bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of popular pulse oximeters compared with simultaneous arterial oxygen saturation or clinical-grade pulse oximetry: a cross-sectional validation study in intensive care patients
Authors: Harskamp Ralf E. , Bekker Luuk , Himmelreich Jelle C.L. , De Clercq Lukas , Karregat Evert P.M. , Sleeswijk Mengalvio E. , Lucassen Wim A.M. 
Published: March 2021

ABSTRACTBackgroundThe demand for pulse oximeters is high in the current COVID-19 pandemic. Despite their popularity, clinical studies to evaluate the reliability in obtaining information on a patient’s oxygenation status, are lacking.AimTo evaluate the performance of pulse oximeters under clinical conditions, with arterial blood gas measurement (SaO2) as reference standard.MethodsWe studied the accuracy of ten top-selling pulse oximeters in Europe and the USA in an intensive care population at the Flevoziekenhuis in Almere, the Netherlands. The studied pulse oximeters were: AFAC FS10D, AGPTEK FS10C, ANAPULSE ANP 100, Cocobear, Contec CMS50D1, HYLOGY MD-H37, Mommed YM101, PRCMISEMED F4PRO, PULOX PO-200, and Zacurate Pro Series 500DL. Adult patients in whom an SaO2 measurement was obtained as part of routine care were asked for inclusion. Directly after obtaining the SaO2 blood sample we obtained the pulse oximeter readings (SpO2) of the investigational devices, in random order. Outcomes were bias (SpO2 – SaO2) mean, root mean square difference (ARMS), mean absolute error (MAE), and accuracy in identifying hypoxemia (SaO2≤90%). As a clinical index test, we included a hospital-grade SpO2-monitor.ResultsIn 35 consecutive patients we obtained 2,258 SpO2-readings and 234 SaO2-samples. Mean bias ranged from −0.6 to −4.8. None of the pulse oximeters had an ARMS≤3%, the requirement set by ISO-standards and required for FDA 501(k) clearance. The MAE ranged from 2.3 to 5.1, and 5 out of 10 pulse oximeters met the requirements of ≤3%. For hypoxemia, negative predictive values were 98-99%. Positive predictive values ranged from 11-30%. Highest accuracy (95%CI) were found for Contec CMS50D1; 91% (86-94) and Zacurate Pro Series 500DL; 90% (85-94). The hospital-grade SpO2-monitor had an ARMS of 3.0 and MAE of 1.9, and an accuracy of 95% (91-97%).ConclusionDirect-to-consumer pulse oximeters do not meet ISO-standards required for FDA-clearance, but can accurately rule out hypoxemia.
Feasibility of Social Media Recruitment for Orofacial Cleft Genetic Research
Authors: Carlock Grace , Manning Kelly , Leslie Elizabeth J. 
Published: March 2021

AbstractObjectiveThis study assessed the feasibility of unpaid social media (SM) advertising to recruit participants affected with an orofacial cleft (OFC) for a genetic study.DesignThis paper is a retrospective analysis of study recruitment based on enrollment and participation in a genetic study. Participants completed a series of enrollment surveys, provided saliva samples for genetic analysis, and completed post-participation feedback surveys.ParticipantsParticipants signed up for the study following SM advertisement. Participants were eligible if: they or a minor in their care were affected by an OFC, the affected participant was not adopted, and the mother of the affected individual had not taken anti-seizure medication during pregnancy. 313 individuals completed initial screening surveys; 306 participants were eligible. 263 individuals completed all online surveys and were sent DNA sample kits. 162 subject DNA samples were returned.Main Outcome MeasuresSuccess of recruitment was evaluated as number of enrolled participants and return rate for DNA samples.Results263 OFC-affected individuals completed the screening process in the first 12 months of recruitment. 162 of 263 affected subject DNA samples were returned within 12 months of sending, for a return rate of 62%. Approximately two-thirds (66.3%) of all returned samples were sent back within the first 6 weeks after receiving DNA kits.ConclusionsUnpaid SM advertising enabled the recruitment of a large cohort of participants in a short time (12 months). SM recruitment was inexpensive and effective for recruiting participants for a genetic study.
Interferons Reshape the 3D Conformation and Accessibility of Macrophage Chromatin
Authors: Platanitis Ekaterini , Grüner Stephan , Geetha Aarathy Ravi Sundar Jose , Boccuni Laura , Vogt Alexander , Novachkova Maria , Sommer Andreas , Müller Mathias , Decker Thomas 
Published: March 2021

