bluuebunny/crossref_metadata_2025 huggingface dataset:
Traditional Versus Virtual Surgery Planning of the Fronto-Orbital Unit in Anterior Cranial Vault Remodeling Surgery
Authors: Ganesh Praveen , Mahipathy Surya Rao Rao Venkata , Rajan Vivakaran Thanga Thirupathi , Sundaramurthy Narayanamurthy , Durairaj Alagar Raja , Jayachandiran Anand Prasath , Nagarjuna Muralidhara
Published: September 2020

Background:

Craniosynostosis correction surgery is a complex procedure, which involves complete dismantling and reassembly of the cranial vault components. The traditional planning method for these surgeries results in increased intra-operative time owing to its highly subjective nature. The advent of virtual surgical planning (VSP) platform has lead to a greater pre-operative insight and precision outcome in calvarial remodeling surgeries. The purpose of this paper is to evaluate intra-operative time and blood loss difference as a measure of surgical efficiency between VSP based template guided Anterior Cranial Vault Reconstruction (ACVR) with Fronto-Orbital Unit Advancement (FOUA) and the traditional surgeries.

Methods:

Data were collected from patients who underwent ACVR with FOUA in our unit. Patients were divided into 2 groups, Template Fronto-Orbital Unit (TFOU) group and Non-template Fronto-Orbital Unit (NFOU) group. In TFOU group, Virtual planning along with fabrication of Template guide was carried out. Patients undergoing ACVR using traditional techniques were categorized as NFOU group. A comparative prospective analysis was carried out in terms of Intra-operative time duration and blood loss. Student ‘t’ test was used to compare the means of the 2 groups.

Results:

A total of 10 patients were included in the present study. There were 5 control (NFOU) and 5 TFOU cases. There was a significant decrease in the operating time in TFOU group compared to the NFOU group. TFOU group also showed reduced intra-operative bleed compared to the NFOU group.

Conclusion:

Virtual surgical planning (VSP) and 3D modeling with prefabricated template guide augurs reliable outcomes and portends the possibility of lesser intra-operative time. It is a valuable tool, which offers enormous benefits in terms of precise pre-surgical planning with predictive results.
Use of Onlay Hydroxyapatite Cement for Secondary Cranioplasty
Authors: Brussius Coelho Marcio , Rtshiladze Michael , Aggarwala Shivani , Hunt Jeremy , Peltz Tim , Gardner Danielle , Gianoutsos Mark
Published: September 2020

Background:

Children who undergo bi-fronto-orbital advancement (BFOA) frequently develop a contour deformity on the temporal and supra-orbital region, with an incidence reported as high as 55% and 75%, respectively. Up to 20% of patients may require correction. Hydroxyapatite cement (HAC) is a good alternative to autogenous tissue. The available literature on its use focusses on the reconstruction of bone defects, but little has been published on its efficacy and safety as an onlay graft over intact cranium.

Objectives:

To describe our institution's experience with HAC in the pediatric population.

Methods:

Retrospective chart review from 1998 to 2018 on all patients from the Craniofacial Unit at the Sydney Children's Hospital who had either coronal or metopic craniosynostosis and underwent BFOA and later in life required cranioplasty with HAC for contour repair.

Findings:

We have performed 166 BFOA and nineteen secondary cranioplasties for contour repair using onlay HAC. The mean age at the time of operation was 14 years. Bi-coronal craniosynostosis was most frequently associated with secondary cranioplasty and 37% had an associated syndrome. The mean volume of HAC used was 37 mL. There was only 1 patient who had a complication (5.3%) and required partial removal of allograft. The mean length of admission was 2 days. Mean follow up time of 22.4 months.

Conclusions:

HAC represents a safe option when used correctly, with low rates of complication and satisfactory cosmetic outcomes.
Variations in Postoperative Management of Pediatric Open-Vault Craniosynostosis
Authors: Srivatsa Shachi , Heiman Adee J. , Gray Megan C. , Carpenter Courtney , Patel Ashit
Published: September 2020

Craniosynostosis is the premature fusion of 1 or more of the calvarial sutures causing a secondary distortion of the skull shape due to lack of growth perpendicular to the fused suture and compensatory overgrowth parallel to the suture. Open vault craniosynostosis repair requires extensive dissection and reshaping of the skull and can be associated with significant pain, commonly undervalued, and underreported in the pediatric cohort. Although there is an extensive body of literature focusing on the operative treatment of craniosynostosis, there is little consensus about optimal postoperative management protocols, including pain control regimens. The purpose of this study was to assess variation in immediate postoperative management protocols within the United States. A Qualtrics-based survey was submitted to all 112 American Cleft Palate-Craniofacial Association-approved craniofacial teams regarding their routine postoperative management protocol. Nineteen responses were obtained. All surgeons reported routine post-op intensive care unit stay. Mean overall length of stay was 3.5 days. Pain control agents included acetaminophen (100%), intravenous opioids (95%), oral opioids (79%), and ketorolac (53%). Eighty-eight percent of surgeons reported utilizing vital signs and observational parameters for pain assessment with 47% reporting the use of a formal pain scale. Sixty-three percent of those surveyed used a drain, 88% used a foley catheter, 75% used postoperative prophylactic antibiotics, and 75% routinely used arterial line monitoring postoperatively. The results of this survey will be the basis for future direction in understanding the efficacy of differing management protocols and further study of pain management in the pediatric craniosynostosis population.
Biomechanical Evaluation of Implant Osseointegration After Guided Bone Regeneration With Different Bone Grafts
Authors: Gunes Nedim , Gul Mehmet , Dundar Serkan , Tekin Samet , Bozoglan Alihan , Ozcan Erhan Cahit , Karasu Necmettin , Toy Vesile Elif , Bingül Muhammet Bahattin
Published: September 2020

