bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fronto-central resting-state 15-29Hz transient beta events change with therapeutic transcranial magnetic stimulation for posttraumatic stress disorder and major depressive disorder
Authors: Morris Alexander T. , Temereanca Simona , Zandvakili Amin , Thorpe Ryan , Sliva Danielle D. , Greenberg Benjamin D. , Carpenter Linda L. , Philip Noah S. , Jones Stephanie R. 
Published: March 2023

ABSTRACTRepetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD) and shows promise for posttraumatic stress disorder (PTSD), yet effectiveness varies. Electroencephalography (EEG) can identify rTMS-associated brain changes. EEG oscillations are often examined using averaging approaches that mask finer time-scale dynamics. Recent advances show some brain oscillations emerge as transient increases in power, a phenomenon termed “Spectral Events,” and that event characteristics correspond with cognitive functions. We applied Spectral Event analyses to identify potential EEG biomarkers of effective rTMS treatment. Resting 8-electrode EEG was collected from 23 patients with MDD and PTSD before and after 5Hz rTMS targeting the left dorsolateral prefrontal cortex. Using an open-source toolbox (https://github.com/jonescompneurolab/SpectralEvents), we quantified event features and tested for treatment associated changes. Spectral Events in delta/theta (1-6 Hz), alpha (7-14 Hz), and beta (15-29 Hz) bands occurred in all patients. rTMS-induced improvement in comorbid MDD PTSD were associated with pre-to post-treatment changes in fronto-central electrode beta event features, including frontal beta event frequency spans and durations, and central beta event maxima power. Furthermore, frontal pre-treatment beta event duration correlated negatively with MDD symptom improvement. Beta events may provide new biomarkers of clinical response and advance the understanding of rTMS.
An investigation of the association between characteristics of local crisis care systems and service use in a national survey
Authors: Rojas-García Antonio , Dalton-Locke Christian , Rains Luke Sheridan , Dare Ceri , Ginestet Cedric , Foye Una , Kelly Kathleen , Landau Sabine , Lynch Chris , McCrone Paul , Nairi Shilpa , Newbigging Karen , Nyikavaranda Patrick , Osborn David , Persaud Karen , Sevdalis Nick , Stefan Martin , Stuart Ruth , Simpson Alan , Johnson Sonia , Lloyd-Evans Brynmor 
Published: March 2023

AbstractBackgroundIn England, a range of mental health crisis care models and approaches to organising crisis care systems have been implemented, but characteristics associated with their effectiveness are poorly understood.AimsTo i) develop a typology of catchment area mental health crisis care systems and ii) investigate how crisis care service models and system characteristics relate to psychiatric hospital admissions and detentions.MethodsData about crisis systems were obtained from a 2019 English national survey. Latent class analyses were conducted to identify discernible typologies, and mixed effects negative binomial regression models were fitted to explore associations between crisis care models and admissions and detention rates, obtained from nationally-reported data.ResultsNo clear typology of catchment area crisis care systems emerged. Regression models suggested that provision of a crisis telephone service within the local crisis system was associated to a 11.6% lower admissions rate and a 15.3% lower detention rate. Provision of a crisis café was associated with a 7.8% lower rate of admissions. The provision of a crisis assessment team separate from the crisis resolution and home treatment service was associated with a 12.8% higher rate of admissions.ConclusionsThe configuration of crisis care systems varies considerably in England, but we could notderive a typology which convincingly categorised crisis care systems. Our results suggest that a crisis phone line and a crisis café may be associated with lower rates of admission, but crisis assessment teams, separate from home treatment teams, may not be associate to reductions in hospital admission and detentions.
Predicting COVID-19 pandemic waves with biologically and behaviorally informed universal differential equations
Authors: Kuwahara Bruce , Bauch Chris T. 
Published: March 2023

