bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analgesic Effectiveness of Liposomal Bupivacaine versus Plain Local Anesthetics for Abdominal Fascial Plane Blocks: A Systematic Review and Meta-analysis of Randomized Trials
Authors: Hussain Nasir , Speer Jarod , Abdallah Faraj W. 
Published: April 2024

Background
Liposomal bupivacaine is reported to prolong the duration of analgesia when used for abdominal fascial plane blocks compared to plain local anesthetics; however, evidence from randomized trials is mixed. This meta-analysis aims to compare the analgesic effectiveness of liposomal bupivacaine to plain local anesthetics in adults receiving abdominal fascial plane blocks.

Methods
Randomized trials comparing liposomal bupivacaine and plain (nonliposomal) local anesthetics in abdominal fascial plane blocks were sought. The primary outcome was area under the curve rest pain between 24 to 72 h postoperatively. Secondary outcomes included rest pain at individual timepoints (1, 6, 12, 24, 48, and 72 h); analgesic consumption at 0 to 24, 25 to 48, and 49 to 72 h; time to analgesic request; hospital stay duration; and opioid-related side effects. Data were pooled using the Hartung-Knapp-Sidik-Jonkman random effects method.

Results
Sixteen trials encompassing 1,287 patients (liposomal bupivacaine, 667; plain local anesthetics, 620) were included. The liposomal bupivacaine group received liposomal bupivacaine mixed with plain bupivacaine in 10 studies, liposomal bupivacaine alone in 5 studies, and both preparations in 1 three-armed study. No difference was observed between the two groups for area under the curve pain scores, with a standardized mean difference (95% CI) of –0.21 cm.h (–0.43 to 0.01; P = 0.058; I2 = 48%). Results were robust to subgroup analysis based on (1) potential conflict of interest and (2) mixing of plain local anesthetics with liposomal bupivacaine. The two groups were not different for any of the day 2 or day 3 secondary outcomes.

Conclusions
This systematic review and meta-analysis suggests similar analgesic effectiveness between liposomal bupivacaine and plain local anesthetics when used for fascial plane block of the abdominal wall. The authors’ analysis does not support an evidence-based preference for liposomal bupivacaine compared to plain local anesthetics for abdominal fascial plane blocks.

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Biomarker-Based Risk Stratification Tool in Pediatric Acute Respiratory Distress Syndrome: Single-Center, Longitudinal Validation in a 2014–2019 Cohort
Authors: Whitney Jane E. , Johnson Grace M. , Varisco Brian M. , Raby Benjamin A. , Yehya Nadir 
Published: April 2024

OBJECTIVES:
The Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model (PARDSEVERE) used age and three plasma biomarkers measured within 24 hours of pediatric acute respiratory distress syndrome (ARDS) onset to predict mortality in a pilot cohort of 152 patients. However, longitudinal performance of PARDSEVERE has not been evaluated, and it is unclear whether the risk model can be used to prognosticate after day 0. We, therefore, sought to determine the test characteristics of PARDSEVERE model and population over the first 7 days after ARDS onset.

DESIGN:
Secondary unplanned post hoc analysis of data from a prospective observational cohort study carried out 2014–2019.

SETTING:
University-affiliated PICU.

PATIENTS:
Mechanically ventilated children with ARDS.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Between July 2014 and December 2019, 279 patients with ARDS had plasma collected at day 0, 266 at day 3 (11 nonsurvivors, two discharged between days 0 and 3), and 207 at day 7 (27 nonsurvivors, 45 discharged between days 3 and 7). The actual prevalence of mortality on days 0, 3, and 7, was 23% (64/279), 14% (38/266), and 13% (27/207), respectively. The PARDSEVERE risk model for mortality on days 0, 3, and 7 had area under the receiver operating characteristic curve (AUROC [95% CI]) of 0.76 (0.69–0.82), 0.68 (0.60–0.76), and 0.74 (0.65–0.83), respectively. The AUROC data translate into prevalence thresholds for the PARDSEVERE model for mortality (i.e., using the sensitivity and specificity values) of 37%, 27%, and 24% on days 0, 3, and 7, respectively. Negative predictive value (NPV) was high throughout (0.87–0.90 for all three-time points).

