bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-stage Reconstruction of Hand Extensor Tendons Using Silicon Rods
Authors: Abdulaziz Mohammad KH.B. , Al-Ali Ahmad B. , Hassan Zakariya , Abdelaty Mahmoud , Alkandari Qutaiba A. , Piccolo Nelson Sarto
Published: October 2021

The extensor system of the hand is an intricate complex component that involves a working balance between the extrinsic and intrinsic muscles of extension. Injuries to the extensor tendons are typically repaired primarily or by tendon transfers or grafts at a second stage. A 16-year-old boy sustained a right hand crush injury following an all-terrain vehicle accident, resulting in the loss of dorsal skin and extensor tendons of digits 3, 4, and 5 involving extensor zones 4–6, and oblique fractures in the second and third metacarpal bones. Primary surgery involved fixation of aforementioned fractures utilizing K-wires along with superficial circumflex iliac artery flap coverage for the raw areas post debridement. Following this, primary extensor tendon reconstruction was performed using silicon Hunter rod implants and autologous tendon grafts via a two-stage approach. Over a 2-year postoperative period, the patient demonstrated active functional extension of all four fingers with some limitations to range of motion. This case report supports the hypothesis that the pseudo-synovial sheaths created by silicone rod implants assist the easy gliding motion of tendon grafts in the second stage of reconstruction, reducing the risk of tendon adhesions, shortening, and extension lag.
Microsurgical Thoracic Duct Lymphovenous Bypass in the Adult Population
Authors: Othman Sammy , Azoury Saïd C. , Klifto Kevin , Toyoda Yoshiko , Itkin Maxim , Kovach Stephen J.
Published: October 2021

Thoracic duct occlusion can lead to devastating complications, resulting in recalcitrant chylothoraces, ascites, generalized lymphedema, metabolic derangement, and death. Lymphatic extravasation has traditionally been managed conservatively and, in recent years, using minimally invasive techniques, such as thoracic duct ligation and embolization. However, these measures are often limited in application and therapeutic success, resulting in chronically difficult conditions with few modalities available for definitive management. Advances in microsurgery have allowed for surgical treatment and resolution of peripherally-based lymphatic pathology, though microsurgical intervention to address central lymphatic abnormalities is scarcely described. This report is the first series detailing experiences utilizing microsurgical thoracic duct lymphovenous bypass in a refractory adult population with thoracic duct occlusion. Four patients successfully underwent the procedure, with three achieving complete resolution of symptoms. The fourth patient enjoyed partial resolution, though ubiquitous lymphatic deformities have conferred recurrent residual lower-extremity peripheral edema requiring future intervention. Postoperatively, patent anastomoses were confirmed under magnetic resonance lymphangiography. This series demonstrates the feasibility of microsurgical thoracic duct lymphovenous bypass as a promising technique in treating patients suffering from thoracic duct occlusion. This intervention is effective for recalcitrant chylothorax, chylous ascites, and generalized lymphedema, particularly when traditional and interventional radiological techniques are unsuccessful.
Thin-Flap Laser In Situ Keratomileusis-Associated Dry Eye: A Comparative Study Between Femtosecond Laser and Mechanical Microkeratome–Assisted Laser In Situ Keratomileusis
Authors: Abdel-Radi Mahmoud , Abdelmotaal Hazem , Anwar Mohamed
Published: October 2021

Objective:

To assess and compare postlaser in situ keratomileusis (LASIK) dry eye after LASIK with planned thin flaps created by a femtosecond laser (FS) and mechanical microkeratome (MK).

Methods:

Patients were stratified according to the flap creation technique into FS and MK groups with planned 100 μm flap thickness in all eyes. Dry eye parameters including tear film break-up time (TBUT), Schirmer I test, ocular surface disease index (OSDI), and lower tear meniscus height and area (tear meniscus height [TMH] and tear meniscus area [TMA]) were assessed before surgery and at 3 and 6 months after surgery.

Results:

The study included 102 eyes of 55 patients (52 eyes underwent FS-LASIK/50 eyes underwent MK-LASIK). The preoperative characteristics including age, gender, and spherical equivalents were similar in both groups (P>0.05). The difference in postoperative flap thickness was statistically significant (P<0.05). In each group, dry eye parameters showed a statistically significant worsening (P value<0.001) at 3 months with later significant improvement at 6 months but did not return to baseline. The mean TBUT, Schirmer I, and lower TMH and TMA were statistically higher, and the mean OSDI was statistically lower in FS-LASIK than the MK-LASIK group at both 3 and 6 months (P value<0.001). The depth of ablation had a statistically significant correlation with Schirmer I at 6 months and OSDI at both 3 and 6 months post-LASIK (P<0.05).

Conclusion:

The use of femtosecond laser technology in performing thin-Flap LASIK eye surgeries has improved the outcome of post-LASIK dry eye when compared with the mechanical microkeratome.
Delayed onset neurologic deterioration following traumatic brain injury
Authors: Bova Michael , Tu Justin , Chang Albert , Weppner Justin
Published: October 2021

Introduction:

Patients with traumatic brain injury (TBI) are at risk of developing idiopathic intracranial hypertension (IIH). IIH is a diagnosis of exclusion but is similar to many other diagnoses. Therefore, a high index of suspicion following TBI is required for appropriate management.

