bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Laboratory Follow-up After Hospitalization for COVID-19 at an Italian Tertiary Care Center
Authors: Spinicci Michele , Vellere Iacopo , Graziani Lucia , Tilli Marta , Borchi Beatrice , Mencarini Jessica , Campolmi Irene , Gori Leonardo , Rasero Laura , Fattirolli Francesco , Olivotto Iacopo , Lavorini Federico , Marchionni Niccolò , Zammarchi Lorenzo , Bartoloni Alessandro ,   Careggi Post-acute COVID-19 Study Group, Fumagalli Carlo , Silverii Maria Vittoria , Ciani Luca , Zocchi Chiara , Tassetti Luigi , Marcucci Rossella , Giusti Betti , Livi Luca , Giovannoni Lorenzo , Parronchi Paola , Almerigogna Fabio , Annunziato Francesco , Mazzoni Alessio , Maggi Laura , Liotta Francesco , Cosmi Lorenzo , Vultaggio Alessandra , Matucci Andrea , Sticci Silvia , Donati Martina , Defraia Cecilia , Giansanti Fabrizio , Bacherini Daniela
Published: February 2021

We evaluated 100 postacute coronavirus disease 2019 (COVID-19) patients a median (interquartile range) of 60 (48–67) days after discharge from the Careggi University Hospital, Italy. Eighty-four (84%) had at least 1 persistent symptom, irrespective of COVID-19 severity. A considerable number of hospital readmissions (10%) and/or infectious diseases (14%) during the postdischarge period were reported.
A Risk Score to Predict Clostridioides difficile Infection
Authors: Aukes Laurie , Fireman Bruce , Lewis Edwin , Timbol Julius , Hansen John , Yu Holly , Cai Bing , Gonzalez Elisa , Lawrence Jody , Klein Nicola P
Published: February 2021

Background

Clostridioides difficile infection (CDI) is a major cause of severe diarrhea. In this retrospective study, we identified CDI risk factors by comparing demographic and clinical characteristics for Kaiser Permanente Northern California members ≥18 years old with and without laboratory-confirmed incident CDI.

Methods

We included these risk factors in logistic regression models to develop 2 risk scores that predict future CDI after an Index Date for Risk Score Assessment (IDRSA), marking the beginning of a period for which we estimated CDI risk.

Results

During May 2011 to July 2014, we included 9986 CDI cases and 2 230 354 members without CDI. The CDI cases tended to be older, female, white race, and have more hospitalizations, emergency department and office visits, skilled nursing facility stays, antibiotic and proton pump inhibitor use, and specific comorbidities. Using hospital discharge as the IDRSA, our risk score model yielded excellent performance in predicting the likelihood of developing CDI in the subsequent 31–365 days (C-statistic of 0.848). Using a random date as the IDRSA, our model also predicted CDI risk in the subsequent 31–365 days reasonably well (C–statistic 0.722).

Conclusions

These results can be used to identify high-risk populations for enrollment in C difficile vaccine trials and facilitate study feasibility regarding sample size and time to completion.
Supplementing Extraoperative Electrocorticography With Real-Time Intraoperative Recordings Using the Same Chronically Implanted Electrodes
Authors: Warsi Nebras M , Narvacan Karl , Donner Elizabeth , Go Cristina , Strantzas Samuel , Ochi Ayako , Otsubo Hiroshi , Sharma Roy , Snead O Carter , Ibrahim George M
Published: February 2021

BACKGROUND

The practice of intraoperative electrocorticography (iECoG) to guide resective epilepsy surgery is variable. Limitations of iECoG include variability in recordings from previously unsampled cortex, increased operative time and cost, and a lack of clear benefit to surgical decision-making.

OBJECTIVE

To describe a simple technique to supplement extraoperative intracranial recordings with real-time iECoG using the same chronically implanted electrodes that overcome some of these limitations.

METHODS

We describe the technical procedure, intraoperative findings, and outcomes of 7 consecutive children undergoing 2-stage resective epilepsy surgery with invasive subdural grid monitoring between January 2017 and December 2019. All children underwent placement of subdural grids, strips, and depth electrodes. Planned neocortical resection was based on extraoperative mapping of ictal and interictal recordings. During resection in the second stage, the same electrodes were used to perform real-time iECoG.

RESULTS

Real-time iECoG using this technique leads to modification of resection for 2 of the 7 children. The first was extended due to an electroencephalographic seizure from a distant electrode not part of the original resection plan. The second was restricted due to attenuation of epileptiform activity following a partial resection, thereby limiting the extent of a Rolandic resection. No infections or other adverse events were encountered.

CONCLUSION

We report a simple technique to leverage chronically implanted electrodes for real-time iECoG during 2-stage resective surgery. This technique presents fewer limitations than traditional approaches and may alter intraoperative decision-making.
Refractory Chronic Pain and Obesity: Promising Implications for Multidisciplinary Pain Rehabilitation
Authors: Pudalov Lauren R , Krause Steven J , Heinberg Leslie J , Hogue Olivia
Published: February 2021

Objective

Individuals with obesity frequently contend with chronic pain, but few studies address the clinical impact of coordinated pain services on this population. The current study addresses this topic by comparing the effectiveness of a comprehensive pain rehabilitation program for patients with and without obesity.

Methods

A retrospective analysis of registry data was conducted. Obesity was considered as one of three weight groups, based on the following body mass index cutoffs: normal weight (18.5 to < 25 kg/m2), overweight (25 to < 30 kg/m2), and obese (> 30 kg/m2). These groups were compared on the Pain Severity Ratings (PSR) Scale, the Pain Disability Index (PDI), and the Depression, Anxiety, Stress Scales—Short Form (DASS-SF).

