bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wisconsin April 2020 Election Not Associated with Increase in COVID-19 Infection Rates
Authors: Berry Andrew C. , Mulekar Madhuri S. , Berry Bruce B. 
Published: April 2020

AbstractBackgroundWisconsin (WI) held a primary election in the midst of the COVID-19 pandemic. Live voting at polls was allowed despite concern over increasing the spread of COVID-19. In addition to 1.1 million absentee ballots cast, 453,222 persons voted live. The purpose of our study was to determine if an increase in COVID-19 activity was associated with the election.MethodsUsing the voting age population for the United States (US), WI, and its 3 largest counties, and daily new COVID-19 case reports from various COVID-19 web-based dashboards, daily new case rates were calculated. With election day April 7, the incubation period included April 12-21. The new case activity in the rest of the US was compared with the Wisconsin activity during the incubation period.ResultsWI daily new case rates were lower than those of the rest of the US for the 10-day period before the election and remained lower during the post exposure incubation period. The ratio of Wisconsin new case rates to US new case rates was 0.34 WI: 1 US for the 10 days leading up to the election and declined to 0.28 WI: 1 US for the 10-day post-incubation period after the election. Similar analysis for Milwaukee county showed a pre-election ratio of 1.02 Milwaukee: 1 US and after the election the ratio was 0.63 Milwaukee: 1 US. Dane county had a pre-election ratio of 0.21 Dane: 1 US case, and it fell to 0.13 Dane: 1 US after the election. Waukesha county had a pre-election ratio of 0.27 Waukesha: 1 US case and that fell to 0.19 Waukesha: 1 US after the election.ConclusionsThere was no increase in COVID-19 new case daily rates observed for Wisconsin or its 3 largest counties following the election on April 7, 2020, as compared to the US, during the post-incubation interval period.
Pharmacokinetic bases of the hydroxychloroquine response in COVID-19: implications for therapy and prevention
Authors: Tarek Mohammad , Savarino Andrea 
Published: April 2020

AbstractChloroquine/hydroxychloroquine has recently been the subject of intense debate in regard to its potential antiviral activity against SARS-Cov-2, the etiological agent of COVID-19. Some report possible curative effects, others do not. In order to shed some light on this rather controversial topic, we used mathematical modelling to simulate possible scenarios of response to hydroxychloroquine in COVID-19 patients. Our computer-aided simulations show that hydroxychloroquine may have an impact on the amplitude of the viral load peak but that viral clearance is not significantly accelerated if the drug is not administered early enough (i.e. when viral loads range from 1 to 1,000 copies/mL). Although some authors had used the trough plasma concentrations or the theoretical drug distribution in the lung to model the effect of chloroquine/hydroxychloroquine on COVID-19, the theoretical drug response based on the trough whole blood concentrations of the drug agreed well with the results of the clinical trials so far reported. Moreover, the effects of chloroquine/hydroxychloroquine could be fully explained when taking into account also the capacity of this drug to raise cell-mediated responses against the productively SARS-Cov-2-infected cells. On the whole, the present study suggests that chloroquine/hydroxychloroquine has a narrow therapeutic window, which overlaps with the highest tolerated doses. These considerations may have implications for development of anti-COVID-19 combination therapies and prevention strategies.
LONG-TERM MORPHOLOGICAL CHANGES IN THE HUMAN CORNEA LAYERS
Authors: Goedert Merry Elizabeth , Lucca Micheline Borges , Beltrão Medeiros Felipe , da Glória Silva Maria , Soares Renata Oliveira , Rezende Gustavo Lara , Catai Chalita Maria Regina , Souza Kückelhaus Selma Aparecida 
Published: April 2020

