bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved diagnostic accuracy for polymyalgia rheumatica using FDG-PET/CT with clinical diagnosis or 2012 ACR/EULAR classification criteria
Authors: Nielsen Andreas Wiggers , van der Geest Kornelis S M , Hansen Ib Tønder , Nielsen Berit Dalsgaard , Kjær Søren Geill , Blegvad-Nissen Jesper , Nienhuis Pieter H , Sandovici Maria , Rewers Kate , Sørensen Christian Møller , Slart Riemer H J A , Gormsen Lars Christian , Brouwer Elisabeth , Hauge Ellen-Margrethe , Keller Kresten Krarup 
Published: July 2024

Abstract

Objective
In routine care, clinicians may employ 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET/CT to validate their initial clinical diagnosis of PMR. Nevertheless, the diagnostic utility of combining FDG-PET/CT findings with clinical presentation has not been explored. Therefore, this study aimed to investigate whether the diagnostic accuracy for PMR could be enhanced by combining FDG-PET/CT findings with the clinical baseline diagnosis or the 2012 ACR/EULAR clinical classification criteria for PMR.

Methods
An investigation and a validation cohort were included from two countries, encompassing 66/27 and 36/21 PMR/non-PMR patients, respectively. The cohorts comprised treatment-naïve patients suspected of PMR, who initially received a clinical baseline diagnosis and underwent FDG-PET/CT scans. The FDG-PET/CT Leuven score was applied to classify patients as either PMR or non-PMR and combined with the clinical baseline diagnosis. Final diagnoses were established through clinical follow-up after 12 or six months in the investigation and validation cohorts, respectively.

Results
In the investigation cohort, a clinical baseline diagnosis yielded a sensitivity/specificity of 94%/82%, compared with 78%/70% using the ACR/EULAR criteria. Combining the clinical baseline diagnosis with a positive Leuven score showed a sensitivity/specificity of 80%/93%, compared with 80%/82% for an ACR/EULAR-Leuven score. In the validation cohort, the baseline diagnosis revealed a sensitivity/specificity of 100%/91%, compared with 92%/76% using the ACR/EULAR criteria. Combining FDG-PET/CT with the baseline diagnosis demonstrated a sensitivity/specificity of 83%/95% compared with 89%/81% for the ACR/EULAR-Leuven score.

Conclusion
Combining FDG-PET/CT findings with the clinical baseline diagnosis or ACR/EULAR clinical classification criteria can improve the diagnostic specificity for PMR.
Impact of real-world implementation of evidence-based insomnia treatment within a large payor-provider health system: initial provider and patient-level outcomes
Authors: Karlin Bradley E , Anderson Ryan J , Rung Jillian M , Drury-Gworek Charlotte , Barrett Tyson S 
Published: July 2024

Abstract

Study Objectives
Insomnia has substantial and wide-ranging negative effects on clinical and functional outcomes and on health care expenditures, yet few individuals receive gold-standard insomnia treatment. The current article examines provider and patient outcomes associated with real-world implementation of Cognitive Behavioral Therapy for Insomnia (CBT-I), as part of a pilot initiative designed to establish initial capability for evidence-based insomnia treatment within one of the largest payor-provider systems in the United States.

Methods
Provider training outcomes were assessed using the CBT-I Competency Rating Scale and self-report measures. Patient outcomes were assessed using the Insomnia Severity Index (ISI) and Patient Health Questionnaire-9.

Results
All clinicians (N = 11) achieved competency in CBT-I and reported large increases in knowledge and confidence related to insomnia and insomnia treatment. Clinicians also reported high intention to deliver CBT-I and significant improvements in overall job satisfaction following competency-based CBT-I training. Among all patients who initiated CBT-I (N = 48), mixed effects modeling demonstrated significant reduction in average ISI scores (12.57 to 5.88, SEs = 1.08-1.14). More than two-thirds of patients (68.8%) completed treatment. Among completers of this brief treatment, mean insomnia severity improvement was 71% (Hedges g = 1.56).

