bluuebunny/crossref_metadata_2025 huggingface dataset:
Preemptive Endoluminal Vacuum Therapy to Reduce Morbidity After Minimally Invasive Ivor Lewis Esophagectomy
Authors: Müller Philip C. , Morell Bernhard , Vetter Diana , Raptis Dimitri A. , Kapp Joshua R. , Gubler Christoph , Gutschow Christian A.
Published: August 2021

Objective:

Preemptive endoluminal vacuum therapy (pEVT) is a novel concept to reduce postoperative morbidity and has the potential to disrupt current treatment paradigms for patients undergoing esophagectomy.

Summary of Background Data:

Endoluminal vacuum therapy is an accepted treatment for AL after esophagectomy.

Methods:

Retrospective analysis of patients undergoing minimally invasive Ivor Lewis esophagectomy with pEVT between 11/2017 and 10/2020. The sponge was removed endoscopically after 4–6 days, and anastomosis and gastric conduit were assessed according to a novel endoscopic grading system. Further management was customized according to endoscopic appearance and clinical course. Endpoints were postoperative morbidity and AL rate, defined according to the Clavien-Dindo (CD) and International Esodata Study Group classifications.

Results:

PEVT was performed in 67 consecutive patients, 57 (85%) were high-risk patients with an ASA score >2, WHO/ECOG score >1, age >65 years, or BMI >29 kg/m2. Thirty patients experienced textbook outcome, and overall minor (≤CD IIIa) and major (≥CD IIIb) morbidity was 40.3% and 14.9% respectively. 30-day-mortality was 0%. Forty-nine patients (73%) had uneventful anastomotic healing after pEVT without further endoscopic treatment. The remaining 18 patients (27%) underwent prolonged EVT with uneventful anastomotic healing in 13 patients (19%), contained AL in 4 patients (6%), and 1 uncontained leakage (1.5%) in a case with proximal gastric conduit necrosis, resulting in an overall AL rate of 7.5%.

Conclusions:

PEVT is an innovative and safe procedure with a promising potential to reduce postoperative morbidity after minimally invasive Ivor Lewis esophagectomy and may be particularly valuable in highly comorbid cases.
Cerebellar Brain Inhibition Is Associated With the Severity of Cervical Dystonia
Authors: Sondergaard Rachel E. , Strzalkowski Nicholas D. J. , Gan Liu Shi , Jasaui Yamile , Furtado Sarah , Pringsheim Tamara M. , Sarna Justyna R. , Avanzino Laura , Kiss Zelma H. T. , Martino Davide
Published: August 2021

Purpose:

Cerebellar connectivity is thought to be abnormal in cervical dystonia (CD) and other dystonia subtypes, based on evidence from imaging studies and animal work. The authors investigated whether transcranial magnetic stimulation–induced cerebellar brain inhibition (CBI), a measure of cerebellar efficiency at inhibiting motor outflow, is abnormal in patients with CD and/or is associated with clinical features of CD. Because of methodological heterogeneity in CBI reporting, the authors deployed additional controls to reduce potential sources of variability in this study.

Methods:

Cerebellar brain inhibition was applied in 20 CD patients and 14 healthy control subjects. Cerebellar brain inhibition consisted of a cerebellar conditioning stimulus delivered at four different interstimulus intervals (ISIs) before a test stimulus delivered to hand muscle representation in the motor cortex. The average ratio of conditioned to unconditioned motor evoked potential was computed for each ISI. Cervical dystonia clinical severity was measured using the Toronto Western Spasmodic Torticollis Rating Scale. Control experiments involved neuronavigated transcranial magnetic stimulation, neck postural control in patients, and careful screening for noncerebellar pathway inhibition via cervicomedullary evoked potentials.

Results:

There was no difference between CBI measured in healthy control subjects and CD patients at any of the four ISIs; however, CBI efficiency was significantly correlated with worsening CD clinical severity at the 5 ms ISI.

Conclusions:

Cerebellar brain inhibition is a variable measure in both healthy control subjects and CD patients; much of this variability may be attributed to experimental methodology. Yet, CD severity is significantly associated with reduced CBI at the 5 ms ISI, suggestive of cerebello-thalamo-cortical tract dysfunction in this disorder.
Gadd45α is involved in regulating activity-dependent and exon-specific BDNF expression in postmitotic cortical neurons
Authors: Feng Yu , Wang Zhen , Wei Wei , Zhang Tingbao , Li Zhengwei , Chen† Jincao , Liu† Kui
Published: August 2021

Objective

This study aimed to explore the epigenetic regulation of activity-dependent and exon-specific brain-derived neurotrophic factor (BDNF) expression under KCl depolarization in primary cortical neurons.

