bluuebunny/crossref_metadata_2025 huggingface dataset:
A - 25 The Role of Prospective Memory in Instrumental Activities of Daily Living and the Use of Compensatory Aids in Mild Cognitive Impairment
Authors: Kozuki Jordan T , Hickman Angela , Sidhu Jasman , Chapp Andrew , Lent David , Wright Matthew , Schmitter-Edgecombe Maureen , Woo Ellen
Published: October 2023

Objective

Prospective memory (PM), which involves remembering to execute a future action, is impacted by Alzheimer’s disease. This study examined the role of PM in instrumental activities of daily living (IADLs) and the use of compensatory aids in mild cognitive impairment (MCI) and healthy aging.

Methods

Participants included 44 healthy older controls and 49 persons with MCI. Simple PM was measured by asking participants to remember to execute a single action- to request a pill after completing each of a series of neuropsychological tests. Complex PM was then measured by asking participants to request a specific number of pills depending on whether a memory test was just completed or a non-memory test was completed. The Instrumental Activities of Daily Living- Compensation (IADL-C) scale was used to assess IADLs and the use of compensatory aids for completing these activities.

Results

Regression analyses revealed that both types of PM together predicted the IADLs of money/self-management skills and home/daily living skills in healthy older controls. Both types of PM also predicted total IADLs in controls. PM did not predict IADLs in MCI or the use of compensatory aids in either group.

Conclusion

Results indicated that PM was predictive of IADLs in healthy older adults. When PM skills are poorer, as in MCI, they are not predictive of IADLs.
A - 138 Using the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System to Understand Complex Associations between Traumatic Brain Injury and Alcohol or Substance Use
Authors: Shirley Kate , Clauss Kate , Cameron David , Krushnic Danielle , Baker-Robinson William , Hannon Sara , O'Neil Maya
Published: October 2023

Objective

Associations between traumatic brain injury (TBI) and alcohol or substance use are complex and likely bidirectional. The purpose of this project was to conduct a proof-of-concept study demonstrating our ability to compile patient-level TBI data from shared studies in the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System to improve our understanding of key TBI outcomes.

Method

We searched the FITBIR database for shared studies reporting alcohol or substance use among participants with TBI. We merged and harmonized data across the relevant studies to determine rates of alcohol or substance use by TBI severity.

Results

In the alcohol use sample (N = 1539), 82% of participants had a history of mild TBI and 46% met criteria for alcohol use disorder (AUD). Participants with a history of mild TBI had 1.34 greater odds of screening positive for AUD (95% CI: 0.98, 1.82) and males had 2.48 increased odds of screening positive for AUD (95% CI: 1.67, 3.68). Unfortunately, due to limited data on substance use we were unable to conduct the intended analyses for this outcome.

Conclusions

Data support research and theory suggesting that rates of AUD are higher among individuals with mild TBI versus those without, particularly among males. Additionally, this proof-of-concept study established methods, created data harmonization and analysis code, and provided the TBI-SUD meta dataset back to FITBIR for dissemination. Further, numerous additional datasets have been shared with the FITBIR platform since the time of these analyses, which will allow our team and others to extend these analyses over time.
Optimization of drug–target affinity prediction methods through feature processing schemes
Authors: Ru Xiaoqing , Zou Quan , Lin Chen
Published: October 2023

Motivation

Numerous high-accuracy drug–target affinity (DTA) prediction models, whose performance is heavily reliant on the drug and target feature information, are developed at the expense of complexity and interpretability. Feature extraction and optimization constitute a critical step that significantly influences the enhancement of model performance, robustness, and interpretability. Many existing studies aim to comprehensively characterize drugs and targets by extracting features from multiple perspectives; however, this approach has drawbacks: (i) an abundance of redundant or noisy features; and (ii) the feature sets often suffer from high dimensionality.

Results

In this study, to obtain a model with high accuracy and strong interpretability, we utilize various traditional and cutting-edge feature selection and dimensionality reduction techniques to process self-associated features and adjacent associated features. These optimized features are then fed into learning to rank to achieve efficient DTA prediction. Extensive experimental results on two commonly used datasets indicate that, among various feature optimization methods, the regression tree-based feature selection method is most beneficial for constructing models with good performance and strong robustness. Then, by utilizing Shapley Additive Explanations values and the incremental feature selection approach, we obtain that the high-quality feature subset consists of the top 150D features and the top 20D features have a breakthrough impact on the DTA prediction. In conclusion, our study thoroughly validates the importance of feature optimization in DTA prediction and serves as inspiration for constructing high-performance and high-interpretable models.

Availability and implementation

https://github.com/RUXIAOQING964914140/FS_DTA.
A Bayesian nonparametric approach to correct for underreporting in count data
Authors: Arima Serena , Polettini Silvia , Pasculli Giuseppe , Gesualdo Loreto , Pesce Francesco , Procaccini Deni-Aldo
Published: October 2023

