bluuebunny/crossref_metadata_2025 huggingface dataset:
Craniofacial Microsurgery: An Integrated Approach to Management of Cleft and Craniofacial Syndromes, Surgical Experience, and Insights
Authors: Sachanandani Neil S. , Powers Jeremy M. , Issa Christopher J. , Oliver Lauren N. , Chaiyasate Kongkrit
Published: March 2021

Ian Jackson and Jack Fisher published one of the earliest reports on microsurgical applications for craniofacial patients in 1989. Since that time, applications of craniofacial surgery and microsurgery have significantly expanded and become more refined. However, there remain certain specific clinical problems in cleft and craniofacial surgery in which traditional craniofacial methods provide variable success or suboptimal outcomes. The purpose of the current study is to share our experience using an integrated approach of craniofacial and microsurgical methods to provide optimal surgical solutions to this complex patient population. The authors performed a retrospective review of 17 patients that utilized craniofacial microsurgery in setting of cleft and craniofacial syndromes performed by the senior author from July 2013 to July 2020. 22 free flaps were performed for 17 patients. The patient age at time of flap reconstruction ranged from 10 to 48 years (mean 21.4 years). There were 8 females and 9 males. There was one total flap loss. Based on our collective experience, the authors present a comprehensive algorithm for the role of microsurgical reconstruction in cleft and craniofacial patients. There are several situations in craniofacial surgery which traditional reconstructive methods require numerous operative interventions to achieve suitable outcomes. Craniofacial Microsurgery techniques can bring in new tissue and may prevent the need to manipulate scarred and multiply operated tissues. The craniofacial surgery team should not hesitate to apply microsurgical solutions to these situations for optimal results.
The Doctor Will “See” You Now – Unmet Expectations of Telemedicine in Plastic Surgery
Authors: Tam Anson K. , Kim Minji , Mathew Prakash J. , Thaller Seth R.
Published: March 2021

Social distancing protocols during the COVID-19 pandemic have resulted in a rapid expansion of telemedicine. It has allowed patients to save time and money on clinic visits, and physicians to communicate with patients who live remotely. Telemedicine has also been valuable in plastic surgery during initial consultations, transfers, and follow up visits. However, given the often-sensitive nature of plastic surgery, the professionalism and expectations of telemedicine have to be reviewed. A comprehensive literature search of the MEDLINE, PubMed, Google Scholar, EMBASE, and Cochrane Central Register of Controlled Trials was conducted for studies published through October 2020 with multiple search terms related to telemedicine and its use in plastic surgery. Data on the effectiveness, challenges, and professionalism of telemedicine were collected. Our review suggests that telemedicine can be an effective mode of communication in many realms of plastic surgery, including cleft care and craniofacial deformities. However, many plastic surgeons are unfamiliar with the existing platforms, and there are no clear guidelines on the most optimal platforms. Physicians have to recognize that patients might have low digital health literacy or may not even possess digital device for telemedicine. There also needs to be an overall improvement in patient education. Given that telemedicine use will continue to increase after the COVID-19 pandemic, regulations on Health Insurance Portability and Accountability Act-compliant platforms and specific guidelines on telemedicine visits, such as undressing, chaperones, privacy matters, need to be established while maintaining a professional relationship between the patient and the physician.
Temporal Artery and Temporal Region Supplied by the Middle Cerebral Artery: An Anatomical Study
Authors: Guler Tugba Morali , Guner Yahya Efe , Korkmaz Ali Can , Gungor Yigit , Sayaci Yagiz Emre , Kose Serdal Kenan , Comert Ayhan , Kahilogullari Gokmen
Published: March 2021

This study was conducted to describe in detail the branching patterns of cortical branches from the middle cerebral artery supplying the feeding of the temporal region, to define the arterial structure of temporal artery (TA) and to determine the effect of this arterial supply to the temporal region. The arteries of brains (n = 22; 44 hemispheres) were prepared for dissection after filling them with colored latex. TA was defined, and its classification was described, specifying its relationship with other cortical branches. A new classification was defined related to TA terminology. TA was found in 95% of cadavers, and it originated as an early branch in 75% and from the inferior trunk in 24% of cadavers. TA was classified as Type 0: No TA, Type I: single branch providing two cortical branches, Type II: single branch providing three or more cortical branches and Type III: double TA. Type I-TA (45%) was the most common, and Type II-TA arterial diameter was significantly larger than that of other types. All cadavers showed the cortical branches of temporal region from middle cerebral artery, anterior TA , middle TA, posterior TA and temporooccipital artery, except temporopolar artery (81%). Temporopolar artery, anterior TA, and middle TA primarily originated from TA, an early branch, but posterior TA and temporooccipital artery primarily originated from the inferior trunk. Detailed knowledge about cortical branches together with TA and also this region's blood supply would enable increased prediction of complications, especially in cases with these region-related pathologies, and would make interventions safer.
Optimizing Nasal Reconstruction in Severe Congenital Nasal Deviations
Authors: Spake Carole S.L. , Beqiri Dardan , Woo Albert
Published: March 2021