Results

Groups differed on baseline pain disability and depression. Patients with obesity had higher scores on both the PDI (P = .028) and the DASS-SF depression subscale (P = .006). Contrary to the hypothesis, after controlling for baseline score and sex there were no significant differences between weight groups with regards to PSR, PDI, or any DASS-SF subscale at discharge. At 1-year follow-up, individuals who were overweight and obese had significantly more anxiety compared to individuals whose weight was in the normal range.

Conclusions

Multidisciplinary pain rehabilitation programs appear to be an effective treatment intervention for patients who have concomitant chronic pain and obesity, to a degree comparable to patients who have chronic pain but do not contend with obesity. Implications for program development, clinical interventions, and future research are discussed.
Incidence of lung cancer following pneumonia in smokers: a population-based study
Authors: Shepshelovich D , Barda N , Goldvaser H , Dagan N , Zer A , Diker-Cohen T , Balicer R , Gafter-Gvili A
Published: February 2021

Background

Pneumonia is more common in smokers compared with non-smokers. A high 1-year prevalence of lung cancer following hospitalization for pneumonia was demonstrated in heavy smokers.

Aim

To assess the association between hospitalization for pneumonia among ever-smokers and subsequent lung cancer risk.

Design

Retrospective analysis.

Methods

The study cohort included all ever-smokers aged 55–80 hospitalized for pneumonia between the years 2010–15 covered by a large medical insurer in Israel. Controls were matched to cases by age in a 4:1 ratio. The primary outcome was the association between hospitalization for pneumonia and subsequent 1-year incidence of lung cancer, adjusted for gender, smoking status (past/current) and pack years. Pre-specified sensitivity analyses excluded heavy smokers (smoking history of more than 30 pack years) and patients diagnosed with lung cancer within 30 days of hospitalization, as they probably had clinical or radiological findings suggestive of lung cancer, making them ineligible for screening.

Results

Lung cancer was identified in 275 of 12 807 (2.1%) patients following hospitalization for pneumonia and in 44 of 51 228 (0.1%) controls (adjusted odds ratio 22.46, 95% CI 16.29–30.96, P < 0.001). Among patients hospitalized for pneumonia, 1-year lung cancer incidence remained high after excluding heavy smokers and patients diagnosed within 30 days of the index date (1.3% and 1.4%, respectively).

Conclusions

Hospitalization for pneumonia is associated with high 1-year incidence of lung cancer in ever-smokers, supporting the important role of the widely used practice of performing follow up imaging post-pneumonia to exclude occult malignancy.
COMPARISON OF THE PERFORMANCE OF TWO OSL READERS FOR THE PERSONAL DOSE EQUIVALENT HP(10) MEASUREMENT
Authors: Njiki Calvin Didier , Ndah Thierry Ndzana , Ben Bolie Germain H , Beyala Ateba Jean Féli , Simo Augustin , Yigbedeck Yolande Huguette Ebele
Published: February 2021

Technical performances of two optically stimulated luminescence readers including, a microStar reader and an Auto 200 reader both manufactured by Landauer, Inc. were studied by the National Radiation Protection Agency Dosimetry Laboratory using manufacturer and International Electrotechnical Commission requirements. The two reader tools demonstrated satisfactory results as they met all the requirements. The two readers showed similar performance for the overall uncertainty and the Coefficient of Variation tests. The microStar reader showed better performances for the linearity and quality control tests, whereas the Auto 200 reader has a lower limit of detection. Moreover, an average shift of 0.08 mSv exists when measuring the doses with the two readers.
Water intake of pigs consuming tiamulin during the nursery phase1
Authors: Vonnahme Kimberly A , Mueller Adam , Nelson Daniel A , Vasquez-Hidalgo Manuel Alexander , Amodie Deborah , Short Thomas H , Mellencamp Martha A , Galina Pantoja Lucina
Published: February 2021

Mass medication to manage population health can be achieved by providing therapeutics in the drinking water. Young nursery pigs are highly sensitive to the flavor and smell of water. Medications that reduce water palatability often lead to an interruption in water and feed intake. With the availability of several generic water-soluble antimicrobials for pigs, questions have arisen about their palatability compared with the original product. In this study, we compared the intake of water containing tiamulin hydrogen fumarate from two different manufacturers with the intake of unmedicated water. The hypothesis was that the intake of tiamulin-containing water would be similar to unmedicated water. Water intake was monitored upon entry into the nursery and just prior to leaving the nursery. Also, average daily gain (ADG) and feed efficiency (FE) were determined. A total of 300 pigs were individually weighed (4.2–10.9 kg; avg = 6.8 kg) for randomization to pen (n = 30 pens). The experiment had two time points: 1) early nursery (periods 1–3) and 2) late nursery (period 4). Pens were randomly assigned to a sequence (period 1–3) in a crossover experimental design containing three 10-d periods, with 5 d for the resetting of baseline where unmedicated water was provided followed by 5 d on tiamulin source addition [i.e., TriamuloxTM (Zoetis, Parsippany, NJ); Denagard (Elanco Animal Health, Greenfield, IN)] or unmedicated water. After period 3 was concluded, all pens were given unmedicated water (via nipple waterers) and the number of pigs per pen was reduced to six pigs to maintain adequate space per pig. Ten days prior to pigs leaving the nursery, a fourth period was performed. After a 5-d water baseline was achieved, pens were treated with either unmedicated water or Triamulox- or Denagard-containing water. Pigs had ad libitum access to water and feed. During the testing periods, daily water intake was measured by a cup water system in each pen. Feed intake was measured every 5 d. There was no effect of treatment on initial body weights or weights at the beginning or end of each period (P ≥ 0.51). Therefore, there was no effect of treatment on ADG (P ≥ 0.23). Water intake (P ≥ 0.16) and FE (P ≥ 0.35) were not affected by treatment. Water consumption was similar among all treatments in each of the four periods. There appears to be no aversion to water intake when tiamulin hydrogen fumarate is added to the drinking water.
Synthesizing the literature on physical activity among children and adolescents affected by cancer: evidence for the international Pediatric Oncology Exercise Guidelines (iPOEG)
Authors: Wurz Amanda , McLaughlin Emma , Lategan Conné , Ellis Kelsey , Culos-Reed S Nicole
Published: February 2021

