bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in the Public IgM Repertoire and its Idiotypic Connectivity in Alzheimer’s Disease and Frontotemporal Dementia
Authors: Pashova-Dimova Shina , Petrov Peter , Karachanak-Yankova Sena , Belezhanska Diana , Zhelev Yavor , Mehrabian Shima , Traykov Lachezar , Pashov Anastas 
Published: July 2024

AbstractAlzheimer’s disease (AD) and frontotemporal dementia (FTD) are prevalent neurodegenerative disorders. Early diagnosis is challenging due to the lack of definitive biomarkers and reliance on invasive procedures. Immune biomarkers, particularly those reflecting the interaction between the central nervous system (CNS) and the peripheral immune system, have shown promise for non-invasive detection through blood samples. This study investigates the reactivity of serum IgM and IgG from AD and FTD patients against a library of mimotopes representing public IgM reactivities in healthy donors. Serum samples from AD, FTD, and other neurodegenerative dementias (ND), and controls were tested on peptide microarrays. The samples were pooled to mitigate individual variability. The reactivity data were analyzed using graphs to represent the cross-reactivity networks. The analysis revealed distinct reactivity patterns for the studied groups. Public IgM reactivities showed significant correlations with neurodegenerative conditions, with AD and FTD exhibiting loss or gain of specific IgM reactivities. Graph analysis highlighted significant differences in graph density, clustering, and assortativity parameters between disease and control groups. Idiotypic reactivities, particularly in IgM, were more connected in healthy controls compared to those with neurodegenerative diseases. Furthermore, clusters of reactivities showed significant distinctions between AD and FTD, with IgG reactivities providing additional differentiation. A number of self proteins related to neurodegeneration proved to have sequences homologous to disease associated mimotopes. Thus, the public IgM repertoire, characterized by its broad reactivity and inherent autoreactivity, offers valuable insights into the immunological alterations in neurodegenerative diseases. The study supports the potential of IgM and IgG reactivity profiles as another compartment of non-invasive biomarkers for early diagnosis and differentiation of AD and FTD.
Sex-Specific causal dynamic between Insulin resistance and MDD, a bidirectional Mendelian randomization study
Authors: Xia Qizhou , Silveira Patricia P. 
Published: July 2024

AbstractAims/hypothesisObservational studies have shown a bidirectional association between major depressive disorder (MDD), Insulin resistance (IR), and related diseases, which varies between sexes and ancestries. We conducted a sex-specific two-sample bidirectional Mendelian randomization (MR) study to assess the causal associations of MDD with Insulin resistance measured through the TG: HDL-C ratio and vice versa using Caucasian and East Asian data.MethodsWe extracted summary-level data for MDD and insulin resistance from corresponding published large genome-wide association studies of individuals of European descent and partially replicated the analyses using available summary data from studies of individuals of East Asian descent. The random-effects inverse-variance weighted method and MRlap method were used for the main analyses for non-overlapping and overlapping samples, respectively.ResultsGenetic liability to MDD was significantly associated with insulin resistance both generally and sex-specifically, while the causal effect of Insulin resistance on MDD is only consistently significant in females. We did not find any significant causal association between IR and MDD using East Asian data, though the beta estimates suggest potentially ancestry-related differences in the direction of effect.Conclusions/interpretationThe present study strengthened the evidence that MDD is a potential risk factor for insulin resistance and that insulin resistance plays a sex—and ancestry-specific role in MDD pathology. Together, these findings could contribute to further our understanding of the comorbidity between MDD and IR-related diseases, allowing for more individualized treatment and diagnosis.
Exploring the potential of Claude 2 for risk of bias assessment: Using a large language model to assess randomized controlled trials with RoB 2
Authors: Eisele-Metzger Angelika , Lieberum Judith-Lisa , Toews Markus , Siemens Waldemar , Heilmeyer Felix , Haverkamp Christian , Boehringer Daniel , Meerpohl Joerg J 
Published: July 2024