CONCLUSIONS:
In this exploratory analysis of the PARDSEVERE model of mortality risk prediction in a population longitudinal series of data from days 0, 3, and 7 after ARDS diagnosis, the diagnostic performance is in the “acceptable” category. NPV was good. A major limitation is that actual mortality is far below the prevalence threshold for such testing. The model may, therefore, be more useful in cohorts with higher mortality rates (e.g., immunocompromised, other countries), and future enhancements to the model should be explored.
Reoperation following Primary Greater Occipital Nerve Decompression Surgery: Incidence, Risk Factors, and Outcomes
Authors: Remy Katya , Hazewinkel Merel H. , Mullen Connor , Hagan Robert R. , Austen William G. , Gfrerer Lisa 
Published: April 2024

Background:
Although nerve decompression surgery is an effective treatment for refractory occipital neuralgia, a proportion of patients experience recurrence of pain and undergo reoperation. This study analyzes the incidence, risk factors, and outcomes of reoperation following primary greater occipital nerve (GON) decompression.

Methods:
A total of 215 patients who underwent 399 primary GON decompressions were prospectively enrolled. Data included patient demographics, medical and surgical history, reoperation rates, intraoperative findings, surgical technique, and postoperative outcomes in terms of pain frequency (days per month), duration (hours per day), intensity (scale, 0 to 10), and migraine headache index. Bivariate analyses, univariable logistic regression analysis, and multivariable logistic regression analysis, were performed.

Results:
Twenty-seven GON decompressions (6.8%) required reoperation with neurectomy at a median follow-up time of 15.5 months (range, 9.8 to 40.5 months). Cervical spine disorders on imaging that did not warrant surgical intervention (OR, 4.88; 95% CI, 1.61 to 14.79; P < 0.01) and radiofrequency ablation (OR, 4.20; 95% CI, 1.45 to 15.2; P < 0.05) were significantly associated with higher rates of reoperation. At 12 months postoperatively, patients who underwent reoperation achieved similar mean reductions in pain frequency, duration, intensity, and migraine headache index, as compared with patients who underwent only primary decompression (P > 0.05).

Conclusion:
Patients with occipital neuralgia who have a history of cervical spine disorders or radiofrequency ablation should be counseled that primary decompression has a higher risk of reoperation, but outcomes are ultimately comparable.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
Pooled screening for CAR function identifies novel IL13Rα2-targeted CARs for treatment of glioblastoma
Authors: Gordon Khloe S. , Perez Caleb R. , Garmilla Andrea , Lam Maxine S.Y. , Aw Joey Jy , Datta Anisha , Lauffenburger Douglas A. , Pavesi Andrea , Birnbaum Michael E. 
Published: April 2024

ABSTRACTChimeric antigen receptor therapies have demonstrated potent efficacy in treating B cell malignancies, but have yet to meaningfully translate to solid tumors. Here, we utilize our pooled screening platform, CARPOOL, to expedite the discovery of CARs with anti-tumor functions necessary for solid tumor efficacy. We performed selections in primary human T cells expressing a library of 1.3×1063rdgeneration CARs targeting IL13Rα2, a cancer testis antigen commonly expressed in glioblastoma. Selections were performed for cytotoxicity, proliferation, memory formation, and persistence upon repeated antigen challenge. Each enriched CAR robustly produced the phenotype for which it was selected, and one enriched CAR triggered potent cytotoxicity and long-term proliferation uponin vitrotumor rechallenge. It also showed significantly improved persistence and comparable antigen-specific tumor control in a microphysiological humanin vitromodel and a xenograft model of human glioblastoma. Taken together, this work demonstrates the utility of extending CARPOOL to diseases beyond hematological malignancies and represents the largest exploration of signaling combinations in human primary cells to date.
A leg model based on anatomical landmarks to study 3D joint kinematics of walking inDrosophila melanogaster
Authors: Haustein Moritz , Blanke Alexander , Bockemühl Till , Büschges Ansgar 
Published: April 2024

