bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonging neutrophil room temperature storage with clinically-approved solutions: Implications for granulocyte transfusion
Authors: Labrecque Marie-Michèle , Allard Marie-Ève , Murru Andréa , Paré Guillaume , Acker Jason P , Lesage Sylvie , Girard Mélissa , Fernandes Maria J
Published: December 2024

Introduction

Granulocyte concentrates (GC) are leukocyte preparations enriched in neutrophils that can potentially save neutropenic patients from life-threatening, antimicrobial-resistant infections. The main challenge of GC transfusions is preserving the viability and antimicrobial activity of neutrophils beyond 24 h to reduce the logistical burden on collection centers and increase the availability of this cell therapy. Thus, the aim of this study was to explore extending the ex vivo viability and antimicrobial activity of GC neutrophils up to 72 h with a unique combination of the clinically-approved additives Plasma-Lyte, SAGM, AS-3 and Alburex.

Methods

Neutrophils isolated from healthy donors were resuspended in autologous plasma (AP) at the same concentration as in GCs and diluted with various combinations of Plasma-Lyte, SAGM, AS-3 and/or Alburex with or without the addition of buffers, and stored at room temperature for up to 72 h. During storage, neutrophil viability, phagocytosis and intracellular reactive oxygen species production were measured by flow cytometry. Extracellular reactive oxygen species production was measured by spectrophotometry and chemotaxis by the number of calcein stained neutrophils that migrated towards the chemotactic peptide, N-Formyl-Met-Leu-Phe (fMLF). The same assays were performed on pooled, residual leukocyte units generated by the Reveos system, after storage in the additive combination that most effectively preserved the viability and function of isolated neutrophils.

Results

The additive combination that best performed in the majority of the assays contained Plasma-Lyte, buffers and AS-3. Neutrophil viability was preserved for a maximum of 48 h and phagocytosis of opsonized bacteria and reactive oxygen species production up to 72 h of storage at room temperature. In contrast, fMLF-induced chemotaxis decreased by 20 % after 24 h storage while extracellular reactive oxygen species production increased significantly within the same time period. Supplementing GCs prepared from pooled, residual leukocyte units with this storage solution after the standard 16-24 h processing period as per the blood center guidelines, did not significantly improve the preservation of neutrophil viability and function.

Conclusion

Our findings provide proof of concept that mixtures of clinically-approved additives can be tailored to significantly prolong the viability and function of freshly isolated neutrophils during room temperature storage. The unique additive composition of this storage solution that we developed for freshly isolated neutrophils, requires further optimization for use with pooled, residual leukocyte units as well as the time point at which the solution is added during processing to prolong the viability and functions of neutrophils in this blood product.
Hierarchical Bayesian models to mitigate systematic disparities in prediction with proxy outcomes
Authors: Mikhaeil Jonas M , Gelman Andrew , Greengard Philip
Published: December 2024

Label bias occurs when the outcome of interest is not directly observable and instead, modelling is performed with proxy labels. When the difference between the true outcome and the proxy label is correlated with predictors, this can yield systematic disparities in predictions for different groups of interest. We propose Bayesian hierarchical measurement models to address these issues. When strong prior information about the measurement process is available, our approach improves accuracy and helps with algorithmic fairness. If prior knowledge is limited, our approach allows assessment of the sensitivity of predictions to the unknown specifications of the measurement process. This can help practitioners gauge if enough substantive information is available to guarantee the desired accuracy and avoid disparate predictions when using proxy outcomes. We demonstrate our approach through practical examples.
Radio Galaxy Zoo data release 1: 100185 radio source classifications from the FIRST and ATLAS surveys
Authors: Wong O Ivy , Garon A F , Alger M J , Rudnick L , Shabala S S , Willett K W , Banfield J K , Andernach H , Norris R P , Swan J , Hardcastle M J , Lintott C J , White S V , Seymour N , Kapińska A D , Tang H , Simmons B D , Schawinski K
Published: December 2024

Radio galaxies can extend far beyond the stellar component of their originating host galaxies, and their radio emission can consist of multiple discrete components. Furthermore, the apparent source structure will depend on survey sensitivity, resolution and the observing frequency. Associated discrete radio components and their originating host galaxy are typically identified through a visual comparison of radio and mid-infrared survey images. We present the first data release of Radio Galaxy Zoo, an online citizen science project that enlists the help of citizen scientists to cross-match extended radio sources from the Faint Images of the Radio Sky at Twenty Centimeters (FIRST) and the Australia Telescope Large Area Survey (ATLAS) surveys, often with complex structure, to host galaxies in 3.6 $\mu$m infrared images from the Wide-field Infrared Survey Explorer (WISE) and the SpitzerSpace Telescope. This first data release consists of 100 185 classifications for 99 146 radio sources from the FIRST survey and 583 radio sources from the ATLAS survey. We include two tables for each of the FIRST and ATLAS surveys: (1) the identification of all components making up each radio source and (2) the cross-matched host galaxies. These classifications have an average reliability of 0.83 based on the weighted consensus levels of our citizen scientists. The reliability of the DR1 catalogue has been further demonstrated through several parallel studies which used the pre-release versions of this catalogue to train and prototype machine learning-based classifiers. We also include a brief description of the radio source populations catalogued by RGZ DR1.
A field-level emulator for modified gravity
Authors: Saadeh Daniela , Koyama Kazuya , Morice-Atkinson Xan
Published: December 2024

