bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Using a Standardized Questionnaire on Sexual History Documentation and Testing to Diagnose Gonorrhea and Chlamydia Among Men Who have Sex with Men with HIV
Authors: deMontigny Avila Danielle , Rabe Brooke , Aravagiri Arunmozhi , Joseph Martin , Lim James Ray M. , Naveed Maryam , Rappel Raina , Villanueva Berna , Khandekar Maithili , Zinkeng Atehkeng , Yates Sarah , Fantry Lori E. 
Published: December 2024

Abstract

Background: Most Neisseria gonorrhoea (GC) and Chlamydia trachomatis (CT) infections in men who have sex with men (MSM) are diagnosed at extragenital sites. However, testing at these sites is often lacking. The purpose of this study was to determine if a standardized questionnaire administered by physicians and clinical assistants improves documentation of sex activity and increases extragenital testing and diagnoses of GC and CT among MSM.

Methods: A standardized sexual history questionnaire was implemented on 11/1/2022. Electronic medical records of 664 MSM with HIV, including 1064 encounters, were reviewed to compare pre- and post- implementation sexual history documentation, adequacy of documentation, extragenital GC and CT testing, and GC and CT diagnoses. Analysis included Chi-square and exact tests and logistic regression adjusting for physician cluster effects.

Results: The standardized questionnaire was used by 53.7% of physicians and 85.9% of coordinators. Documentation of whether sexual activity occurred increased from 79.3% [95%confidence interval (CI) 0.758- 0.828] in the pre-intervention pre-COVID-19 period to 95.2% (95% CI 0.925-0.970) in the post-intervention period with an adjusted odds ratio of 4.7 (95% CI 2.7-8.8). Specific questions about anal and oral sex increased from 42.0% to 88.1% (p < 0.001) and 23.7% to 88.7% (p < 0.001), respectively. Anal and pharyngeal testing increased from 14.4% to 20.2% (p = 0.040) and 17.2% to 23.3% (p = 0.045), respectively.

Conclusions: This study demonstrates that using a standardized questionnaire during clinical encounters can improve documentation of sexual activity and testing for GC and CT at extragenital sites.
Protective Behaviors Following Digital COVID-19 Exposure Notifications, Washington State, September 1, 2021, to March 1, 2022
Authors: Briggs Nicole L. , Guthrie Brandon L. , Elder Adam S. , Revere Debra , Molino Andrea R. , West Laura M. , Higgins Amanda , Karras Bryant T. , Baseman Janet G. 
Published: December 2024

Context:
Digital exposure notification (EN) systems were widely used to supplement public health case investigations and contact tracing during the 2019 coronavirus disease (COVID-19) pandemic. In Washington State, the state Department of Health (DOH) implemented one such system, WA Notify, which generated ENs based on smartphone Bluetooth proximity detection. However, the privacy preserving measures of this technology prevented collection of information on how users responded after seeing an EN on their device.

Objective:
To understand the influence of ENs on intended and implemented protective behaviors among WA Notify users.

Design:
Two self-report surveys were administered by the WA DOH: a baseline survey regarding planned protective behaviors, available immediately after seeing an EN, and a follow-up survey distributed 2 weeks later regarding actual protective behaviors implemented. Self-reported planned and implemented protective behaviors were compared across 3 time periods relevant to the COVID-19 pandemic. Poisson regression was used to compare the probability of engaging in various protective behaviors across demographic characteristics and other contextual factors.

Setting:
Washington State.

Participants:
A total of 4280 individuals who chose to respond to both surveys and who completed the initial survey between September 1, 2021, and March 1, 2022.

Main Outcome Measure(s):
Self-reported plans for and engagement in protective behaviors (quarantining, testing, and symptom watching).

Results:
The proportion of individuals who reported implementing quarantining and symptom watching after seeing an EN was higher than the proportion that reported planning to engage in each respective behavior. Respondents who reported experiencing symptoms when seeing an EN were more likely to quarantine and test for COVID-19 compared to those with no symptoms.