AbstractIn the early stages of the COVID-19 pandemic, it became clear that pandemic waves and population responses were locked in a mutual feedback loop. The initial lull following strict interventions in the first wave often led to a second wave, as restrictions were relaxed. We test the ability of new hybrid machine learning techniques, namely universal differential equations (UDEs) with learning biases, to make predictions in a such a dynamic behavior-disease setting. We develop a UDE model for COVID-19 and test it both with and without learning biases describing simple assumptions about disease transmission and population response. Our results show that UDEs, particularly when supplied with learning biases, are capable of learning coupled behavior-disease dynamics and predicting second waves in a variety of populations. The model predicts a second wave of infections 55% of the time across all populations, having been trained only on the first wave. The predicted second wave is larger than the first. Without learning biases, model predictions are hampered: the unbiased model predicts a second wave only 25% of the time, typically smaller than the first. The biased model consistently predicts the expected increase in the transmission rate with rising mobility, whereas the unbiased model predicts a decrease in mobility as often as a continued increase. The biased model also achieves better accuracy on its training data thanks to fewer and less severely divergent trajectories. These results indicate that biologically informed machine learning can generate qualitatively correct mid to long-term predictions of COVID-19 pandemic waves.Significance statementUniversal differential equations are a relatively new modelling technique where neural networks use data to learn unknown components of a dynamical system. We demonstrate for the first time that this technique is able to extract valuable information from data on a coupled behaviour-disease system. Our model was able to learn the interplay between COVID-19 infections and time spent travelling to retail and recreation locations in order to predict a second wave of cases, having been trained only on the first wave. We also demonstrate that adding additional terms to the universal differential equation’s loss function that penalize implausible solutions improves training time and leads to improved predictions.
Tryptophan catabolites, inflammation, and insulin resistance as determinants of chronic fatigue syndrome and affective symptoms in Long COVID
Authors: Al-Hakeim Hussein Kadhem , Abed Anwar Khairi , Moustafa Shatha Rouf , Almulla Abbas F , Maes Michael 
Published: March 2023

AbstractBackgroundCritical COVID-19 disease is accompanied by depletion of plasma tryptophan (TRY) and increases in indoleamine-dioxygenase (IDO)-stimulated production of neuroactive tryptophan catabolites (TRYCATs), including kynurenine (KYN) and quinolinic acid. The TRYCAT pathway has not been studied extensively in association with the physiosomatic and affective symptoms of Long COVID.MethodsIn the present study, we measured serum tryptophan (TRY), TRYCATs, insulin resistance (using the HOMA2-IR index), C-reactive protein (CRP), physiosomatic, depression and anxiety symptoms in 90 Long COVID patients, 3-10 months after remission of acute infection.ResultsWe were able to construct an endophenotypic class of severe Long COVID (22% of the patients) with very low TRY and oxygen saturation (SpO2, during acute infection), increased kynurenine, KYN/TRY ratio, CRP, and very high ratings on all symptom domains. One factor could be extracted from physiosomatic symptoms (including chronic fatigue-fibromyalgia), depression, and anxiety symptoms, indicating that all domains are manifestations of the common physio-affective phenome. Three Long COVID biomarkers (CRP, KYN/TRY, IR) explained around 40% of the variance in the physio-affective phenome. The latter and the KYN/TRY ratio were significantly predicted by peak body temperature (PBT) and lowered SpO2 during acute infection. One validated latent vector could be extracted from the three symptom domains and a composite based on CRP, KYN/TRY, IR (Long COVID), and PBT and SpO2 (acute COVID-19).ConclusionThe physio-affective phenome of Long COVID is a manifestation of inflammatory responses during acute and Long COVID and lowered plasma tryptophan and increased kynurenine may contribute to these effects.
Synergic activity of FGFR2 and MEK inhibitors in the treatment of FGFR2-amplified cancers of unknown primary
Authors: Cavazzoni Andrea , Salamon Irene , Fumarola Claudia , Gallerani Giulia , Laprovitera Noemi , Gelsomino Francesco , Riefolo Mattia , Rihawi Karim , Porcellini Elisa , Rossi Tania , Mazzeschi Martina , Naddeo Maria , Serravalle Salvatore , Broseghini Elisabetta , Agostinis Federico , Deas Olivier , Roncarati Roberta , Durante Giorgio , Lauriola Mattia , Garajova Ingrid , Calin George A. , Bonafè Massimiliano , D’Errico Antonia , Petronini Pier Giorgio , Cairo Stefano , Ardizzoni Andrea , Sales Gabriele , Ferracin Manuela 
Published: March 2023