We propose a nonparametric compound Poisson model for underreported count data that introduces a latent clustering structure for the reporting probabilities. The latter are estimated with the model’s parameters based on experts’ opinion and exploiting a proxy for the reporting process. The proposed model is used to estimate the prevalence of chronic kidney disease in Apulia, Italy, based on a unique statistical database covering information on m = 258 municipalities obtained by integrating multisource register information. Accurate prevalence estimates are needed for monitoring, surveillance, and management purposes; yet, counts are deemed to be considerably underreported, especially in some areas of Apulia, one of the most deprived and heterogeneous regions in Italy. Our results agree with previous findings and highlight interesting geographical patterns of the disease. We compare our model to existing approaches in the literature using simulated as well as real data on early neonatal mortality risk in Brazil, described in previous research: the proposed approach proves to be accurate and particularly suitable when partial information about data quality is available.
COVID-19 Impact on Children’s Social Work Practice and Social Worker Well-being: A Mixed Methods Study from Northern Ireland and Great Britain during 2020–2022
Authors: McFadden Paula , Ross Jana , MacLochlainn Justin , Mallett John , McGrory Susan , Currie Denise , Schroder Heike , Nicholl Patricia , Ravalier Jermaine , Manthorpe Jill
Published: October 2023

Social workers were heavily impacted by the COVID-19 pandemic. In this study, we examined the well-being, burnout and work conditions of UK children’s social workers at five time points of the COVID-19 pandemic. This was a cross-sectional mixed methods study analysing data from 1,621 social workers who worked in children’s services in the UK in 2020–2022. Data were collected using anonymous online surveys which included both quantitative and qualitative questions. The mental well-being of participants decreased as the pandemic progressed and work-related burnout increased. In the later stages of the pandemic, children’s social workers in Northern Ireland fared better than their Great Britain counterparts in relation to their well-being and levels of burnout. Thematic analysis of qualitative data revealed four major themes: Changes in service demand and referrals, Adapted ways of working, Staff shortages and Emotional impact. The findings highlight the challenges that the children’s social workers encountered during the COVID-19 pandemic and have implications for policy, practice and research.
Cardiac resynchronization therapy from an iliac approach in a patient without superior access: a case report
Authors: Xu Lei , Su Yangang , Qin Shengmei , Ge Junbo
Published: October 2023

Background

Cardiac resynchronization therapy (CRT) has been shown to benefit patients with heart failure and left bundle branch block (LBBB). However, CRT implantation is challenging when the superior venous access is not feasible.

Case summary

A 50-year-old man with a history of dilated cardiomyopathy and complete LBBB was referred to our hospital for CRT management. Angiography showed that the left and right brachiocephalic veins were occluded. Cardiac resynchronization therapy was finally implanted via the iliac vein. Follow-up echocardiography showed improved cardiac function, and the pacing system was functioning properly.

Discussion

The iliac vein access is feasible for CRT implantation with good stability, which can be a viable alternative to avoid unnecessary risk associated with thoracotomy and epicardial lead placement.
Subacute right coronary artery thrombosis treated by using Excimer Laser Coronary Angioplasty: a case report
Authors: Faria Daniel , Jeronimo Adrián , Escaned Javier , Nuñez-Gil Ivan J
Published: October 2023

Background

Managing high thrombotic burden in the context of myocardial infarction remains a challenging scenario.

Case summary

A 51-year-old male was admitted for a subacute inferior myocardial infarction with persistent chest pain. Emergent coronary angiography showed an ostial–proximal thrombotic occlusion of a large ectatic right coronary artery. Several balloon inflations were performed that were not able to improve distal TIMI flow beyond II. With the intent of vaporizing the remaining thrombus, Excimer Laser Coronary Angioplasty was performed with a favourable outcome.

Discussion

The present case constitutes an opportunity to revisit percutaneous and non-percutaneous strategies to tackle persistent coronary thrombus showing a contemporary approach to niche technologies such as laser angioplasty.
Practice makes perfect? Institutional coronary artery bypass case volumes and outcomes
Authors: Schwann Thomas A , Engoren Milo , Gaudino Mario F , Mentz Graciela , Saadat Siavash , Engelman Daniel , Lobdell Kevin W , Vekstein Andrew M , Habib Robert H
Published: October 2023

OBJECTIVES

Older studies of coronary artery bypass grafting (CABG) institutional case volumes and outcomes reported conflicting results. We explored this association in the rapidly changing contemporary practice of American surgeons using the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database.

METHODS

The 2018–2019 isolated primary CABG experience in the STS Adult Cardiac Surgery Database was analysed (241 902 patients; 1014 hospitals; 2718 surgeons). Generalized Estimating Equations were used to estimate coefficients between CABG institutional case volumes and outcomes. The observed-to-expected ratios based on STS risk models were used to assess risk-adjusted operative mortality (OM), mortality/major morbidity (MM) and deep sternal wound infections (DSWI) as a function of institutional case volumes.

RESULTS

The mean (standard deviation) OM, MM and DSWI rates were 2.1% (2.7), 11.1% (9.2) and 0.6% (0.5), respectively. The mean (standard deviation) institutional case volumes per study period was 239 (192); 23% and 9% of institutions performed <100 and >500 cases/study period, respectively. There was a weak negative correlation between expected mortality (R2 –0.0014), OM (R2 –0.0272), MM (R2 –0.1213) and DSWI (R2 –0.003) and institutional case volumes.