Stage IV surveys like LSST and Euclid present a unique opportunity to shed light on the nature of dark energy. However, their full constraining power cannot be unlocked unless accurate predictions are available at all observable scales. Currently, only the linear regime is well understood in models beyond $\Lambda$CDM: on the non-linear scales, expensive numerical simulations become necessary, whose direct use is impractical in the analyses of large data sets. Recently, machine learning techniques have shown the potential to break this impasse: by training emulators, we can predict complex data fields in a fraction of the time it takes to produce them. In this work, we present a field-level emulator capable of turning a $\Lambda$CDM N-body simulation into one evolved under $f(R)$ gravity. To achieve this, we build on the map2map neural network, using the strength of modified gravity $|f_{\mathrm{ R}_0}|$ as style parameter. We find that our emulator correctly estimates the changes it needs to apply to the positions and velocities of the input N-body particles to produce the target simulation. We test the performance of our network against several summary statistics, finding $1{{\ \rm per\ cent}}$ agreement in the power spectrum up to $k \sim 1$ h Mpc$^{-1}$, and $1.5{{\ \rm per\ cent}}$ agreement against the independent boost emulator emantis. Although the algorithm is trained on fixed cosmological parameters, we find it can extrapolate to models it was not trained on. Coupled with available field-level emulators and simulation suites for $\Lambda$CDM, our algorithm can be used to constrain modified gravity in the large-scale structure using full information available at the field level.
Psi-GAN: a power-spectrum-informed generative adversarial network for the emulation of large-scale structure maps across cosmologies and redshifts
Authors: Bhambra Prabh , Joachimi Benjamin , Lahav Ofer , Piras Davide
Published: December 2024

Simulations of the dark matter distribution throughout the Universe are essential in order to analyse data from cosmological surveys. N-body simulations are computationally expensive, and many cheaper alternatives (such as lognormal random fields) fail to reproduce accurate statistics of the smaller, non-linear scales. In this work, we present Psi-GAN (power-spectrum-informed generative adversarial network), a machine learning model that takes a two-dimensional lognormal dark matter density field and transforms it into a more realistic field. We construct Psi-GAN so that it is continuously conditional, and can therefore generate realistic realizations of the dark matter density field across a range of cosmologies and redshifts in $z \in [0, 3]$. We train Psi-GAN as a generative adversarial network on $2\, 000$ simulation boxes from the Quijote simulation suite. We use a novel critic architecture that utilizes the power spectrum as the basis for discrimination between real and generated samples. Psi-GAN shows agreement with N-body simulations over a range of redshifts and cosmologies, consistently outperforming the lognormal approximation on all tests of non-linear structure, such as being able to reproduce both the power spectrum up to wavenumbers of $1~h~\mathrm{Mpc}^{-1}$, and the bispectra of target N-body simulations to within ${\sim }5$ per cent. Our improved ability to model non-linear structure should allow more robust constraints on cosmological parameters when used in techniques such as simulation-based inference.
The fragmentation of molecular clouds in starburst environments
Authors: Cusack Matt T , Clark Paul C , Glover Simon C O , Klessen Ralf S , Girichidis Philipp , Whitworth Anthony P , Priestley Felix D
Published: December 2024

A significant amount of star formation occurs and has occurred in environments unlike the solar neighbourhood. The majority of stars formed closer to the peak of the cosmic star formation rate ($z \rm \gt 1.3$) and a great deal of star formation presently occurs in the central molecular zone (CMZ) of the Galaxy. These environments are unified by the presence of a high interstellar radiation field (ISRF) and a high cosmic ray ionization rate (CRIR). Numerical studies of stellar birth typically neglect this fact, and those that do not have thus far been limited in scope. In this work, we present the first comprehensive analysis of hydrodynamical simulations of star formation in extreme environments where we have increased the ISRF and CRIR to values typical of the CMZ and starburst galaxies. We note changes in the fragmentation behaviour on both the core and stellar system scale, leading to top-heavy core and stellar system mass functions in high ISRF/CRIR clouds. Clouds fragment less on the core scale, producing fewer but more massive cores. Conversely, the cores fragment more intensely and produce richer clusters of stellar systems. We present a picture where high ISRF/CRIR clouds fragment less on the scale of cores and clumps, but more on the scale of stellar systems. The change in fragmentation behaviour subsequently changes the mass function of the stellar systems that form through enhanced accretion rates.
Glucocorticoid tapering pace in microscopic polyangiitis and granulomatosis with polyangiitis in Japanese real-world practice: A propensity score-matched retrospective cohort study from the J-CANVAS registry
Authors: Nishioka Ryo , Omura Satoshi , Nakagomi Daiki , Abe Yoshiyuki , Kadoya Masatoshi , Takizawa Naoho , Nomura Atsushi , Kukida Yuji , Kondo Naoya , Yamano Yasuhiko , Yanagida Takuya , Endo Koji , Hirata Shintaro , Matsui Kiyoshi , Takeuchi Tohru , Ichinose Kunihiro , Kato Masaru , Yanai Ryo , Matsuo Yusuke , Shimojima Yasuhiro , Okazaki Ryota , Takata Tomoaki , Ito Takafumi , Moriyama Mayuko , Takatani Ayuko , Miyawaki Yoshia , Ito-Ihara Toshiko , Kawaguchi Takashi , Yajima Nobuyuki , Kida Takashi , Kawahito Yutaka , Mizushima Ichiro
Published: December 2024

Objective

To assess the prevalence and outcomes among regimens of glucocorticoid tapering for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in real-world practice.

