bluuebunny/crossref_metadata_2025 huggingface dataset:
Ga-68 DOTATATE PET/CT and F-18 FDG PET/CT in the evaluation of low and intermediate versus high-grade neuroendocrine tumors
Authors: You Helena , Kandathil Asha , Beg Muhammad , De Blanche Lorraine , Kazmi Syed , Subramaniam Rathan M.
Published: July 2020

Objective

We investigated the role of Ga-68 DOTATATE PET/CT in comparison to F-18 FDG PET/CT in patients with low and intermediate versus high-grade neuroendocrine tumors (NETs).

Methods

We identified 81 patients who underwent Ga-68 DOTATATE PET/CT at our institution between May 2017 and December 2018 and met inclusion criteria of biopsy-proven NET with known Ki-67 index, histologic grade, or differentiation. Patients were divided into two groups. Control group included Ki-67 ≤20%, grade 1 or 2, or well-differentiated tumors. Experimental group included Ki-67 >20%, grade 3, or poorly-differentiated tumors.

Results

Mean age was 57 years, with 36 males and 45 females. Most common primary sites were small bowel, pancreas, and lung. Most common distant metastatic sites were liver and bone. In the control group (n = 67), median Ki-67 was 4% (range 1–30%). 55/67 (82.1%) DOTATATE and 6/11 (54.5%) FDG scans were positive (P = 0.04). Positive scans showed >10 lesions in 25/55 (45.5%) DOTATATE and 1/6 (16.7%) FDG scans (P = 0.18). 40/55 (72.7%) positive DOTATATE and 3/6 (50%) FDG scans showed distant disease (P = 0.25). In the experimental group (n = 14), median Ki-67 was 68% (range 25–95%). All 14 DOTATATE and all nine FDG scans were positive. Positive scans showed >10 lesions in 4/14 (28.6%) DOTATATE and 5/9 (55.6%) FDG scans (P = 0.20). 10/14 (71.4%) positive DOTATATE and 7/9 (77.8%) FDG scans showed distant disease (P = 0.74).

Conclusion

All patients with high grade, poorly-differentiated NETs had positive DOTATATE PET/CTs. In these patients, DOTATATE PET/CT did not significantly differ from FDG PET/CT in identifying >10 lesions or distant disease.
Role of 18F-FDG PET-derived parameters for predicting complete response to chemoradiotherapy in squamous cell anal carcinoma
Authors: Filippi Luca , Fontana Antonella , Spinelli Gian Paolo , Rossi Lugi , Bagni Oreste
Published: July 2020

Purpose

We aimed to evaluate the accuracy of metabolic parameters, calculated on pretreatment positron emission computed tomography (PET/CT) with 18fluorodeoxyglucose (18F-FDG), for predicting complete response to chemoradiotherapy (CRT) of patients affected by squamous cell anal carcinoma (SCAC).

Patients and methods

Clinical records of 20 patients affected by SCAC and treated with CRT were retrospectively evaluated. 18F-FDG PET/CT was performed at time 0 (baseline) and time 1 (12 weeks after CRT). The following parameters were extracted from PET at time 0: standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Response was assessed according to PET response criteria in solid tumors and classified as complete metabolic response (CMR), partial metabolic response (PMR) and progressive metabolic disease (PMD). Receiver operating characteristic analysis was performed to analyze the predictive value of each PET-derived parameter on CMR.

Results

Sixteen patients were finally enrolled. All presented increased 18F-FDG uptake in the primary tumor and 11 (68.7%) also showed metastatic lymph nodes. At PET/CT performed at time 1, 11 subjects (68.7%) presented CMR, three (18.7%) had PMR and the remaining two (12.5%) showed PMD (i.e. hepatic metastases). Among baseline PET-derived parameters, both MTV and TLG efficiently predicted response to CRT with an area under the curve of 0.9 (cutoff 62.3 cm3, sensitivity 80%, specificity 100%, P = <0.0001) and 0.87 (cutoff 654.1 g, sensitivity 80%, specificity 100%, P = 0.004), respectively.

Conclusion

Among PET-derived parameters, both MTV and TLG presented a high predictive value on subjects’ outcome after CRT.
The Professional Case Manager and Social Justice, Inclusion, and Equity: A Time for Reflection and Action
Authors: Tahan Hussein M.
Published: July 2020

Social justice, inclusion and equity are everyone's responsibility. We achieve these values when we recognize and accept the characteristics of every person as a unique individual. Professional case managers, or other healthcare practitioners and leaders, have an obligation to advance the health, human and social outcomes of the people they serve, regardless of the social group they belong to and irrespective of their determinants of diversity. It is time to address social justice, inclusion and equity as ethical principles of practice for the professional case manager.
Hemorrhagic Pseudocyst
Authors: Hu Mindy Bizhe , Kesha Kilak , Glenn Charley , Stables Simon , Tse Rexson
Published: July 2020

Mass lesions in the brain encompass a wide range neoplastic and nonneoplastic entities. These can present as a diagnostic pitfall, with nonspecific, overlapping symptoms and similar appearances on radiology. They may cause death through varied mechanisms, either specific to the underlying pathophysiology or due to the space-occupying effect of the lesion. We report a case of fatal hemorrhagic cerebral pseudocyst, a rare mass lesion, associated with a cerebral varix, causing death in a morbidly obese individual. To the best of our knowledge, there is no previous documentation in the postmortem literature of this entity as a cause of death. This case aims to document this rare entity in the differential diagnosis of a tumor-like lesion in the brain, highlight the clinical difficulty in its assessment, and demonstrate an uncommon mechanism of death, of a mass lesion acting as a focus causing seizures, with resulting hypoxia due to effects of morbid obesity and heart failure.
Utility of Body Habitus Parameters to Determine and Improve the Accuracy of the Broselow Tape
Authors: Saeed Wajeeha , Talathi Saurabh , Suneja Upma , Gupta Neha , Mandadi Akhila Reddy , Xu Hongyan , Leber Mark , Waseem Muhammad
Published: July 2020

Objectives

The aims of this study were to determine and improve accuracy of the Broselow Tape (BT) in estimating children's weight by adding body habitus parameters.

