bluuebunny/crossref_metadata_2025_split huggingface dataset:
Who are the patients who use non-pharmacological home remedies? Cross-sectional study in Switzerland and France
Authors: Sebo Paul , Winkler Neria E , Morel Marie , Moussa Mohamed Amir , Haller Dagmar M , Maisonneuve Hubert 
Published: May 2024

Abstract

Background
Many patients may be tempted to use non-pharmacological home remedies (NPHRs) to relieve various complaints. To the best of our knowledge, there is little data on the characteristics of patients using NPHRs. In this cross-sectional study carried out between March 2020 and July 2021, we examined the socio-demographic factors underlying their use in patient populations in Switzerland and France.

Methods
Using official registries, we randomly selected 50 primary care physicians (PCPs) in Geneva (Switzerland) and Lyon/Grenoble (France). Seven research assistants consecutively recruited patients from PCP waiting rooms (20–25 patients per practice). Patients completed a paper-based questionnaire assessing the use [yes/no] of 304 NPHRs for 79 medical conditions. The NPHR list was developed by our team with input from 97 patients. We used univariable and multivariable logistic regressions, adjusting for intra-cluster correlations, to examine associations between NPHR use and patient characteristics (gender, age, practice location, nationality, education level, and self-rated health).

Results
Of the 1198 eligible patients, 1012 agreed to participate (85%). Overall, 635 patients (63%) reported using at least one of the remedies tested in the study. In multivariable analysis, women (OR = 1.7 [95%CI = 1.3–2.3], P-value &lt; 0.001), younger patients (&lt; 40 years: OR = 2.1 [95%CI = 1.6–2.9], P-value &lt; 0.001), and French patients (OR = 1.6 [95%CI = 1.1–2.3], P-value &lt; 0.001) tended to use NPHRs more often than other patients.

Conclusions
Many patients, particularly women, young people, and French patients, reported using NPHRs. This survey’s findings hold the potential to inform healthcare providers, policymakers, and researchers about the diverse preferences that shape patients’ healthcare choices.
The entrepreneurial edge: evidence of social identity and other-orientation in communities of interest
Authors: Halbinger Maria A , Reichstein Toke , Melillo Francesca 
Published: May 2024

Abstract
Communities of interest are heralded as hotbeds for entrepreneurship. However, the social identification members of such communities are subject to may be detrimental to their proclivity to pursuing ideas through firm foundation and, thus, their propensity to become entrepreneurs. While other-oriented members tend to be associated with firm foundation, the association is significantly reduced and even negatively associated with firm foundation when the individual strongly identifies with a community of interest with collective values due to a shift in their attention toward community engagement as opposed to firm foundation. This paper draws from field studies, a problem-solving task, and survey data to empirically support our hypotheses. The study highlights the importance of integrating social identification and other-orientation when studying communities of interest in relation to entrepreneurship.
Lower seawater pH reduces the foraging activity of the Florida stone crab, Menippe mercenaria (Say, 1818) (Decapoda: Brachyura: Menippidae)
Authors: Jarrett Morgan L , Smith Abigail L , Langford Gabriel J , Gravinese Philip M 
Published: May 2024

Abstract
Anthropogenic activities like habitat degradation, excess nutrient runoff, and sewage outfalls can decrease seawater pH in coastal environments. Coastal waters can also experience frequent fluctuations in seawater pH due to biological activity (i.e., photosynthesis and respiration). Commercially important species like the Florida stone crab, Menippe mercenaria (Say, 1818), inhabit coastal waters and experience fluctuations in seawater pH on both diurnal and seasonal scales. Organisms exposed to reductions in seawater pH may have difficulty sensing chemical cues due to physiological changes and the associated metabolic stress of compensating for a more acidic environment. Here we determined the foraging activity of the Florida stone crab when exposed to reduced pH conditions (control pH 7.8, reduced pH 7.6). The impacts of reduced pH on foraging activity were determined by monitoring activity time, stress, predation attempts, and handling time when crabs were exposed to lower seawater pH for 12 hrs. Crabs exposed to reduced pH conditions experienced elevated stress levels and reduced activity than crabs in the control pH treatment. These results suggest that exposure to more extreme pH conditions may limit the foraging activity of stone crabs.
Interference of hemoglobin variants with HbA1c measurements by six commonly used HbA1c methods
Authors: Li Mingyang , Ge Song , Shu Xin , Wu Xiongjun , Liu Haiyan , Xu Anping , Ji Ling 
Published: May 2024

Abstract

Background
Glycated hemoglobin, or hemoglobin A1c (HbA1c), serves as a crucial marker for diagnosing diabetes and monitoring its progression. We aimed to assess the interference posed by common Hb variants on popular HbA1c measurement systems.