ABSTRACTSystematic reviews are essential for evidence based healthcare, but conducting them is time and resource consuming. To date, efforts have been made to accelerate and (semi-) automate various steps of systematic reviews through the use of artificial intelligence and the emergence of large language models (LLMs) promises further opportunities. One crucial but complex task within systematic review conduct is assessing the risk of bias of included studies. Therefore, the aim of this study was to test the LLM Claude 2 for risk of bias assessment of 100 randomized controlled trials using the revised Cochrane risk of bias tool (“RoB 2”; involving judgements for five specific domains and an overall judgement). We assessed the agreement of risk of bias judgements by Claude with human judgements published in Cochrane Reviews. The observed agreement between Claude and Cochrane authors ranged from 41% for the overall judgement to 71% for domain 4 (“outcome measurement”). Cohen’s κ was lowest for domain 5 (“selective reporting”; 0.10 (95% confidence interval (CI): −0.10-0.31)) and highest for domain 3 (“missing data”; 0.31 (95% CI: 0.10-0.52)), indicating slight to fair agreement. Fair agreement was found for the overall judgement (Cohen’s κ: 0.22 (95% CI: 0.06-0.38)). Sensitivity analyses using alternative prompting techniques or the more recent version Claude 3 did not result in substantial changes. Currently, Claude’s RoB 2 judgements cannot replace human risk of bias assessment. However, the potential of LLMs to support risk of bias assessment should be further explored.
Examining National Health Insurance Fund Members’ preferences and trade-offs for the attributes of contracted outpatient facilities in Kenya: a discrete choice experiment
Authors: Kazungu Jacob , Barasa Edwine , Nonvignon Justice , Quaife Matthew 
Published: July 2024

AbstractPatient choice of health facilities is increasingly gaining recognition for potentially enhancing the attainment of health system goals globally. In Kenya, National Health Insurance Fund (NHIF) members are required to choose an NHIF-contracted outpatient facility before accessing care. Understanding their preferences could support resource allocation decisions, enhance the provision of patient-centered care, and deepen NHIF’s purchasing decisions. We employed a discrete choice experiment to examine NHIF members’ preferences for attributes of NHIF-contracted outpatient facilities in Kenya. We developed a d-efficient experimental design with six attributes, namely availability of drugs, distance from household to facility, waiting time at the facility until consultation, cleanliness of the facility, attitude of health worker, and cadre of health workers seen during consultation. Data were then collected from 402 NHIF members in six out of 47 counties. Choice data were analysed using panel mixed multinomial logit and latent class models. NHIF members preferred NHIF-contracted outpatient facilities that always had drugs [β=1.572], were closer to their households [β=-0.082], had shorter waiting times [β=-0.195], had respectful staff [β=1.249] and had either clinical officers [β=0.478] or medical doctors [β=1.525] for consultation. NHIF members indicated a willingness to accept travel 17.8km if drugs were always available, 17.7km to see a medical doctor for consultation, and 14.6km to see respectful health workers. Furthermore, NHIF members indicated a willingness to wait at a facility for 8.9 hours to ensure the availability of drugs, 8.8 hours to see a doctor for consultation, and 7.2 hours to see respectful health workers. Understanding NHIF member preferences and trade-offs can inform resource allocation at counties, service provision across providers, and purchasing decisions of purchasers such as the recently formed social health insurance authority in Kenya as a move towards UHC.
Assessing the clinical meaningfulness of slowing CDR-SB progression with disease-modifying therapies for Alzheimer disease
Authors: Hartz Sarah M. , Schindler Suzanne E. , Streitz Marissa L. , Moulder Krista L. , Mozersky Jessica , Wang Guoqiao , Xiong Chengjie , Morris John C. 
Published: July 2024