Nasal deviations pose a 2-fold task for plastic surgeons, as the correction must often address both functional and aesthetic challenges. Regardless of the etiology of the nasal deviation, the principles of treatment have been previously extensively described. The authors present an extreme case of congenital nasal deviation in an 18-year-old male acquired as a result of abnormal in-utero positioning during a multigestational pregnancy. Through this case, the authors demonstrate effective use of previously described surgical principles in treating a severe congenital nasal deviation and reinforce the importance of postoperative nasal manipulation to maintain the desired outcome.
Single-Cell Transcriptomics Reveals Compartment-Specific Differences in Immune Responses and Contributions for Complement Factor 3 in Hemorrhagic Shock Plus Tissue Trauma
Authors: Fu Guang , Chen Tianmeng , Wu Junru , Jiang Ting , Tang Da , Bonaroti Jillian , Conroy Julia , Scott Melanie J. , Deng Meihong , Billiar Timothy R.
Published: March 2021

Hemorrhagic shock with tissue trauma (HS/T) leads to the activation of a system-wide immune-inflammatory response that involves all organs and body compartments. Recent advances in single-cell analysis permit the simultaneous assessment of transcriptomic patterns in a large number of cells making it feasible to survey the landscape of immune cell responses across numerous anatomic sites. Here, we used single-cell RNA sequencing of leukocytes from the blood, liver, and spleen to identify the major shifts in gene expression by cell type and compartment in a mouse HS/T model. At 6 h, dramatic changes in gene expression were observed across multiple-cell types and in all compartments in wild-type mice. Monocytes from circulation and liver exhibited a significant upregulation of genes associated with chemotaxis and migration and a simultaneous suppression of genes associated with interferon signaling and antigen presentation. In contrast, liver conventional DC exhibited a unique pattern compared with other myeloid cells that included a pronounced increase in major histocompatibility complex class II (MHCII) gene expression. The dominant pattern across all compartments for B and T cells was a suppression of genes associated with cell activation and signaling after HS/T. Using complement factor 3 (C3) knockout mice we unveiled a role for C3 in the suppression of monocyte Major Histocompatibility Complex class II expression and activation of gene expression associated with migration, phagocytosis and cytokine upregulation, and an unexpected role in promoting interferon-signaling in a subset of B and T cells across all three compartments after HS/T. This transcriptomic landscape study of immune cells provides new insights into the host immune response to trauma, as well as a rich resource for further investigation of trauma-induced immune responses and complement in driving interferon signaling.
Levosimendan Ameliorates Post-resuscitation Acute Intestinal Microcirculation Dysfunction Partly Independent of its Effects on Systemic Circulation: A Pilot Study on Cardiac Arrest in a Rat Model
Authors: Jia Tianyuan , Wang Shiwei , Luo Chengzhun , Wang Zida , Liu Guoxiang , Shang Zhaoming , Lu Xiaoye , Yang Qian , Zhu Changqing
Published: March 2021

Background:

Cardiac arrest (CA) is recognized as a life-threatening disease; however, the initial resuscitation success rate has increased due to advances in clinical treatment. Levosimendan has shown potential benefits in CA patients. However, its exact function on intestinal and systemic circulation in CA or post-cardiac arrest syndrome (PCAS) remained unclear. This study preliminarily investigated the link between dynamic changes in intestine and systemic hemodynamics post-resuscitation after levosimendan administration.

Methods:

Twenty-five rats were randomized into three groups: sham control group (n = 5), levosimendan group (n = 10), and vehicle group (n = 10). Intestinal microcirculation was observed using a sidestream dark-field imaging device at baseline and each hour of the return of spontaneous circulation (≤6 h). Systemic hemodynamics, serum indicators of cardiac injury, and tissue perfusion/metabolism were measured by echo-cardiography, a biological signal acquisition system, and an enzyme-linked immunosorbent assay, respectively.

Results:

Myocardial injury and global and intestinal perfusion/metabolism were significantly improved by levosimendan treatment. There was no statistically significant difference in the mean arterial pressure values between the vehicle and levosimendan groups (P > 0.05). The intestinal and systemic circulation measurements showed poor correlation (Pearson r-value of variable combinations in the levosimendan group was much less than 0.75; P < 0.01, levosimendan vs. vehicle group).

Conclusions:

Levosimendan significantly reduced the cardiac injury and corrected the metabolic status in an experimental rat model of ventricular fibrillation induced CA and cardiopulmonary resuscitation. Levosimendan may ameliorate PCAS-induced intestinal microcirculation dysfunction, partly independent of its effects on macrocirculation.
Sinus, disabling tension-type, and temporomandibular joint headaches
Authors: Kaniecki Robert
Published: March 2021

Purpose of review

Clinicians frequently face questions from headache patients regarding the roles played by sinus issues, muscle tension, and temporomandibular joint (TMJ) problems. This review highlights new concepts regarding the diagnosis and management of these headache conditions and their differentiation from migraine.

Recent findings

Recent research has clarified the roles played by pathology in the paranasal sinuses and TMJ in patients reporting headache. Additional information from physiologic studies in patients with tension-type headache (TTH) has improved the understanding of this condition.

Improved understanding of sinus headache, disabling TTH, and TMJ headache and their differentiation from migraine will lead to reductions in unnecessary diagnostic procedures and unwarranted medical and surgical procedures. More expedient recognition of the origin of headache should lead to improved therapeutic outcomes.
Vector-borne protozoal infections of the CNS: cerebral malaria, sleeping sickness and Chagas disease
Authors: Singh Gagandeep , Njamnshi Alfred K. , Sander Josemir W.
Published: March 2021

Purpose of review

Malaria, Chagas Disease and Human African Trypanosomiasis are vector-borne protozoan illnesses, frequently associated with neurological manifestations. Intriguing but ignored, limited mainly to resource-limited, tropical settings, these disorders are now coming to light because of globalisation and improved diagnosis and treatment. Enhanced understanding of these illnesses has prompted this review.

