bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycobacteriumdormancy and antibiotic tolerance within the retinal pigment epithelium of ocular tuberculosis
Authors: Liu Rachel , Dang Joshua N. , Lee Rhoeun , Lee Jae Jin , Kesavamoorthy Niranjana , Ameri Hossein , Rao Narsing , Eoh Hyungjin 
Published: March 2024

AbstractTuberculosis (TB) is a leading cause of death among infectious diseases worldwide due to latent TB infection, which is the critical step for the successful pathogenic cycle. In this stage,Mycobacterium tuberculosisresides inside the host in a dormant and antibiotic-tolerant state. Latent TB infection can lead to a multisystemic diseases becauseM. tuberculosisinvades virtually all organs, including ocular tissues. Ocular tuberculosis (OTB) occurs when the dormant bacilli within ocular tissues reactivate, originally seeded by hematogenous spread from pulmonary TB. Timely and accurate diagnosis as well as efficient chemotherapies are crucial in preventing poor visual outcomes of OTB patients. Histological evidence suggests that retinal pigment epithelium (RPE) cells play a central role in immune privilege and in the protection from the antibiotic effects, making them an anatomical niche for invadingM. tuberculosis. RPE cells exhibit high tolerance to environmental redox stresses, allowing phagocytosedM. tuberculosisbacilli to maintain viability in a dormant state. However, the microbiological and metabolic mechanisms determining the interaction between the RPE intracellular environment and phagocytosedM. tuberculosisare largely unknown. Here, liquid chromatography mass spectrometry (LC-MS) metabolomics was used to illuminate the metabolic state within RPE cells reprogrammed to harbor dormantM. tuberculosisbacilli and enhance the antibiotic tolerance. The results have led to propose a novel therapeutic option to synthetically kill the dormantM. tuberculosisinside the RPE cells by modulating the phenotypic state ofM. tuberculosis, thus laying the foundation for a new, innovative regimen for treating OTB.ImportanceUnderstanding the metabolic environment within the retinal pigment epithelium (RPE) cells altered by infection withM. tuberculosisand mycobacterial dormancy is crucial to identify new therapeutic methods to cure OTB. The present study showed that RPE cellular metabolism is altered to foster intracellular M. tuberculosis to enter into the dormant and drug tolerant state, thereby blunting the efficacy of anti-TB chemotherapy. RPE cells serve as an anatomical niche as the cells protect invading bacilli from antibiotic treatment. LC-MS metabolomics of RPE cells after co-treatment with H2O2 and M. tuberculosis infection showed that intracellular environment within RPE cells is enriched with greater level of oxidative stress. The antibiotic tolerance of intracellularM. tuberculosiswithin RPE cells can be restored by a metabolic manipulation strategy such as co-treatment of antibiotic with the most downstream glycolysis metabolite, phosphoenolpyruvate.
Modelling timelines to elimination of sleeping sickness in the DRC accounting for possible cryptic human and animal transmission
Authors: Crump Ronald E , Aliee Maryam , Sutherland Samuel A , Huang Ching-I , Crowley Emily H , Spencer Simon E F , Keeling Matt J , Shampa Chansy , Miaka Erick Mwamba , Rock Kat S 
Published: March 2024

AbstractSleeping sickness (gambiense human African trypanosomiasis, gHAT) is a vector-borne disease targeted for global elimination of transmission (EoT) by 2030. There are, however, unknowns that have the potential to hinder the achievement and measurement of this goal. These include asymptomatic gHAT infections (inclusive of the potential to self-cure or harbour skin-only infections) and whether gHAT infection in animals can contribute to the transmission cycle in humans. Using modelling we explore how cryptic (undetected) transmission impacts the monitoring of progress towards as well as the achievement of the EoT goal. We have developed gHAT models that include either asymptomatic or animal transmission, and compare these to a baseline gHAT model without either of these transmission routes, to explore the potential role of cryptic infections on the EoT goal. Each model was independently calibrated using available historic human case data for 2000––2020 (obtained from the World Health Organization’s HAT Atlas) which includes routine data from active and passive screening for five different health zones in the Democratic Republic of the Congo (DRC).Our results suggest that when matched to past case data, we estimated similar numbers of new human infections between model variants, although human infections were slightly higher in the models with cryptic infections. We simulated the continuation of screen-confirm-and-treat interventions and found that forward projections from the animal and asymptomatic transmission models produced lower probabilities of EoT than the baseline model. Simulation of a (as yet to be available) screen-and-treat strategy found that removing a parasitological confirmation step was predicted to have a more noticeable benefit to transmission reduction under the asymptomatic model compared to the others. Our simulations suggest vector control could greatly impact all transmission routes in all models, although this resource-intensive intervention should be carefully prioritised.
Molecular basis for the activation of the Fatty Acid Kinase complex ofStaphylococcus aureus
Authors: Myers Megan J. , Xu Zhen , Ryan Benjamin J. , DeMars Zachary R. , Ridder Miranda J. , Johnson David K. , Krute Christina N. , Flynn Tony S. , Kashipathy Maithri M. , Battaile Kevin P. , Schnicker Nicholas , Lovell Scott , Freudenthal Bret D. , Bose Jeffrey L. 
Published: March 2024