Methods

We investigated BDNF exon I, exon IV and the growth arrest and DNA damage-inducible protein 45 alpha (Gadd45α) transcription levels under KCl-induced neuronal activation in postmitotic neurons. Gadd45α occupancy at BDNF I and IV promoter was measured by chromatin immunoprecipitation (ChIP) followed by quantitative PCR; DNA methylation level was checked by methylated DNA immunoprecipitation (MeDIP) followed by qPCR. In addition, lentiviral shRNA targeting Gadd45α was used to knockdown Gadd45α expression.

Results

BDNF exon I and IV mRNA expressions were both highly induced by KCl depolarization. However, ChIP analysis demonstrated a significantly increased Gadd45α occupancy only at the BDNF P1 promotor, but not P4, which is associated with reducing DNA methylation within BDNF P1 promoter. Furthermore, after the lentiviral-mediated knockdown of Gadd45α, the increased Gadd45α occupancy at the BDNF P1 was inhibited, which was accompanying the complete blocking of the demethylation effect at P1. Nonetheless, the induction of BDNF exon I mRNA by KCl was only partially prevented by Gadd45α shRNA, indicting other mechanisms involved in regulating BDNF exon I expression.

Conclusions

DNA demethylation mediated by Gadd45α protein involves promoting the regulation of activity-dependent BDNF exon I expression in neurons.
Cognition and motor learning in a Parkinson’s disease cohort: importance of recall in episodic memory
Authors: Chung Yu-Chen , Fisher Beth E. , Finley James M. , Kim Aram , Petkus Andrew J. , Schiehser Dawn M. , Jakowec Michael W. , Petzinger Giselle M.
Published: August 2021

Impaired motor learning in individuals with Parkinson’s disease is often attributed to deficits in executive function, which serves as an important cognitive process supporting motor learning. However, less is known about the role of other cognitive domains and its association with motor learning in Parkinson’s disease. The objective of this study was to investigate the associations between motor learning and multiple domains of cognitive performance in individuals with Parkinson’s disease. Twenty-nine participants with Parkinson’s disease received comprehensive neuropsychological testing, followed by practice of a bimanual finger sequence task. A retention test of the finger sequence task was completed 24 h later. Hierarchical linear regressions were used to examine the associations between motor learning (acquisition rate and retention) and cognitive performance in five specific cognitive domains, while controlling for age, sex, and years of Parkinson’s disease diagnosis. We found that a higher acquisition rate was associated with better episodic memory, specifically better recall in visual episodic memory, in individuals with Parkinson’s disease. No significant associations were observed between retention and cognitive performance in any domains. The association between motor acquisition and episodic memory indicates an increased dependency on episodic memory as a potential compensatory cognitive strategy used by individuals with Parkinson’s disease during motor learning.
Changes in the connection network of whole-brain fiber tracts in patients with Alzheimer’s disease have a tendency of lateralization
Authors: He Fangmei , Li Youjun , Li Chenxi , Zhao Jie , Liu Tian , Fan Liming , Zhang Xi , Wang Jue
Published: August 2021

Alzheimer’s disease is a common progressive neurodegenerative disorder in the elderly. Diffusion tensor imaging (DTI) has been widely used to explore structural integrity and to describe white matter degeneration in Alzheimer’s disease. Previous research has indicated that the change of connections between white matter fiber tracts is very important for investigating the brain function of Alzheimer’s disease patients. However, whether white matter features can be used as potential biomarkers for predicting Alzheimer’s disease tendency requires more in-depth research. In this study, we investigated the relationship between the damage in white matter tracts and the decline of cognitive function in Alzheimer’s disease. DTI data were collected from 38 Alzheimer’s disease patients and 30 normal controls. Fiber assignment by continuous tracking approach was used to establish connections between different brain regions of the whole brain, network-based statistical analysis and support vector machine classification analysis were used to explore the connection of whole-brain fiber bundles between the two groups. Most importantly, our results showed that the connections between brain regions of Alzheimer’s disease patients were damaged, and the damage were mainly located in the right hemisphere, there was a certain degree of lateralization effect. Using whole-brain fiber bundle connection network as a feature for classification, we found it helped to improve the classification accuracy in Alzheimer’s disease patients, which is useful for early clinical diagnosis of Alzheimer’s disease. These findings further suggested that we can use the whole-brain fiber bundle connection network of Alzheimer’s disease patients as a potential diagnostic indicator of Alzheimer’s disease in the future.
From vesicles to materials: bioinspired strategies for fabricating hierarchically structured soft matter
Authors: Amstad Esther , Harrington Matthew J.
Published: August 2021