Recent findings

Methods of diagnosis have currently transitioned from blood smear examinations to immunological assays and molecular methods. Tools to assess neurological involvement, such as magnetic resonance imaging, are now increasingly available in regions and countries with high infection loads. Sleep and other electrophysiological technologies (electroencephalography, actigraphy) are also promising diagnostic tools but requiring field-validation. Access to treatments was formerly limited, even as limitations of agents used in the treatment are increasingly recognised. Newer agents are now being developed and trialled, encouraged by improved understanding of the disorders’ molecular underpinnings.

Prompt diagnosis and treatment are crucial in ensuring cure from the infections. Attention should also be due to the development of globally applicable treatment guidelines, the burden of neurological sequelae and elimination of the zoonoses from currently endemic regions.
Rapid detection of SARS-CoV-2 variants of concern identifying a cluster of B.1.1.28/P.1 variant in British Columbia, Canada
Authors: Matic Nancy , Lowe Christopher F. , Ritchie Gordon , Stefanovic Aleksandra , Lawson Tanya , Jang Willson , Young Matthew , Dong Winnie , Brumme Zabrina L. , Brumme Chanson J. , Leung Victor , Romney Marc G.
Published: March 2021

Using a real-time RT-PCR-based algorithm to detect SARS-CoV-2 variants of concern, we rapidly identified 77 variants (57-B.1.1.7, 7-B.1.351, and 13-B.1.1.28/P.1). This protocol enabled our laboratory to screen all SARS-CoV-2 positive samples for variants, and identified a cluster of B.1.1.28/P.1 cases, a variant not previously known to circulate in British Columbia.
Autologous cardiac micrografts as support therapy to coronary artery bypass surgery
Authors: Nummi Annu , Mulari Severi , Stewart Juhani A. , Kivistö Sari , Teittinen Kari , Nieminen Tuomo , Lampinen Milla , Pätilä Tommi , Sintonen Harri , Juvonen Tatu , Kupari Markku , Suojaranta Raili , Kankuri Esko , Harjula Ari , Vento Antti ,   AADC consortium
Published: March 2021

Objectives

Cardio-regenerative cell therapies offer additional biologic support to coronary artery bypass surgery (CABG) for treating the myocardium suffering from or damaged by ischemia. This phase 1, open-label study assessed the safety and feasibility of epicardial transplantation of atrial appendage micrografts (AAMs) in patients undergoing CABG surgery.

Methods

Twelve consecutive patients destined for CABG surgery were included in the study. Six patients received AAMs during their operation and six patients were CABG-operated without AAMs treatment. Data from 30 elective CABG patients was collected for a conjunctive control group. The AAMs were processed during the operation from a biopsy collected from the right atrial appendage. They were delivered epicardially on the infarct scar site identified in preoperative CMR. The primary outcome measures at six-months follow-up were i) patient safety in terms of hemodynamic and cardiac function over time and ii) feasibility of therapy administration in a clinical setting. Secondary outcome measures were left ventricular wall thickness, change in myocardial scar tissue volume, changes in left ventricular ejection fraction, plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, NYHA class, number of days in hospital and changes in the quality of life.

Results

Epicardial transplantation of AAMs was safe and feasible to be performed in conjunction with CABG surgery. CMR demonstrated an increase in viable cardiac tissue at the infarct site in patients receiving AAMs treatment.

Conclusion

Transplantation of AAMs shows good clinical applicability as adjuvant therapy to cardiac surgery and can additionally serve as a delivery platform for cardiac gene therapies.

Trial Registration

ClinicalTrials.gov identifier NCT02672163
A genetic and transcriptomic assessment of theKTN1gene in Parkinson’s disease risk
Authors: Moore Anni , Bandres-Ciga Sara , Blauwendraat Cornelis , Diez-Fairen Monica
Published: March 2021

Parkinson’s disease (PD) is a progressive neurological disorder caused by both genetic and environmental factors. A recent finding has suggested an association betweenKTN1genetic variants and changes in its expression in the putamen and substantia nigra brain regions and an increased risk for PD. Here, we examine the link between PD susceptibility andKTN1using individual-level genotyping data and summary statistics from the most recent genome-wide association studies (GWAS) for PD risk and age at onset from the International Parkinson’s Disease Genomics Consortium (IPDGC), as well as whole-genome sequencing data from the Accelerating Medicines Partnership Parkinson’s disease (AMP-PD) initiative. To investigate the potential effect of changes inKTN1expression on PD compared to healthy individuals, we further assess publicly available expression quantitative trait loci (eQTL) results from GTEx v8 and BRAINEAC and transcriptomics data from AMP-PD. Overall, we found no genetic associations betweenKTN1and PD in our cohorts but found potential evidence of differences in mRNA expression, which needs to be further explored.
Weak anti-SARS-CoV-2 antibody response after the first injection of an mRNA COVID-19 vaccine in kidney transplant recipients
Authors: Benotmane Ilies , Gautier-Vargas Gabriela , Cognard Noelle , Olagne Jerome , Heibel Francoise , Braun-Parvez Laura , Martzloff Jonas , Perrin Peggy , Moulin Bruno , Fafi-Kremer Samira , Caillard Sophie
Published: March 2021