Methods
A total of 63 variant and nonvariant samples with target values assigned by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)-calibrated methods were included. We assessed 6 methods for measuring HbA1c in the presence of HbS, HbC, HbD, HbE, and fetal hemoglobin (HbF): 2 cation-exchange high-performance liquid chromatography (HPLC) methods (Bio-Rad D-100 and HLC-723 G8), a capillary electrophoresis (CE) method (Sebia Capillarys 3 TERA), an immunoassay (Roche c501), an enzyme assay system (Mindray BS-600M), and a boronate affinity method (Primus Premier Hb9210).

Results
The HbA1c results for nonvariant samples from the 6 methods were in good agreement with the IFCC-calibrated method results. The Bio-Rad D-100, Capillarys 3, Mindray BS-600M, Premier Hb9210, and Roche c501 showed no interference from HbS, HbC, HbD, and HbE. Clinically significant interference was observed for the HLC-723 G8 standard mode. Elevated HbF levels caused significant negative biases for all 6 methods, which increased with increasing HbF concentration.

Conclusion
Elevated levels of HbF can severely affect HbA1c measurements by borate affinity, immunoassays, and enzyme assays.
Parsing the roles of DExD-box proteins DDX39A and DDX39B in alternative RNA splicing
Authors: Banerjee Shefali , Nagasawa Chloe K , Widen Steven G , Garcia-Blanco Mariano A 
Published: May 2024

Abstract
DExD-box RNA proteins DDX39A and DDX39B are highly homologous paralogs that are conserved in vertebrates. They are required for energy-driven reactions involved in RNA processing. Although we have some understanding of how their functions overlap in RNA nuclear export, our knowledge of whether or not these proteins have specific or redundant functions in RNA splicing is limited. Our previous work has shown that DDX39B is responsible for regulating the splicing of important immune transcripts IL7R and FOXP3. In this study, we aimed to investigate whether DDX39A, a highly homologous paralog of DDX39B, plays a similar role in regulating alternative RNA splicing. We find that DDX39A and DDX39B have significant redundancy in their gene targets, but there are targets that uniquely require one or the other paralog. For instance, DDX39A is incapable of complementing defective splicing of IL7R exon 6 when DDX39B is depleted. This exon and other cassette exons that specifically depend on DDX39B have U-poor/C-rich polypyrimidine tracts in the upstream intron and this variant polypyrimidine tract is required for DDX39B dependency. This study provides evidence that despite a high degree of functional redundancy, DDX39A and DDX39B are selectively required for the splicing of specific pre-mRNAs.
Separating action and knowledge
Authors: Kelley Mikayla 
Published: May 2024

Abstract
Intentional action is often accompanied by knowledge of what one is doing—knowledge that appears non-observational and non-inferential. G.E.M. Anscombe defends the stronger claim that intentional action always comes with such knowledge. Among those who follow Anscombe, some have altered the features, content, or species of the knowledge claimed to necessarily accompany intentional action. In this paper, I argue that there is no knowledge condition on intentional action, no matter the assumed features, content, or species of the knowledge. Further, rather than follow the usual methodology in this debate of arguing by counterexample, I present an argument that explains why we continue to find counterexamples: intentional action and knowledge are regulated by thresholds under distinct pressures; in particular, the threshold of control regulating intentional action is disparately influenced by the role of intentional action in practical normativity.
Biomechanical Comparison of Different Surgical Strategies for Skip-level Cervical Degenerative Disc Disease
Authors: Xu Hanpeng , Liu Ziwen , Yang Yuming , Miao Jun , Wang Bingjin , Yang Cao 
Published: May 2024

Study Design:
We constructed finite element (FE) models of the cervical spine consisting of C2-C7 and predicted the biomechanical effects of different surgical procedures and instruments on adjacent segments, internal fixation systems, and the overall cervical spine through FE analysis.

Objective:
To compare the biomechanical effects between zero-profile device and cage-plate device in skip-level multistage anterior cervical discectomy and fusion (ACDF).

Summary of Background Data:
ACDF is often considered as the standard treatment for degenerative cervical spondylosis. However, the selection of surgical methods and instruments in cases of skip-level cervical degenerative disc disease is still controversial.

