bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-Specific Vascularized Tumor Model: Blocking TAM Recruitment with Multispecific Antibodies Targeting CCR2 and CSF-1R
Authors: Nguyen Huu Tuan , Gurvich Nadia , Gillrie Mark Robert , Offeddu Giovanni , Humayun Mouhita , Kan Ellen L. , Wan Zhengpeng , Coughlin Mark Frederick , Zhang Christie , Vu Vivian , Ling Lee Sharon Wei , Tan Seng-Lai , Barbie David , Hsu Jonathan , Kamm Roger D. 
Published: November 2023

AbstractTumor-associated inflammation drives cancer progression and therapy resistance, with the infiltration of monocyte-derived tumor-associated macrophages (TAMs) associated with poor prognosis in diverse cancers. Targeting TAMs holds potential against solid tumors, but effective immunotherapies require testing on immunocompetent human models prior to clinical trials. Here, we develop an in vitro model of microvascular networks that incorporates tumor spheroids or patient tissues. By perfusing the vasculature with human monocytes, we investigate monocyte trafficking into the tumor and evaluate immunotherapies targeting the human tumor microenvironment. Our findings demonstrate that macrophages in vascularized breast and lung tumor models can enhance monocyte recruitment via TAM-produced CCL7 and CCL2, mediated by CSF-1R. Additionally, we assess a novel multispecific antibody targeting CCR2, CSF-1R, and neutralizing TGF-β, referred to as CSF1R/CCR2/TGF-β Ab, on monocytes and macrophages using our 3D models. This antibody repolarizes TAMs towards an anti-tumoral M1-like phenotype, reduces monocyte chemoattractant protein secretion, and effectively blocks monocyte migration. Finally, we show that the CSF1R/CCR2/TGF-β Ab inhibits monocyte recruitment in patient-specific vascularized tumor models. Overall, this vascularized tumor model offers valuable insights into monocyte recruitment and enables functional testing of innovative therapeutic antibodies targeting TAMs in the tumor microenvironment (TME).
Framewise multi-echo distortion correction for superior functional MRI
Authors: Van Andrew N. , Montez David F. , Laumann Timothy O. , Suljic Vahdeta , Madison Thomas , Baden Noah J. , Ramirez-Perez Nadeshka , Scheidter Kristen M. , Monk Julia S. , Whiting Forrest I. , Adeyemo Babatunde , Chauvin Roselyne J. , Krimmel Samuel R. , Metoki Athanasia , Rajesh Aishwarya , Roland Jarod L. , Salo Taylor , Wang Anxu , Weldon Kimberly B. , Sotiras Aristeidis , Shimony Joshua S. , Kay Benjamin P. , Nelson Steven M. , Tervo-Clemmens Brenden , Marek Scott A. , Vizioli Luca , Yacoub Essa , Satterthwaite Theodore D. , Gordon Evan M. , Fair Damien A. , Tisdall M. Dylan , Dosenbach Nico U.F. 
Published: November 2023

AbstractFunctional MRI (fMRI) data are severely distorted by magnetic field (B0) inhomogeneities which currently must be corrected using separately acquired field map data. However, changes in the head position of a scanning participant across fMRI frames can cause changes in the B0 field, preventing accurate correction of geometric distortions. Additionally, field maps can be corrupted by movement during their acquisition, preventing distortion correction altogether. In this study, we use phase information from multi-echo (ME) fMRI data to dynamically sample distortion due to fluctuating B0 field inhomogeneity across frames by acquiring multiple echoes during a single EPI readout. Our distortion correction approach, MEDIC (Multi-Echo DIstortion Correction), accurately estimates B0 related distortions for each frame of multi-echo fMRI data. Here, we demonstrate that MEDIC’s framewise distortion correction produces improved alignment to anatomy and decreases the impact of head motion on resting-state functional connectivity (RSFC) maps, in higher motion data, when compared to the prior gold standard approach (i.e., TOPUP). Enhanced framewise distortion correction with MEDIC, without the requirement for field map collection, furthers the advantage of multi-echo over single-echo fMRI.
Sigma receptor ligands are potent anti-prion compounds that act independently of sigma receptor binding
Authors: Mercer Robert C. C. , Le Nhat T. T. , Houser Mei C. Q. , Beeler Aaron B. , Harris David A. 
Published: November 2023

