bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nontraumatic Acute Hyperextension Myelopathy Associated With Weightlifting
Authors: Cipriano Kevin , Mansfield J. Taylor , Batal Hannie , Gosai Erika 
Published: October 2020

Abstract
We describe the clinical course of a 56-yr-old woman without a significant medical history presenting with nontraumatic paraplegia found to have an infarction of the conus medullaris after intensive lumbar hyperextension exercises. This condition, known as surfer’s myelopathy, has been described in multiple case reports that attributed a similar mechanism and presentation. We present a case of surfer’s myelopathy associated with weightlifting, which has not been previously reported. We conclude that this diagnosis should be considered in patients who present after spine hyperextension activity with nontraumatic paraplegia. Furthermore, we support the nomenclature change to “acute hyperextension myelopathy,” better reflecting the underlying pathophysiology.
Tuberculosis symptom screening for children and adolescents living with HIV in six high HIV/TB burden countries in Africa
Authors: Vonasek Bryan , Kay Alexander , Devezin Tara , Bacha Jason M. , Kazembe Peter , Dhillon Dilsher , Dlamini Sandile , Haq Heather , Thahane Lineo , Simon Katie , Matshaba Mogomotsi , Sanders Jill , Minde Mercy , Wanless Sebastian , Nyasulu Phoebe , Mandalakas Anna 
Published: October 2020

Objectives:
The WHO recommends that children and adolescents living with HIV (CALHIV) complete TB symptom screening at every clinical encounter but evidence supporting this recommendation is limited. We evaluated the performance of the recommended TB symptom screening in six high-burden TB/HIV countries.

Design:
Retrospective longitudinal cohort.

Methods:
We extracted data from electronic medical records of CALHIV receiving care from clinics in Botswana, Eswatini, Lesotho, Malawi, Tanzania, and Uganda from January 2014 to June 2017. We defined incident TB cases as those prescribed TB treatment within 30 days of TB diagnosis. We analyzed the most recent symptom screen preceding a TB diagnosis. In accordance with WHO guidelines, positive screens were defined as current fever, cough, poor weight gain, or recent TB contact. Odds of TB disease was modeled by screen result and age at which screening was conducted.

Results:
Twenty thousand seven hundred and six patients collectively had 316 740 clinic visits, of which 240 161 (75.8%) had documented TB symptom screens. There were 35 701 (14.9%) positive TB symptom screens, and 1212 incident TB diagnoses. Sensitivity and specificity of the TB symptom screen to diagnose TB were 61.2% (95% CI 58.4--64.0) and 88.8% (95% CI 88.7--88.9), respectively. Log odds of documented TB for positive or negative screens was statistically different only for screens conducted at ages 7--17.

Conclusion:
Although specificity was high, the sensitivity of the TB symptom screen to detect TB in CALHIV was low. More accurate screening approaches are needed to optimally identify TB disease in CALHIV.
Financial incentives to increase pediatric HIV testing: a randomized trial
Authors: Njuguna Irene N. , Wagner Anjuli D. , Neary Jillian , Omondi Vincent O. , Otieno Verlinda A. , Orimba Anita , Mugo Cyrus , Babigumira Joseph B. , Levin Carol , Richardson Barbra A. , Maleche-Obimbo Elizabeth , Wamalwa Dalton C. , John-Stewart Grace , Slyker Jennifer 
Published: October 2020

Background:
Financial incentives can motivate desirable health behaviors, including adult HIV testing. Data regarding the effectiveness of financial incentives for HIV testing in children, who require urgent testing to prevent mortality, are lacking.

Methods:
In a five-arm unblinded randomized controlled trial, adults living with HIV attending 19 HIV clinics in Western Kenya, with children 0–12 years of unknown HIV status, were randomized with equal allocation to $0, $1.25, $2.50, $5 or $10. Payment was conditional on child HIV testing within 2 months. Block randomization with fixed block sizes was used; participants and study staff were unblinded at randomization. Primary analysis was intent-to-treat, with predefined primary outcomes of completing child HIV testing and time to testing.