Conclusion:
Plans to engage in protective behaviors after initially seeing an EN can change and may be influenced by evolving personal and contextual factors. Future digital EN systems can be improved through messaging tailored to encourage protective behaviors relevant to disease prevention.
M102, a combined NRF2 and HSF-1 activator for neuroprotection in amyotrophic lateral sclerosis
Authors: Keerie Amy F. , Martins Raquel Rua , Allen Chloe F. , Bowden Katie , Al Mashhadi Sufana , Marlow Thomas , Myszczynska Monika , Thakur Nikitha , Beal Selina N. , Shaw Allan , Suresh Shivani , McKinnon Scott N. , Daniel Alex , Wells Tyler , Kalfus Ira N. , Shan Ning , Shaw Pamela J. , Ferraiuolo Laura , Mead Richard J. 
Published: December 2024

AbstractM102 is a central nervous system (CNS) penetrant small molecule electrophile which activatesin vivothe NFE2-related factor 2 antioxidant response element (NRF2-ARE) pathway, as well as transcription of heat-shock element (HSE) associated genes. In the TDP-43Q331Ktransgenic mouse model of ALS dosed subcutaneously at 5mg/kg OD or 2.5mg/kg BD with M102, significant improvements in compound muscle action potential (CMAP) amplitude of hind limb muscles and gait parameters were observed at 6 months of age, with associated target engagement.An oral dose response study of M102 in SOD1G93Atransgenic mice showed a dose-dependent improvement in the CMAP of hindlimb muscles which correlated with preservation of lumbar spinal motor neurons at the same time point. These data enabled prediction of human efficacious exposures and doses, which were well within the safety margin predicted from Good Laboratory Practice (GLP) toxicology studies.A parallel program of workin vitroshowed that M102 rescued motor neuron survival in co-culture with patient-derived astrocytes from sporadic,C9orf72andSOD1cases. Markers of oxidative stress, as well as indices of TDP-43 proteinopathy were also reduced by exposure to M102 in thesein vitromodels.This comprehensive package of preclinical efficacy data across two mouse models as well as patient-derived astrocyte toxicity assays, provides a strong rationale for clinical evaluation of M102 in ALS patients. Combined with the development of target engagement biomarkers and the completed preclinical toxicology package, a clear translational pathway to testing in ALS patients has been developed.One Sentence SummaryM102, a dual NRF2/HSF1 activator, slows disease progression in 2 mouse models and exerts neuroprotection in human cellular models of ALS.
The strength of selection for costly toxin production increases with growth rate
Authors: Bisesi Ave T. , Chacón Jeremy M. , Smanski Michael J. , Harcombe William R. 
Published: December 2024

ABSTRACTMicrobes adopt a diversity of strategies to successfully compete with coexisting strains for space and resources. One common strategy is the production of toxic compounds to inhibit competitors, but the strength and direction of selection for this strategy varies depending on the environment. In particular, existing theoretical and experimental evidence suggests growth in spatially-structured environments makes toxin production more beneficial because competitive interactions are localized. Because higher growth rates increase the localization of resource competition in a structured environment, theory predicts that toxin production should be especially beneficial under these conditions. We tested this hypothesis by developing a genome-scale metabolic modeling approach and complementing it with comparative genomics to investigate the impact of growth rate on selection for costly toxin production. Our modeling approach expands the current abilities of the dynamic flux balance analysis platform COMETS to incorporate signaling and toxin production. Using this capability, we find that our modeling framework predicts that the strength of selection for toxin production increases as growth rate increases. This finding is supported by comparative genomics analyses that include diverse microbial species. Our work emphasizes that toxin production is more likely to be maintained in rapidly-growing, spatially-structured communities, thus improving our ability to manage critical microbial communities and informing natural product discovery.
Motor imagery and execution activate similar finger representations that are spatially consistent over time
Authors: Odermatt Ingrid Angela , Schönberg Laura , Heimhofer Caroline , Freund Patrick , Wenderoth Nicole , Kikkert Sanne 
Published: December 2024