CONCLUSIONS

CABG outcomes generally improve with increasing institutional case volumes. Given the large number of CABG cases performed nationally, even the documented weak correlation has the potential to appreciably decrease OM, MM and DSWI if cases are performed at higher volume institutions. Studies focusing on additional hospital and surgeon factors are warranted to further define quality improvement opportunities.
Oxidative Stress Factors Mediate the Association Between Life’s Essential 8 and Accelerated Phenotypic Aging: NHANES 2005–2018
Authors: Liu Wen , Wang Jia , Wang Miao , Hou Huimin , Ding Xin , Ma Lingzhi , Liu Ming
Published: October 2023

Cardiovascular health (CVH) is a well-known predictor of morbidity and mortality, while phenotypic age (PhenoAge) is a promising biomarker of aging. This study aimed to explore the association between Life’s Essential 8 (LE8), a novel CVH measure, and PhenoAge acceleration (PhenoAgeAccel), as well as the potential mediating role of oxidative stress biomarkers in this relationship. A total of 23 896 individuals were included in the National Health and Nutrition Examination Survey database (2005–2018). Life’s Essential 8 scores were categorized into low, moderate, and high groups. PhenoAge, measured through clinical laboratory blood chemistries, served as a marker of biological aging. Weighted linear regression analyses were performed to assess the association between LE8 scores and PhenoAgeAceel. In the multivariable linear regression, LE8 scores were significantly and inversely associated with PhenoAgeAccel, showing a decreased risk in the moderate CVH group (β −2.98; 95% CI −3.29, −2.66) and high CVH group (β −4.72; 95% CI −5.08, −4.35) compared to the low CVH group. When treated as a continuous variable, each 10-point increase in LE8 scores corresponded to a 1.14-year decrease in PhenoAge (β −1.14; 95% CI −1.21, −1.06). Among the 8 individual components in LE8, 7 exhibited a significant negative correlation with PhenoAgeAccel, except for blood lipids. Additionally, mediation analysis revealed that oxidative stress biomarkers, including γ-glutamyltransferase, bilirubin, and uric acid, collectively mediated 17.1% of the associations between LE8 scores and PhenoAgeAccel (p < .001). Higher LE8 scores, representing ideal CVH, are significantly related to a deceleration in PhenoAge, and oxidative stress biomarkers may play a mediating role in this relationship.
Combining uncertainty-aware predictive modeling and a bedtimeSmart Snackintervention to prevent nocturnal hypoglycemia in people with type 1 diabetes on multiple daily injections
Authors: Mosquera-Lopez Clara , Roquemen-Echeverri Valentina , Tyler Nichole S , Patton Susana R , Clements Mark A , Martin Corby K , Riddell Michael C , Gal Robin L , Gillingham Melanie , Wilson Leah M , Castle Jessica R , Jacobs Peter G
Published: October 2023

Objective

Nocturnal hypoglycemia is a known challenge for people with type 1 diabetes, especially for physically active individuals or those on multiple daily injections. We developed an evidential neural network (ENN) to predict at bedtime the probability and timing of nocturnal hypoglycemia (0-4 vs 4-8 h after bedtime) based on several glucose metrics and physical activity patterns. We utilized these predictions in silico to prescribe bedtime carbohydrates with a Smart Snack intervention specific to the predicted minimum nocturnal glucose and timing of nocturnal hypoglycemia.

Materials and methods

We leveraged free-living datasets collected from 366 individuals from the T1DEXI Study and Glooko. Inputs to the ENN used to model nocturnal hypoglycemia were derived from demographic information, continuous glucose monitoring, and physical activity data. We assessed the accuracy of the ENN using area under the receiver operating curve, and the clinical impact of the Smart Snack intervention through simulations.

Results

The ENN achieved an area under the receiver operating curve of 0.80 and 0.71 to predict nocturnal hypoglycemic events during 0-4 and 4-8 h after bedtime, respectively, outperforming all evaluated baseline methods. Use of the Smart Snack intervention reduced probability of nocturnal hypoglycemia from 23.9 ± 14.1% to 14.0 ± 13.3% and duration from 7.4 ± 7.0% to 2.4 ± 3.3% in silico.

Discussion

Our findings indicate that the ENN-based Smart Snack intervention has the potential to significantly reduce the frequency and duration of nocturnal hypoglycemic events.

Conclusion

A decision support system that combines prediction of minimum nocturnal glucose and proactive recommendations for bedtime carbohydrate intake might effectively prevent nocturnal hypoglycemia and reduce the burden of glycemic self-management.
Sequential autoencoders for feature engineering and pretraining in major depressive disorder risk prediction
Authors: Jones Barrett W , Taylor Warren D , Walsh Colin G
Published: October 2023

Objectives

We evaluated autoencoders as a feature engineering and pretraining technique to improve major depressive disorder (MDD) prognostic risk prediction. Autoencoders can represent temporal feature relationships not identified by aggregate features. The predictive performance of autoencoders of multiple sequential structures was evaluated as feature engineering and pretraining strategies on an array of prediction tasks and compared to a restricted Boltzmann machine (RBM) and random forests as a benchmark.

Materials and Methods

We study MDD patients from Vanderbilt University Medical Center. Autoencoder models with Attention and long-short-term memory (LSTM) layers were trained to create latent representations of the input data. Predictive performance was evaluated temporally by fitting random forest models to predict future outcomes with engineered features as input and using autoencoder weights to initialize neural network layers. We evaluated area under the precision-recall curve (AUPRC) trends and variation over the study population’s treatment course.

Results

The pretrained LSTM model improved predictive performance over pretrained Attention models and benchmarks in 3 of 4 outcomes including self-harm/suicide attempt (AUPRCs, LSTM pretrained = 0.012, Attention pretrained = 0.010, RBM = 0.009, random forest = 0.005). The use of autoencoders for feature engineering had varied results, with benchmarks outperforming LSTM and Attention encodings on the self-harm/suicide attempt outcome (AUPRCs, LSTM encodings = 0.003, Attention encodings = 0.004, RBM = 0.009, random forest = 0.005).