Results:
Of 452 caregivers, 90, 89, 93, 92 and 88 were randomized to $0, $1.25, $2.50, $5.00, and $10.00, respectively. Of those, 31 (34%), 31 (35%), 44 (47%), 51 (55%), and 54 (61%) in the $0, $1.25, $2.50, $5.00, and $10.00 arms, respectively, completed child testing. Compared with the $0 arm, and adjusted for site, caregivers in the $10.00 arm had significantly higher uptake of testing [relative risk: 1.80 (95% CI 1.15--2.80), P = 0.010]. Compared with the $0 arm, and adjusted for site, time to testing was significantly faster in the $5.00 and $10.00 arms [hazard ratio: 1.95 (95% CI 1.24--3.07) P = 0.004, 2.42 (95% CI 1.55--3.79), P < 0.001, respectively).

Conclusion:
Financial incentives are effective in improving pediatric HIV testing among caregivers living with HIV.

Registration:
NCT03049917.
Estimating epidemiologic dynamics from cross-sectional viral load distributions
Authors: Hay James A. , Kennedy-Shaffer Lee , Kanjilal Sanjat , Lennon Niall J. , Gabriel Stacey B. , Lipsitch Marc , Mina Michael J. 
Published: October 2020

AbstractEstimating an epidemic’s trajectory is crucial for developing public health responses to infectious diseases, but incidence data used for such estimation are confounded by variable testing practices. We show instead that the population distribution of viral loads observed under random or symptom-based surveillance, in the form of cycle threshold (Ct) values, changes during an epidemic and that Ct values from even limited numbers of random samples can provide improved estimates of an epidemic’s trajectory. Combining multiple such samples and the fraction positive improves the precision and robustness of such estimation. We apply our methods to Ct values from surveillance conducted during the SARS-CoV-2 pandemic in a variety of settings and demonstrate new approaches for real-time estimates of epidemic trajectories for outbreak management and response.
An epigenetic proxy of chronic inflammation outperforms serum levels as a biomarker of brain ageing
Authors: Conole Eleanor L.S. , Stevenson Anna J. , Green Claire , Harris Sarah E. , Maniega Susana Muñoz , Valdés-Hernández María del. C , Harris Mathew A. , Bastin Mark E. , Wardlaw Joanna M. , Deary Ian J. , Miron Veronique E. , Whalley Heather C. , Marioni Riccardo E. , Cox Simon R. 
Published: October 2020

AbstractLow-level chronic inflammation increases with age and is associated with cognitive decline. DNA methylation (DNAm) levels may provide more stable reflections of cumulative inflammatory burden than traditional serum approaches. Using structural and diffusion MRI data from 521 individuals aged 73, we demonstrate that a DNAm proxy of C-Reactive Protein (CRP) shows significantly (on average 6.4-fold) stronger associations with brain structural outcomes than serum CRP. We additionally find that DNAm CRP has an inverse association with global and domain-specific (speed, visuospatial and memory) cognitive functioning, and that brain structure partially mediates this CRP-cognitive association (up to 29.4%), dependent on lifestyle and health factors. These data support the hypothesis that chronic systemic inflammation may contribute to neurodegenerative brain changes which underlie differences in cognitive ability in later life. DNA methylation-based predictors could be used as proxies for chronic inflammatory status.
Estimating the Burden of COVID-19 Symptoms Among Participants at the 2020 USA Curling Club Nationals Tournament
Authors: Luethy Paul M. 
Published: October 2020

