bluuebunny/crossref_metadata_2025_split huggingface dataset:
STability and Shelf-Life of Plasma Bubbling Treated Cow Milk
Authors: Dash Samarpita , Jaganmohan R. 
Published: February 2022

ABSTRACTThe demand of consumers for naturality of food with minimal processing was forced to the scientists for the discovery of non-thermal plasma which is now an emerging technology for the preservation and decontamination of highly perishable food such as milk. In this study, the microbial and physicochemical characteristics of plasma bubbling of raw cow milk were analysed and a comparison of boiled raw cow milk, commercially available pasteurised and UHT milk was observed. Again, shelf-life study was experimented for the plasma bubbling of milk with respect to raw cow milk sample (control). The plasma bubbling was generated at a voltage (200V), the flow rate of air 10 litres/hour (L/h) and applied to fresh cow milk for 5, 10, and 15 minutes (min) of time interval with 100 mL of the sample volume at room temperature. A significant reduction was observed in coliform and yeast at 200V, 10L/h, 15 min time interval of treatment. The pH of the milk was increased significantly to 6.85 after exposure to plasma bubbling. Whereas, a decreasing value was noticed in total soluble solids (TSS) and titratable acid (TA) with respect to time given by the plasma bubbling. Further a nondetrimental effect was observed for the nutrient content of plasma bubbling of milk. The result of the study indicates that plasma bubbling at (200V, 10L/h,100mL,15 min) treatment improves the quality of milk. This study shows that indirect dielectric barrier discharge (DBD) (plasma bubbling) may offer an effective microbial reduction without affecting the quality attributes. The plasma bubbling processing is an initiative for cow raw milk pasteurisation, which could have a future perspective on industrial food applications.
Bayesian Emulation and History Matching of JUNE
Authors: Vernon Ian , Owen Jonathan , Aylett-Bullock Joseph , Cuesta-Lazaro Carolina , Frawley Jonathan , Quera-Bofarull Arnau , Sedgewick Aidan , Shi Difu , Truong Henry , Turner Mark , Walker Joseph , Caulfield Tristan , Fong Kevin , Krauss Frank 
Published: February 2022

AbstractWe analyse June : a detailed model of Covid-19 transmission with high spatial and demographic resolution, developed as part of the RAMP initiative. June requires substantial computational resources to evaluate, making model calibration and general uncertainty analysis extremely challenging. We describe and employ the Uncertainty Quantification approaches of Bayes linear emulation and history matching, to mimic the June model and to perform a global parameter search, hence identifying regions of parameter space that produce acceptable matches to observed data.
Gamma connectivity predicts response to intermittent Theta Burst Stimulation in Alzheimer’s disease: A randomised controlled trial
Authors: Hoy Kate E. , Emonson Melanie R. L. , Bailey Neil W. , Rogers Caitlyn , Coyle Hannah , Stockman Freya , Fitzgerald Paul B. 
Published: February 2022

AbstractAlzheimer’s disease is characterised by progressive cognitive decline for which there are currently no effective treatments. There is growing evidence that neural network dysfunction is a likely proximate cause of cognitive impairment in Alzheimer’s and, as such, may represent a promising therapeutic target. Here we investigated whether a course of intermittent Theta Burst Stimulation (iTBS) could modulate functional connectivity and cognitive function in mild to moderate Alzheimer’s disease. Fifty-eight participants were randomised to receive a course of either active or sham iTBS. Stimulation was applied to four brain sites sequentially in each treatment session: left DLPFC, right DLPFC, left PPC, and right PPC. Neurobiological (EEG), cognitive (CogState, ADASCog), and functional (QoL-AD, GDS) assessments were undertaken at baseline and end of treatment. Cognitive and functional assessments were also conducted at 3-months (blinded) and 6-months (active group only) following end of treatment. Active iTBS resulted in a significant and large increase in resting state gamma connectivity as well as improved delayed recall on an episodic memory task. Both baseline gamma connectivity, and change in gamma connectivity, were found to be predictive of improved delayed recall following active treatment. These findings support future research into iTBS for the treatment of Alzheimer’s disease focussing on protocol optimisation.
MEDIAL FRONTAL CORTEX GAMMA-AMINOBUTYRIC ACID CONCENTRATIONS IN PSYCHOSIS AND MOOD DISORDERS: A META-ANALYSIS OF PROTON MAGNETIC RESONANCE SPECTROSCOPY STUDIES
Authors: Simmonite Molly , Steeby Clara J. , Taylor Stephan F. 
Published: February 2022