Discussion

Improvement in prediction resulting from pretraining has the potential for increased clinical impact of MDD risk models. We did not find evidence that the use of temporal feature encodings was additive to predictive performance in the study population. This suggests that predictive information retained by model weights may be lost during encoding. LSTM pretrained model predictive performance is shown to be clinically useful and improves over state-of-the-art predictors in the MDD phenotype. LSTM model performance warrants consideration of use in future related studies.

Conclusion

LSTM models with pretrained weights from autoencoders were able to outperform the benchmark and a pretrained Attention model. Future researchers developing risk models in MDD may benefit from the use of LSTM autoencoder pretrained weights.
Capital shocks and the great urban divide
Authors: Daams Michiel N , McCann Philip , Veneri Paolo , Barkham Richard , Schoenmaker Dennis
Published: October 2023

This article exploits signals of capital pricing and availability in US cities which are obtained from uniquely detailed data on real estate investments. We identify how places were differently affected by the global financial crisis and provide insights which offer an alternative explanation of why US economic growth continues to experience spatial divergence after many decades of convergence. Investment pricing uncovers that before the crisis capital was allocated efficiently across localities, whereas the global financial shock favored large and prosperous places. These findings point to persistent post-crisis asymmetry in local capital market conditions and underscore the capital risk-safety aspects of agglomeration.
Polyamines mediate the inhibitory effect of drought stress on nitrogen reallocation and utilization to regulate grain number in wheat
Authors: Li Juan , Li Qi , Guo Nian , Xian Qinglin , Lan Bing , Nangia Vinay , Mo Fei , Liu Yang
Published: October 2023

Drought stress poses a serious threat to grain formation in wheat. Nitrogen (N) plays crucial roles in plant organ development; however, the physiological mechanisms by which drought stress affects plant N availability and mediates the formation of grains in spikes of winter wheat are still unclear. In this study, we determined that pre-reproductive drought stress significantly reduced the number of fertile florets and the number of grains formed. Transcriptome analysis demonstrated that this was related to N metabolism, and in particular, the metabolism pathways of arginine (the main precursor for synthesis of polyamine) and proline. Continuous drought stress restricted plant N accumulation and reallocation rates, and plants preferentially allocated more N to spike development. As the activities of amino acid biosynthesis enzymes and catabolic enzymes were inhibited, more free amino acids accumulated in young spikes. The expression of polyamine synthase genes was down-regulated under drought stress, whilst expression of genes encoding catabolic enzymes was enhanced, resulting in reductions in endogenous spermidine and putrescine. Treatment with exogenous spermidine optimized N allocation in young spikes and leaves, which greatly alleviated the drought-induced reduction in the number of grains per spike. Overall, our results show that pre-reproductive drought stress affects wheat grain numbers by regulating N redistribution and polyamine metabolism.
NMPFamsDB: a database of novel protein families from microbial metagenomes and metatranscriptomes
Authors: Baltoumas Fotis A , Karatzas Evangelos , Liu Sirui , Ovchinnikov Sergey , Sofianatos Yorgos , Chen I-Min , Kyrpides Nikos C , Pavlopoulos Georgios A
Published: October 2023

The Novel Metagenome Protein Families Database (NMPFamsDB) is a database of metagenome- and metatranscriptome-derived protein families, whose members have no hits to proteins of reference genomes or Pfam domains. Each protein family is accompanied by multiple sequence alignments, Hidden Markov Models, taxonomic information, ecosystem and geolocation metadata, sequence and structure predictions, as well as 3D structure models predicted with AlphaFold2. In its current version, NMPFamsDB hosts over 100 000 protein families, each with at least 100 members. The reported protein families significantly expand (more than double) the number of known protein sequence clusters from reference genomes and reveal new insights into their habitat distribution, origins, functions and taxonomy. We expect NMPFamsDB to be a valuable resource for microbial proteome-wide analyses and for further discovery and characterization of novel functions. NMPFamsDB is publicly available in http://www.nmpfamsdb.org/ or https://bib.fleming.gr/NMPFamsDB.
A biomimetic chip to assess subcutaneous bioavailability of monoclonal antibodies in humans
Authors: Chandran Suja Vineeth , Qi Qin M , Halloran Kevin , Zhang Jifeng , Shaha Suyog , Prakash Supriya , Kumbhojkar Ninad , Deslandes Antoine , Huille Sylvain , Gokarn Yatin R , Mitragotri Samir
Published: October 2023

Subcutaneous (subQ) injection is a common route for delivering biotherapeutics, wherein pharmacokinetics is largely influenced by drug transport in a complex subQ tissue microenvironment. The selection of good drug candidates with beneficial pharmacokinetics for subQ injections is currently limited by a lack of reliable testing models. To address this limitation, we report here a Subcutaneous Co-Culture Tissue-on-a-chip for Injection Simulation (SubCuTIS). SubCuTIS possesses a 3D coculture tissue architecture, and it allows facile quantitative determination of relevant scale independent drug transport rate constants. SubCuTIS captures key in vivo physiological characteristics of the subQ tissues, and it differentiates the transport behavior of various chemically distinct molecules. We supplemented the transport measurements with theoretical modeling, which identified subtle differences in the local absorption rate constants of seven clinically available mAbs. Accounting for first-order proteolytic catabolism, we established a mathematical framework to assess clinical bioavailability using the local absorption rate constants obtained from SubCuTIS. Taken together, the technology described here broadens the applicability of organs-on-chips as a standardized and easy-to-use device for quantitative analysis of subQ drug transport.
Phylogeny and classification of jumping plant lice of the subfamily Liviinae (Hemiptera: Psylloidea: Liviidae) based on molecular and morphological data
Authors: Burckhardt Daniel , Serbina Liliya Š , Malenovský Igor , Queiroz Dalva L , Aléné Désirée C , Cho Geonho , Percy Diana M
Published: October 2023