Methods

This cross-sectional study was conducted in an urban hospital pediatric clinic. Children up to 8 years old coming in for well-child visit were included. Children with acute illness or presence of any chronic condition potentially resulting in growth disturbance and out of BT height range were excluded. The following body habitus parameters were measured using the Centers for Disease Control and Prevention guidelines: actual weight, predicted weight using BT (BTW), mid-thigh circumference (MTC), body mass index, mid-arm circumference, and waist-to-hip ratio.

Results

A total of 301 children were enrolled. Of these, 151 were male (50%). Hispanics constituted 160 (53.2%). There was a positive linear association between BTW and actual weight in the overall cohort (adjusted R
2 = 0.9164, P < 0.001). However, there was a difference in this association among children younger than 2 years and children older than 2 years (adjusted R
2 = 0.89 vs 0.4841). Incorporating MTC and/or waist circumference along with BTW in the model increased the accuracy, providing a better estimate of actual weight (adjusted R
2 = 0.94, P < 0.001).

Conclusions

We conclude that there might be inaccuracies in the weight predicted by BT in our patient population, especially those weighing more than 15 kg and older than 2 years. Our study also demonstrates that MTC correlates closely with the actual weight and could be used in addition to BT for more accurate weight estimation.
The Utility of Donor-specific Antibody Monitoring and the Role of Kidney Biopsy in Simultaneous Liver and Kidney Recipients With De Novo Donor-specific Antibodies
Authors: Parajuli Sandesh , Aziz Fahad , Blazel Justin , Muth Brenda L. , Garg Neetika , Mohamed Maha , Rice John , Mezrich Joshua D. , Hidalgo Luis G. , Mandelbrot Didier
Published: July 2020

Background.

There is limited information about the utility of donor-specific antibody (DSA) against HLA monitoring and the role of protocol kidney biopsy for de novo DSA (dnDSA) in simultaneous liver and kidney (SLK) transplant recipients.

Methods.

We analyzed SLK transplant recipients transplanted between January 2005 and December 2017, who had DSA checked posttransplant. Patients were divided into 2 groups based on whether they developed dnDSA posttransplant (dnDSA+) or not (dnDSA−). Kidney graft rejection ±45 d of dnDSA and a kidney death–censored graft survival were the primary endpoints.

Results.

A total of 83 SLK transplant recipients fulfilled our selection criteria. Of those, 23 were dnDSA+ and 60 were dnDSA−. Twenty-two of 23 dnDSA+ patients had DSA against class II HLA, predominantly against DQ. Fifteen recipients underwent kidney biopsy ±45 d of dnDSA. Six of these were clinically indicated due to kidney graft dysfunction. The other 9 had a protocol kidney biopsy only due to dnDSA, and 6 of these 9 had a rejection. Also, 3 recipients had sequential biopsies of both the kidney and liver grafts. Among those with sequential biopsies of both grafts, there was a difference between the organs in the rate and types of rejections. At last follow up, dnDSA was not associated with graft failure of either the kidney or liver.

Conclusions.

Although our study was limited by a small sample size, it suggests the potential utility of DSA monitoring and protocol kidney biopsy for dnDSA.
Beading of injured axons driven by tension- and adhesion-regulated membrane shape instability
Authors: Shao Xueying , Sørensen Maja Højvang , Xia Xingyu , Fang Chao , Hui Tsz Hin , Chang Raymond Chuen Chung , Chu Zhiqin , Lin Yuan
Published: July 2020

The formation of multiple beads along an injured axon will lead to blockage of axonal transport and eventually neuron death, and this has been widely recognized as a hallmark of nervous system degeneration. Nevertheless, the underlying mechanisms remain poorly understood. Here, we report a combined experimental and theoretical study to reveal key factors governing axon beading. Specifically, by transecting well-developed axons with a sharp atomic force microscope probe, significant beading of the axons was triggered. We showed that adhesion was not required for beading to occur, although when present strong axon–substrate attachments seemed to set the locations for bead formation. In addition, the beading wavelength, representing the average distance between beads, was found to correlate with the size and cytoskeleton integrity of axon, with a thinner axon or a disrupted actin cytoskeleton both leading to a shorter beading wavelength. A model was also developed to explain these observations which suggest that axon beading originates from the shape instability of the membrane and is driven by the release of work done by axonal tension as well as the reduction of membrane surface energy. The beading wavelength predicted from this theory was in good agreement with our experiments under various conditions. By elucidating the essential physics behind axon beading, the current study could enhance our understanding of how axonal injury and neurodegeneration progress as well as provide insights for the development of possible treatment strategies.
Enhanced flight performance in non-uniformly flexible wings
Authors: Vincent Lionel , Zheng Min , Costello John H. , Kanso Eva
Published: July 2020