AbstractWalking is the most common form of how animals move on land. The model organismDrosophila melanogasterhas become increasingly popular for studying how the nervous system controls behavior in general and walking in particular. Despite recent advances in tracking and modeling leg movements of walkingDrosophilain 3D, there are still gaps in knowledge about the biomechanics of leg joints due to the tiny size of fruit flies. For instance, the natural alignment of joint rotational axes was largely neglected in previous kinematic analyses. In this study we therefore present a detailed kinematic leg model in which not only the segment lengths but also the main rotational axes of the joints were derived from anatomical landmarks, namely the joint condyles. Our model with natural oblique joint axes is able to adapt to the 3D leg postures of straight and forward walking fruit flies with high accuracy. When we compared our model to an orthogonalized version, we observed that our model showed a smaller error as well as differences in the used range of motion (ROM), highlighting the advantages of modeling natural rotational axes alignment for the study of joint kinematics. We further found that the kinematic profiles of front, middle, and hind legs differed in the number of required degrees of freedom as well as their contributions to stepping, time courses of joint angles, and ROM. Our findings provide deeper insights into the joint kinematics of walking inDrosophila, and, additionally, help to develop dynamical, musculoskeletal, and neuromechanical simulations.
Phthalates are detected in the follicular fluid of adolescents and oocyte donors with associated changes in the cumulus cell transcriptome
Authors: Gokyer Dilan , Laws Mary J. , Kleinhans Anna , Riley Joan K. , Flaws Jodi A. , Babayev Elnur 
Published: April 2024

AbstractPurposeTo investigate follicular fluid (FF) phthalate levels in adolescents undergoing fertility preservation compared to oocyte donors and explore its association with ovarian reserve and cumulus cell gene expression.Methods20 Adolescents (16.7 ± 0.6 years old) and 24 oocyte donors (26.2 ± 0.4 years old) undergoing fertility preservation were included in the study. Patient demographics, ovarian stimulation and oocyte retrieval outcomes were analyzed for each group. FF levels of 9 phthalate metabolites were assessed individually and as molar sums representative of common compounds (all phthalates: ƩPhthalates; DEHP: ƩDEHP), exposure sources (plastics: ƩPlastic; personal care products: ƩPCP), and modes of action (anti-androgenic: ƩAA) and compared between the two groups.ResultsFollicular fluid ƩPlastic and ƩPCP levels were significantly higher in adolescents compared to oocyte donors (p<0.05). Follicular fluid ƩDEHP, ƩPlastic, ƩPCP, ƩAA, and ƩPhthalates levels were positively associated with antral follicle count (AFC) (p<0.05) in oocyte donors when adjusted for age, BMI, and race/ethnicity. RNA-seq analysis revealed 248 differentially expressed genes (DEGs) in cumulus cells of adolescents within the top quartile (n=4) of FF ƩPhthalates levels compared to the adolescents within the bottom half (n=9). Genes enriched in pathways involved in cell motility and development were significantly downregulated.ConclusionAdolescents undergoing fertility preservation cycles demonstrate higher levels of phthalate metabolites in their follicular fluid compared to oocyte donors. Phthalate metabolite levels in FF are associated with higher AFC levels in oocyte donors. Higher phthalate levels in FF are associated with alterations in the cumulus cells transcriptome in adolescents.Capsule SummaryPhthalates are detected in the follicular fluid of adolescents and oocytes donors, and the levels are increased in the follicular fluid of adolescents. Higher total phthalate levels in follicular fluid are associated with altered cumulus cells transcriptome in adolescents.
Comparative specialization of intrinsic cardiac neurons in humans, mice, and pigs
Authors: Tompkins John D. , Hoover Donald B. , Havton Leif A. , Patel Janaki C. , Cho Youngjin , Smith Elizabeth H. , Biscola Natalia P. , Ajijola Olujimi A. , Shivkumar Kalyanam , Ardell Jeffrey L. 
Published: April 2024