Using molecular (COI, Cytb, H3, wg, 12S, 16S, and 28S) and morphological data (61 characters of adults and immatures), the phylogenetic relationships of the 20 nominal genera of Liviinae were analysed, and the monophyly of the subfamily was tested relative to the other two subfamilies of Liviidae. The analyses of the molecular, morphological, and combined datasets provided similar results with a strong or moderate support in the molecular and combined analyses for the subfamilies of Liviidae and two clades in Liviinae given tribal rank (Liviini and Paurocephalini stat. rev.). Three of the six previously recognized genera were confirmed as monophyletic (Aphorma, Camarotoscena, and Livia) and three were shown to be polyphyletic: Diclidophlebia s.l. (Diclidophlebia s.s., Haplaphalara stat. rev., Klyveria Burckhardt, Serbina and Malenovský, gen. nov., Melanastera Serbina, Malenovský, Queiroz and Burckhardt, gen. nov. and Woldaia stat. rev.), Paurocephala s.l. (Liella Burckhardt, Serbina and Malenovský, gen. nov. and Paurocephala s.s.), and Syntomoza s.l. (Anomoterga stat. rev. and Syntomoza s.s.). The new generic definitions require 38 new and eight revived combinations, including the transfer of two species to other families. All genera of Liviinae are diagnosed and keys are provided for their identification. A checklist of world Liviinae is supplemented.
Compost Filling Methods Affect Green Mold Disease Incidence in Commercial Mushrooms
Authors: Coles Phillip S. , McGiffen Milton E. , Xu Huaying , Frutos Moises
Published: October 2023

Green mold (Trichoderma aggressivum) is an invasive disease of commercial mushrooms introduced into the United States from Europe that now has spread to commercial mushrooms throughout North America. We examined potential sources of invasive green mold inoculum and the association with different compost filling technologies on a large actively producing commercial mushroom farm. Green mold foci were sampled bed by bed, which generated 20,906 data points. Logistic regression was used to determine treatment differences. Mechanical filling of compost into the beds reduced green mold incidence over hand filling, apparently due to the reduced incidence of worker contact with the floor and between beds. Lower growing beds located closer to the floor had a higher incidence of green mold for both mechanical and hand-filled beds. We conclude that mechanical filling and generally reducing contact with the floor and between beds will reduce spread of green mold in commercial mushroom production.
Defining chronic rejection in vascularized composite allografts – do we have reliable surrogates to look for?
Authors: Kanitakis Jean
Published: October 2023

Purpose of review

Chronic rejection (CR) is a major threat in the field of vascularized composite tissue allografts (VCAs) as it causes graft dysfunction and usually graft loss. Unfortunately, knowledge of CR in VCA is incomplete because of the limited number of VCA recipients, the heterogeneous nature of VCAs and the short follow-up.

Recent findings

The diagnosis of CR in VCA has relied on clinical and pathological findings. Clinical changes include graft fibrosis, dyschromia and ischemic/necrotic ulcerations. Pathological changes primarily affect allograft vessels and manifest with graft vasculopathy (i.e. myo-intimal proliferation and luminal narrowing of allograft vessels, leading to graft ischemia). Attempts are made to diagnose CR with non- or minimally-invasive techniques, such as imaging studies (ultrasound biomicroscopy, functional magnetic resonance imaging) and serum biomarkers. These techniques provide interesting results and further insight into the mechanisms of CR in VCA.

The diagnosis of CR in VCA still relies mainly on clinicopathological graft alterations; unfortunately, these become overt rather late during the rejection process, when reversal of CR is problematic. More recent, minimally- or non-invasive techniques have provided encouraging results, but their usefulness in the diagnosis of CR requires further studies. These data highlight the paramount importance of CR prevention.
Novel Clinically Translatable Iron Oxide Nanoparticle for Monitoring Anti-CD47 Cancer Immunotherapy
Authors: Roudi Raheleh , Pisani Laura , Pisani Fabrizio , Kiru Louise , Daldrup-Link Heike E.
Published: October 2023

Objectives

A novel clinically translatable iron oxide nanoparticle (IOP) is currently being tested in phase 2 clinical trials as a magnetic resonance imaging (MRI) contrast agent for hepatocellular carcinoma diagnosis. The purpose of our study is to evaluate if this IOP can detect activation of tumor-associated macrophages (TAMs) due to CD47 mAb-targeted immunotherapy in 2 mouse models of osteosarcoma.

Materials and Methods

The toxicity, biodistribution, and pharmacokinetics of IOP were evaluated in 77 female and 77 male rats. Then, 24 female BALB/c mice with intratibial murine K7M2 tumors and 24 female NOD scid gamma mice with intratibial human 143B osteosarcoma xenografts were treated with either CD47 mAb (n = 12) or control antibody (n = 12). In each treatment group, 6 mice underwent MRI scans before and after intravenous infusion of either IOP or ferumoxytol (30 mg Fe/kg). Tumor T2* values and TAM markers F4/80, CD80, CD206, and Prussian blue staining were compared between different experimental groups using exact 2-sided Wilcoxon rank sum tests.

