bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Severity of Depressive Symptoms as an Independent Predictor of Sustained Virological Response During Treatment of Hepatitis C With Pegylated Interferon-α2a and Oral Ribavirin
Authors: Pawłowski Tomasz , Radkowski Marek , Perlejewski Karol , Laskus Tomasz , Małyszczak Krzysztof 
Published: January 2024

ABSTRACT

Background
Sustained virological response (SVR) is the best indicator of successful therapy for hepatitis C virus (HCV) infection. Patients with chronic HCV infection treated with pegylated interferon-α and ribavirin (PEG-IFN-α/RBV) can achieve SVR 56% of the time.

Objectives
This study aimed to evaluate baseline predictors of SVR in patients treated with PEG-IFN-α/RBV for HCV chronic infection.

Methods
A total of 101 patients receiving PEG-IFN-α/RBV for chronic HCV infection participated in the prospective cohort study. Symptoms of depression were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) before the treatment. The multivariate regression analysis was applied to determine predictors of SVR.

Results
Of a total of 101 patients included, 99 patients reached the primary end point—24 weeks after completing treatment. After the initial analysis of probable predictive variables, the logistic analysis included age, sex, HCV genetic type, and MADRS score. The HCV genotype (odds ratio = 0.22 [confidence interval = 0.073–0.68, p = .008) and MADRS score (OR = 0.88 [confidence interval = 0.80–0.98), p = .013]) predicted an SVR outcome.

Conclusions
The severity of depressive symptoms before treatment and HCV genotype are independent predictors of SVR.
Preexisting Psychiatric Conditions as Risk Factors for Diagnosed Long COVID-19 Syndrome Within Aggregated Electronic Health Record Data
Authors: Bobak Lukas , Dorney Ian , Kovacevich Alexsandra , Barnett Brian , Kaelber David C. 
Published: January 2024

ABSTRACT

Objective
This study aimed to investigate the frequency of long COVID diagnosis among patients infected with severe acute respiratory syndrome coronavirus 2 with preexisting psychiatric conditions versus those without preexisting psychiatric conditions.

Methods
The TriNetX Analytics platform, an aggregated electronic health record research network containing the deidentified electronic health record data of more than 90 million patients, was queried for patients who were diagnosed with COVID-19 infection based on International Classifications of Disease, Tenth Revision codes. Patients were stratified based on their preexisting psychiatric conditions, and new diagnoses of long COVID were recorded and reported as the primary outcome.

Results
Among 1,180,948 patients previously diagnosed with COVID-19, 17,990 patients (1.52%) were diagnosed with long COVID based on the newly implemented International Classifications of Disease, Tenth Revision code “U09: post–COVID-19 condition.” After propensity score matching, patients with any preexisting psychiatric diagnosis had a 1.52 (95% confidence interval [CI] = 1.47–1.58) times greater prevalence of diagnosed long COVID within 180 days of infection than patients without preexisting psychiatric diagnoses. Patients with diagnosed anxiety disorders (relative risk [RR] = 1.64; 95% CI = 1.57–1.71), mood disorders (RR = 1.65; 95% CI = 1.57–1.72), bipolar disorder (RR = 1.37; 95% CI = 1.21–1.54), major depressive disorder (RR = 1.69; 95% CI = 1.56–1.83), psychotic disorders (RR = 1.23; 95% CI = 1.06–1.44), and substance use disorders (RR = 1.28; 95% CI = 1.22–1.36) had higher risks for long COVID diagnoses when compared with patients without preexisting psychiatric illness at the time of diagnosis.

Conclusions
Multiple preexisting psychiatric diagnoses are associated with an increased risk of being diagnosed with long COVID after COVID-19 infection.
Optimism and Sleep in Aging Women: Bidirectional Relationships
Authors: Monroe Addison D. , Judge Stephanie T. , Bass Chelsea L. , Crofford Leslie J. , Segerstrom Suzanne C. 
Published: January 2024

Objective
Sleep quality and duration are important for biological restoration and promotion of psychological well-being. Optimism may facilitate or result from sufficient sleep, but questions remain as to directionality. The present study tested how optimism is associated with levels of and variability in sleep quantity and quality in a longitudinal burst design.

Methods
Midlife and older women (N = 199) reported their sleep quantity and quality in online diaries for a 7-day period, every 3 months for 2 years. Optimism was measured at baseline and end-of-study. Multilevel models tested the effects of optimism on sleep. Linear regression models tested the effect of sleep on optimism.