ABSTRACTBackgroundAbnormalities of gamma-aminobutyric acid-ergic (GABAegic) systems may play an important role in psychosis spectrum and mood disorders. Proton magnetic resonance spectroscopy allows for non-invasive in vivo quantification of GABA; however, studies of GABA in psychosis have yielded inconsistent findings. This may stem from grouping together disparate voxels from functionally heterogeneous regions.MethodsWe searched the PubMed database for magnetic resonance spectroscopy studies of medial frontal cortex (MFC) GABA in patients with psychosis, bipolar disorder, depression, and individuals meeting ultra-high risk for psychosis criteria. Voxel placements were classified as rostral-, rostral-mid-, mid-, or posterior MFC, and random effects meta-analyses conducted for each group, for each MFC sub-region.ResultsOf 341 screened articles, 23 studies of psychosis (752 patients,856 controls), 6 studies of bipolar disorder (129 patients, 94 controls), 20 studies of depression (463 cases, 449 controls) and 7 studies of ultra-high risk (229 patients, 232 controls) met inclusion criteria. Meta-analysis revealed lower mid-(SMD = -0.28, 95% confidence interval [CI] = -0.48 to -0.07, p < .01) and posterior (SMD = -0.29, 95% CI = -0.49 to -0.09, p <.01) MFC GABA in psychosis, and increased rostral GABA in bipolar disorder (SMD = 0.76, 95% CI = 0.25 to 1.25, p < .01). In depression, reduced rostral MFC GABA (SMD = -0.36, 95% CI = -0.64 to -0.08, p = .01) did not survive correction for multiple comparisons.ConclusionsThese results substantiate the relevance in the ethology of psychosis spectrum and mood disorders and underline the importance of voxel placement.
Breakthrough SARS-CoV-2 infections in immune mediated disease patients undergoing B cell depleting therapy
Authors: Calabrese Cassandra M , Kirchner Elizabeth , Husni Elaine M , Moss Brandon P , Fernandez Anthony J , Jin Yuxuan , Calabrese Leonard H 
Published: February 2022

AbstractObjectivesImmunocompromised patients with immune mediated inflammatory diseases (IMIDs), undergoing therapy with B cell depleting agents are among the most vulnerable to experience severe COVID-19 disease as well as respond sub-optimally to SARS CoV-2 vaccines yet little is known about the frequency or severity of breakthrough infection in this population. We have analyzed a large cohort of vaccinated IMIDs patients undergoing B cell depleting therapy for the presence of breakthrough infection and assessed their outcomes.MethodsUtilizing specific ICD codes the pharmacy records and COVID-19 registry at the Cleveland clinic were used to identify all patients with IMIDS treated with B cell depleting monoclonal antibodies who were vaccinated against SARs CoV-2 and experienced breakthrough infections. Each EMR record was hand-reviewed to extract clinical data including vaccine history, demographics, comorbidities, other therapies, details of B cell depleting therapy, and outcomes. Univariate and multivariable logistic/proportional-odds regression models were used to examine the risk factors for severe outcomes.ResultsOf 1696 IMIDS patients on B cell depleting therapies 74 developed breakthrough COVID-19. Outcomes were severe with 24 (35%) hospitalized, 11 (15%) patients requiring critical care and 6 (8 %) deaths. Monoclonal antibodies were used on an outpatient basis to treat 21 with only a single patient requiring hospitalization without oxygen support and no deaths.ConclusionsIn IMIDS patients on B cell depleting therapies breakthrough infections are frequent and associated with severe outcomes. Outpatient use of monoclonal antibody therapy was associated with enhanced clinical outcomes.
Psychological and financial impacts of COVID-19-related travel measures: An international cross-sectional study
Authors: McDermid Pippa , Sooppiyaragath Soumya , Craig Adam , Sheel Meru , Blazek Katrina , Talty Siobhan , Seale Holly 
Published: February 2022