The flexibility of biological propulsors such as wings and fins is believed to contribute to the higher performance of flying and swimming animals compared with their engineered peers. Flexibility seems to follow a universal design rule that induces bending patterns at about one-third from the distal tip of the propulsor’s span. However, the aerodynamic mechanisms that shaped this convergent design and the potential improvement in performance are not well understood. Here, we analyse the effect of heterogeneous flexibility on the flight performance (range and descent angle) of passively tumbling wings. Using experiments, numerical simulations, and scaling analysis, we demonstrate that spanwise tip flexibility that follows this empirical rule leads to improved flight performance. Improvement in flight range seems to be related to flutter-induced drag reduction. This mechanism is independent of the wing’s auto-rotation and represents a more general trait of wings with non-uniform tip flexibility.
Do people imitate when making decisions? Evidence from a spatial Prisoner’s Dilemma experiment
Authors: Grujić Jelena , Lenaerts Tom
Published: July 2020

How do people decide which action to take? This question is best answered using Game Theory, which has proposed a series of decision-making mechanisms that people potentially use. In network simulations, wherein games are repeated and pay-off differences can be observed, those mechanisms often rely on imitation of successful behaviour. Surprisingly, little to no evidence has been provided about whether people actually imitate more successful opponents when altering their actions in that context. By comparing two experimental treatments wherein participants play the iterated Prisoner’s Dilemma game in a lattice, we aim to answer whether more successful actions are imitated. While in the first treatment, participants have the possibility to use pay-off differences in making their decision, the second treatment hinders such imitation as no information about the gains is provided. If imitation of the more successful plays a role then there should be a difference in how players switch from cooperation to defection between both treatments. Although, cooperation and pay-off levels do not appear to be significantly different between both treatments, detailed analysis shows that there are behavioural differences: when confronted with a more successful co-player, the focal player will imitate her behaviour as the switching is related to the experienced pay-off inequality.
C,N-codoped MoSi
2
ceramic with excellent heat resistance for microwaves absorption application
Authors: Yang Zhiqian , Xu Chang , Xia Yilu , Xiong Ziming
Published: July 2020

Microwave absorption (MA) materials with high heat resistance have a wide range of applications in many fields. In this work, a C,N-codoped MoSi
2
ceramic was prepared via a facile solid-phase reaction method and its MA properties was investigated. On the one hand, the results indicate that this ceramic possesses excellent heat resistance and the weight of the MoSi
2
is almost constant when the temperature is lower than 800°C. On the other hand, this ceramic shows good MA performance when the filler loading ratio increases to 30 vol%, the value of reflection loss (RL) could reach to −17.70 dB at 7.44 GHz with the thickness of 2.0 mm and the effective electromagnetic absorption bandwidth (RL below −10 dB) could reach to 1.88 GHz (9.28–11.16 GHz) with the thickness of 1.5 mm. Multi-polarization resonance loss is considered as the predominant attention mechanism on the MA performance of this MoSi
2
ceramic. This research provides a new idea for understanding resonance mechanism and greatly expands the application scope of MoSi
2
ceramic in MA area.
Synthesis and characterization of geminis and implications of their micellar solution on ninhydrin and metal amino acid complex
Authors: Kumar Dileep , Rub Malik Abdul , Asiri Abdullah M.
Published: July 2020

In our study, three gemini dicationic surfactants with different methylene group spacer (16-6-16, 16-5-16 and 16-4-16) have been synthesized and characterized in solution by
1
H NMR spectroscopic technique. The implications of gemini micellar solution on ninhydrin and metal amino acid complex ([Cu(II)-Trp]
+
) were performed by the means of single-beam UV–visible spectroscopy. The absorbance was noted at regular time intervals and values of rate constant (

k
ψ

) were determined by using a computer-based program. Synthesized surfactants proved as an efficient catalyst on the interaction of ninhydrin with metal amino acid complex as compared with conventional surfactant and aqueous systems. The required description regarding the implications of gemini dicationic surfactants are provided in the text in detail. The conductivity technique was applied in order to get critical micelle concentration (cmc) of geminis in the presence and absence of reactants. Catalytic results developed in gemini dicationic surfactant system were explained effectively by pseudo-phase model. Various thermodynamic quantities,
viz
., activation energy,
E
a
, activation enthalpy, Δ
H
#
, and activation entropy, Δ
S
#
, were obtained on interaction of ninhydrin with [Cu(II)-Trp]
+
in gemini systems by applying Eyring equation. A detailed explanation about these evaluated parameters was also made.
Fokas method for linear boundary value problems involving mixed spatial derivatives
Authors: Batal A. , Fokas A. S. , Özsarı T.
Published: July 2020

We obtain solution representation formulae for some linear initial boundary value problems posed on the half space that involve mixed spatial derivative terms via the unified transform method (UTM), also known as the Fokas method. We first implement the method on the second-order parabolic PDEs; in this case one can alternatively eliminate the mixed derivatives by a linear change of variables. Then, we employ the method to biharmonic problems, where it is not possible to eliminate the cross term via a linear change of variables. A basic ingredient of the UTM is the use of certain invariant maps. It is shown here that these maps are well defined provided that certain analyticity issues are appropriately addressed.
Acoustic and inertial modes in planetary-like rotating ellipsoids
Authors: Vidal Jérémie , Cébron David
Published: July 2020

