bluuebunny/crossref_metadata_2025_split huggingface dataset:
Should Pharmacists Lead Medication Reconciliation in Critical Care? A One-Stem Interventional Study in an Egyptian Intensive Care Unit
Authors: El Hadidi Seif , Hamdi Mohamed , Sabry Nirmeen 
Published: February 2022

Objectives
The main objective was to compare physician-obtained medication histories to the practice of medication reconciliation undertaken by a pharmacist in the intensive care unit (ICU).

Methods
A one-stem interventional study involving 500 adults 18 years and older admitted to the ICU (50 beds) of an Egyptian Joint Commission International–accredited reference hospital was conducted. The primary outcome measure was the proportion of ICU patients with missing medications in the cohorts of physician versus pharmacist-led medication reconciliation. The secondary outcome measure was the percentage of patients who had at least one clinical condition or adverse event (AE) that was left untreated during hospitalization of the 2 arms of patients after reconciliation.

Results
A total of 500 patients received reconciliation. Medication discrepancies in the cohort of physician-led reconciliation were greater than that of the pharmacist (26.1% versus 2.6%, P = 0.001). The most common discrepancy was indication with no medication, which was found to be greater in the physician-led cohort of patients than that of the pharmacist cohort (25.2% versus 2.6%, P = 0.001). Untreated AEs in the former cohort were present in 9.1% of cases versus 1.5% in the pharmacist-led reconciliation cohort (P = 0.001).

Conclusions
The present study revealed that pharmacist-led medication reconciliation in ICU has dramatically decreased medication discrepancies and AEs in adults with acute ICU admissions.
Spectral dynamic causal modeling of mindfulness, mind-wandering, and resting-state in the triple network using fMRI
Authors: Kim Hyun-Chul , Lee Jong-Hwan 
Published: February 2022

Objective
Functional connectivity in intrinsic brain networks, namely, the triple network, which includes the salience network, default mode network (DMN) and central executive network (CEN), has been suggested as prominent, major networks involved in human cognition and mental state–mindfulness, mind-wandering and resting-state. Despite the established roles of functional connections within and between intrinsic networks, there has been limited research on the effective connectivity of mindfulness, mind-wandering and resting-state using the triple network, as well as on their direct comparisons.

Methods
We employed spectral dynamic causal modeling to compare effective connectivity patterns across mindfulness (i.e. attention focused on physical sensations of breathing), mind-wandering (i.e. connecting thoughts) and resting-state (i.e. relaxing while remaining calm and awake) conditions using functional MRI data of healthy subjects who underwent ambulatory training by practicing mindfulness and mind-wandering (N = 59).

Results
When comparing mindfulness and mindwandering conditions, our analysis results revealed that salience network and CEN interacted depending on mindfulness or mind-wandering. When mindfulness or mind-wandering was compared to resting-state, mindfulness increased the effective connectivity from the left CEN to salience network through DMN, whereas mindwandering increased the effective connectivity from the DMN to right CEN.

Conclusion
To the best of our knowledge, this is the first study to examine possible differences in effective connectivity patterns among mindfulness, mind-wandering and resting-state using the triple network. We believe that our findings will provide deeper insights into the neural substrates of mindfulness compared to mind-wandering and resting-state.
The level of liver and renal function biomarker abnormalities among hospitalized COVID-19 patients in Ethiopia
Authors: Tsegay Yakob Gebregziabher , Bitew Molalegne , Workneh Tigist , Atlaw Assegdew , Aragaw Mintsnot , Gemechu Mesay , Brhane Nega 
Published: February 2022