Physical activity (PA), including exercise, is safe and beneficial for children and adolescents affected by cancer. Yet, no efforts have been made to collate the breadth of review and experimental articles exploring the effects of PA in this cohort. Thus, a scoping review of review and experimental articles reporting on the effects of PA for children and adolescents affected by cancer was undertaken. Review and experimental articles published in English, summarizing or reporting on the effects of PA interventions for children and adolescents affected by cancer were included. Articles were identified through prior literature, systematic searching, reference list scanning, stakeholder engagement, and a database update. Data were extracted, collated, assessed for quality (reviews) or risk of bias (experimental articles), and summarized narratively. A total of 1,380 articles were identified; 20 review and 69 experimental articles were included. Articles explored PA behavior, physical, psychosocial, cognitive, and “other” outcomes. Improvements, no change, or mixed results were reported across the majority of outcomes explored. Two PA-related adverse events (e.g., a treatable injury, fatigue) were described. Included articles varied greatly in quality and risk of bias. Findings confirm that PA for children and adolescents affected by cancer is a rapidly growing field. More adequately powered research, focused on priority outcomes, adopting appropriate study designs, and adhering to reporting standards is required. Addressing these gaps will enable a better understanding of the effects of PA. Nevertheless, the literature confirms moving more is beneficial and safe for children and adolescents affected by cancer.
Polycyclic Aromatic Hydrocarbon-DNA Adducts in Gulf of Mexico Sperm Whale Skin Biopsies Collected in 2012
Authors: Poirier Miriam C , Marsili Letizia , Fossi Maria Cristina , Godard-Codding Céline A. J , Hernandez-Ramon Elena E , Si Nancy , Divi Kathyayini V , Divi Rao L , Kerr Iain , Wise John Pierce , Wise Catherine F , Wise Sandra S , Aboueissa Abou El-Makarim , Wise James T. F , Wise John Pierce
Published: February 2021

The northern Gulf of Mexico has a long history of polycyclic aromatic hydrocarbon (PAH) contamination from anthropogenic activities, natural oil seepages, and the 2010 Deepwater Horizon explosion and oil spill. The continental shelf of the same area is a known breeding ground for sperm whales (Physeter macrocephalus). To evaluate PAH-DNA damage, a biomarker for potential cancer risk, we compared skin biopsies collected from Gulf of Mexico sperm whales in 2012 with skin biopsies collected from sperm whales in areas of the Pacific Ocean in 1999–2001. All samples were obtained by crossbow and comprised both epidermis and subcutaneous blubber. To evaluate exposure, 7 carcinogenic PAHs were analyzed in lipids extracted from Pacific Ocean sperm whale blubber, pooled by sex, and location. To evaluate PAH-DNA damage, portions of all tissue samples were formalin-fixed, paraffin-embedded, sectioned, and examined for PAH-DNA adducts by immunohistochemistry (IHC) using an antiserum elicited against benzo[a]pyrene-modified DNA, which crossreacts with several high molecular weight carcinogenic PAHs bound to DNA. The IHC showed widespread epidermal nuclear localization of PAH-DNA adducts in the Gulf of Mexico whales (n = 15) but not in the Pacific Ocean whales (n = 4). A standard semiquantitative scoring system revealed significantly higher PAH-DNA adducts in the Gulf of Mexico whales compared to the whales from the Pacific Ocean study (p = .0002).
ATAC-Seq Data for Genome-Wide Profiling of Transcription Factor Binding Sites in the Rice False Smut Fungus Ustilaginoidea virens
Authors: Chen Xiaoyang , Liu Hao , Chen Xiaolin , Huang Junbin , Hsiang Tom , Zheng Lu
Published: February 2021

Identification of transcription factor binding sites is one of the most important steps in understanding the function of transcription factors and regulatory networks in organisms. The assay for transposase accessible chromatin sequencing (ATAC-seq) is a simple protocol for detection of open chromatin that could be a powerful tool to advance studies of protein-DNA interactions. Although ATAC-seq has been used in systematic identification of cis-regulatory regions in animal and plant genomes, this method has been rarely applied in fungi. Here, we describe a valuable ATAC-seq resource in the genome of an economically important phytopathogen, the rice false smut fungus Ustilaginoidea virens. The ATAC-seq data of U. virens mycelia collected from potato sucrose broth (PSB) and PSB supplied with rice spikelet extract were both generated. This is the first genome-wide profiling of open chromatin and transcription factor binding sites in U. virens.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Effect of Sacroiliac Fusion and Pelvic Fixation on Rod Strain in Thoracolumbar Fusion Constructs
Authors: Mushlin Harry M. , Shea Phelan , Brooks Daina M. , Hayward Gerald M. , Ferrick Bryan J. , Olexa Joshua , Bucklen Brandon S. , Sansur Charles
Published: February 2021

Study Design.

