bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the likelihood of elevated transaminases in lung cancer patients undergoing immune checkpoint blockade
Authors: Shek Dmitrii , Gao Bo , Carlino Matteo S , Nagrial Adnan , Moujaber Tania , Karikios Deme , Pires da Silva Ines , Read Scott A , Ahlenstiel Golo 
Published: May 2024

ABSTRACTBackgroundThe recent implementation of immune-checkpoint inhibitors (ICIs) has markedly changed the management and clinical outcomes for patients with advanced non-small cell lung cancer (NSCLC). Despite higher efficacy, ICIs are associated with a range of immune-related adverse events (irAEs). This retrospective study aimed to investigate the incidence of ICI-related transaminitis/hepatitis in NSCLC patients as well as to establish if any pre-treatment clinical parameters can predict the onset of liver toxicity.MethodsWe examined medical records of N=420 NSCLC patients treated across two health districts in Sydney, Australia between 2016 to 2020. R packages (corrplot and ggcorrplot) were used to construct correlation matrices and to calculate the correlation p-value using Spearman method. Logistic regression models were used to determine association of clinical parameters with elevated LFTs.ResultsN=185 patients were considered eligible. n=37 (20%) had elevation of liver transaminases at any stage post-ICI commencement, although only n=10 were deemed as those having ICI-related hepatitis. Most of these patients (n=29 [78%]) developed elevated LFTs within 3 months post-therapy initiation. Regression model established that pre-treatment ratio of serum protein (SP) to total bilirubin (TB) showed significant association with the elevated transaminases. Moreover, most of the patients (n=34 [94%]) with elevated LFTs had SP/TB<4. Using a second cohort of melanoma patients, the linear regression model did not establish a significant association between the SP/TB ratio and elevated LFTs. Nonetheless, n=31 (70.5%) patients with immune-mediated transaminitis in the melanoma cohort had SP/TB<4.ConclusionOur study has established a clinical risk factor associated with the elevation of LFTs in NSCLC patients, thus potentially enabling their prediction at the pre-treatment stage. However, its predictive accuracy was not confirmed in melanoma patients, stressing that ‘one size does not fit it all’ when developing predictive scores for irAEs in different patient cohorts.
Reliability and competitiveness of a novel balance field test: A cross-sectional pilot study
Authors: Jarnig Gerald , Kerbl Reinhold , van Poppel Mireille N.M. 
Published: May 2024

AbstractBalancing tests in the field provide important information about the physical fitness and injury risk of athletes. These tests provide useful data on an athlete’s ability to maintain balance in dynamic and unforeseen circumstances, allowing for a more detailed assessment of their athletic performance. We have designed a novel balance test and tested main quality criteria and competitiveness for it. A total of 117 children (girls = 52.1%) aged 10.4 ± 0.5 years participated in the tests. The raw ABC scores show good to excellent test-retest reliability for all participants. Girls show a higher reliability (excellent) than boys (moderate to good). The comparison of raw data of the performance in the ABC and existing balance field tests shows strong correlation of the results. The test duration of the ABC is significantly (p<.001) shorter than that of existing balance field tests. The statistical and graphical analysis of the calculation of the normal distribution shows that the results of the ABC are closer to the normal distribution than those of the existing balance field tests.The combination of high reliability and competitiveness makes the Austrian Balance Check an extremely attractive option for various areas of application. Overall, the novel designed test is a promising instrument that has the potential to significantly improve the standards of balance testing procedures in the field. The authors recommend a large-scale study to review the test quality criteria of the ABC, including gold standard comparison and development of age- and gender-specific reference values, in order to increase interest in implementing the Austrian Balance Check in international test batteries.
Crosstalk between plasma membrane andStaphylococcusα-hemolysin during oligomerization
Authors: Chatterjee Arnab , Roy Anupam , Sathees Thejas , Chakraborty Debajyoti , Das Partho Pratim , Mondal Bapan , Kishore Prithiv , Ghoshal Bartika , Jhunjhunwala Siddharth , Ganji Mahipal , Dutta Somnath 
Published: May 2024