AbstractGram-positive bacteria utilize a Fatty Acid Kinase (FAK) complex to harvest fatty acids from the environment. The complex, consisting of the fatty acid kinase, FakA, and an acyl carrier protein, FakB, is known to impact virulence and disease outcomes. However, FAK’s structure and enzymatic mechanism remain poorly understood. Here, we used a combination of modeling, biochemical, and cell-based approaches to establish critical details of FAK activity. Solved structures of the apo and ligand-bound FakA kinase domain captured the protein state through ATP hydrolysis. Additionally, targeted mutagenesis of an understudied FakA Middle domain identified critical residues within a metal-binding pocket that contribute to FakA dimer stability and protein function. Regarding the complex, we demonstrated nanomolar affinity between FakA and FakB and generated computational models of the complex’s quaternary structure. Together, these data provide critical insight into the structure and function of the FAK complex which is essential for understanding its mechanism.
Lossless Single-Molecule Counting To Absolute Quantify Proteoforms
Authors: Gross Tobias , Hundertmark Tobias , Csiszár Villő , Sulyok András Attila , Gross Nina , Breiden Maike , Kitschen Niklas , von Groll Uritza , Niemöller Christoph , Sánchez-Martín Pablo , Hein Anne , Göpffert Jens , Szórádi Tamás , Lübbert Philipp , Koltay Peter , Porschewski Peter , von Stetten Felix , Zengerle Roland , Jeney Csaba 
Published: March 2024

AbstractA novel immunoassay, termed Protein Interaction Coupling (PICO), is introduced to deliver unequivocal, reference-free quantification of proteoforms - absolute quantification. PICO employs a compartmentalized, homogeneous single-molecule assay with a lossless and highly sensitive signal generation, capable of detecting down to a few molecules per reaction. Additionally, it utilises a background-free, digital enumeration principle, known as the decouplexing. PICO is presented as exact mathematical theories, providing a theoretical comprehension of its chemistry. Consequently, PICO demonstrates absolute quantification, as exemplified with recombinant and non-recombinant ErbB2 and multi-tagged peptide rTRX targets, validating absolute quantification against internal and external references in both analytical and cellular matrices. Furthermore, PICO enables combinatorial multiplexing (cplex), a readout between any two antibodies, demonstrated by an 8-plex antibody, 12-cplex PICO, measuring functional changes of ErbB pathway upon mock and dactolisib treatment delivering absolute quantitative cellular stoichiometry. PICO possesses immense potential for versatile, standardized, and accurate protein measurements, offering insights into physiological and perturbed cellular processes.
Health-Related Effects of Real-Time Circuit Tele-Training and Gym Resistance-Aerobic Training in Ambulatory Adults with Cerebral Palsy
Authors: Aviram Ronit , Parmet Yisrael , Bar-Haim Simona 
Published: March 2024

ABSTRACTObjectiveTo compare the impacts of gym training and circuit Zoom-tele-training on health parameters in ambulatory adults with spastic cerebral palsy.MethodsParticipants were divided into three groups: The Gym-group that underwent resistance-and-aerobic training program (n=12), the Zoom-group that underwent a circuit Zoom-tele-training program (n=14), and the Control-group that was on a waitlist and underwent no training (n=14). The two training gropes exercised bi-weekly for 12-week. Measurements included blood pressure, waist circumference, BMI, 15-repetition maximum-strength tests, and a LALA aerobic shuttle test analyzed using a linear mixed model.ResultsWeight circumference decreased in both the Gym and Zoom groups (P=.0202 and P=.0014 respectively); in addition, in both these groups systolic (P=.018, P=.0001 respectively) and diastolic (P=.086 -marginal significance, P<.0001 respectively) blood pressure decreased, with a more pronounced reduction in the diastolic blood pressure for the Zoom-group (P=.043). Maximum aerobic speed increased (P<.0001) in the Zoom-group, with the Gym-group achieving the same speed with a lower peak heart rate (P=.0144). Strength significantly improved in the Zoom group for row (P=.05) and knee-extension (P<.0001) exercises. The Gym group improved in all strength measures (Row P<.0001, Chest-press P<.0001, and Knee-extension P<.0001). The Gym-group’s gains were greater than the Zoom-group’s in the row (P<.0001) and knee-extension (P=.005) exercises. The Control-group experienced a rise in BMI (P=.0256), waist circumference (P=.056 marginal significance), and systolic blood pressure (P=.055 marginal significance).ConclusionBoth exercise programs effectively reduced health-risk factors. The Zoom-group excelled in improving aerobic capacity and diastolic blood pressure, while the Gym-group demonstrated superior strength gains. Not exercising was detrimental to body mass, waist circumference, and blood pressure.ImpactExercise programs enhance long life heath and prevent health deterioration in adults with cerebral palsy. Results endorse using waist circumference and blood pressure measures as valuable clinical outcomes for adults with cerebral palsy.
BC-Predict: Mining of signal biomarkers and multilevel validation of cascade classifier for early-stage breast cancer subtyping and prognosis
Authors: Muthamilselvan Sangeetha , Palaniappan Ashok 
Published: March 2024