Methods

We retrospectively examined the Japan Collaborative Registry of Antineutrophil Cytoplasmic Antibodies-associated Vasculitis (J-CANVAS) registry, and evaluated the prevalence of glucocorticoid tapering regimens in the PEXIVAS trial. In patients with newly diagnosed MPA and GPA, we compared outcomes among standard and reduced pace regimens. Relapse-free survival rates were compared after propensity score matching.

Results

Of 364 eligible patients, 113 (31.0%) received standard tapering and 251 slower tapering. After matching, 87 pairs no significant difference was observed in relapse-free survival (P = .506). Regarding the reduced regimen, there were so few patients (14/364, 3.8%) that statistical analysis was not performed.

Conclusions

The glucocorticoid tapering for MPA and GPA in Japanese real-world practice was found to be generally slower than the standard regimen revealing a huge evidence-practice gap. Additionally, slower tapering did not improve relapse-free survival and might cause unnecessary glucocorticoid exposure.
Defining gene ends: RNA polymerase II CTD threonine 4 phosphorylation marks transcription termination regions genome-wide
Authors: Kopczyńska Magda , Saha Upasana , Romanenko Anastasiia , Nojima Takayuki , Gdula Michał R , Kamieniarz-Gdula Kinga
Published: December 2024

Defining the beginning of a eukaryotic protein-coding gene is relatively simple. It corresponds to the first ribonucleotide incorporated by RNA polymerase II (Pol II) into the nascent RNA molecule. This nucleotide is protected by capping and maintained in the mature messenger RNA (mRNA). However, in higher eukaryotes, the end of mRNA is separated from the sites of transcription termination by hundreds to thousands of base pairs. Currently used genomic annotations only take account of the end of the mature transcript – the sites where pre-mRNA cleavage occurs, while the regions in which transcription terminates are unannotated. Here, we describe the evidence for a marker of transcription termination, which could be widely applicable in genomic studies. Pol II termination regions can be determined genome-wide by detecting Pol II phosphorylated on threonine 4 of its C-terminal domain (Pol II CTD-T4ph). Pol II in this state pauses before leaving the DNA template. Up to date this potent mark has been underused because the evidence for its place and role in termination is scattered across multiple publications. We summarize the observations regarding Pol II CTD-T4ph in termination regions and present bioinformatic analyses that further support Pol II CTD-T4ph as a global termination mark in animals.
Homologous recombination shapes the architecture and evolution of bacterial genomes
Authors: Torrance Ellis L , Diop Awa , Bobay Louis-Marie
Published: December 2024

Homologous recombination is a key evolutionary force that varies considerably across bacterial species. However, how the landscape of homologous recombination varies across genes and within individual genomes has only been studied in a few species. Here, we used Approximate Bayesian Computation to estimate the recombination rate along the genomes of 145 bacterial species. Our results show that homologous recombination varies greatly along bacterial genomes and shapes many aspects of genome architecture and evolution. The genomic landscape of recombination presents several key signatures: rates are highest near the origin of replication in most species, patterns of recombination generally appear symmetrical in both replichores (i.e. replicational halves of circular chromosomes) and most species have genomic hotspots of recombination. Furthermore, many closely related species share conserved landscapes of recombination across orthologs indicating that recombination landscapes are conserved over significant evolutionary distances. We show evidence that recombination drives the evolution of GC-content through increasing the effectiveness of selection and not through biased gene conversion, thereby contributing to an ongoing debate. Finally, we demonstrate that the rate of recombination varies across gene function and that many hotspots of recombination are associated with adaptive and mobile regions often encoding genes involved in pathogenicity.
Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) for small-cell lung cancer better preserves white matter networks compared to conventional PCI
Authors: Colaes Rob , Blommaert Jeroen , Lambrecht Maarten , de Ruiter Michiel B , Pullens Pim , de Ruysscher Dirk , Belderbos José , Sunaert Stefan , Schagen Sanne B , Deprez Sabine
Published: December 2024

Background

Hippocampal avoidance during prophylactic cranial irradiation (HA-PCI) is proposed to reduce neurocognitive decline, while preserving the benefits of PCI. We evaluated whether (HA-)PCI induces changes in white matter (WM) microstructure and whether sparing the hippocampus has an impact on preserving brain network topology. In addition, we evaluated associations between topological metrics with hippocampal volume and neuropsychological outcomes.

Methods

In this multicenter randomized phase 3 trial (NCT01780675), small-cell lung cancer (SCLC) patients underwent neuropsychological testing and diffusion tensor imaging (DTI) before, 4 months (33 PCI, 37 HA-PCI) and 1 year (19 PCI, 17 HA-PCI) after (HA-)PCI. Changes in WM microstructure were investigated using whole-brain voxel-based analysis of fractional anisotropy (FA) and mean diffusivity (MD). Both hippocampal and whole-brain graph measures were used to evaluate the topological organization of structural networks. Correlation analysis was performed to associate topological metrics with neuropsychological outcomes and hippocampal volume.