AbstractBackgroundCOVID-19 pandemic is unprecedented public health emergency and added burden to developing countries. The pandemic cause multi organ failures (MOF) predominantly affects lung, cardiac, renal and liver organs as severity of the disease exacerbates. That is the rationale to execute this study with the aim to determine the magnitude of abnormal organ function test parameters and its association between markers of organ failure and disease severity in patients infected with COVID-19 admitted at Millennium COVID-19 Care Center (CCC).MethodsA cross-sectional study was conducted among COVID-19 patients admitted at Millennium COVID-19 Care and Treatment Center (MCCTC) from May 2021 up to Oct 2021. In this study 500 participant’s information were collected from the laboratory database of Millennium COVID-19 care center. Data were analyzed using SPSS version 25. P-value <0.05 was considered significantly associated.ResultThe median age of the 500 study participants was 55.6±7.7 years, and from these 67.6% of patients were males. Liver function parameters Aspartae transferase (AST),) alanine aminotransferase (ALT) and Alakaline phosphatase (ALP) the mean value of overall patients were elevated and three of these parameters were highly elevated among critical patients (56.9±57.7, 58.5±6, and 114.6±6) respectively. All study participants had an elevated Creatinine. 66.8% males, 65% Intensive care unit (ICU), had an elevated serum value of ALT and AST respectively. Troponin was found elevated among males (54%) and 59% among ICU (critical) patients.ConclusionLiver and renal function test biomarkers such as creatine kinase muscle-brain isoenzymes (CK-MB), troponin, AST, ALT and Creatinine serum value was found elevated among ICU than non ICU patients. Organ function biomarkers are a candidate for predicting COVID-19 disease severity in order to guide clinical care.
Pan-cancer detection and typing by mining patterns in large genome-wide cell-free DNA sequencing datasets
Authors: Che Huiwen , Jatsenko Tatjana , Lenaerts Liesbeth , Dehaspe Luc , Vancoillie Leen , Brison Nathalie , Parijs Ilse , Van Den Bogaert Kris , Fischerova Daniela , Heremans Ruben , Landolfo Chiara , Testa Antonia Carla , Vanderstichele Adriaan , Liekens Lore , Pomella Valentina , Wozniak Agnieszka , Dooms Christophe , Wauters Els , Hatse Sigrid , Punie Kevin , Neven Patrick , Wildiers Hans , Tejpar Sabine , Lambrechts Diether , Coosemans An , Timmerman Dirk , Vandenberghe Peter , Amant Frédéric , Vermeesch Joris Robert 
Published: February 2022

AbstractBackgroundCell-free DNA (cfDNA) analysis holds great promise for non-invasive cancer screening, diagnosis and monitoring. We hypothesized that mining the patterns of big datasets of shallow whole genome sequencing cfDNA from cancer patients could improve cancer detection.MethodsBy applying unsupervised clustering and supervised machine learning on large shallow whole-genome sequencing cfDNA datasets from healthy individuals (n=367), patients with different hematological (n=238) and solid malignancies (n=320), we identify cfDNA signatures that enable cancer detection and typing.ResultsUnsupervised clustering revealed cancer-type-specific sub-grouping. Classification using supervised machine learning model yielded an overall accuracy of 81.62% in discriminating malignant from control samples. The accuracy of disease type prediction was 85% and 70% for the hematological and solid cancers, respectively. We demonstrate the clinical utility of our approach by classifying benign from invasive and borderline adnexal masses with an AUC of 0.8656 and 0.7388, respectively.ConclusionsThis approach provides a generic and cost-effective strategy for non-invasive pan-cancer detection.
No evidence of progressive pro-inflammatory cytokine storm in brain dead organ donors - A time course analysis using clinical samples
Authors: Bera Kasia D , Tabak Joel , Ploeg Rutger J 
Published: February 2022

AbstractOrgan donation after brain death (DBD) is an important source of transplanted organs as chronic undersupply means many patients die whilst awaiting a transplant. Improving organ quality and graft survival is key to reducing waiting lists. The interval between brain death confirmation and organ procurement offers an opportunity to reduce organ injury or encourage repair, yet data is lacking on the effects of brain injury on future grafts and which pathways to target. In fact, the consensus view has been that brain death exposes organs to a progressively pro-inflammatory environment, suggesting organ procurement must occur within a limited time window. Here, we developed a novel method of studying time-course changes in serum proteins in a DBD cohort from a UK biobank. Individual donor trajectories were combined to determine the time course of pro-inflammatory (Tumour Necrosis Factor alpha, Interleukin 6, Complement) mediators and markers of central nervous injury (Neuron Specific Enolase, Glial Fibrillary Acidic Protein) after confirmation of brain death. We found no evidence of a rise of TNF-alpha, NSE, IL-6 or C5a with prolonged duration of brain death, questioning the consensus view of progressively pro-inflammatory environment. We also identified complement as a potential target for therapeutic intervention to improve organ quality.
Interactive network-based clustering and investigation of multimorbidity association matrices with associationSubgraphs
Authors: Strayer Nick , Zhang Siwei , Yao Lydia , Vessels Tess , Bejan Cosmin A , Hsi Ryan S , Shirey-Rice Jana K , Balko Justin M , Johnson Douglas B , Philips Elizabeth J , Bick Alex , Edwards Todd L , Velez Edwards Digna R , Pulley Jill M , Wells Quinn S , Savona Michael R , Cox Nancy J , Roden Dan M , Ruderfer Douglas M , Xu Yaomin 
Published: February 2022