AbstractPrion diseases are invariably fatal neurodegenerative diseases of humans and other animals for which there are no treatment options. Previous work from our laboratory identified phenethyl piperidines as novel class of anti-prion compounds. While working to identify the molecular target(s) of these molecules, we unexpectedly discovered ten novel anti-prion compounds based on their known ability to bind to the sigma receptors, σ1R and2R, which are currently being tested as therapeutic or diagnostic targets for cancer and neuropsychiatric disorders. Surprisingly, however, knockout of the respective genes encoding σ1R and σ2R (Sigmar1andTmem97), in prion infected N2a cells did not alter the anti-prion activity of these compounds, demonstrating that these receptors are not the direct targets responsible the anti-prion effects of their ligands. Further investigation of the most potent molecules established that they are efficacious against multiple prion strains and protect against downstream prion-mediated synaptotoxicity. While the precise details of the mechanism of action of these molecules remains to be determined, the present work forms the basis for further investigations of these compounds in pre-clinical studies. Given the therapeutic utility of several of the tested compounds, including rimcazole and haloperidol for neuropsychiatric conditions, (+)-pentazocine for neuropathic pain, and the ongoing clinical trials of SA 4503 and ANAVEX2-73 for ischemic stroke and Alzheimer’s disease, respectively, this work has immediate implications for the treatment of human prion disease.
Associations of salivary cortisol with cardiovascular parameters and mortality in the MRC National Survey of Health and Development (NSHD)
Authors: Al Saikhan Lamia , Williams Dylan M , Captur Gaby , Hughes Alun D , Davis Daniel , Chaturvedi Nish 
Published: November 2023

AbstractObjectivesHypothalamic-pituitary-adrenal (HPA) dysregulation is a postulated risk factor for cardiovascular disease but results from previous studies have been mixed. We examined cross-sectional associations of diurnal patterns of salivary cortisol with 10 subclinical measures of cardiovascular disease (including pulse wave velocity, carotid intima-media thickness, and measures of heart structure and function), and prospective associations of cortisol variation with cardiovascular (CV) and non-cardiovascular (NCV) mortality.MethodsWe included up to 1,263 participants of the MRC National Survey for Health and Development birth cohort, who had participated in serial diurnal salivary cortisol sampling in 2006-2010 (aged 60–64 years). We used multivariable linear and multinomial logistic regression to estimate associations of cortisol awakening response (CAR), slope and area under the curve (AUC) with subclinical cardiovascular measures, and multivariable Cox regression to estimate associations of the three cortisol metrics with all-cause, CV and NCV mortality.ResultsAll associations with subclinical cardiovascular measures were weak and most were compatible with the null hypothesis. Each standard deviation (SD) higher cortisol AUC was associated with a 1.9% (95%-CI 0.3-3.5) higher pulse wave velocity. A shallow cortisol slope (per SD gradient) was associated with a 1.4% lower intima media thickness (95%-CI −2.6, − 0.2), and lower odds of concentric remodelling (OR 0.83, 95%-CI 0.70-0.99). Given the multiple analyses performed, these could be chance findings. AUC, cortisol slope and CAR were not convincingly associated with cardiovascular or total mortality, although the 95% confidence intervals of hazard ratio estimates were wide.ConclusionsThis study provides little evidence for clinically important associations of salivary cortisol and subclinical cardiovascular measures and mortality.
Distinct catecholaminergic pathways projecting to hippocampal CA1 transmit contrasting signals during navigation in familiar and novel environments
Authors: Heer Chad M , Sheffield Mark E J 
Published: November 2023