AbstractINTRODUCTIONFor many patients and caregivers, a major goal of disease-modifying treatments (DMT) for Alzheimer disease (AD) dementia is to extend independence in instrumental and basic activities of daily living (IADLs and BADLs). The goal of this study was to estimate the effect of treatments on the time remaining independent in IADLs and BADLs.METHODSParticipants at the Knight Alzheimer Disease Research Center were selected who were potentially eligible for recent DMT trials: age ≥ 60 years at baseline, clinical diagnosis of very mild or mild AD dementia (global Clinical Dementia Rating® (CDR®) score 0.5 or 1), biomarker confirmation of amyloid pathology, and at least one follow-up CDR assessment within 5 years. For IADLs, a subset of the Functional Assessment Questionnaire (FAQ) was examined that rated the degree of independence in the following: paying bills, driving, remembering medications and appointments, and preparing meals. For BADLs, the Personal Care domain of the CDR was used. Mixed-effects logistic and ordinal regression models were used to examine the relationship between CDR Sum Boxes (CDR-SB) and the individual functional outcomes and their components. The change in CDR-SB over time was estimated with linear mixed effects models.RESULTS282 participants were followed for an average of 2.9 years (SD 1.3 years). For 50% of individuals, loss of independence in IADLs occurred at CDR-SB>4.5 and in BADLs at CDR-SB>11.5. For individuals with a baseline CDR-SB=2, treatment with lecanemab would extend independence in IADLs for 10 months (95% CI 4-18 months) and treatment with donanemab in the low/medium tau group would extend independence in IADLs by 13 months (95% CI 6-24 months).DISCUSSIONIndependence in ADLs can be related to CDR-SB and used to demonstrate the effect of AD treatments in extending the time of independent function, a meaningful outcome for patients and their families.
Allosteric regulation of the tyrosine phosphatase PTP1B by a protein-protein interaction
Authors: Chartier Cassandra A. , Woods Virgil A. , Xu Yunyao , van Vlimmeren Anne E. , Johns Andrew C. , Jovanovic Marko , McDermott Ann E. , Keedy Daniel A. , Shah Neel H. 
Published: July 2024

AbstractThe rapid identification of protein-protein interactions has been significantly enabled by mass spectrometry (MS) proteomics-based methods, including affinity purification-MS, crosslinking-MS, and proximity-labeling proteomics. While these methods can reveal networks of interacting proteins, they cannot reveal how specific protein-protein interactions alter protein function or cell signaling. For instance, when two proteins interact, there can be emergent signaling processes driven purely by the individual activities of those proteins being co-localized. Alternatively, protein-protein interactions can allosterically regulate function, enhancing or suppressing activity in response to binding. In this work, we investigate the interaction between the tyrosine phosphatase PTP1B and the adaptor protein Grb2, which have been annotated as binding partners in a number of proteomics studies. This interaction has been postulated to co-localize PTP1B with its substrate IRS-1 by forming a ternary complex, thereby enhancing the dephosphorylation of IRS-1 to suppress insulin signaling. Here, we report that Grb2 binding to PTP1B also allosterically enhances PTP1B catalytic activity. We show that this interaction is dependent on the proline-rich region of PTP1B, which interacts with the C-terminal SH3 domain of Grb2. Using NMR spectroscopy and hydrogen-deuterium exchange mass spectrometry (HDX-MS) we show that Grb2 binding alters PTP1B structure and/or dynamics. Finally, we use MS proteomics to identify other interactors of the PTP1B proline-rich region that may also regulate PTP1B function similarly to Grb2. This work presents one of the first examples of a protein allosterically regulating the enzymatic activity of PTP1B and lays the foundation for discovering new mechanisms of PTP1B regulation in cell signaling.Significance StatementProtein-protein interactions are critical for cell signaling. The interaction between the phosphatase PTP1B and adaptor protein Grb2 co-localizes PTP1B with its substrates, thereby enhancing their dephosphorylation. We show that Grb2 binding also directly modulates PTP1B activity through an allosteric mechanism involving the proline-rich region of PTP1B. Our study reveals a novel mode of PTP1B regulation through a protein-protein interaction that is likely to be exploited by other cellular interactors of this important signaling enzyme.
Titration-WB: A methodology for accurate quantitative protein determination overcoming reproducibility errors
Authors: Maestri Alice , Ehrenborg Ewa , Werngren Olivera , Olin Maria , Hagberg Carolina E. , Pedrelli Matteo , Parini Paolo 
Published: July 2024