AbstractEngagement of macrophages in innate immune responses is directed and enhanced by type I and type II interferons. An essential component of IFN activity is the use of JAK-STAT signal transduction for the transcriptional control of interferon-stimulated genes (ISG). Here, we study the immediate early nuclear response to type I IFN and IFN-γ in murine macrophages. Despite their distinct immunological activities, both IFN types triggered highly overlapping epigenomic and transcriptional changes. These changes included a rapid rearrangement of the 3D chromatin organization and an increase of DNA accessibility at ISG loci. ISGF3, the major transcriptional regulator of ISG, controlled homeostatic as well as induced-state DNA accessibility at a subset of ISG. Increases in DNA accessibility correlated with the appearance of activating histone marks at surrounding nucleosomes. Collectively our data emphasize changes in the three-dimensional nuclear space and epigenome as an important facet of transcriptional control by the IFN-induced JAK-STAT pathway.
PathogenicMAST3variants in the STK domain are associated with epilepsy
Authors: Spinelli Egidio , Christensen Kyle R , Bryant Emily , Schneider Amy , Rakotomamonjy Jennifer , Muir Alison M , Giannelli Jessica , Littlejohn Rebecca O , Roeder Elizabeth R , Schmidt Berkley , Wilson William G , Marco Elysa J , Iwama Kazuhiro , Kumada Satoko , Pisano Tiziano , Barba Carmen , Brilstra Eva H , van Jaarsveld Richard H , Matsumoto Naomichi , Rodan Lance H , McWalter Kirsty , Guerrini Renzo , Scheffer Ingrid E , Mefford Heather C , Mandelstam Simone , Laux Linda , Millichap John J , Guemez-Gamboa Alicia , Nairn Angus C , Carvill Gemma L 
Published: March 2021

AbstractObjectiveThe MAST family of microtubule-associated serine-threonine kinases (STK) have distinct expression patterns in the developing and mature human and mouse brain. To date, onlyMAST1has been associated with neurological disease, withde novovariants in individuals with a neurodevelopmental disorder, including a mega corpus callosum.MethodsUsing exome sequencing we identifyMAST3missense variants in individuals with epilepsy. We also assess the effect of these variants on the ability of MAST3 to phosphorylate the target gene product ARPP-16 in HEK293T cells.ResultsWe identifyde novomissense variants in the STK domain in 11 individuals, including two recurrent variants p.G510S (n=5) and p.G515S (n=3). All 11 individuals had Developmental and epileptic encephalopathy, with 8 having normal development prior to seizure onset at < 2 years of age. All patients developed multiple seizures types, while 9/11 had seizures triggered by fever and 9/11 had drug-resistant seizures.In vitroanalysis of HEK293T cells transfected withMAST3cDNA carrying a subset of these patient-specific missense variants demonstrated variable but generally lower expression, with concomitant increased phosphorylation of the MAST3 target, ARPP-16, compared to wildtype. These findings suggest the patient-specific variants may confer MAST3 gain-of-function. Moreover, single-nuclei RNA sequencing and immunohistochemistry shows thatMAST3expression is restricted to excitatory neurons in the cortex late in prenatal development and postnatally.InterpretationIn summary, we describeMAST3as a novel epilepsy-associated gene with a potential gain-of-function pathogenic mechanism that may be primarily restricted to excitatory neurons in the cortex.
Quantified Flu: an individual-centered approach to gaining sickness-related insights from wearable data
Authors: Tzovaras Bastian Greshake , Senabre Enric , Alexiou Karolina , Baldy Lukaz , Morane Basille , Bussod Ilona , Fribourg Melvin , Wac Katarzyna , Wolf Gary , Ball Mad 
Published: March 2021