AbstractThe COVID-19 pandemic has been a significant cause of global morbidity and mortality, with evidence suggesting that activities involving heavier breathing, such as singing and exercise, can result in increased risk for disease transmission. The USA Curling Club Nationals is a week-long curling tournament to determine the men’s and women’s club-level champions. The 2020 tournament took place March 7-14 at the Potomac Curling Club in Laurel, MD, and featured teams from across the United States. Preventative measures, such as increased cleaning and disinfection of surfaces, single use and disposable food containers, and canceling traditional event banquets were implemented. Despite these measures, players, coaches, officials, volunteers, and spectators contracted the virus as a result of participation in the event. We surveyed participants to assess total positivity, potential days of transmission, and the burden of symptoms experienced among the participants. We found that 55.6% of all participants reported experiencing symptoms consistent with COVID-19, with nearly all experiencing more than one symptom. Although most participants’ symptoms resolved quickly, 9.6% of all participants experienced symptoms for at least one month and 12.6% of all participants reported taking at least 30 days before they felt they had returned to normal. As a result of this study, we believe curling tournaments have the potential to be high-risk events for the transmission of COVID-19. Further infection prevention measures that were not yet publicly implemented at the time of this tournament may be an effective method of lowering transmission risk, although further research is required.
Gargle-Direct: Extraction-Free Detection of SARS-CoV-2 using Real-time PCR (RT-qPCR) of Saline Gargle Rinse Samples
Authors: Gadkar Vijay J. , Goldfarb David M. , Young Virginia , Watson Nicole , Hoang Linda , Lee Tracy , Prystajecky Natalie , Al-Rawahi Ghada N. , Srigley Jocelyn A , Tilley Peter 
Published: October 2020

ABSTRACTBackgroundSaline mouth rinse/gargle samples have recently been shown to be a suitable option for swab-independent self-collection for SARS-CoV-2 diagnosis. We sought to evaluate a simplified process for direct reverse transcriptase PCR (RT-qPCR) testing of this novel sample type and to compare performance with routine RT-qPCR using automated nucleic acid extraction.MethodsClinical saline mouth rinse/gargle samples were subjected to automated nucleic acid extraction (“standard method”), followed by RT-qPCR using three assays including the FDA authorized US-CDC’s N1/N2 assay, which was the reference standard for determining sensitivity/specificity. For extraction-free workflow, an aliquot of each gargle sample underwent viral heat inactivation at 65 °C for 20 minutes followed by RT-qPCR testing, without an intermediate extraction step. An in-house validated RT-qPCR lab developed test (LDT), targeting the SARS-CoV-2’s S/ORF8 genes (SORP triplex assay) and the N1/N2 US-CDC assay was used to evaluate the extraction-free protocol. To improve the analytical sensitivity, we developed a single-tube hemi-nested (STHN) version of the SORP triplex assay.ResultsA total of 38 SARS-CoV-2 positive and 75 negative saline mouth rinse/gargle samples were included in this evaluation. A 100% concordance in detection rate was obtained between the standard method and the extraction-free approach for the SORP assay. An average increase of +2.63 to +5.74 of the cycle threshold (CT) values was observed for both the SORP and N1/N2 assay when extraction-free was compared between the standard method. The average ΔCT [ΔCT=CT(Direct PCR)-CT(Extracted RNA)], for each of the gene targets were: S (ΔCT= +4.24), ORF8 (ΔCT=+2.63), N1 (ΔCT=+2.74) and N2 (ΔCT=+5.74). The ΔCT for the STHN SORP assay was +1.51 and −2.05 for the S and ORF8 targets respectively, when extracted method was compared to the standard method.ConclusionOur Gargle-Direct SARS-CoV-2 method is operationally simple, minimizes pre-analytical sample processing and is potentially implementable by most molecular diagnostic laboratories. The empirical demonstration of single-tube hemi-nested RT-qPCR, to specifically address and alleviate the widely-acknowledged problem of reduced analytical sensitivity of detection of extraction-free templates, should help diagnostic laboratories in choosing Gargle-Direct protocol for high-throughput testing.
Two modes of inhibitory neuronal shutdown distinctly amplify seizures in humans
Authors: Ahmed Omar J. , John Tibin T. , Sudhakar Shyam K. , Brennan Ellen K.W. , Gonzalez Alcides Lorenzo , Naftulin Jason S. , Eskandar Emad , Madsen Joseph R. , Cosgrove G. Rees , Blum Andrew S. , Potter N. Stevenson , Mashour George A. , Hochberg Leigh R. , Cash Sydney S. 
Published: October 2020

