bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial Intelligence for COVID-19 Risk Classification in Kidney Disease: Can Technology Unmask an Unseen Disease?
Authors: Monaghan Caitlin , Larkin John W. , Chaudhuri Sheetal , Han Hao , Jiao Yue , Bermudez Kristine M. , Weinhandl Eric D. , Dahne-Steuber Ines A. , Belmonte Kathleen , Neri Luca , Kotanko Peter , Kooman Jeroen P. , Hymes Jeffrey L. , Kossmann Robert J. , Usvyat Len A. , Maddux Franklin W. 
Published: June 2020

AbstractBackgroundWe developed two unique machine learning (ML) models that predict risk of: 1) a major COVID-19 outbreak in the service county of a local HD population within following week, and 2) a hemodialysis (HD) patient having an undetected SARS-CoV-2 infection that is identified after following 3 or more days.MethodsWe used county-level data from United States population (March 2020) and HD patient data from a network of clinics (February-May 2020) to develop two ML models. First was a county-level model that used data from general and HD populations (21 variables); outcome of a COVID-19 outbreak in a dialysis service area was defined as a clinic being located in one of the national counties with the highest growth in COVID-19 positive cases (number and people per million (ppm)) in general population during 22-28 Mar 2020. Second was a patient-level model that used HD patient data (82 variables) to predict an individual having an undetected SARS-CoV-2 infection that is identified in subsequent ≥3 days.ResultsAmong 1682 counties with dialysis clinics, 82 (4.9%) had a COVID-19 outbreak during 22-28 Mar 2020. Area under the receiver operating characteristic curve (AUROC) for the county-level model was 0.86 in testing dataset. Top predictor of a county experiencing an outbreak was the COVID-19 positive ppm in the general population in the prior week. In a select group (n=11,664) used to build the patient-level model, 28% of patients had COVID-19; prevalence was by design 10% in the testing dataset. AUROC for the patient-level model was 0.71 in the testing dataset. Top predictor of an HD patient having a SARS-CoV-2 infection was mean pre-HD body temperature in the prior week.ConclusionsDeveloped ML models appear suitable for predicting counties at risk of a COVID-19 outbreak and HD patients at risk of having an undetected SARS-CoV-2 infection.
Transmission of SARS-CoV-2 by inhalation of respiratory aerosol in the Skagit Valley Chorale superspreading event
Authors: Miller Shelly L. , Nazaroff William W , Jimenez Jose L. , Boerstra Atze , Buonanno Giorgio , Dancer Stephanie J. , Kurnitski Jarek , Marr Linsey C. , Morawska Lidia , Noakes Catherine 
Published: June 2020

AbstractDuring the 2020 COVID-19 pandemic, an outbreak occurred following attendance of a symptomatic index case at a regular weekly rehearsal on 10 March of the Skagit Valley Chorale (SVC). After that rehearsal, 53 members of the SVC among 61 in attendance were confirmed or strongly suspected to have contracted COVID-19 and two died. Transmission by the airborne route is likely. It is vital to identify features of cases such as this so as to better understand the factors that promote superspreading events. Based on a conditional assumption that transmission during this outbreak was by inhalation of respiratory aerosol, we use the available evidence to infer the emission rate of airborne infectious quanta from the primary source. We also explore how the risk of infection would vary with several influential factors: the rates of removal of respiratory aerosol by ventilation; deposition onto surfaces; and viral decay. The results indicate an emission rate of the order of a thousand quanta per hour (mean [interquartile range] for this event = 970 [680-1190] quanta per hour) and demonstrate that the risk of infection is modulated by ventilation conditions, occupant density, and duration of shared presence with an infectious individual.Practical ImplicationsDuring respiratory disease pandemics, group singing indoors should be discouraged or at a minimum carefully managed as singing can generate large amounts of airborne virus (quanta) if any of the singers is infected.Ventilation requirements for spaces that are used for singing (e.g., buildings for religious services and rehearsal/performance) should be reconsidered in light of the potential for airborne transmission of infectious diseases.Meetings of choirs and other kinds of singing groups during pandemics should only be in spaces that are equipped with a warning system of insufficient ventilation which may be detected with CO2 “traffic light” monitors.Systems that combine the functions heating and ventilation (or cooling and ventilation) should be provided with a disclaimer saying “do not shut this system off when people are using the room; turning off the system will also shut down fresh air supply, which can lead to the spread of airborne infections.”
Evaluation of a Novel Therapeutic Repetitive Transcranial Magnetic Stimulation Technique Optimized for Increased Accessibility in Major Depression
Authors: Miron Jean-Philippe , Voetterl Helena , Fox Linsay , Hyde Molly , Mansouri Farrokh , Dees Sinjin , Zhou Ryan , Sheen Jack , Mir-Moghtadaei Arsalan , Blumberger Daniel M. , Daskalakis Zafiris J. , Vila-Rodriguez Fidel , Downar Jonathan 
Published: June 2020