Data concerning the anti-SARS-CoV-2 antibody response after mRNA COVID-19 vaccine in kidney transplant recipients (KTRs) are currently lacking. Here, we sought to examine this issue by analyzing the serological response observed in 241 KTRs after a first vaccine injection. Our results indicate that KTRs have a weak anti-SARS-CoV-2 antibody response, ultimately resulting in a low seroconversion rate (26/241, 10.8%). This phenomenon likely stems from a high immunosuppression burden in this clinical population.
RubricOE: a learning framework for genetic epidemiology
Authors: Saha Subrata , Guzmán-Sáenz Aldo , Bose Aritra , Utro Filippo , Platt Daniel E. , Parida Laxmi
Published: March 2021

Genetic epidemiology is a growing area of interest in the past years due to the availability of genetic data with the decreasing cost of sequencing. Machine learning (ML) algorithms can be a very useful tool to study the genetic factors on disease incidence or on different traits characterizing a population. There are many challenges that plagues the field of genetic epidemiology including the unbalanced case-control data sets, fallibility of standard genome wide association studies with single marker analysis, heavily underdetermined systems with millions of markers in contrast of a few thousands of samples, to name a few. Ensemble ML methods can be a very useful tool to tackle many of these challenges and thus we propose RubricOE, a pipeline of ML algorithms with error bar computations to obtain interpretable genetic and non-genetic features from genomic or transcriptomic data combined with clinical factors in the form of electronic health records. RubricOE is shown to be robust in simulation studies, detecting true associations with traits of interest in arbitrarily structured multi-ethnic populations.
A longitudinal resource for studying connectome development and its psychiatric associations during childhood
Authors: Tobe Russell H. , MacKay-Brandt Anna , Lim Ryan , Kramer Melissa , Breland Melissa M. , Tu Lucia , Tian Yiwen , Trautman Kristin Dietz , Hu Caixia , Sangoi Raj , Alexander Lindsay , Gabbay Vilma , Castellanos F. Xavier , Leventhal Bennett L. , Craddock R. Cameron , Colcombe Stanley J. , Franco Alexandre R. , Milham Michael P.
Published: March 2021

Most psychiatric disorders are chronic, associated with high levels of disability and distress, and present during pediatric development. Scientific innovation increasingly allows researchers to probe brain-behavior relationships in the developing human. As a result, ambitions to (1) establish normative pediatric brain development trajectories akin to growth curves, (2) characterize reliable metrics for distinguishing illness, and (3) develop clinically useful tools to assist in the diagnosis and management of mental health and learning disorders have gained significant momentum. To this end, the NKI-Rockland Sample initiative was created to probe lifespan development as a large-scale multimodal dataset. The NKI-Rockland Sample Longitudinal Discovery of Brain Development Trajectories substudy (N=369) is a 24- to 30-month multi-cohort longitudinal pediatric investigation (ages 6.0-17.0 at enrollment) carried out in a community-ascertained sample. Data include psychiatric diagnostic, medical, behavioral, and cognitive phenotyping, as well as multimodal brain imaging (resting fMRI, diffusion MRI, morphometric MRI, arterial spin labeling), genetics, and actigraphy. Herein, we present the rationale, design, and implementation of the Longitudinal Discovery of Brain Development Trajectories protocol.
Forecasting the COVID-19 epidemic integrating symptom search behavior: an infodemiology study
Authors: Rabiolo Alessandro , Alladio Eugenio , Morales Esteban , McNaught Andrew I , Bandello Francesco , Afifi Abdelmonem A. , Marchese Alessandro
Published: March 2021

Background

Previous studies have suggested associations between trends of web searches and COVID-19 traditional metrics. It remains unclear whether models incorporating trends of digital searches lead to better predictions.

Methods

An open-access web application was developed to evaluate Google Trends and traditional COVID-19 metrics via an interactive framework based on principal components analysis (PCA) and time series modelling. The app facilitates the analysis of symptom search behavior associated with COVID-19 disease in 188 countries. In this study, we selected data of eight countries as case studies to represent all continents. PCA was used to perform data dimensionality reduction, and three different time series models (Error Trend Seasonality, Autoregressive integrated moving average, and feed-forward neural network autoregression) were used to predict COVID-19 metrics in the upcoming 14 days. The models were compared in terms of prediction ability using the root-mean-square error (RMSE) of the first principal component (PC1). Predictive ability of models generated with both Google Trends data and conventional COVID-19 metrics were compared with those fitted with conventional COVID-19 metrics only.

Findings

The degree of correlation and the best time-lag varied as a function of the selected country and topic searched; in general, the optimal time-lag was within 15 days. Overall, predictions of PC1 based on both searched termed and COVID-19 traditional metrics performed better than those not including Google searches (median [IQR]: 1.43 [0.74-2.36] vs. 1.78 [0.95-2.88], respectively), but the improvement in prediction varied as a function of the selected country and timeframe. The best model varied as a function of country, time range, and period of time selected. Models based on a 7-day moving average led to considerably smaller RMSE values as opposed to those calculated with raw data (median [IQR]: 0.74 [0.47-1.22] vs. 2.15 [1.55-3.89], respectively).

Interpretation

The inclusion of digital online searches in statistical models may improve the prediction of the COVID-19 epidemic.

