bluuebunny/crossref_metadata_2025_split huggingface dataset:
A broad-based probe-free qPCR assay for detection and discrimination of three human herpes viruses
Authors: Gupta Anshu , Lawrence Shelley M. , Fraley Stephanie I. 
Published: October 2020

AbstractHuman cytomegalovirus (HCMV) and herpes simplex viruses (HSV) 1 and 2 are double stranded DNA viruses that establish lifetime latency in a host upon initial infection. Primary infection or reactivation of latent virus during pregnancy can transmit the virusin uteroor during natural childbirth to the fetus. The majority of these infections are asymptomatic at birth but may present later with potentially lethal disseminated infection or meningitis (HSV), or long-term neurodevelopmental sequelae including sensorineural hearing loss or neurodevelopmental impairments (HCMV). Unfortunately, early signs and symptoms of disseminated viral infections may be misdiagnosed as bacterial sepsis. Therefore, immediate testing for viral etiologies may not be ordered or even considered by skilled clinicians. In asymptomatic HCMV infections, early detection is necessary to monitor for and treat future neurologic sequelae. In acutely ill-appearing infants, specific detection of viruses against other disease-causing agents is vital to inform correct patient management, including early administration of the correct antimicrobial(s). An ideal test should be rapid, inexpensive, require low sample volumes, and demonstrate efficacy in multiple tissue matrices to aid in timely clinical decision-making for neonatal infections. This work discusses the development of a rapid probe-free qPCR assay for HSV and HCMV that enables early and specific detection of these viruses in neonates. The assay’s probe free chemistry would allow easier extension to a broad-based multiplexed pathogenic panel as compared to assays utilizing sequence-specific probes or nested PCR.
Delay and bias in PubMed medical subject heading (MeSH®) indexing of respiratory journals
Authors: Hadfield Ruth M. 
Published: October 2020

AbstractIntroductionPubMed is a primary global open-access literature research database. Articles on PubMed are indexed manually with medical subject headings (MeSH®) to facilitate more complete literature searches. We aimed to determine the length of delay from publication to MeSH® indexing for key respiratory journals and to investigate whether delays are increasing over time and whether there are country or impact-factor specific biases in indexing.MethodsPubMed was searched for the keyword ‘asthma’ for the 10 year period June 2009 to June 2019. MEDLINE fields including journal title, publication date, PubMed entrez date and MeSH® indexing date were extracted and delay in indexing was calculated in days.ResultsTwenty-nine respiratory journals had delay from publication to MeSH® indexing ranging from an average of 153.6 days to 409.9 days; 5/29 (17.2%) had never been indexed for PubMed. There was a significantly longer delay in MeSH® indexing for UK-based publications (mean delay of 281.7 days) compared to USA-based publications (mean delay of 214.9 days; mean difference 66.8 days, 95% CI 60.8, 72.8, P < 0.0001). Delays in MeSH® indexing increased over time.ConclusionThere are long and increasing delays in PubMed MeSH® indexing of respiratory journals. All PubMed users should be aware that systematic literature searches that rely on MeSH® search terms or utilise PubMed filters are likely to exclude recent research and citations from key journals. Researchers and clinicians need to be aware of these delays and biases to ensure their literature searches are both up-to-date and complete.
Analysis of serum trace elements, macro-minerals, antioxidants, malondialdehyde and immunoglobulins in seborrheic dermatitis patients: A case-control investigation
Authors: Jahan Ishrat , Islam Md. Rabiul , Islam Md. Reazul , Ali Rubaiya , Rahman S. M. Matiur , Nahar Zabun , Hasnat Abul , Islam Md. Saiful 
Published: October 2020