ABSTRACTPurposeTo describe and compare the morphology of the corneal layers from adults and aging individuals.MethodsThe study was conducted with normal corneas (n = 15) of predominantly male individuals grouped into two classes (group I: < 40 years; group II: ≥ 40 years). To describe and to compare the corneas, the thickness of the layers, the integrity of the stromal lamellae and the endothelial lesions, SEM images of the central and peripheral regions of each cornea were quantified.ResultsThe total thickness of the cornea was largest in the periphery only for group I. The Bowman, Descemet and endothelium layers of group I were thicker at the periphery of the corneas than their respective central regions, while for group II, this difference was observed only in the Bowman layer. Comparison between groups showed that the Bowman layer was thicker (central region), while the Descemet membrane and endothelium were thinner in group II; A greater number of endothelial lesions in both regions of the corneas was observed in group II, but no difference in the total number of interlamellar slits.ConclusionsThe morphological changes observed in group II could be related to the reduction in the pool of stem cell of limbus and, despite the corneas being from healthy individuals, these changes could compromise the success of transplantation. Our results point to an update of corneal uptake protocols and they may aid in the refractive surgeries interventions in individuals from different age groups.
Potential Role of Personal Protective Equipment Use in the Protection Against COVID-19 Infection Among Health Care Workers
Authors: Wang Wei , Min Yuan-Zeng , Yang Chun-Mei , Hong Hai-Ou , Xue Tian , Gao Yong , Jin Tengchuan , Lu Zhao-Hui , Zhang Liang-Ming , Zheng Xueying , Luo Sihui , Bao Wei , Weng Jian-Ping 
Published: April 2020

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has posed a major challenge for protecting health care workers (HCWs) against the infection. Use of personal protective equipment (PPE) in health care workplace is recommended as a high priority. In order to investigate the relationship between PPE use and the number of COVID-19 cases among HCWs, we conducted a molecular epidemiological study among 142 HCWs who were dispatched from Hefei to work in Wuhan and 284 HCWs who remained in Hefei, China; both provided care for patients with COVID-19. Nucleic acid testing and SARS-CoV-2 specific antibody (IgM, IgG, IgA) detection were performed to confirm SARS-CoV-2 infection among those HCWs. We also extracted publicly released data on daily number of COVID-19 cases among HCWs, daily number of HCWs who were dispatched to Hubei province since January 24, and daily production of PPE in China and daily demand and supply of PPE in Hubei province. Our laboratory testing confirmed that none of the 142 HCWs who were dispatched to work in Wuhan and 284 HCWs who remained in Hefei were infected by SARS-CoV-2. Consistent with these findings, as of April 15, 2020, none of the 42,600 HCWs who were successively dispatched to Hubei province since January 24, 2020 was reported to have COVID-19. These HCWs were provided with adequate supply of PPE as committed by their original institutions or provinces. In contrast, during the early phase of COVID-19 epidemic in Hubei province, a substantial shortage of PPE and an increasing number of COVID-19 infection among HCWs were reported. With the continuing increase in domestic production of PPE in China, the PPE supply started to meet and then exceed the demand. This coincided with a subsequent reduction in the number of reported COVID-19 cases among HCWs. In conclusion, our findings indicate that COVID-19 infection among HCWs could be completely prevented. Appropriate and adequate PPE might play a crucial role in protecting HCWs against COVID-19 infection.
Estimation of SARS-CoV-2 infection fatality rate by real-time antibody screening of blood donors
Authors: Erikstrup Christian , Hother Christoffer Egeberg , Vestager Pedersen Ole Birger , Mølbak Kåre , Skov Robert Leo , Holm Dorte Kinggaard , Sækmose Susanne , Nilsson Anna Christine , Brooks Patrick Terrence , Kjærgaard Boldsen Jens , Mikkelsen Christina , Gybel-Brask Mikkel , Sørensen Erik , Dinh Khoa Manh , Mikkelsen Susan , Møller Bjarne Kuno , Haunstrup Thure , Harritshøj Lene , Jensen Bitten Aagaard , Hjalgrim Henrik , Lillevang Søren Thue , Ullum Henrik 
Published: April 2020

AbstractBackgroundThe pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has tremendous consequences for our societies. Knowledge of the seroprevalence of SARS-CoV-2 is needed to accurately monitor the spread of the epidemic and also to calculate the infection fatality rate (IFR). These measures may help the authorities to make informed decisions and adjust the current societal interventions. Blood donors comprise approximately 4.7% of the similarly aged population of Denmark and blood is donated in all areas of the country. The objective of this study was to perform real-time seroprevalence surveying among blood donors as a tool to estimate previous SARS-CoV-2 infections and the population based IFR.MethodsAll Danish blood donors aged 17-69 years giving blood April 6 to 17 were tested for SARS-CoV-2 immunoglobulin M and G antibodies using a commercial lateral flow test. Antibody status was compared between areas and an estimate of the IFR was calculated. The seroprevalence was adjusted for assay sensitivity and specificity taking the uncertainties of the test validation into account when reporting the 95% confidence intervals (CI).ResultsThe first 9,496 blood donors were tested and a combined adjusted seroprevalence of 1.7% (CI: 0.9-2.3) was calculated. The seroprevalence differed across areas. Using available data on fatalities and population numbers a combined IFR in patients younger than 70 is estimated at 82 per 100,000 (CI: 59-154) infections.ConclusionsThe IFR was estimated to be slightly lower than previously reported from other countries not using seroprevalence data. The IFR, including only individuals with no comorbidity, is likely several fold lower than the current estimate. This may have implications for risk mitigation. We have initiated real-time nationwide anti-SARS-CoV-2 seroprevalence surveying of blood donations as a tool in monitoring the epidemic.
Cognitive Processing dissociation by mental effort manipulation in long demanding tasks
Authors: Alves Marcus Vinicius , Tassini Susanny , Aedo-Jury Felipe , Bueno Orlando F. A. 
Published: April 2020