ABSTRACTBACKGROUNDRepetitive transcranial magnetic stimulation (rTMS) is effective in major depressive disorder (MDD). However, technical complexity and operational costs might have been barriers for its wide use and implementation in some jurisdictions, thereby decreasing accessibility.OBJECTIVEOur main goal was to test the feasibility of a novel rTMS protocol optimized for practicality, scalability and cost-effectiveness. We hypothesized that our novel rTMS protocol would be simple to implement and well-tolerated, but less costly and allow for more treatment capacity.METHODSTreatment was administered in an open-room setting, allowing a single technician to attend to multiple patients. Large non-focal parabolic coils held by custom-built arms allowed simple yet efficient and accurate placement. We employed a low-frequency (LF) 1 Hz stimulation protocol (360 pulses per session), delivered on the most affordable FDA-approved devices. MDD participants received an initial accelerated rTMS course (arTMS) of 6 sessions/day over 5 days (30 total), followed by a tapering course of daily sessions (up to 25) to decrease the odds of relapse. The self-reported Beck Depression Inventory II (BDI-II) was used to measure severity of depression.RESULTSForty-eight (48) patients completed the arTMS course. No serious adverse events occurred, and all patients reported manageable pain levels. Response and remission rates were 35.4% and 27.1% on the BDI-II, respectively, at the end of the tapering course.CONCLUSIONIf rTMS could be delivered for lower cost at higher volume, while preserving efficacy, safety and tolerability, it could warrant further investigation of this treatment as a first-line intervention in MDD.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT04376697
Commercial Airline Protocol during Covid-19 Pandemic: An Experience of Thai Airways International
Authors: Pongpirul Krit , Kaewpoungngam Kanitha , Chotirosniramit Korn , Theprugsa Sinnop 
Published: June 2020

AbstractIntroductionCoronavirus disease 2019 (COVID-19) pandemic has affected the aviation industry. Existing protocols have relied on scientifically questionable evidence and might not lead to the optimal balance between public health safety and airlines’ financial viability.ObjectiveTo explore the implementation feasibility of Thai Airways International protocol from the perspectives of passengers and aircrews.DesignAn online questionnaire survey of passengers and an in-depth interview with aircrews.SettingTwo randomly selected repatriation flights operated by Thai Airways International using Boeing 777 aircraft (TG476 from Sydney and TG492 from Auckland to Bangkok)Participants377 Thai passengers and 35 aircrews.ResultsThe mean age of passengers was 28.14 (95%CI 26.72 to 29.55) years old; 57.03% were female. TG492 passengers were mostly students and significantly younger than that of TG476 (p<0.0001) with comparable flying experience (p=0.1192). The average body temperature was 36.52 (95%CI 36.48 to 36.55) degrees Celsius. Passengers estimated average physical distances of 1.59 (95%CI 1.48 to 1.70), 1.41 (95%CI 1.29 to 1.53), and 1.26 (95%CI 1.12 to 1.41) meters at check-in, boarding, and in-flight, respectively. Passengers were checked for body temperature during the flight 1.97 (95%CI 1.77 to 2.18) times on average which is significantly more frequent in longer than shorter flight (p<0.0001). Passengers moved around or went to the toilet during the flight 2.00 (95%CI 1.63 to 2.37) and 2.08 (95%CI 1.73 to 2.43) times which are significantly more frequent in longer than shorter flight (p=0.0186 and 0.0049, respectively). The aircrews were satisfied with the protocol and provided several practical suggestions.ConclusionThe protocol was well received by the passengers and aircrews of the repatriation flights with some suggestions for improvement.
Worsening of kidney function is the major mechanism of heart failure in hypertension: the ALLHAT study
Authors: Khayyat-Kholghi Maedeh , Oparil Suzanne , Davis Barry R. , Tereshchenko Larisa G. 
Published: June 2020