AbstractBackgroundThere are many theories abound; the exact mechanism for the pathophysiology of seborrheic dermatitis (SD) remains unknown. Neuropsychiatric disorders, stress, weakened or irregular immune responses, fungal infections, etc. are thought to be associated with the development of SD. The present study aimed to determine the serum levels of trace elements (TEs), macro-minerals (MMs), antioxidant vitamins, malondialdehyde (MDA), and immunoglobulins in SD patients to explore their role in the disease progression.MethodsThis prospective case-control study recruited 75 SD patients and 76 healthy controls (HCs) matched by age and gender. Serum TEs and MMs were analyzed by the flame atomic absorption spectroscopy and graphite furnace atomic absorption spectrometry. RP-HPLC was used to determine the serum levels of vitamin A and E. Serum MDA levels were measured by UV spectrophotometry as a marker of lipid peroxidation, whereas the turbidimetric method was used to quantify the serum levels of immunoglobulins.ResultsWe found significantly higher concentrations of serum copper, manganese, and iron, calcium, and magnesium in SD patients compared to HCs. Serum levels of vitamin E significantly decreased and serum levels of MDA significantly increased in SD patients. Besides, the lower concentrations of immunoglobulin A, G, and M were observed in SD patients when compared to HCs. The present study also found a positive correlation between serum Zn and Ca levels (r = 0.365, p = 0.009) in SD patients; whereas a negative relation was detected between serum Cu and Ca levels (r = -0.298, p = 0.035).ConclusionsThe present study suggests that increased levels of TEs, MMs, MDA, and decreased levels of immunoglobulins and vitamin E are strongly associated with the pathophysiology of SD. Moreover, these alterations may provide a predictive tool for the assessment and management of SD patients.
Transposon-insertion sequencing in a clinical isolate ofLegionella pneumophilaidentifies essential genes and determinants of natural transformation
Authors: Hardy Léo , Juan Pierre-Alexandre , Coupat-Goutaland Bénédicte , Charpentier Xavier 
Published: October 2020

AbstractLegionella pneumophilais a Gram-negative bacterium ubiquitous in freshwater environments which, if inhaled, can cause a severe pneumonia in humans. The emergence ofL. pneumophilais linked to several traits selected in the environment, the acquisition of some of which involved intra- and interkingdown horizontal gene transfer events. Transposon-insertion sequencing (TIS) is a powerful method to identify the genetic basis of selectable traits as well as to identify fitness determinants and essential genes, possible antibiotic targets. TIS has not yet been used to its full power inL. pneumophila, possibly because of difficulty to obtain a high-saturation transposon insertion library. Indeed, we found that ST1 isolates, to which belong the commonly used laboratory strains, are poorly permissive to saturating mutagenesis by conjugation-mediated transposon delivery. In contrast, we obtained high-saturation libraries in non-ST1 clinical isolates, offering the prospect of using TIS on unalteredL. pneumophilastrains. Focusing on one of them, we therefore used TIS to identify essential genes inL. pneumophila. We also revealed that TIS could be used to identify genes controlling vertical transmission of mobile genetic elements. We then applied TIS to identify all the genes required forL. pneumophilato develop competence and undergo natural transformation, defining the set of major and minor Type IV pilins that are engaged in DNA uptake. This work paves the way for the functional exploration of theL. pneumophilagenome by TIS and the identification of the genetic basis of other life traits of this species.ImportanceLegionella pneumophilais the etiologic agent of a severe form of nosocomial and community-acquired pneumonia in humans.L. pneumophilais found in man-made and freshwater environments which are the causing source of the infection. The environmental life traits ofL. pneumophila, such as its abilities to form biofilms, resist biocides and unicellular predators, are essential to its ability to accidentally infect humans. A comprehensive identification of the genetic basis of these life traits could be obtained through the use of transposon-insertion sequencing. Yet, this powerful approach, had not been fully implemented inL. pneumophila. Here we described the successful implementation of the transposon-sequencing approach in a clinical isolate ofL. pneumophila. We identify essential genes, potential drug targets, and genes required for horizontal gene transfer by natural transformation. This work represents an important step towards identifying the genetic basis of the many life traits of this environmental and pathogenic species.
Development, evaluation, and validation of machine learning models for COVID-19 detection based on routine blood tests
Authors: Federico Cabitza , Andrea Campagner , Davide Ferrari , Chiara Di Resta , Daniele Ceriotti , Eleonora Sabetta , Alessandra Colombini , Elena De Vecchi , Giuseppe Banfi , Massimo Locatelli , Anna Carobene 
Published: October 2020