ABSTRACTSummaryMaking sense of association networks is vitally important to many areas of high-dimensional analysis. Unfortunately, as the data-space dimensions grow, the number of association pairs increases in O(n2); this means traditional visualizations such as heatmaps quickly become too complicated to parse effectively. Here we present associationSubgraphs: a new interactive visualization method to quickly and intuitively explore high-dimensional association datasets using network science-derived statistics and visualization. As a use case example, we apply associationSubgraphs to a phenome-wide multimorbidity association matrix generated from an electronic health record (EHR) and provided an online, interactive demonstration for exploring multimorbidity subgraphs.AvailabilityAn R package implementing both algorithm and visualization components of associationSubgraphs is available at https://github.com/tbilab/associationsubgraphs. Online documentation is available at https://prod.tbilab.org/associationsubgraphs_info/. A demo using a multimorbidity association matrix is available at https://prod.tbilab.org/associationsubgraphs-example/.
Active perceptual learning involves motor exploration and adaptation of predictive sensory integration
Authors: Hirano Masato , Furuya Shinichi 
Published: February 2022

AbstractWe perceive the external world through both externally generated and self-generated sensory stimuli (i.e., passive and active perception). While the performance in passive perception is improved by training or repetition through the functional and structural reorganization of the central nervous system (i.e., perceptual learning), the mechanisms by which perceptual learning occurs in active perception remain unclear. Here, we sought to explore the mechanisms underlying the improvement of active somatosensory perception and sensorimotor skills through active perceptual learning. Because we previously found that active perceptual learning depends on the expertise of the motor task to be performed, this study focused primarily on trained individuals. To this end, active haptic training (AHT) that targets the active somatosensory perception during the piano keystroke was used as a means of inducing active perceptual learning. We found four main results. First, participants actively modulated the muscle coordination patterns to optimize the movements required by the task through AHT without any explicit instruction on it by the experimenter, suggesting the involvement of active exploration in active perceptual learning. Second, AHT increased the relative reliance on afferent sensory information relative to the predicted one during the piano keystroke. Third, perceptual sensitivity of externally generated keystroke motions remained unchanged through AHT. Finally, AHT improved feedback control of repetitive keystroke movements in expert pianists. These results suggest that active perceptual learning involves changes in both the predictive integration process and active exploration and that the improved feedback control of fine movements benefits from the improvement in active perception.Significant statementOur ability to perceive both externally generated and self-generated sensory stimuli can be enhanced through training, known as passive and active perceptual learning. Here, we sought to explore the mechanisms underlying active perceptual learning by using active haptic training (AHT), which has been demonstrated to enhance the somatosensory perception of a finger in a trained motor skill. First, AHT reorganized the muscular coordination during the piano keystroke. Second, AHT increased the relative reliance on afferent sensory information relative to predicted one, in contrast to no increment of overall perceptual sensitivity. Finally, AHT improved feedback movement control of keystrokes. These results suggest that active perceptual learning involves active exploration and adaptation of predictive sensory integration, which underlies the co-enhancement of active perception and feedback control of movements.
Placebo response in chronic peripheral neuropathic pain trials: systematic review and meta-analysis
Authors: Duarte Gonçalo S , Mainoli Beatrice , Rodrigues Filipe B , Rato Fábio , Machado Tiago , Ferreira Joaquim J , Costa João 
Published: February 2022