AbstractIntrinsic cardiac neurons (ICNs) play a crucial role in the proper functioning of the heart; yet a paucity of data pertaining to human ICNs exists. We took a multidisciplinary approach to complete a detailed cellular comparison of the structure and function of ICNs from mice, pigs, and humans. Immunohistochemistry of whole and sectioned ganglia, transmission electron microscopy, intracellular microelectrode recording and dye filling for quantitative morphometry were used to define the neurophysiology, histochemistry, and ultrastructure of these cells across species. The densely packed, smaller ICNs of mouse lacked dendrites, formed axosomatic connections, and had high synaptic efficacy constituting an obligatory synapse. At Pig ICNs, a convergence of subthreshold cholinergic inputs onto extensive dendritic arbors supported greater summation and integration of synaptic input. Human ICNs were tonically firing, with synaptic stimulation evoking large suprathreshold excitatory postsynaptic potentials like mouse, and subthreshold potentials like pig. Ultrastructural examination of synaptic terminals revealed conserved architecture, yet small clear vesicles (SCVs) were larger in pigs and humans. The presence and localization of ganglionic neuropeptides was distinct, with abundant VIP observed in human but not pig or mouse ganglia, and little SP or CGRP in pig ganglia. Action potential waveforms were similar, but human ICNs had larger after-hyperpolarizations. Intrinsic excitability differed; 93% of human cells were tonic, all pig neurons were phasic, and both phasic and tonic phenotypes were observed in mouse. In combination, this publicly accessible, multimodal atlas of ICNs from mice, pigs, and humans identifies similarities and differences in the evolution of ICNs.
The Cell Death Census 2024
Authors: Miari Mariam , Regnell Elsa , Aits Sonja 
Published: April 2024

AbstractCell death plays a pivotal role in many physiological processes, such as cell homeostasis, embryonic development, immune defence and in the pathophysiology of numerous diseases, such as cancer, infections and degenerative diseases. However, the lack of a comprehensive and up-to-date resource on cell death regulators poses a signiﬁcant challenge to researchers in the ﬁeld. Existing databases are often limited in scope, differ in content and are updated irregularly. This deﬁciency impedes progress in understanding the intricate molecular mechanisms governing cell death and hampers the development of targeted therapies. To address this, we have performed a census of the existing cell death databases as well as the cell death-associated entries in the UniProt and Gene Ontology databases. To ensure high quality, we have focused on manually curated entries rather than those created from automatic prediction tools. The results have been consolidated into a joint database of the known cell death regulators, including both proteins and non-coding RNAs. The Cell Death Census 2024 results and the associated python code for database parsing, cleaning and merging is publicly available athttps://github.com/Aitslab/CellDeathCensus/.
Quality of care for chronic conditions: Identifying specificities of quality aims based on scoping review and Delphi survey
Authors: Ku Grace Marie V. , van de Put Willem , Katsuva Deogratias , Ag Ahmed Mohamad Ali , Rosenberg Megumi , Meessen Bruno 
Published: April 2024

ABSTRACTBackgroundThere is a need to implement good quality chronic care to address the ballooning burden of chronic conditions affecting all countries globally. However, to our knowledge, no systematic attempts have yet been made to define and specify aims for chronic care quality.ObjectiveWe conducted a scoping review and Delphi survey to establish and validate a comprehensive specification of chronic care quality aims.MethodologyThe Institute of Medicine’s (IOM) quality of care definition and aims was utilised as our base. We purposively selected scientific and grey literature that have acknowledged and unpacked the plurality of quality in chronic care and which proposed/made use of frameworks and studied their implementation or investigated minimum two IOM care quality aims and their implementation. We critically analysed the literature deductively and inductively. We validated our findings through Delphi survey involving international chronic care experts, mostly coming from/have expertise on low-and-middle-income countries.ResultsWe considered the natural history of chronic conditions and the journey of a person with chronic condition to define and identify aims of chronic care quality. We noted that the six IOM aims apply but with additional meanings. We identified a seventh aim, continuity, which relates well to the issue of chronicity. Our panellists agreed with the specifications. Several provided contextualised interpretations and concrete examples.ConclusionsChronic conditions pose specific challenges underscoring the relevance of tailoring quality of care aims. Operationalization of this tailored definition and specified aims to improve, measure and assure quality of chronic care can be next steps.
Immune system homeostasis in people with multiple long-term conditions determines susceptibility to organ injury and mortality following cardiac surgery
Authors: Lai Florence Y , Adebayo Adewale S , Sheikh Sophia , Roman Marius , Joel-David Lathishia , Aujla Hardeep , Chad Tom , Tomkova Kristina , Ladak Shameem , Condorelli Gianluigi , Zakkar Mustafa , Solomon Charles , Woźniak Marcin J , Murphy Gavin J 
Published: April 2024