AbstractPatients with cancer of unknown primary (CUP) carry the burden of an aggressive disease and reduced access to therapies. Experimental models are pivotal for CUP biology investigation and drug testing. We derived two CUP cell lines (CUP#55 and #96), and corresponding patient-derived xenografts (PDXs), from ascites tumor cells. CUP cell lines and PDXs underwent histological, immune-phenotypical, molecular, and genomic characterization confirming the features of the original tumor. The tissue-of-origin prediction was obtained from the tumor microRNA expression profile and confirmed by single-cell transcriptomics. Genomic testing and FISH analysis identified FGFR2 gene amplification in both models, in the form of homogenously staining region (HSR) in CUP#55 and double minutes in CUP#96. FGFR2 was recognized as the main oncogenic driver and therapeutic target. FGFR2-targeting drug BGJ-398 (infigratinib) in combination with the MEK inhibitor trametinib proved to be synergic and exceptionally active, bothin vitroandin vivo. The effects of the combined treatment by single-cell gene expression analysis revealed a remarkable plasticity of tumor cells and the greater sensitivity of cells with epithelial phenotype. This study brings personalized therapy closer to CUP patients and provides the rationale for FGFR2 and MEK targeting in metastatic tumors with FGFR2 pathway activation.
mRNA aggregates harness danger response for potent cancer immunotherapy
Authors: Mendez-Gomez Hector R. , DeVries Anna , Castillo Paul , Stover Brian D. , Qdaisat Sadeem , Von Roemeling Christina , Ogando-Rivas Elizabeth , Weidert Frances , McGuiness James , Zhang Dingpeng , Chung Michael C. , Li Derek , Zhang Chong , Marconi Christiano , Campaneria Yodarlynis , Chardon-Robles Jonathan , Grippin Adam , Karachi Aida , Thomas Nagheme , Huang Jianping , Milner Rowan , Sahay Bikash , Sawyer W. Gregory , Ligon John A. , Silver Natalie , Simon Eugenio , Cleaver Brian , Wynne Kristine , Hodik Marcia , Molinaro Anette , Guan Juan , Kellish Patrick , Doty Andria , Lee Ji-Hyun , Carrera-Justiz Sheila , Rahman Maryam , Gatica Sebastian , Mueller Sabine , Prados Michael , Ghiaseddin Ashley , Mitchell Duane A. , Sayour Elias J. 
Published: March 2023

AbstractMessenger RNA (mRNA) has emerged as a remarkable tool for COVID-19 prevention but its use for induction of therapeutic cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Herein, we develop a facile approach for substantially enhancing immunogenicity of tumor-derived mRNA in lipid-particle (LP) delivery systems. By using mRNA as a molecular bridge with ultrapure liposomes and foregoing helper lipids, we promote the formation of ‘onion-like’ multi-lamellar RNA-LP aggregates (LPA). Intravenous administration of RNA-LPAs mimics infectious emboli and elicits massive DC/T cell mobilization into lymphoid tissues provoking cancer immunogenicity and mediating rejection of both early and late-stage murine tumor models. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for toll-like receptor engagement, RNA-LPAs stimulate intracellular pathogen recognition receptors (RIG-I) and reprogram the TME thus enabling therapeutic T cell activity. RNA-LPAs were safe in acute/chronic murine GLP toxicology studies and immunologically active in client-owned canines with terminal gliomas. In an early phase first-in-human trial for patients with glioblastoma, we show that RNA-LPAs encoding for tumor-associated antigens elicit rapid induction of pro-inflammatory cytokines, mobilization/activation of monocytes and lymphocytes, and expansion of antigen-specific T cell immunity. These data support the use of RNA-LPAs as novel tools to elicit and sustain immune responses against poorly immunogenic tumors.
Reduced effectiveness of repeat influenza vaccination: distinguishing among within-season waning, recent clinical infection, and subclinical infection
Authors: Bi Qifang , Dickerman Barbra A. , Nguyen Huong Q. , Martin Emily T. , Gaglani Manjusha , Wernli Karen J. , Balasubramani G.K. , Flannery Brendan , Lipsitch Marc , Cobey Sarah ,   the US Flu Vaccine Effectiveness Network Investigators
Published: March 2023

