bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the KISS principle (Keep It Simple) for decision support systems
Authors: Eduardo Anderson Aires , Sousa Roberto Alves de , Loureiro Rafael Maffei , Tachibana Adriano , dos Santos André Pires 
Published: August 2022

AbstractThe current existence of massive data has not proved to be sufficient, by itself, for the quality of decision-making in organizations that provide health services. Thus, decision support systems (DSS) have a high strategic potential. However, initiatives focusing on the implementation of such systems commonly frustrate the involved professionals, precisely because of the challenges at data-collection stage. In this context, here we propose a conceptual model of DSS, prioritizing pipelines composed of simple algorithms, presenting low resource consumption for implementation. Our experimental implementation confirmed the computational characteristics preconized by the conceptual model, presenting the potential to mitigate a series of critical points reported by other authors and that negatively impact the real-world implementation of DSSs. Future work should empirically quantify the gains that the implementation of our model can yield, as well as experimentally explore its implementation for more complex organizational scenarios.
EMERGE: Evaluating the value of measuring random plasma glucose values for managing hyperglycemia in the inpatient setting
Authors: Manzoor Saba , Colacci Mike , Moggridge Jason , Gyenes Michelle , Biering-Sørensen Tor , Højbjerg Lassen Mats C. , Razak Fahad , Verma Amol , Sarma Shohinee , Fralick Michael 
Published: August 2022

AbstractImportanceA diagnosis of diabetes is considered when a patient has hyperglycemia with a random plasma glucose ≥200 mg/dL. However, in the inpatient setting, hyperglycemia is frequently non-specific, especially among patients who are acutely unwell. As a result, patients with transient hyperglycemia may be incorrectly labeled as having diabetes, leading to unnecessary treatment, and potential harm.Design, Setting, and ParticipantsWe conducted a multicentre cohort study of patients hospitalized at seven hospitals in Ontario, Canada and identified those with a glucose value ≥200 mg/dL. We validated a definition for diabetes using manual chart review that included physician notes, pharmacy notes, home medications, and hemoglobin A1C. Among patients with a glucose value ≥200 mg/dL, we identified patients without diabetes who received a diabetes medication, and the number who experienced hypoglycaemia during the same admission.Main Outcomes and MeasuresTo determine the diagnostic value of using random blood glucose to diagnose diabetes in the inpatient setting, and its impact on patient outcomes.ResultsWe identified 328,786 hospitalizations from hospital between 2010 and 2020. A blood glucose value of ≥200 mg/dL had a positive predictive value of 68% and a negative predictive value of 90% for a diagnosis of diabetes. Of the 76,967 patients with an elevated glucose value reported, 16,787 (21.8%) did not have diabetes, and of these, 5,375 (32%) received a diabetes medication. Hypoglycemia was frequently reported among the 5,375 patients that received a diabetes medication, with 1,406 (26.2%) experiencing hypoglycemia and 405 (7.5%) experiencing severe hypoglycemia.Conclusions and RelevanceElevated plasma glucose in hospital is common but does not necessarily indicate a patient has diabetes. Furthermore, it can lead to treatment with diabetes medications with potential harm. Our findings highlight that clinicians should be cautious when responding to elevated random plasma glucose tests in the inpatient setting.
Plumage color evolves as distinct dorsal and ventral modules in Australasian honeyeaters
Authors: Friedman Nicholas R. , Remeš Vladimír 
Published: August 2022

AbstractMany animals exhibit contrast between their dorsal and ventral coloration. If selection acts differently on dorsal versus ventral coloration, these body parts should evolve as independent modules of trait evolution, irrespective of ancestral covariance. Here, we compare the evolution of feather color across 11 body regions for a clade of Australasian songbirds (Meliphagoidea). We find evidence for three modules of covarying color regions: dorsal, ventral, and flight feathers. Among these modules, ventral feathers had color that was highly labile, evolving at 3 times the rate for dorsal plumage and 20 times the rate for flight feathers. While both dorsal and ventral plumage tend to be correlated with precipitation or the degree of vegetation, we find that dorsal plumage is twice as similar to colors of background substrates in satellite photos. This finding, which a direct effect of climate in Gloger’s rule does not predict, adds support for background matching as an explanation for geographic gradients in animal color. Furthermore, it suggests that selection for background matching has had a greater effect on dorsal plumage than ventral plumage color. Overall, differential selection on ventral and dorsal colors likely maintains these as distinct modules over evolutionary time scales – a novel explanation for dorsoventral contrast in pigmentation.
Pinging the brain to reveal the hidden attentional priority map using encephalography
Authors: Duncan Dock , van Moorselaar Dirk , Theeuwes Jan 
Published: August 2022