ABSTRACTInhibitory neurons are critical for normal brain function but dysregulated in disorders such as epilepsy. At least two theories exist for how inhibition may acutely decrease during a seizure: hyperpolarization of fast-spiking (FS) inhibitory neurons by other inhibitory neurons, or depolarization block (DB) of FS neurons resulting in an inability to fire action potentials. Firing rate alone is unable to disambiguate these alternatives. Here, we show that human FS neurons can stop firing due to both hyperpolarization and DB within the same seizure. However, only DB of FS cells is associated with dramatic increases in local seizure amplitude, unobstructed traveling waves, and transient increases in excitatory neuronal firing. This result is independent of seizure etiology or focus. Computational models of DB reproduce thein vivohuman biophysics. These methods enable intracellular decoding using only extracellular recordings in humans and explain the otherwise ambiguous inhibitory neuronal control of human seizures.
Heme induces mRNA expression and activation of tissue factor by TLR4 dependent mechanisms
Authors: Hounkpe B.W. , Moraes C.R.P. , do Santos M.N.N. , Costa F. F. , De Paula E.V. 
Published: October 2020

AbstractIntroductionHemolytic diseases such as Sickle Cell Disease (SCD) are characterized by a natural propensity for both arterial and venous thrombosis. Evidence showing that heme can induce tissue factor (TF) expression in endothelial cells and TF-dependent coagulation activation in animal models of SCD suggest that heme can contribute to hypercoagulability in this condition. We recently demonstrated that heme can induce coagulation activation in whole blood of healthy volunteers in a TF-dependent fashion.MethodsHerein, we aimed to evaluate whether this heme-induced coagulation activity was dependent on the expression and/or activation of hematopoietic TF in human mononuclear cells. TF mRNA expression was evaluated by qPCR and TF procoagulant activity was evaluated using a 2-stage assay based on the generation of FXa.ResultsHeme was capable of inducing TF expression and activation in a TLR4-dependent pathway. This activity was further amplified after TNF-α-priming.ConclusionOur results provide additional evidences on the mechanisms by which heme is involved in the pathogenesis of hypercoagulability in hemolytic diseases.
Estimating COVID-19 cases and outbreaks on-stream through phone-calls
Authors: Alvarez Ezequiel , Obando Daniela , Crespo Sebastian , Garcia Enio , Kreplak Nicolas , Marsico Franco 
Published: October 2020

AbstractOne of the main problems in controlling COVID-19 epidemic spread is the delay in confirming cases. Having information on changes in the epidemic evolution or outbreaks rise before lab-confirmation is crucial in decision making for Public Health policies. We present an algorithm to estimate on-stream the number of COVID-19 cases using the data from telephone calls to a COVID-line. By modeling the calls as background (proportional to population) plus signal (proportional to infected), we fit the calls in Province of Buenos Aires (Argentina) with coefficient of determination R2 > 0.85. This result allows us to estimate the number of cases given the number of calls from a specific district, days before the lab results are available. We validate the algorithm with real data. We show how to use the algorithm to track on-stream the epidemic, and present the Early Outbreak Alarm to detect outbreaks in advance to lab results. One key point in the developed algorithm is a detailed track of the uncertainties in the estimations, since the alarm uses the significance of the observables as a main indicator to detect an anomaly. We present the details of the explicit example in Villa Azul (Quilmes) where this tool resulted crucial to control an outbreak on time. The presented tools have been designed in urgency with the available data at the time of the development, and therefore have their limitations which we describe and discuss. We consider possible improvements on the tools, many of which are currently under development.
Extracorporeal Blood Purification in moderate and severe COVID-19 patients: a prospective cohort study
Authors: Rosalia Rodney Alexander , Ugurov Petar , Neziri Dashurie , Despotovska Simona , Kostoska Emilja , Veljanovska-Kiridjievska Lidija , Kuzmanov Dimche , Trifunovski Aleksandar , Villa Gianluca , Popevski Dijana , Mitrev Zan 
Published: October 2020