Funding

EOSCsecretariat.eu has received funding from the European Union’s Horizon Programme call H2020-INFRAEOSC-05-2018-2019, grant Agreement number 831644.
A Recovery Algorithm and Pooling Designs for One-Stage Noisy Group Testing under the Probabilistic Framework
Authors: Liu Yining , Kadyan Sachin , Pe’er Itsik
Published: March 2021

Group testing saves time and resources by testing each pre-assigned group instead of each individual, and one-stage group testing emerged as essential for cost-effectively controlling the current COVID-19 pandemic. Yet, the practical challenge of adjusting pooling designs based on infection rate has not been systematically addressed. In particular, there are both theoretical interests and practical motivation to analyze one-stage group testing at finite, practical problem sizes, rather than asymptotic ones, under noisy, rather than perfect tests, and when the number of positives is randomly distributed, rather than fixed.

Here, we study noisy group testing under the probabilistic framework by modeling the infection vector as a random vector with Bernoulli entries. Our main contributions include a practical one-stage group testing protocol guided by maximizing pool entropy and a maximum-likelihood recovery algorithm under the probabilistic framework. Our findings high-light the implications of introducing randomness to the infection vectors – we find that the combinatorial structure of the pooling designs plays a less important role than the parameters such as pool size and redundancy.
Exploring provider perspectives on patients with atrial fibrillation who are not prescribed anticoagulation therapy
Authors: Yao Catherine , Jones Aubrey E. , Slager Stacey , Fagerlin Angela , Witt Daniel M.
Published: March 2021

Background

Evidence-based guidelines strongly recommend oral anticoagulants to prevent stroke in patients with non-valvular atrial fibrillation (AF). However, many patients are not prescribed guideline recommended anticoagulant therapy.

Objectives

To explore themes underlying anticoagulant prescribing or discontinuation in patients with AF and compare and contrast prescribing preferences between cardiologists and general practitioners.

Methods

Providers at the University of Utah Health system were recruited to participate in semi-structured interviews. An interview guide directed the 15-minute interviews with focus on anticoagulant prescribing practices for patients with AF. Interviews were transcribed verbatim. Two reviewers independently read transcripts and labeled passages of text corresponding with key concepts and themes.

Results

Of the eleven practitioners interviewed, seven practiced in cardiology, two in internal medicine and two in family medicine. The most prominent reasons cited for not prescribing anticoagulation for stroke prevention in AF patients were concerns about intracranial bleeding, followed by gastrointestinal bleeding. Other common reasons were increased age, thrombocytopenia, chemotherapy, previous or concerns of noncompliance, and comorbidities. Providers believed patient refusal of anticoagulants was related to fear of bleeding, medication burden, or warfarin’s negative reputation. All prescribers reported similar prescribing strategies, including using risk stratification, shared decision making, and utilizing specialized anticoagulation clinics and pharmacists as resources.

Conclusion

Fear of bleeding was a common theme underlying anticoagulant underutilization in patients with AF. Identifying major reasons directly from providers can be utilized to develop patient education addressing common fears and misconceptions, promote shared decision making, and provide provider education and resources to achieve appropriate anticoagulant prescribing.
Development and validation of a clinical and genetic model for predicting risk of severe COVID-19
Authors: Dite Gillian S. , Murphy Nicholas M. , Allman Richard
Published: March 2021

Clinical and genetic risk factors for severe COVID-19 are often considered independently and without knowledge of the magnitudes of their effects on risk. Using SARS-CoV-2 positive participants from the UK Biobank, we developed and validated a clinical and genetic model to predict risk of severe COVID-19. We used multivariable logistic regression on a 70% training dataset and used the remaining 30% for validation. We also validated a previously published prototype model. In the validation dataset, our new model was associated with severe COVID-19 (odds ratio per quintile of risk=1.77, 95% confidence interval [CI]=1.64, 1.90) and had excellent discrimination (area under the receiver operating characteristic curve=0.732, 95% CI=0.708, 0.756). We assessed calibration using logistic regression of the log odds of the risk score, and the new model showed no evidence of over- or under-estimation of risk (α=−0.08; 95% CI=−0.21, 0.05) and no evidence or over- or under-dispersion of risk (β=0.90, 95% CI=0.80, 1.00). Accurate prediction of individual risk is possible and will be important in regions where vaccines are not widely available or where people refuse or are disqualified from vaccination, especially given uncertainty about the extent of infection transmission among vaccinated people and the emergence of SARS-CoV-2 variants of concern.

Key results

Accurate prediction of the risk of severe COVID-19 can inform public heath interventions and empower individuals to make informed choices about their day-to-day activities.

Age and sex alone do not accurately predict risk of severe COVID-19.

Our clinical and genetic model to predict risk of severe COVID-19 performs extremely well in terms of discrimination and calibration.
The Value of Rapid Antigen Tests to Identify Carriers of Viable SARS-CoV-2
Authors: Shidlovskaya Elena V. , Kuznetsova Nadezhda A. , Divisenko Elizaveta V. , Nikiforova Maria A. , Siniavin Andrei E. , Ogarkova Daria A. , Shagaev Aleksandr V. , Semashko Maria A. , Tkachuk Artem P. , Burgasova Olga A. , Gushchin Vladimir A.
Published: March 2021