1Abstract1Studies have reported that prior-season influenza vaccination is associated with higher risk of clinical influenza infection among vaccinees. This effect might arise from incomplete consideration of within-season waning and recent infection. Using data from the US Flu Vaccine Effectiveness (VE) Network (2011-2012 to 2018-2019 seasons), we found that repeat vaccinees were vaccinated earlier in a season by one week. After accounting for waning VE, repeat vaccinees were still more likely to test positive for A(H3N2) (OR=1.11, 95%CI:1.02-1.21) but not for influenza B or A(H1N1). We found that clinical infection influenced individuals’ decision to vaccinate in the following season while protecting against clinical infection of the same (sub)type. However, adjusting for recent clinical infections did not strongly influence the estimated effect of prior-season vaccination. In contrast, we found that adjusting for subclinical infection could theoretically attenuate this effect. Additional investigation is needed to determine the impact of subclinical infections on VE.Summary of main points: Two potential factors, timing of vaccination and clinical infection history, cannot fully explain the increased influenza infection risk in repeat vaccinees compared with non-repeat vaccinees. Subclinical infection in the previous season may explain the effect.
Modelling the impact of hybrid immunity on future COVID-19 epidemic waves
Authors: Le Thao P. , Abell Isobel , Conway Eamon , Campbell Patricia T. , Hogan Alexandra B. , Lydeamore Michael J. , McVernon Jodie , Mueller Ivo , Walker Camelia R. , Baker Christopher M. 
Published: March 2023

AbstractSince the emergence of SARS-CoV-2 (COVID-19), there have been multiple waves of infection and multiple rounds of vaccination rollouts. Both prior infection and vaccination can prevent future infection and reduce severity of outcomes, combining to form hybrid immunity against COVID-19 at the individual and population level. Here, we explore how different combinations of hybrid immunity affect the size and severity of near-future Omicron waves. To investigate the role of hybrid immunity, we use an agent-based model of COVID-19 transmission with waning immunity to simulate outbreaks in populations with varied past attack rates and past vaccine coverages, basing the demographics and past histories on the World Health Organization (WHO) Western Pacific Region (WPR). We find that if the past infection immunity is high but vaccination levels are low, then the secondary outbreak with the same variant can occur within a few months after the first outbreak; meanwhile, high vaccination levels can suppress near-term outbreaks and delay the second wave. Additionally, hybrid immunity has limited impact on future COVID-19 waves with immune-escape variants. Enhanced understanding of the interplay between infection and vaccine exposure can aid anticipation of future epidemic activity due to current and emergent variants, including the likely impact of responsive vaccine interventions.
Dengue virus infected patients can generate false positives in the ‘gold standard’Leptospiraspp. microscopic agglutination test (MAT), immunofluorescence assays (IFAs), and immunoblot assays due to cross-reactive IgG and/or IgM antibodies against their outer surface membrane proteins
Authors: Romero-Vivas Claudia M. , Cuello-Pérez Margarett , Falconar Andrew K. 
Published: March 2023

AbstractThere are overlapping world distributions of the mosquito-borne dengue viruses (DENVs) and water-borne bacterial disease leptospirosis which cause large numbers of human infections and fatalities. As such, early differential diagnosis is required for appropriate early leptospirosis antibiotic therapy or DENV patient supportive care, but co-infections have also been reported. From 200 paired (S1 and S2) serum samples collected from suspected DENV infected patients, 70 (35%) were confirmed as ‘on-going’ infections by demonstrating>4-fold S1 to S2 sample increased anti-DENV IgG and/or IgM ELISA titers. Of those, 8.57% (6/70) also displayed>4-fold increased S1 to S2 sample titers in the ‘gold standard’Leptospiraspp. microscopic agglutination test (MAT) and paraformaldehyde (cell-membrane-impermeable fixative) treated leptospires in immunofluorescence assays (IFAs) due to cross-reactions with 68-72 and 38-42 KDa outer surface membrane antigens present on allLeptospiraspp. serovars tested. While DENV-1, -2 or -3 serotypes were isolated from their S1 sera: a)Leptospiraspp. could not be isolated from them, b) their S1 sera were all PCR-negative using aLeptospiraspp.-specific gene target, and c) their S2 sera were all negative using a commercial anti-Leptospiraspp. IgM ELISA. As such, we believe this is the first report of DENVs causing false positive reactions in the ‘gold standard’Leptospiraspp. MAT, IFAs, and immunoblot assays and which needs further assessments using patients’ samples which were possibly falsely reported as ‘DENV-Leptospiraspp. co-infections’ in other studies, and to identify these 68-72 and 38-42 KDaLeptospiraspp. outer surface membrane antigens by proteomic analyses.
Improved performance of nucleic acid-based assays for genetically diverse norovirus surveillance
Authors: Oh Chamteut , Zhou Aijia , O’Brien Kate , Schmidt Arthur R , Shisler Joanna L. , Schmidt Arthur R , Keefer Laura , Brown William M. , Nguyen Thanh H. 
Published: March 2023