AbstractNeuromodulatory inputs to the hippocampus play pivotal roles in modulating synaptic plasticity, shaping neuronal activity, and influencing learning and memory. Recently it has been shown that the main sources of catecholamines to the hippocampus, ventral tegmental area (VTA) and locus coeruleus (LC), may have overlapping release of neurotransmitters and effects on the hippocampus. Therefore, to dissect the impacts of both VTA and LC circuits on hippocampal function, a thorough examination of how these pathways might differentially operate during behavior and learning is necessary. We therefore utilized 2-photon microscopy to functionally image the activity of VTA and LC axons within the CA1 region of the dorsal hippocampus in head-fixed male mice navigating linear paths within virtual reality (VR) environments. We found that within familiar environments some VTA axons and the vast majority of LC axons showed a correlation with the animals’ running speed. However, as mice approached previously learned rewarded locations, a large majority of VTA axons exhibited a gradual ramping-up of activity, peaking at the reward location. In contrast, LC axons displayed a pre-movement signal predictive of the animal’s transition from immobility to movement. Interestingly, a marked divergence emerged following a switch from the familiar to novel VR environments. Many LC axons showed large increases in activity that remained elevated for over a minute, while the previously observed VTA axon ramping-to-reward dynamics disappeared during the same period. In conclusion, these findings highlight distinct roles of VTA and LC catecholaminergic inputs in the dorsal CA1 hippocampal region. These inputs encode unique information, with reward information in VTA inputs and novelty and kinematic information in LC inputs, likely contributing to differential modulation of hippocampal activity during behavior and learning.
Circular extrachromosomal DNA inEuglena gracilisunder normal and stress conditions
Authors: Gumińska Natalia , Hałakuc Paweł , Zakryś Bożena , Milanowski Rafał 
Published: November 2023

AbstractExtrachromosomal circular DNA (eccDNA) enhances genomic plasticity, augmenting its coding and regulatory potential. Advances in high-throughput sequencing have enabled the investigation of these structural variants. Although eccDNAs have been investigated in numerous taxa, they remained understudied in euglenids. Therefore, we examined eccDNAs predicted from Illumina sequencing data ofEuglena gracilisZ SAG 1224–5/25, grown under optimal photoperiod and exposed to UV irradiation. We identified approximately 1000 unique eccDNA candidates, about 20% of which were shared across conditions. We also observed a significant enrichment of mitochondrially encoded eccDNA in the UV-irradiated sample. Furthermore, we found that the heterogeneity of eccDNA was reduced in UV-exposed samples compared to cells that were grown in optimal conditions. Hence, eccDNA appears to play a role in the response to oxidative stress in Euglena, as it does in other studied organisms. In addition to contributing to the understanding of Euglena genomes, our results contribute to the validation of bioinformatics pipelines on a large, non-model genome.
Validation of Diabetes Prediction Scores: Does adding a high risk for depression increase the area under the curve?
Authors: Salinero-Fort MA , Mostaza J , Lahoz C , Cárdenas-Valladolid J , Iriarte-Campo V , Estirado-de Cabo E , García-Iglesias F , González-Alegre T , Fernández-Puntero B , Cornejo-del Río V , Sánchez-Arroyo V , Sabín-Rodriguez C , López-López S , Gómez-Campelo P , Taulero-Escalera B , Rodriguez-Artalejo F , San Andrés-Rebollo FJ , de Burgos-Lunar C 
Published: November 2023

AbstractBackgroundDiabetes risk scores include age, waist circumference, body mass index, hypertension, use of blood pressure medication, and metabolic and lifestyle variables. Although patients with major depressive disorder have a higher risk of diabetes, none of the diabetes risk scores includes high risk of depression as an additional item.AimTo validate three diabetes risk scores (FINDRISC, DESIR, ADA) in the Spanish population aged >45 years with the aim of predicting diabetes and to test the value of adding high risk of depression, defined as a PHQ-9 questionnaire score ≥10, to the risk score with the best discriminative performance.MethodsProspective population-based cohort study in Madrid (Spain). FINDRISC, DESIR, ADA, PHQ-9, and OGTT values were measured at baseline. Participants with OGTT <200 mg/dl (n= 1,242) were followed up for a median of 7.3 years using their general practitioner’s electronic health record (EHR) and telephone contact. Incident diabetes was identified as treatment for diabetes, fasting plasma glucose ≥126 mg/dl, a new diagnosis in the EHR, or self-reported diagnosis. At the end of the study, the performance of diabetes risk scores, including a modified original FINDRISC score with a new variable for high risk of depression (FINDRISC-MOOD), was assessed.ResultsDuring follow-up, 104 (8.4%; 95% CI, 6.8-9.9) participants developed diabetes, and 185 had a PHQ-9 score ≥10. The AUROC values were 0.70 (95% CI, 0.67-0.72) for FINDRISC-MOOD and 0.68 (95% CI, 0.65-0.71) for the original FINDRISC. The AUROC for DESIR and ADA were 0.66 (95% CI, 0.63-0.68) and 0.66 (95% CI, 0.63-0.69), respectively. There were no significant differences in the AUROC between FINDRISC-MOOD and the remaining scores.ConclusionFINDRISC-MOOD performed slightly better than the other risk scores, although the differences were not significant. FINDRISC-MOOD could be used to identify the risk of future diabetes.
Airway and respiratory complications during anaesthesia and associated with peri‐operative cardiac arrest as reported to the 7th National Audit Project of the Royal College of Anaesthetists
Authors: Cook T. M. , Oglesby F. , Kane A. D. , Armstrong R. A. , Kursumovic E. , Soar J. 
Published: November 2023