AbstractDisease heterogeneity is the hallmark of breast cancer, which remains a scourge and the most common malignancy among women. With a steep increase in breast cancer morbidity and mortality, there exists a critical need for effective early-stage theragnostic and prognostic biomarkers. This would help in patient stratification and optimal treatment selection towards better disease management. In this study, we examined four key problems with respect to the characterization of breast cancer heterogeneity, namely: (i) cancer screening; (ii) identification of metastatic cancers; (iii) molecular subtype (TNBC, HER2, or luminal); and (iv) histological subtype (ductal or lobular). We mined the available public-domain transcriptomic data of breast cancer patients from the TCGA and other databases using stage-encoded statistical models of gene expression, and identified stage-salient, monotonically expressed, and problem-specific biomarkers. Next we trained different classes of machine learning algorithms targeted at the above problems and embedded in these feature spaces. Hyperparameters specific to each algorithm were optimized using 10-fold cross-validation on the training dataset. The optimized models were evaluated on the holdout testset to identify the overall best model for each problem. The best model for each problem was validated with: (i) multi-omics data from the same cohort (miRNA and methylation profiles); (ii) external datasets from out-of-domain cohorts; and (iii) state of the art, including commercially available breast cancer panels. External validation of our models matched or bested available benchmarks in the respective problem domains (balanced accuracies of 97.42% for cancer vs normal; 88.22% for metastatic v/s non metastatic; 88.79% for ternary molecular subtyping; and ensemble accuracy of 94.23% for histological subtyping). We have translated the results into BC-Predict, a freely available web-server that forks the best models developed for each problem, and provides the cascade annotation of input instance(s) of expression data, along with uncertainty estimates. BC-Predict is meant for academic use and has been deployed at:https://apalania.shinyapps.io/BC-Predict.
Versatile gamma-tubulin complexes contribute to the dynamic organization of MTOCs duringDrosophilaspermatogenesis
Authors: Alzyoud Elham , Németh Dóra , Vedelek Viktor , Szögi Titanilla , Tóth Viktória Petra , Krecsmarik Mónika , Ábrahám Edit , Lipinszki Zoltán , Sinka Rita 
Published: March 2024

AbstractThe initiation of microtubule formation is facilitated by γ-tubulin and γ-Tubulin Ring Complex (γ-TuRC) in various microtubule-organizing centers (MTOCs). While the heterogeneity of tissue-specific MTOCs and γ-TuRC inDrosophilatestis has been described, their molecular composition and physiological significance are poorly understood. We investigated the testis-specific distribution and biochemical interaction of the canonical γ-TuRC proteins Grip163 and Grip84. We found that while Grip163 is present on the centrosome and basal body, Grip84 localizes to the centrosome and Golgi in spermatocytes and colocalizes with the testis-specific γ-TuRC at the basal body, apical nuclear tip, and near the elongated mitochondria after meiosis. We also show the apical nuclear tip localization of some γ-TuRC interacting partners and prove their binding to testis-specific γ-TuRC proteins. These results highlight and prove the importance of the different γ-TuRCs in organizing the diverse MTOCs present during the extensive rearrangement of cell organelles during the spermatogenesis ofDrosophila.
String fragmentation of a quark pair with entangled spin states: Application to
e+e−
annihilation
Authors: Kerbizi A. , Artru X. 
Published: March 2024

We present a recursive quantum mechanical model for the fragmentation of a string stretched between a quark and an antiquark with entangled spin states. The quarks are assumed to be produced in the e+e− annihilation process via the exchange of a virtual photon and the correlations between their spin states are described by a joint spin-density matrix. The string fragmentation process is formulated at the amplitude level by using the splitting matrices of the recent string+P30 model of polarized quark fragmentation with pseudoscalar and vector meson emissions and accounts for the systematic propagation of the spin correlations in the fragmentation chain. The model is formulated as a recursive recipe suitable for a Monte Carlo implementation. It reproduces the expected angular correlation, due to the Collins effect, between back-to-back pseudoscalar and/or vector mesons. For the latter, this correlation also involves the momenta of the decay products. We use the model for studying the sign of the Collins asymmetry for back-to-back vector and pseudoscalar mesons.