The search for effective methods to detect patients who excrete a viable virus is one of the urgent tasks of modern biomedicine. In the present study, we examined the diagnostic value of two antigen tests BIOCREDIT COVID-19 Ag (RapiGEN Inc., Korea) and SGTI-flex COVID-19 Ag (Sugentech Inc., Korea) for their diagnostic value in identifying patients who excrete viable SARS-CoV-2. As part of the study, we examined samples from 106 patients who had just been admitted to the hospital, who had undergone quantitative RT-PCR and assessment of viability of SARS-CoV-2 using cell culture. Sensitivity was 0.786 (0.492–0.953) for SGTI-flex COVID-19 Ag and 1 (0.768– 1) for Biocredit COVID-19 Ag. Specificity of rapid tests was significantly higher than that of RT-PCR and was 0.663 (0.557–0.758) and 0.674 (0.568–0.768) for SGTI-flex COVID-19 Ag and Biocredit COVID-19 Ag versus 0.304 (0.213–0.409) obtained for PCR. Thus, for tasks of identifying viable SARS-CoV-2 during screening of conditionally healthy people, as well as monitoring those quarantined, rapid tests show significantly better results.
Brain connectivity and motor improvements after ballet intervention in multiple sclerosis: pilot
Authors: Camacho Paul B. , Sutton Brad P. , López-Ortiz Citlali
Published: March 2021

Background and Purpose

A pilot study to determine feasibility of detecting changes in structural connectivity (SC) and resting-state functional connectivity (RSFC) occur alongside motor improvements after participation in the Targeted Ballet Program (TBP) in adults with relapsing-remitting multiple sclerosis (RRMS).

Methods

Five participants (four female) with RRMS between the ages of 38-64 with the following characteristics at baseline: Expanded Disability Status Scale 2.0-6.0, International Cooperative Ataxia Rating Scale (ICARS) > 7, Symbol-Digit Modality Test > 22, and no relapses or initiation of medications indicated to affect mobility within the past 30 days. Participants were asked to complete 12 weeks (one hour, twice per week) of the TBP. Magnetic resonance imaging data was collected pre- and post-intervention for SC and RSFC network analysis.

Results

Increases in two RRMS-related graph theoretical measures (mean strength and mean clustering coefficient) for RSFC (p < 0.05) are detectable alongside significant reduction in ataxia (ICARS: p = 0.01012, Smoothness Index: p = 0.04995), and increase in balance (Mini-BESTest: p = 0.01474) following participation in the well-tolerated TBP.

Discussion and Conclusions

Significant increases in mean strength and mean clustering coefficient of RSFC suggest functional neurological improvements after participation in the TBP. The relationship between these network changes and clinical improvements in balance and amelioration of ataxia after participation in the TBP requires a larger randomized-controlled clinical trial of the TBP in persons with RRMS.
Isofurans and isoprostanes as markers of delayed brain injury and mitochondrial dysfunction following aneurysmal subarachnoid hemorrhage. A prospective observational study
Authors: Gomes Joao A. , Milne Ginger , Kallianpur Asha , Shriver Leah
Published: March 2021

Introduction

F2-Isoprostanes (F2-IsoPs) and Isofurans (IsoF), specific markers of lipid peroxidation in vivo, have been reported to be elevated and have prognostic implications following subarachnoid hemorrhage (SAH). Platelet activation and vasoconstriction are attributed to these compounds. Elevated IsoF: F2-IsoPs ratios have been previously suggested as indicative of mitochondrial dysfunction. In this small study we examined their performance as specific biomarkers for delayed brain injury (DBI) development following SAH. We also explored if evidence of mitochondrial dysfunction could be found in a cohort of SAH patients.

Methods

Eighteen patients with SAH and 7 controls with normal neuroimaging and CSF analysis results underwent CSF sampling and abstraction of clinical, demographic, and laboratory data. Samples (two) of CSF were collected on day 1 and once on days 5-8 post-bleed. F2-IsoP and IsoF assays were performed at Vanderbilt Eicosanoid Core Lab by gas chromatography/mass spectroscopy. Levels are expressed in median (IQR) for non-parametric data. Repeated sample measurement were compared using the Wilcoxon signed-rank test, whereas the Mann Whitney test was used for other non-parametric data.

Results

Mean age was 61.2 + 15.7 (SAH cases) vs. 47.6 + 10 (controls) years, and 80% of SAH patients were female. Median Hunt-Hess score was 3 (2-4) and modified Fisher scale 3 (3-4). Thirty nine percent of patients developed DBI. F2-IsoP were significantly higher in SAH cases than in controls [47.5 (30.2-53.5) vs. 26.0 (21.2-34.5) pg/mL]. No significant differences were observed in patients with or without DBI [41 (33.5-52) vs. 44 (28.5-55.5) pg/mL]. IsoF were elevated in the second CSF sample in 9 patients, but undetectable in the remainder cases and all controls. Patients who developed DBI had significantly higher IsoF than cases who did not [(57 (34-72) vs. 0 (0-34) pg/mL]. Patients who met criteria for delayed injury had a significantly higher IsoF: F2IsoPs ratio on the late CSF sample [1.03 (1-1.38) vs. 0 (0-0.52)].

Conclusions

Preliminary findings from this study suggest that IsoF may represent a specific biomarker predicting DBI following SAH and provide possible evidence of CNS mitochondrial dysfunction in SAH. Future studies to further explore the value of IsoF as biomarkers of secondary brain injury and the contribution of mitochondrial dysfunction and ferroptosis to clinical outcomes following SAH seem warranted.
Infections in childhood and subsequent diagnosis of autism spectrum disorders and intellectual disability: a register-based cohort study
Authors: Karlsson Håkan , Sjöqvist Hugo , Brynge Martin , Gardner Renee , Dalman Christina
Published: March 2021

Objective

To explore the associations between childhood infections and subsequent diagnoses of autism spectrum disorder (ASD), intellectual disability (ID) and their co-occurrence.