Methods:
Three FE models were constructed, which used noncontiguous 2-level Zero-P (NCZP) devices for C3/4 and C5/6, a noncontiguous 2-level cage-plate (NCCP) for C3/4 and C5/6, and a contiguous 3-level cage-plate (CCP) for C3/6. Simulate daily activities in ABAQUS. The range of motion (ROM), von Mises stress distribution of the endplate and internal fixation system, and intervertebral disc pressure (IDP) of each model were recorded and compared.

Results:
Similar to the stress of the cortical bone, the maximum stress of the Zero-P device was higher than that of the CP device for most activities. The ROM increments of the superior, inferior, and intermediate segments of the NCZP model were lower than those of the NCCP and CCP models in many actions. In terms of the IDP, the increment value of stress for the NCZP model was the smallest, whereas those of the NCCP and CCP models were larger. Similarly, the increment value of stress on the endplate also shows the minimum in the NCZP model.

Conclusions:
Noncontiguous ACDF with zero-profile can reduce the stress on adjacent intervertebral discs and endplates, resulting in a reduced risk of adjacent segment disease development. However, the high cortical bone stress caused by the Zero-P device may influence the risk of fractures.
Biophysical mapping of TREM2-ligand interactions reveals shared surfaces for engagement of multiple AD ligands
Authors: Greven Jessica A. , Wydra Joshua R. , Greer Rory A. , Camitta Christopher , Song Yuhua , Brett Tom J. , Alexander-Brett Jennifer M. 
Published: May 2024

AbstractTREM2 is a signaling receptor expressed on microglia that has emerged as an important potential drug target for Alzheimer’s disease and other neurodegenerative diseases. While a number of TREM2 signaling ligands have been identified, little is known regarding the structural details of how it engages them. To better understand this, we created a protein library of 28 different TREM2 variants and 11 different sTREM2 variants that could be used to map interactions with various ligands using biolayer interferometry (BLI). The variants are located in previously identified putative binding surfaces on TREM2 called the hydrophobic site, basic site, and site 2. We found that mutations to the hydrophobic site ablated binding to apoE4, oAb42, and TDP-43. Competition binding experiments further supported that apoE4 and oAb42 share overlapping binding sites on TREM2. In contrast, binding to IL-34 was mediated by the basic site at a surface centering on R76. Competition binding experiments validated a unique site for IL-34, showing little to no competition with either oAb42 or apoE4. Altogether, our results suggest that TREM2 utilizes the hydrophobic site (consisting of CDR1, CDR2, and CDR3) as a common site to engage multiple ligands, and further implies that pharmaceutical strategies targeting this surface might be effective to modulate TREM2 functions.
Role of human challenge trials (HCTs) in drug development for respiratory syncytial virus (RSV)
Authors: Kundu Prosenjit , Quinn Mark , Christensen Jared C. , Thomas Elaine , Toussi Sima S. , Alami Negar Niki , Banerjee Anindita 
Published: May 2024

AbstractHuman challenge trials (HCTs) are powerful in establishing early proof-of-concept for experimental drugs and understanding disease pathogenesis. In this study, we conducted a comprehensive assessment of HCTs to understand the viral load dynamics and symptom score kinetics of respiratory syncytial virus (RSV) to facilitate drug development for RSV. We estimated viral load (VL) and symptom related measures in placebo and relative reduction (RR) of the measures in the experimental drug using a systematic search on double-blind, placebo-controlled RSV HCTs from clinical databases. We used random-effects meta-analysis, except for time to mean peak VL and time to mean peak total symptom score (TSS), where descriptive statistics were summarized. Number of studies varied across measures, from 4 (151 subjects in total) to 7 (247 subjects in total). Overall, treatment reductions of 54% (95% CI: 32% – 76%, I2= 91%) and 76% (95% CI: 68% – 85%, I2= 19%) are observed in mean VL area under curve (AUC) and mean TSS AUC, respectively. In placebo, mean time to mean peak VL/TSS was 6.99/7.09 days (95% CI: 6.24/6.06 – 7.74/8.12 days). In comparison to other viruses in HCTs, peak VL occurs earlier for influenza (1.7 days) and at similar time for SARS-nCoV-2 (7 days), whereas peak TSS occurs earlier for influenza (2.9 days) and later for SARS-nCoV-2 (7.9 days). Our findings will inform researchers on disease course and VL kinetics, critical data needed for designing RSV treatment studies and understanding implications in clinical practice.
Multiplexed single cell transcriptomics optimizes mesodermal patterning and hemogenic endothelial output from murine embryonic stem cells
Authors: Varnum-Finney Barbara , Heck Adam M. , Srivatsan Sanjay R. , Dozono Stacey , Wellington Rachel , Nourigat-McKay Cynthia , Dignum Tessa , Trapnell Cole , Hadland Brandon 
Published: May 2024