The bounded oscillations of rotating fluid-filled ellipsoids can provide physical insight into the flow dynamics of deformed planetary interiors. The inertial modes, sustained by the Coriolis force, are ubiquitous in rapidly rotating fluids and Vantieghem (2014,
Proc. R. Soc. A
,
470
, 20140093.
doi:10.1098/rspa.2014.0093
) pioneered a method to compute them in incompressible fluid ellipsoids. Yet, taking density (and pressure) variations into account is required for accurate planetary applications, which has hitherto been largely overlooked in ellipsoidal models. To go beyond the incompressible theory, we present a Galerkin method in rigid coreless ellipsoids, based on a global polynomial description. We apply the method to investigate the normal modes of fully compressible, rotating and diffusionless fluids. We consider an idealized model, which fairly reproduces the density variations in the Earth’s liquid core and Jupiter-like gaseous planets. We successfully benchmark the results against standard finite-element computations. Notably, we find that the quasi-geostrophic inertial modes can be significantly modified by compressibility, even in moderately compressible interiors. Finally, we discuss the use of the normal modes to build reduced dynamical models of planetary flows.
Multiple Rayleigh waves guided by the planar surface of a continuously twisted structurally chiral material
Authors: Mackay Tom G. , Lakhtakia Akhlesh
Published: July 2020

The Stroh formalism was adapted for Rayleigh-wave propagation guided by the planar traction-free surface of a continuously twisted structurally chiral material (CTSCM), which is an anisotropic solid that is periodically non-homogeneous in the direction normal to the planar surface. Numerical studies reveal that this surface can support either one or two Rayleigh waves at a fixed frequency, depending on the structural period and orientation of the CTSCM. In the case of two Rayleigh waves, each wave possesses a different wavenumber. The Rayleigh wave with the larger wavenumber is more localized to the surface and has a phase speed that changes less as the angular frequency varies in comparison with the Rayleigh wave with the smaller wavenumber.
Recombinant subtype A and B human respiratory syncytial virus clinical isolates co-infect the respiratory tract of cotton rats
Authors: Rennick Linda J. , Nambulli Sham , Lemon Ken , Olinger Grace Y. , Crossland Nicholas A. , Millar Emma L. , Duprex W. Paul
Published: July 2020

Human respiratory syncytial virus (HRSV) is an important respiratory pathogen causing a spectrum of illness, from common cold-like symptoms, to bronchiolitis and pneumonia requiring hospitalization in infants, the immunocompromised and the elderly. HRSV exists as two antigenic subtypes, A and B, which typically cycle biannually in separate seasons. There are many unresolved questions in HRSV biology regarding the interactions and interplay of the two subtypes. Therefore, we generated a reverse genetics system for a subtype A HRSV from the 2011 season (A11) to complement our existing subtype B reverse genetics system. We obtained the sequence (HRSVA11) directly from an unpassaged clinical sample and generated the recombinant (r) HRSVA11. A version of the virus expressing enhanced green fluorescent protein (EGFP) from an additional transcription unit in the fifth (5) position of the genome, rHRSVA11EGFP(5), was also generated. rHRSVA11 and rHRSVA11EGFP(5) grew comparably in cell culture. To facilitate animal co-infection studies, we derivatized our subtype B clinical isolate using reverse genetics toexpress the red fluorescent protein (dTom)-expressing rHRSVB05dTom(5). These viruses were then used to study simultaneous in vivo co-infection of the respiratory tract. Following intranasal infection, both rHRSVA11EGFP(5) and rHRSVB05dTom(5) infected cotton rats targeting the same cell populations and demonstrating that co-infection occurs in vivo. The implications of this finding on viral evolution are important since it shows that inter-subtype cooperativity and/or competition is feasible in vivo during the natural course of the infection.
Contact tracing during Phase I of the COVID-19 pandemic in the Province of Trento, Italy: key findings and recommendations
Authors: Fateh-Moghadam Pirous , Battisti Laura , Molinaro Silvia , Fontanari Steno , Dallago Gabriele , Binkin Nancy , Zuccali Mariagrazia
Published: July 2020

Introduction

Contact tracing is a key pillar of COVID-19 control. In response to the COVID-19 epidemic in the Autonomous Province of Trento (Italy) a software was developed to standardize data collection and facilitate surveillance of contacts and outbreaks and map the links between bases and contacts. In this paper, we present the results of contact tracing efforts during Phase I of the epidemic (March-April, 2020, mostly under lockdown), including sociodemographic characteristics of contacts who became cases and of the cases who infected one or more contact.

Methods

A contact tracing website was developed that included components for geolocation and linking of cases and contacts using open source software. Information on community-based confirmed and probable cases and their contacts was centralized on the website. Information on cases came directly from the central case database, information on contacts was collected by telephone interviews following a standard questionnaire. Contacts were followed via telephone, emails, or an app.

Results

The 2,812 laboratory-diagnosed community cases of COVID-19 had 6,690 community contacts, of whom 890 (13.3%) developed symptoms. Risk of developing symptomatic disease increased with age and was higher in workplace contacts than cohabitants or non-cohabiting family or friends. The greatest risk of transmission to contacts was found for the 14 cases <15 years of age (22.4%); 8 of the 14, who ranged in age from <1 to 11 years) infected 11 of 49 contacts. Overall, 606 outbreaks were identified, 74% of which consisted of only two cases.