AbstractBackgroundWearables have been used widely for monitoring health in general, and recent research results show that they can be used for predicting infections based on physiological symptoms. So far, the evidence has been generated in large, population-based settings. In contrast, the Quantified Self and Personal Science communities are composed of people interested in learning about themselves individually using their own data, often gathered via wearable devices.ObjectiveWe explore how a co-creation process involving a heterogeneous community of personal science practitioners can develop a collective self-tracking system to monitor symptoms of infection alongside wearable sensor data.MethodsWe engaged in a co-creation and design process with an existing community of personal science practitioners, jointly developing a working prototype of an online tool to perform symptom tracking. In addition to the iterative creation of the prototype (started on March 16, 2020), we performed a netnographic analysis, investigating the process of how this prototype was created in a decentralized and iterative fashion.ResultsThe Quantified Flu prototype allows users to perform daily symptom reporting and is capable of visualizing those symptom reports on a timeline together with the resting heart rate, body temperature, and respiratory rate as measured by wearable devices. We observe a high level of engagement, with over half of the 92 users that engaged in the symptom tracking becoming regular users, reporting over three months of data each. Furthermore, our netnographic analysis highlights how the current Quantified Flu prototype is a result of an interactive and continuous co-creation process in which new prototype releases spark further discussions of features and vice versa.ConclusionsAs shown by the high level of user engagement and iterative development, an open co-creation process can be successfully used to develop a tool that is tailored to individual needs, decreasing dropout rates.
Therapeutic Anticoagulation in Critically Ill Patients with Covid-19 – Preliminary Report
Authors:   The REMAP-CAP,   ACTIV-4a,   ATTACC Investigators, Zarychanski Ryan 
Published: March 2021

AbstractBackgroundThrombosis may contribute to morbidity and mortality in Covid-19. We hypothesized that therapeutic anticoagulation would improve outcomes in critically ill patients with Covid-19.MethodsWe conducted an open-label, adaptive, multiplatform, randomized, clinical trial. Patients with severe Covid-19, defined as the requirement for organ support with high flow nasal cannula, non-invasive ventilation, invasive ventilation, vasopressors, or inotropes, were randomized to receive therapeutic anticoagulation with heparin or pharmacological thromboprophylaxis as per local usual care. The primary outcome was an ordinal scale combining in-hospital mortality (assigned –1) and days free of organ support to day 21.ResultsTherapeutic anticoagulation met the pre-defined criteria for futility in patients with severe Covid-19. The primary outcome was available for 1,074 participants (529 randomized to therapeutic anticoagulation and 545 randomized to usual care pharmacological thromboprophylaxis). Median organ support-free days were 3 days (interquartile range –1, 16) in patients assigned to therapeutic anticoagulation and 5 days (interquartile range –1, 16) in patients assigned to usual care pharmacological thromboprophylaxis (adjusted odds ratio 0.87, 95% credible interval (CrI) 0.70-1.08, posterior probability of futility [odds ratio<1.2] 99.8%). Hospital survival was comparable between groups (64.3% vs. 65.3%, adjusted odds ratio 0.88, 95% CrI 0.67-1.16). Major bleeding occurred in 3.1% of patients assigned to therapeutic anticoagulation and 2.4% of patients assigned to usual care pharmacological thromboprophylaxis.ConclusionsIn patients with severe Covid-19, therapeutic anticoagulation did not improve hospital survival or days free of organ support compared to usual care pharmacological thromboprophylaxis.Trial registration numbers NCT02735707, NCT04505774, NCT04359277, NCT04372589
A Software Solution for Clinical Protocol Management
Authors: Almeida João Rafael , Oliveira José Luís 
Published: March 2021