SummaryThe infectious microbeStaphylococcus aureusreleases an array of cytotoxic pore-forming toxins (PFTs) that severely damage the cell membrane during bacterial infection. However, the interaction interfaces between the host cell and toxin were merely explored. Herein, we monitored the active oligomeric states facilitated membrane disruption processes such as lysis, and protrusion in the plasma membrane and lipid membrane. Furthermore, necrosis was triggered in the neutrophil-like cells upon synergistic binding and oligomerization of the monomeric α-HL. Additionally, we solved RBC membrane stabilized structure of different conformational states of this β-PFT using a single-particle cryo-EM. We further confirmed that internal membrane fluidity was the deterministic factor associated with the formation of intermediate pre-pores, heptameric pore-like, and complete pore species. Together, this is the first study to unveil the structure-function analysis of pre-pore to pore transition of any small β-PFT during its crosstalk with the cell.Highlightsα-HL promotes necrosis in HL60 cells and lysis of shorter lipid bilayer region.Cryo-EM of small PFT in the cellular environment.Structural characterization of heptameric pore, pore-like, and pre-pore complex in the presence of RBCs.Bilayer phase behavior (Ld/Lo) governs different conformational and geometrical variants of α-HL.
Functional interrogation of cellular Lp(a) uptake by genome-scale CRISPR screening
Authors: Khan Taslima G. , Cunha Juliana Bragazzi , Raut Chinmay , Burroughs Michael , Goonewardena Sascha N. , Smrcka Alan V. , Speliotes Elizabeth K. , Emmer Brian T. 
Published: May 2024

ABSTRACTAn elevated level of lipoprotein(a), or Lp(a), in the bloodstream has been causally linked to the development of atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Steady state levels of circulating lipoproteins are modulated by their rate of clearance, but the identity of the Lp(a) uptake receptor(s) has been controversial. In this study, we performed a genome-scale CRISPR screen to functionally interrogate all potential Lp(a) uptake regulators in HuH7 cells. Strikingly, the top positive and negative regulators of Lp(a) uptake in our screen wereLDLRandMYLIP, encoding the LDL receptor and its ubiquitin ligase IDOL, respectively. We also found a significant correlation for other genes with established roles in LDLR regulation. No other gene products, including those previously proposed as Lp(a) receptors, exhibited a significant effect on Lp(a) uptake in our screen. We validated the functional influence of LDLR expression on HuH7 Lp(a) uptake, confirmedin vitrobinding between the LDLR extracellular domain and purified Lp(a), and detected an association between loss-of-functionLDLRvariants and increased circulating Lp(a) levels in the UK Biobank cohort. Together, our findings support a central role for the LDL receptor in mediating Lp(a) uptake by hepatocytes.
Unraveling the Interplay between Stability and Flexibility in Design of Polyethylene Terephthalate (PET) Hydrolases
Authors: Xu Shiqinrui , Huo Chengze , Chu Xiakun 
Published: May 2024

AbstractThe accumulation of polyethylene terephthalate (PET), a widely used polyester plastic in packaging and textiles, poses a global environmental crisis. Biodegradation presents a promising strategy for PET recycling, with PET hydrolases (PETase) undertaking the task at the molecular level. Unfortunately, due to its low thermostability, PETase can only operate at ambient temperatures with low PET depolymerization efficiency, hindering its practical application in industry. Currently, efforts to engineer PETase have primarily focused on enhancing its thermostability. However, increased stability often reduces the structural dynamics necessary for substrate binding, potentially slowing down the enzymatic activity. To elucidate the delicate balance between stability and flexibility in optimizing PETase catalytic activity, we performed theoretical investigations on both wild-type PETase (WT-PETase) and a thermophilic variant (Thermo-PETase) using molecular dynamics simulations and frustration analysis. Despite being initially designed to stabilize the native structure of enzyme, our findings reveal that Thermo-PETase exhibits an unprecedented increase in structural flexibility at the PET binding and catalytic sites, beneficial for substrate recruitment and product release, compared to WT-PETase. Upon PET binding, we observed that structural dynamics of Thermo-PETase are largely quenched, facilitating subsequent chemical reactions. Compared to WT-PETase, Thermo-PETase forms more extensive interactions with PET, resulting in a higher population of catalytically competent enzyme-substrate states, thus contributing to increased catalytic activity. Our theoretical results are consistent with experimental findings and further suggest that Thermo-PETase exhibits higher catalytic activity than WTPETase across a broad temperature range by leveraging stability and flexibility at high and low temperatures, respectively. Our findings offer valuable insights into how PETase optimizes its enzymatic performance by balancing stability and flexibility, paving the way for future PETase design strategies.
Symmetry, gauge freedoms, and the interpretability of sequence-function relationships
Authors: Posfai Anna , McCandlish David M. , Kinney Justin B. 
Published: May 2024