SummaryEarly patterning of mesodermal precursor populations is a key step of hematopoietic development in the embryo. To better understand this process, we employed sci-Plex, a high-throughput method of measuring multiplexed perturbations at the single-cell level, to evaluate the transcriptional response of mouse embryonic stem cells subjected to a gradient of two key morphogens in early mesoderm/hematopoietic development, Activin and BMP4. sci-Plex revealed varying combinations of Activin and BMP4 temporally influenced mesoderm patterning in vitro and subsequent production of cell types reflecting their in vivo counterparts. We leveraged sci-Plex data to further optimize the generation of intraembryonic-like hemogenic endothelial cells that serve as the precursors of hematopoietic lineages, including hematopoietic stem cells. This study highlights the utility of sci-Plex to dissect how dose and temporal integration of interacting signal pathways determines cell fates and serves as a resource to analyze cell fate choices in early mesoderm patterning at single cell resolution.
Epidermal Growth Factor Receptor Regulates Beclin-1 in Hyperoxia
Authors: Harris Zachary M. , Korde Asawari , Khoury Johad , Manning Edward P. , Stanley Gail , Sun Ying , Hu Buqu , Shin Hyeon Jun , Joerns John , Clark Brian , Placek Lindsey , Unutmaz Derya , Chun Hyung , Sharma Lokesh , Sauler Maor , Rajagopalan Govindarajan , Zhang Xuchen , Wang He , Kang Min-Jong , Koff Jonathan L. 
Published: May 2024

ABSTRACTIntroductionMore than 300,000 patients are placed on mechanical ventilation in the ICU annually in the United States. Many of these patients will require hyperoxia (>70% oxygen) to prevent tissue hypoxia. We have previously shown that the tyrosine kinase receptor epidermal growth factor receptor (EGFR) regulates alveolar epithelial apoptosis in hyperoxia. Mice with reduced total EGFR activity (EGFRWa5/+mice) show improved survival and reduced markers of ALI compared with WT in hyperoxia. How EGFR regulates additional cell death pathways in hyperoxia remains to be explored.MethodsWe tested the hypothesis that EGFR regulates the molecule coiled-coil moesin-like BCL2-interacting protein (Beclin-1 [BCN1]), which is known to induce autophagy, in hyperoxia. Effects of 100% oxygen were studied in EGFRWa5/+mice and wildtype (WT) littermates. Mice were exposed to 100% oxygen for 24, 48, and 72 hours and compared with normoxia controls. Lungs were analyzed for BCN1 via Western blot (WB), RT-qPCR, immunohistochemistry (IHC), and flow cytometry. Whole-lung and cell-specific analyses were completed. The specific BCN1 phosphorylation site (p-BCN1), serine residue 91 and 94 (Ser91, −94) for mouse (Ser93, −96 for human), that regulates autophagy was examined.ResultsIn WT mice, hyperoxia induced increased whole-lung BCN1 compared with normoxia via WB and RT-qPCR. Whole-lung and epithelial-specific p-BCN1 was increased compared with normoxia via IHC and flow cytometry. Hyperoxia led to increased autophagy via WB and RT-qPCR. EGFRWa5/+mice showed increased BCN1 and reduced p-/total BCN1 ratios in hyperoxia compared with WT via WB. EGFRWa5/+mice also showed increased BCN1 via RT-qPCR and decreased epithelial-specific p-/total BCN1 ratios via flow cytometry, although this did not reach statistical significance. EGFRWa5/+mice showed reduced autophagy via WB compared with WT in hyperoxia.ConclusionsHyperoxia induced increased whole-lung and epithelial-specific BCN1 in hyperoxia and resulted in increased autophagy. Decreased EGFR activity, which leads to improved survival in hyperoxia, resulted in decreased whole-lung p-/total BCN1 ratios and decreased epithelial-specific p-/total BCN1 ratios in hyperoxiain vivo. Because BCN1 and autophagy can regulate cell death, EGFR regulation of p-BCN1 and autophagy is a mechanism in hyperoxia with therapeutic potential.
Evolutionary rewiring of the dynamic network underpinning allosteric epistasis in NS1 of influenza A virus
Authors: Gonzales James , Kim Iktae , Hwang Wonmuk , Cho Jae-Hyun 
Published: May 2024