Results
Baseline optimism was associated with higher sleep quality (γ = 2.13 [1.16 to 3.11], p < .0001) and lower intraindividual variability (IIV; night-to-night and wave-to-wave) in sleep quantity (night-to-night: γ = −0.07 [−0.13 to −0.005], p = .03; wave-to-wave: b = −0.07 [−0.12 to −0.02], p = .003). In turn, higher average sleep quality (but not quantity) was associated with higher optimism at end-of-study (b = 0.02 [0.007 to 0.03], p = .002). Variability in sleep was unrelated to optimism.

Conclusions
Optimism may play an important role in maintaining sleep quality and consistency in sleep quantity, perhaps by buffering stress. Similarly, sleep quality may play an important role in maintaining optimism. The cycle whereby optimism and sleep enhance one another could improve physical health and psychological well-being among aging adults.
Role of Shear Wave Elastography of Placenta in Prediction of Preeclampsia in High-Risk Pregnancy
Authors: Singh Tulika , Roy Choudhury Shayeri , Singh Mandeep , Singla Veenu , Jain Vanita 
Published: January 2024

Abstract
The aim of our study was to compare the placental elasticity values between normal pregnancies and preeclamptic pregnancies and evaluate the utility of shear-wave elastography of the placenta as a predictor for preeclampsia in high-risk pregnancy. A prospective study was performed with 90 singleton high-risk pregnancies having any of the 7 risk factors for developing preeclampsia (primigravida, history of preeclampsia, family history of preeclampsia, history of pregestational diabetes, chronic hypertension, advanced maternal age [≥40 years], and body mass index ≥26 kg/m2) were enrolled in the study. Shear-wave elastography was performed in all patients at 20 to 24 weeks' gestation and at 34 to 36 weeks' gestation, at 2 sites: center and edge of the placenta. The patients were divided into 2 groups: normal pregnancies (group A) or developed preeclampsia (group B). Women with posterior placentation, obstetric disorders other than preeclampsia, or multiple gestation were excluded from the study. Group comparisons were done using the χ
2 test or Fisher exact test. Shear-wave elasticity values at 20 to 24 weeks' gestation for group B at the center of the placenta (21.73 vs 9.72 kPa) and at the edge of the placenta (21.6 kPa vs 10.15 kPa) were significantly higher than those for group A (P < 0.05). Similar results were seen at 34 to 36 weeks' gestation. With a cutoff of 13.1 kPa, we attained sensitivity of 95.2%, specificity of 92.8% and diagnostic accuracy of 93.3% for predicting development of preeclampsia. Patients with preeclampsia have a significantly higher stiffness of the placenta. Shear-wave elastography is useful to evaluate placental function. Elastography can be used as a supplementary tool for prediction of preeclampsia.
Post-operative pain management by nurses in an intensive care unit: a best practice implementation project
Authors: Moraes Érica Brandão de , Antunes Juliane de Macedo , Ferrari Maria Fernanda Muniz , Fontes Bárbara Ventura , Pereira Renata Castro da Silva , Ogawa Luciana , Daher Donizete Vago 
Published: January 2024

ABSTRACTIntroduction:Post-operative pain is the most prevalent type of acute pain. Nurses are the health care professionals who most frequently assess pain, as well as evaluating the patient's response to pain management treatment and monitoring for the occurrence of adverse events. Thus, to improve outcomes and quality of care, the interventions used by nurses should be based on best practices.Objectives:The aim of this project was to implement best practices in post-operative pain management in an intensive care unit.Methods:This evidence implementation project was conducted in a hospital for the surgical treatment of orthopedic diseases and trauma. The project followed the JBI Evidence Implementation Framework. The project used JBI PACES software as well as JBI's Getting Research into Practice (GRiP) audit and feedback tools to develop eight audit criteria for the baseline and follow-up audits.Results:The baseline audit showed that Criteria 3 and 6 had low compliance, with few patients having documented plans and goals, and receiving multimodal analgesia in the ICU, respectively. Criteria 7 and 8, which assessed the use of opioids and follow-up by a pain specialist, revealed compliance of 60% and 50%, respectively. Criterion 3 improved from 0% to 20%. Criteria 6, 7, and 8 also improved, rising to 30%, 22.8%, and 50%, respectively.Conclusion:The project improved compliance with best practices in post-operative pain management. Further studies are needed to ensure the project's long-term sustainability.
Development of a NanoBRET assay for evaluation of 14-3-3σ molecular glues
Authors: Vickery Holly R. , Virta Johanna M. , Konstantinidou Markella , Arkin Michelle R. 
Published: January 2024