AbstractFinger representations in the sensorimotor cortex can be activated even in the absence of somatosensory input or motor output through mere top-down processes, such as motor imagery. While executed finger movements activate finger representations in the primary sensorimotor cortex that are spatially consistent over time within participants, the stability of top-down activated finger representations remains largely unexplored. Given the increasing use of top-down activated sensorimotor representations to both plan implantation of and control brain-computer interfaces, it is crucial to understand the stability of these representations. Here, we investigated the spatial consistency, and thereby reliability, of finger representations activated through motor imagery in the primary somatosensory and primary motor cortex over time. To assess this, participants performed imagined and executed individual finger movements in two 3T fMRI sessions that were ∼2 weeks apart. We observed highly consistent univariate finger-selective activity clusters and multivariate vertex-wise activity patterns within participants over time in both the motor imagery and motor execution task. Using a multivariate across-task decoding approach, we further found that motor execution and motor imagery activate similar finger representations in both the primary somatosensory and primary motor cortex. This demonstrates that motor imagery can be used to identify finger representations related to movement execution. Our findings not only validate the use of top-down processes for brain-computer interface planning and control, but also open up new opportunities for the development of sensorimotor training interventions that do not rely on overt movements.
Biomechanical resilience of the femoral neck post-remission of Cushing’s Syndrome: a comparative analysis using QCT-based Finite Element models
Authors: Soudah Eduardo , Giuliodori Agustina , Hernández Joaquín A. 
Published: December 2024

ABSTRACTThis study aims at evaluating femoral bone-related mechanical properties in female patients with long-term remission of Cushing’s Syndrome (CS). Sixty-four female subjects were included in this study and stratified in two groups: (a) 32 long-term remission of CS patients, and (b) 32 healthy (paired) control subjects. Quantitative Computed Tomography (QCT) was used to derive patient-specific Finite Element (FE) models. A sideways-fall impact was simulated for each subject and the resulting stress and strain values were compare among the two different groups. Our findings indicate that women with CS in remission exhibit impaired biomechanical properties in the femoral neck compared to controls, suggesting compromised bone properties in this population.
Femoral bone growth predictions based on personalized multi-scale simulations: Validation and sensitivity analysis of a mechanobiological model
Authors: Koller Willi , Svehlik Martin , Wallnöfer Elias , Kranzl Andreas , Mindler Gabriel , Baca Arnold , Kainz Hans 
Published: December 2024

AbstractMusculoskeletal function is pivotal to long-term health. However, various patient groups develop torsional deformities, leading to clinical, functional problems. Understanding the interplay between movement pattern, bone loading and growth is crucial for improving the functional mobility of these patients and preserving long-term health.Multi-scale simulations in combination with a mechanobiological bone growth model have been used to estimate bone loads and predict femoral growth trends based on cross-sectional data. The lack of longitudinal data in previous studies hindered refinements of the mechanobiological model and validation of subject-specific growth predictions, thereby limiting clinical applications.This study aimed to validate the growth predictions using magnetic resonance images and motion capture data - collected longitudinally - from ten growing children. Additionally, a sensitivity analysis was conducted to refine model parameters.A linear regression model based on physical activity information, anthropometric data, and predictions from the refined mechanobiological model explained 70% of femoral anteversion development. Notably, the direction of femoral development was accurately predicted in 18 out of 20 femurs, suggesting that growth predictions could help to revolutionize treatment strategies for torsional deformities.Statements and DeclarationsThe authors have no relevant financial or non-financial interests to disclose.
Anti-fibrotic Effects of Atorvastatin Delivered via Keratin-based Hydrogels
Authors: Carroll Evan , Tarabokija Andrew , Chaudhry Henna , Meer Allison , de Guzman Roche C. 
Published: December 2024