The aim of this study was to compare the biomechanical osseointegration of titanium implants after guided bone regeneration (GBR) with a hydroxyapatite graft, deproteinized bovine bone graft, human-derived allograft, and calcium sulfate bone graft. Thirty-two female Sprague Dawley rats were divided into four groups, each containing eight (n = 8) rats: hydroxyapatide (HA), deproteinized bovine bone graft (DPBB), allograft (ALG), and calcium sulfate. Bone defects were created in the tibia of the rats, which were grafted with HA, DPBB, ALG, or CP bone grafts for the purpose of GBR. Ninety days after surgery, machine-surfaced titanium implants were inserted into the area where GBR had been undertaken. After 90 days of the surgical insertion of the implants, the rats were sacrificed, the implants with surrounding bone tissue were removed, and biomechanical osseointegration (N/cm) analysis was performed. No statistically significant differences were found among the groups in osseointegration (N/cm) three months after the GBR procedures (P > 0.05). According to the biomechanical results, none of the grafts used in this study was distinctly superior to any of the others.
Spontaneous Bone Flap Resorption Following Cranioplasty Using Autologous Bone
Authors: da Costa Benalia Victor Hugo , Pedrozo Charles Alfred Grander , Kormanski Matheus Kohama , Veiga José Carlos Esteves , de Aguiar Guilherme Brasileiro
Published: September 2020

Cranioplasty is a common neurosurgical procedure. The main reasons for performing cranioplasty are, in addition to aesthetic correction and protection of the brain, the reestablishment of the adequate flow of cerebrospinal fluid and the prevention of complications inherent to the perpetuation of bone failure. In our institution the patient's autologous bone remains the best method for performing cranioplasty, despite the existence of other heterologous grafts and bone substitutes. Despite representing for us, the best material for cranioplasty, the use of autologous grafting is subject to complications. In this paper, the authors present the case of a patient who underwent cranioplasty with autologous bone that progressed with spontaneous resorption of the bone flap. The authors herein briefly discuss the case and review the literature on the subject, with an emphasis on the factors that can lead to such an outcome.
A New Solution for Routine Endoscopic Aerosol-Generating Procedures (AGPs) in the COVID-19 Pandemic
Authors: Gallo Oreste , Locatello Luca Giovanni , Orlando Pietro , Bruno Chiara , Maggiore Giandomenico , Signorini Patrizia , Adembri Chiara
Published: September 2020

Introduction:

There is urgent need to find a swift and cheap way to safely perform routine endoscopic procedures during the otolaryngological and anesthesiological practice. We want to share our experience of a novel device, inspired by the pediatric head box experience.

Materials and Methods:

Five otolaryngologists and four anesthesiologists were asked to visualize the glottic plane by using the device. A total of 15 attempts was allowed to reach the vocal folds within 60 seconds after entering the box. Student's t-test for unpaired samples was used to compare groups.

Results:

Transnasal laryngoscopy through our endobox could be successfully performed by all the physicians involved and the mean number of attempts before visualizing and passing the glottis for the first time was 2.8 (range 1–5) in the otolaryngologists’ group versus 3.2 (range 1–6) in the anesthesiologists’ group (P=0.583). Out of the 15 attempts, the group of otolaryngologists reached the glottis 10.2 times, on average, against 9.7 in the other group (P=0.692).

Conclusions:

Our endobox seems a practical and feasible strategy to control droplets diffusion during standard ear, nose, and throat and anesthesiological practice.
The Introduction of Community-Engaged Learning Into a DPD Community Nutrition Course
Authors: Allsopp Marie A. K. , Buys David R.
Published: September 2020

The objective of this article is to describe the development process of incorporating community-engaged learning activities in the Mississippi Delta to an undergraduate, community nutrition course for didactic programs in dietetics (DPD) students. Lessons learned from this experience indicate that it is crucial to include service-learning experts in the planning process, meet the needs of key stakeholders, and obtain student buy-in. These lessons as well as others learned have important implications for pedagogy practice. Integrating community-engaged learning activities into community nutrition courses is one way of serving at-risk communities.
Hamiltonian modelling of macro-economic urban dynamics
Authors: Monechi Bernardo , Ibáñez-Berganza Miguel , Loreto Vittorio
Published: September 2020

The rapid urbanization makes the understanding of the evolution of urban environments of utmost importance to steer societies towards better futures. Many studies have focused on the emerging properties of cities, leading to the discovery of scaling laws mirroring the dependence of socio-economic indicators on city sizes. However, few efforts have been devoted to the modelling of the dynamical evolution of cities, as reflected through the mutual influence of socio-economic variables. Here, we fill this gap by presenting a maximum entropy generative model for cities written in terms of a few macro-economic variables, whose parameters (the effective Hamiltonian, in a statistical-physical analogy) are inferred from real data through a maximum-likelihood approach. This approach allows for establishing a few results. First, nonlinear dependencies among indicators are needed for an accurate statistical description of the complexity of empirical correlations. Second, the inferred coupling parameters turn out to be quite robust along different years. Third, the quasi time-invariance of the effective Hamiltonian allows guessing the future state of a city based on a previous state. Through the adoption of a longitudinal dataset of macro-economic variables for French towns, we assess a significant forecasting accuracy.
Super-spreading events initiated the exponential growth phase of COVID-19 with ℛ
0
higher than initially estimated
Authors: Kochańczyk Marek , Grabowski Frederic , Lipniacki Tomasz
Published: September 2020