AbstractWestern blot (WB) technique is widely used to identify and quantify proteins in biological samples, but it is poorly accurate and precise for quantitative purposes. Merging the WB with the titration assay, we established a reliable method for protein quantification based on the slope of the linear function for signal-intensity/total protein loaded. Titration-WB unravels systematic and operator errors, compensates for problems in antibody affinity/avidity, and permits trustworthy inter-WB comparison.
Molecular basis of FIGNL1 in dissociating RAD51 from DNA and chromatin
Authors: Carver Alexander , Yu Tai-Yuan , Yates Luke A , White Travis , Wang Raymond , Lister Katie , Jasin Maria , Zhang Xiaodong 
Published: July 2024

AbstractMaintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central player of several crucial processes in repairing and protecting genome integrity, forms filaments on DNA. RAD51 filaments are tightly regulated. One of these regulators is FIGNL1, that prevents persistent RAD51 foci post-damage and genotoxic chromatin association in cells. The cryogenic electron microscopy structure of FIGNL1 in complex with RAD51 reveals that the FIGNL1 forms a non-planar hexamer and RAD51 N-terminus is enclosed in the FIGNL1 hexamer pore. Mutations in pore loop or catalytic residues of FIGNL1 render it defective in filament disassembly and are lethal in mouse embryonic stem cells. Our study reveals a unique mechanism for removing RAD51 from DNA and provides the molecular basis for FIGNL1 in maintaining genome stability.
Multi-ion Frequency Reference Using Dynamical Decoupling
Authors: Pelzer Lennart , Dietze Kai , Martínez-Lahuerta Víctor José , Krinner Ludwig , Kramer Johannes , Dawel Fabian , Spethmann Nicolas C. H. , Hammerer Klemens , Schmidt Piet O. 
Published: July 2024

We present the experimental realization of a continuous dynamical decoupling scheme which suppresses leading frequency shifts in a multi-ion frequency reference based on Ca+40. By near-resonant magnetic coupling of the S21/2 and D25/2 Zeeman sublevels using radio-frequency dressing fields, engineered transitions with reduced sensitivity to magnetic-field fluctuations are obtained. A second stage detuned dressing field reduces the influence of amplitude noise in the first stage driving fields and decreases 2nd-rank tensor shifts, such as the electric quadrupole shift. Suppression of the quadratic dependence of the quadrupole shift to 3(2)  mHz/μm2 and coherence times of 290(20) ms on the optical transition are demonstrated even within a laboratory environment with significant magnetic field noise. Besides removing inhomogeneous line shifts in multi-ion clocks, the demonstrated dynamical decoupling technique may find applications in quantum computing and simulation with trapped ions by a tailored design of decoherence-free subspaces.

Published by the American Physical Society
2024
Kilonova light-curve interpolation with neural networks
Authors: Peng Yinglei , Ristić Marko , Kedia Atul , O'Shaughnessy Richard , Fontes Christopher J. , Fryer Chris L. , Korobkin Oleg , Mumpower Matthew R. , Villar V. Ashley , Wollaeger Ryan T. 
Published: July 2024

Kilonovae are the electromagnetic transients created by the radioactive decay of freshly synthesized elements in the environment surrounding a neutron star merger. To study the fundamental physics in these complex environments, kilonova modeling requires, in part, the use of radiative transfer simulations. The microphysics involved in these simulations results in high computational cost, prompting the use of emulators for parameter inference applications. Utilizing a training set of 22 248 high-fidelity simulations (composed of 412 unique ejecta parameter combinations evaluated at 54 viewing angles), we use a neural network to efficiently train on existing radiative transfer simulations and predict light curves for new parameters in a fast and computationally efficient manner. Our neural network can generate millions of new light curves in under a minute. We discuss our emulator's degree of off-sample reliability and parameter inference of the AT2017gfo observational data. Finally, we discuss tension introduced by multiband inference in the parameter inference results, particularly with regard to the neural network's recovery of viewing angle.