AbstractImplantations of degradable biomaterials for drug delivery or restoration and regenerative medicine cause fibrosis and acute inflammation which may lead to chronic side effects. Additionally, the fibrous encapsulation can itself inhibit the local cells from proliferating and forming new healthy tissue. Current drug delivery models require a new method to decrease the adverse effects following implantation of biomaterials in patients and inhibit the activation signaling sent to quiescent fibroblasts. This research details the novel chemical and physical properties of reduced keratin (KTN) hydrogels extracted from residual human hair with sheared cuticle layers, obtained from barbershops and beauty salons. KTN hydrogels with and without calcium ions conjugated with atorvastatin (Ator), which is thought to affect TGF-ß signaling pathways directly by competitively inhibiting key signal transmitters and cellular responses, were investigated via electron microscopy, absorbance spectroscopy, and computational modeling and simulation to observe the proliferative inhibition of fibroblastic cells in comparison to the alginate hydrogel controls. Hydrogel extracts were tested for non-cytotoxic effects via L929 adipose fibroblast cell culture following ISO 10993-5 standard for safety of medical device biomaterials. Two cell models were exposed to increasing serial concentrations of Ator to evaluate the half maximal effective concentration (EC50). For quiescent fibroblasts, Ator’s EC50was observed at 368 μM in PBS. For mesenchymal stem cells (MSCs), Ator’s EC50was observed at 209 μM in PBS. The mass of drug was normalized in all groups after calculating their timed absorption and release, and KTN hydrogels conjugated with calcium ions and Ator (ATCK) completely absorbed the drug < 0.5 h while KTN hydrogels with Ator alone (ATKR) completely absorbed the drug at 1h. After 7d in PBS, ATCK released Ator at 2.2 ± 0.7% while Ator in calcium alginate spheres (ATLG) was released at 7.8 ± 1.1% and ATKR released 11.2 ± 4.3% of drug. On-going research focuses on other active fibroblastic cell types andin vivoexperimentation to observe foreign body response in subcutaneous mouse tissue.
Extracellular adenosine deamination primes tip organizer development inDictyostelium
Authors: Hathi Pavani , Baskar Ramamurthy 
Published: December 2024

AbstractAmmonia is a morphogen inDictyosteliumand is known to arise from the catabolism of proteins and RNA. However, we show that extracellular adenosine deamination catalyzed by adenosine deaminase related growth factor (ADGF), is a major source of ammonia and demonstrate a direct role of ammonia in tip organizer development. The tip formed during early development inDictyosteliumis functionally similar to the embryonic organizer of higher vertebrates.adgfmutants fail to establish an organizer and this could be reversed by exposing the mutants to volatile ammonia. Interestingly, bacteria physically separated from theadgf−mounds in a partitioned dish also rescues the mound arrest phenotype suggesting a cross kingdom interaction driving development. Both the substrate, adenosine and the product, ammonia regulateadgfexpression, andadgfacts downstream of the histidine kinasedhkDin regulating tip formation. Thus, the consecutive transformation of extracellular cAMP to adenosine, and adenosine to ammonia are integral steps duringDictyosteliumdevelopment. Remarkably, in higher vertebrates,adgfexpression is elevated during gastrulation and thus adenosine deamination may be an evolutionarily conserved process driving organizer development.
A Mathematical Framework for the Quantitative Analysis of Genetic Buffering
Authors: Karagiannis Jim 
Published: December 2024

AbstractGenetic buffering plays a pivotal role in orchestrating the relationship between genotype and phenotype in outbred populations. While high-throughput screens have identified many instances of genetic buffering – through the detection of “synthetic lethality” or “synthetic sickness” – a formal and general method for its quantitative analysis across systems is lacking. In this report, an axiomatic mathematical framework that can be used to classify, quantify, and compare buffering relationships between genes is described. Importantly, this methodology employs a ratio scale as its basis, thereby permitting the definition of a novel neutrality model for gene interaction that is referred to as the “parallel” model. This model does not contradict, and instead complements, the commonly used “product” model (more aptly referred to herein as the “serial” neutrality model). Moreover, simple extensions of this newly developed framework permit the unambiguous definition and classification of gene interactions in a formal, general, and mathematical way. Consequently, the concept of genetic buffering as first conceived by Leland Hartwell becomes a specific case within a comprehensive model of gene interaction.
Identification and Pharmacological Characterization of Multiple Allosteric Binding Sites on the Free Fatty Acid 1 Receptor
Authors: Chaturvedi Siddhant , Venka Krishna , Singh Rahul , Kumar Mohandas 
Published: December 2024