The basic reproduction number

R

0

of the coronavirus disease 2019 has been estimated to range between 2 and 4. Here, we used an SEIR model that properly accounts for the distribution of the latent period and, based on empirical estimates of the doubling time in the near-exponential phases of epidemic progression in China, Italy, Spain, France, UK, Germany, Switzerland and New York State, we estimated that

R

0

lies in the range 4.7–11.4. We explained this discrepancy by performing stochastic simulations of model dynamics in a population with a small proportion of super-spreaders. The simulations revealed two-phase dynamics, in which an initial phase of relatively slow epidemic progression diverts to a faster phase upon appearance of infectious super-spreaders. Early estimates obtained for this initial phase may suggest lower

R

0

.
Acidiluteibacter ferrifornacis gen. nov., sp. nov., a new member of the Flavobacteriales from Tielu Harbour, Hainan, PR China
Authors: Gui Xi , Wu Shufei , Huang Fanghang , Wang Yiran , He Ruyue , Zhao Jing
Published: September 2020

A novel bacterial strain of the family ‘Vicingaceae’ was isolated from mangrove of Tielu Harbour, Hainan, PR China. Strain S-15T was a Gram-stain-negative, short-rod-shaped, yellow-pigmented that could grow at 10–42 °C (optimum, 26–35 °C), at pH 5.0–9.0 (optimum, pH 5.5) and in 0.5–10.0 % w/v sea salt (optimum, 3.5–4.0 %). Cells of strain S-15T were 0.9–1.4 µm long, 0.8–0.9 µm wide, catalase-positive and oxidase-positive. Colonies on modified marine agar 2216 were 0.5–2.0 mm in diameter after incubation for 72 h at 28 °C. Analysis of 16S rRNA gene sequences revealed that strain S-15T was most closely related to

Vicingus serpentipes

ANORD5T (89.8 %). The major respiratory quinone of strain S-15T was menaquinone MK-7, and the dominant fatty acids were C15:0 iso, C15:1 iso G and C17:0 iso 3-OH. The major polar lipids were two unidentified aminolipids, phosphatidylethanolamine and six unidentified lipids. Analyses showed that the genome size was 3.52 Mb and the DNA G+C content was 35.6 mol%, which were higher than

V. serpentipes

ANORD5T with 2.92 Mb genome size and 31.0 mol% G+C content, respectively. Based on morphological, physiological and phylogenetic data, strain S-15T is considered a type strain of a new species and a new genus of the family ‘Vicingaceae’ for which the name Acidiluteibacter ferrifornacis gen. nov., sp. nov. is proposed. The type strain of Acidiluteibacter ferrifornacis is S-15T (=MCCC 1K03817T=JCM 33804T).
Reliable detection of focal-onset seizures in the human anterior nucleus of the thalamus using non-linear machine learning
Authors: Toth Emilia , Kumar Sachin S , Chaitanya Ganne , Riley Kristen , Balasubramanian Karthi , Pati Sandipan
Published: September 2020

Objective

There is an unmet need to develop seizure detection algorithms from brain regions outside the epileptogenic cortex. The study aimed to demonstrate the feasibility of classifying seizures and interictal states from local field potentials (LFPs) recorded from the human thalamus-a subcortical region remote to the epileptogenic cortex. We tested the hypothesis that spectral and entropy-based features extracted from LFPs recorded from the anterior nucleus of the thalamus (ANT) can distinguish its state of ictal recruitment from other interictal states (including awake, sleep).

Approach

Two supervised machine learning tools (random forest and the random kitchen sink) were used to evaluate the performance of spectral (discrete wavelet transform-DWT), and time-domain (multiscale entropy-MSE) features in classifying seizures from interictal states in patients undergoing stereo EEG evaluation for epilepsy surgery. Under the supervision of IRB, field potentials were recorded from the ANT in consenting adults with drug-resistant temporal lobe epilepsy. Seizures were confirmed in the ANT using line-length and visual inspection. Wilcoxon rank-sum (WRS) method was used to test the differences in spectral patterns between seizure and interictal (awake and sleep) states.

Main Results

79 seizures (10 patients) and 158 segments (approx. 4 hours) of interictal stereo EEG data were analyzed. The mean seizure detection latencies with line length in the ANT varied between seizure types (range 5-34 seconds). However, the DWT and MSE in the ANT showed significant changes for all seizure types within the first 20 seconds after seizure onset. The random forest (accuracy 93.9 % and false-positive 4.6%) and the random kitchen sink (accuracy 97.3% and false-positive 1.8%) classified seizures and interictal states.