AbstractBackgroundThe rRT-PCR test, the current gold standard for the detection of coronavirus disease (COVID-19), presents with known shortcomings, such as long turnaround time, potential shortage of reagents, false-negative rates around 15–20%, and expensive equipment. The hematochemical values of routine blood exams could represent a faster and less expensive alternative.MethodsThree different training data set of hematochemical values from 1,624 patients (52% COVID-19 positive), admitted at San Raphael Hospital (OSR) from February to May 2020, were used for developing machine learning (ML) models: the complete OSR dataset (72 features: complete blood count (CBC), biochemical, coagulation, hemogasanalysis and CO-Oxymetry values, age, sex and specific symptoms at triage) and two sub-datasets (COVID-specific and CBC dataset, 32 and 21 features respectively). 58 cases (50% COVID-19 positive) from another hospital, and 54 negative patients collected in 2018 at OSR, were used for internal-external and external validation.ResultsWe developed five ML models: for the complete OSR dataset, the area under the receiver operating characteristic curve (AUC) for the algorithms ranged from 0.83 to 0.90; for the COVID-specific dataset from 0.83 to 0.87; and for the CBC dataset from 0.74 to 0.86. The validations also achieved good results: respectively, AUC from 0.75 to 0.78; and specificity from 0.92 to 0.96.ConclusionsML can be applied to blood tests as both an adjunct and alternative method to rRT-PCR for the fast and cost-effective identification of COVID-19-positive patients. This is especially useful in developing countries, or in countries facing an increase in contagions.
Impact of COVID-19-lockdown and vulnerability factors on cognitive functioning and mental health in Italian population
Authors: Fiorenzato Eleonora , Zabberoni Silvia , Costa Alberto , Cona Giorgia 
Published: October 2020

ABSTRACTThe COVID-19 outbreak and its associated restrictive measures, such as lockdown, exposed most individuals to an unprecedented stressful situation, increasing worldwide the prevalence of mental health disorders.Here, we aimed at exploring for the first time the effect of COVID-19-lockdown on subjective cognitive functioning as well as mental health, in terms of its prevalence and clinical severity. In addition, potential risk factors characterizing more vulnerable groups were investigated. A nationwide cross-sectional online-survey was conducted during the final phase of lockdown in Italy (after 7-10 weeks of home confinement), leading to a sample of 1215 participants.We found lockdown can have a severe impact on subjective cognitive functioning, along with mental health disorders. Namely, under restrictions, cognitive complaints were mostly perceived in everyday tasks involving attention, temporal orientation and executive functions; while no changes in language abilities were reported. Conversely, a paradoxical effect was observed in memory domain, with people experiencing a reduction of memory failures compared to pre-lockdown times.Further, higher severity and prevalence of depression, anxiety disorders and of other psychological issues (involving sleep, appetite, libido and hypochondria) were observed – with a prevalence of mild-to-severe depression and anxiety rising up to 32.30% and 35.72% respectively, under restrictions.Being female, young (<45 years), repeatedly exposed to COVID-19-media, working from home or being unemployed were identified as relevant risk factors for experiencing cognitive worsening and mental health disorders, related to the COVID-19 lockdown. Being resident in high infection-prevalence areas was related to higher level of depression and health anxiety. As lockdown and quarantine measures could be reimposed, health officials have to carefully consider these more vulnerable groups in their decision-making process, to develop an effective global and long-term response to the mental health challenges of this pandemic as well as to implement psychological interventions and specific guidelines, particularly about COVID-19-media exposure.
Pitfalls in EEG analysis in patients with non-convulsive status epilepticus
Authors: Wang Ying , Zibrandtsen Ivan C , Lazeron Richard HC , van Dijk Johannes P , Long Xi , Aarts Ronald M , Wang Lei , Arends Johan BAM 
Published: October 2020