Conclusions
Findings provide support for the feasibility and effectiveness of real-world CBT-I implementation, extending past findings to a private, payor-provider context. Patient and provider-level outcomes suggest the significant opportunity private systems may have in increasing the availability of gold-standard treatment for insomnia.
The Impact of Strengths-Based Working on Long-Term Housing Outcomes: A Qualitative Comparative Analysis
Authors: Gellen Sandor , Fox Chris 
Published: July 2024

Abstract
Strengths-based working (SBW) is being adopted across multiple sectors, but the evidence base for its effectiveness is limited. In this assessment of a social outcomes contract, authors evaluated the impact of SBW on the delivery of homelessness-related outcomes for a high-risk client group. The novel impact evaluation design first identified characteristics in frontline staff associated with SBW and then decoded conjectural causal links between these characteristics and their clients’ social outcomes using qualitative comparative analysis. Data were collected from 65 frontline workers, measuring reflective practice, self-efficacy, and innovativeness. Authors found that clients of staff who most strongly exhibited characteristics associated with SBW achieved better long-term outcomes. This article makes four important contributions to our understanding of SBW. First, authors show how it is possible to undertake rigorous impact evaluation of SBW in a complex setting and identify moderately complex causal relations with limited sample size. Second, authors propose and test the presence of key characteristics associated with SBW and, in doing so, contribute to the theoretical understanding of SBW. Third, authors present new evidence on the effectiveness of SBW. Finally, the article demonstrates how social outcomes contracts can provide a framework for testing innovative social interventions.
Difficult to treat Pseudomonas: successful salvage therapy with cefepime-zidebactam
Authors: Sebastian Anjely , Naik Shivdas , Varma Muralidhar , Sreekumar N C , Thomas Joseph , Rao Tanvi , Shah Birva J , Gupta Nitin 
Published: July 2024

Abstract
Carbapenem-resistant Pseudomonas aeruginosa (CRPa) infection is extremely challenging to manage. Cefepime-zidebactam is a novel combination that can be considered for salvage therapy when no other antimicrobials are susceptible. A 15-y-old boy presented with 56% thermal burns, followed by skin and soft tissue infection, secondary bacteraemia, complicated parapneumonic effusion and endophthalmitis due to CRPa, which was not susceptible to any of the routinely available antibiotics. He was treated with cefepime-zidebactam for 45 d, with which he recovered.
The CentiMarker Project: Standardizing Quantitative Alzheimer’s disease Fluid Biomarkers for Biologic Interpretation
Authors: Wang Guoqiao , Li Yan , Xiong Chengjie , Cao Yuchen , Schindler Suzanne E. , McDade Eric , Blennow Kaj , Hansson Oskar , Dage Jeffrey L. , Jack Clifford R. , Teunissen Charlotte E. , Shaw Leslie M , Zetterberg Henrik , Ibanez Laura , Timsina Jigyasha , Carlos Cruchaga ,   the DIAN-TU Study Team, Bateman Randall J. 
Published: July 2024

ABSTRACTIntroductionBiomarkers have been essential to understanding Alzheimer’s disease (AD) pathogenesis, pathophysiology, progression, and treatment effects. However, each biomarker measure is a representation of the biological target, the assay used to measure it, and the variance of the assay. Thus, biomarker measures are difficult to compare without standardization, and the units and magnitude of effect relative to the disease are difficult to appreciate, even for experts. To facilitate quantitative comparisons of AD biomarkers in the context of biologic and treatment effects, we propose a biomarker standardization approach between normal ranges and maximum abnormal AD ranges, which we refer to as CentiMarker, similar to the Centiloid approach used in PET.MethodsWe developed a standardization scale that creates percentile values ranging from 0 for a normal population to 100 for the most abnormal measures across disease stages. We applied this scale to CSF and plasma biomarkers in autosomal dominant AD, assessing the distribution by estimated years from symptom onset, between biomarkers, and across cohorts. We then validated this approach in a large national sporadic AD cohort.ResultsWe found the CentiMarker scale provided an easily interpretable metric of disease abnormality. The biologic changes, range, and distribution of several AD fluid biomarkers including amyloid-β, phospho-tau and other biomarkers, were comparable across disease stages in both early onset autosomal dominant and sporadic late onset AD.DiscussionThe CentiMarker scale offers a robust and versatile framework for the standardized biological comparison of AD biomarkers. Its broader adoption could facilitate biomarker reporting, allowing for more informed cross-study comparisons and contributing to accelerated therapeutic development.
Cervical Cancer Screening Seeking Behavior among Female Community Health Volunteers of Surkhet District
Authors: Thapa Yamuna , Bhatta Bimala 
Published: July 2024