Results

Biodistribution and safety evaluations of IOP were favorable for doses of less than 50 mg Fe/kg body weight in female and male rats. Both IOP and ferumoxytol caused negative enhancement (darkening) of the tumor tissue. Both murine and human osteosarcoma tumors treated with CD47 mAb demonstrated significantly shortened T2* relaxation times after infusion of IOP or ferumoxytol compared with controls (all P's < 0.05). Higher levels of F4/80+CD80+ were found in murine and human osteosarcomas treated with CD47 mAb compared with sham-treated controls (all P's < 0.05). In addition, murine CD47 mAb-treated tumors after infusion of either IOP or ferumoxytol showed significantly higher numbers of Prussian blue–positive cells compared with controls (P < 0.05). There was no significant difference of F4/80+CD206+ cells among any of the groups (all P's > 0.05).

Conclusions

Iron oxide nanoparticle–enhanced MRI can be used to diagnose CD47 mAb-mediated TAM-activation in osteosarcomas.
Metal Artifact Reduction in Photon-Counting Detector CT
Authors: Skornitzke Stephan , Mergen Victor , Biederer Jürgen , Alkadhi Hatem , Do Thuy D. , Stiller Wolfram , Frauenfelder Thomas , Kauczor Hans-Ulrich , Euler André
Published: October 2023

Objectives

With the introduction of clinical photon-counting detector computed tomography (PCD-CT) and its novel reconstruction techniques, a quantitative investigation of different acquisition and reconstruction settings is necessary to optimize clinical acquisition protocols for metal artifact reduction.

Materials and Methods

A multienergy phantom was scanned on a clinical dual-source PCD-CT (NAEOTOM Alpha; Siemens Healthcare GmbH) with 4 different central inserts: water-equivalent plastic, aluminum, steel, and titanium. Acquisitions were performed at 120 kVp and 140 kVp (CTDIvol 10 mGy) and reconstructed as virtual monoenergetic images (VMIs; 110–150 keV), as T3D, and with the standard reconstruction “none” (70 keV VMI) using different reconstruction kernels (Br36, Br56) and with as well as without iterative metal artifact reduction (iMAR). Metal artifacts were quantified, calculating relative percentages of metal artifacts. Mean CT numbers of an adjacent water-equivalent insert and different tissue-equivalent inserts were evaluated, and eccentricity of metal rods was measured. Repeated-measures analysis of variance was performed for statistical analysis.

Results

Metal artifacts were most prevalent for the steel insert (12.6% average artifacts), followed by titanium (4.2%) and aluminum (1.0%). The strongest metal artifact reduction was noted for iMAR (with iMAR: 1.4%, without iMAR: 10.5%; P < 0.001) or VMI (VMI: 110 keV 2.6% to 150 keV 3.3%, T3D: 11.0%, and none: 16.0%; P < 0.001) individually, with best results when combining iMAR and VMI at 110 keV (1.2%). Changing acquisition tube potential (120 kV: 6.6%, 140 kV: 5.2%; P = 0.33) or reconstruction kernel (Br36: 5.5%, Br56: 6.4%; P = 0.17) was less effective. Mean CT numbers and standard deviations were significantly affected by iMAR (with iMAR: −3.0 ± 21.5 HU, without iMAR: −8.5 ± 24.3 HU; P < 0.001), VMI (VMI: 110 keV −3.6 ± 21.6 HU to 150 keV −1.4 ± 21.2 HU, T3D: −11.7 ± 23.8 HU, and none: −16.9 ± 29.8 HU; P < 0.001), tube potential (120 kV: −4.7 ± 22.8 HU, 140 kV: −6.8 ± 23.0 HU; P = 0.03), and reconstruction kernel (Br36: −5.5 ± 14.2 HU, Br56: −6.8 ± 23.0 HU; P < 0.001). Both iMAR and VMI improved quantitative CT number accuracy and metal rod eccentricity for the steel rod, but iMAR was of limited effectiveness for the aluminum rod.

Conclusions

For metal artifact reduction in PCD-CT, a combination of iMAR and VMI at 110 keV demonstrated the strongest artifact reduction of the evaluated options, whereas the impact of reconstruction kernel and tube potential was limited.
European Guideline Robin Sequence An Initiative From the European Reference Network for Rare Craniofacial Anomalies and Ear, Nose and Throat Disorders (ERN-CRANIO)
Authors:   By the Working Group on Writing a European Guideline on Robin Sequence
Published: October 2023

A European guideline on Robin Sequence was developed within the European Reference Network for rare and/or complex craniofacial anomalies and ear, nose, and throat disorders. The guideline provides an overview of optimal care provisions for patients with Robin Sequence and recommendations for the improvement of care.
Outcomes of Decompressive Craniectomy in the Management of Traumatic Brain Injury: A Ten-Year Retrospective Analysis
Authors: Zeynal Mete , Akyüz Mehmet Emin
Published: October 2023

Objective:

This study aimed to investigate factors associated with patient outcomes after decompressive craniectomy for severe traumatic brain injury (TBI) and to compare the authors’ findings with the existing literature.

Methods:

The authors conducted a retrospective analysis of 50 patients who underwent decompressive craniectomy for severe TBI between 2013 and 2023. Patient characteristics, including age, sex, Glasgow Coma Scale (GCS) score, Injury Severity Score (ISS), electrolyte imbalances, nosocomial infections, and hospital stay duration, were collected. Outcomes were assessed at 12 months postsurgery, and statistical analyses were performed to determine factors associated with favorable and unfavorable outcomes.