Significance

These results suggest that features extracted from the thalamic LFPs can be trained to detect seizures that can be used for monitoring seizure counts and for closed-loop seizure abortive interventions.
Testing the Ability of Convolutional Neural Networks to Learn Radiomic Features
Authors: Klyuzhin Ivan S. , Xu Yixi , Ortiz Anthony , Ferres Juan Lavista , Hamarneh Ghassan , Rahmim Arman
Published: September 2020

Background and Objective

Radiomics and deep learning have emerged as two distinct approaches to medical image analysis. However, their relative expressive power remains largely unknown. Theoretically, hand-crafted radiomic features represent a mere subset of features that neural networks can approximate, thus making deep learning a more powerful approach. On the other hand, automated learning of hand-crafted features may require a prohibitively large number of training samples. Here we directly test the ability of convolutional neural networks (CNNs) to learn and predict the intensity, shape, and texture properties of tumors as defined by standardized radiomic features.

Methods

Conventional 2D and 3D CNN architectures with an increasing number of convolutional layers were trained to predict the values of 16 standardized radiomic features from real and synthetic PET images of tumors, and tested. In addition, several ImageNet-pretrained advanced networks were tested. A total of 4000 images were used for training, 500 for validation, and 500 for testing.

Results

Features quantifying size and intensity were predicted with high accuracy, while shape irregularity and heterogeneity features had very high prediction errors and generalized poorly. For example, mean normalized prediction error of tumor diameter with a 5-layer CNN was 4.23 ± 0.25, while the error for tumor sphericity was 15.64 ± 0.93. We additionally found that learning shape features required an order of magnitude more samples compared to intensity and size features.

Conclusions

Our findings imply that CNNs trained to perform various image-based clinical tasks may generally under-utilize the shape and texture information that is more easily captured by radiomics. We speculate that to improve the CNN performance, shape and texture features can be computed explicitly and added as auxiliary variables to the networks, or supplied as synthetic inputs.
Effect of daily human movement on some characteristics of dengue dynamics
Authors: Tocto-Erazo Mayra R. , Olmos-Liceaga Daniel , Montoya-Laos Jose A.
Published: September 2020

Human movement is a key factor in infectious diseases spread such as dengue. Here, we explore a mathematical modeling approach based on a system of ordinary differential equations to study the effect of human movement on characteristics of dengue dynamics such as the existence of endemic equilibria, and the start, duration, and amplitude of the outbreak. The model considers that every day is divided into two periods: high-activity and low-activity. Periodic human movement between patches occurs in discrete times. Based on numerical simulations, we show unexpected scenarios such as the disease extinction in regions where the local basic reproductive number is greater than 1. In the same way, we obtain scenarios where outbreaks appear despite the fact that the local basic reproductive numbers in these regions are less than 1 and the outbreak size depends on the length of high-activity and low-activity periods.
Supporting decision-making on allocation of ICU beds and ventilators in pandemics
Authors: Cardona Magnolia , Dobler Claudia C. , Koreshe Eyza , Heyland Daren K , Nguyen Rebecca , Sim Joan P.Y. , Clark Justin , Psirides Alex
Published: September 2020

As the world struggles with the COVID-19 pandemic, health service demands have increased to a point where healthcare resources may prove inadequate to meet demand. Guidelines and tools on how to best allocate intensive care beds and ventilators developed during previous epidemics can assist clinicians and policy-makers to make consistent, objective and ethically sounds decisions about resource allocation when healthcare rationing is inevitable. This scoping review of 62 published guidelines, triage protocols, consensus statements and prognostic tools from crisis and non-crisis situations sought to identify a multiplicity of objective factors to inform healthcare rationing of critical care and ventilator care. It also took ethical considerations into account. Prognostic indicators and other decision tools presented here can be combined to create locally-relevant triage algorithms for clinical services and policy makers deciding about allocation of ICU beds and ventilators during a pandemic. Community awareness of the triage protocol is recommended to build trust and alleviate anxiety among the public. This review provides a unique resource and is intended as a discussion starter for clinical services and policy makers to consider formalising an objective triage consensus document that fits the local context.

Take-home message

An evidence-based catalogue of objective variables from 62 published resources tested in crisis and non-crisis situations can help clinicians make locally relevant triage decisions on ICU and ventilator allocation in inevitable COVID-19 health rationing.
Panbio antigen rapid test is reliable to diagnose SARS-CoV-2 infection in the first 7 days after the onset of symptoms
Authors: Linares Manuel , Pérez-Tanoira Ramón , Romanyk Juan , Pérez-García Felipe , Gómez-Herruz Peña , Arroyo Teresa , Cuadros Juan
Published: September 2020

Background

Real-time reverse transcription polymerase chain reaction (RT-qPCR) is the current recommended laboratory method to diagnose SARS-CoV-2 acute infection, several factors such as requirement of special equipment, time consuming, high cost and skilled staff limit the use of these molecular techniques. A more rapid and high-throughput method is in growing demand.

Methods

Evaluate the performances of the Panbio™ COVID-19 AG Rapid Test Device (Nasopharyngeal), a rapid immunochromatographic test for the detection of SARS-CoV-2 antigen, in comparison to RT-qPCR.

Results

The RDT evaluated in this study showed a high sensitivity and specificity in samples mainly obtained during the first week of symptoms and with high viral loads.

Conclusions

This assay seems to be an effective strategy for controlling the COVID-19 pandemic for the rapid identification and isolation of SARS-CoV-2 infected patients.
The impact of COVID-19 infection on maternal and reproductive health care services in governmental health institutions of Dessie town, North-East Ethiopia, 2020 G.C.
Authors: Temesgen Kibir , Workie Amare , Dilnessa Tenagnework
Published: September 2020

Background

The COVID 19 pandemic is causing huge stress on the health care system of all countries in the world. The impact of the pandemic is both social and economic. Pregnancy is an exciting and sometimes stressful experience. Being pregnant during a disease outbreak may add extra anxiety and concern for pregnant women and for those who provide care for them [1, 2].