Results

Both HA-PCI and PCI were associated with decreased FA in major WM tracts, such as the corpus callosum, at 4 months and 1 year post-treatment. While these FA decreases did not differ significantly between treatment groups, only PCI demonstrated increased MD over time. In addition, PCI showed decreased global efficiency and increased characteristic path length over time when compared with HA-PCI. Significant correlations were found between whole-brain graph measures and neuropsychological outcomes.

Conclusion

While both techniques induce important changes in the WM microstructure, HA-PCI might better preserve the topological organization of brain networks than PCI. The neuroprotective role of hippocampal sparing still needs further investigation.
Validation of the EORTC QLQ-C30 and QLQ-BN20, including WHO performance status interrater reliability, for evaluation of patients with intracranial meningiomas
Authors: Nilsson Robert F , Ström Erik , Bergenheim A Tommy , Sjöberg Rickard L , Lindvall Peter , Holmgren Klas
Published: December 2024

Background

The EORTC questionnaires QLQ-C30 and QLQ-BN20 are commonly used to evaluate health-related quality of life in patients with meningiomas but have not undergone a disease-specific validation. The study aimed to address this issue and to determine the interrater reliability of WHO performance status (PS) assessments in these patients.

Methods

This population-based study included prospectively enrolled intracranial meningiomas treated at Umeå University Hospital between October 14, 2010, and December 31, 2021, followed up until March 30, 2023. Patients were assessed by the EORTC questionnaires before and at 3 months after surgery. WHO PS categorized as high (0–1) or low (2–5) were evaluated for interrater reliability and used together with sick-leave status to determine the questionnaires’ clinical validity. Remaining psychometric properties of the questionnaires were analyzed by conventional methods.

Results

Of 513 eligible surgeries, 454 (88.5%) had responded to at least 1 questionnaire. WHO PS interrater agreement was 94.4%. The EORTC questionnaires’ ability to distinguish between clinically distinct groups was high. Items correlated better with their own scale than others (most r > 0.70). Items measuring various aspects of the same construct showed good internal consistency (nearly all α > 0.70). Questionnaire responsiveness to symptom changes over time was acceptable. Several scales displayed floor and ceiling effects.

Conclusions

The EORTC QLQ-C30 and QLQ-BN20 are overall valid instruments to evaluate patients with intracranial meningiomas but require awareness of certain limitations when specific functions and symptoms are addressed. WHO PS assessments can be applied to meningioma patients with high reproducibility between observers.
Diet–Gut Microbiota Relations: Critical Appraisal of Evidence From Studies Using Metagenomics
Authors: Lotankar Mrunalini , Houttu Noora , Mokkala Kati , Laitinen Kirsi
Published: December 2024

Diet may influence the gut microbiota and subsequently affect the host’s health. Recent developments in methods analyzing the composition and function of the gut microbiota allow a deeper understanding of diet–gut microbiota relationships. A state-of-the-art methodology, shotgun metagenomics sequencing, offers a higher taxonomic resolution of the gut microbiota at the bacterial species and strain levels, and more accurate information regarding the functional potential of gut microbiota. Here, the available evidence on the relationship between diet and gut microbiota was critically reviewed, focusing on results emerging from recent metagenomics sequencing studies applied in randomized controlled trials and observational studies. The PubMed and Embase databases were used to search publications between January 2011 and September 2023. Thus far, the number of studies is limited, and the study designs and methods utilized have been variable. Nevertheless, the cumulative evidence from interventions relates to dietary fiber as a modifier of bacterial species, such as Anaerostipes hadrus and Faecalibacterium prausnitzii. Furthermore, observational studies have detected associations between different dietary patterns and food groups with certain microbial species. Utilization of metagenomics sequencing is becoming more common and will undoubtedly provide further insights into diet–gut microbiota relationships at the species level as well as their functional pathways in the near future. For reproducible results and to draw reliable conclusions across various studies on diet–gut microbiota relationships, there is a need for harmonization of the study designs and standardized ways of reporting.
The lifecycle and evolution of new regimens on the National Comprehensive Cancer Network Guidelines for newly diagnosed multiple myeloma
Authors: Mohyuddin Ghulam Rehman , Almasri Jehad , Goodman Aaron , Haslam Alyson , Prasad Vinay
Published: December 2024

Introduction

Prior studies have evaluated the level of evidence behind treatment options listed in the National Comprehensive Cancer Network (NCCN) guidelines, but no study has categorized the life cycle of regimens listed in the NCCN guidelines. We longitudinally assessed the life cycle for each regimen for newly diagnosed multiple myeloma. We track the date of first clinical data, the date of regimen addition to NCCN guidelines, the date phase 3 data (if performed) were reported, and the results of phase 3 trials.

Methods

We systematically examined NCCN guidelines from January 2000 to April 2021. The primary objective of our study was to assess the life cycle of each drug/regimen listed on the NCCN guidelines. We systematically examined the following aspects for each regimen: (1) the inception of prospective clinical data, (2) its inclusion in the NCCN guidelines, (3) the completion of a randomized trial (if done), (4) the presence of an overall survival benefit in such trials, and (5) the removal of a regimen from NCCN guidelines (if done) and its corresponding timeline.