In vitro biomechanical study.

Objective.

Investigate effects of sacroiliac joint (SIJ) fusion and iliac fixation on distal rod strain in thoracolumbar fusions.

Summary of Background Data.

Instrument failure is a multifactorial, challenging problem frequently encountered by spinal surgeons. Increased rod strain may lead to instrumentation failure and rod fracture.

Methods.

Seven fresh frozen human cadaveric specimens (T9–pelvis) used. Six operative constructs tested to investigate changes in rod strain at L5–S1 and S1–Ilium rods, posterior pedicle screws/rods from T10–S1 (PS), PS + bilateral iliac screw fixation, PS + unilateral iliac screw fixation (UIS), PS+UIS+3 unilateral SIJ screws, PS + 3 unilateral SIJ screws, and PS +6 bilateral SIJ screws. Uniaxial strain gauges were used to measure surface strain of rods during flexion-extension.

Results.

In flexion-extension, bilateral iliac screws added significant strain to L5–S1 compared with long fusion constructs ending at S1 (PS) (P < 0.05). Unilateral iliac fixation exhibited highest strain to L5–S1 ipsilateral rod, was significantly higher compared with bilateral iliac fixation and PS construct. Unilateral and bilateral SIJ fusion did not significantly change L5–S1 rod strain compared with PS. When measuring S1–Ilium rod strain, unilateral pelvic fixation had highest reported rod strain, approached significance compared with bilateral iliac screws (P = 0.054). Addition of contralateral SIJ fusion did not affect rod strain at S1–ilium on side with unilateral fixation.

Conclusion.

Results showed additional fixation below S1 to pelvis added significant rod strain. Unilateral pelvic screws had highest rod strain; SIJ fusion did not affect rod strain. Findings can help guide surgeons when associated risk of rod failure is a consideration.

Level of Evidence: N/A
The Changing Role of Chest Pain in the Emergency Department Observation Unit
Authors: Terry Nataisia , Franks Nicole , Moran Tim , Pitts Steve , Osborne Anwar , Ross Michael A.
Published: February 2021

Background:

This study objective was to describe changes in the utilization of a protocol-driven emergency department observation unit (EDOU) for chest pain over time.

Methods:

This is a retrospective serial cross-sectional study of data from a clinical data warehouse of a single integrated healthcare system. We estimated long-term trends (2009–2019) in EDOU visits at 4 system hospitals, using monthly proportions as the main outcome, and month of visit as the exposure variable, accounting for age and sex. Rate changes associated with compulsory use of the History, EKG, Age, Risk factors, Troponin (HEART) score in 2016 were analyzed.

Results:

There were 83,168 EDOU admissions among 1.3 million ED visits during the study interval, with an average admission rate of 5.9% of ED visits. The most common conditions were chest pain (41.2%), transient ischemic attack (7.8%), dehydration (6.3%), syncope (5.8%), and abdominal pain (5.2%). In each hospital, there was a temporal annual decline in the proportion of EDOU visits for chest pain protocols ranging from −7.9% to −2.8%, an average rate of −3.3% per year (95% CI, −4.6% to −2.0%) or a 54% (from 54% to 25%) relative decline in over the 11-year study interval. This decline was significantly steeper in younger middle–aged patients (ages 39–49). The HEART score intervention had a small impact on baseline decline of −3.1% at the 2 intervention hospitals, reducing it by −1.5% (95% CI, −2.2% to −0.8%).

Conclusions:

Utilization of the EDOU for chest pain decreased over time, with corresponding increases in other conditions. This decline preceded the introduction of the HEART score.
The Impact of Accelerated Diagnostic Protocol Implementation on Chest Pain Observation Unit Utilization
Authors: Husain Iltifat , Mahler Simon A. , Hiestand Brian C. , Miller Chadwick D. , Stopyra Jason P.
Published: February 2021

Background:

Data evaluating the impact of the history, ECG, age, risk factors, and troponin (HEART) Pathway on observation unit (OU) use is limited. The objective of this study is to determine how HEART Pathway implementation affects OU use.

Methods:

An analysis of OU registry data from October 2012 to October 2016, 2 years before and after HEART Pathway implementation at an academic medical center, was conducted. Adult patients placed in the OU for chest pain were included. The proportion of patients placed in the OU chest pain protocol per total OU volume and hospitalization and myocardial infarction (MI) rates were determined. Proportions before versus after implementation were compared using χ2 tests and age was compared using a Mann-Whitney U test.

Results:

During the study period, 1688 patients with chest pain before HEART Pathway implementation and 1692 after were included. The proportion of chest pain patients in the OU per total OU volume decreased following implementation from (57% [1688/2968] to 43.6% [1692/3882]; P < 0.001). Before HEART Pathway implementation, the hospitalization rate was 10.4% (175/1688) versus 12.4% (210/1692) after (P = 0.07). More patients were diagnosed with MI following implementation (0.8% [14/1665] vs. 2.0% [33/1686]; P = 0. 008). Median age was older postimplementation (52 years [IQR: 45–59 years] vs. 54 years [IQR: 48–64 years]; P < 0. 001).

Conclusions:

HEART Pathway implementation resulted in management of higher risk patients in the OU. Following implementation, OU chest pain patients were older and were more likely to be hospitalized or diagnosed with MI.
Two-paired Mini-incisional Entropion Surgery for Involutional Entropion
Authors: Ozdemir Ibrahim
Published: February 2021

Purpose:

The aim of this study is to describe “2-paired mini-incisional entropion surgery” for involutional entropion.