AbstractWe report the development of a 384-well formatted NanoBRET assay to characterize molecular glues of 14-3-3/client interactions in living cells. The seven isoforms of 14-3-3 are dimeric hub proteins with diverse roles including transcription factor regulation and signal transduction. 14-3-3 interacts with hundreds of client proteins to regulate their function and is therefore an ideal therapeutic target when client selectivity can be achieved. We have developed the NanoBRET system for three 14-3-3σ client proteins CRAF, TAZ, and estrogen receptor α (ERα), which represent three specific binding modes. We have measured stabilization of 14-3-3σ/client complexes by molecular glues with EC50values between 100 nM and 1 μM in cells, which align with the EC50values calculated by fluorescence anisotropy in vitro. Developing this NanoBRET system for the hub protein 14-3-3σ allows for a streamlined approach, bypassing multiple optimization steps in the assay development process for other 14-3-3σ clients. The NanoBRET system allows for an assessment of PPI stabilization in a more physiologically relevant, cell-based environment using full-length proteins. The method is applicable to diverse protein-protein interactions (PPIs) and offers a robust platform to explore libraries of compounds for both PPI stabilizers and inhibitors.Abstract Figure
Kinetoplastid kinetochore proteins KKT14-KKT15 are divergent Bub1/BubR1-Bub3 proteins
Authors: Ballmer Daniel , Carter William , van Hooff Jolien J. E. , Tromer Eelco C. , Ishii Midori , Ludzia Patryk , Akiyoshi Bungo 
Published: January 2024

AbstractFaithful transmission of genetic material is crucial for the survival of all organisms. In many eukaryotes, a feedback control mechanism called the spindle checkpoint ensures chromosome segregation fidelity by delaying cell cycle progression until all chromosomes achieve proper attachment to the mitotic spindle. Kinetochores are the macromolecular complexes that act as the interface between chromosomes and spindle microtubules. While most eukaryotes have canonical kinetochore proteins that are widely conserved, kinetoplastids such asTrypanosoma bruceihave a seemingly unique set of kinetochore proteins including KKT1–25. Available evidence suggests thatT. bruceilacks components of the spindle checkpoint and is unable to delay cell cycle progression in response to spindle defects. It therefore remains poorly understood how kinetoplastids regulate cell cycle progression or ensure chromosome segregation fidelity. Here, we report a crystal structure of the C-terminal domain of KKT14 fromApiculatamorpha spiralisand uncover that it is a pseudokinase. Its structure is most similar to the kinase domain of Bub1, a key component of the spindle checkpoint in other eukaryotes. In addition, KKT14 inT. bruceiand other trypanosomatids has a putative ABBA motif that is present in Bub1 and its paralog BubR1. We also find that the N-terminal part of KKT14 interacts with KKT15, whose WD40 repeat beta-propeller is phylogenetically closely related to a direct interactor of Bub1/BubR1 called Bub3. Our findings indicate that KKT14-KKT15 are divergent orthologs of Bub1/BubR1-Bub3, which promote accurate chromosome segregation in trypanosomes.
Uncovering the Elusive Structures and Mechanisms of Prevalent Antidepressants
Authors: Lin Jieye , Bu Guanhong , Unge Johan , Gonen Tamir 
Published: January 2024

AbstractMost treatments to alleviate major depression work by either inhibiting human monoamine transporters, vital for the reuptake of monoamine neurotransmitters, or by inhibiting monoamine oxidases, which are vital for their degradation. The analysis of the experimental 3D structures of those antidepressants in their drug formulation state is key to precision drug design and development. In this study, we apply microcrystal electron diffraction (MicroED) to reveal the atomic 3D structures for the first time of five of the most prevalent antidepressants (reboxetine, pipofezine, ansofaxine, phenelzine, bifemelane) directly from the commercially available powder of the active ingredients. Their modes of binding are investigated by molecular docking, revealing the essential contacts and conformational changes into the biologically active state. This study underscores the combined use of MicroED and molecular docking to uncover elusive drug structures and mechanisms to aid in further drug development pipelines.
Epstein–Barr Virus BALF0/1 Subverts the Caveolin and ERAD Pathways to Target B-cell Receptor Complexes for Degradation
Authors: Yiu Stephanie Pei Tung , Weekes Michael , Gewurz Benjamin E. 
Published: January 2024