Certain organisms including species of mollusks, polychaetes, onychophorans and arthropods produce exceptional polymeric materials outside their bodies under ambient conditions using concentrated fluid protein precursors. While much is understood about the structure-function relationships that define the properties of such materials, comparatively less is understood about how such materials are fabricated and specifically, how their defining hierarchical structures are achieved via bottom-up assembly. Yet this information holds great potential for inspiring sustainable manufacture of advanced polymeric materials with controlled multi-scale structure. In the present perspective, we first examine recent work elucidating the formation of the tough adhesive fibres of the mussel byssus via secretion of vesicles filled with condensed liquid protein phases (coacervates and liquid crystals)—highlighting which design principles are relevant for bio-inspiration. In the second part of the perspective, we examine the potential of recent advances in drops and additive manufacturing as a bioinspired platform for mimicking such processes to produce hierarchically structured materials.

This article is part of the theme issue ‘Bio-derived and bioinspired sustainable advanced materials for emerging technologies (part 1)’.
Revisiting the methods for detecting Mycobacterium tuberculosis: what has the new millennium brought thus far?
Authors: Campelo Thales Alves , Cardoso de Sousa Paulo Rafael , Nogueira Lucas de Lima , Frota Cristiane Cunha , Zuquim Antas Paulo Renato
Published: August 2021

Tuberculosis (TB) affects around 10 million people worldwide in 2019. Approximately 3.4 % of new TB cases are multidrug-resistant. The gold standard method for detecting

Mycobacterium tuberculosis

, which is the aetiological agent of TB, is still based on microbiological culture procedures, followed by species identification and drug sensitivity testing. Sputum is the most commonly obtained clinical specimen from patients with pulmonary TB. Although smear microscopy is a low-cost and widely used method, its sensitivity is 50–60 %. Thus, owing to the need to improve the performance of current microbiological tests to provide prompt treatment, different methods with varied sensitivity and specificity for TB diagnosis have been developed. Here we discuss the existing methods developed over the past 20 years, including their strengths and weaknesses. In-house and commercial methods have been shown to be promising to achieve rapid diagnosis. Combining methods for mycobacterial detection systems demonstrates a correlation of 100 %. Other assays are useful for the simultaneous detection of

M. tuberculosis

species and drug-related mutations. Novel approaches have also been employed to rapidly identify and quantify total mycobacteria RNA, including assessments of global gene expression measured in whole blood to identify the risk of TB. Spoligotyping, mass spectrometry and next-generation sequencing are also promising technologies; however, their cost needs to be reduced so that low- and middle-income countries can access them. Because of the large impact of

M. tuberculosis

infection on public health, the development of new methods in the context of well-designed and -controlled clinical trials might contribute to the improvement of TB infection control.
Staffing and Capacity Planning for SARS-CoV-2 Monoclonal Antibody Infusion Facilities: A Performance Estimation Calculator based on Discrete-Event Simulations
Authors: Çağlayan Çağlar , Thornhill Jonathan , Stewart Miles A. , Lambrou Anastasia S. , Richardson Donald , Rainwater-Lovett Kaitlin , Freeman Jeffrey D. , Pfundt Tiffany , Redd John T.
Published: July 2021

Objective

The COVID-19 pandemic has significantly stressed healthcare systems. The addition of monoclonal antibody (mAb) infusions, which prevent severe disease and reduce hospitalizations, to the repertoire of COVID-19 countermeasures offers the opportunity to reduce system stress but requires strategic planning and use of novel approaches. Our objective was to develop a web-based decision-support tool to help existing and future mAb infusion facilities make better and more informed staffing and capacity decisions.