AbstractAttention has been usefully thought of as organized in priority maps – putative maps of space where attentional priority is weighted across spatial regions in a winner-take-all competition for attentional deployment. Recent work has highlighted the influence of past experiences on the weighting of spatial priority – called selection history. Aside from being distinct from more well-studied, top-down forms of attentional enhancement, little is known about the neural substrates of history-mediated attentional priority. Using a task known to induce statistical learning of target distributions, in an EEG study we demonstrate that this otherwise invisible, latent attentional priority map can be visualized during the intertrial period using a ‘pinging’ technique in conjunction with multivariate pattern analyses. Our findings not only offer a novel method of visualizing the history-mediated attentional priority map, but also shed light on the underlying mechanisms allowing our past experiences to influence future behaviour.
Interpretable prognostic modeling of endometrial cancer
Authors: Zagidullin Bulat , Pasanen Annukka , Loukovaara Mikko , Bützow Ralf , Tang Jing 
Published: August 2022

AbstractEndometrial carcinoma (EC) is one of the most common gynecological cancers in the world. In this work we apply Cox proportional hazards (CPH) and optimal survival tree (OST) algorithms to the retrospective prognostic modeling of disease-specific survival in 842 EC patients. We demonstrate that the linear CPH models are preferred for the EC risk assessment based on clinical features alone, while the interpretable, non-linear OST models are favored when patient profiles are enriched with tumor molecular data. By studying the OST decision path structure, we show how explainable tree models recapitulate existing clinical knowledge prioritizing L1 cell-adhesion molecule and estrogen receptor status indicators as key risk factors in the p53 abnormal EC subgroup. We believe that visually interpretable tree algorithms are a promising method to explore feature interactions and generate novel research hypotheses. To aid further clinical adoption of advanced machine learning techniques, we stress the importance of quantifying model discrimination and calibration performance in the development of explainable clinical prediction models.
Age-related decrease in appetitive associative memory in fruit flies
Authors: König Christian , Gerber Bertram 
Published: August 2022

ABSTRACTMemory scores are dynamic across developmental stages. In particular, memory scores typically decrease from late adolescence into old age, reflecting complex changes in mnemonic and sensory-motor faculties, metabolic and motivational changes, and changes in cognitive strategy as well. In Drosophila melanogaster, such age-related decreases in memory scores have been studied intensely for the association of odours with electric shock punishment. We report that odour-sucrose reward memory scores likewise decrease as the flies age. This was observed after one-trial and after two-trial conditioning, and for both immediate testing and for recall tests one day later. This decrease was already particularly pronounced in relatively young animals, in the first 2-3 weeks after adult hatching, and was more pronounced in female than in male flies.
Differences in the inflammatory proteome of East African and Western European adults and associations with environmental and dietary factors
Authors: Temba Godfrey S. , Vadaq Nadira , Kullaya Vesla , Pecht Tal , Lionetti Paolo , Cavalieri Duccio , Schultze Joachim L. , Kavishe Reginald , Joosten Leo A.B. , van der Ven Andre J. , Mmbaga Blandina T. , Netea Mihai G. , de Mast Quirijn 
Published: August 2022

AbstractNon-communicable diseases (NCDs) are rising rapidly in urbanizing populations in sub-Saharan Africa. Assessment of inflammatory and metabolic characterstics of an urbanizing African population and the comparison with populations outside Africa could provide insight in the pathophysiology of the rapidly increasing epidemic of NCDs, including the role of environmental and dietary changes. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we examined differences in the inflammatory proteome in healthy Tanzanian and healthy Dutch adults. We show that healthy Tanzanians display a pro-inflammatory phenotype compared to Dutch subjects, with enhanced activity of the Wnt/β-catenin signalling pathway and higher concentrations of different metabolic regulators such as 4E-BP1 and fibroblast growth factor 21. Among the Tanzanian volunteers, food-derived metabolites were identified as an important driver of variation in inflammation-related molecules, emphasizing the potential importance of lifestyle changes. These findings endorse the importance of the current dietary transition in the NCDs epidemic in sub-Saharan Africa and the inclusion of underrepresented populations in systems immunology studies.
Liraglutide protects against diastolic dysfunction and improves ventricular protein translation
Authors: Rutledge Cody , Enriquez Angela , Redding Kevin , Lopez Mabel , Mullett Steven , Wendell Stacy , Jurczak Michael , Goetzman Eric , Kaufman Brett A. 
Published: August 2022