SummaryThe 7th National Audit Project (NAP7) of the Royal College of Anaesthetists studied complications of the airway and respiratory system during anaesthesia care including peri‐operative cardiac arrest. Among 24,721 surveyed cases, airway and respiratory complications occurred commonly (n = 421 and n = 264, respectively). The most common airway complications were: laryngospasm (157, 37%); airway failure (125, 30%); and aspiration (27, 6%). Emergency front of neck airway was rare (1 in 8370, 95%CI 1 in 2296–30,519). The most common respiratory complications were: severe ventilation difficulty (97, 37%); hyper/hypocapnia (63, 24%); and hypoxaemia (62, 23%). Among 881 reports to NAP7 and 358 deaths, airway and respiratory complications accounted for 113 (13%) peri‐operative cardiac arrests and 32 (9%) deaths, with hypoxaemia as the most common primary cause. Airway and respiratory cases had higher and lower survival rates than other causes of cardiac arrest, respectively. Patients with obesity, young children (particularly infants) and out‐of‐hours care were overrepresented in reports. There were six cases of unrecognised oesophageal intubation with three resulting in cardiac arrest. Of these cases, failure to correctly interpret capnography was a recurrent theme. Cases of emergency front of neck airway (6, approximately 1 in 450,000) and pulmonary aspiration (11, approximately 1 in 25,000) leading to cardiac arrest were rare. Overall, these data, while distinct from the 4th National Audit Project, suggest that airway management is likely to have become safer in the last decade, despite the surgical population having become more challenging for anaesthetists.
Novel identification of t(14;18)(q32;q21)/IGH::MALT1 in chronic lymphocytic leukaemia
Authors: Kumar Jyoti , Ewalt Mark D. , Zhang Yanming , Yao JinJuan , Thompson Meghan C. , Dogan Ahmet 
Published: November 2023

SummaryChronic lymphocytic leukaemia (CLL) is a clonal B‐cell malignancy and remains a chronic disease despite improvements in clinical outcomes since the use of targeted therapies. Both clinical and biological parameters are important for determining prognosis. Unlike other mature B‐cell lymphomas, translocations involving the immunoglobulin heavy chain (IGH) locus are uncommon in CLL. There have been few case reports of CLL harbouring t(14;18)/IGH::BCL2 and t(14;19)/IGH::BCL3. Here we describe the first two cases of patients with CLL with documented t(14;18)(q32;q21)/IGH::MALT1. Both cases in this report were associated with lower‐risk biological parameters. Thus, FISH testing for MALT1 in cases with unknown IGH translocation partners in the setting of CLL should be implemented in clinical practice to better define such cases.
Perspectives of young adults diagnosed with early psychosis using coordinated specialty care in Texas on substance use and substance use interventions
Authors: Myers Neely Laurenzo , Wilkey Justin , Chacon Marne , Hutnyan Matthew , Janssen Claire , Tarvin Halle , Cohen Deborah , Holmes Imani , Klodnick Vanessa Vorhies , Mihiret Mesganaw A. , Reznik Samantha J. , Shimizu Taylor Khouw , Stein Emily , Lopez Molly A. 
Published: November 2023