Methods:

This study was a retrospective single-surgeon case series. Patients who underwent different entropion surgeries were reviewed. Patients with involutional entropion were divided into 3 groups according to the type of surgery performed by a single surgeon: 2-paired mini-incisional entropion surgery; transconjunctival retractor reinsertion; or transcutaneous retractor reinsertion. Patients were followed up to 35 months after the surgery. Operation time, complications, and success were compared between groups.

Results:

Sixty-six lower eyelids of 60 patients were evaluated. The recurrence was 7.7% in the transcutaneous group, was 5.9% in the 2-paired mini-incisional entropion surgery group, and was 5.3% in the transconjunctival group. The total chance of success in 24-month period was 94.7% in the transconjunctival approach group, was 94.1% in the 2-paired mini-incisional entropion surgery group, and was 92.3% in the transcutaneous group.

Conclusion:

The 2-paired mini-incisional entropion surgery can be used for entropion repair alone or in combination with horizontal tightening surgeries.
Delayed Gastric Emptying in Prelung Transplant Patients Is Associated With Posttransplant Acute Cellular Rejection Independent of Reflux
Authors: Derousseau Taylor , Chan Walter W. , Cangemi David , Kaza Vaidehi , Lo Wai-Kit , Gavini Sravanya
Published: February 2021

Goal:

The goal of this study was to evaluate the relationship between pretransplant delayed gastric emptying (DGE) and posttransplant acute cellular rejection (ACR) in lung transplant recipients.

Background:

DGE is very prevalent (23% to 91%) after lung transplantation but pretransplant prevalence has not been well studied. DGE may lead to poor posttransplant outcomes by predisposing to microaspiration. Pretransplant testing for DGE may help identify patients at risk for negative posttransplant outcomes including ACR.

Materials and Methods:

A retrospective review of a prospectively collected database of consecutive patients undergoing prelung transplant evaluation at a tertiary referral center from 2010 to 2015 was performed. Patients with pretransplant gastric emptying scintigraphy were included in the study. ACR diagnosis was made using International Society for Heart and Lung Transplantation (ISHLT) histologic criteria. Typical gastroparesis symptoms at the time of gastric emptying scintigraphy and pretransplant 24-hour pH impedance monitoring (MII-pH) data was collected. Logistic regression was used for multivariate analysis. Subgroup analyses were performed to account for gastroesophageal reflux (GER).

Results:

A total of 83 subjects (18 with DGE, 51.8% male, mean age: 53.6 y) met the criteria for inclusion. Patients with DGE were more likely to have typical symptoms of gastroparesis, though 61.1% of DGE patients were asymptomatic. ACR was more prevalent in patients with DGE (33.3% vs. 12.3%, P=0.04). This correlation was independent of GER as measured by MII-pH on subgroup analysis (75% vs. 14.3%, n=0.02).

Discussion:

Lung transplant recipients with pretransplant DGE have a higher incidence of ACR, independent of GER. Routine pretransplant testing for DGE may help identify patients at greater risk for adverse posttransplant outcomes as the majority of patients with DGE are asymptomatic.
Inflammatory Bowel Disease and COVID-19
Authors: Schlabitz Franziska , Teich Niels , Riesner-Wehner Anica , Böhm Sebastian , Greinert Robin , Eisenmann Stephan , Michl Patrick , Walldorf Jens
Published: February 2021

Objective:

Knowledge about SARS-CoV2 and coronavirus disease 2019 (COVID-19) is growing fast. Massive changes in the health care system imposed by the COVID-19 pandemic clearly impact the overall quality of medical care. In this survey, we aim to explore experiences and concerns of patients with inflammatory bowel disease (IBD) regarding the current pandemic.

Methods:

A 40-item web-based questionnaire on disease-related experiences and concerns during the COVID-19 pandemic was made available to patients with IBD from 28 April 2020 to 31 July 2020.

Results:

An increased risk of SARS-CoV2 infection was a concern for 56.7% of the 1199 patients (aged 41.3±12.8, women 77%, Crohn’s disease 58.8%, ulcerative colitis 38.5%); 61.7% feared an increased risk of severe disease course of COVID-19. Effective preventive measures in either outpatient practices or hospitals were observed by 84.7% of the patients. Appointments with an IBD specialist were canceled in 38.7%, frequently on the patients’ initiative. Telecommunication visits were considered an acceptable alternative to personal visits by 71.0%. Medication was reduced or paused in 6.9% because of the pandemic. A swab (SARS-CoV2-PCR) was done in 13.2% of the patients; only 3 patients (0.25%) were tested positive.

Conclusion:

The COVID-19 pandemic is a major concern of patients with IBD. However, the cumulative prevalence in our cohort is low. Patients at risk should be identified and counseled individually. When required because of the local COVID-19 situation, telecommunication visits and liberal prescription policies are advisable to reduce in-person contacts, while ensuring continuous therapy and maintaining communication with patients.
Predicting Kidney Discard Using Machine Learning
Authors: Barah Masoud , Mehrotra Sanjay
Published: February 2021

Background.

Despite the kidney supply shortage, 18%–20% of deceased donor kidneys are discarded annually in the United States. In 2018, 3569 kidneys were discarded.

Methods.

We compared machine learning (ML) techniques to identify kidneys at risk of discard at the time of match run and after biopsy and machine perfusion results become available. The cohort consisted of adult deceased donor kidneys donated between December 4, 2014, and July 1, 2019. The studied ML models included Random Forests (RF), Adaptive Boosting (AdaBoost), Neural Networks (NNet), Support Vector Machines (SVM), and K-nearest Neighbors (KNN). In addition, a Logistic Regression (LR) model was fitted and used for comparison with the ML models’ performance.