Discussion

The open-source software program permitted the centralized tracking of contacts and rapid identification of links between cases. Workplace contacts were at higher risk of developing symptoms. Although childhood contacts were less likely to become cases, children were more likely to infect household members, perhaps because of the difficulty of successfully isolating children in household settings.
SARS-CoV-2 Infection and Stroke: Coincident or Causal?
Authors: Walker Melanie , Young Christopher C. , Sharma Malveeka , Levitt Michael R. , Tirschwell David L. ,   the WWAMI Stroke Investigators
Published: July 2020

Neurological manifestations of SARS-CoV-2 infection described in isolated case reports and single institutions do not accurately reflect the clinical spectrum of disease across all geographies in a global pandemic. Data collected during peak of the Covid-19 pandemic from stroke centers in five states reveal few similarities to what has recently been published. Given the diversity in phenotype, we caution policymakers and health care providers when considering cerebrovascular complications from SARS-CoV-2 infection.
Blood Pressure and Risk of Atrial Fibrillation: A Mendelian Randomization Study
Authors: Hyman Matthew C. , Levin Michael G. , Gill Dipender , Walker Venexia M. , Georgakis Marios K. , Davies Neil , Marchlinski Francis E. , Damrauer Scott M.
Published: July 2020

Importance

Observational studies have shown an association between hypertension and atrial fibrillation (AF). Aggressive blood pressure management in patients with known AF reduces overall arrhythmia burden, but it remains unclear whether hypertension is causative for AF.

Objective

The primary objective of this study was to investigate the relationship between blood pressure and risk of AF using genetic proxies for blood pressure within a Mendelian randomization (MR) framework. We secondarily explored the relationship between genetically proxied use of anti-hypertensive drugs and risk of AF.

Design

Two-sample MR was performed using an inverse-variance weighted meta-analysis with weighted median MR and Egger intercept tests performed as sensitivity analyses. Genetic proxies for the anti-hypertensive drug classes were used to investigate the impact of these therapies on the risk of AF.

Setting

International Consortium of Blood Pressure, UK Biobank and Atrial Fibrillation Genetics Consortium.

Participants

Summary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) were obtained from the International Consortium of Blood Pressure and the UK Biobank discovery analysis (>750,000 individuals of European ancestry).

Summary statistics for AF were obtained from the 2018 Atrial Fibrillation Genetics Consortium multi-ethnic GWAS (>65,000 AF cases and >522,000 referents).

Exposure

Genetically predicted SBP, DBP and PP as quantified by risk scores.

Main Outcome

Odds ratio for AF per 10 mmHg increase in genetically proxied blood pressure.

Results

Ten mmHg increases in genetically proxied SBP, DBP or PP were associated with increased odds of AF (SBP: OR 1.17, 95% CI 1.11-1.22, p=1⨯ 10−11; DBP: OR 1.25, 95% CI 1.16-1.35, p=3⨯ 10−8; PP: OR 1.1, 95% CI 1.0-1.2, p=0.05). Ten mmHg decreases in SBP estimated by genetic proxies of anti-hypertensive medications showed calcium channel blockers (OR 0.66, 95% CI 0.57-0.76, p=8⨯ 10−9) and beta-blockers (OR 0.61, 95% CI 0.46-0.81, p=6⨯ 10−4) decreased the risk of AF.

Conclusions and Relevance

Blood pressure-increasing genetic variants were associated with increased risk of AF, consistent with a causal relationship between blood pressure and AF. These data support the concept that blood pressure reduction through pharmacologic intervention, and specifically calcium channel blockade or beta blockade could reduce the risk of AF.
A HYBRID KNOWLEDGE-BASED AND MODIFIED REGRESSION ANALYSIS APPROACH FOR COVID-19 TRACKING IN USA
Authors: Hussein Rafaat
Published: July 2020

Since its appearance in 2019, the covid-19 virus deluged the world with unprecedented data in short time. Despite the countless worldwide pertinent studies and advanced technologies, the spread is neither contained nor defeated. In fact, there is a record surge in the number of confirmed new cases since July 2020. This article presents a new predictive Knowledge-based (KB) toolkit named CORVITT (Corona Virus Tracking Toolkit) and modified linear regression model. This hybrid approach uses the confirmed new cases and demographic data, implemented. CORVITT is not an epidemiological model, in the sense that it does not model disease transmission, nor does it use underlying epidemiological parameters like the reproductive rate. It forecasts the spread in order to assist the official to make proactive intervention.
Impact of the COVID-19 Pandemic on the Short-term Course of Obsessive-Compulsive Disorder
Authors: Sharma Lavanya P , Balachander Srinivas , Thamby Abel , Bhattacharya Mahashweta , Kishore Chethana , Shanbhag Vandita , Jaisoorya TS , Narayanaswamy Janardhanan C , Arumugham Shyam Sundar , Reddy YC Janardhan
Published: July 2020

Background

There is an understandable concern that obsessive-compulsive disorder (OCD) may worsen during the COVID-19 pandemic, but there is little empirical data. We report the impact of COVID-19 pandemic on the short-term course of OCD. We also assessed for predictors of relapse and emergence of COVID–19–themed obsessive–compulsive symptoms.

Methods

A cohort of patients with a primary diagnosis of OCD (n=240) who were on regular follow-up at a tertiary care specialty OCD Clinic in India were assessed telephonically, about 2 months after the declaration of the pandemic (‘pandemic’ cohort). Data from the medical records of an independent set of patients with OCD (n=207) who were followed–up during the same period, one year prior, was used for comparison (historical controls).

Results

The ‘pandemic’ group and historical controls did not differ in the trajectories of the Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores (Chi-square for likelihood-ratio test of the Group × Time interaction = 2.73, p= 0.255) and relapse rate [21% vs 20%, adjusted odds ratio = 0.81 (95% CI 0.41 -1.59, p=0.535]. Pre-existing contamination symptoms and COVID-19-related health anxiety measured by the COVID-Threat Scale did not predict relapse. Only a small proportion of patients (6%) reported COVID-19-themed obsessive-compulsive symptoms.

Limitations

Follow-up 2 months after pandemic declaration may be too early understand the true impact.

Conclusions

The COVID-19 pandemic, at least in the short-run, did not influence the course of illness in those who were on medications. It would be pertinent to evaluate the long-term impact of the pandemic on the course of OCD.