AbstractNucleic acid-based assays, such as polymerase chain reaction (PCR), that amplify and detect organism-specific genome sequences are a standard method for infectious disease surveillance. However, challenges arise for virus surveillance because of their genetic diversity. Here, we calculated the variability of nucleotides within the genomes of ten human viral speciesin silicoand found that endemic viruses exhibit a high percentage of variable nucleotides (e.g., 51.4% for norovirus GII). This genetic diversity led to variable probability of detection of PCR assays (the proportion of viral sequences that contain the assay’s target sequences divided by the total number of viral sequences). We then experimentally confirmed that the probability of the target sequence detection is indicative of the number of mismatches between PCR assays and norovirus genomes. Next, we developed a degenerate PCR assay that detects 97% of known norovirus GII genome sequences and recognized norovirus in eight clinical samples. In contrast, previously developed assays with 31% and 16% probability of detection had 1.1 and 2.5 mismatches on average, respectively, which negatively impacted RNA quantification. Additionally, the two PCR assays with lower probability of detection also resulted in false negatives for wastewater-based epidemiology. Our findings suggest that the probability of detection serves as a simple metric for evaluating nucleic acid-based assays for genetically diverse virus surveillance.ImportanceNucleic acid-based assays, such as polymerase chain reaction (PCR), that amplify and detect organism-specific genome sequences are a standard method for infectious disease surveillance. However, challenges arise for virus surveillance because of the rapid evolution and genetic variation of viruses. The study analyzed clinical and wastewater samples using multiple PCR assays and found significant performance variation among the PCR assays for genetically diverse norovirus surveillance. This finding suggests that some PCR assays may miss detecting certain virus strains, leading to a compromise in detection sensitivity. To address this issue, we propose a metric called the probability of detection, which can be simply calculatedin silicousing a code developed in this study, to evaluate nucleic acid-based assays for genetically diverse virus surveillance. This new approach can help improve the sensitivity and accuracy of virus detection, which is crucial for effective infectious disease surveillance and control.
Comparison of Capillary Blood Self-Collection using the Tasso-SST Device with Venous Phlebotomy for anti-SARS-CoV-2 Antibody Measurement
Authors: King Elise R. , Garrett Haley E. , Abernathy Haley , Cassidy Caitlin A. , Cabell Cameron R. , Shook-Sa Bonnie E. , Juliano Jonathan J. , Boyce Ross M. , Aiello Allison E. , Ciccone Emily J. 
Published: March 2023

AbstractMeasuring seroprevalence over time is a valuable epidemiological tool for improving our understanding of COVID-19 immunity. Due to the large number of collections required for population surveillance as well as concerns about potential infection risk to the collectors, self-collection approaches are being increasingly pursued. To advance this methodology, we collected paired venous and capillary blood samples by routine phlebotomy and Tasso-SST device respectively from 26 participants and measured total immunoglobulin (Ig) and IgG antibodies to the SARS-CoV-2 receptor binding domain (RBD) by enzyme-linked immunosorbent assay (ELISA) on both specimens. Qualitatively, no discrepancies were noted in binary results between Tasso and venipuncture-derived plasma. Furthermore, in vaccinated participants, correlation between Tasso and venous total Ig and IgG specific antibody quantitative levels was high (Total Ig: ρ = 0.72, 95% CI (0.39- 0.90); IgG: ρ = 0.85, 95% CI (0.54, 0.96)). Our results support the use of Tasso at-home collection devices for antibody testing.