AbstractBackgroundHuman Papilloma virus (HPV) associated cervical cancer is the fourth most common cancer in women worldwide and it is the leading cause of death among women in Nepal. The screening seeking behavior encompasses a woman’s decision to engage in medical evaluations essential for the early detection and prophylaxis of cervical cancer. Even though there is a proven importance of cervical cancer screening, the incidence and mortality rate in Nepal is high. Therefore, we aimed to assess the cervical cancer screening seeking behavior and its associated factors among female community health volunteers (FCHVs) of Surkhet district, Nepal.MethodsA community based cross-sectional study was carried out in the municipalities and rural municipalities of Surkhet district. A pre-tested structured interview was conducted among 148 FCHVs from 30-49 years.ResultsThis study showed that 90 (60.8%) of FCHVs have cervical cancer screening seeking behavior. Age (AOR: 7.2, 95% CI: 3.01-17.3) and marital status (AOR: 9.2, 95% CI: 2.6-166.2) of FCHVs were significant factors for cervical cancer seeking behavior.ConclusionThese findings highlight the importance of demographic factors in promoting screening participation among FCHVs. Enhancing cervical cancer screening rates among FCHVs requires multifaceted approaches that address both individual perceptions and barriers. Interventions should focus on increasing accessibility, improving education and awareness programs, and providing tailored support to different demographic groups.
Gz Enhanced Signal Transduction assaY (GZESTY) for GPCR deorphanization
Authors: Franchini Luca , Porter Joseph J. , Lueck John D. , Orlandi Cesare 
Published: July 2024

AbstractG protein-coupled receptors (GPCRs) are key pharmacological targets, yet many remain underutilized due to unknown activation mechanisms and ligands. Orphan GPCRs, lacking identified natural ligands, are a high priority for research, as identifying their ligands will aid in understanding their functions and potential as drug targets. Most GPCRs, including orphans, couple to Gi/o/zfamily members, however current assays to detect their activation are limited, hindering ligand identification efforts.We introduce GZESTY, a highly sensitive, cell-based assay developed in an easily deliverable format designed to study the pharmacology of Gi/o/z-coupled GPCRs and assist in deorphanization. We optimized assay conditions and developed an all-in-one vector employing novel cloning methods to ensure the correct expression ratio of GZESTY components. GZESTY successfully assessed activation of a library of ligand-activated GPCRs, detecting both full and partial agonism, as well as responses from endogenous GPCRs. Notably, with GZESTY we established the presence of endogenous ligands for GPR176 and GPR37 in brain extracts, validating its use in deorphanization efforts. This assay enhances the ability to find ligands for orphan GPCRs, expanding the toolkit for GPCR pharmacologists.
Mechanisms Ensuring Fidelity of Family X DNA Polymerases in Programmed DNA rearrangements in Paramecium tetraurelia
Authors: Nourisson Antonin , Missoury Sophia , Haouz Ahmed , Delarue Marc 
Published: July 2024

ABSTRACTRepairing programmed DNA double-strand breaks (DSBs) is crucial in the lifecycle ofParamecium tetraurelia, especially during its sexual reproduction phase when its somatic highly polyploid macronucleus is lost. The formation of a new macronucleus involves Programmed Genome Rearrangements, introducing DNA DSBs at approximately 45,000 loci.P. tetraureliaemploys a Non-Homologous End Joining (NHEJ)-related mechanism for the systematic repair of these DSBs. Four genes encoding DNA polymerases of family X are present in the genome, one of which was found recently to colocalize with other proteins of NHEJ. The question arises as to how they make almost no error. Here we show that these enzymes are most similar to metazoan DNA polymerase λ and exhibit high fidelity through two different molecular mechanisms. Using X-ray structure determination of polymerase lambda mutants recapitulating sequence determinants ofP. tetraureliaPolXs, we find both a local conformational change that involves exchanging partners in a crucial salt bridge in the active site upon binding of correct dNTPs, and a larger conformational change involving the closure of Loop3. This stabilizes the template DNA in the active site, only in the presence of the correct incoming dNTP. Differences with human pol λ and pol β are discussed.GRAPHICAL ABSTRACT
Regeneration following tissue necrosis is mediated by non-apoptotic caspase activity
Authors: Klemm Jacob W. , Hazel Chloe Van , Harris Robin E. 
Published: July 2024