During the initial stages of the pandemic, it appeared Africa would be spared the burden of COVID-19. However, by April 7th, a total of 45 countries within the WHO African region had reported over 7000 cases (although some place it at over 10 000), with at least 292 deaths and 612 people recovered. Ethiopia, being one of the developing countries trying to address the diverse needs of its people, is currently at the verge of the epidemic [5, 7].

Objectives

The general objective of this study was to assess the impact of COVID-19 infection on maternal and reproductive health care services among mothers getting service in governmental health institutions of Dessie town, 2020 G.C.

Methods

Institution based cross sectional study design using mixed (quantitative supplemented with qualitative) method was employed to identify the impact of COVID-19 infection on maternal and reproductive health care services among women who get service in governmental health institutions of Dessie town. The study was conducted from July 1-15 / 2020.

Result

According to this study, Six percent (6%) of antenatal care attendees, 18% of delivery care attendees and nearly half (46.7%) of postnatal care attendees reported inappropriate service delivery due to fear of health care providers, shortage medical supplies and staff work load. The study also showed that utilization of these services was decreased due to fear of clients to go to health institutions.

Conclusion and recommendation

This study concluded that COVID-19 significantly affects the quality and utilization of maternal and reproductive health care services. The study also showed that utilization of these services was decreased due to fear of clients to go to health institutions. Ministry of health should continue maternity and reproductive health care services such as family planning to be prioritized as an essential core health service.
The ground level ozone concentration is inversely correlated with the number of COVID-19 cases in Warsaw, Poland
Authors: Wiśniewski Oskar , Kozak Wiesław , Wiśniewski Maciej
Published: September 2020

COVID-19, which is a consequence of infection with the novel viral agent SARS-CoV-2, first identified in China (Hubei Province), has been declared a pandemic by the WHO. As of September 10, 2020, over 70,000 cases and over 2,000 deaths have been recorded in Poland. Of the many factors contributing to the level of transmission of the virus, the weather appears to be significant. In this work we analyse the impact of weather factors such as temperature, relative humidity, wind speed and ground level ozone concentration on the number of COVID-19 cases in Warsaw, Poland. The obtained results show an inverse correlation between ground level ozone concentration and the daily number of COVID-19 cases.
IS THE INVERSE ASSOCIATION BETWEEN PARKINSON’S DISEASE AND SMOKING DUE TO CONFOUNDING?
Authors: Davis Susan M.
Published: September 2020

Parkinson’s disease (PD) is inversely associated with smoking. Whether this association is due to a causal relationship or to confounding by a covariate of smoking is still debated.

This study included populations of the United States and ten U.S. states from 2004 to 2016. The ten U.S. states included the five states with the highest PD incidence rates in 2017 (Vermont, Maine, Kansas, Missouri, Colorado) and the five states with the lowest PD incidence rates in 2017 (Arkansas, Mississippi, South Dakota, Nebraska, Alabama). The study used scatter plots to explore the association between PD incidence and smoking and the association between PD incidence and a covariate of smoking, lower endoscopy utilization.

The results indicate that there is a weaker association between PD and smoking when compared to the association between PD and lower endoscopy utilization. For PD incidence verses current smoking, the coefficient of determination (R2) for the United States was 0.813 and ranged from a low of 0.000 for Arkansas to 0.798 for Colorado (average R2 for the ten states was 0.391). For PD incidence verses lower endoscopy utilization, the R2 for the United States was 0.995 and ranged from a low of 0.871 for South Dakota to 0.997 for Colorado (average R2 for the ten states was 0.959).

The results suggest that the inverse association between PD incidence and smoking is confounded by the direct association between PD and lower endoscopy utilization. Further investigation of a possible relationship between PD incidence and lower endoscopy utilization is warranted.
Elevated serum uric acid is a facilitating mechanism for insulin resistance mediated accumulation of visceral adipose tissue
Authors: Fernández-Chirino Luisa , Antonio-Villa Neftali Eduardo , Fermín-Martínez Carlos Alberto , Márquez-Salinas Alejandro , Guerra Enrique C. , Vargas-Vázquez Arsenio , Almeda-Valdés Paloma , Gómez-Velasco Donají , Viveros-Ruiz Tania Leticia , Rojas Rosalba , Aguilar Salinas Carlos A. , Bello-Chavolla Omar Yaxmehen
Published: September 2020

OBJECTIVE

Serum uric acid (SUA) has been associated to cardiometabolic conditions such as insulin resistance (IR) and visceral adipose tissue (VAT) accumulation. Here, we aimed to clarify a unifying mechanism linking elevated SUA to IR and VAT.

METHODS

We conducted analyses in 226 subjects from the UIEM cohort with both euglycemic hyperinsulinemic clamp (EHC) and dual X-ray absorptiometry (DXA) measurements for IR and VAT accumulation, and explored the role of SUA and adiponectin by developing a network of causal mediation analyses to assess their impact on IR and VAT. These models were then translated to two population-based cohorts comprising 6,337 subjects from NHANES 2003-2004 and 2011-2012 cycles in the US and ENSANUT Medio Camino 2016 in Mexico, using HOMA2IR and adipoIR as indicators of peripheral and adipose tissue IR, and METS-VF as a surrogate for VAT accumulation.