ABSTRACTBackgroundThe impact of COVID-19 international travel restrictions has to date, not been fully explored, and with the ongoing threat that new variants could potentially restrict movement further, it is important to consider the impacts that travel restrictions have on community members. This study aimed to evaluate the psychological and financial impact of COVID-19 travel restrictions on those separated from their partners or immediate families, as well as temporary visa holders who were unable to migrate.MethodsBetween 4 November 2021 to 1 December 2021, we executed a cross-sectional online survey targeting three specific groups; (1) those stranded from their partners; (2) those stranded from immediate families; and (3) temporary visa holders unable to migrate or cross international borders. We collected data on respondents’ demographic profile; the nature of COVID-19-related travel impacts; depression, anxiety, and stress levels (using the validated DASS-21); and finally, data on respondents financial, employment and accommodation situation.Results1363 respondents located globally completed the survey. 71.2% reported financial stress, 76.8% (, SD=5.94) reported moderate-to-extremely severe depression, 51.6% (, SD=5.49) moderate-to-extremely severe anxiety, and 62.6% (, SD=5.55) moderate-to-extremely severe stress levels. Statistically significant factors associated with moderate-to-extremely severe depression, anxiety, and stress included being female, chronic illness, and experiencing financial stress. Employment during COVID-19 – specifically essential services workers or unemployed – was associated with higher levels of anxiety and stress, with only essential workers being a predictor of higher stress severity. Factors that provided psychological protection included being older and having children.ConclusionThis study is one of the first to explore the impact COVID-19-related international travel restrictions have had on the financial status and psychological health of affected individuals. It highlights the significant human cost associated with the restrictions and identifies psychologically vulnerable populations. These results will help the design of targeted health and social policy responses.
High-dimension to high-dimension screening for detecting genome-wide epigenetic regulators of gene expression
Authors: Ke Hongjie , Ren Zhao , Chen Shuo , Tseng George C , Qi Jianfei , Ma Tianzhou 
Published: February 2022

AbstractMotivationThe advancement of high-throughput technology characterizes a wide range of epigenetic modifications across the genome involved in disease pathogenesis via regulating gene expression. The high-dimensionality of both epigenetic and gene expression data make it challenging to identify the important epigenetic regulators of genes. Conducting univariate test for each epigenetic-gene pair is subject to serious multiple comparison burden, and direct application of regularization methods to select epigenetic-gene pairs is computationally infeasible. Applying fast screening to reduce dimension first before regularization is more efficient and stable than applying regularization methods alone.ResultsWe propose a novel screening method based on robust partial correlation to detect epigenetic regulators of gene expression over the whole genome, a problem that includes both high-dimensional predictors and high-dimensional responses. Compared to existing screening methods, our method is conceptually innovative that it reduces the dimension of both predictor and response, and screens at both node (epigenetic features or genes) and edge (epigenetic-gene pairs) levels. We develop data-driven procedures to determine the conditional sets and the optimal screening threshold, and implement a fast iterative algorithm. Simulations and two applications to long non-coding RNA and DNA methylation regulation in Kidney cancer and Glioblastoma Multiforme illustrate the validity and advantage of our method.AvailabilityThe R package, related source codes and real data sets used in this paper are provided at https://github.com/kehongjie/rPCor.
Supervised Rank aggregation (SRA): A novel rank aggregation approach for ensemble-based feature selection
Authors: Jain Rahi , Xu Wei 
Published: February 2022

AbstractBackgroundFeature selection (FS) is critical for high dimensional data analysis. Ensemble based feature selection (EFS) is a commonly used approach to develop FS techniques. Rank aggregation (RA) is an essential step of EFS where results from multiple models are pooled to estimate feature importance. However, the literature primarily relies on rule-based methods to perform this step which may not always provide an optimal feature set.Method and ResultsThis study proposes a novel Supervised Rank Aggregation (SRA) approach to allow RA step to dynamically learn and adapt the model aggregation rules to obtain feature importance. The approach creates a performance matrix containing feature and model performance value from all models and prepares a supervised learning model to get the feature importance. Then, unsupervised learning is performed to select the features using their importance. We evaluate the performance of the algorithm using simulation studies and implement it into real research studies, and compare its performance with various existing RA methods. The proposed SRA method provides better or at par performance in terms of feature selection and predictive performance of the model compared to existing methods.ConclusionSRA method provides an alternative to the existing approaches of RA for EFS. While the current study is limited to the continuous cross-sectional outcome, other endpoints such as longitudinal, categorical, and time-to-event medical data could also be used.
Distinct components of cardiovascular health are linked with age-related differences in cognitive abilities
Authors: King Deborah L. O. , Henson Richard N. , Kievit Rogier , Wolpe Noham , Brayne Carol , Tyler Lorraine K. , Rowe James B. ,   Cam-CAN, Tsvetanov Kamen A. 
Published: February 2022