AbstractIntroductionCOVID-19 is characterised by hyperinflammation and coagulopathy. Severe cases often develop respiratory distress, requiring mechanical ventilation and critical cases progressing to ARDS. Control of hyperinflammation has been proposed as a possible therapeutic avenue for COVID-19; extracorporeal blood purification (EBP) modalities offer an attractive mean to ameliorate maladaptive inflammation.With this work, we describe the longitudinal variation of parameters of systemic inflammation in critically ill COVID-19 patients treated with blood purification using AN69ST (oXiris®) hemodiafilter.MethodsWe performed a time-series analysis of 44 consecutive COVID-19 cases treated with the AN69ST (oXiris®) cytokine adsorbing hemodiafilter; we visualise longitudinal results of biochemical, inflammatory, blood gas- and vital sign parameters.ResultsBlood purification was indicated for suspected hyperinflammation or hypercoagulation, (= CRP ≥ 100 mg/L and/or IL-6 ≥ 40 pg/mL and/or Ferritin ≥ 500 ng/mL and/or Lactate Dehydrogenase > 365 U/L or D-dimers > 2000 ng/mL). All patients were treated with ≥ 1 cycle extracorporeal continuous venovenous hemofiltration (CVVHF) with cytokine adsorbing hemodiafilter (CAH); of these, 30 severe patients received CVVHF-CAH within 4 – 12 hours of hospitalisation. Another 14 patients admitted with mild-to-moderate symptoms progressed to severe disease and placed on EBP during the course of hospitalisation. The treatment was associated with a reduction of Ferritin, C-reactive protein, Fibrinogen, several inflammatory markers and a resolution of numerous cytopenias. The observed mortality across the cohort was 36.3% across the cohort.ConclusionExtracorporeal blood purification with cytokine adsorbing hemofilter was associated with a decrease in the acute phase proteins CRP, Ferritin, and resolution of numerous cytopenias. Repetitive hemofiltration has been associated with lower levels of IL-6 in COVID-19 patients.
Predicting mortality of individual COVID-19 patients: A multicenter Dutch cohort
Authors: Ottenhoff Maarten C. , Ramos Lucas L. , Potters Wouter , Janssen Marcus L.F. , Hubers Deborah , Piña-Fuentes Dan , Thomas Rajat , van der Horst Iwan C.C. , Herff Christian , Kubben Pieter , Elbers Paul W.G. , Marquering Henk A. , Welling Max , Hu Shi , Simsek Suat , de Kruif Martijn D. , Dormans Tom , Fleuren Lucas M. , Schinkel Michiel , Noordzij Peter G. , van den Bergh Joop P. , Wyers Caroline E. , Buis David T. B. , Wiersinga Joost , van den Hout Ella H.C. , Reidinga Auke C. , Rusch Daisy , Sigaloff Kim C.E. , Douma Renée , de Haan Lianne , Fridgeirsson Egill A. , van den Oever Niels C. Gritters , Rennenberg Roger J.M.W. , van Wingen Guido A. , Aries Marcel J.H. , Beudel Martijn 
Published: October 2020