Methods

The association between specialized care for any infection, defined by ICD-codes and later ASD or ID was investigated in a register-based cohort of 556,732 individuals born 1987-2010, resident in Stockholm County, followed from birth to their 18th birthday or December 31, 2016. We considered as potential confounders children’s characteristics, family socioeconomic factors, obstetric complications, and parental histories of both treatment for infection and psychiatric disorders in survival analyses with extended Cox regression models. Residual confounding by shared familial factors was addressed in sibling analyses using within-strata estimation in Cox regression models. Sensitivity analyses with exclusion of congenital causes of ASD/ID and documented risk for infections were also performed.

Results

Crude estimates indicated that infections during childhood were associated with later ASD and ID with largest risks observed for diagnoses involving ID. Inclusion of covariates, exclusion of congenital causes of ASD/ID from the population and sibling comparisons highlighted the potential for confounding by both heritable and non-heritable factors, though risks remained in all adjusted models. In adjusted sibling comparisons, excluding congenital causes, infections were associated with later ‘ASD without ID’ (HR 1.24, 95%CI 1.15-1.33), ‘ASD with ID’ (1.57, 1.35-1.82) and ‘ID without ASD’ (2.01, 1.76-2.28). Risks associated with infections varied by age at exposure and by age at diagnosis of ASD/ID.

Conclusions

Infections during childhood cannot be excluded in the etiology of ASD, particularly ASD with co-occurring ID.
Wastewater Surveillance of SARS-CoV-2 across 40 U.S. states
Authors: Wu Fuqing , Xiao Amy , Zhang Jianbo , Moniz Katya , Endo Noriko , Armas Federica , Bushman Mary , Chai Peter R , Duvallet Claire , Erickson Timothy B , Foppe Katelyn , Ghaeli Newsha , Gu Xiaoqiong , Hanage William P , Huang Katherine H , Lee Wei Lin , Matus Mariana , McElroy Kyle A , Rhode Steven F , Wuertz Stefan , Thompson Janelle , Alm Eric J
Published: March 2021

Wastewater-based disease surveillance is a promising approach for monitoring community outbreaks. Here we describe a nationwide campaign to monitor SARS-CoV-2 in the wastewater of 159 counties in 40 U.S. states, covering 13% of the U.S. population from February 18 to June 2, 2020. Out of 1,751 total samples analyzed, 846 samples were positive for SARS-CoV-2 RNA, with overall viral concentrations declining from April to May. Wastewater viral titers were consistent with, and appeared to precede, clinical COVID-19 surveillance indicators, including daily new cases. Wastewater surveillance had a high detection rate (>80%) of SARS-CoV-2 when the daily incidence exceeded 13 per 100,000 people. Detection rates were positively associated with wastewater treatment plant catchment size. To our knowledge, this work represents the largest-scale wastewater-based SARS-CoV-2 monitoring campaign to date, encompassing a wide diversity of wastewater treatment facilities and geographic locations. Our findings demonstrate that a national wastewater-based approach to disease surveillance may be feasible and effective.
Model Based Estimation of the SARS-CoV-2 Immunization Level in Austria and Consequences for Herd Immunity Effects
Authors: Bicher Martin , Rippinger Claire , Schneckenreither Günter , Weibrecht Nadine , Urach Christoph , Zechmeister Melanie , Brunmeir Dominik , Huf Wolfgang , Popper Niki
Published: March 2021

Several systemic factors indicate, that worldwide herd immunity against COVID-19 will probably not be achieved in 2021. Vaccination programs are limited by availability of doses, the number of people already infected is still too low to have a disease preventing impact and new emerging variants of the virus seem to partially neglect developed antibodies from previous infections. Nevertheless, after one year of COVID-19 observing high numbers of reported cases in most European countries, we might expect that the immunization level should have an impact on the spread of SARS-CoV-2. We used an agent-based simulation model to reproduce the COVID-19 pandemic in Austria to estimate the immunization level of the population as of February 2021. We ran several simulations of an uncontrolled epidemic wave with varying initial immunization scenarios to assess the effect on the effective reproduction number. We also used a classic differential equation SIR-model to cross-validate the simulation model. As of February 2021, 14.7% of the Austrian population has been affected by a SARS-CoV-2 infection which causes a 9% reduction of the effective reproduction number and a 24.7% reduction of the prevalence peak compared to a fully susceptible population. This estimation is now recomputed on a regular basis to publish model based analysis of immunization level in Austria also including the fast growing effects of vaccination programs. This provides substantial information for decision makers to evaluate the necessity of NPI-measures based on the estimated impact of natural and vaccinated immunization.
Differential Impacts of COVID-19 Lockdowns on PM2.5 across the United States
Authors: Chen Kevin L. , Henneman Lucas R.F. , Nethery Rachel C.
Published: March 2021

The COVID-19 pandemic has induced large-scale social, economic, and behavioral changes, presenting a unique opportunity to study how air pollution is affected by unprecedented societal shifts. At each of 455 PM2.5 monitoring sites across the United States, we conduct a causal inference analysis to determine the impacts of COVID-19 interventions and behavioral changes (“lockdowns”) on PM2.5 concentrations. Our approach allows for rigorous confounding adjustment and provides highly spatio-temporally resolved effect estimates. We find that, with the exception of the Southwest, most of the US experienced increases in PM2.5 during lockdown, compared to the concentrations expected under business-as-usual. To investigate possible drivers of this phenomenon, we use regression to characterize the relationship of many environmental, geographical, meteorological, mobility, and socioeconomic factors with the lockdown-attributable changes in PM2.5. Our findings have immense environmental policy relevance, suggesting that large-scale mobility and economic activity reductions may be insufficient to substantially and uniformly reduce PM2.5.
Repeated Testing Necessary: Assessing Negative Predictive Value of SARS-CoV-2 qPCR in a Population of Young Adults
Authors: Thompson Elaine E. , Rosenthal Joseph H. , Wren James , Seetao Erik , Olson Niels H.
Published: March 2021