AbstractBackgroundWe aimed to quantify the extent to which the effect of antihypertensive drugs on incident heart failure (HF) is mediated by their effect on kidney function. We hypothesized that the dynamic change in kidney function is the mechanism behind differences in the rate of incident HF in ALLHAT participants randomized to lisinopril, amlodipine, and doxazosin, in comparison to those randomized to chlorthalidone.MethodsCausal mediation analysis of ALLHAT data (1994-2002) included participants with available baseline and 24-48 month estimated glomerular filtration rate (eGFR) (n=27,918; mean age 66±7.4; 32.4% black, 56.3% men). Change in eGFR was the mediator. Incident symptomatic HF was the primary outcome. Hospitalized/fatal HF was the secondary outcome. Linear regression (for mediator) and logistic regression (for outcome) analyses were adjusted for demographics, cardiovascular disease, and risk factors.ResultsThere were 1,769 incident HF events, including 1,359 hospitalized/fatal HF events. In fully adjusted causal mediation analysis, the relative change in eGFR mediated 38% of the effect of amlodipine, 25.5% of doxazosin, and 6.3% of lisinopril on incident symptomatic HF, and 42% of the effect of amlodipine, 55.3% of doxazosin, and 12.7% of lisinopril on hospitalized/fatal HF. In lisinopril arm, eGFR changes had an opposite effect on symptomatic versus hospitalized/fatal HF outcomes. Reduction in eGFR by at least 40% explained > 50% of increased risk in hospitalized/fatal HF but 18-25% reduction of symptomatic HF risk.ConclusionOn the risk difference scale, change in eGFR accounts for more than 50% of the mechanism by which antihypertensive medications affect HF.Clinical Trial RegistrationURL:www.clinicaltrials.govUnique identifier:NCT00000542.
The sensorimotor strategies and neuronal representations of tactile shape discrimination in mice
Authors: Rodgers Chris C , Nogueira Ramon , Pil B Christina , Greeman Esther A , Fusi Stefano , Bruno Randy M 
Published: June 2020

SummaryHumans and other animals can identify objects by active touch, requiring the coordination of exploratory motion and tactile sensation. The brain integrates movements with the resulting tactile signals to form a holistic representation of object identity. We developed a shape discrimination task that challenged head-fixed mice to discriminate concave from convex shapes. Behavioral decoding revealed that mice did this by comparing contacts across whiskers. In contrast, mice performing a shape detection task simply summed up contacts over whiskers. We recorded populations of neurons in the barrel cortex, which processes whisker input, to identify how it encoded the corresponding sensorimotor variables. Neurons across the cortical layers encoded touch, whisker motion, and task-related signals. Sensory representations were task-specific: during shape discrimination, neurons responded most robustly to behaviorally relevant whiskers, overriding somatotopy. We suggest a similar dynamic modulation may underlie object recognition in other brain areas and species.
Diagnostic Evidence GAuge of Single cells (DEGAS): A flexible deep-transfer learning framework for prioritizing cells in relation to disease
Authors: Johnson Travis S. , Yu Christina Y. , Huang Zhi , Xu Siwen , Wang Tongxin , Dong Chuanpeng , Shao Wei , Zaid Mohammad Abu , Huang Xiaoqing , Wang Yijie , Bartlett Christopher , Zhang Yan , Walker Brian A. , Liu Yunlong , Huang Kun , Zhang Jie 
Published: June 2020

AbstractWe proposeDEGAS(Diagnostic Evidence GAuge of Single cells), a novel deep transfer learning framework, to transfer disease information from patients to cells. We call such transferrable information “impressions,” which allow individual cells to be associated with disease attributes like diagnosis, prognosis, and response to therapy. Using simulated data and ten diverse single cell and patient bulk tissue transcriptomic datasets from Glioblastoma Multiforme (GBM), Alzheimer’s Disease (AD), and Multiple Myeloma (MM), we demonstrate the feasibility, flexibility, and broad applications of theDEGASframework.DEGASanalysis on newly generated myeloma single cell transcriptomics led to the identification ofPHF19highmyeloma cells associated with progression.
High-frequency oscillations in the internal globus pallidus: a pathophysiological biomarker in Parkinson's disease?
Authors: Johnson Luke A , Aman Joshua E , Yu Ying , Escobar Sanabria David , Wang Jing , Hill Meghan , Dharnipragada Rajiv , Patriat Remi , Fiecas Mark , Li Laura , Schrock Lauren E , Cooper Scott E , Johnson Matthew D , Park Michael C , Harel Noam , Vitek Jerrold L 
Published: June 2020