AbstractTissue necrosis is a devastating complication for many human diseases and injuries. Unfortunately, our understanding of necrosis and how it impacts surrounding healthy tissue – an essential consideration when developing effective methods to treat such injuries – has been limited by a lack of robust genetically tractable models. Our lab previously established a method to study necrosis-induced regeneration in theDrosophilawing imaginal disc, which revealed a unique phenomenon whereby cells at a distance from the injury upregulate caspase activity in a process called Necrosis-induced Apoptosis (NiA) that is vital for regeneration. Here we have further investigated this phenomenon, showing that NiA is predominantly associated with the highly regenerative pouch region of the disc, shaped by genetic factors present in the presumptive hinge. Furthermore, we find that a proportion of NiA fail to undergo apoptosis, instead surviving effector caspase activation to persist within the tissue and stimulate reparative proliferation late in regeneration. This proliferation relies on the initiator caspase Dronc, and occurs independent of JNK, ROS or mitogens associated with the previously characterized Apoptosis-induced Proliferation (AiP) mechanism. These data reveal a new means by which non-apoptotic Dronc signaling promotes regenerative proliferation in response to necrotic damage.
Decoding protein phosphorylation during oocyte meiotic divisions using phosphoproteomics
Authors: Peshkin Leonid , Daldello Enrico Maria , Van Itallie Elizabeth , Sonnett Matthew , Kreuzer Johannes , Haas Wilhelm , Kirschner Marc W , Jessus Catherine 
Published: July 2024

ABSTRACTOocyte meiotic divisions represent a critical process in sexual reproduction, as a diploid non-dividing oocyte is transformed into a haploid fertilizable egg, as a prelude for the subsequent embryonic divisions and differentiation. Although cell differentiation and proliferation are governed by transcription, oocyte maturation and early embryonic divisions depend entirely on changes in protein abundance and post- translational modifications. Here, we analyze the abundance and phosphorylation of proteins duringXenopusoocyte meiotic maturation. We reveal significant shifts in protein stability, related to spindle assembly, DNA replication and RNA-binding. Our analysis pinpoints broad changes in phosphorylation correlating with key cytological meiotic milestones, noteworthy changes in membrane trafficking, nuclear envelope disassembly and modifications in microtubule dynamics. Additionally, specific phosphorylation events target regulators of protein translation, Cdk1 and the Mos/MAPK pathway, thereby providing insight into the dynamics of Cdk1 activity, as related to the meiotic cell cycle. This study sheds light on the orchestration of protein dynamics and phosphorylation events during oocyte meiotic divisions, providing a rich resource for understanding the molecular pathways orchestrating meiotic progression in the frog, and most likely applicable to other vertebrate species.
Peri-mitochondrial actin filaments inhibit Parkin assembly via disruption of ER- mitochondrial contact
Authors: Fung Tak Shun , Ghosh Amrapali , Tigano Marco , Higgs Henry N , Chakrabarti Rajarshi 
Published: July 2024