Highlights
Predicting Onset of COVID-19 with Mobility-Augmented SEIR Model
Authors: Wu Neo , Ben Xue , Green Bradley , Rough Kathryn , Venkatramanan Srinivasan , Marathe Madhav , Eastham Paul , Sadilek Adam , O’Banion Shawn
Published: July 2020

Timely interventions and early preparedness of healthcare resources are crucial measures to tackle the COVID-19 disease. To aid these efforts, we developed the Mobility-Augmented SEIR model (MA-SEIR) that leverages Google’s aggregate and anonymized mobility data to augment classic compartmental models. We show in a retrospective analysis how this method can be applied at an early stage in the COVID-19 epidemic to forecast its subsequent spread and onset in different geographic regions, with minimal parameterization of the model. This provides insight into the role of near real-time aggregate mobility data in disease spread modeling by quantifying substantial changes in how populations move both locally and globally. These changes would be otherwise very hard to capture using less timely data.
Transport effect of COVID-19 pandemic in France
Authors: Guan Lina , Prieur Christophe , Zhang Liguo , Prieur Clémentine , Georges Didier , Bellemain Pascal
Published: July 2020

An extension of the classical pandemic SIRD model is considered for the regional spread of COVID-19 in France under lockdown strategies. This compartment model divides the infected and the recovered individuals into undetected and detected compartments respectively. By fitting the extended model to the real detected data during the lockdown, an optimization algorithm is used to derive the optimal parameters, the initial condition and the epidemics start date of regions in France. Considering all the age classes together, a network model of the pandemic transport between regions in France is presented on the basis of the regional extended model and is simulated to reveal the transport effect of COVID-19 pandemic after lockdown. Using the the measured values of displacement of people mobilizing between each city, the pandemic network of all cities in France is simulated by using the same model and method as the pandemic network of regions. Finally, a discussion on an integro-differential equation is given and a new model for the network pandemic model of each age class is provided.
Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Kenyan blood donors
Authors: Uyoga Sophie , M.O. Adetifa Ifedayo , Karanja Henry K. , Nyagwange James , Tuju James , Wanjiku Perpetual , Aman Rashid , Mwangangi Mercy , Amoth Patrick , Kasera Kadondi , Ng’ang’a Wangari , Rombo Charles , Yegon Christine , Kithi Khamisi , Odhiambo Elizabeth , Rotich Thomas , Orgut Irene , Kihara Sammy , Otiende Mark , Bottomley Christian , N. Mupe Zonia , W. Kagucia Eunice , E Gallagher Katherine , Etyang Anthony , Voller Shirine , N. Gitonga John , Mugo Daisy , N. Agoti Charles , Otieno Edward , Ndwiga Leonard , Lambe Teresa , Wright Daniel , Barasa Edwine , Tsofa Benjamin , Bejon Philip , I. Ochola-Oyier Lynette , Agweyu Ambrose , Scott J. Anthony G. , Warimwe George M.
Published: July 2020

Background

There are no data on SARS-CoV-2 seroprevalence in Africa though the COVID-19 epidemic curve and reported mortality differ from patterns seen elsewhere. We estimated the anti-SARS-CoV-2 antibody prevalence among blood donors in Kenya.

Methods

We measured anti-SARS-CoV-2 spike IgG prevalence by ELISA on residual blood donor samples obtained between April 30 and June 16, 2020. Assay sensitivity and specificity were 83% (95% CI 59-96%) and 99.0% (95% CI 98.1-99.5%), respectively. National seroprevalence was estimated using Bayesian multilevel regression and post-stratification to account for non-random sampling with respect to age, sex and region, adjusted for assay performance.

Results

Complete data were available for 3098 of 3174 donors, aged 15-64 years. By comparison with the Kenyan population, the sample over- represented males (82% versus 49%), adults aged 25-34 years (40% versus 27%) and residents of coastal Counties (49% versus 9%). Crude overall seroprevalence was 5.6% (174/3098). Population-weighted, test- adjusted national seroprevalence was 5.2% (95% CI 3.7– 7.1%). Seroprevalence was highest in the 3 largest urban Counties - Mombasa (9.3% [95% CI 6.4-13.2%)], Nairobi (8.5% [95% CI 4.9-13.5%]) and Kisumu (6.5% [95% CI 3.3-11.2%]).

Conclusions

We estimate that 1 in 20 adults in Kenya had SARS-CoV-2 antibodies during the study period. By the median date of our survey, only 2093 COVID-19 cases and 71 deaths had been reported through the national screening system. This contrasts, by several orders of magnitude, with the numbers of cases and deaths reported in parts of Europe and America when seroprevalence was similar.
Cell-Free DNA in Blood Reveals Significant Cell, Tissue and Organ Specific injury and Predicts COVID-19 Severity
Authors: Cheng Alexandre Pellan , Cheng Matthew Pellan , Gu Wei , Lenz Joan Sesing , Hsu Elaine , Schurr Erwin , Bourque Guillaume , Bourgey Mathieu , Ritz Jerome , Marty Francisco , Chiu Charles Y. , Vinh Donald Cuong , De Vlaminck Iwijn
Published: July 2020