AbstractObjectiveElectroencephalography (EEG) interpretations through visual (by human raters) and automated (by computer technology) analysis are still not reliable for the diagnosis of non-convulsive status epilepticus (NCSE). This study aimed to identify typical pitfalls in the EEG analysis and make suggestions as to how those pitfalls might be avoided.MethodsWe analyzed the EEG recordings of individuals who had clinically confirmed or suspected NCSE. Epileptiform EEG activity during seizures (ictal discharges) were visually analyzed by two independent raters. We investigated whether unreliable EEG visual interpretations quantified by low inter-rater agreement can be predicted by the characteristics of ictal discharges and individuals’ clinical data. In addition, the EEG recordings were automatically analyzed by in-house algorithms. To further explore the causes of unreliable EEG interpretations, two epileptologists analyzed EEG patterns most likely misinterpreted as ictal discharges based on the differences between the EEG interpretations through the visual and automated analysis.ResultsShort ictal discharges with a gradual onset (developing over 3 seconds in length) were liable to be misinterpreted. An extra 2 minutes of ictal discharges contributed to an increase in the kappa statistics of > 0.1. Other problems were the misinterpretation of abnormal background activity (slow wave activities, other abnormal brain activity, and the ictal-like movement artifacts), continuous interictal discharges, and continuous short ictal discharges.ConclusionA longer duration criterion for NCSE-EEGs than 10 seconds that commonly used in NCSE working criteria is needed. Using knowledge of historical EEGs, individualized algorithms, and context-dependent alarm thresholds may also avoid the pitfalls.
A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment
Authors: Cornelison R. C. , Yuan J. X. , Tate K. M. , Petrosky A. , Beeghly G. F. , Bloomfield M. , Schwager S. C. , Berr A. L. , Cimini D. , Bafakih F. F. , Mandell J. W. , Purow B. W. , Horton B. J. , Munson J. M. 
Published: October 2020

AbstractGlioblastoma is an aggressive brain cancer characterized by diffuse infiltration. Infiltrated glioma cells persist in the brain post-resection where they interact with glial cells and experience interstitial fluid flow. We recreate this infiltrative microenvironmentin vitrobased on resected patient tumors and examine malignancy metrics (invasion, proliferation, and stemness) in the context of cellular and biophysical factors and therapies. Our 3D tissue-engineered model comprises patient-derived glioma stem cells, human astrocytes and microglia, and interstitial fluid flow. We found flow contributes to all outcomes across seven patient-derived lines, and glial effects are driven by CCL2 and differential glial activation. We conducted a six-drug screen using four outcomes and find expression of putative stemness marker CD71, opposed to viability IC50, significantly predicts murine xenograft survival. Our results dispute the paradigm of viability as predictive of drug efficacy. We posit this patient-centric, infiltrative tumor model is a novel advance towards translational personalized medicine.
Optimal versus approximate channel selection methods for EEG decoding with application to topology-constrained neuro-sensor networks
Authors: Mundanad Narayanan Abhijith , Patrinos Panagiotis , Bertrand Alexander 
Published: October 2020

AbstractChannel selection or electrode placement for neural decoding is a commonly encountered problem in electroencephalography (EEG). Since evaluating all possible channel combinations is usually infeasible, one usually has to settle for heuristic methods or convex approximations without optimality guarantees. To date, it remains unclear how large the gap is between the selection made by these approximate methods and the truly optimal selection. The goal of this paper is to quantify this optimality gap for several state-of-the-art channel selection methods in the context of least-squares based neural decoding. To this end, we reformulate the channel selection problem as a mixed-integer quadratic program (MIQP), which allows the use of efficient MIQP solvers to find the optimal channel combination in a feasible computation time for up to 100 candidate channels. As this reveals the exact solution to the combinatorial problem, it allows to quantify the performance losses when using state-of-the-art sub-optimal (yet faster) channel selection methods. In a context of auditory attention decoding, we find that a greedy channel selection based on the utility metric does not show a significant optimality gap compared to optimal channel selection, whereas other state-of-the-art greedy orl1-norm penalized methods do show a significant loss in performance. Furthermore, we demonstrate that the MIQP formulation also provides a natural way to incorporate topology constraints in the selection, e.g., for electrode placement in neuro-sensor networks with galvanic separation constraints. Furthermore, a combination of this utility-based greedy selection with an MIQP solver allows to perform a topology constrained electrode placement, even in large scale problems with more than 100 candidate positions.
Simulating digital micromirror devices for patterning coherent excitation light in structured illumination microscopy
Authors: Lachetta Mario , Sandmeyer Hauke , Sandmeyer Alice , Schulte am Esch Jan , Huser Thomas , Müller Marcel 
Published: October 2020