Patient concerns:

A 59-year-old-female presented with moderate TBI due to motor vehicle collision. Her initial symptoms included headache and dizziness, which resolved quickly. Over the following two months she developed worsened headaches with vomiting, progressive vision impairment, worsening balance, and gait ataxia. The patient had no medical history.

Diagnosis:

Delayed-onset IIH following moderate TBI, diagnosed with a constellation of findings including brain magnetic resonance imaging showing moderate-to-severe flattening of the adenohypophysis, symmetric fluid signal along the optic nerves, ophthalmologic examination revealing early papilledema, and lumbar puncture revealed elevated opening pressures.

Intervention:

A six-month course of acetazolamide resulted in resolution of the patient's IIH.

Outcomes:

A six-month course of acetazolamide resulted in improvements in the patient's symptoms, including headaches, vision impairment, balance, and ataxia. Repeat lumbar puncture showed normal opening pressure.

Conclusion:

This case demonstrates the acute management and subsequent improvement of delayed onset IIH following moderate TBI. As IIH is a diagnosis of exclusion, physicians caring for patients with brain injuries should be aware of the presenting signs, symptoms, and diagnostic criteria of IIH.
Comparing Published Gut Microbiome Taxonomic Data Across Multinational Studies
Authors: Meeks Brianna K. , Maki Katherine A. , Ames Nancy J. , Barb Jennifer J.
Published: October 2021

Background

Nurse researchers are well poised to study the connection of the microbiome to health and disease. Evaluating published microbiome results can assist with study design and hypothesis generation.

Objectives

This article aims to present and define important analysis considerations in microbiome study planning and to identify genera shared across studies despite methodological differences. This methods article will highlight a workflow that the nurse scientist can use to combine and evaluate taxonomy tables for microbiome study or research proposal planning.

Methods

We compiled taxonomy tables from 13 published gut microbiome studies that had used Ion Torrent sequencing technology. We searched for studies that had amplified multiple hypervariable (V) regions of the 16S rRNA gene when sequencing the bacteria from healthy gut samples.

Results

We obtained 15 taxonomy tables from the 13 studies, comprised of samples from four continents and eight V regions. Methodology among studies was highly variable, including differences in V regions amplified, geographic location, and population demographics. Nevertheless, of the 354 total genera identified from the 15 data sets, 25 were shared in all V regions and the four continents. When relative abundance differences across the V regions were compared, Dorea and Roseburia were statistically different. Taxonomy tables from Asian subjects had increased average abundances of Prevotella and lowered abundances of Bacteroides compared with the European, North American, and South American study subjects.

Discussion

Evaluating taxonomy tables from previously published literature is essential for study planning. The genera found from different V regions and continents highlight geography and V region as important variables to consider in microbiome study design. The 25 shared genera across the various studies may represent genera commonly found in healthy gut microbiomes. Understanding the factors that may affect the results from a variety of microbiome studies will allow nurse scientists to plan research proposals in an informed manner. This work presents a valuable framework for future cross-study comparisons conducted across the globe.
Adapting Research to a Global Pandemic
Authors: Vigoureux Taylor F. D. , Mu Christina X. , Mason Tina M. , Gonzalez Brian D. , Lee Soomi
Published: October 2021

Background

Mandated social distancing practices and quarantines in response to COVID-19 have resulted in challenges for research on healthcare workers, such as hospital nurses. It remains unknown whether nursing studies utilizing complex methodology like sleep actigraphy and ecological momentary assessment (EMA) can be conducted remotely without compromising data quality.

Objectives

We aimed to (a) disseminate our remote study protocol for sleep actigraphy and EMA data from hospital nurses during COVID-19, (b) assess feasibility and acceptability of this approach for studies on hospital nurses, and (c) examine the reliability and ecological validity of sleep characteristics measured across 14 days.

Methods

Using an online platform, we provided 86 outpatient nurses from a cancer hospital with detailed video/text instructions regarding the study and facilitated virtual study onboarding meetings. Feasibility was assessed by comparing adherence rates to a similar in-person study of nurses from the same hospital; acceptability was evaluated through content analysis of qualitative study feedback. Multilevel modeling was conducted to assess changes in sleep characteristics as a function of study day and daily stressful experiences.

Results

Adherence to EMA (91.8%) and actigraphy (97.9%) was high. EMA adherence was higher than the in-person study of inpatient day-shift nurses from the same hospital. Content analyses revealed primarily positive feedback, with 51.2% reporting “easy, clear, simple onboarding” and 16.3% reporting the website was “helpful.” Six participants provided only negative feedback. Sleep characteristics did not change as a function of study day except for self-reported quality, which increased slightly during Week 1 and regressed toward baseline after that. A higher incidence of stressor days or higher stressor severity followed nights with shorter-than-usual time in bed or poorer-than-usual sleep quality, supporting the ecological validity for these methods of assessing sleep in nurses.

Discussion

Findings suggest that a fully remote study protocol for EMA and actigraphy studies in nursing yields robust feasibility, acceptability, reliability, and validity. Given the busy schedules of nurses, the convenience of this approach may be preferable to traditional in-person data collection. Lessons learned from COVID-19 may apply to improving nursing research postpandemic.
Conducting Neonatal Intensive Care Unit Research During a Pandemic
Authors: Nist Marliese Dion , Casavant Sharon G. , Dail Robin B. , Everhart Kayla C. , Sealschott Stephanie , Cong Xiaomei S.
Published: October 2021

Background

The coronavirus pandemic disrupted normal clinical operations and research. Nurse scientists conducting research studies in the neonatal intensive care unit experienced significant challenges to continuing their research studies amid national lockdowns and hospital visitation restrictions.