AbstractAbnormal oscillatory neural activity in the basal ganglia is thought to play a pathophysiological role in Parkinson’s disease. Many patient studies have focused on beta frequency band (13-35 Hz) local field potential activity in the subthalamic nucleus, however increasing evidence points to alterations in neural oscillations in high frequency ranges (>100 Hz) having pathophysiological relevance. Prior studies have found that power in subthalamic high frequency oscillations (HFOs) is positively correlated with dopamine tone and increased during voluntary movements, implicating these brain rhythms in normal basal ganglia function. Contrary to this idea, in the current study we present a combination of clinical and preclinical data that support the hypothesis that HFOs in the internal globus pallidus (GPi) are a pathophysiological feature of Parkinson’s disease. Spontaneous and movement-related pallidal field potentials were recorded from deep brain stimulation (DBS) leads targeting the GPi in five externalized Parkinson’s disease patients, on and off dopaminergic medication. We identified a prominent oscillatory peak centered at 200-300 Hz in the off-medication rest recordings in all patients. High frequency power increased during movement, and the magnitude of modulation was negatively correlated with bradykinesia. Moreover, high frequency oscillations were significantly attenuated in the on-medication condition, suggesting they are a feature of the parkinsonian condition. To further confirm that GPi high frequency oscillations are characteristic of dopamine depletion, we also collected field potentials from DBS leads chronically implanted in three rhesus monkeys before and after the induction of parkinsonism with the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). High frequency oscillations and their modulation during movement were not prominent in the normal condition but emerged in the parkinsonian condition in the monkey model. These data provide the first evidence demonstrating that exaggerated, movement-modulated high frequency oscillations in the internal globus pallidus are a pathophysiological feature of Parkinson’s disease, and motivate additional investigations into the functional roles of high frequency neural oscillations across the basal ganglia-thalamocortical motor circuit and their relationship to motor control in normal and diseased states. These findings also provide rationale for further exploration of these signals for electrophysiological biomarker-based device programming and stimulation strategies in patients receiving deep brain stimulation therapy.
Predation drives specialized host plant associations in preadapted milkweed bugs (Heteroptera: Lygaeinae)
Authors: Petschenka Georg , Halitschke Rayko , Roth Anna , Stiehler Sabrina , Tenbusch Linda , Züst Tobias , Hartwig Christoph , Gámez Juan Francisco Moreno , Trusch Robert , Deckert Jürgen , Chalušová Kateřina , Vilcinskas Andreas , Exnerová Alice 
Published: June 2020

AbstractHost plant specialization across herbivorous insects varies dramatically, but the underlying evolutionary mechanisms are little-known. The milkweed bugs (Heteroptera: Lygaeinae) are ancestrally associated with plants of the Apocynaceae from which they commonly sequester cardiac glycosides for defense, facilitated by resistant Na+/K+-ATPases and adaptations for transport, storage and discharge of toxins. Here, we show that three Lygaeinae species independently colonized four novel non-apocynaceous hosts, convergently producing cardiac glycosides. A fourth species shifted to a new source of toxins by tolerating and sequestering alkaloids from meadow saffron (Colchicum autumnale, Colchicaceae). Across three species tested, feeding on seeds containing toxins did not improve growth, but sequestration mediated protection against predatory lacewing larvae and birds. We conclude that physiological preadaptations and convergent phytochemistry facilitated novel specialized host associations. Therefore, selection by predators on sequestration of defenses, rather than the exploitation of novel dietary resources, can lead to obligatory specialized host associations in generalist insects.
Cdc42 GTPase Activating Proteins (GAPs) Maintain Generational Inheritance of Cell Polarity and Cell Shape in Fission Yeast
Authors: Pino Marbelys Rodriguez , Nuñez Illyce , Chen Chuan , Das Maitreyi E. , Wiley David J. , D’Urso Gennaro , Buchwald Peter , Vavylonis Dimitrios , Verde Fulvia 
Published: June 2020

