Second Language Vowel Contrasts and the Role of Phonological Short-Term Memory and Nonverbal Intelligence
Authors: Georgiou Georgios P. , Giannakou Aretousa 
Published: February 2024

AbstractAlthough extensive research has focused on the perceptual abilities of second language (L2) learners, a significant gap persists in understanding how cognitive functions like phonological short-term memory (PSTM) and nonverbal intelligence (IQ) impact L2 speech perception. This study sets out to investigate the discrimination of L2 English monophthongal vowel contrasts and to assess the effect of PSTM and nonverbal IQ on L2 speech perception. The participants consisted of adult monolingually-raised Greek speakers, who completed an AX discrimination test, a digit span test, and a nonverbal intelligence test. A control group of English speakers also completed the AX test. Data were analyzed using Bayesian regression models. The results revealed that Greek speakers exhibited below chance discrimination for the majority of L2 vowel contrasts, consistently underperforming in comparison to the control group. Intriguingly, the study did not provide substantial evidence in favor of more accurate discrimination of L2 contrasts by Greek participants with high PSTM compared to those with low PSTM. However, the study yielded compelling evidence indicating that Greek participants with higher IQ demonstrated superior accuracy in discriminating most L2 contrasts compared to their lower IQ counterparts. The limited influence of PSTM on speech perception suggests the need for further exploration, considering the potential impact of test methodologies and the intricate interplay of other confounding factors. Furthermore, the study uncovers a noteworthy relationship between nonverbal IQ and L2 speech perception, likely linked with the association of high IQ with enhanced attentional capacities, information processing abilities, and learning skills—all of which are pivotal for accurate speech perception.
Geotechnical characteristics and seismic stability evaluation of pumice-fall deposits soil on collapse slope by the 2018 Hokkaido eastern Iburi earthquake
Authors: Kawajiri Shunzo , Watanabe Tatsuya , Yamaguchi Kohei , Minabe Yuki , Nakamura Dai , Kawaguchi Takayuki , Yamashita Satoshi 
Published: February 2024

AbstractThe September 6, 2018, earthquake in the eastern part of Hokkaido, Japan, caused extensive slope failures in Atsuma-town, Hokkaido, Japan. In this study, the authors performed in situ investigations, including trenching and portable dynamic cone penetration tests, on weathered fallen pumice sediments, which are one of the causes of the slope failures. In addition, we performed direct box shear tests on undisturbed samples collected from an undisturbed area under various shear conditions to characterize mechanical properties of the soil. The parameters obtained from the mechanical tests were used to evaluate slope stability under normal and seismic conditions with an infinite-length slope model. The results showed that the slopes where seismic failures occurred had a fragile layer from the surface to a depth of approximately 1.5 m, which generally corresponded to the depth of failure. Weathered pumice deposits with extremely high-water content existed at the boundary between the weak layer and the basement layer, and their shear strength was velocity dependent. It has been shown that an infinite-length slope stability analysis can be performed by using mechanical parameters for which velocity dependence of horizontal acceleration and shear strength due to seismic motion are accounted for.
Regulatory independence may limit electoral holdup but entrench capture
Authors: Schram Arthur , Ule Aljaž 
Published: February 2024

AbstractPrivate infrastructure investment is profitable only if followed by a sufficiently high price, but pricing may be subject to regulation. We study markets where regulation is determined by elected policymakers. If price regulation is subject to manipulation then private investors may delay investment fearing an electoral pressure on future prices, leading to a holdup inefficiency. This could possibly be alleviated by regulatory independence, where policymakers can no longer influence the prices. However, to encourage investment the policymakers may install regulation that serves the interests of the infrastructure owners (“regulatory capture”) and lead to inefficient pricing. Regulatory independence can then be detrimental as it may entrench this capture. Whether inefficiencies can be moderated by creating regulatory independence therefore depends on the policymakers’ objectives. We provide experimental evidence for such capture entrenchment and detrimental effects of regulatory independence that therefore arise. Even without independence, the uninformed voters do not provide sufficient pressure to remove these effects. On the other hand, we observe that regulatory independence does reduce holdup inefficiency when policymakers align with the public interest.
Virtue, Authenticity and Irony: Themes from Sartre and Williams
Authors: Thomas Alan 
Published: February 2024

AbstractIn the course of criticizing indirect forms of consequentialism Bernard Williams argued that because virtues of character enter into the very content of the self, they cannot be instrumentalised. They must, instead, be viewed as cognitive responses to intrinsic value. This paper investigates this argument and relates it to similar claims in the work of Sartre. The inalienability of the first personal point of view represents a common theme and informs a further argument that an agent can only think of him or herself as merely one amongst others via a distinctive ethical use of the trope of irony.