Results

Twenty-one regimens were added across 50 NCCN guideline document iterations during a 22-year period. The median time from when clinical data were first presented to when a regimen was first listed in the guidelines was 15 months. Phase 3 studies were conducted for 17 regimens (80%), with a surrogate endpoint (response rate or progression-free survival) as endpoint for all trials, other than one. The median time from a regimen being included in the NCCN guideline to its phase 3 data publication was 43 months. The primary endpoint was met for 13 trials (81%). No regimen was removed for a phase 3 endpoint not being met. Six regimens (38%) showed overall survival benefit. Five (23%) regimens were removed from NCCN guidelines, with none being due to failure in phase 3 testing.

Conclusion

Myeloma NCCN guidelines remain relevant and current, adding new regimens with promising early-phase data, and removing regimens that become obsolete over time. However, this process is inconsistent and may benefit from standardization.
Effects of Educational Interventions Designed to Develop Physical Therapist Learners’ Clinical Reasoning: A Systematic Review
Authors: Fu Wing , Baldwin Tobi F , Brechter Jacklyn H , Erickson Mark R , Kobal Kara , LaFay Vicki , Miller Teresa M , Morales Jaclyn
Published: December 2024

Objective

The objective of this systematic review was to investigate the effects of educational interventions designed to develop physical therapist learners’ clinical reasoning across the full continuum of professional development.

Data Sources

A systematic search was conducted of 6 databases, the entire Journal of Physical Therapy Education collection, and the reference lists of included articles through March 2022.

Study Selection

English-language primary relevant research studies of all research designs were included while grey literature was excluded.

Data Extraction and Synthesis

Two reviewers independently extracted data from and determined risk of bias of each of the 40 included studies. Disagreements were resolved by consensus or use of a third reviewer. A narrative synthesis summarized and explained the quantitative data. Meta-analysis was not possible due to data heterogeneity. Qualitative data were synthesized using thematic analysis.

Main Outcome(s) and Measure(s)

Main outcomes were effects of the educational interventions per the Kirkpatrick model.

Results

Forty articles met the inclusion criteria. Twenty-two of the 33 studies with quantitative data involving student or practicing physical therapists reported statistically significant positive outcomes. Three major themes emerged from thematic analysis of 23 studies: perceived educational gain, valued elements of educational interventions, and identified challenges to learning.

Conclusions and Relevance

Educational interventions that appeared to have a positive impact on learning outcomes were identified. However, the available research lacks rigor for the authors to develop evidence-based guidelines to support the development of clinical reasoning in physical therapist learners. Given the importance of clinical reasoning, high quality studies are warranted. This comprehensive systematic review appeared to be the first one in the profession to have investigated the effects of educational interventions designed to develop learners’ clinical reasoning across the entire professional development. Educators and researchers may benefit from the findings to develop educational interventions and future studies.
The impact of an online, lifestyle intervention programme on the lives of patients with a rheumatic and musculoskeletal disease: a pilot study
Authors: van Slingerland Kim , Kranenburg Laura J C , Wilmsen Nathalie , Coles Emma , Dolhain Radboud J E M , de Jong Pascal H P
Published: December 2024

Objectives

To evaluate the short- and long-term effects of an online, interactive, multifactorial lifestyle intervention programme (Leef! Met Reuma) on health risk and all ICHOM-recommended patient-reported outcome measures (PROMs) in patients with an inflammatory arthritis (IA), osteoarthritis (OA) or fibromyalgia (FM).

Methods

Patients with an IA, OA or FM could register for the lifestyle intervention programme. The programme consists of a 3-month intensive part followed by a 21-month aftercare period and focuses on four pillars, namely nutrition, exercise, relaxation and sleep. Health risk and PROMs are collected 3-monthly during the first 6 months and 6-monthly during the next 18 months. Health risk includes self-reported weight, waist circumference and BMI. Following PROMs were included: pain, morning stiffness severity, fatigue, Health Assessment Questionnaire, quality of life, perceived stress, sleep disturbance and impact on life. Descriptive statistics were used to assess the change in health risk and PROMs during the intensive part of the programme and aftercare period.

Results

Of the 264 patients studied, 88, 105 and 71 were diagnosed with IA, OA and FM, respectively. Health risk significantly improved in all three diagnosis groups during the intensive part of the programme. The mean BMI reduction was −1.36 (0.26), −1.22 (0.23) and −1.48 (0.33), whereafter it stabilized in the aftercare period. All PROMs showed a similar trend.

Conclusion

An online, interactive lifestyle intervention programme has a positive long-term effect, even after 2 years of follow-up, on health risk and all PRO domains in patients with an IA, OA and FM.
Highly Curated and Reliable E-Probes for Detection of Viral Pathogens in Unassembled HTS Datasets from Hops
Authors: Pasha Ali , Espindola Andres S. , Ziebell Heiko , Ochoa-Corona Francisco M.
Published: December 2024