AbstractThe highly conserved small GTPase Cdc42 regulates polarized cell growth and morphogenesis from yeast to humans. We previously reported that Cdc42 activation exhibits oscillatory dynamics inSchizosaccharomyces pombecells. Mathematical modeling suggests that this dynamic behavior enables a variety of symmetric and asymmetric Cdc42 distributions to coexist in cell populations. For individual wild type cells, however, growth follows a stereotypical pattern where Cdc42 distribution is initially asymmetrical in young daughter cells and becomes more symmetrical as cell volume increases, enabling bipolar growth activation. To explore whether different states of Cdc42 activation are possible in a biological context, we examinedS. pombe rga4Δ mutant cells, lacking the Cdc42 GTPase activating protein (GAP) Rga4. We found that monopolarrga4Δ mother cells divide asymmetrically leading to the emergence of both symmetric and asymmetric Cdc42 distributions inrga4Δ daughter cells. Using genetic screening approaches to identify mutants that alter therga4Δ phenotype, we tested the predictions of different computational models that reproduce the unequal fate of daughter cells. We found experimentally that the unequal distribution of active Cdc42 GTPase in daughter cells is consistent with an unequal inheritance of another Cdc42 GAP, Rga6, in the two daughter cells. Our findings highlight the crucial role of Cdc42 GAP protein localization in determining the morphological fate of cell progeny and ensuring consistent Cdc42 activation and growth patterns across generations.
Oral drug repositioning candidates and synergistic remdesivir combinations for the prophylaxis and treatment of COVID-19
Authors: Bakowski Malina A. , Beutler Nathan , Chen Emily , Nguyen Tu-Trinh H. , Kirkpatrick Melanie G. , Parren Mara , Yang Linlin , Ricketts James , Gupta Anil K. , Hull Mitchell V. , Schultz Peter G. , Burton Dennis R. , Chatterjee Arnab K. , McNamara Case W. , Rogers Thomas F. 
Published: June 2020

AbstractThe ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. A high-throughput, high-content imaging assay of human HeLa cells expressing the SARS-CoV-2 receptor ACE2 was used to screen ReFRAME, a best-in-class drug repurposing library. From nearly 12,000 compounds, we identified 66 compounds capable of selectively inhibiting SARS-CoV-2 replication in human cells. Twenty-four of these drugs show additive activity in combination with the RNA-dependent RNA polymerase inhibitor remdesivir and may afford increased in vivo efficacy. We also identified synergistic interaction of the nucleoside analog riboprine and a folate antagonist 10-deazaaminopterin with remdesivir. Overall, seven clinically approved drugs (halofantrine, amiodarone, nelfinavir, simeprevir, manidipine, ozanimod, osimertinib) and 19 compounds in other stages of development may have the potential to be repurposed as SARS-CoV-2 oral therapeutics based on their potency, pharmacokinetic and human safety profiles.
The nucleus serves as the pacemaker for the cell cycle
Authors: Afanzar O. , Buss G. K , Stearns T. , Ferrell J. E. 
Published: June 2020

AbstractMitosis is a dramatic cellular process that affects all parts of the cell. InXenopusembryos and extracts it is driven by the activation of a bistable trigger circuit, whose various components are localized in the nucleus, centrosome, and cytoplasm. In principle, whichever cellular location has the fastest intrinsic rhythm should act as a pacemaker for the process. Here we followed tubulin polymerization and depolymerization inXenopusegg extracts supplemented with demembranated sperm, and thereby identified locations where mitosis first occurred. We found that mitosis was commonly first initiated at sperm-derived nuclei and their accompanying centrosomes, and then spread outward in circular trigger waves. The cell cycle was ∼20% more rapid at the nucleus/centrosome-associated trigger wave sources than in the regions of the extract that appeared not to be entrained by trigger waves. Nuclei produced from phage DNA, which did not possess centrosomes, also acted as trigger wave sources, but purified centrosomes in the absence of nuclei did not. We conclude that the nucleus accelerates mitotic entry and propose that it acts as a pacemaker for cell cycle.One Sentence SummaryStudies in cyclingXenopusegg extracts show that mitosis first occurs in the nucleus and then spreads outward through the cytoplasm in circular trigger waves.