ABSTRACTVascular, cardiovascular and neurovascular ageing processes contribute to cognitive impairment. However, the unique and synergistic contributions of cardiovascular factors to cognitive function remain unclear because they are often condensed into a single composite score or examined in isolation of each other. We hypothesized that vascular risk factors, electrocardiographic features and blood pressure indices reveal multiple latent vascular factors, with independent contributions to age differences in cognition. In a population-based deep-phenotyping study of cognition across the lifespan (n=708, age 18-88), path analysis revealed three latent vascular factors dissociating the autonomic nervous system response from two components of blood pressure. These three factors made unique and additive contributions to the variability in crystallized and fluid intelligence. The discrepancy in fluid relative to crystallized intelligence, indicative of cognitive decline, was associated with a latent vascular factor predominantly expressing pulse pressure, suggesting that higher pulse pressure is associated with cognitive decline from expected performance. This association varied with age, such that higher factor scores predicted a greater cognitive discrepancy in older individuals. Controlling pulse pressure may help to preserve cognitive function, particularly in older adults. Our findings highlight the need to better understand the multifactorial nature of vascular aging, its effects on neurocognitive function, and the modifiable risks of cognitive decline.
Single Injection Nerve Blocks Plus IV Lidocaine Infusions as an Alternative to Continuous Nerve Blocks for Perioperative Pain Management: A retrospective review
Authors: Gromov Dmitriy , Kearns Jeremy , Chelly Jacques E 
Published: February 2022

AbstractPurposeContinuous nerve blocks (CNBs) and intravenous lidocaine infusions (IV Lido) represent an effective approach to perioperative pain management. We hypothesized that a single injection nerve block (SNB) plus intravenous lidocaine infusion (IV Lido) would be as effective as CNBs. Furthermore, since recently, the use of facial plane blocks are increasingly advocated, we compared CNBs vs SNBs plus IV Lido in patients undergoing erector spinae plane (ESP) and quadratus lumborum (QL) blocks for video assisted thoracic surgery (VATS) and abdominal/retroperitoneal surgeries, respectively.Patients and MethodUsing our IRB approved registry (PRO10120146), we retrospectively reviewed the electronic record of 105 patients, including 51 patients who underwent VATS and received either single injection erector plane block (SESPB) plus IV lido or continuous erector spinae plane block (CESPB), and 54 patients who underwent major abdominal surgery and received either single injection quadratus lumborum block (SQLB) plus IV Lido or continuous quadratus lumborum block (CQLB). Demographics, verbal pain scores (0-10), and opioid consumption (morphine intravenous equivalent; MIVE), all in the context of the same multimodal approach (acetaminophen, ketamine, dexmedetomidine, and ketorolac) were collected at 24, 48, and 72 hours after surgery. Alpha was set to 0.05.ResultsSNBs plus IV Lido were as effective as CNBs regarding pain control and total MIVE at 24, 48, or 72 hours after surgery. Subgroup analysis indicated similar findings were observed in patients who underwent VATS or major abdominal surgery.ConclusionsThis analysis suggests that SNBs plus IV Lido are as effective as CNBs for perioperative pain management when ESP or QL blocks are used for VATS or major abdominal surgery, respectively.
Spillover Benefit of Pre-Exposure Prophylaxis for HIV Prevention: Evaluating the Importance of Effect Modification using an Agent-Based Model
Authors: Buchanan Ashley L. , Park Carolyn J. , Bessey Sam , Goedel William C. , Murray Eleanor J. , Friedman Samuel R. , Halloran M. Elizabeth , Katenka Natallia V. , Marshall Brandon D.L. 
Published: February 2022