Objectives

The purpose of this article is to describe the challenges encountered by nurse scientists conducting research studies in the neonatal intensive care unit during the pandemic, the creative solutions devised to overcome these barriers, and the lessons learned during this unprecedented time.

Methods

Using our pandemic area studies as exemplars, we highlight the barriers encountered in continuing our research in the intense environment of the neonatal intensive care unit.

Results

Visitor restrictions limited the presence of parents and researchers in the neonatal intensive care unit during the pandemic, causing disruptions to participant recruitment and data collection. Laboratory closures further limited research activities during the pandemic. Strategies to overcome these barriers include building formal collaborations among researchers and clinicians, creating the infrastructure to support virtual recruitment and electronic consent, and developing contingency plans for studies involving the analysis of biological samples.

Discussion

The neonatal intensive care unit is a unique environment because of vulnerable patient population and need for researchers to interact with parents to recruit study participants. Implementing the strategies developed during the coronavirus pandemic may allow for the continuation of research activities during future public health crises.
Improving reproducibility of proton MRS brain thermometry: theoretical and empirical approaches
Authors: Dong Zhengchao , Kantrowitz Joshua T. , Mann J. John
Published: October 2021

Purpose

In 1H MRS-based thermometry of brain, averaging temperatures measured from more than one reference peak offers several advantages including improving the reproducibility, i.e., precision, of the measurement. This paper proposes theoretically and empirically optimal weighting factors to improve the weighted average of temperatures measured from three references.

Methods

We first proposed concepts of equivalent noise and equivalent signal-to-noise ratio in terms of frequency measurement and a concept of relative frequency that allows the combination of different peaks in a spectrum for improving the precision of frequency measurement. Based on these, we then derived a theoretically optimal weighting factor and proposed an empirical weighting factor, both involving equivalent noise levels, for a weighted average of temperatures measured from three references, i.e., the singlets of NAA, Cr, and Ch, in 1H MR spectrum. We assessed these two weighting factors by comparing their errors in measurement of temperatures with the errors of temperatures measured from individual references; we also compared these two new weighting factors with two previously proposed weighting factors. These errors were defined as the standard deviations (SDs) in repeated measurements or in Monte Carlo studies.

Results

Both the proposed theoretical and empirical weighting factors outperformed the two previously proposed weighting factors as well as the three individual references in all phantom and in vivo experiments. In phantom experiments with 4 Hz or 10 Hz line broadening, the theoretical weighting factor outperformed the empirical one, but the latter was superior in all other repeated and Monte Carlo tests performed on phantom and in vivo data.

Conclusion

The proposed weighting factors are superior to the two previously proposed weighting factors and can improve the reproducibility of temperature measurement using the 1H MRS-based thermometry.
Clinical indicants and electrophysiological patterns of sciatic nerve in patients after total hip replacement
Authors: Ostrovskij V.V. , Tolkachev V.S. , Bazhanov S.P. , Korshunova G.A. , Chekhonatsky A.A.
Published: October 2021

Background

The incidence of sciatic nerve (SN) damage after a total hip replacement (THR) is 10 percent. The underdiagnosis of paucisymptomatic sciatic neuropathy may lead to the unsatisfactory outcome of the treatment in these patients featured by frequent chronic pain syndrome. This research was aimed at the evaluation of the dynamics of clinical and electrophysiological patterns in SN after THR.

Material and methods

The research involved 16 individuals 45 to 68 years old with primary idiopathic coxarthrosis who underwent THR in the Scientific Research Institute of Traumatology, Orthopedics and Neurosurgery, Federal State Budgetary Educational Institution of Higher Education ‘V.I. Razumovsky Saratov State Medical University’, the Russian Federation Ministry of Healthcare. We compared the findings of clinical and neurologic examinations (VAS, muscle strength, and sensitivity evaluation) as well as ENMG before surgeries and 14 days after them.

Results

In the evaluation of the clinical score in 9 patients, we observed some negative changes featured by paresthesia around the area of the SN innervation. The analysis of changes in ENMG findings revealed the decrease in M-response amplitudes of both peroneal and tibial nerves by more than 10 percent of the age-appropriate normal value; this was more prominent in patients who had undergone the lengthening of extremities in more than 3 cm.

Conclusion

THR is associated with a higher risk of traction and entrapment changes in SN that lead to the progress of their neuropathies in the post-operative period.

Reviewers

Assoc. Prof. Ulyanov V.Yu., MD, DSc;

Assoc. Prof. Gulyaev D.A., MD, DSc
Nutritional deficiency recapitulates intestinal injury associated with environmental enteric dysfunction in patient-derived Organ Chips
Authors: Bein Amir , Fadel Cicely W. , Swenor Ben , Cao Wuji , Powers Rani K. , Camacho Diogo M. , Naziripour Arash , Parsons Andrew , LoGrande Nina , Sharma Sanjay , Kim Seongmin , Jalili-Firoozinezhad Sasan , Grant Jennifer , Breault David T. , Iqbal Junaid , Ali Asad , Denson Lee A , Moore Sean R. , Prantil-Baun Rachelle , Goyal Girija , Ingber Donald E.
Published: October 2021