Quantitative models that describe how biological sequences encode functional activities are ubiquitous in modern biology. One important aspect of these models is that they commonly exhibit gauge freedoms, i.e., directions in parameter space that do not affect model predictions. In physics, gauge freedoms arise when physical theories are formulated in ways that respect fundamental symmetries. However, the connections that gauge freedoms in models of sequence-function relationships have to the symmetries of sequence space have yet to be systematically studied. Here we study the gauge freedoms of models that respect a specific symmetry of sequence space: the group of position-specific character permutations. We find that gauge freedoms arise when model parameters transform under redundant irreducible matrix representations of this group. Based on this finding, we describe an “embedding distillation” procedure that enables analytic calculation of the number of independent gauge freedoms, as well as efficient computation of a sparse basis for the space of gauge freedoms. We also study how parameter transformation behavior affects parameter interpretability. We find that in many (and possibly all) nontrivial models, the ability to interpret individual model parameters as quantifying intrinsic allelic effects requires that gauge freedoms be present. This finding establishes an incompatibility between two distinct notions of parameter interpretability. Our work thus advances the understanding of symmetries, gauge freedoms, and parameter interpretability in sequence-function relationships.Significance StatementGauge freedoms—diections in parameter space that do not affect model predictions—are ubiquitous in mathematical models of biological sequence-function relationships. But in contrast to theoretical physics, where gauge freedoms play a central role, little is understood about the mathematical properties of gauge freedoms in models of sequence-function relationships. Here we identify a connection between specific symmetries of sequence space and the gauge freedoms present in a large class of commonly used models for sequence-function relationships. We show that this connection can be used to perform useful mathematical computations, and we discuss the impact of model transformation properties on parameter interpretability. The results fill a major gap in the understanding of quantitative sequence-function relationships.
A Survey of Individuals’ Willingness to Share Real-World Data Post-Mortem with Researchers
Authors: Hendricks-Sturrup Rachele M. , Lu Christine Y. 
Published: May 2024

AbstractBackgroundPosthumous data use policy within the broader scope of navigating post-mortem data privacy is a procedurally complex landscape for those engaged in data collection and sharing, and data-driven health research.ObjectiveTo help address some of this complexity by exploring patterns in individuals’ willingness to donate data with health researchers after death and developing practical recommendations.MethodsAn electronic survey was conducted in April 2021 among adults (≥18 years of age) registered in ResearchMatch (www.researchmatch.org), a national health research registry. Descriptive and multinomial logistic regression analyses were conducted at a 95% confidence level to determine the association between willingness to donate data after death overall and across each demographic category (education level, age range, duration of using online medical websites, annual frequency of getting ill) and based on the overall quantity at which individuals expressed willingness to donate data (some, all, none) with researchers.ResultsOf 399 responses, most participants were willing to donate health data (electronic medical record data [67%], prescription history data [63%], genetic data [54%], and fitness tracker data [53%]) after death. We identified that individuals were more likely to donate some data after death (versus no data) if they had longer duration of using online medical websites (relative risk ratio = 1.22, p<0.05, 95% CI: 1.01 to 1.48). No additional significant findings were observed between willingness to donate all, some, or none of their data after death and other demographic factors.ConclusionsThere are opportunities to enhance practices to engage patients in health systems’ online medical websites as one potential mechanism to encourage or inspire individuals in posthumous data donation for health research purposes.
Custodial symmetry breaking and Higgs boson signatures at the LHC
Authors: Butterworth Jon , Debnath Hridoy , Fileviez Pérez Pavel , Mitchell Francis 
Published: May 2024

We discuss the simplest model that predicts a tree-level modification of the ρ parameter from a shift in the W-mass without changing the prediction for the Z mass. This model predicts a new neutral Higgs and two charged Higgses, with very similar masses and suppressed couplings to the Standard Model fermions. We discuss the decay properties of these new scalar bosons, and the main signatures at the Large Hadron Collider. Comparing these signatures for the first time to the latest measurements, we show that while masses around 200 GeV are excluded for some scenarios, over a wide range of model parameter space the new bosons can have a mass close to the electroweak scale without violating existing limits from experimental searches or destroying the agreement with measurements. We investigate the scenario where the new neutral Higgs is fermiophobic and has a large branching ratio into W gauge bosons and/or photons, and show that this could lead to a signal in the diphoton mass spectrum at low Higgs masses. We discuss the different signatures that can motivate new measurements and searches at the Large Hadron Collider.