AbstractWe developed an agent-based model using a trial emulation approach to quantify effect measure modification of key variables on spillover effects of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in Atlanta, GA. PrEP may impact not only the individual prescribed, but also their partners and beyond, known as spillover. We simulated a two-stage randomized trial with eligible components (≥3 agents and ≥1 HIV+ agent) first randomized to intervention or control (no PrEP). Within intervention components, agents were randomized to PrEP with intervention coverage of 70%, providing insight into a high PrEP coverage strategy. We evaluated effect modification by component level characteristics and estimated spillover effects using an extension of randomization-based estimators. We observed an attenuation of the spillover effect when agents were in components with a higher prevalence of either drug use or bridging potential (if an agent acts as a mediator between ≥2 connected groups of agents). The estimated spillover effects were larger in magnitude among components with either higher HIV prevalence or greater density (number of existing compared to all possible partnerships). Consideration of effect modification is important when evaluating the spillover of PrEP among MSM.
Loss of E-cadherin Induces IGF1R Activation Revealing a Targetable Pathway in Invasive Lobular Breast Carcinoma
Authors: Elangovan Ashuvinee , Hooda Jagmohan , Savariau Laura , Puthanmadhomnarayanan Susrutha , Yates Megan E. , Chen Jian , Brown Daniel D. , McAuliffe Priscilla F. , Oesterreich Steffi , Atkinson Jennifer M. , Lee Adrian V. 
Published: February 2022

AbstractNo Special Type breast cancer (NST; commonly known as Invasive Ductal Carcinoma (IDC)) and Invasive Lobular Carcinoma (ILC) are the two major histological subtypes of breast cancer with significant differences in clinicopathological and molecular characteristics. The defining pathognomonic feature of ILC is loss of cellular adhesion protein, E-cadherin (CDH1). We have previously shown that E-cadherin functions as a negative regulator of the Insulin-like Growth Factor 1 Receptor (IGF1R) and propose that E-cadherin loss in ILC sensitizes cells to growth factor signaling which thus alters their sensitivity to growth factor signaling inhibitors and their downstream activators. To investigate this potential therapeutic vulnerability, we generated CRISPR-mediatedCDH1knockout (CDH1KO) IDC cell lines (MCF7, T47D, ZR75.1) to uncover the mechanism by which loss of E-cadherin results in IGF pathway activation.CDH1KO cells demonstrated enhanced invasion and migration that was further elevated in response to IGF1, serum and Collagen I.CDH1KO cells exhibited increased sensitivity to IGF resulting in elevated downstream signaling. Despite minimal differences in membranous IGF1R levels between wildtype (WT) andCDH1KO cells, significantly higher ligand-receptor interaction was observed in theCDH1KO cells, potentially conferring enhanced downstream signaling activation. Critically, increased sensitivity to IGF1R, PI3K, Akt and MEK inhibitors was observed inCDH1KO cells and ILC patient-derived organoids, suggesting that these targets require further exploration in ILC treatment and thatCDH1loss may be exploited as a biomarker of response for patient stratification.
Systematic Elucidation and Pharmacological Targeting of Tumor-Infiltrating Regulatory T Cell Master Regulators
Authors: Obradovic Aleksandar , Ager Casey , Turunen Mikko , Nirschl Thomas , Khosravi-Maharlooei Mohsen , Jackson Christopher , Yegnasubramanian Vassan , DeMarzo Angelo , Kochel Christina , Allaf Mohamad , Bivalacqua Trinity , Lim Michael , Karan Charles , Drake Charles G. , Califano Andrea 
Published: February 2022

AbstractDue to their immunosuppressive role, tumor-infiltrating regulatory T cells (TI-Tregs) represent attractive therapeutic targets. Analysis of TI vs. peripheral Tregs (P-Tregs) from 36 patients, across four malignancies, identified 17 candidate Master Regulators (MRs), predicted to mechanistically regulate TI-Tregs transcriptional state. In vivo, pooled CRISPR-KO screening, using a hematopoietic stem cell transplant model, confirmed essentiality of 7 of 17 MRs in TI-Treg recruitment and/or retention to the TME, without affecting other T cell subtypes, while individual knockout of the most significant MR (TRPS1) significantly reduced tumor allograft growth. TI-Treg drug perturbation profile analysis identified drugs capable of inverting the TI-Treg-specific MR activity signature at low concentration. Low dose treatment with gemcitabine (top prediction) inhibited tumor growth in immunocompetent but not immunocompromised allografts, increased PD-1 inhibitor efficacy, and depleted TI-Tregs in vivo. The study provides key insight into Treg infiltration mechanism and a gene reporter assay to identify additional small molecule inhibitors.Graphical Abstract