Results.

RF outperformed other ML models. Of 8036 discarded kidneys in the test dataset, LR correctly classified 3422 kidneys, whereas RF correctly classified 4762 kidneys (area under the receiver operative curve [AUC]: 0.85 versus 0.888, and balanced accuracy: 0.681 versus 0.759). For the kidneys with kidney donor profile index of >85% (6079 total), RF significantly outperformed LR in classifying discard and transplant prediction (AUC: 0.814 versus 0.717, and balanced accuracy: 0.732 versus 0.657). More than 388 kidneys were correctly classified using RF. Including biopsy and machine perfusion variables improved the performance of LR and RF (LR’s AUC: 0.888 and balanced accuracy: 0.74 versus RF’s AUC: 0.904 and balanced accuracy: 0.775).

Conclusions.

Kidneys that are at risk of discard can be more accurately identified using ML techniques such as RF.
What Therapeutic Regimen Will Be Optimal for Initial Clinical Trials of Pig Organ Transplantation?
Authors: Bikhet Mohamed , Iwase Hayato , Yamamoto Takayuki , Jagdale Abhijit , Foote Jeremy B. , Ezzelarab Mohamed , Anderson Douglas J. , Locke Jayme E. , Eckhoff Devin E. , Hara Hidetaka , Cooper David K.C.
Published: February 2021

We discuss what therapeutic regimen might be acceptable/successful in the first clinical trial of genetically engineered pig kidney or heart transplantation. As regimens based on a calcineurin inhibitor or CTLA4-Ig have proved unsuccessful, the regimen we administer to baboons is based on induction therapy with antithymocyte globulin, an anti-CD20 mAb (Rituximab), and cobra venom factor, with maintenance therapy based on blockade of the CD40/CD154 costimulation pathway (with an anti-CD40 mAb), with rapamycin, and a corticosteroid. An anti-inflammatory agent (etanercept) is administered for the first 2 wk, and adjuvant therapy includes prophylaxis against thrombotic complications, anemia, cytomegalovirus, and pneumocystis. Using this regimen, although antibody-mediated rejection certainly can occur, we have documented no definite evidence of an adaptive immune response to the pig xenograft. This regimen could also form the basis for the first clinical trial, except that cobra venom factor will be replaced by a clinically approved agent, for example, a C1-esterase inhibitor. However, none of the agents that block the CD40/CD154 pathway are yet approved for clinical use, and so this hurdle remains to be overcome. The role of anti-inflammatory agents remains unproven. The major difference between this suggested regimen and those used in allotransplantation is the replacement of a calcineurin inhibitor with a costimulation blockade agent, but this does not appear to increase the complications of the regimen.
Active perception during angiogenesis: filopodia speed up Notch selection of tip cells

in silico
and
in vivo
Authors: Zakirov Bahti , Charalambous Georgios , Thuret Raphael , Aspalter Irene M. , Van-Vuuren Kelvin , Mead Thomas , Harrington Kyle , Regan Erzsébet Ravasz , Herbert Shane Paul , Bentley Katie
Published: February 2021

How do cells make efficient collective decisions during tissue morphogenesis? Humans and other organisms use feedback between movement and sensing known as ‘sensorimotor coordination’ or ‘active perception’ to inform behaviour, but active perception has not before been investigated at a cellular level within organs. Here we provide the first proof of concept
in silico
/
in vivo
study demonstrating that filopodia (actin-rich, dynamic, finger-like cell membrane protrusions) play an unexpected role in speeding up collective endothelial decisions during the time-constrained process of ‘tip cell’ selection during blood vessel formation (angiogenesis). We first validate simulation predictions
in vivo
with live imaging of zebrafish intersegmental vessel growth. Further simulation studies then indicate the effect is due to the coupled positive feedback between movement and sensing on filopodia conferring a bistable switch-like property to Notch lateral inhibition, ensuring tip selection is a rapid and robust process. We then employ measures from computational neuroscience to assess whether filopodia function as a primitive (basal) form of active perception and find evidence in support. By viewing cell behaviour through the ‘basal cognitive lens' we acquire a fresh perspective on the tip cell selection process, revealing a hidden, yet vital time-keeping role for filopodia. Finally, we discuss a myriad of new and exciting research directions stemming from our conceptual approach to interpreting cell behaviour.

This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens’.
Evolutionary analysis of rabies virus using the partial Nucleoprotein and Glycoprotein gene in Mumbai region of India
Authors: Pharande Rajesh Raghunanth , Majee Sharmila Badal , Gaikwad Satish S. , Moregoankar S. D. , Bannalikar AnilKumar , Doiphode Aakash , Gandge Rajashri , Dighe Dhananjay , Ingle Sonal , Mukherjee Sandeepan
Published: February 2021