Environmental Enteric Dysfunction (EED) is a chronic inflammatory condition of the intestine characterized by villus blunting, compromised intestinal barrier function, and reduced nutrient absorption. Here, we show that key genotypic and phenotypic features of EED-associated intestinal injury can be reconstituted in a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by organoid-derived intestinal epithelial cells from EED patients and cultured in niacinamide- and tryptophan-deficient (-N/-T) medium. Exposure of EED Intestine Chips to -N/-T deficiencies resulted in transcriptional changes similar to those seen in clinical EED patient samples including congruent changes in six of the top ten upregulated genes. Exposure of EED Intestine Chips or chips lined by healthy intestinal epithelium (healthy Intestine Chips) to -N/-T medium resulted in severe villus blunting and barrier dysfunction, as well as impairment of fatty acid uptake and amino acid transport. EED Intestine Chips exhibited reduced secretion of cytokines at baseline, but their production was significantly upregulated compared to healthy Intestine Chips when exposed to -N/-T deficiencies. The human Intestine Chip model of EED-associated intestinal injury may be useful for analyzing the molecular, genetic, and nutritional basis of this disease and can serve as a preclinical model for testing potential EED therapeutics.
Colorectal cancer is associated with the presence of cancer driver mutations in normal colon
Authors: Matas Julia , Kohrn Brendan , Fredrickson Jeanne , Carter Kelly , Yu Ming , Wang Ting , Gui Xianyong , Soussi Thierry , Moreno Victor , Grady William M. , Peinado Miguel A. , Risques Rosa Ana
Published: October 2021

While somatic mutations in colorectal cancer (CRC) are well characterized, little is known about the accumulation of cancer mutations in the normal colon prior to cancer. Here we have developed and applied an ultra-sensitive, single-molecule mutational test based on CRISPR-DS technology, which enables mutation detection at extremely low frequency (<0.001) in normal colon from patients with and without CRC. We found oncogenic KRAS mutations in the normal colon of about one third of patients with CRC but in none of the patients without CRC. Patients with CRC also carried more TP53 mutations than patients without cancer, and these mutations were more pathogenic and formed larger clones, especially in patients with early onset CRC. Most mutations in normal colon were different from the driver mutations in tumors suggesting that the occurrence of independent clones with pathogenic KRAS and TP53 mutations is a common event in the colon of individuals that develop CRC.

SIGNIFICANCE

Our results suggest a prevalent process of somatic mutation and evolution in the normal colon of patients with CRC, which can be detected by ultra-sensitive sequencing of driver genes and potentially employed clinically for CRC risk prediction.
Impact Of Adaptive Natural Killer Cells, KLRC2 Genotype and Cytomegalovirus Reactivation On Late Mortality In Patients With Severe Covid-19 Lung Disease
Authors: Jaiswal Sarita Rani , Arunachalam Jaganath , Bhardwaj Ashutosh , Saifullah Ashraf , Lakhchaura Rohit , Soni Mayank , Bhagawati Gitali , Chakrabarti Suparno
Published: October 2021

Objective

COVID-19 infection results in severe lung disease in a small but significant number of infected patients. The etiopathogenesis in a subset of such patients, who continue to have progressive pulmonary disease following virus clearance remains unexplored.

Methods

We investigated the role of NKG2C+/NKG2A-adaptive natural killer (ANK) cells, KLRC2 genotype and cytomegalovirus reactivation in 22 such patients.

Results

The median duration of virus positivity was 23 days and the median duration of hospitalisation was 48 days. The overall survival at 60 days in this group was 50%. Older age and comorbidities impacted survival negatively. CMV viremia was documented in 11 patients, with a survival of 25% vs 80% in those without viremia with viral load correlating with mortality. ANK cells were markedly depressed in all patients at day 15. However, persistently low ANK cells at 30 days along with an inversely high NKG2C-/NKG2A+inhibitory NK cells significantly correlated with high CMV viremia as well as mortality, irrespective of KLRC2 genotype. Day 30 ANK cells were significantly lower in KLRC2 deletion group. IFN-gamma and Perforin release were severely compromised in all patients at day +15, with significant improvement in the survivors at day +30, but not in those with adverse outcome.

Conclusion

Patients with severe lung disease even after negative SARS-CoV-2 status, with persistently reduced and functionally compromised ANK cells, are more likely to have CMV reactivation and an adverse outcome, independent of KLRC2 genotype.
Microstructural deficits in the thalamus of major depressive disorder
Authors: Zhang Yuxuan , Zhang Yingli , Ai Hui , Van Dam Nicholas T. , Qian Long , Hou Gangqiang , Xu Pengfei
Published: October 2021