AbstractAimDespite known prevalence of substance use (SU) among young people experiencing early psychosis and increasing evidence for the relationship between certain substances (e.g., cannabis) and psychosis, there are no specialized interventions developed for effectively addressing substance use among young people participating in coordinated early psychosis services. This study elicited the perspectives of young people with early psychosis participating in Coordinated Specialty Care (CSC) programs about their substance use, including their motivations and concerns around their use, and their ideas on how to best support young people who are interested in reducing or quitting substance use.MethodsWe recruited young adults (ages 18 to 30) from CSC programs across Texas through flyers sent to program staff inviting young persons willing to talk about substance use to engage in a 60–90 min person‐centered, semi‐structured, audio‐recorded Zoom interview.ResultsA total of 22 young adults were recruited and 18 completed an interview. Participants described mixed positive and negative responses to substance use, and while many understood the importance of discontinuing substance use, many expressed ambivalence related to social, contextual, mental and physical factors that motivated them to keep using. Participants desired practical substance use information, opportunities to explore their substance use ambivalence in supportive relationships, positive peer communities to support healthy choices, help engage, with work, school, and hobbies, and strategies for addressing psychological and physical pain that did not include substance use.ConclusionStudy findings illuminate what motivates young people with early psychosis to initiate, continue, or cut back on substance use, and ideas for CSC practices for exploring substances and helping young people to reduce substance use.
Shrinkage, microstructure, and mechanical properties of sintered 3D‐printed silica via stereolithography
Authors: Evans Peter , Turner Griffin , Patel Raj , Moghadasi Mohammadamin , Yang Qirong , Pei Zhijian , Ma Chao , Paramore James D. , Butler Brady G. , Xie Kelvin Y. 
Published: November 2023

AbstractStereolithography has been used to create ceramic parts with complex geometry that is difficult to achieve with conventional fabrication techniques. This study used stereolithography to print silica honeycomb structures with a commercial Formlabs Form2 printer. The printed samples were sintered at different temperatures, and the print shape was retained up to 1300°C, but significant distortion from partial melting occurred at 1400°C. Higher sintering temperatures lead to more shrinkage, but it is non‐uniform among directions, with the open cell plane shrinking more than the dense plane of the sample. As expected, the density of samples also increases with the sintering temperature. At higher sintering temperatures, there is an increase in cristobalite and a decrease in quartz, tridymite, and amorphous silica. Regarding mechanical properties, the out‐of‐plane compressive strength is approximately one order of magnitude higher than the in‐plane compressive strength. When compressed along the out‐of‐plane direction, the samples sintered at lower temperatures surprisingly exhibit higher strength, which is explained by the micro‐cracking mechanism. As expected, the samples sintered at higher temperatures display higher strength when compressed along the in‐plane direction.
Unlocking nutritional and functional insights: exploring the impact of germination time on bean protein isolate
Authors: Srenuja Dekka , Hema Vincent , Anand Maria Tito , Jagan Mohan Rangarajan , Vidyalakshmi Rajagopal 
Published: November 2023

SummaryThe study aims to investigate the effect of germination time on kidney bean protein isolate (KBPI), enhancing its nutritional and functional qualities to fill a knowledge gap. Using an alkaline extraction‐isoelectric precipitation strategy, KBPI was extracted with different germination periods (0–72 h). Germination up to 48 h significantly increased GKBPI (germinated kidney bean protein isolate) yield to 44.01%–50.01%, with G48H at 81.20% showing the highest protein recovery at 45 °C. Essential amino acids like valine and threonine were notably retained up to 48 h at 45 °C, preserving GKBPI's nutritional profile. Gelling capacity, protein solubility, foaming and emulsification properties were favourable at 35 °C with 48‐h germinated samples, making GKBPI versatile for food applications. GKBPI also displayed antioxidant activity, with DPPH% values ranging from 20.19% to 24.47%. After 72 h of germination, phytic acid levels decreased by 47.94%, leading to higher in vitro protein digestibility (IVDP) in G48R (germinated kidney bean for 48 h at 35 °C alkali extraction temperature; 82.82%) and G48H (germinated kidney bean for 48 h at 45 °C alkali extraction temperature; 85.55%) due to reduced anti‐nutrients. The study delves into the novelty of germination time's impact on KBPI. Extended germination, up to 48 h, increases protein yield, recovery, IVDP, antioxidant activity and enhances functional properties and reduced anti‐nutrients which indicates that GKBPI has significant potential as an ingredient for various food applications. However, further research is needed for in vitro data, toxins profile and a comprehensive understanding of its practical, economic and health‐related implications.