Nearly 1.7 million cases of dog bites are reported every year in India and many cases of animal rabies are left unattended and undiagnosed. Therefore, a mere diagnosis of rabies is not sufficient to understand the epidemiology and the spread of the rabies virus (RV) in animals. There is a paucity of information about the evolutionary dynamics of RV in dogs and its biodiversity patterns in India. In total, 50 dog-brain samples suspected of rabies were screened by the nucleoprotein- (N) and glycoprotein- (G) gene PCR. The N and G genes were subsequently sequenced to understand the molecular evolution in these genes. The phylogenetic analysis of the N gene revealed that six isolates in the Mumbai region belonged to a single Arctic lineage. Time-scaled phylogeny by Bayesian coalescent analysis of the partial N gene revealed that the time to the most recent common ancestor (TMRCA) for the sequences belonged to the cluster from 2006.68 with a highest posterior density of 95 % betweeen 2005–2008, which is assigned to Indian lineage I. Migration pattern revealed a strong Bayes factor between Mumbai to Delhi, Panji to Hyderabad, Delhi to Chennai, and Chennai to Chandigarh. Phylogenetic analysis of the G gene revealed that the RVs circulating in the Mumbai region are divided into three lineages. Time-scaled phylogeny by the Bayesian coalescent analysis method estimated that the TMRCA for sequences under study was from 1993 and Indian clusters was from 1962. In conclusion, the phylogenetic analysis of the N gene revealed that six isolates belonged to single Arctic lineages along with other Indian isolates and they were clustered into a single lineage but divided into three clades based on the G-gene sequences. The present study highlights and enhances the current molecular epidemiology and evolution of RV and revealed strong location bias and geographical clustering within Indian isolates on the basis of N and G genes.
Longitudinal serology in SARS-CoV-2 infected individuals in India – a prospective cohort study
Authors: Thiruvengadam Ramachandran , Chattopadhyay Souvick , Mehdi Farha , Desiraju Bapu Koundinya , Chaudhuri Susmita , Singh Savita , Bhartia Vandita , Kshetrapal Pallavi , Natchu Uma Chandra Mouli , Wadhwa Nitya , Sopory Shailaja , Wahi Mudita , Pandey Anil K. , Das Asim , Anand Nidhi , Sharma Nandini , Sharma Pragya , Saxena Sonal , Sindhu Deepa , Sindhu Brahmdeep , Sharma Dharmendra , Dang Navin , Batra Gaurav , Kang Gagandeep , Bhatnagar Shinjini ,   for DBT India Consortium for COVID-19 Research
Published: February 2021

Clinical and epidemiological characteristics of SARS-CoV-2 infection are now widely available, but there are few data on longitudinal serology in large cohorts, particularly from low-and middle-income countries. We established an ongoing prospective cohort of 3840 SARS-CoV-2 RT-PCR positive individuals in the Delhi-National Capital Region of India, to document clinical and immunological characteristics during illness and convalescence. The IgG responses to the receptor binding domain (RBD) and nucleocapsid were assessed at 0-7, 10-28 days and 6-10 weeks after infection. The clinical predictors of seroconversion were identified by multivariable regression analysis. The seroconversion rates in the post-infection windows of 0–7 days, 10–28 days and 6–10 weeks were 46%, 84.7% and 85.3% respectively (n=782). The proportion with a serological response increased with severity of COVID-19 disease. All participants with severe disease, 89.6% with mild to moderate infection and 77.3% of asymptomatic participants had IgG antibodies to the RBD antigen. The threshold values in the nasopharyngeal viral RNA RT-PCR in a subset of asymptomatic and symptomatic seroconverters were comparable (p value: 0.48), with similar results among non-seroconverters (p value: 0.16) (n=169). This is the first report of longitudinal humoral immune responses to SARS-CoV-2 infection over a period of ten weeks from South Asia. The low seropositivity in asymptomatic participants and differences between assays highlight the importance of contextualizing the understanding of population serosurveys.

We measured anti-SARS-CoV-2 RBD and NC protein IgG in a multi-hospital-based prospective cohort from northern India up to ten weeks post-infection. The lower seroconversion rate among asymptomatic RT-PCR positive participants has public health significance particularly for interpreting community seroprevalence estimates.
A single mRNA immunization boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection
Authors: Stamatatos Leonidas , Czartoski Julie , Wan Yu-Hsin , Homad Leah J. , Rubin Vanessa , Glantz Hayley , Neradilek Moni , Seydoux Emilie , Jennewein Madeleine F. , MacCamy Anna J. , Feng Junli , Mize Gregory , De Rosa Stephen C. , Finzi Andrés , Lemos Maria P. , Cohen Kristen W. , Moodie Zoe , McElrath M. Juliana , McGuire Andrew T.
Published: February 2021

Emerging SARS-CoV-2 variants have raised concerns about resistance to neutralizing antibodies elicited by previous infection or vaccination. We examined whether sera from recovered and naïve donors collected prior to, and following immunizations with existing mRNA vaccines, could neutralize the Wuhan-Hu-1 and B.1.351 variants. Pre-vaccination sera from recovered donors neutralized Wuhan-Hu-1 and sporadically neutralized B.1.351, but a single immunization boosted neutralizing titers against all variants and SARS-CoV-1 by up to 1000-fold. Neutralization was due to antibodies targeting the receptor binding domain and was not boosted by a second immunization. Immunization of naïve donors also elicited cross-neutralizing responses, but at lower titers. Our study highlights the importance of vaccinating both uninfected and previously infected persons to elicit cross-variant neutralizing antibodies.
RISK OF HOSPITALISATION WITH COVID-19 AMONG TEACHERS COMPARED TO HEALTHCARE WORKERS AND OTHER WORKING-AGE ADULTS. A NATIONWIDE CASE-CONTROL STUDY
Authors: Lynda Fenton , Ciara Gribben , David Caldwell , Sam Colville , Jen Bishop , Martin Reid , Jane White , Campbell Marion , Hutchinson S , Robertson C , Helen M Colhoun , Rachael Wood , Paul M McKeigue , David A McAllister
Published: February 2021

Objective

To determine the risk of hospitalisation with COVID-19 and severe COVID-19 among teachers and their household members, overall and compared to healthcare workers and the general working-age population.