Results

SUA has a mediating role inside a bidirectional relationship between IR and visceral obesity, which was similar using either gold standard measurements or surrogate measures for IR and VAT. Furthermore, adiponectin acts as a linking mediator between elevated SUA and both peripheral IR and VAT accumulation. The proportion of the mechanism for IR-mediated (in either peripheral or adipose tissue) VAT accumulation was greater, compared to VAT-mediated IR accumulation (10.53%[9.23%-12.00%] to 5.44%[3.78%-7.00%]). Normal-range SUA levels can be used to rule-out underlying cardio-metabolic abnormalities in both men and women.

CONCLUSIONS

Elevated SUA acts as mediator inside the bidirectional relationship between IR and VAT accumulation and these observations could be applicable at a phenotype scale.
Monitoring drinking water quality in nationally representative household surveys: cross-sectional analysis of 20 Multiple Indicator Cluster Surveys 2014-2019
Authors: Bain Rob , Johnston Rick , Khan Shane , Hancioglu Attila , Slaymaker Tom
Published: September 2020

Background

The Sustainable Development Goals set an ambitious new benchmark for safely managed drinking water services (SMDW), but many countries lack data on the availability and quality of drinking water.

Objectives

To quantify the availability and microbiological quality of drinking water, monitor SMDW and examine risk factors for E. coli contamination in 20 low-and middle-income countries.

Methods

A new water quality module for household surveys was implemented in Multiple Indicator Cluster Surveys. Teams used portable equipment to measure E. coli at the point of collection (PoC, n=48,323) and at the point of use (PoU, n=51,345) and asked respondents about the availability and location of drinking water services. E. coli levels were classified into risk categories and SMDW was calculated at the household- and domain-levels. Modified Poisson regression was used to explore risk factors for contamination.

Results

E. coli was commonly detected at PoC (range 16-90%) and was more likely at PoU (range 20-97%). Coverage of SMDW was 56% points lower than improved drinking water with water quality the limiting factor for SMDW in 14 countries. Detection of E. coli at PoC was associated with use of improved water sources (RR=0.64 [0.52-0.78]) located on premises (RR=0.78 [0.67-0.91]) but not with availability (RR=0.94 [0.82-1.06]). Households in the richest quintile (RR=0.67 [0.50-0.90]) and in communities with high (>75%) improved sanitation coverage (RR=0.95 [0.91-0.98]) were less likely to use contaminated water at PoU whereas animal ownership (RR=1.08 [1.03-1.14]) and rural residence (RR=1.11 [1.03-1.19]) increased risk of contamination.

Discussion

Water quality data can be reliably collected in household surveys and can be used to assess inequalities in service levels, to track the SDG indicator of SMDW, and to examine risk factors for contamination. There is an urgent need to implement scalable and sustainable interventions to reduce exposure to faecal contamination through drinking water.
D-dimer dynamics in hospitalized COVID-19 patients: potential utility for diagnosis of pulmonary embolism
Authors: Cerdà Pau , Ribas Jesus , Iriarte Adriana , Mora-Luján José María , Torres Raquel , Río Belén del , Jofre Héctor Ignacio , Ruiz Yolanda , Huguet Marta , Fuset Maria Paz , Martínez-Yélamos Sergio , Santos Salud , Llecha Núria , Corbella Xavier , Riera-Mestre Antoni
Published: September 2020

Background

A higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19. The main objective was to assess clinical and weekly laboratory differences in hospitalized COVID-19 patients according to occurrence of PE.

Methods

This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion. Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset were compared between PE and non-PE patients.

Results

Ninety-two patients were included, 29 (32%) had PE. PE patients were younger (63.9 (SD13.7) vs 69.9 (SD12.5) years). Clinical symptoms and COVID-19 CT features were similar in both groups. PE was diagnosed after a mean of 20.0 (SD8.6) days from the onset of COVID-19 symptoms. Corticosteroid boluses were more frequently used in PE patients (62% vs. 43%). Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1-11208.9] vs 626.0 [374.0-2382.2]; p=0.04); 3 (3893.1 [1388.2-6694.0] vs 1184.4 [461.8-2447.8]; p=0.03); and 4 (2736.3 [1202.1-8514.1] vs 1129.1 [542.5-2834.6]; p=0.01). Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02-23.05] vs 1.57 [0.64-2.71], p=0.003); ROC curve AUC was 0.879 (p=0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively.

Conclusions

Among hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset in patients who develop PE. This difference is more pronounced when the fold increase between weeks 1 and 2 is compared.
Privacy-Protecting, Reliable Response Data Discovery Using COVID-19 Patient Observations
Authors: Kim Jihoon , Neumann Larissa , Paul Paulina , Aratow Michael , Bell Douglas S. , Doctor Jason N. , Hinske Ludwig C. , Jiang Xiaoqian , Kim Katherine K. , Matheny Michael E. , Meeker Daniella , Pletcher Mark J. , Schilling Lisa M. , SooHoo Spencer , Xu Hua , Zheng Kai , Ohno-Machado Lucila ,   for the R2D2 Consortium
Published: September 2020

There is an urgent need to answer questions related to COVID-19’s clinical course and associations with underlying conditions and health outcomes. Multi-center data are necessary to generate reliable answers, but centralizing data in a single repository is not always possible. Using a privacy-protecting strategy, we launched a public Questions & Answers web portal (https://covid19questions.org) with analyses of comorbidities, medications and laboratory tests using data from 202 hospitals (59,074 COVID-19 patients) in the USA and Germany. We find, for example, that 8.6% of hospitalizations in which the patient was not admitted to the ICU resulted in the patient returning to the hospital within seven days from discharge and that, when adjusted for age, mortality for hospitalized patients was not significantly different by gender or ethnicity.