Implementing high-throughput sequencing (HTS) in virus detection has recently become widespread. Bioinformatics expertise, programming skills, and access to high-capacity computers are essential for HTS data analysis. A bioinformatic detection system that addresses these HTS constraints and performs searches on non-normalized HTS data was adopted; the E-probe Diagnostic Nucleic-acid Analysis (EDNA). The EDNA theoretical framework was later updated for cross-platform accessibility via a web browser and renamed Microbe Finder (MiFi®). In this study, the MiFi® platform was used to design e-probes for two viroids and three viruses that infect the hop plant (Humulus lupulus L.). These e-probes have undergone a rigorous curation process followed by in silico validation to determine their theoretical limit of detection. Interestingly, curated 40nt e-probes of all targeted pathogens in this study proved a better combination of sensitivity and specificity for their target genomes than other e-probe lengths. Additionally, an in vitro limit of detection was performed by constructing an artificial positive control (APC) plasmid that contained all curated e-probes. The stock plasmid was serially diluted before sequencing to validate the detection limit. The curated and validated e-probes successfully detected the targeted pathogens when applied to HTS datasets previously analyzed using other bioinformatics tools. The e-probes developed in this study allow the direct detection of targeted hop viruses and viroids in unassembled HTS datasets.
PAI‐1 promotes human endometrial stromal decidualization via inhibiting VEGFR2/PI3K/AKT signaling pathway mediated F‐actin reorganization
Authors: Zhao Huishan , Liu Juan , Yin Shuyuan , Bao Hongchu
Published: December 2024

Decidualization of endometrial stromal cells is a prerequisite for successful embryo implantation and early pregnancy. Decidualization dysregulation results in implantation failure. In our previous study, we reported that PAI‐1 is abnormally downregulated in the endometrial tissue samples of patients with recurrent implantation failure. This study will explore the dynamic expression changes of PAI‐1 in the endometrium during the menstrual cycle and its molecular mechanism affecting endometrial decidualization. Our findings indicated that the abundance of PAI‐1 increased in the mid‐secretory phase and attached a peak in the decidual phase in the endometrium of women with regular menstrual cycles. In human endometrial stromal cells (HESCs), PAI‐1 knockdown attenuated endometrial decidualization by upregulating VEGFR2/PI3K/AKT signaling pathway and impaired the F‐actin reorganization. Furthermore, axitinib (a VEGFR2 inhibitor) was used to inhibit the VEGFR2 protein activity and the results suggested that it eliminated the effects of PAI‐1 on PI3K/AKT signaling pathways and F‐actin remodeling. In addition, the interaction between PAI‐1 and KNG1 was confirmed by coimmunoprecipitation assay in HESCs. Altogether, PAI‐1‐KNG1 may enhance the decidualization of endometrium by inhibiting VEGFR2/PI3K/AKT signaling pathway‐mediated F‐actin reorganization in healthy females.
Identification of apigenin as a multi‐target inhibitor against SARS‐CoV‐2 by computational exploration
Authors: Huang Juanjuan , Jin Yixuan , Wu Runze , Xie Hanxi , Yang Ming , Jia Jiwei , Wang Guoqing
Published: December 2024

Multi‐target strategy can serve as a valid treatment for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), but existing drugs most focus on a single target. Thus, multi‐target drugs that bind multiple sites simultaneously need to be urgently studied. Apigenin has antiviral and anti‐inflammatory properties. Here, we comprehensively explored the potential effect and mechanism of apigenin in SARS‐CoV‐2 treatment by a network algorithm, deep learning, molecular docking, molecular dynamics (MD) simulation, and normal mode analysis (NMA). KATZ‐based VDA prediction method (VDA‐KATZ) indicated that apigenin may provide a latent drug therapy for SARS‐CoV‐2. Prediction of DTA using convolution model with self‐attention (CSatDTA) showed potential binding affinity of apigenin with multiple targets of virus entry, assembly, and cytokine storms including cathepsin L (CTSL), membrane (M), envelope (E), Toll‐like receptor 4 (TLR4), nuclear factor‐kappa B (NF‐κB), NOD‐like receptor pyrin domain‐containing protein 3 (NLRP3), apoptosis‐associated speck‐like protein (ASC), and cysteinyl aspartate‐specific proteinase‐1 (Caspase‐1). Molecular docking indicated that apigenin could effectively bind these targets, and its stability was confirmed using MD simulation and NMA. Overall, apigenin is a multi‐target inhibitor for the entry, assembly, and cytokine storms of SARS‐CoV‐2.
Covert Critical Illness Encephalopathy: Impairments That Escape Detection by Guideline Recommended, Protocolized Assessments
Authors: Shirodkar Ruhi , Bourgeois Isaac J. , Kim Minjee , Kimchi Eyal Y. , Liotta Eric M. , Maas Matthew B.
Published: December 2024

Objectives:

To determine whether cognitive impairments of important severity escape detection by guideline-recommended delirium and encephalopathy screening instruments in critically ill patients.

Design:

Cross-sectional study with random patient sampling.

Setting:

ICUs of a large referral hospital with protocols implementing the Society of Critical Care Medicine’s ICU Liberation Bundle.

Patients:

Patients with a heterogeneous mix of primary organ system conditions leading to critical illness and with no abnormal findings scored in Confusion Assessment Method for the ICU (CAM-ICU) screening, Richmond Agitation-Sedation Scale (RASS) 0, and Glasgow Coma Scale (GCS) 15, indicating they were alert, fully oriented, and following commands with no delirium or findings to indicate subsyndromal delirium.

Interventions:

None.