Macroscopic structural abnormalities in the thalamus and thalamic circuits have been shown to contribute to the neuropathology of major depressive disorder (MDD). However, cytoarchitectonic properties underlying these macroscopic abnormalities remain unknown. The purpose of this study was to identify systematic deficits of brain architecture in depression, from structural brain network organization to microstructural properties. A multi-modal neuroimaging approach including diffusion, anatomical and quantitative magnetic resonance imaging (MRI) was used to examine structural-related alternations in 56 MDD patients compared with 35 age- and sex-matched controls. Structural networks were constructed and analyzed using seed-based probabilistic tractography. Morphometric measurements, including cortical thickness and voxel-based morphometry (VBM), were evaluated across the whole brain. A conjunction analysis was then conducted to identify key regions showing common structural alternations across modalities. The microstructural properties, macromolecular tissue volume (MTV) and T1 relaxation times of identified key regions were then calculated. Results showed multiple alterations of structural connectivity within a set of subcortical areas and their connections to cortical regions in MDD patients. These subcortical regions included the putamen, thalamus and caudate, which are predominately involved in the limbic-cortical-striatal-pallidal-thalamic network (LCSPT). Structural connectivity was disrupted within and between large-scale networks, mainly including subcortical networks, default mode networks and salience/ventral attention networks. Consistently, these regions also exhibited widespread volume reductions in MDD patients, specifically the bilateral thalamus, left putamen and right caudate. Importantly, the microstructural properties, T1 relaxation time of left thalamus were increased and negatively correlated with its gray matter volume in MDD patients. The present work to date sheds light on the neuropathological disruptions of LCSPT circuit in MDD, providing the first multi-modal neuroimaging evidence for the macro-micro structural abnormalities of the thalamus in patients with MDD. These findings have implications in understanding the abnormal changes of brain structures across development of MDD.
Modeling and analysis of COVID-19 infected persons during repeated waves in Japan
Authors: Hashiguchi Koichi
Published: October 2021

A model for estimating the number of COVID-19 infected persons (infecteds) is proposed based on the exponential function law of the SIR model. This model is composed of several equations expressing the number of infecteds, considering the onset after an incubation period, infectivity, wavy infection persistence with repeated infection spread and convergence with insufficient quarantine. This model is applied to the infection in Japan, which is currently suffering from the 5th wave, and the initial number of infecteds and various related parameters are calculated by curve fitting of the cumulative number of infecteds to the total cases in the database. As a minimum boundary of the number of infecteds for the infection continuation up to the 5th wave, the initial number of infecteds at the outbreak of infection is more than an order of magnitude higher than the actual initial cases. A convergence ratio (cumulative number of infecteds / total cases) at the end of the first wave is obtained as 1.5. The quarantine rate and social distancing ratio based on the SIQR model are evaluated, and the social distancing ratio increases sharply just after the government’s declaration of emergency. The quarantine rate closely equals the positive rate by PCR tests, meaning that the number of infecteds, which had been unknown, is on the order of almost the same as the number of tests.
Evaluation of the Therapeutic Potential of Oral Phycocyanin-Rich Spirulina Extract in Neuropsychiatric Disorders
Authors: Donen Anna , Lifschytz Tzuri , Wolf Gilly , Ben-Ari Hagar , Lotan Amit , Lerer Leonard , Lerer Bernard
Published: October 2021

Aim

Spirulina is a microalga that is widely used as a food supplement and is regarded as having performance enhancing and health promoting properties. We conducted a preliminary evaluation of the possible antidepressant, anti-anxiety, pro-socialization and cognition-enhancing effects of Spirulina in mouse models.

Methods

Sixty male BalbC mice aged 3 weeks were administered phycocyanin-rich Spirulina extract (PRSE, 545 mg/kg), fluoxetine (20 mg/kg) or water orally for 5 weeks. During the last 2 weeks of the experiment a series of behavioral-cognitive tests was performed to evaluate motor activity, antidepressant and anti-anxiety effects, socialization and cognitive effects. Effects of PRSE and fluoxetine were compared to those of water.

Results

There was a significant effect of PRSE in the activity domain, manifesting as an increase in velocity in the open field (p=0.0007 vs. water). Fluoxetine significantly enhanced immobility in the tail suspension test and the forced swim test reflecting the known antidepressant effect of this compound, but not PRSE. There were no significant effects of PRSE in tests of anxiety, socialization or cognition.

Conclusions

The most striking observation in this study was that PRSE significantly enhanced activity in the open field test. Further studies are indicated to confirm and extend this finding and investigate possible mechanisms of action. The results of the current study do not support sporadic reports of possible antidepressant or cognition-enhancing effects of PRSE. Nevertheless, additional studies are indicated using depression models rather than naïve mice, alternative mouse strains, using additional cognitive tests, and administering higher PRSE doses.
Effectiveness of the BNT162b2 (Pfizer-BioNTech) and the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines for reducing susceptibility to infection with the Delta variant (B.1.617.2) of SARS-CoV-2
Authors: Pattni Karan , Hungerford Daniel , Adams Sarah , Buchan Iain , Cheyne Christopher P , García-Fiñana Marta , Hall Ian , Hughes David M , Overton Christopher , Zhang Xingna , Sharkey Kieran J.
Published: October 2021

Background

From January to May 2021 the alpha variant (B.1.1.7) of SARS-CoV-2 was the most commonly detected variant in the UK, but since then the Delta variant (B.1.617.2), first detected in India, has become the predominant variant. The UK COVID-19 vaccination programme started on 8th December 2020. Most vaccine effectiveness studies to date have focused on the alpha variant. We therefore aimed to estimate the effectiveness of the BNT162b2 (Pfizer-BioNTech) and the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in preventing infection with respect to the Delta variant in a UK setting.

Methods

We used anonymised public health record data linked to infection data (PCR) using the Combined Intelligence for Population Health Action resource. We then constructed an SIR epidemic model to explain SARS-CoV-2 infection data across the Cheshire and Merseyside region of the UK.