AbstractClinical treatments are mostly the result of consecutive success of medical procedures. The patterns in those procedures lead to creation of clinical guidelines which are currently essential to have better health treatments. The use of electronic health record systems (EHR) helps the patient management, but it fails in the treatment guidance due to the lack of clinical decision support systems. Although these systems have decision-making features incorporated, they are not designed for treatment management and guidance. In some top edge systems, this functionality was improved and integrated, but either they are tight to the typically complex EHR. Or, many times the independent solutions lack generality to support users and disease-specific protocols.In this paper, we purpose a decision support web tool which works independently from EHR systems. This solution allows clinicians to build and manage rule-based clinical protocols, by facilitating health care treatments, reducing time, and increasing medication accuracy. Moreover, it also enables protocol sharing among distinct institutions and physicians, creating a larger database of clinical guidelines and a network of speciliased physicians in types of diseases.The proposed system was evaluated with the implementation of distinct clinical protocols, from different medical fields. In this validation, we describe all the steps in the transformation of a clinical guideline, from the traditional format, into a ready-to-use protocol with guidance and recommendation features.The purposed system was developed with the collaboration of health professionals from different Portuguese healthcare institutions, which helped in the identification of system requirements and gaps of the current systems.
Temporal Aspects of the Association between Exposure to the World Trade Center Disaster and Risk of Skin Melanoma
Authors: Boffetta Paolo , Goldfarb David G. , Zeig-Owens Rachel , Kristjansson Dana , Li Jiehui , Brackbill Robert M. , Farfel Mark R. , Cone James E. , Yung Janette , Kahn Amy R. , Qiao Baozhen , Schymura Maria J. , Webber Mayris P. , Prezant David J. , Dasaro Christopher R. , Todd Andrew C. , Hall Charles B. 
Published: March 2021

AbstractRescue/recovery workers who responded to the World Trade Center (WTC) attacks on 9/11/2001 were exposed to known/suspected carcinogens. Studies have identified an increased risk of skin melanoma in this population, but the temporal aspects of the association have not been investigated. A total of 44,540 non-Hispanic White workers from the WTC Combined Rescue/Recovery Cohort were observed between 3/12/2002 and 12/31/2015. Cancer data were obtained via linkages with 13 state registries. Poisson regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI), using the New York State population as reference; change points in the HRs were estimated using profile likelihood. We observed 247 incident cases of skin melanoma. No increase in incidence was detected between 2002 and 2004. Beginning in 2005, the HR was 1.34 (95% CI 1.18-1.52). A dose-response relationship was observed according to time worked on the WTC effort. Risk of melanoma among non-Hispanic White WTC rescue/recovery workers was elevated, beginning in 2005. While WTC-related exposure to ultraviolet radiation or other agents might have contributed to this result, exposures other than the WTC effort and enhanced medical surveillance cannot be discounted. Our results support the continued surveillance of this population for melanoma.
A tale of three SARS-CoV-2 variants with independently acquired P681H mutations in New York State
Authors: Lasek-Nesselquist Erica , Pata Janice , Schneider Erasmus , George Kirsten St. 
Published: March 2021

AbstractSeveral SARS-CoV-2 variants of concern have independently acquired some of the same Spike protein mutations - notably E484K, N501Y, S477N, and K417T - associated with increased viral transmission and/or reduced sensitivity to neutralization by antibodies. Repeated evolution of the same mutations, particularly in variants that are now rapidly spreading in various regions of the world, suggests a fitness advantage. Mutations at position P681 in Spike – possibly affecting viral transmission - have also evolved multiple times, including in two variants of concern. Here, we describe three variants circulating in New York State that have independently acquired a P681H mutation and the different trajectories they have taken. While one variant rose to high prevalence since later summer 2020 it appears to be in decline. The other two variants were more recently detected in New York and harbor additional Spike mutations that might be cause for continued monitoring. The latter two P681H variants have shown moderate increases in prevalence but ultimately all might be subject to the same fate as more competitive variants come to dominate the scene.
Gene expression shapes the patterns of parallel evolution of herbicide resistance in the agricultural weedMonochoria vaginalis
Authors: Tanigaki Shinji , Uchino Akira , Okawa Shigenori , Miura Chikako , Hamamura Kenshiro , Matsuo Mitsuhiro , Yoshino Namiko , Ueno Naoya , Toyama Yusuke , Fukumi Naoya , Kijima Eiji , Masuda Taro , Shimono Yoshiko , Tominaga Tohru , Iwakami Satoshi 
Published: March 2021