AbstractIndividuals uses cognitive resources to modulate performance in demanding tasks and a non-invasive and reliable way of measuring mental effort is pupillometry. This study aimed to test the mental effort related to different processing systems in long tasks with controlled and automatic demands. We conducted two experiments with healthy subjects: in Experiment 1 (n=15), using a metronome to ensure control on task pace, participants performed a serial number generation task (Counting; little to no effort tasks), a random number generation (RNG; effortful tasks), and no task (Unfilled interval; no effort at all). In experiment 2, (n=15) participants performed counting tasks with or without additional intermediary beeps produced by a metronome to assess the effect of a possible increase in effort demanded by the distractors. Experiment 1 showed differences between unfilled interval, counting and RNG. Experiment 2 showed that the intermediate beep made the counting tasks more demanding than the normal counting tasks. Notable in both experiments was the tendency of participants to demand mental effort at the beginning of the trial. These results indicate that previously effortless automatic tasks can become controlled, or at least more demanding, with a simple experimental manipulation. They also reveal that tasks that require mental effort over a long period will demand more than automatic ones, but even so the peak of this demand is in the initial trial period. Moreover, they reveal the high sensitivity of pupillometry for the measurement of mental effort employing different processing systems and cognitive resource modulation.
Cancer-specific loss ofTERTactivation sensitizes glioblastoma to DNA damage
Authors: Amen Alexandra M. , Fellmann Christof , Soczek Katarzyna M. , Ren Shawn M. , Lew Rachel J. , Knott Gavin J. , Park Jesslyn E. , McKinney Andrew M. , Mancini Andrew , Doudna Jennifer A. , Costello Joseph F. 
Published: April 2020

AbstractMost glioblastomas (GBMs) achieve cellular immortality by acquiring a mutation in the telomerase reverse transcriptase (TERT) promoter.TERTpromoter mutations create a binding site for a GA binding protein (GABP) transcription factor complex, whose assembly at the promoter is associated withTERTreactivation and telomere maintenance. Here, we demonstrate increased binding of a specific GABPB1L isoform-containing complex to the mutantTERTpromoter. Furthermore, we find thatTERTpromoter mutant GBM cells, unlike wild-type cells, exhibit a critical near-term dependence on GABPB1L for proliferation, both in cell culture and post-tumor establishmentin vivo. Upregulation of the protein paralogue GABPB2, which is normally expressed at very low levels, can rescue this dependence. More importantly, when combined with frontline temozolomide (TMZ) chemotherapy, inducible GABPB1L knockdown and the associatedTERTreduction led to an impaired DNA damage response that resulted in profoundly reduced growth of intracranial GBM tumors. Together, these findings provide new insights into the mechanism of cancer-specificTERTregulation, uncover rapid effects of GABPB1L-mediatedTERTsuppression in GBM maintenance, and establish GABPB1L inhibition in combination with chemotherapy as a novel therapeutic strategy forTERTpromoter mutant GBM.
Toward Minimally Invasive Therapeutic Ultrasound: Ultrasound-guided Ablation in Neuro-oncology
Authors: Belzberg Micah , Mahapatra Smruti , Chavez Francisco , Morrison Kyle , Xiong Kah Timothy , Gamo Nao J. , Restaino Stephen , Iyer Rajiv , Groves Mari , Thakor Nitish , Theodore Nicholas , Luciano Mark G. , Brem Henry , Cohen Alan R. , Manbachi Amir 
Published: April 2020