Results

We determined that the effectiveness of the Oxford-AstraZeneca vaccine in reducing susceptibility to infection is 39% (95% credible interval [34,43]) and 64% (95% credible interval [61,67]) for a single dose and a double dose respectively. For the Pfizer-BioNTech vaccine, the effectiveness is 20% (95% credible interval [10,28]) and 84% (95% credible interval [82,86]) for a single-dose and a double dose respectively.

Conclusion

Vaccine effectiveness for reducing susceptibility to SARS-CoV-2 infection shows noticeable improvement after receiving two doses of either vaccine. Findings also suggest that a full course of the Pfizer-BioNTech provides the optimal protection against infection with the Delta variant. This would advocate for completing the full course programme to maximise individual protection and reduce transmission.
SARS-CoV-2 vaccine antibody response and breakthrough infection in dialysis
Authors: Anand Shuchi , Montez-Rath Maria E. , Han Jialin , Garcia Pablo , Cadden LinaCel , Hunsader Patti , Morgan Curt , Kerschmann Russell , Beyer Paul , Dittrich Mary , Block Geoffrey A , Chertow Glenn M , Parsonnet Julie
Published: October 2021

Background

Patients receiving dialysis are a sentinel population for groups at high risk for death and disability from COVID-19. Understanding correlates of protection post-vaccination can inform immunization and mitigation strategies.

Methods

Monthly since January 2021, we tested plasma from 4791 patients receiving dialysis for antibodies to the receptor-binding domain (RBD) of SARS-CoV-2 using a high-throughput assay. We qualitatively assessed the proportion without a detectable RBD response and among those with a response, semiquantitative median IgG index values. Using a nested case-control design, we matched each breakthrough case to five controls by age, sex, and vaccination-month to determine whether peak and pre-breakthrough RBD IgG index values were associated with risk for infection post-vaccination.

Results

Among 2563 vaccinated patients, the proportion without a detectable RBD response increased from 6.6% [95% CI 5.5-8.1] in 14-30 days post-vaccination to 20.2% [95% CI 17.1-23.8], and median index values declined from 92.7 (95% CI 77.8-107.5) to 3.7 (95% CI 3.1-4.3) after 5 months. Persons with SARS-CoV-2 infection prior-to-vaccination had higher peak index values than persons without prior infection, but values equalized by 5 months (p=0.230). Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days pre-breakthrough. Peak and pre-breakthrough RBD values <23 (equivalent to <506 WHO BAU/mL) were associated with higher odds for breakthrough infection (OR: 3.7 [95% CI 2.0-6.8] and 9.8 [95% CI 2.9-32.8], respectively).

Conclusions

The antibody response to SARS-CoV-2 vaccination wanes rapidly, and in persons receiving dialysis, the persisting antibody response is associated with risk for breakthrough infection.
Detection of neutralizing antibodies against SARS-CoV-2 by using a commercial surrogate virus neutralization ELISA: can it substitute the classical neutralization test?
Authors: Hofmann Natalie , Grossegesse Marica , Neumann Markus , Schaade Lars , Nitsche Andreas
Published: October 2021

Background

High-throughput detection of neutralizing antibodies against SARS-CoV-2 presents a valuable tool for vaccine trials or investigations of population immunity. We evaluate the performance of the first commercial surrogate virus neutralization test (sVNT, GenScript Biotech) against SARS-CoV-2 plaque reduction neutralization test (PRNT) in convalescent and vaccinated individuals. We compare it to five other ELISAs, two of which are designed to detect neutralizing antibodies.

Results

In 491 pre-vaccination serum samples, sVNT missed 23.6% of PRNT-positive samples when using the manufacturer-recommended cutoff of 30% binding inhibition. Introducing a equivocal area between 15 and 35% maximized sensitivity and specificity against PRNT to 72.8–93.1 % and 73.5– 97.6%, respectively. The overall diagnostic performance of the other ELISAs for neutralizing antibodies was below that of sVNT. Vaccinated individuals exhibited higher antibody titers by PRNT (median 119.8, IQR 56.7–160) and binding inhibition by sVNT (median 95.7, IQR 88.1–96.8) than convalescent patients (median 49.1, IQR 20–62; median 52.9, IQR 31.2–76.2).

Conclusion

GenScript sVNT is suitable to screen for SARS-CoV-2-neutralizing antibodies; however, to obtain accurate results, confirmatory testing by PRNT in a equivocal area is required. This equivocal area may require adaptation for use in vaccinated individuals, due to higher antibody titers.
Breastfeeding infants receive neutralizing antibodies and cytokines from mothers immunized with a COVID-19 mRNA vaccine
Authors: Narayanaswamy Vignesh , Pentecost Brian , Schoen Corina N. , Alfandari Dominique , Schneider Sallie S. , Baker Ryan , Arcaro Kathleen F.
Published: October 2021

Objective

To evaluate the immune response to COVID-19 mRNA-based vaccines present in breastmilk and the transfer of the immune response to the breastfeeding child.

Methods

A prospective cohort study enrolled 30 lactating women who received an mRNA-based COVID-19 vaccine between January and April 2021. Women provided serial milk samples, which included milk expressed before vaccination, milk expressed across 2-3 weeks after the first dose, and milk expressed across 3 weeks after the second dose. Women also were asked to provide their blood, spotted on cards (dried blood spots; DBS) 19 days after the first dose and 21 days after the second dose. Stool samples from the breastfed infants were collected 21 days after mothers received their second dose. Pre-pandemic samples of milk, DBS cards, and infant stool from prior studies were also utilized. Milk and infant stool samples were tested by ELISA for receptor-binding domain (RBD)-specific IgA and IgG. Milk samples were tested for the presence of neutralizing antibodies against the spike and four variants of concern (VOCs): D614G, B.1.1.7 (alpha), B.1.351 (beta), and P.1 (gamma). Milk samples were also tested by electrochemiluminescence assay for levels of 10 cytokines.