AbstractPurposeDiastolic dysfunction is an increasingly common cardiac pathology linked to heart failure with preserved ejection fraction. Previous studies have implicated glucagon-like peptide 1 (GLP-1) receptor agonists as potential therapies for improving diastolic dysfunction. In this study, we investigate the physiologic and metabolic changes in a mouse model of angiotensin II (AngII) mediated diastolic dysfunction with and without the GLP-1 receptor agonist liraglutide (Lira).MethodsMice were divided into sham, AngII, or AngII + Lira therapy for 4 weeks. Mice were monitored for cardiac function, weight change, and blood pressure at baseline and after 4 weeks of treatment. After 4 weeks of treatment, tissue was collected for histology, protein analysis, targeted metabolomics, and protein synthesis assays.ResultsAngII treatment causes diastolic dysfunction when compared to sham mice. Lira partially prevents this dysfunction. The improvement in function in Lira mice is associated with dramatic changes in amino acid accumulation in the heart. Lira mice also have improved markers of protein translation by Western blot and increased protein synthesis by puromycin assay, suggesting that increased protein turnover protects against fibrotic remodeling and diastolic dysfunction seen in the AngII cohort. Lira mice also lost lean muscle mass compared to the AngII cohort, raising concerns about peripheral muscle scavenging as a source of the increased amino acids in the heart.ConclusionsLira therapy protects against AngII-mediated diastolic dysfunction, at least in part by promoting amino acid uptake and protein turnover in the heart. Liraglutide therapy is associated with loss of mean muscle mass, and long-term studies are warranted to investigate sarcopenia and frailty with liraglutide therapy in the setting of diastolic disease.
Mechanisms of Dominant Electrophysiological Features of Four Subtypes of Layer 1 Interneurons
Authors: Meng John Hongyu , Schuman Benjamin , Rudy Bernardo , Wang Xiao-Jing 
Published: August 2022

AbstractNeocortical Layer 1 (L1) consists of the distal dendrites of pyramidal cells and GABAergic interneurons (INs) and receives extensive long-range “top-down” projections, but L1 INs remain poorly understood. In this work, we systematically examined the distinct dominant electrophysiological features for four unique IN subtypes in L1 that were previously identified from mice of either gender: Canopy cells show an irregular firing pattern near rheobase; Neurogliaform cells (NGFCs) are late-spiking, and their firing rate accelerates during current injections; cells with strong expression of theα7 nicotinic receptor (α7 cells), display onset (rebound) bursting; vasoactive intestinal peptide (VIP) expressing cells exhibit high input resistance, strong adaptation, and irregular firing. Computational modeling revealed that these diverse neurophysiological features could be explained by an extended exponential-integrate-and-fire neuron model with varying contributions of a slowly inactivatingK+channel (SIK), a T-typeCa2+channel, and a spike-triggeredCa2+-dependentK+channel. In particular, we show that irregular firing results from square-wave bursting through a fast-slow analysis. Furthermore, we demonstrate that irregular firing is frequently observed in VIP cells due to the interaction between strong adaptation and a SIK channel. At last, we reveal that the VIP andα7 cell models resonant with Alpha/Theta band input through a dynamic gain analysis.Significance StatementIn the neocortex, about 25% of neurons are interneurons. Interestingly, only somas of interneurons reside within Layer 1 (L1) of the neocortex, but not of excitatory pyramidal cells. L1 interneurons are diverse and believed to be important in the cortical-cortex interactions, especially top-down signaling in the cortical hierarchy. However, the electrophysiological features of L1 interneurons are poorly understood. Here, we systematically studied the electrophysiological features within each L1 interneuron subtype. Furthermore, we build computational models for each subtype and study the mechanisms behind these features. These electrophysiological features within each subtype should be incorporated to elucidate how different L1 interneuron subtypes contribute to communication between cortexes.
RTNet neural network exhibits the signatures of human perceptual decision making
Authors: Rafiei Farshad , Shekhar Medha , Rahnev Dobromir 
Published: August 2022

AbstractConvolutional neural networks show promise as models of biological vision. However, their decision behavior, including the facts that they are deterministic and use equal number of computations for easy and difficult stimuli, differs markedly from human decision-making, thus limiting their applicability as models of human perceptual behavior. Here we develop a new neural network, RTNet, that generates stochastic decisions and human-like response time (RT) distributions. We further performed comprehensive tests that showed RTNet reproduces all foundational features of human accuracy, RT, and confidence and does so better than all current alternatives. To test RTNet’s ability to predict human behavior on novel images, we collected accuracy, RT, and confidence data from 60 human subjects performing a digit discrimination task. We found that the accuracy, RT, and confidence produced by RTNet for individual novel images correlated with the same quantities produced by human subjects. Critically, human subjects who were more similar to the average human performance were also found to be closer to RTNet’s predictions, suggesting that RTNet successfully captured average human behavior. Overall, RTNet is a promising model of human response times that exhibits the critical signatures of perceptual decision making.
Identification of DOT1L Inhibitor in a Screen for Factors that Promote Dopaminergic Neuron Survival
Authors: Cui Jun , Carey Joseph , Pera Renee A. Reijo 
Published: August 2022