SummaryDigital micromirror devices (DMDs) are spatial light modulators that employ the electro-mechanical movement of miniaturized mirrors to steer and thus modulate the light reflected of a mirror array. Their wide availability, low cost and high speed make them a popular choice both in consumer electronics such as video projectors, and scientific applications such as microscopy.High-end fluorescence microscopy systems typically employ laser light sources, which by their nature provide coherent excitation light. In super-resolution microscopy applications that use light modulation, most notably structured illumination microscopy (SIM), the coherent nature of the excitation light becomes a requirement to achieve optimal interference pattern contrast. The universal combination of DMDs and coherent light sources, especially when working with multiple different wavelengths, is unfortunately not straight forward. The substructure of the tilted micromirror array gives rise to ablazed grating, which has to be understood and which must be taken into account when designing a DMD-based illumination system.Here, we present a set of simulation frameworks that explore the use of DMDs in conjunction with coherent light sources, motivated by their application in SIM, but which are generalizable to other light patterning applications. This framework provides all the tools to explore and compute DMD-based diffraction effects and to simulate possible system alignment configurations computationally, which simplifies the system design process and provides guidance for setting up DMD-based microscopes.
Arabidopsisinositol polyphosphate kinase activities regulate COP9 deneddylation functions in phosphate-homeostasis
Authors: Walia Yashika , Noopur Medha , Sahoo Bhaskar Chandra , Bhattacharya Ishana , Kasera Mritunjay , Pullagurla Naga Jyothi , Saxena Shobhita , Liu Guizhen , Schaaf Gabriel , Jessen Henning , Laha Debabrata , Bhattacharjee Souvik , Bhattacharjee Saikat 
Published: October 2020

AbstractPlant Cullin RING Ubiquitin E3 ligases (CRLs) facilitate targeted protein degradation during physiological development and adaptation to stress. The deneddylase activity of COP9 signalosome (CSN) regulates cellular ratios of neddylated cullins available for the continuum of CRL functions. While selective inositol polyphosphates (InsPs) function as co-factors in plant responses involving the ubiquitylation of negative regulators, a relationship to CSN-CRL activities has not yet been established. Here, we show that the twoArabidopsis thalianaInsP-kinases IPK1 and ITPK1 physically interact and metabolically connect with the CSN holo-complex to modulate cullin deneddylation efficiency. Specifically, functional deficiency of ITPK1 lowers cullin deneddylation rates and disrupts the dissociation equilibrium of CSN5, the deneddylase catalytic subunit, and CUL1 with the holo-complex. Our results identify a novel auto-regulatory switch of CSN functions, defined by deneddylation activity. We further demonstrate that phosphate starvation response (PSR), which is induced in Pi-starved wild-type plants and constitutive in the above InsP-kinase mutants, is orchestrated in part by reduced deneddylation rates that, in turn, affect the stability of SPX4, a key negative regulator of PSR. Pharmacological inhibition of cullin neddylation stabilizes SPX4 and impairs PSR, thus linking CSN-CRL dynamics to phosphate (Pi)-sensing. Conversely, when exposed to compounds that inhibit CSN5 deneddylase activity, wild-type plants display phenotypes similar to the above InsP-kinase mutants. Overall, our data reveal that the regulation of plant Pi-starvation responses by specific InsP-kinases is caused by a direct role of these kinases in balancing coordination between CRL-CSN activities.