Results

Milk from COVID-19-immunized women neutralized the spike and four VOCs and this response is primarily IgG-driven. The immune response in milk also included significantly elevated levels of interferon-γ (IFN-γ). The immune response to maternal vaccination was reflected in breastfed babies; anti-RBD IgG and anti-RBD IgA was detected in 33% and 30% of infant stool samples, respectively. Levels of anti-RBD antibodies in infant stool correlated with maternal vaccine side-effects.

Conclusion

Humoral and cellular immune responses to mRNA-based COVID-19 vaccination are present in the breastmilk of most women. The milk anti-RBD antibodies can neutralize SARS-CoV-2 spike and VOCs. Importantly, we describe for the first time the transfer of anti-RBD antibodies to breastfed infants, with the potential to confer passive immunity against SARS-CoV-2.
Leaders’ gender and the fight against COVID-19: investigation, replication, and a possible explanation
Authors: Maaravi Yossi , Gur Tamar , Arie Yossi Gur
Published: October 2021

Objectives

To investigate the alleged relationship between leaders’ gender and COVID-19 related cases and deaths in different countries across the globe.

Study design

The relationship between leaders’ gender and percent of women in parliament to COVID-19 cases and death per million was investigated in three time points (10 months) across 180 countries, controlling for possible covariates.

Methods

Three different types of analyses were run: (1) Six basic t-tests; (2) Two repeated-measure ANOVA tests analyzing change over time; (3) Six stepwise regression analyses for both leaders’ gender and the percentage of women in parliament.

Results

Our findings suggest that, contrary to some research and popular media headlines, and in-line with recent academic research, leadership gender is not a significant factor in explaining the variation between countries in the fight against the COVID-19 pandemic.

Conclusions

We suggest that this alleged relationship may stem from an illusory correlation. We argue that the uncertainty, stress, and anxiety that prevail in these times of global pandemic may be the breeding ground for judgmental biases of this sort.
Cnidarian hair cell development illuminates an ancient role for the class IV POU transcription factor in defining mechanoreceptor identity
Authors: Ozment Ethan , Tamvacakis Arianna N. , Zhou Jianhong , Rosiles-Loeza Pablo Yamild , Escobar-Hernandez Esteban Elías , Fernandez-Valverde Selene L. , Nakanishi Nagayasu
Published: October 2021

Although specialized mechanosensory cells are found across animal phylogeny, early evolutionary histories of mechanoreceptor development remain enigmatic. Cnidaria (e.g. sea anemones and jellyfishes) is the sister group to well-studied Bilateria (e.g. flies and vertebrates), and has two mechanosensory cell types – a lineage-specific sensory-effector known as the cnidocyte, and a classical mechanosensory neuron referred to as the hair cell. While developmental genetics of cnidocytes is increasingly understood, genes essential for hair cell development are unknown. Here we show that the class IV POU homeodomain transcription factor (POU-IV) – an indispensable regulator of mechanosensory cell differentiation in Bilateria and cnidocyte differentiation in Cnidaria – controls hair cell development in the sea anemone cnidarian Nematostella vectensis. N. vectensis POU-IV is postmitotically expressed in tentacular hair cells, and is necessary for development of the apical mechanosensory apparatus, but not of neurites, in hair cells. Moreover, it binds to deeply conserved DNA recognition elements, and turns on a unique set of effector genes – including the transmembrane-receptor-encoding gene polycystin 1 – specifically in hair cells. Our results suggest that POU-IV directs differentiation of cnidarian hair cells and cnidocytes via distinct gene regulatory mechanisms, and support an evolutionarily ancient role for POU-IV in defining the mature state of mechanosensory neurons.
The accumulation of lncRNAs in hybrid with DNA in patients with psoriasis reveals a decrease in the levels of RNase HII transcripts in the skin
Authors: Mehmetbeyoglu Ecmel , Kianmehr Leila , Borlu Murat , Yilmaz Zeynep , Kılıc Seyma Basar , Rajabi-Maham Hassan , Taheri Serpil , Rassoulzadegan Minoo
Published: October 2021

Long functional non-coding RNAs (lncRNAs) have been in the limelight in aging research because short telomeres are associated with higher levels of TERRA (Telomeric Repeat containing RNA). The genomic instability caused in Immune-mediated inflammatory diseases (IMID) especially in patients with psoriasis, which lead to short telomeres in psoriasis lesions, is a mechanism leading to cell aging. Research on the fraction of TERRA in hybrid with DNA offers avenues for new strategies. Skin samples were fractionated to obtain the RNA associated with DNA as a R-loop structure. TERRA analysis was performed by RT-qPCR and RNA-seq analysis. The higher amount of TERRA levels attached with each chromosome end was found with psoriasis patients. The increased levels of TERRA linked with telomeres correlate with the decrease in the RNase-HII transcript which means the unresolved DNA/RNA hybrids may ultimately facilitate the formation of skin lesions. LncRNAs have multiple molecular functions, including the regulation of heterochromatin, which controls genome stability and epigenome shaping and may be used as a trans-generational prognostic marker in patients with psoriasis.
Evaluation of real-life use of Point-Of-Care Rapid Antigen TEsting for SARS-CoV-2 in schools (EPOCRATES)
Authors: Blanchard Ana C. , Desforges Marc , Labbé Annie-Claude , Nguyen Cat Tuong , Petit Yves , Besner Dominic , Zinszer Kate , Séguin Olivier , Laghdir Zineb , Adams Kelsey , Benoit Marie-Ève , Leduc Geneviève , Longtin Jean , Ragoussis Ioannis , Buckeridge David L. , Quach Caroline
Published: October 2021