Design

Population-based nested case-control study.

Settings

Scotland, March 2020 to January 2021. Before and after schools re-opened in early August 2020.

Participants

All cases of COVID-19 in Scotland in adults ages 21 to 65 (n = 83,817) and a random sample of controls matched on age, sex and general practice (n = 841,708).

Exposure

Individuals identified as actively teaching in a Scottish school by the General Teaching Council for Scotland, and household members of such individuals identified via the Unique Property Reference Number.

Comparator

Individuals identified as healthcare workers in Scotland, their household members, and the remaining “general population” of working-age adults.

Main outcomes

The primary outcome was hospitalisation with COVID-19 defined in anyone testing positive with COVID-19 in hospital, admitted to hospital within 28 days of a positive test, and/or diagnosed with COVID-19 on discharge from hospital. Severe COVID-19 was defined as individuals admitted to intensive care or dying within 28 days of a positive test or assigned COVID-19 as a cause of death.

Results

Most teachers were young (mean age 42), female (80%) and had no underlying conditions (84%). The cumulative incidence (risk) of hospitalisation with COVID-19 was below 1% for all of the working age adults. In the period after school re-opening, compared to the general population, in conditional logistic regression models adjusting for age, sex, general practice, deprivation, underlying conditions and number of adults in the household, the relative risk in teachers (among 18,479 cases and controls) for hospitalisation was rate ratio (RR) 0.97 (95%CI 0.72-1.29) and for severe COVID-19 was RR 0.27 (95%CI 0.09-0.77). Equivalent rate ratios for household members of teachers were 0.97 (95%CI 0.74-1.27) and 0.67 (95%CI 0.36-1.24), and for healthcare workers were 1.82 (95%CI 1.55-2.14) and 1.76 (95%CI 1.22-2.56), respectively.

Conclusion

Compared to working-age adults who are otherwise similar, teachers and their household members are not at increased risk of hospitalisation with COVID-19 and are at lower risk of severe COVID-19. These findings are broadly reassuring for adults engaged in face to face teaching.
Mendelian randomization analysis identified genes potentially pleiotropically associated with periodontitis
Authors: Wang Feng , Liu Di , Zhuang Yong , Feng Bowen , Lu Wenjin , Yang Jingyun , Zhuang Guanghui
Published: February 2021

Objective

To prioritize genes that were pleiotropically or potentially causally associated with periodontitis.

Methods

We applied the summary data-based Mendelian randomization (SMR) method integrating genome-wide association study (GWAS) for periodontitis and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with periodontitis. We performed separate SMR analysis using CAGE eQTL data and GTEx eQTL data. SMR analysis were done for participants of European and East Asian ancestries, separately.

Results

We identified multiple genes showing pleiotropic association with periodontitis in participants of European ancestry and participants of East Asian ancestry.PDCD2(corresponding probe: ILMN_1758915) was the top hit showing pleotropic association with periodontitis in participants of European ancestry, andBX093763(corresponding probe: ILMN_1899903) and AC104135.3 (corresponding probe: ENSG00000204792.2) were the top hits in participants of East Asian ancestry using CAGE eQTL data and GTEx eQTL data, respectively.

Conclusion

We identified multiple genes that may be involved in the pathogenesis of periodontitis in participants of European ancestry and participants of East Asian ancestry. Our findings provided important leads to a better understanding of the mechanisms underlying periodontitis and revealed potential therapeutic targets for the effective treatment of periodontitis.
Emergence of an early SARS-CoV-2 epidemic in the United States
Authors: Zeller Mark , Gangavarapu Karthik , Anderson Catelyn , Smither Allison R. , Vanchiere John A. , Rose Rebecca , Snyder Daniel J. , Dudas Gytis , Watts Alexander , Matteson Nathaniel L. , Robles-Sikisaka Refugio , Marshall Maximilian , Feehan Amy K. , Sabino-Santos Gilberto , Bell-Kareem Antoinette R. , Hughes Laura D. , Alkuzweny Manar , Snarski Patricia , Garcia-Diaz Julia , Scott Rona S. , Melnik Lilia I. , Klitting Raphaëlle , McGraw Michelle , Belda-Ferre Pedro , DeHoff Peter , Sathe Shashank , Marotz Clarisse , Grubaugh Nathan , Nolan David J. , Drouin Arnaud C. , Genemaras Kaylynn J. , Chao Karissa , Topol Sarah , Spencer Emily , Nicholson Laura , Aigner Stefan , Yeo Gene W. , Farnaes Lauge , Hobbs Charlotte A. , Laurent Louise C. , Knight Rob , Hodcroft Emma B. , Khan Kamran , Fusco Dahlene N. , Cooper Vaughn S. , Lemey Phillipe , Gardner Lauren , Lamers Susanna L. , Kamil Jeremy P. , Garry Robert F. , Suchard Marc A. , Andersen Kristian G.
Published: February 2021

The emergence of the early COVID-19 epidemic in the United States (U.S.) went largely undetected, due to a lack of adequate testing and mitigation efforts. The city of New Orleans, Louisiana experienced one of the earliest and fastest accelerating outbreaks, coinciding with the annual Mardi Gras festival, which went ahead without precautions. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large, crowded events may have accelerated early transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana initially had limited sequence diversity compared to other U.S. states, and that one successful introduction of SARS-CoV-2 led to almost all of the early SARS-CoV-2 transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras and that the festival dramatically accelerated transmission, eventually leading to secondary localized COVID-19 epidemics throughout the Southern U.S.. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate COVID-19 epidemics on a local and regional scale.