Published by the American Physical Society
2024
Probabilistic model for the gravitational wave signal from merging black holes
Authors: Khan Sebastian 
Published: May 2024

Parametrized models that predict the gravitational-wave (GW) signal from merging black holes are used to extract source properties from GW observations. The majority of research in this area has focused on developing methods capable of producing highly accurate, point estimate, predictions for the GW signal. A key element missing from every model used in the analysis of GW data is an estimate for how confident the model is in its prediction. This omission increases the risk of biased parameter estimation of source properties. Current strategies include running analyses with multiple models to measure systematic bias however, this fails to accurately reflect the true uncertainty in the models. In this work we develop a probabilistic extension to the phenomenological modeling workflow for nonspinning black holes and demonstrate that the model not only produces accurate point estimates for the GW signal but can be used to provide well-calibrated local estimates for its uncertainty. Our analysis highlights that there is a lack of numerical relativity (NR) simulations available at multiple resolutions which can be used to estimate their numerical error and implore the NR community to continue to improve their estimates for the error in NR solutions published. Waveform models that are not only accurate in their point-estimate predictions but also in their error estimates are a potential way to mitigate bias in GW parameter estimation of compact binaries due to unconfident waveform model extrapolations.

Published by the American Physical Society
2024
Wheeling towards sustainability: the nexus of external pressures, green innovation and circular supply chain excellence
Authors: Singh Rohit Kumar 
Published: May 2024

PurposeThe study aims to investigate the firm reaction to external pressures and the subsequent transformation to green innovation (GI) and sustainability, leading to an enhanced circular supply chain performance. The research examined the effect of coercive, normative and mimetic pressures on GI within the Indian tire industry context.Design/methodology/approachThe authors have designed a self-administered questionnaire and received 283 responses. Nonresponse bias analysis was conducted first before proceeding to other assumptions such as constant variance and normality. The confirmatory factor analysis was used to check the data’s integrity and reliability. The PLS-structural equation modeling (SEM) is used to validate the constructs and test the established hypotheses.FindingsExternal regulatory pressures significantly impact the tire industry’s move towards GI. Normative pressures from societal expectations and industry standards, along with mimetic pressures where companies emulate best practices, both drive the industry toward sustainable initiatives. Further, a clear positive relationship emerges between GI and sustainable supply chain practices (SSCP). This shift emphasizes recycling, reusing and reducing waste and showcases the industry’s commitment to minimizing its environmental impact.Originality/valueUnlike existing literature that predominantly explores SSCP, the study introduces an integrated framework that intertwines institutional pressures (IP), green innovation (GI), and SSCP to elevate circular supply chain practices (CSCP). The current study highlights the relationships and practical implications within the Indian tire industry.
Religiosity and entrepreneurship: women entrepreneurs in Turkiye
Authors: Ozasir Kacar Sibel 
Published: May 2024

PurposeThe purpose of this study is to showcase how entrepreneurial opportunities can be contextually formed differently for women entrepreneurs concerning their relationship with religion. This article reveals the multi-level and nuanced relationship between religiosity and entrepreneurship through a contextual lens by studying the interaction in a specific national country, Turkiye.Design/methodology/approachThe study uses the life stories of 10 Turkish women entrepreneurs operating in Turkiye. Data were selected purposefully to conduct an in-depth analysis. Thematic content analysis with a discursive approach and deductive and inductive coding methods were performed.FindingsThe findings suggest that the relationship between religiosity and entrepreneurial opportunities is highly contextual and nuanced. Religiosity brings trust and provides access to religious networks which can lead to entrepreneurial opportunities, while leaving people outside of this network bereft of these benefits. The creation of a closed circle for its beneficiaries is a feature of a social network, yet the results show that contextual forces of politics and gender can lead women entrepreneurs outside of this religious network to limit their possibilities of accessing public funding and facilities based on their perceptions as well as negative experiences. It is also seen that religiosity at a certain level is necessary to operate in conservative settings and traditionally masculine business environments with patriarchal practices and norms, as well as due to the religious affinity of the ruling political party. However, because of perceptions and discursive meanings attached to religion and religiosity in the country, women entrepreneurs need to be cautious in expressing their religiosity and find a balance so that they are not seen as unprofessional, incompetent and unqualified as well as do not jeopardise their business due to a controversial religious affiliation.Originality/valueThis paper is of value as it studies religiosity from a contextual perspective enabling and constraining women entrepreneurs in their entrepreneurship in relation to gendered and political structures. In this way, it displays the multiple ways of limitation and support that religiosity can bring for them concerning entrepreneurial opportunities. Turkiye provides a rich context with its mixed religious and secular societal norms and values and neo-liberal institutions and policies to examine the so-far underexplored issue of religiosity in the field of entrepreneurship.