Determining when individuals should be released from quarantine is critical for successfully managing a COVID-19 outbreak and local protocols frequently call for testing during the quarantine period, generally after a reasonable incubation period, which raises a question about the interpretation of test results during the quarantine period. We report the negative predictive value of SARS-CoV-2 qPCR tests based on a retrospective longitudinal analysis of 5349 qPCR tests collected from 1227 US service members infected with COVID-19 aboard the USS Theodore Roosevelt (CVN-71) aircraft carrier. In our retrospective evaluation of recovering qPCR-positive quarantined crew members undergoing repeated testing, the negative predictive value is 80% for tests occurring as late as seven weeks following an initial positive qPCR test result. Repeated qPCR testing is necessary to ensure that a once-infected person is no longer shedding viral RNA. When deciding the stringency of exit criteria, we recommend considering local operational and community risk factors.
Evaluating risk detection methods to uncover ontogenic-mediated adverse drug effect mechanisms in children
Authors: Giangreco Nicholas P. , Tatonetti Nicholas P.
Published: March 2021

Background

Identifying adverse drugs effects (ADEs) in children is essential for preventing disability and death from marketed drugs. At the same time, however, detection is challenging due to dynamic biological processes during growth and maturation, called ontogeny, that alter pharmacokinetics and pharmacodynamics. As a result, current data mining methodologies have been limited to event surveillance and have not focused on investigating adverse event mechanisms. There is an opportunity to design data mining methodologies to identify and evaluate drug event patterns within observational databases for ontogenic-mediated adverse event mechanisms. The first step of which is to establish statistical models that can identify temporal trends of adverse effects across childhood.

Results

Using simulation, we evaluated a population stratification method (the proportional reporting ratio or PRR) and a population modeling method (the generalized additive model or GAM) to identify and quantify ADE risk at varying reporting rates and dynamics. We found that GAMs showed improved performance over the PRR in detecting dynamic drug event reporting across child developmental stages. Moreover, GAMs exhibited normally distributed and robust ADE risk estimation at all development stages by sharing information across child development stages.

Conclusions

Our study underscores the opportunity for using population modeling techniques, which leverages drug event reporting across development stages, to identify adverse drug effect risk resulting from ontogenic mechanisms.
A Dynamical Map to Describe COVID-19 Epidemics
Authors: dos Reis Eduardo V. M. , Savi Marcelo A.
Published: March 2021

Nonlinear dynamics perspective is an interesting approach to describe COVID-19 epidemics, providing information to support strategic decisions. This paper proposes a dynamical map to describe COVID-19 epidemics based on the classical susceptible-exposed-infected-recovered (SEIR) differential model, incorporating vaccinated population. On this basis, the novel map represents COVID-19 discrete-time dynamics by adopting three populations: infected, cumulative infected and vaccinated. The map promotes a dynamical description based on algebraic equations with a reduced number of variables and, due to its simplicity, it is easier to perform parameter adjustments. In addition, the map description allows analytical calculations of useful information to evaluate the epidemic scenario, being important to support strategic decisions. In this regard, it should be pointed out the estimation of the number death cases, infectious rate and the herd immunization point. Numerical simulations show the model capability to describe COVID-19 dynamics, capturing the main features of the epidemic evolution. Reported data from Germany, Italy and Brazil are of concern showing the map ability to describe different scenario patterns that include multi-wave and plateaus behaviors. The effect of vaccination is analyzed considering different campaign strategies, showing its importance to control the epidemics.
A single motor neuron determines the rhythm of early motor behaviour inCiona
Authors: Akahoshi Taichi , Oonuma Kouhei , Murakami Makoto , Horie Takeo , Kusakabe Takehiro G. , Oka Kotaro , Hotta Kohji
Published: March 2021

Vertebrate rhythmic motor behaviour is generated by the central pattern generator (CPG) located in the spinal cord. However, the development of the CPG has not been elucidated at the single-neuron level. We found that a single pair of motor neurons (A10.64/MN2) constitutes the CPG and regulates rhythmic early motor behaviour in the proto-chordate,Ciona. This pair of cells exhibited Ca2+oscillation with an 80-sec interval at the mid-tailbud stage and 25 sec at the late tailbud stage. The Ca2+oscillation occurred independently in a dissociated single cell. In the late tailbud stage, the Ca2+oscillation began to coincide in phase with the ipsilateral tail muscle contraction, which corresponds to rhythmic early motor behaviour. Interestingly, the number and frequency of tail muscle contractions gradually coincided with spikes in the burst of membrane potential as the embryos developed toward late tailbud stage. Photoablation of A10.64/MN2 abolished the rhythmic early motor behaviour. These findings indicate that the early spontaneous rhythmic motor behaviour ofCionais directly regulated by A10.64/MN2 as an essential component of the CPG. Our findings shed light on the development and evolution of chordate rhythmic behaviours.