AbstractThe evolution of herbicide resistance in weeds is an example of parallel evolution, through which genes encoding herbicide target proteins are repeatedly represented as evolutionary targets. The number of herbicide target-site genes differs among species, and little is known regarding the effects of duplicate gene copies on the evolution of herbicide resistance. We investigated the evolution of herbicide resistance inMonochoria vaginalis, which carries five copies of sulfonylurea target-site acetolactate synthase (ALS) genes. Suspected resistant populations collected across Japan were investigated for herbicide sensitivity andALSgene sequences, followed by functional characterisation andALSgene expression analysis. We identified over 60 resistant populations, all of which carried resistance-conferring amino acid substitutions exclusively inMvALS1orMvALS3. AllMvALS4alleles carried a loss-of-function mutation. Although the enzymatic properties of ALS encoded by these genes were not markedly different, the expression ofMvALS1andMvALS3was prominently higher among allALSgenes. The higher expression ofMvALS1andMvALS3is the driving force of the biased representation of genes during the evolution of herbicide resistance inM. vaginalis. Our findings highlight that gene expression is a key factor in creating evolutionary hotspots.
Beyond Turing:Far-from-equilibriumpatterns and mechano-chemical feedback
Authors: Veerman Frits , Mercker Moritz , Marciniak-Czochra Anna 
Published: March 2021

AbstractTuring patterns are commonly understood as specific instabilities of a spatially homogeneous steady state, resulting from activator-inhibitor interaction destabilised by diffusion. We argue that this view is restrictive and its agreement with biological observations is problematic. We present two alternative to the ‘classical’ Turing analysis of patterns. First, we employ the abstract framework of evolution equations to enable the study offar-from-equilibriumpatterns. Second, we introduce a mechano-chemical model, with the surface on which the pattern forms being dynamic and playing an active role in the pattern formation, effectively replacing the inhibitor. We highlight the advantages of these two alternatives vis-à-vis the ‘classical’ Turing analysis, and give an overview of recent results and future challenges for both approaches.
Behavior emerges from unstructured muscle activity in response to neuromodulation
Authors: Elliott Amicia D. , Berndt Adama , Houpert Matthew , Roy Snehashis , Scott Robert L. , Chow Carson C. , Shroff Hari , White Benjamin H. 
Published: March 2021

SummaryIdentifying neural substrates of behavior requires defining actions in terms that map onto brain activity. Brain and muscle activity naturally correlate via the output of motor neurons, but apart from simple movements it has been difficult to define behavior in terms of muscle contractions. By mapping the musculature of the pupal fruit fly and comprehensively imaging muscle activation at single cell resolution, we here describe a multiphasic behavioral sequence inDrosophila. Our characterization identifies a previously undescribed behavioral phase and permits extraction of major movements by a convolutional neural network. We deconstruct movements into a syllabary of co-active muscles and identify specific syllables that are sensitive to neuromodulatory manipulations. We find that muscle activity shows considerable variability, which reduces upon neuromodulation. Our work provides a platform for studying whole-animal behavior, quantifying its variability across multiple spatiotemporal scales, and analyzing its neuromodulatory regulation at cellular resolution.
The dynamics of decision making and action during active sampling
Authors: Ozbagci Duygu , Moreno-Bote Ruben , Soto-Faraco Salvador 
Published: March 2021

AbstractEmbodied Cognition Theories (ECTs) propose that the decision process continues to unfold during the execution of choice actions, and its outcome manifests itself in these actions. Scenarios where actions not only express choice but also help sample information can provide a valuable test of this framework. Remarkably almost no studies so far have addressed this scenario. Here, we present a study testing just this paradigmatic situation with humans. On each trial, subjects categorized a central object image, blurred to different extents (2AFC task) by moving a cursor toward the left or right of the display. Upward cursor movements, orthogonal with respect to choice options, reduced the image blur and could be freely used to actively sample information. Thus, actions for decision and actions for sampling were made orthogonal to each other. We analyzed response trajectories to test a central prediction of ECTs; whether information-sampling movements co-occurred with the ongoing decision process. Trajectory data revealed were bimodally distributed, with one kind being direct towards one response option (non-sampling trials), and the other kind containing an initial upward component before veering off towards an option (sampling trials). This implies that there was an initial decision at the early stage of a trial whether to sample information or not. Importantly, the trajectories in sampling trials were not purely upward, but rather had a significant horizontal deviation that was visible early on in the movement. This result suggests that movements to sample information exhibit an online interaction with the decision process. The finding that decision processes interact with actions to sample information supports the ECT under novel, ecologically relevant constrains.