Measurements and Main Results:

We evaluated 50 patients, age 54 ± 16 years. Trained critical care nurses assessed patients at regular intervals using the CAM-ICU, RASS, and GCS per a protocol. We performed a battery of psychometric cognitive tests using the NIH Toolbox. Executive functions linked to attention and inhibitory control, and processing speed were 1.5 sd below population norm (both p < 0.01). Working memory and cognitive flexibility were also significantly, but less severely, impaired (p < 0.01 and p = 0.026). Nearly two-thirds (64%) of the patients scored at least 1.5 sd worse than demographically adjusted means in two or more cognitive domains, a commonly used diagnostic criterion for cognitive impairment.

Conclusions:

Substantial cognitive impairment is present among critically ill patients with no abnormalities detected by standard delirium and encephalopathy assessments.
Morphine-induced side effects can be differentially modulated by cannabidiol in male and female rats
Authors: Alves Jesus Carlos Henrique , Volpe Jaqueline , Sotomaior Bruna Bittencourt , Barbosa Maria Augusta Ruy , Ferreira Matheus Vinicius , Fiatcoski Fernanda , Genaro Karina , de Souza Crippa José Alexandre , Pires Souto Dênio Emanuel , Maria da Cunha Joice
Published: December 2024

Opioid use disorder is a public health problem that includes symptoms such as withdrawal syndrome and opioid-induced hyperalgesia. Currently, drugs to treat side effects of opioids also have undesirable effects, which lead to limitations. This study investigated the effect of a treatment with cannabidiol in morphine-induced hyperalgesia and withdrawal behavior in morphine-dependent rats. Male and female rats were submitted to a morphine-induced physical dependence protocol consisting of a twice daily treatment with morphine (filtered solution, dose of 7.89 mg/kg, 1 ml/kg, s.c.) for 10 days. Nociception was measured using the hot plate test and morphine-induced thermal hyperalgesia was equally achieved following 7–10 days of morphine administration in male and female rats. Repeated treatment with cannabidiol (30 mg/kg) was sufficient to prevent thermal hyperalgesia in male and female rats. Subsequently, rats received an acute administration of naloxone (2 mg/kg. s.c.), 90 min after the morphine treatment on day 11, the number of withdrawal behaviors was scored. Rats that received treatment exclusively with morphine presented significant withdrawal behaviors compared to control (Water). Morphine-dependent female rats showed a prevalent stereotyped behavior of rearing, whereas male rats had teeth chattering behavior as the most preeminent. Treatment with cannabidiol on day 11 partially attenuated withdrawal behavior in morphine-dependent male rats, with mild effects in female rats (high withdrawal responders only). Altogether, our data provide evidence of an anti-hyperalgesic effect of cannabidiol in rats. Male and female rats treated chronically with morphine exhibited withdrawal behaviors in different ratios, and cannabidiol treatment attenuated withdrawal behavior in a sex-dependent manner.
Effect of acute treatment with the glucagon-like peptide-1 receptor agonist, liraglutide, and estrus phase on cue- and drug-induced fentanyl seeking in female rats
Authors: Urbanik Luke A. , Booth Jennifer L. , Acharya Nikhil K. , Evans Brianna B. , Grigson Patricia S.
Published: December 2024

Opioid use disorder (OUD) is a crisis in the USA. Despite advances with medications for OUD, overdose deaths have continued to rise and are largely driven by fentanyl. We have previously found that male rats readily self-administer fentanyl, with evident individual differences in fentanyl taking, seeking, and reinstatement behaviors. We also have shown that acute treatment with the glucagon-like peptide-1 receptor (GLP-1R) agonist, liraglutide, can reduce fentanyl seeking behavior in male rats. However, given that females are significantly more vulnerable to drug-related cues, drug cravings, and to the development of OUD compared to males, it is imperative that we investigate the biological risk factors on fentanyl use disorder. Further, preclinical models report that females in estrus have increased fentanyl intake, more rapid development of OUD, and enhanced relapse vulnerability compared to those in a non-estrus phase. Thus, we aimed here to understand the effect of estrus phase on our model of OUD and on the effectiveness of acute liraglutide treatment. Herein, we show that female rats readily self-administer fentanyl (1.85 μg/infusion) intravenously, with marked individual differences in fentanyl taking behavior. Additionally, rats in the estrus phase exhibited greater fentanyl intake compared with those in a non-estrus phase, greater cue-induced fentanyl seeking, and greater drug-induced reinstatement of fentanyl seeking. Finally, acute liraglutide treatment (0.3 mg/kg s.c.) reduced cue-induced fentanyl seeking and blocked drug-induced reinstatement of fentanyl seeking, particularly when tested in estrus. Overall, these data support the broad effectiveness of acute GLP-1R agonists as a promising non-opioid treatment for OUD.
Menopausal hormone therapy use among active duty service women
Authors: Janvrin Miranda L. , Banaag Amanda , Brown Jill , Shvartsman Katerina , Koehlmoos Tracey P.
Published: December 2024

Objective

Menopausal hormone therapy (HT) has been shown to be effective in alleviating symptoms of menopause. While previous literature has described the frequency of HT use for the relief of menopausal symptoms in both the general and veteran female populations, there is currently no literature describing this frequency within the female active duty population. This study aims to address this gap in knowledge by conducting a retrospective cross-sectional study of HT receipt in active duty service women (ADSW) ages 45 to 64 during fiscal years (FYs) 2018 to 2022.