AbstractParkinson’s disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra region of the midbrain. Diagnostic criteria for PD require that at least two of three motor signs are observed: tremor, rigidity, and/or bradykinesia. The most common and effective treatment for PD is Levodopa (L-DOPA) which is readily converted to DA and has been the primary treatment since the 1960’s. Dopamine agonists have also been developed but are less effective than L-DOPA. Although the lack of a model system to study PD has hampered efforts to identify treatments, diverse screening strategies have been proposed for identification of new pharmaceutical candidates. Here, we describe a pilot screen to identify candidate molecules from a bioactive compound library, that might increase formation, maintenance and/or survival of DA neurons in vitro. The screen used a previously characterized reporter construct consisting of the luciferase gene inserted downstream of the endogenous tyrosine hydroxylase (TH) gene and neurons differentiated from human pluripotent stem cells for 18 days. The reporter mimics expression of TH and includes a secreted luciferase whose activity can be measured non-invasively over multiple timepoints. Screening of the bioactive compound library resulted in the identification of a single molecule, SGC0946, that is an inhibitor of DOT1L (Disruptor Of Telomeric silencing 1-Like) which encodes a widely-conserved histone H3K79 methyltransferase that is able to both activate and repress gene transcription. Our results indicate that SGC0946 increased reporter luciferase activity with a single treatment at 8-hours post-plating being equivalent to continuous treatment. Moreover, data suggested that the total number of neurons differentiated in the assays was comparable from experiment to experiment under different SGC0946 treatments over time. In contrast, data suggested that the survival and/or maintenance of DA neurons might be specifically enhanced by SGC0946 treatment. These results confirm other reports that indicate inhibition of DOT1L may play an important role in maintenance and survival of neural progenitor cells (NPCs) and their lineage-specific differentiation.
Individual differences in information processing during sleep and wake predict sleep-based memory consolidation of complex rules
Authors: Richter Madison , Cross Zachariah R. , Bornkessel-Schlesewsky Ina 
Published: August 2022

AbstractMemory is critical for many cognitive functions, from remembering facts, to learning complex environmental rules. While memory encoding occurs during wake, memory consolidation is associated with sleep-related neural activity. Further, research suggests that individual differences in alpha frequency during wake (∼ 7 – 13 Hz) modulate memory processes, with higher individual alpha frequency (IAF) associated with greater memory performance. However, the relationship between wake-related EEG individual differences, such as IAF, and sleep-related neural correlates of memory consolidation has been largely unexplored, particularly in a complex rule-based memory context. Here, we aimed to investigate whether wake-derived IAF and sleep neurophysiology interact to influence rule learning in a sample of 35 healthy adults (16 males; mean age = 25.4, range: 18 – 40). Participants learned rules of a modified miniature language prior to either 8hrs of sleep or wake, after which they were tested on their knowledge of the rules in a grammaticality judgement task. Results indicate that sleep neurophysiology and wake-derived IAF do not interact but modulate memory for complex linguistic rules separately. Phase-amplitude coupling between slow oscillations and spindles during non-rapid eye-movement (NREM) sleep also promoted memory for rules that were analogous to the canonical English word order. As an exploratory analysis, we found that rapid eye-movement (REM) sleep theta power at posterior regions interacts with IAF to predict rule learning and proportion of time in REM sleep predicts rule learning differentially depending on grammatical rule type. Taken together, the current study provides behavioural and electrophysiological evidence for a complex role of NREM and REM sleep neurophysiology and wake-derived IAF in the consolidation of rule-based information.
A Rigid Parallel-Plate Artificial Placenta Oxygenator with a Hemocompatible Blood Flow Path
Authors: Blauvelt David G. , Higgins Nicholas C. , De Bianca , Goodin Mark S. , Wright Nathan , Blaha Charles , Moyer Jarrett , Chui Benjamin W. , Baltazar Francisco J. , Oishi Peter , Roy Shuvo 
Published: August 2022

AbstractExtremely preterm infants have poor clinical outcomes due to lung immaturity. An artificial placenta could provide extracorporeal gas exchange, allowing normal lung growth outside of the uterus, thus improving outcomes. However, current devices in development use hollow-fiber membrane oxygenators, which have a high rate of bleeding and clotting complications. Here, we present a novel style of oxygenator composed of a stacked array of rigid and flat silicon semi-permeable membranes. Using computational fluid dynamic (CFD) modeling, we demonstrated favorable hemocompatibility properties, including laminar blood flow, low pressure drop, and minimal cumulative shear stress. We then constructed and tested prototype devices on the benchtop and in an extracorporeal pig model. At 20 mL/min of blood flow, the oxygenators exhibited an average oxygen flux of 0.081 ± 0.020 mL (mean ± standard error) and a pressure drop of 2.25 ± 0.25 mmHg. This study demonstrates the feasibility of a building a stacked flat-plate oxygenator with a blood flow path informed by CFD.