ABSTRACTEpstein–Barr virus (EBV) establishes persistent infection, causes infectious mononucleosis, is a major trigger for multiple sclerosis and contributes to multiple cancers. Yet, knowledge remains incomplete about how the virus remodels host B cells to support lytic replication. We previously identified that EBV lytic replication results in selective depletion of plasma membrane B-cell receptor (BCR) complexes, comprised of immunoglobulin and the CD79A and CD79B signaling chains. Here, we used proteomic and biochemical approaches to identify that the EBV early lytic protein BALF0/1 is responsible for EBV lytic cycle BCR degradation. Mechanistically, an immunoglobulin heavy chain cytoplasmic tail KVK motif was required for ubiquitin-mediated BCR degradation, while CD79A and CD79B were dispensable. BALF0/1 subverted caveolin-mediated endocytosis to internalize plasma membrane BCR complexes and to deliver them to the endoplasmic reticulum. BALF0/1 stimulated immunoglobulin heavy chain cytoplasmic tail ubiquitination, which together with the ATPase valosin-containing protein/p97 drove ER-associated degradation of BCR complexes by cytoplasmic proteasomes. BALF0/1 knockout reduced the viral load of secreted EBV particles from B-cells that expressed a monoclonal antibody against EBV glycoprotein 350 and increased viral particle immunoglobulin incorporation. Consistent with downmodulation of plasma membrane BCR, BALF0/1 overexpression reduced viability of a diffuse large B-cell lymphoma cell line dependent upon BCR signaling. Collectively, our results suggest that EBV BALF0/1 downmodulates immunoglobulin upon lytic reactivation to block BCR signaling and support virion release.SIGNIFICANCEEBV uses a biphasic lifecycle, in which it switches between a latent state that facilitates immune evasion and a lytic state, where virion are secreted. However, when EBV infects a B-cell that makes antibody against a virion protein, EBV must have a strategy to escape becoming trapped, since maturing virion and antibody each traffic through the secretory pathway. We identified that an EBV-encoded protein expressed, BALF0/1, associates with and targets immunoglobulin complexes for degradation. Intriguingly, BALF0/1 subverts the caveolin-1 and ERAD pathways to route antibody from the plasma membrane to cytoplasmic proteasomes for degradation. We present evidence that this enhances EBV secretion from cells that produce antibody against a viral glycoprotein, which could otherwise trap virus.
The volitional control of individual motor units is constrained within low-dimensional neural manifolds by common inputs
Authors: Rossato Julien , Avrillon Simon , Tucker Kylie , Farina Dario , Hug François 
Published: January 2024

AbstractThe implementation of low-dimensional movement control by the central nervous system has been debated for decades. In this study, we investigated the dimensionality of the control signals received by spinal motor neurons when controlling either the ankle or knee joint torque. We first identified the low-dimensional latent factors underlying motor unit activity during torque- matched isometric contractions. Subsequently, we evaluated the extent to which motor units could be independently controlled. To this aim, we used an online control paradigm in which participants received the corresponding motor unit firing rates as visual feedback. We identified two main latent factors, regardless of the muscle group (vastus lateralis-medialis and gastrocnemius lateralis-medialis). The motor units of the gastrocnemius lateralis could be controlled largely independently from those of the gastrocnemius medialis during ankle plantarflexion. This dissociation of motor unit activity imposed similar behavior to the motor units that were not displayed in the feedback. Conversely, it was not possible to dissociate the activity of the motor units between the vastus lateralis and medialis muscles during the knee extension tasks. These results demonstrate that the number of latent factors estimated from linear dimensionality reduction algorithms does not necessarily reflect the dimensionality of volitional control of motor units. Overall, individual motor units were never controlled independently of all others but rather belonged to synergistic groups. Together, these findings provide evidence for a low-dimensional control of motor units constrained by common inputs, with notable differences between muscle groups.Significance statementIn this study, we initially examined the latent factors underlying motor unit activity in the vastii or gastrocnemii muscles during torque-matched isometric contractions. We then explored the extent to which these motor units could be controlled independently, using an online control paradigm where participants received visual information on motor unit firing rates. Although participants were able to dissociate the activity of a few motor unit pairs (from the gastrocnemius medialis and lateralis muscles), our results provide direct evidence of a low- dimensional control, constrained by common inputs, limiting flexibility in motor unit recruitment. Furthermore, we show that the number of latent factors identified by dimensionality reduction algorithms does not necessarily reflect the dimensionality of volitional control of motor units.
Implication of structural constrains facilitating the functional evolution ofPseudomonas aeruginosaKPR2 into a versatile α-keto acid reductase
Authors: Choudhury Gourab Basu , Datta Saumen 
Published: January 2024