COVID-19 primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell, tissue, and organ specific injury due to COVID-19, using genome-wide methylation profiling of circulating cell-free DNA in plasma. We assessed the utility of this test to identify subjects with severe disease in two independent, longitudinal cohorts of hospitalized patients. Cell-free DNA profiling was performed on 104 plasma samples from 33 COVID-19 patients and compared to samples from patients with other viral infections and healthy controls. We found evidence of injury to the lung and liver and involvement of red blood cell progenitors associated with severe COVID-19. The concentration of cfDNA correlated with the WHO ordinal scale for disease progression and was significantly increased in patients requiring intubation. This study points to the utility of cell-free DNA as an analyte to monitor and study COVID-19.
RSGSA: a Robust and Stable Gene Selection Algorithm
Authors: Saha Subrata , Soliman Ahmed , Rajasekaran Sanguthevar
Published: July 2020

Nowadays we are observing an explosion of gene expression data with phenotypes. It enables researchers to efficiently identify genes responsible for certain medical condition as well as classify them for drug target. Like any other phenotype data in medical domain, gene expression data with phenotypes also suffers from being very underdetermined system. In a very large set of features but a very small sample size domains (e.g., DNA microarray, RNA-seq data, GWAS data, etc.), it is often reported that several different spurious feature subsets may yield equally optimal results. This phenomenon is known asinstability. Considering these facts, we have developed a very robust and stable supervised gene selection algorithm to select the most discriminating non-spurious set of genes from the gene expression datasets with phenotypes.Stabilityandrobustnessis ensured by class and instance levels perturbations, respectively.

We have performed rigorous experimental evaluations using 10 real gene expression microarray datasets with phenotypes. It revealed that our algorithm outperforms the state-of-the-art algorithms with respect to stability and classification accuracy. We have also done biological enrichment analysis based on gene ontology-biological processes (GO-BP) terms, disease ontology (DO) terms, and biological pathways.
Intersection of structural and functional connectivity of the nucleus basalis of Meynert in Parkinson’s disease dementia and Lewy body dementia
Authors: Oswal Ashwini , Gratwicke James , Akram Harith , Jahanshahi Marjan , Zaborszky Laszlo , Brown Peter , Hariz Marwan , Zrinzo Ludvic , Foltynie Tom , Litvak Vladimir
Published: July 2020

Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) are related conditions that are associated with cholinergic system dysfunction. Dysfunction of the nucleus basalis of Meynert (NBM), a basal forebrain structure that provides the dominant source of cortical cholinergic innervation, has been implicated in the pathogenesis of both PDD and DLB. Here we leverage the temporal resolution of magnetoencephalography (MEG) with the spatial resolution of MRI tractography in order to explore the intersection offunctionalandstructuralconnectivity of the NBM in a unique cohort of PDD and DLB patients undergoing Deep Brain Stimulation (DBS) of this structure. We observe that NBM-corticalstructuralandfunctionalconnectivity correlate within spatially and spectrally segregated networks including: 1) a beta band network to supplementary motor area (SMA), where activity in the SMA was found to drive activity in the NBM, 2) a delta/theta band network to medial temporal lobe structures encompassing the parahippocampal gyrus and 3) a delta/theta band network to visual areas including lingual gyrus. These findings reveal functional networks of the NBM that are likely to subserve important roles in motor control, memory and visual function respectively. Furthermore, they motivate future studies aimed at disentangling network contribution to disease phenotype.
HIT-scISOseq: High-throughput and High-accuracy Single-cell Full-length Isoform Sequencing for Corneal Epithelium
Authors: Zheng Ying-Feng , Chen Zhi-Chao , Shi Zhuo-Xing , Hu Kun-Hua , Zhong Jia-Yong , Wang Chun-Xiao , Shi Wen , Chen Ying , Xie Shang-Qian , Luo Feng , Bo Xiao-Chen , Tang Chong , Liu Yi-Zhi , Xiao Chuan-Le
Published: July 2020

Single-cell isoform sequencing can reveal transcriptomic dynamics in individual cells invisible to bulk- and single-cell RNA analysis based on short-read sequencing. However, current long-read single-cell sequencing technologies have been limited by low throughput and high error rate. Here we introduce HIT-scISOseq for high-throughput single-cell isoform sequencing. This method was made possible by full-length cDNA capture using biotinylated PCR primers, and by our novel library preparation procedure that combines head-to-tail concatemeric full-length cDNAs into a long SMRTbell insert for high-accuracy PacBio sequencing. HIT-scISOseq yields > 10 million high-accuracy full-length isoforms in a single PacBio Sequel II 8M SMRT Cell, providing > 8 times more data output than the standard single-cell isoform PacBio sequencing protocol. We exemplified HIT-scISOseq by first studying transcriptome profiles of 4,000 normal and 8,000 injured corneal epitheliums from cynomolgus monkeys. We constructed dynamic transcriptome landscapes of known and rare cell types, revealed novel isoforms, and identified injury-related splicing and switching events that are previously not accessible with low throughput isoform sequencing. HIT-scISOseq represents a high-throughput, cost-effective, and technically simple method to accelerate the burgeoning field of long-read single-cell transcriptomics.
Natural Antisense Transcript ofPeriod2, Per2AS, regulates the amplitude of the mouse circadian clock
Authors: Mosig Rebecca A. , Castaneda Allison N. , Deslauriers Jacob C. , Frazier Landon P. , He Kevin L. , Maghzian Naseem , Pokharel Aarati , Schrier Camille T. , Zhu Lily , Koike Nobuya , Tyson John J. , Green Carla B. , Takahashi Joseph S. , Kojima Shihoko
Published: July 2020