Results:

Younger age, higher GCS scores, and lower ISS were significantly associated with favorable outcomes. Electrolyte imbalances, particularly hyponatremia, and hyperkalemia, were linked to unfavorable outcomes. Nosocomial infections were significantly more common in patients with unfavorable outcomes. Longer hospital stays were also associated with worse outcomes.

Conclusions:

The authors’ findings highlight the importance of individualized patient management based on age, admission GCS score, ISS, electrolyte imbalances, nosocomial infections, and hospital stay duration to maximize the potential for favorable outcomes. These results contribute to the growing literature on decompressive craniectomy for TBI and provide valuable insights for clinicians in optimizing patient management.
Generating a Prioritised List of Operative Procedures for Simulation-Based Assessment of General Surgery Trainees through Consensus
Authors: Toale Conor , Morris Marie , Konge Lars , Nayahangan Leizl Joy , Roche Adam , Heskin Leonie , Kavanagh Dara O
Published: October 2023

Objective:

to develop appropriate content for high-stakes simulation-based assessments of operative competence in general surgery training through consensus.

Summary Background Data:

Valid methods of summative operative competence assessment are required by competency-based training programmes in surgery.

Method:

An online Delphi consensus study was conducted. Procedures were derived from the competency expectations outlined by the Joint Commission on Surgical Training (JCST) curriculum 2021, and subsequent brainstorming. Procedures were rated according to their perceived importance, perceived procedural risk, how frequently they are performed, and feasibility, by a purposive sample of thirty surgical trainers and a five-person steering group. A modified Copenhagen Academy for Medical Education and Simulation Needs Assessment Formula (CAMES NAF) was applied to generated data in order to produce ranked procedural lists, which were returned to participants for re-prioritization.

Results:

Prioritised lists were generated for simulation-based operative competence assessments at two key stages of training; end of ‘phase 2’ prior to development of a sub-specialty interest, and end of ‘phase 3’ i.e. end-of-training certification. A total of 21 and 16 procedures were deemed suitable for assessments at each of these stages respectively.

Conclusions:

This study describes a national needs assessment approach to content generation for simulation-based assessments of operative competence in general surgery using Delphi consensus methodology. The prioritised procedural lists generated by this study can be used to further develop operative skill assessments for use in high-stakes scenarios such as trainee progression, entrustment and end-of-training certification prior to subsequent validity testing.
Liver-specific glucocorticoid action in alcoholic liver disease: study of glucocorticoid receptor knockout and knockin mice
Authors: Wang Yazheng , Lu Hong
Published: October 2023

Background

Glucocorticoids are the only first-line drugs for severe alcoholic hepatitis (AH), with limited efficacy and various side effects on extrahepatic tissues. Liver-targeting glucocorticoid therapy may have multiple advantages over systemic glucocorticoid for AH. The purpose of this study was to determine the role of hepatocellular glucocorticoid receptor (GR) in alcoholic steatosis (AS) and AH.

Methods

AS was induced by a high-fat diet plus binge alcohol in adult male and female mice with liver-specific knockout (LKO) and heterozygote of GR. AH was induced by chronic-plus-binge in middle-aged male mice with liver-specific knockin of GR. Changes in hepatic mRNA and protein expression were determined by qPCR and Western blot.

Results

GR LKO aggravated steatosis and decreased hepatic expression and circulating levels of albumin in both genders of AS mice but only increased markers of liver injury in male AS mice. Marked steatosis in GR LKO mice was associated with induction of lipogenic genes and down-regulation of bile acid synthetic genes. Hepatic protein levels of GR, hepatocyte nuclear factor 4α, and phosphorylated STAT3 were gene-dosage-dependently decreased, whereas that of lipogenic ATP citrate lyase was increased in male GR heterozygote and LKO mice. Interestingly, hepatic expression of estrogen receptor α (ERα) was induced, and the essential estrogen-inactivating enzyme sulfotransferase 1E1 was gene-dosage-dependently down-regulated in GR heterozygote and knockout AS mice, which was associated with induction of ERα-target genes. Liver-specific knockin of GR protected against liver injury and steatohepatitis in middle-aged AH mice.

Conclusions

Hepatocellular GR is important for protection against AS and AH.
Hypoxic injury triggers maladaptive repair in human kidney organoids
Authors: Nunez-Nescolarde Ana B. , Piran Mehran , Perlaza-Jiménez Laura , Barlow Chris K. , Steele Joel R. , Deveson Deanna , Lee Han-Chung , Moreau Julie L. M. , Schittenhelm Ralf B. , Nikolic-Paterson David J. , Combes Alexander N.
Published: October 2023

Acute kidney injury (AKI) is a common clinical disorder linked to high rates of illness and death. Ischemia is a leading cause of AKI, which can result in chronic kidney disease (CKD) through a maladaptive repair process characterised by failed epithelial regeneration, inflammation, and metabolic dysregulation. No targeted therapies exist to prevent the AKI to CKD transition and insight into ischemic AKI and maladaptive repair in humans remains limited. In this study, we report that human kidney organoids recapitulate select molecular and metabolic signatures of AKI and maladaptive repair in response to hypoxic injury. Transcriptional, proteomic, and metabolomic profiling revealed signatures of tubular injury, cell death, cell cycle arrest and altered metabolism in kidney organoids cultured in hypoxic conditions. After recovery in normoxic conditions, injured organoids displayed increased signatures associated with maladaptive repair like TNF, NF-κB, and JAK-STAT pathways, and S100A8/9. Single cell RNA sequencing localised biomarkers of AKI and maladaptive repair such as GDF15, MMP7, ICAM1, TGFB1, SPP1, C3 and CCN1 to injured proximal and distal tubules. Metabolic phenotypes linked to CKD were also evident including dysregulated glycolysis and gluconeogenesis, amino acid, bicarbonate and lipid metabolism, and elevated ceramide levels. Our multi-omic analysis provides compelling evidence for the use of kidney organoids as a model of human ischemic AKI and maladaptive repair, highlighting new and conserved biomarkers and mechanisms, and opportunities for drug screening.