One Sentence Summary

Publicly Sharing Knowledge on COVID19 Without Sharing Patient-Level Data: A Privacy-Protecting Multivariate Analysis Approach
Single-cell Profiling of the Response to Poly I:C in Peripheral Blood Mononuclear Cells in Severe Asthma
Authors: Chen Ailu , Diaz-Soto Maria P. , Sanmamed Miguel F. , Adams Taylor , Schupp Jonas C. , Gupta Amolika , Britto Clemente , Sauler Maor , Yan Xiting , Liu Qing , Nino Gustavo , Cruz Charles S. Dela , Chupp Geoffrey L. , Gomez Jose L.
Published: September 2020

Background

Asthma has been associated with impaired interferon responses. Multiple cell types have been implicated in these impaired responses and may be responsible for increased exacerbations and immunopathology of asthma.

Objective

Characterize the single-cell response to Poly I:C of peripheral blood mononuclear cells (PBMCs) of patients with severe asthma (SA).

Methods

Two complementary single-cell methods, DropSeq for single-cell RNA sequencing (scRNA-Seq) and mass cytometry (CyTOF), were used to profile PBMCs of SA and healthy controls (HC). Poly I:C and unstimulated cells were analyzed in this study.

Results

PBMCs (n=9,414) from five SA (n=6,099) and three HC (n=3,315) were profiled using scRNA-Seq. Six main cell subsets, including CD4+ T cells, CD8+ T cells, natural killer (NK) cells, B cells, dendritic cells (DCs), and monocytes, were identified. CD4+ T cells were the main cell type and demonstrated a pro-inflammatory profile characterized by increasedJAK1expression in unstimulated cells. Following Poly I:C stimulation, PBMCs from SA had a robust induction of interferon pathways compared with HC. Additional analyses to identify core regulators of the enhanced interferon response in SA identifiedIRF1, STAT1, IRF7, STAT2, andIRF9. CyTOF profiling of Poly I:C and unstimulated PBMCs (n=120,000) from the same individuals (SA=4; HC=2) demonstrated higher numbers of CD8+ effector cells and Th1 CD4+ T cells in unstimulated conditions, followed by a decrease of these two cell subsets after poly I:C stimulation.

Conclusion

Single-cell profiling of PBMCs with scRNA-seq and CyTOF in patients with SA identified activation of pro-inflammatory pathways at baseline and strong response to Poly I:C, as well as quantitative changes in CD8+ effector cells and Th1 cells. Thus, transcriptomic and cell quantitative changes are associated with immune cell heterogeneity in severe asthma.

Key Messages

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Single-cell RNA sequencing identified a pro-inflammatory status in unstimulated PBMCs of severe asthmatics.

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Mass cytometry identified quantitative differences in CD8+ effector cells and Th1 cells of severe asthmatics.

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The response to Poly I:C stimulation, an interferon agonist, was not impaired in a subgroup of patients with severe asthma.

Capsule summary

Single-cell profiling of PBMCs in severe asthmatics characterized gene expression responses to an interferon agonist and quantitative differences in distinct cell populations. Comprehensive single-cell immune may help identify key cell features responsible for asthma heterogeneity.
Identification and Epidemiological Characterization of Non-obese Type 2 Diabetic Sub-populations in the NFHS-4 Study using an Unsupervised Machine Learning Approach
Authors: Bej Saptarshi , Sarkar Jit , Biswas Saikat , Mitra Pabitra , Chakrabarti Partha , Wolkenhauer Olaf
Published: September 2020

Studies on Type 2 Diabetes Mellitus (T2DM) have revealed heterogeneous sub-populations in terms of underlying pathologies. However, identification of subpopulations in epidemiological datasets remain unexplored. We here focus on the detection of T2DM clusters in epidemiological data, specifically analysing the National Family Health Survey-4 (NFHS-4) dataset containing a wide spectrum of features, including medical history, dietary and addiction habits, socio-economic and lifestyle patterns of 10,125 T2DM patients.

Epidemiological data provide challenges for analysis due to the diverse types of features in it. In this case, applying the state-of-the-art dimension reduction tool UMAP conventionally was found to be ineffective for the NFHS-4 dataset, which contains continuous, ordinal and nominal feature types. Continuous features, although smaller in numbers, had a overpowering effect on the distribution of clusters.

To address this problem, we implemented a distributed clustering workflow combining different similarity measure settings of UMAP, for clustering continuous, ordinal and nominal features separately. We integrated the reduced dimensions from each feature-type-distributed clustering to obtain interpretable and unbiased clustering of the data.

Our analysis reveals four significant clusters, with two of them comprising mainly of non-obese T2DM patients. These non-obese clusters has lower mean age and majorly comprises of rural residents. Surprisingly, one of the obese clusters had 90% of the T2DM patients practising non-vegetarian diet though they did not show an increased intake of plant-based protein-rich foods.