Methods

We used the Military Health System (MHS) Data Repository (MDR) to conduct a retrospective study of ADSW ages 45 to 64 in the US Army, Air Force, Navy, and Marine Corps during FY 2018 to 2022. Study analyses included descriptive statistics on participant demographics and HT type. Logistic regressions were performed to assess for significant associations between participant demographics and receipt of HT.

Results

We identified a total of 13,629 women aged 45 to 64 on active duty service in the US Army, Air Force, Navy, and Marine Corps during FY 2018 to 2022, of whom 1,290 (9.5%) received HT. Significantly lower odds for receipt of HT was observed among ADSW ages 45 to 49, 60 to 64, of Asian/Pacific Islander race, and all ranks below Senior Officer. No significant associations were observed by Service branch.

Conclusions

The prevalence of HT use among ADSW ages 45 to 65 is lower than HT use among the US veteran population age 45 and older but higher than among the US general population age 45 and older.
The role of short luteal phases on cycle regularity during the perimenopausal transition
Authors: Visby Madsen Caroline , Adornetto Gianluca , Kirkegaard Kirstine
Published: December 2024

Objective

The aim of the study was to explore the correlation between short luteal phases and cycle irregularity in perimenopausal women.

Methods

In this feasibility pilot study, daily salivary-progesterone measurements from presumed perimenopausal women have been analyzed using the inne minilab—an at-home system for ovulation and cycle tracking. Data were collected between 2020 to August 2022 from 29 women from Germany and Austria from users over the age of 42 years. Mean age was 44.5 years. The women were divided into two groups based on the presence of short luteal phases. Wilcoxon rank sum test was used to compare the two groups with regard to perimenopausal characteristics: cycle length variability, occurrence, and frequency of short cycles, long cycles, and anovulatory cycles.

Results

A significant correlation (P value =0.02) was found between short luteal phases and short cycle length under 23 days, with a median of two short cycles in the short luteal phase positive group compared to a median of 0 short cycles in the negative group. However, this correlation did not persist when adjusting for number of observations per participant. No difference was found when comparing other cycle characteristics

Conclusions

These findings could suggest that it may not be feasible to utilize the occurrence of short luteal phases in the context of expressing the likelihood of cycle irregularity, length, or anovulation. However, because of the small sample size in this study, the null findings could be due to lack of power. Larger studies would be needed to determine how short luteal phases may be correlated to cycle regularity.
Primary Care Screening for Nonalcoholic Fatty Liver Disease Among People With HIV in the United States: A Real-World Provider Survey
Authors: Price Jennifer C. , Hirose Kyoko , Chalasani Naga , Crandall Holly , Heath Sonya , Loomba Rohit , Naggie Susanna , Sterling Richard K. , Sulkowski Mark , Wilson Laura , Lake Jordan E.
Published: December 2024

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in people with HIV (PWH) and increases the risk of hepatic fibrosis and hepatocellular carcinoma. We sent an online survey to providers of the American Academy of HIV Medicine. Of respondents (n = 214, 8% response rate), 65% reported screening for NAFLD in PWH, with 28% routinely screening all patients. Most respondents refer patients to hepatology if workup suggests another coexisting liver disease or cirrhosis, with the primary goals of referral being additional diagnostic testing (60%) or specific treatments (75%). The most common barriers to screening were feeling unsure of what tests to order (28%) and how to conclusively diagnose NAFLD (29%). Most respondents were interested in society guidelines (73%) and NAFLD education for patients (57%) and providers (55%). Our findings support the development of NAFLD clinical practice guidelines for HIV providers and the inclusion of PWH in clinical trials of novel agents.
Unusual Presentation of a Pediatric Burkitt’s Lymphoma With Infiltration of the Interatrial Septum
Authors: Abdelmohsen Gaser , Alamri Aliaa , Algiraigri Ali , Elnakeeb Mohamed , Maghrabi Khadijah
Published: December 2024

Background:

Burkitt’s lymphoma (BL) is the most common subtype of non-Hodgkin lymphoma in children, typically presenting with extranodal masses in areas such as the abdomen, face, and neck. Cardiac involvement in BL is extremely rare, especially in pediatric patients, and has significant implications for diagnosis, management, and prognosis.

Case Presentation:

A 6-year-old male patient with Burkitt’s lymphoma, presenting with an uncommon infiltration of the interatrial septum, is described. The patient initially presented with a painful right facial mass, bilateral periorbital edema, and a history of fever, weight loss, and lower limb pain. Imaging revealed extensive disease, including a right masticator muscle mass, mandibular infiltration, and multiple soft tissue and skeletal lesions, along with significant thickening of the interatrial septum. A diagnosis of Stage III Burkitt’s lymphoma was confirmed through biopsy and immunohistochemical analysis. The patient was treated according to the ANHL1131 protocol, including Rituximab and multi-agent chemotherapy. Remarkably, the cardiac infiltration showed substantial regression on follow-up echocardiography after chemotherapy.

Conclusions:

This case underscores the importance of a comprehensive cardiac evaluation in pediatric patients with Burkitt’s lymphoma, particularly when presenting with atypical manifestations such as interatrial septum involvement. The findings demonstrate that systemic chemotherapy can effectively treat cardiac infiltration, even in complex cases with extensive disease. This report highlights the need for awareness of rare cardiac presentations in pediatric lymphoma and the critical role of advanced imaging modalities in diagnosis and management. Continuous monitoring and early implementation of cardioprotective strategies are essential to optimize outcomes in such cases.