Published by the American Physical Society
2024
Modeling the unphysical pseudomode model with physical ensembles: Simulation, mitigation, and restructuring of non-Markovian quantum noise
Authors: Cirio Mauro , Luo Si , Liang Pengfei , Nori Franco , Lambert Neill 
Published: July 2024

The influence of a Gaussian environment on a quantum system can be described by effectively replacing the continuum with a discrete set of ancillary quantum and classical degrees of freedom. This defines a pseudomode model which can be used to classically simulate the reduced system dynamics. Here we consider an alternative point of view and analyze the potential benefits of an analog or digital quantum simulation of the pseudomode model itself. Superficially, such a direct experimental implementation is, in general, impossible due to the unphysical properties of the effective degrees of freedom involved. However, we show that the effects of the unphysical pseudomode model can still be reproduced using measurement results over an ensemble of physical systems involving ancillary harmonic modes and an optional stochastic driving field. This is done by introducing an extrapolation technique whose efficiency is limited by stability against imprecision in the measurement data. We examine how such a simulation would allow us to (i) perform a quantum simulation of the effects of complex nonperturbative and non-Markovian environments in regimes that are challenging for classical simulation; (ii) conversely, mitigate potential unwanted non-Markovian noise present in quantum devices; and (iii) restructure some of the properties of a given physical bath, such as its temperature.

Published by the American Physical Society
2024
Do many options result in listening to oneself or others during boycott campaigns?
Authors: Yan Xiuyan , Kim Changju , Kim Jungkeun , Inoue Masato 
Published: July 2024

PurposeThis study empirically investigates whether and how boycott attitudes and subjective norms influence the impact of the perceived behavioral control of boycotts on boycott intention.Design/methodology/approachTo test our hypotheses, we perform a hierarchical linear regression analysis using data from Japanese (n = 500) and South Koreans (n = 571).FindingsBoycott attitudes strengthen the positive effect of perceived behavioral control on boycott intentions for Japanese and South Koreans. Contrary to our assumptions, while the direct impact of perceived behavioral control on boycott intention is not significant, there is a negative moderating effect of subjective norms for Japanese consumers.Originality/valueWe argue that when perceived behavioral control is evident in boycotts, consumers listen more to themselves than to others. Our cross-national analysis of actual boycott campaigns is the first study on boycott research to offer implications for the interaction effects among the three key antecedents of psychological motivation factors in the theory of planned behavior.
The psychedelic mind: Current user perceptions of psychedelic drugs and their use
Authors: McGruddy Sarah , Whelan Jai , Mills Ethan , Boardman Alexander , Ward Ryan D. 
Published: July 2024

Purpose
Psychedelic drugs can induce altered states of consciousness characterised by changes in visual perception, tactile sensation, cognition, and emotion. Although there is a history of misinformation surrounding these drugs, recent investigation has reinvigorated interest. However, little research has assessed the attitudes of psychedelic consumers regarding these substances. The current study aims to explore the attitudes and perceptions of people with experience with psychedelic drugs, specifically surrounding psychedelic drugs themselves and their use within Aotearoa New Zealand.

Design/methodology/approach
Nineteen individuals with experience of psychedelic use were recruited to participate across eight groups in semi-structured, exploratory interviews, where a range of topics associated with psychedelics were discussed. Reflexive thematic analysis of the data focussed on participants’ current perceptions and attitudes.

Findings
Four themes were produced: (1) a negative historical influence on current perceptions of psychedelics; (2) knowledge is key but not everyone has it; (3) prohibition is not working, policy needs to change; (4) psychedelics have therapeutic potential. These themes emphasise key features of people with experience of psychedelic drugs’ current views and highlight potential areas for future investigation and intervention.

Social implications
Findings indicate a need for greater public knowledge and awareness of psychedelics in Aotearoa society. Findings also inform information, education and policy, which in turn will reduce the stigma and associated harm that those who have used or use psychedelic drugs may experience.

Originality/value
To the best of the authors’ knowledge, qualitative research aiming to understand attitudes and perspectives surrounding psychedelic drugs and their use from a drug users’ perspective have not yet been assessed.