Our findings demonstrate the presence of a heterogeneity among T2DM patients with regard to socio-demography and dietary pattern. These results support the development of demography-specific screening criteria for T2DM as well as a demography-specific lifestyle modification guide-lines.
T cell anergy in COVID-19 reflects virus persistence and poor outcomes
Authors: Renner Kerstin , Müller Christine , Tiefenböck Charlotte , Salewski Jan-Niklas , Winter Frederike , Buchtler Simone , Malfertheiner Maximilian V. , Lubnow Matthias , Lunz Dirk , Graf Bernhard , Hitzenbichler Florian , Hanses Frank , Poeck Hendrik , Kreutz Marina , Orsó Evelyn , Burkhardt Ralph , Niedermair Tanja , Brochhausen Christoph , Gessner André , Salzberger Bernd , Mack Matthias
Published: September 2020

Coronavirus disease 2019 (COVID-19) can lead to severe pneumonia and hyperinflammation. So far, insufficient or excessive T cell responses were described in patients. We applied novel approaches to analyze T cell reactivity and showed that T anergy is already present in non-ventilated COVID-19 patients, very pronounced in ventilated patients, strongly associated with virus persistence and reversible with clinical recovery. T cell activation was measured by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood and proved to be much more meaningful than classical readouts with PBMCs. Monocytes responded stronger in males than females and IL-2 partially reversed T cell anergy. Downstream markers of T cell anergy were also found in fresh blood samples of critically ill patients with severe T cell anergy. Based on our data we were able to develop a score to predict fatal outcomes and to identify patients that may benefit from strategies to overcome T cell anergy.
An Introduction to Proximal Causal Learning
Authors: Tchetgen Eric J Tchetgen , Ying Andrew , Cui Yifan , Shi Xu , Miao Wang
Published: September 2020

A standard assumption for causal inference from observational data is that one has measured a sufficiently rich set of covariates to ensure that within covariate strata, subjects are exchangeable across observed treatment values. Skepticism about the exchangeability assumption in observational studies is often warranted because it hinges on investigators’ ability to accurately measure covariates capturing all potential sources of confounding. Realistically, confounding mechanisms can rarely if ever, be learned with certainty from measured covariates. One can therefore only ever hope that covariate measurements are at best proxies of true underlying confounding mechanisms operating in an observational study, thus invalidating causal claims made on basis of standard exchangeability conditions. Causal learning from proxies is a challenging inverse problem which has to date remained unresolved. In this paper, we introduce a formal potential outcome framework for proximal causal learning, which while explicitly acknowledging covariate measurements as imperfect proxies of confounding mechanisms, offers an opportunity to learn about causal effects in settings where exchangeability on the basis of measured covariates fails. Sufficient conditions for nonparametric identification are given, leading to the proximal g-formula and corresponding proximal g-computation algorithm for estimation. These may be viewed as generalizations of Robins’ foundational g-formula and g-computation algorithm, which account explicitly for bias due to unmeasured confounding. Both point treatment and time-varying treatment settings are considered, and an application of proximal g-computation of causal effects is given for illustration.
Nature and dimensions of the cytokine storm and its attenuation by convalescent plasma in severe COVID-19
Authors: Bandopadhyay Purbita , D’Rozario Ranit , Lahiri Abhishake , Sarif Jafar , Ray Yogiraj , Paul Shekhar Ranjan , Roy Rammohan , Maiti Rajshekhar , Chaudhuri Kausik , Bagchi Saugata , Maiti Ayan , Perwez Md. Masoom , Sarkar Biswanath Sharma , Roy Devlina , Chakraborty Rahul , Vasudevan Janani Srinivasa , Sharma Sachin , Biswas Durba , Maiti Chikam , Saha Bibhuti , Bhattacharya Prasun , Pandey Rajesh , Chatterjee Shilpak , Paul Sandip , Ganguly Dipyaman
Published: September 2020

In a randomized control trial on convalescent plasma therapy (CPT) in severe COVID-19, we characterized the nature, in terms of abundance of forty eight cytokines, and dimensions, in terms of their interrelationships, of the hyper-immune activation-associated ‘cytokine storm’ in patients suffering from acute respiratory distress syndrome. We found reduced plasma level of the chemokine MCP3 to be a key correlate for clinical improvement, irrespective of therapeutic regimen. We also identified an anti-inflammatory role of CPT independent of its neutralizing antibody content, and a linear regression analysis revealed that neutralizing antibodies as well as the anti-inflammatory effect of CPT both contribute to marked immediate reductions in hypoxia, as compared to patients on standard therapy.
Developing a machine learning environmental allergy prediction model from real world data through a novel decentralized mobile study platform
Authors: Sarabu Chethan , Steyaert Sandra , Shah Nirav R.
Published: September 2020

Environmental allergies cause significant morbidity across a wide range of demographic groups. This morbidity could be mitigated through individualized predictive models capable of guiding personalized preventive measures. We developed a predictive model by integrating smartphone sensor data with symptom diaries maintained by patients. The machine learning model was found to be highly predictive, with an accuracy of 0.801. Such models based on real-world data can guide clinical care for patients and providers, reduce the economic burden of uncontrolled allergies, and set the stage for subsequent research pursuing allergy prediction and prevention. Moreover, this study offers proof-of-principle regarding the feasibility of building clinically useful predictive models from “messy,” participant derived real-world data.