ABSTRACTFree fatty acid receptor 1 (FFA1 or GPR40), activated by medium- and long-chain fatty acids, amplifies glucose-stimulated insulin secretion, making it a promising target for type 2 diabetes. Radioligand studies revealed distinct binding sites for partial and full agonists, with full agonists showing positive cooperativity. Functional assays demonstrated positive cooperativity between agonists and varying interactions with the endogenous fatty acid DHA. These findings suggest three allosterically linked binding sites on FFA1, with activation influenced by key arginine residues. Potent ligands with strong cooperativity hold significant therapeutic potential.
Peptide Information Compression Technology (PICT): A New Frontier in Therapeutic Peptide Discovery
Authors: Wang Hong , Wang Zhu-Yin , Jiang Wei-Ming , Wang Qin-Qin , Miao Lin , Wang Deng , Wang Hai-Tao , Tung Shiu-Feng , Yang Jin-Rui , Yang Bin , Liang Xu-Bo , Li Zhen-Wan , Wang Xue-Ping , Zou Sheng , He Feng , Guo Xiao-Tao , Yan Yuan , Xu Kai-Min , Wang Xiao-Qi , Wang Xin-Bo , Liu Hui-Qing , Li Xiang-Qun 
Published: December 2024

AbstractTherapeutic peptides hold tremendous market potential, yet the discovery methods for active peptides lag considerably behind those for small molecules and biological macromolecule drugs. Due to their respective limitations, traditional peptide compound synthesis and display libraries fail to meet the growing demands of the peptide drug market. Here, we introduce a novel Peptide Information Compression Technology (PICT) and, based on this technology, a large-scale physical peptide library and its accompanying high-throughput screening (HTS) platform. By screening for inhibitors of TSLP/TSLPR/IL7Rα and antagonists of MC3R at both the molecular and cellular levels, we have identified active molecules in the single-digital micromolar and nanomolar ranges, respectively. This demonstrates the immense application value of Peptide Information Compression Technology in the efficient discovery of peptide drugs.
Deconvoluting TCR-dependent & -independent activation is vital for reliable Ag-specific CD4+T cell characterization by AIM assay
Authors: Zheng Ming Z. M. , Burmas Lauren , Tan Hyon-Xhi , Trieu Mai-Chi , Lee Hyun Jae , Rawlinson Daniel , Haque Ashraful , Kent Stephen J. , Wheatley Adam K. , Juno Jennifer A. 
Published: December 2024

AbstractAIM assays are thought to detect antigen (Ag)-specific T cell responses in an HLA- and cytokine-independent manner. Recent studies using AIM assays identified prominent Th17-like (CCR6+) CD4+T cells and circulating follicular T helper cells (cTfh) in anti-viral contexts, but were not observed with peptide/HLA tetramer staining. We demonstrate that CD39+Treg-like and CD26hiTh22-like cells can be activated by cytokines in a TCR-independent manner duringin vitroAg stimulation, leading to non-specific upregulation of prototypical AIM readouts. Transcriptional analysis of memory CD4+T cells that underwent TCR-dependent or -independent activation enabled discrimination ofbona fideAg-specific T cells from cytokine-activated Treg and Th22 cells. CXCR4 downregulation emerged as a hallmark of clonotypic expansion and TCR-dependent activation in memory CD4+T cells and cTfh. Tracking tetramer-binding cells during re-stimulation showed that CXCR4-CD137+cells provide a more accurate measure of the Ag-specific population than standard AIM readouts. This modified assay excludes the predominately CCR6+cytokine-activated T cells that contribute to an average 12-fold overestimation of the Ag-specific population. As AIM assays enable the rapid study of T cell responses against emerging pathogens, our findings provide a highly accurate approach to characterize genuine Ag-specific T cell responses that contribute to protective immunity.