ABSTRACTObjectiveTo estimate the magnitude of the placebo and nocebo responses in chronic peripheral neuropathic pain (CNP) and explore possible associations with trial characteristics.MethodsWe searched CENTRAL, MEDLINE, and Embase for randomized controlled trials (RCTs) from inception to May 2020. We included placebo-controlled RCTs of ≥8 weeks investigating first-line pharmacological interventions for CNP. Primary endpoints were the placebo response, the proportion of patients receiving placebo with pain intensity reduction (PIR) ≥30% from baseline, and the nocebo response, the proportion of patients receiving placebo experiencing adverse events (AEs). Screening, data extraction, and bias assessment (with the Cochrane risk of bias tool) were conducted by independent reviewers. We pooled data using a random-effects model.ResultsWe included 50 trials, with a combined 5,693 participants allocated to placebo, conducted between 1998 and 2020. Overall, 38% of patients receiving placebo reported PIR≥30% (95% CI 34 to 42, I2=86%); 23% reported PIR≥50% (95% CI 20 to 26; I2=81%). 50% of patients receiving placebo reported AEs (95% CI 0.43 to 0.58; I2=97%); 2% reported serious AEs (95% CI 2 to 3; I2=58%). In patients receiving active interventions, the placebo response accounts for 75% of the treatment effect on PIR≥30%, and the nocebo response accounts for 75% of the AEs. Interpreted inversely, only 25% of responses and 25% of adverse events can be attributed to the intervention. Publication year positively correlated with PIR≥30% and negatively correlated with AEs. Female sex negatively correlated with AEs.ConclusionsThe placebo and nocebo responses in parallel-designed RCTs in CNP are substantial and should be considered in trial interpretation and in the design of future trials.
Integration of proteomics and metabolomics – insights into inflammation, metabolic dysregulation, and vascular aspects in AD
Authors: Borkowski Kamil , Seyfried Nicholas T. , Arnold Matthias , Lah James J. , Levey Allan I. , Hales Chadwick M. , Dammer Eric B. , Blach Colette , Louie Gregory , Kaddurah-Daouk Rima , Newman John W. ,   Alzheimer’s Disease Metabolomics Consortium
Published: February 2022

AbstractIntegration of the omics data, including metabolomics and proteomics, provides a unique opportunity to search for new associations in the context of metabolic disorders, including Alzheimer’ s disease. Using targeted metabolomics, we have previously profiled lipid mediators, including oxylipins, endocannabinoids, bile acids and steroids in 293 CSF and 202 matched plasma samples from AD cases and healthy controls, and identified both central and peripheral metabolites of the inflammation-regulating cytochrome p450/soluble epoxide hydrolase pathway as strong predictors for the AD pathology. Additionally, using proteomics, we have identified five cerebrospinal fluid protein panels, involved in regulation of energy metabolism, vasculature, myelin/oligodendrocyte, glia/inflammation, and synapses/neurons affected in AD, and reflective of AD-related changes in brain. In the current manuscript, using metabolomics-proteomics data integration, we describe new associations between peripheral and central lipid mediators, with the above-described cerebrospinal fluid protein panels. Particularly strong associations were observed between cytochrome p450/soluble epoxide hydrolase metabolites, bile acids and CSF proteins involved in glycolysis, blood coagulation and vascular inflammation and the regulators of extracellular matrix. Those metabolic associations were not observed at the gene-coexpression level in the central nervous system, showing the importance of pathway interaction investigation on the level of the terminal part of the biochemical “ omic” cascade. In summary, this manuscript provides new information regarding the Alzheimer’ s disease, linking both central and peripheral inflammatory cascade of cytochrome p450/soluble epoxide hydrolase and bile acids metabolism with AD-affected processes and illustrates the necessity for the “ omics” data integration to uncover associations beyond gene co-expression.
Single-cell immune profiling reveals novel thymus-seeding populations, T cell commitment, and multi-lineage development in the human thymus
Authors: Cordes Martijn , Canté-Barrett Kirsten , van den Akker Erik B. , Moretti Federico A. , Kiełbasa Szymon M. , Vloemans Sandra , Garcia-Perez Laura , Teodosio Cristina , van Dongen Jacques J.M. , Pike-Overzet Karin , Reinders Marcel J.T. , Staal Frank J.T. 
Published: February 2022

SummaryT cell development in the mouse thymus has been studied rather extensively; in contrast, strikingly little is known regarding T cell development in the human thymus. To close this knowledge gap, we used a combination of single-cell techniques and functional assays to perform deep immune profiling of human T cell development, focusing on the initial stages of pre-lineage commitment. We identified three thymus-seeding progenitor populations that also have counterparts in the bone marrow. In addition, we found that the human thymus physiologically supports the development of monocytes, dendritic cells, and NK cells, as well as limited development of B cells. These results are an important step towards monitoring and guiding regenerative therapies in patients following hematopoietic stem cell transplantation.
Porphyrin overdrive rewires pan-cancer cell metabolism
Authors: Adapa Swamy R. , Hunter Gregory A. , Amin Narmin E. , Marinescu Christopher , Borsky Andrew , Sagatys Elizabeth M. , Sebti Said M. , Reuther Gary W. , Ferreira Gloria C. , Jiang Rays H.Y. 
Published: February 2022