Circadian transcriptome studies identified a novel transcript at thePeriod2 (Per2)locus, which we namedPer2AS. Per2ASis a long non-coding RNA transcribed from the antisense strand ofPer2, and is expressed rhythmically and anti-phasic toPer2mRNA. Previously, we mathematically tested the hypothesis thatPer2ASandPer2mutually inhibit each other’s expression by forming a double negative feedback loop, and found thatPer2ASexpands the oscillatory domain. In this study, we have experimentally tested this prediction by perturbing the expression ofPer2ASin mouse fibroblasts. We found thatPer2ASrepressesPer2pre-transcriptionallyin cisand regulates the amplitude of the circadian clock, but not period or phase. Unexpectedly, we also found thatPer2positively regulatesPer2ASpost-transcriptionally, indicating thatPer2ASandPer2form a single negative feedback loop. Because knock-down ofPer2does not recapitulate the phenotypes ofPer2ASperturbation andPer2ASalso activatesBmal1 in trans, we propose thatPer2ASregulates the amplitude of the circadian clock without producing a protein by rewiring the molecular clock circuit.
Human thymopoiesis produces polyspecific CD8+α/β T cells responding to multiple viral antigens
Authors: Quiniou Valentin , Barennes Pierre , Mhanna Vanessa , Stys Paul , Vantomme Hélène , Zhou Zhicheng , Martina Federica , Coatnoan Nicolas , Barbié-Sastre Michèle , Pham Hang-Phuong , Clemenceau Béatrice , Vié Henri , Shugay Mikhail , Six Adrien , Brandao Barbara , Mallone Roberto , Mariotti-Ferrandiz Encarnita , Klatzmann David
Published: July 2020

T cell receptors (TCRs) are formed by stochastic gene rearrangements, theoretically generating >1019sequences. They are selected during thymopoiesis, which releases a repertoire of about 108unique TCRs per individual. How evolution shaped a process that produces TCRs that can effectively handle a countless and evolving set of infectious agents is a central question of immunology. The paradigm is that a diverse enough repertoire of TCRs should always provide a proper, though rare, specificity for any given need. Expansion of such rare T cells would provide enough fighters for an effective immune response and enough antigen-experienced cells for memory. We show here that human thymopoiesis releases a large population of CD8+T cells harboring α/β paired TCRs that (i) have high generation probabilities and (ii) a preferential usage of some V and J genes, (iii) are shared between individuals and (iv) can each recognize and be activated by multiple unrelated viral peptides, notably from EBV, CMV and influenza. These polyspecific T cells may represent a first line of defense that is mobilized in response to infections before a more specific response subsequently ensures viral elimination. Our results support an evolutionary selection of polyspecific α/β TCRs for broad antiviral responses and heterologous immunity.
Pulmonary function and risk of Alzheimer dementia: two-sample Mendelian randomization study
Authors: Russ Tom C. , Harris Sarah E. , Batty G. David
Published: July 2020

Dementia is a major global public health concern and in addition to recognised risk factors there is emerging evidence that poorer pulmonary function is linked with subsequent dementia risk. However, it is unclear if this observed association is causal or whether it might result from confounding. Therefore, we present the first two-sample Mendelian randomisation study of the association between pulmonary function and Alzheimer dementia using the most recent genome-wide association studies to produce instrumental variables for both. We found no evidence of a causal effect of reduced Forced Expiratory Volume in 1 second (FEV1) or Forced Vital Capacity (FVC) on Alzheimer dementia risk (both P>0.35). However, the FEV1/FVC ratio was associated with Alzheimer dementia risk with, in fact, superior function predicting an increased dementia risk (OR 1.12, 95%CI 1.02-1.23; P=0.016) which may result from survivor bias. While we can conclude that there is no causal link between impaired pulmonary function and Alzheimer dementia, our study sheds less light on potential links with other types of dementia.
Increasing power in the analysis of responder endpoints in rheumatology: a software tutorial
Authors: McMenamin Martina , Grayling Michael J , Berglind Anna , Wason James MS
Published: July 2020

Background

Composite responder endpoints feature frequently in rheumatology due to the multifaceted nature of many of these conditions. Current analysis methods used to analyse these endpoints discard much of the data used to classify patients as responders; they are therefore highly inefficient and result in low power.

Methods

We highlight a novel augmented methodology that uses more of the information available to improve the precision of reported treatment effects. Since these methods are more challenging to implement, we have developed free, user friendly software available in a web-based interface. The software consists of two programs: one that supports the analysis of responder endpoints; the second is used for sample size estimation. We demonstrate the augmented analysis method and its software using the MUSE study, a phase IIb trial in patients with systemic lupus erythematosus.

Results

We show the software can be used to analyse the trial with efficiency gains translating to a reduction in required sample size of 63%. Furthermore, we illustrate how the software can be used to choose the sample size needed in a future trial that will use the novel approach as the primary analysis method.

Conclusion

We encourage trialists to utilise the software we have developed to implement augmented methodology in future studies to improve efficiency.
Prevalence of amyloid blood clots in COVID-19 plasma
Authors: Pretorius Etheresia , Venter Chantelle , Laubscher Gert Jacobus , Lourens Petrus Johannes , Steenkamp Janami , Kell Douglas B
Published: July 2020

The rapid detection of COVID-19 uses genotypic testing for the presence of SARS-Cov-2 virus in nasopharyngeal swabs, but it can have a poor sensitivity. A rapid, host-based physiological test that indicated whether the individual was infected or not would be highly desirable. Coagulaopathies are a common accompaniment to COVID-19, especially micro-clots within the lungs. We show here that microclots can be detected in the native plasma of COVID-19 patient, and in particular that such clots are amyloid in nature as judged by a standard fluorogenic stain. This provides a rapid and convenient test (P<0.0001), and suggests that the early detection and prevention of such clotting could have an important role in therapy.