Materials and Methods

Using real-world observations from three medical centers operating with federal field team support, we developed a discrete-event simulation model and performed simulation experiments to assess performance of mAb infusion sites under different conditions.

Results

162,000 scenarios were evaluated by simulations. Our analyses revealed that it was more effective to add check-in staff than to add additional nurses for middle-to-large size sites with ≥ 2 infusion nurses; that scheduled appointments performed better than walk-ins when patient load was not high; and that reducing infusion time was particularly impactful when load on resources was only slightly above manageable levels.

Discussion

Physical capacity, check-in staff, and infusion time were as important as nurses for mAb sites. Health systems can effectively operate an infusion center under different conditions to provide mAb therapeutics even with relatively low investments in physical resources and staff.

Conclusion

Simulations of mAb infusion sites were used to create a capacity planning tool to optimize resource utility and allocation in constrained pandemic conditions, and more efficiently treat COVID-19 patients at existing and future mAb infusion sites.
DERIVATION AND VALIDATION OF A CLINICAL SCORE TO PREDICT DEATH AMONG NON-PALLIATIVE COVID-19 PATIENTS PRESENTING TO EMERGENCY DEPARTMENTS: THE CCEDRRN COVID MORTALITY SCORE
Authors: Hohl Corinne M. , Rosychuk Rhonda J. , Archambault Patrick M. , O’Sullivan Fiona , Leeies Murdoch , Mercier Éric , Clark Gregory , Innes Grant D. , Brooks Steven C. , Hayward Jake , Ho Vi , Jelic Tomislav , Welsford Michelle , Sivilotti Marco L.A. , Morrison Laurie J. , Perry Jeffrey J.
Published: July 2021

Background

Predicting mortality from coronavirus disease 2019 (COVID-19) using information available when patients present to the Emergency Department (ED) can inform goals-of-care decisions and assist with ethical allocation of critical care resources.

Methods

We conducted an observational study to develop and validate a clinical score to predict ED and in-hospital mortality among consecutive non-palliative COVID-19 patients. We recruited from 44 hospitals participating in the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) between March 1, 2020 and January 31, 2021. We randomly assigned hospitals to derivation or validation, and pre-specified clinical variables as candidate predictors. We used logistic regression to develop the score in a derivation cohort, and examined its performance in predicting ED and in-hospital mortality in a validation cohort.

Results

Of 8,761 eligible patients, 618 (7·01%) died. The score included age, sex, type of residence, arrival mode, chest pain, severe liver disease, respiratory rate, and level of respiratory support. The area under the curve was 0·92 (95% confidence intervals [CI] 0·91–0·93) in derivation and 0·92 (95%CI 0·89–0·93) in validation. The score had excellent calibration. Above a score of 15, the observed mortality was 81·0% (81/100) with a specificity of 98·8% (95%CI 99·5–99·9%).

Interpretation

The CCEDRRN COVID Mortality Score is a simple score that accurately predicts mortality with variables that are available on patient arrival without the need for diagnostic tests.

Trial registration

Clinicaltrials.gov, NCT04702945
Impact of B.1.351 (beta) SARS-CoV-2 variant on BNT162b2 mRNA vaccine effectiveness in long-term care facilities of eastern France: a retrospective cohort study
Authors: Lefèvre Benjamin , Tondeur Laura , Madec Yoann , Grant Rebecca , Lina Bruno , van der Werf Sylvie , Rabaud Christian , Fontanet Arnaud , Legoff Antoine
Published: July 2021

Background

We aimed to assess the effectiveness of the BNT162b2 mRNA vaccine against B.1.351 (beta) variant among residents of long-term care facilities (LCTFs) in eastern France.

Methods

We used routinely collected surveillance and COVID-19 vaccination data to conduct a retrospective cohort study of SARS-CoV-2 B.1.351 infection incidence and vaccine effectiveness among LCTFs residents in eastern France between 15 January and 19 May 2021. Data from secondary RT-PCR screening were used to identify B.1.351 variants.

Findings

Included in our analysis were 378 residents from five LCTFs: 287 (76%) females, with median (IQR) age of 89 (83-92) years. Two B.1.351 outbreaks took place in LTCFs in which more than 70% of residents had received two doses of BNT162b2 mRNA vaccine, which included 11 cases of severe disease and six deaths among those who had received two doses. Vaccine effectiveness (95% CI) seven days after the second dose of vaccine was 49% (14-69) against any infection with B.1.351 and 86% (67-94) against severe forms of COVID-19. In multivariable analysis, females were less likely to develop severe forms of disease (IRR = 0.35, 95% CI = 0.20-0.63).