ABSTRACTIntroductionTo improve patient outcomes (eg, reducing blood loss and infection), practitioners have gravitated toward noninvasive and minimally invasive surgeries (MIS), which demand specialized toolkits. Focused ultrasound, for example, facilitates thermal ablation from a distance, thereby reducing injury to surrounding tissue. Focused ultrasound can often be performed noninvasively; however, it is more difficult to carry out in neuro-oncological tumors, as ultrasound is dramatically attenuated while propagating through the skull. This shortcoming has prompted exploration of MIS options for intracranial placement of focused ultrasound probes, such as within the BrainPath™(NICO Corporation, Indianapolis, IN). Herein, we present the design, development, andin vitrotesting of an image-guided, focused ultrasound prototype designed for use in MIS procedures. This probe can ablate neuro-oncological lesions despite its small size.Materials & MethodsPreliminary prototypes were iteratively designed, built, and tested. The final prototype consisted of three 8-mm-diameter therapeutic elements guided by an imaging probe. Probe functionality was validated on a series of tissue-mimicking phantoms.ResultsLesions were created in tissue-mimicking phantoms with average dimensions of 2.5×1.2×6.5mm and 3.4×3.25×9.36mm after 10- and 30-second sonification, respectively. 30s sonification with 118W power at 50% duty cycle generated a peak temperature of 68°C. Each ablation was visualized in real time by the built-in imaging probe.ConclusionWe developed and validated an ultrasound-guided focused ultrasound probe for use in MIS procedures. The dimensional constraints of the prototype were designed to reflect those of BrainPath trocars, which are MIS tools used to create atraumatic access to deep-seated brain pathologies.HIGHLIGHTSAn ultrasound-guided, focused ultrasound prototype was developed and validatedThe therapeutic transducer (1.5MHz) consisted of three 8-mm circular elementsElements were placed on a 9×32mm curved rectangular aperture: 45mm radius curvatureFunctionality was examined on tissue-mimicking phantoms2.5×1.2×6.5mm and 3.4×3.25×9.36mm lesions were seen for 10 and 30s sonification
The case for formal methodology in scientific reform
Authors: Devezer Berna , Navarro Danielle J. , Vandekerckhove Joachim , Buzbas Erkan Ozge 
Published: April 2020

AbstractCurrent attempts at methodological reform in sciences come in response to an overall lack of rigor in methodological and scientific practices in experimental sciences. However, most methodological reform attempts suffer from similar mistakes and over-generalizations to the ones they aim to address. We argue that this can be attributed in part to lack of formalism and first principles. Considering the costs of allowing false claims to become canonized, we argue for formal statistical rigor and scientific nuance in methodological reform. To attain this rigor and nuance, we propose a five-step formal approach for solving methodological problems. To illustrate the use and benefits of such formalism, we present a formal statistical analysis of three popular claims in the metascientific literature: (a) that reproducibility is the cornerstone of science; (b) that data must not be used twice in any analysis; and (c) that exploratory projects imply poor statistical practice. We show how our formal approach can inform and shape debates about such methodological claims.
Synchronous spiking associated with high gamma oscillations in prefrontal cortex exerts top-down control over a 5Hz-rhythmic modulation of spiking in locus coeruleus
Authors: Totah Nelson K. , Logothetis Nikos K. , Eschenko Oxana 
Published: April 2020

AbstractThe brainstem noradrenergic locus coeruleus (LC) is reciprocally connected with the prefrontal cortex (PFC). Strong coupling between LC spiking and depolarizing phase of slow (1 – 2 Hz) waves in the PFC field potentials during sleep and anesthesia suggests that the LC drives cortical state transition. Reciprocal LC-PFC connectivity should also allow interactions in the opposing (top-down) direction, but prior work has only studied prefrontal control over LC activity using direct electrical (or optogenetic) stimulation paradigms. Here, we describe the physiological characteristics of naturally occurring top-down prefrontal-coerulear interactions. Specifically, we recorded LC multi-unit activity (MUA) simultaneously with PFC single unit and local field potential (LFP) activity in urethane-anesthetized rats. We observed cross-regional coupling between the phase of ~5 Hz oscillations in LC population spike rate and the power of PFC LFP oscillations within the high Gamma (hGamma) range (60 – 200 Hz). Specifically, transient increases in PFC hGamma power preceded peaks in the ~5 Hz LC-MUA oscillation. Analysis of cross-regional transfer entropy demonstrated that the PFC hGamma transients were predictive of a transient increase in LC-MUA. A ~29 msec delay between these signals was consistent with the conduction velocity from the PFC to the LC. Finally, we showed that PFC hGamma transients are associated with synchronized spiking of a subset (27%) of PFC single units. Our data suggest that, PFC hGamma transients may indicate the timing of the top-down excitatory input to LC, at least under conditions when LC neuronal population activity fluctuates rhythmically at ~5 Hz. Synchronized PFC neuronal spiking that occurs during hGamma transients may provide a previously unknown mode of top-down control over the LC.
Synaptic Plasticity in Correlated Balanced Networks
Authors: Akil Alan Eric , Rosenbaum Robert , Josić Krešimir 
Published: April 2020