ABSTRACTBackgroundPeople with Multiple Long-Term Conditions (MLTC) experience higher rates of organ failure and death following cardiac surgery. The aim of this study was to identify disease processes in MLTC associated with increased susceptibility to organ injury post-surgery.MethodsUnsupervised machine learning methods were applied to pre-surgery biomarkers of haematological, cardiac, liver, and renal disease from four intensively phenotyped cardiac surgery cohorts. The resulting MLTC clusters were then matched to a fifth cohort where single nuclei RNA sequencing (snRNAseq) was performed on atrial biopsies collected at surgery.ResultsK-means clustering identified two MLTC clusters. Cluster 1 had lower rates of chronic kidney disease and anaemia and increased immune system activation pre-surgery. Cluster 2 had more severe cardiorenal disease, anaemia, and elevated biomarkers of immunological ageing pre-surgery. Cluster 2 had significantly higher rates of organ injury relative to Cluster 1. The results were consistent across internal and external validation analyses.Analysis of snRNAseq data in biopsies from Cluster 1 demonstrated enrichment for immune response genes in cardiomyocytes, naive T/B lymphocytes and progenitor cells, and activation of non-tissue resident macrophages relative to Cluster 2. Cluster 2 showed enrichment for senescent/ effector memory T cells, dysregulated activation of tissue-resident macrophages, and cardiomyocyte dedifferentiation relative to Cluster 1.In UK Biobank, genetic modification of genes differentially expressed between the two MLTC phenotypes altered 90-day mortality post-surgery.ConclusionsImmune system homeostasis determines susceptibility to organ injury and death in people with MLTC undergoing cardiac surgery and represents a previously unrecognised target for organ protection interventions.
Tandem RAman Microscopy (TRAM): integration of spontaneous and coherent Raman scattering offering data fusion analysis to improve optical biosensing
Authors: Brzozowski K. , Pieczara A. , Nowakowska A. , Korona W. , Orzechowska B. , Firlej J. , Wislocka-Orlowska A. , Baranska M. 
Published: April 2024

AbstractWe provide Tandem RAman Microscopy (TRAM), a cutting-edge multimodal microscope that integrates the methods of Stimulated Raman Scattering (SRS), Coherent anti-Stokes Raman Scattering (CARS), and spontaneous (Resonance) Raman Scattering ((R)RS). The device facilitates sequential Continuous Wave (CW) driven RS imaging to collect full spectra from every sample location and rapid pulsed-wave-driven SRS-CARS scanning at specific wavenumbers, offering a reliable and efficient analytical tool. The fingerprint spectral region can be included in the spectral imaging capabilities of CARS and SRS. Data collected from a sample area using several techniques can be integrated and analyzed, significantly increasing reliability and predictions. We analyzed thein vitromodel of nonadherent leukocytes (LC) to illustrate the capabilities of this unique system, emphasizing the benefits of measuring the same sample with three different Raman techniques without having to transfer it between microscopes. Data fusion allowed for the correct classification of two subtypes of LC based on the partial least squares (PLS) discrimination, increasing the prediction accuracy from approximately 83% in the case of textural and morphological data (SRS) to 100% when combined with spectral data (SRS and RS). We also present RRS images of LC labeled with astaxanthin, and reference data from SRS and CARS microscopy. Additionally, polystyrene beads were investigated as a non-biological material. The advantages of each Raman technique are utilized when (R)RS, SRS, and CARS are combined into a single device. This paves the way for dependable chemical characterization in a wide range of scientific and industrial fields.