Human kidney organoids recapitulate molecular and metabolic signatures of ischemic acute kidney injury and maladaptive repair, providing new insight into human disease mechanisms and opportunities for drug development.
Beyond the nucleus: Plastic chemicals activate G protein-coupled receptors
Authors: McPartland Molly , Stevens Sarah , Bartosova Zdenka , Gisnås Vardeberg Ingrid , Völker Johannes , Wagner Martin
Published: October 2023

Abstract Figure

G protein-coupled receptors (GPCRs) are central mediators of cell signaling and physiological function. Despite their biological significance, GPCRs have not been widely studied in the field of toxicology. Herein, we investigated these receptors are novel targets of plastic chemicals using a high-throughput drug screening assay with 126 human non-olfactory GPCRs. In a first-pass screen, we tested the activity of triphenol phosphate, bisphenol A, and diethyl phthalate as well as three real-world mixtures of chemicals extracted from plastic food packaging covering all major polymer types. We found 11 GPCR-chemical interactions, of which the chemical mixtures exhibited the most robust activity at Adenosine receptor 1 (ADORA1) and Melatonin receptor 1 (MTNR1A) in a confirmatory secondary screen. We further confirmed that polyvinyl chloride and polyurethane products contain ADORA1 or MTNRA1 agonists using pharmacological knockdown experiments. Finally, an analysis of the associated gene ontology terms suggests that ADORA1 and MTNR1A activation may be linked to downstream effects on circadian and metabolic processes. Our findings exemplify the diversity of endpoints plastic chemicals can target and demonstrate the relevance of non-genomic pathways which have thus far remained unexplored.
Opposing neural processing modes alternate rhythmically during sustained auditory attention
Authors: Kasten Florian H. , Busson Quentin , Zoefel Benedikt
Published: October 2023

During continuous tasks, humans show spontaneous fluctuations in performance, putatively caused by varying attentional resources allocated to process external information. If neural resources are used to process other, presumably “internal” information, sensory input can be missed and explain an apparent dichotomy of “internal” versus “external” attention.

In the current study, we extracted presumed neural signatures of these attentional modes in human electroencephalography (EEG): neural entrainment and α-oscillations (∼10-Hz), linked to the processing and suppression of sensory information, respectively. We tested whether they exhibit structured fluctuations over time, while listeners attended to an ecologically relevant stimulus like speech and completed a task that required full and continuous attention.

Results showed an antagonistic relation between neural entrainment to speech and spontaneous α-oscillations in two distinct brain networks – one specialized in the processing of external information, the other reminiscent of the dorsal attention network. These opposing neural modes underwent slow, periodic fluctuations around ∼0.07 Hz and were related to the detection of auditory targets. Our study might have tapped into a general attentional mechanism that is conserved across species and has important implications for situations in which sustained attention to sensory information is critical.

Graphical Abstract
Recurrent hybridization and gene flow shaped Norway and Siberian spruce evolutionary history over multiple glacial cycles
Authors: Zhou Qiujie , Karunarathne Piyal , Andersson-Li Lili , Chen Chen , Opgenoorth Lars , Heer Katrin , Vendramin Giovanni Giuseppe , Piotti Andrea , Nakvasina Elena , Lascoux Martin , Milesi Pascal
Published: October 2023

Over the last decades, extensive genome-wide resequencing studies have highlighted the extent of hybridization and introgression between closely related species. Animal and plant species went through cycles of contractions and expansions as a result of glacial cycles. These repeated sequences of reproductive isolation and admixture at continental scales have led to the accumulation over time of an ancient, deep-seated and complex genetic structure. This structure was blurred by extensive gene flow, or reinforced by strong local adaptation. This already multi-layered structure has often been further enhanced by hybridization.

We investigated this complexity in Norway spruce (Picea abies) and Siberian spruce (P. obovata), two closely related species dominating Eurasian boreal forests and forming a vast hybrid zone. Here, we genotyped 542 individuals of both species and their hybrids at 480K SNPs. Individuals came from 55 populations, extending from western Europe to Siberia with a focus on the main hybrid zone. Despite extensive gene flow and a clear Isolation-by-Distance pattern at the continental scale, distinct genetic clusters emerged, indicating barriers and corridors to migration. Coalescent-based demographic inferences revealed that Norway and Siberian spruce repeatedly hybridized during the Pleistocene with introgression pattern varying depending on the latitude. In northern ranges,P. obovataexpanded intoP. abieswhileP. abiesexpanded intoP. obovatain the southern parts. Two cryptic refugia located in the large hybrid zone played a critical role in shaping the current distribution of the two species. Our study highlights the importance of considering the whole species complex instead of separate entities to shed light on their complex demographic histories.