AbstractViral proteins frequently mutate to evade or antagonize host innate immune responses, yet the impact of these mutations on the molecular energy landscape remains unclear. Epistasis, the intramolecular communications between mutations, often renders the combined mutational effects unpredictable. Nonstructural protein 1 (NS1) is a major virulence factor of the influenza A virus (IAV) that activates host PI3K by binding to its p85β subunit. Here, we present the deep analysis for the impact of evolutionary mutations in NS1 that emerged between the 1918 pandemic IAV strain and its descendant PR8 strain. Our analysis reveal how the mutations rewired inter-residue communications which underlies long-range allosteric and epistatic networks in NS1. Our findings show that PR8 NS1 binds to p85β with approximately 10-fold greater affinity than 1918 NS1 due to allosteric mutational effects. Notably, these mutations also exhibited long-range epistatic effects. NMR chemical shift perturbation and methyl-axis order parameter analyses revealed that the mutations induced long-range structural and dynamic changes in PR8 NS1, enhancing its affinity to p85β. Complementary MD simulations and graph-based network analysis uncover how these mutations rewire dynamic residue interaction networks, which underlies the long-range epistasis and allosteric effects on p85β-binding affinity. Significantly, we find that conformational dynamics of residues with high betweenness centrality play a crucial role in communications between network communities and are highly conserved across influenza A virus evolution. These findings advance our mechanistic understanding of the allosteric and epistatic communications between distant residues and provides insight into their role in the molecular evolution of NS1.
Circadian clock neurons use activity-regulated gene expression for structural plasticity
Authors: Lymer Seana , Patel Keyur , Lennon Jennifer , Blau Justin 
Published: May 2024

SummaryDrosophilas-LNv circadian pacemaker neurons show dramatic structural plasticity, with their projections expanded at dawn and then retracted by dusk. This predictable plasticity makes s-LNvs ideal to study molecular mechanisms of plasticity. Although s-LNv plasticity is controlled by their molecular clock, changing s-LNv excitability also regulates plasticity. Here, we tested the idea that s-LNvs use activity-regulated genes to control plasticity. We found that inducing expression of either of the activity-regulated transcription factors Hr38 or Sr (orthologs of mammalian Nr4a1 and Egr1) is sufficient to rapidly expand s-LNv projections. Conversely, transiently knocking down expression of eitherHr38orsrblocks expansion of s-LNv projections at dawn. We show that Hr38 rapidly induces transcription ofsif,which encodes a Rac1 GEF required for s-LNv plasticity rhythms. We conclude that the s-LNv molecular clock controls s-LNv excitability, which couples to an activity-regulated gene expression program to control s-LNv plasticity.
Genotypic identification of polyclonal plasma cells in plasma cell dyscrasias shows an aberrant single-cell phenotype with clinical implications
Authors: Da Vià Matteo Claudio , Lazzaroni Francesca , Matera Antonio , Marella Alessio , Maeda Akhiro , Magistris Claudio De , Pettine Loredana , Fabris Sonia , Pioggia Stefania , Marchetti Alfredo , Barbieri Marzia , Lonati Silvia , Cattaneo Alessandra , Tornese Marta , Scopetti Margherita , Latifinavid Nayyer , Castellano Giancarlo , Torricelli Federica , Neri Antonino , Fokkema Cathelijne , Coupedo Tom , Lionetti Marta , Passamonti Francesco , Bolli Niccolò 
Published: May 2024

SUMMARYMultiple Myeloma (MM) is driven by clonal plasma cell (PC)-intrinsic factors and changes in the tumorigenic microenvironment (TME). To investigate if residual polyclonal PCs (pPCs) are disrupted, single-cell (sc) RNAseq and sc B-cell receptor analysis were applied in a cohort of 46 samples with PC dyscrasias and 18 healthy donors (HDs). Out of n=213,074CD138posPCs, 42,717 were genotypically identified as pPCs. Compared to HDs, we detected quantitative and qualitative differences in pPCs of patients showing immunoparesis, where we showed a pro-inflammatory status, driven by specific cellular interactions with TME. Finally, we derived a “hPC signature” that, once inferred in the CoMMpass dataset, was predictive of PFS and OS. Our findings show that genotypic, single-cell identification of pPCs in PC dyscrasias has relevant pathogenic and clinical implications.