Background

We evaluated the use of rapid antigen detection tests (RADT) for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in school settings to determine RADT’s performance compared to PCR.

Methods

In this real-world, prospective observational cohort study, high-school students and staff were recruited from two high-schools in Montreal (Canada) and followed from January 25th to June 10th, 2021. Twenty-five percent of asymptomatic participants were tested weekly by RADT (nasal) and PCR (gargle). Class contacts of cases were tested. Symptomatic participants were tested by RADT (nasal) and PCR (nasal and gargle). The number of cases and outbreaks were compared to other high schools in the same area.

Results

Overall, 2,099 students and 286 school staff members consented to participate. The overall RADT’s specificity varied from 99.8 to 100%, with a lower sensitivity, varying from 28.6% in asymptomatic to 83.3% in symptomatic participants. Secondary cases were identified in 10 of 35 classes. Returning students to school after a 7-day quarantine, with a negative PCR on D6-7 after exposure, did not lead to subsequent outbreaks. Of cases for whom the source was known, 37 of 57 (72.5%) were secondary to household transmission, 13 (25%) to intra-school transmission and one to community contacts between students in the same school.

Conclusion

RADT did not perform well as a screening tool in asymptomatic individuals. Reinforcing policies for symptom screening when entering schools and testing symptomatic individuals with RADT on the spot may avoid subsequent significant exposures in class.

Table of Contents Summary

Rapid antigen tests were compared to standard PCR to diagnose SARS-CoV-2 infections in high-school students. They performed better in symptomatic individuals.

What’s Known on This Subject

Rapid antigen detection tests (RADT) are often used to diagnose respiratory pathogens at the point-of-care. Their performance characteristics vary, but they usually have high specificity and moderate sensitivity compared with PCR.

What This Study Adds

RADT sensitivity ranged from 28.6% in asymptomatic individuals to 83.3% in symptomatic individuals. Return to school after 7 days of quarantine was safe in exposed students. Secondary cases were identified in 28% of classes with an index case.
Examining the Association between the COVID-19 Pandemic and Self-Harm Death Counts in Four Canadian Provinces
Authors: Isnar Shelly , Oremus Mark
Published: October 2021

Governments implemented lockdowns and other physical distancing measures to stop the spread of SARS-CoV-2 (COVID-19). Resulting unemployment, income loss, poverty, and social isolation, coupled with daily reports of dire news about the COVID-19 pandemic, could serve as catalysts for increased self-harm deaths (SHD). This ecological study examined whether observed SHD counts were higher than predicted SHD counts during the pandemic period in the Canadian provinces of Alberta, British Columbia, Ontario, and Québec. The study also explored whether SHD counts during the pandemic were affected by lockdown severity (measured using the lockdown stringency index [LSI]) and COVID-19 case numbers. We utilized publicly available SHD data from January 2018 through November 2020, and employed AutoRegressive Integrated Moving Average (ARIMA) modelling, to predict SHD during the COVID-19 period (March 21 to November 28, 2020). We used Poisson and negative binomial regression to assess ecological associations between the LSI and COVID-19 case numbers, controlling for seasonality, and SHD counts during the COVID-19 period. On average, observed SHD counts were lower than predicted counts during this period (p < 0.05 [except Alberta]). Additionally, LSI and COVID-19 case numbers were not statistically significantly associated with SHD counts.
Cue-specific remodeling of the neuronal transcriptome through intron retention programs
Authors: Mazille Maxime , Scheiffele Peter , Mauger Oriane
Published: October 2021

Sub-cellular compartmentalization through the nuclear envelope has for a long time been primarily considered a physical barrier that separates nuclear and cytosolic contents. More recently, nuclear compartmentalization has emerged to harbor key regulatory functions in gene expression. A sizeable proportion of protein-coding mRNAs is more prevalent in the nucleus than in the cytosol reflecting the existence of mechanisms to control mRNA release into the cytosol. However, the biological relevance of the nuclear retention of mRNAs remains unclear. Here, we provide a comprehensive map of the subcellular localization of mRNAs in mature neurons and reveal that transcripts stably retaining introns are broadly targeted for nuclear retention. We systematically probed these transcripts upon neuronal stimulation and found that sub-populations of nuclear-retained transcripts are bi-directionally regulated in response to cues: some appear targeted for degradation while others undergo splicing completion to generate fully mature mRNAs which are exported to the cytosol to increase functional gene expression. Remarkably, different forms of stimulation mobilize distinct groups of intron-retaining transcripts and this selectivity arises from the activation of specific signaling pathways. Overall, our findings uncover cue-specific control of intron retention as a major regulator of acute remodeling of the neuronal transcriptome.