AbstractThe dynamics of local cortical networks are irregular, but correlated. Dynamic excitatory– inhibitory balance is a plausible mechanism that generates such irregular activity, but it remains unclear how balance is achieved and maintained in plastic neural networks. In particular, it is not fully understood how plasticity induced changes in the network affect balance, and in turn, how correlated, balanced activity impacts learning. How does the dynamics of balanced networks change under different plasticity rules? How does correlated spiking activity in recurrent networks change the evolution of weights, their eventual magnitude, and structure across the network? To address these questions, we develop a general theory of plasticity in balanced networks. We show that balance can be attained and maintained under plasticity induced weight changes. We find that correlations in the input mildly, but significantly affect the evolution of synaptic weights. Under certain plasticity rules, we find an emergence of correlations between firing rates and synaptic weights. Under these rules, synaptic weights converge to a stable manifold in weight space with their final configuration dependent on the initial state of the network. Lastly, we show that our framework can also describe the dynamics of plastic balanced networks when subsets of neurons receive targeted optogenetic input.
Parkinson Disease-Linked Parkin Mediates Redox Reactions That Lower Oxidative Stress In Mammalian Brain
Authors: El Kodsi Daniel N. , Tokarew Jacqueline M. , Sengupta Rajib , Lengacher Nathalie A. , Ng Andy C. , Boston Heather , Jiang Qiubo , Palmberg Carina , Pileggi Chantal , Shutinoski Bojan , Li Juan , Nguyen Angela P. , Fehr Travis K. , Im Doo Soon , Callaghan Steve , Park David S. , LaVoie Matthew J. , Chan Jennifer A. , Takanashi Masashi , Hattori Nobutaka , Ratan Rajiv R. , Zecca Luigi , Puente Lawrence , Shaw Gary S. , Harper Mary-Ellen , Holmgren Arne , Tomlinson Julianna J. , Schlossmacher Michael G. 
Published: April 2020

SUMMARYWe recently hypothesized that parkin plays a role in redox homeostasis and provided evidence that it directly reduces hydrogen peroxide (H2O2)in vitro. Here, we examined this anti-oxidant activityin vivo. Informed by findings in human brain, we demonstrate that elevated oxidative stress promotes parkin insolubility in mice. In normal mouse brain parkin was partially oxidized,e.g., at cysteines 195 and 252, which was augmented by oxidative stress. Although under basal conditions H2O2levels were unchanged in adultprkn-/-brain, a parkin-dependent reduction of cytosolic H2O2was observed when mitochondria were impaired, either due to neurotoxicant exposure (MPTP) orSod2haploinsufficiency. In accordance, markers of oxidative stress,e.g., protein carbonylation and nitrotyrosination, were elevated in the cytosol but not in mitochondria fromprkn-/-mice. Nevertheless, this rise in oxidative stress led to changes in mitochondrial enzyme activities and the metabolism of glutathione in cells and mammalian brain. In parkin’s absence reduced glutathione concentrations were increased including in human cortex. This compensation was not due to new glutathione synthesis but attributed to elevated oxidized glutathione (GSSG)-reductase activity. Moreover, we discovered that parkin also recycled GSSG to its reduced form. With this reaction, parkin became S-glutathionylated,e.g., at cysteines 59 and human-specific 95. This oxidative modification was reversed by glutaredoxin. Our results demonstrate that cytosolic parkin mediates anti-oxidant reactions including H2O2reduction and glutathione regeneration. These reducing activities lead to a range of oxidative modifications in parkin itself. In parkin-deficient brain oxidative stress rises despite changes to maintain redox balance.