AbstractMitochondrial damage represents a dramatic change in cellular homeostasis, necessitating metabolic adaptation as well as clearance of the damaged organelle. One rapid response to mitochondrial damage is peri-mitochondrial actin polymerization within 2 mins, which we term ADA (AcuteDamaged-inducedActin). ADA is vital for a metabolic shift from oxidative phosphorylation to glycolysis upon mitochondrial dysfunction. In the current study we investigated the effect of ADA on Pink1/Parkin mediated mitochondrial quality control. We show that inhibition of proteins involved in the ADA pathway significantly accelerates Parkin recruitment onto depolarized mitochondria. Addressing the mechanism by which ADA resists Parkin recruitment onto depolarized mitochondria, we found that ADA disrupts ER- mitochondrial contacts in an Arp2/3 complex-dependent manner. Interestingly, over-expression of ER-mitochondrial tethers overrides the effect of ADA, allowing rapid recruitment of not only Parkin but also LC3 after mitochondrial depolarization. During chronic mitochondrial dysfunction, Parkin and LC3 recruitment are completely blocked, which is reversed rapidly by inhibiting ADA. Taken together we show that ADA acts as a protective mechanism, delaying mitophagy following acute damage, and blocking mitophagy during chronic mitochondrial damage.
The intersection of endocrine signaling and neuroimmune communication regulates neonatal nociception
Authors: Fadaka Adewale O. , Dourson Adam J. , Hofmann Megan C. , Gupta Prakriti , Raut Namrata G.R. , Jankowski Michael P. 
Published: July 2024

AbstractNeonatal pain is a significant clinical issue but the mechanisms by which pain is produced early in life are poorly understood. Our recent work has linked the transcription factor serum response factor downstream of local growth hormone (GH) signaling to incision-related hypersensitivity in neonates. However, it remains unclear if similar mechanisms contribute to inflammatory pain in neonates. We found that local GH treatment inhibited neonatal inflammatory myalgia but appeared to do so through a unique signal transducer and activator of transcription (STAT) dependent pathway within sensory neurons. The STAT1 transcription factor appeared to regulate peripheral inflammation itself by modulation of monocyte chemoattractant protein 1 (MCP1) release from sensory neurons. Data suggests that STAT1 upregulation, downstream of GH signaling, contributes to neonatal nociception during muscle inflammation through a novel neuroimmune loop involving cytokine release from primary afferents. Results could uncover new ways to treat muscle pain and inflammation in neonates.Graphical Abstract
Optimization of flight conditions based on performance sensitivity analysis for jet transport aircraft
Authors: Jiang Wei , Guo Hun , Zhu Danye , Chang Ray C. 
Published: July 2024

Purpose
This study aims to enhance the fuel efficiency of jet transport aircraft based on mathematical models and flight crew operating manual (FCOM) for the purpose to assist the civil aviation industry in improving flight safety and operational efficiency.

Design/methodology/approach
The research applies flight data mining and fuzzy logic modeling technologies to set up lift-to-drag ratio (L/D) models and nine models of thrust, Mach number, engine pressure ratio and fuel flow rate to estimate the deviation of each flight parameter. All performance deviations are calculated based on the values of flight data recorded in the quick access recorder and FCOM at the observed flight conditions. The L/D model can obtain the influence of each flight parameter and estimate the insufficient amount of each parameter by averaging it with the least square method. In the estimation of optimal altitude, nine models are built based on data from FCOM to estimate the optimal altitude and complete comparative analysis of the airspeed, Mach number and fuel flow rate at the optimal altitude.

Findings
Analyze 11 relevant parameters from the sensitivity derivative of L/D model to obtain how each parameter affected fuel consumption and explore the causes of additional fuel consumption. Complete the estimation of the optimal cruise altitude of the aircraft, and calculate the comparative analysis of the altitude, speed, Mach number and other parameters with the sensitivity derivative of the L/D. The estimation of the optimal cruise altitude of the aircraft can meet the analysis of the sensitivity derivative.

Research limitations/implications
This study is to enhance the fuel efficiency of jet commercial transport based on mathematical model and FCOM. FCOM is required to conduct this study. The estimation of the optimal cruise altitude through the nine models of the aircraft could meet the analysis of the sensitivity derivative.

Practical implications
The object of present research is to demonstrate the effectiveness of optimization of flight conditions through model analysis to get knowledge of the effects of each influencing flight variable to L/D for future flight operations’ reference.

Social implications
The model-based derivative analysis had the ability to perform derivative prediction analysis on any input parameters, more flight parameters could be optimized in future research to help airlines improve flight safety and operational efficiency.

Originality/value
The present enhancement method of fuel efficiency is an innovation to examine the abnormal aircraft performance and its flight operations, thereby to explore the causes of additional fuel consumption. The present method can become an auxiliary tool for flight operations quality assurance to improve fuel efficiency for the airlines.