Porphyrin overdrive rewires pan-cancer cell metabolismAll cancer cells reprogram metabolism to support aberrant growth. Here, we report that cancer cells employ and depend on imbalanced and dynamic heme metabolic pathways for their oncogenic growth. We coined this essential metabolic rewiring ‘porphyrin overdrive’ and determined that it is cancer-universal, cancer-essential, and cancer-specific. While porphyrin overdrive is absent in differentiated cells or somatic stem cells, it is present in patient-derived tumor progenitor cells, demonstrated by single cell RNAseq, and in early embryogenesis. Among the major drivers are proteins involved in biosynthesis of heme intermediates and heme trafficking. CRISPR/Cas9 editing to engineer leukemia cells with impaired heme biosynthetic steps confirmed our whole genomic data analyses that porphyrin overdrive is linked to oncogenic states and cellular differentiation. In conclusion, we identified a dependence of cancer cells on non-homeostatic heme metabolism, and we targeted this cancer metabolic vulnerability with a novel “bait-and-kill” strategy to eradicate malignant cells.One-Sentence SummaryPorphyrin overdrive reprograms cancer cellular metabolism.
Comparing the value of mono- versus coculture for high-throughput compound screening in hematological malignancies
Authors: Herbst Sophie A. , Kim Vladislav , Roider Tobias , Schitter Eva C. , Bruch Peter-Martin , Liebers Nora , Kolb Carolin , Knoll Mareike , Lu Junyan , Dreger Peter , Müller-Tidow Carsten , Zenz Thorsten , Huber Wolfgang , Dietrich Sascha 
Published: February 2022

AbstractLarge-scale compound screens are a powerful model system for understanding variability of treatment response and for discovering druggable tumor vulnerabilities of hematological malignancies. However, as mostly performed in a monoculture of tumor cells, these assays disregard modulatory effects of thein vivomicroenvironment. It is an open question whether and to what extent coculture with bone marrow stromal cells could improve the biological relevance of drug testing assays over monoculture. Here, we measured ex vivo sensitivity of 108 primary blood cancer samples to 50 drugs in monoculture and in coculture with bone marrow stromal cells. Stromal coculture conferred resistance to 52 % of compounds in chronic lymphocytic leukemia (CLL) and to 36% of compounds in acute myeloid leukemia (AML), including chemotherapeutics, BCR inhibitors, proteasome inhibitors and BET inhibitors. While most of the remaining drugs were similarly effective in mono- and coculture, only the JAK inhibitors ruxolitinib and tofacitinib exhibited increased efficacy in AML and CLL stromal coculture. We further confirmed the importance of JAK-STAT signaling for stroma-mediated resistance by showing that stromal cells induce phosphorylation of STAT3 in CLL cells. We genetically characterized the 108 cancer samples and found that drug-gene associations agreed well between mono- and coculture. Overall, effect sizes were lower in coculture, thus more drug-gene associations were detected in monoculture than in coculture. Our results suggest a two-step strategy for drug perturbation testing, with large-scale screening performed in monoculture, followed by focused evaluation of potential stroma-mediated resistances in coculture.
Single cell analysis of gene expression in the substantia nigra pars compacta of a pesticide-induced mouse model of Parkinson’s disease
Authors: Khan Arshad H. , Lee Lydia K. , Smith Desmond J. 
Published: February 2022

AbstractExposure to pesticides in humans increases the risk of Parkinson’s disease (PD), but the mechanisms remain poorly understood. To elucidate these pathways, we dosed C57BL/6J mice with a combination of the pesticides maneb and paraquat (MNPQ). Behavioral analysis revealed motor deficits consistent with PD. Single cell RNA sequencing of substantia nigra pars compacta revealed both cell-type specific genes and genes expressed differentially between pesticide and control, including Fam241b, Emx2os, Bivm, Gm1439, Prdm15 and Rai2. Neurons had the largest number of significant differentially expressed genes, but comparable numbers were found in astrocytes and less so in oligodendrocytes. In addition, network analysis revealed enrichment in functions related to the extracellular matrix. These findings emphasize the importance of support cells in pesticide-induced PD and refocus our attention away from neurons as the sole agent of this disorder.