AbstractProtein structure and function dynamics in molecular evolution are intertwined. Theoretical concepts linking structure, function, and evolution of a protein, while often intuitive, necessitate validation through investigations in real-world systems. Our study empirically explores the implications of multiple panE2 gene copies in an organism, shedding light on the functional roles and evolutionary trajectories ofPseudomonas aeruginosa’ssecond copy of Ketopantoate reductase (PaKPR2) and its inactivity against the natural substrate Ketopantoate. Evolutionary changes in functional traits were examined around the active site through crystal structures and biochemical analysis. Primarily, apoKPR2 structures reveal a transformed active site cleft, forming a two-sided pocket, while substrate entry is regulated by a molecular gate. Despite cleft closure, molecular interaction properties and activity analysis of PaKPR2 suggest that it can be a versatile keto-acid reductase. However, detailed structural insights from the ligand-bound binary complex of PaKPR2-NADPH and PaKPR2-Ketoisoleucine reveal that the ligand-binding interactions at the active site are conserved and restricted to the molecules of appropriate shape and size that can be accommodated in the available space. Finally, a ternary complex structure, PaKPR2-NADP+-KIC, was solved to understand its functional evolution in terms of the residue microenvironment at the catalytic site. Collectively, the results give detailed visual experiences of different structural perspectives of the protein’s functional evolution.
Structural basis of archaeal RNA polymerase transcription elongation and Spt4/5 recruitment
Authors: Tarau Daniela , Grünberger Felix , Pilsl Michael , Reichelt Robert , Heiß Florian , König Sabine , Urlaub Henning , Hausner Winfried , Engel Christoph , Grohmann Dina 
Published: January 2024

AbstractArchaeal transcription is carried out by a multi-subunit RNA polymerase (RNAP) that is highly homologous in structure and function to eukaryotic RNAP II. Among the set of basal transcription factors, only Spt5 is found in all domains of life but Spt5 has been shaped during evolution, which is also reflected in the heterodimerization of Spt5 with Spt4 in Archaea and Eukaryotes. To unravel the mechanistic basis of Spt4/5 function in Archaea, we performed structure-function analyses using the archaeal transcriptional machinery ofPyrococcus furiosus(Pfu). We report single-particle cryo-electron microscopy reconstructions of apo RNAP and the archaeal elongation complex (EC) in the absence and presence of Spt4/5. Surprisingly,PfuSpt4/5 also binds the RNAP in the absence of nucleic acids in a distinct super-contracted conformation. We show that the RNAP clamp/stalk module exhibits conformational flexibility in the apo state of RNAP and that the enzyme contracts upon EC formation or Spt4/5 engagement. We furthermore identified a contact of the Spt5-NGN domain with the DNA duplex that stabilizes the upstream boundary of the transcription bubble and impacts Spt4/5 activityin vitro. This study, therefore, provides the structural basis for Spt4/5 function in archaeal transcription and reveals a potential role beyond the well-described support of elongation.
Identification and validation of ITS2-specific universal primers for DNA barcoding in plants
Authors: Bhat Ajay R , Hegde Subrahmanya , Kammar Supriya S , Muthamma MB , Mudgal Gaurav , R Charukesi , Mohan Thotegowdanapalya C 
Published: January 2024

AbstractAccurate identification of plant species is fundamental for various purposes, including biodiversity conservation and effective utilization of plants. Molecular-based techniques, particularly DNA barcoding, have emerged as a rapid and accurate alternative to traditional taxonomic methods for plant species identification. DNA barcoding involves analysing specific DNA regions to classify and identify organisms. Among different barcode markers, internal transcribed spacer 2 (ITS2) has gained prominence due to its shorter length and ease of sequencing. In this study we present a comprehensive survey of the literature, identifying a universal set of primers for ITS2 and validating their universality through in silico and in vitro analyses. This manuscript provides valuable insights into establishing a standardized approach for DNA barcoding using ITS2, helping researchers select appropriate primers for accurate plant species identification and classification. Standardized universal primers alleviate the time-consuming primer selection process, promoting efficient and reliable DNA barcoding practices within the plant scientific community.