Published by the American Physical Society
2024
Unleashing the power of clustering: a qualitative study of cluster organizations’ role in advancing green transformation
Authors: Mackiewicz Marta , Kuberska Dominika 
Published: March 2024

Purpose
The purpose of this study is to ascertain how cluster organisations have been fostering green transformation in Poland.

Design/methodology/approach
This paper adopts a multiple case study approach. Data collection methods involved in-depth interviews with cluster organisation managers and researchers to identify support measures for green transformation and to investigate the factors influencing their actions as well as a comprehensive analysis of documents, including cluster organisations‘ strategies.

Findings
Cluster organisations manage and participate in actions that create favourable conditions for pursuing low-carbon and circular economy ventures. They not only assist their members in overcoming obstacles related to green transformation but also engage non-members – which can lead to spillovers reaching beyond their borders. Their engagement takes place across all phases of the green transformation process.

Research limitations/implications
For various reasons, the research was designed as qualitative to understand the opinions and experiences of various actors engaged in green transformation within cluster organisations’ ecosystems. The key factor influencing this decision stems from the fact that knowledge of the involvement of cluster organisations in supporting green transformation still needs to be completed and scattered. The limitations of the study include limited access to information and the fact that qualitative research allows for a certain amount of subjectivity, and the results should be generalised carefully. Moreover, the interviews were carried out with a non-random sample of participants. Another limitation of the study is related to biased views, which could have been shared by interviewees acting as representatives of the studied cluster organisations.

Practical implications
Cluster organisations have emerged as drivers of circular transition by promoting sustainable practices such as material recycling, biological recovery and parts harvesting. These initiatives contribute to reducing waste, conserving resources, and minimising the environmental footprint of industries. These organisations can be active agents of transformation, orchestrating collaborative efforts that have a far-reaching impact on industries and economies.

Originality/value
This is one of the first and most comprehensive studies on the role of cluster organisations in Poland in supporting green transformation. This paper identifies and systematises the actions undertaken to provide a clear understanding of the internal processes within cluster organisations.
Corporate social performance and board gender diversity: the moderating role of governance
Authors: Phillips Cynthia R , Stefanidis Abraham , Shoaf Victoria 
Published: March 2024

Purpose
Drawing on legitimacy and upper-echelon theory, this paper aims to investigate the moderating role of corporate governance in the relationship between corporate social performance (CSP) and board gender diversity (BGD).

Design/methodology/approach
Using Morgan Stanley Capital International measures of social and governance performance, the authors use 2,950 firm-year observations from US companies for the years 2016–2020 to show that good performance on social issues drives BGD.

Findings
The panel data model indicates that the relationship between CSP and BGD is strengthened when firms display robust corporate governance.

Originality/value
This study contributes to the extant literature through empirical consideration of CSP as a predictor of BGD, a relationship that has rarely been examined. It further highlights the significant role of corporate governance in ensuring that women have access to corporate boards. Discussion and findings highlight that social performance and governance may significantly contribute to the diversity of socially cognizant boards.
Does social capital affect supply chain performance? Establishing an underlying mechanism and a boundary condition
Authors: Chohan Aisha , Hussain Ghulam , Shafique Imran 
Published: March 2024

PurposeThis study examines the direct and indirect effects of social capital on supply chain performance via supply chain quality integration (SCQI), which refers to integrating supply chain partners from the perspective of quality management. It also examines the moderating role of environmental uncertainty in the link between social capital and SCQI and determines the conditional indirect effect of social capital on supply chain performance via SCQI.Design/methodology/approachData were collected using a time-lagged research design through a self-administered survey of supply chain professionals in manufacturing firms in Pakistan. Hayes’ PROCESS Macro was used to test the hypotheses.FindingsThe results show a positive relationship between social capital and supply chain performance. SCQI partially mediates the relationship between social capital and supply chain performance. Environmental uncertainty significantly moderates that relationship in such a way that firms that operate under high environmental uncertainty are more likely to use their social capital to develop SCQI than firms that operate under low environmental uncertainty.Practical implicationsThe study has practical implications for managers who seek to implement SCQI practices using social capital. Leveraging social capital across the supply chain fosters strong connections and a quality-oriented approach across the supply chain, and improves overall performance. Managers can use the power of social capital to navigate environmental uncertainty.Originality/valueThis study’s originality lies in its drawing on the dynamic capability theory and contingency theory and integrating the dispersed scholarly work on social capital, SCQI, and supply chain performance under the boundary condition of environmental uncertainty.