ABSTRACTObjectiveDevelop and validate models that predict mortality of SARS-CoV-2 infected patients admitted to the hospital.DesignRetrospective cohort studySettingA multicenter cohort across ten Dutch hospitals including patients from February 27 to June 8 2020.ParticipantsSARS-CoV-2 positive patients (age ≥ 18) admitted to the hospital.Main Outcome Measures21-day mortality evaluated by the area under the receiver operatory curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value. The predictive value of age was explored by comparison with age-based rules used in practice and by excluding age from analysis.Results2273 patients were included, of whom 516 had died or discharged to palliative care within 21 days after admission. Five feature sets, including premorbid, clinical presentation and laboratory & radiology values, were derived from 80 features. Additionally, an ANOVA-based data-driven feature selection selected the ten features with the highest F-values: age, number of home medications, urea nitrogen, lactate dehydrogenase, albumin, oxygen saturation (%), oxygen saturation is measured on room air, oxygen saturation is measured on oxygen therapy, blood gas pH and history of chronic cardiac disease. A linear logistic regression (LR) and non-linear tree-based gradient boosting (XGB) algorithm fitted the data with an AUC of 0.81 (95% confidence interval 0.77 to 0.85) and 0.82 (0.79 to 0.85), respectively, using the ten selected features. Both models outperformed age-based decision rules used in practice (AUC of 0.69, 0.65 to 0.74 for age > 70). Furthermore, performance remained stable when excluding age as predictor (AUC of 0.78, 0.75 to 0.81)ConclusionBoth models showed excellent performance and had better test characteristics than age-based decision rules, using ten admission features readily available in Dutch hospitals. The models hold promise to aid decision making during a hospital bed shortage.
Adaptive translational pausing is a hallmark of the cellular response to severe environmental stress
Authors: Jobava Raul , Mao Yuanhui , Guan Bo-Jhih , Krokowski Dawid , Shu Erica , Hu Di , Chukwurah Evelyn , Wu Jing , Gao Zhaofeng , Zagore Leah L. , Merrick William C. , Zhang Youwei , Qi Xin , Jankowsky Eckhard , Topisirovic Ivan , Licatalosi Donny D. , Qian Shu-Bing , Hatzoglou Maria 
Published: October 2020

SummaryMammalian cells have to adapt to environmental challenges that range from mild to severe stress. While the cellular response to mild stress has been widely studied, how cells respond to severe stress remains unclear. We show here that under severe stress conditions, cells induce a transient hibernation-like mechanism that anticipates recovery. We demonstrate that thisAdaptivePausingResponse (APR) is a coordinated cellular response that limits ATP supply and consumption though mitochondrial fragmentation and widespread pausing of mRNA translation. This pausing is accomplished by ribosome stalling at translation initiation codons, which keeps mRNAs poised to resume translation upon recovery from severe stress. We further show that recovery from severe stress involves adaptive ISR (Integrated Stress Response) signaling that in turn permits cell cycle progression, resumption of growth, and reversal of mitochondria fragmentation. Our findings indicate that cells can respond to severe stress through the APR, a mechanism that preserves vital elements of cellular function under harsh environmental conditions.
SARS-CoV-2 infects carotid arteries: implications for vascular disease and organ injury in COVID-19
Authors: Pfefferle Susanne , Günther Thomas , Puelles Victor G. , Heinrich Fabian , Nörz Dominik , Czech-Sioli Manja , Carsten Alexander , Krasemann Susanne , Wong Milagros N. , Oestereich Lisa , Magnus Tim , Allweiss Lena , Edler Carolin , Schröder Ann Sophie , Dandri Maura , Huber Tobias B. , Glatzel Markus , Püschel Klaus , Grundhoff Adam , Lütgehetmann Marc , Aepfelbacher Martin , Fischer Nicole 
Published: October 2020

AbstractStroke and central nervous system dysfunction are cardinal symptoms in critically ill corona virus disease 19 (COVID-19) patients. In an autopsy series of 32 COVID-19 patients, we investigated whether carotid arteries were infected with SARS-CoV-2 by employing genomic, virologic, histochemical and transcriptomic analyses. We show that SARS-CoV-2 productively infects and modulates vascular responses in carotid arteries. This finding has far reaching implications for the understanding and clinical treatment of COVID-19.