Interpretation

We observed reduced vaccine effectiveness associated with B.1.351, as well as B.1.351 outbreaks in two LTCFs among individuals who had received two doses of vaccine. Our findings highlight the need to maintain SARS-CoV-2 surveillance in these high-risk settings beyond the current COVID-19 mass vaccination campaign, and advocate for a booster vaccine dose prior to the next winter season.
Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study
Authors: Chia Po Ying , Xiang Ong Sean Wei , Chiew Calvin J , Ang Li Wei , Chavatte Jean-Marc , Mak Tze-Minn , Cui Lin , Kalimuddin Shirin , Chia Wan Ni , Tan Chee Wah , Ann Chai Louis Yi , Tan Seow Yen , Zheng Shuwei , Pin Lin Raymond Tzer , Wang Linfa , Leo Yee-Sin , Lee Vernon J , Lye David Chien , Young Barnaby Edward
Published: July 2021

Objectives

Highly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns (VOCs) with mutations in the spike protein are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections.

Methods

We conducted a multi-centre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared the clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals.

Results

Of 218 individuals with B.1.617.2 infection, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). PCR cycle threshold (Ct) values were similar between both vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients, however, these titers were significantly lower against B.1.617.2 as compared with the wildtype vaccine strain.

Conclusion

The mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of COVID-19 pandemic.
Promoting Resilience in Healthcare Workers during the COVID-19 Pandemic with a Brief Online Intervention
Authors: DeTore NR , Sylvia L , Park ER , Burke A , Levison JH , Shannon A , Choi KW , Jain FA , Coman DC , Herman J , Perlis R , Fava M , Holt DJ
Published: July 2021

Introduction

The psychological wellbeing of healthcare workers has been impacted by the high levels of stress many have experienced during the COVID-19 pandemic. This study aimed to examine the feasibility and acceptability of a brief online course focused on introducing skills that could increase resilience and decreases emotional distress in healthcare workers during the pandemic.

Materials and Methods

Employees of a large healthcare system completed a survey at baseline, one month, and two months later. The online course, called Resilience Training for Healthcare Workers, consists of three 12-20 minute videos focused on evidence-based skills that support aspects of emotional resilience: mindfulness, mentalization, and self-compassion.

Results

A total of 554 participants completed the baseline survey, endorsing moderate to high levels of emotional distress. Of those who completed all three assessments and participated in the course (n = 38), significant improvements in resilience and reductions in emotional distress were found across two months, in comparison to those who did not participate in the course.

Discussion

These findings suggest that a brief, online intervention can improve the mental health of healthcare workers during a crisis such as the COVID-19 pandemic.
Correlation of SARS-CoV-2 Breakthrough Infections to Time-from-vaccine; Preliminary Study
Authors: Mizrahi Barak , Lotan Roni , Kalkstein Nir , Peretz Asaf , Perez Galit , Ben-Tov Amir , Chodick Gabriel , Gazit Sivan , Patalon Tal
Published: July 2021

The short-term effectiveness of a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine was widely demonstrated. However, long term effectiveness is still unknown. A nationwide vaccination campaign was initiated early in Israel, allowing for a real-world evaluation of the interaction between protection and time-from-vaccine. The Delta (B.1.617.2) variant became the dominant strain in Israel in June 2021, as Israel is currently experiencing a new surge of cases. Leveraging the centralized computerized database of Maccabi Healthcare Services (MHS), we assessed the correlation between time-from-vaccine and incidence of breakthrough infection. We found that the risk for infection was significantly higher for early vaccinees compared to those vaccinated later. This preliminary finding should prompt further investigagions into long-term protection against different strains, and prospective clinical trials to examine the effect of a booster vaccine against breakthrough infection.
Advances in Classifying the Stages of Diabetic Retinopathy Using Convolutional Neural Networks in Low Memory Edge Devices
Authors: Paul Aditya Jyoti
Published: July 2021

Diabetic Retinopathy (DR) is a severe complication that may lead to retinal vascular damage and is one of the leading causes of vision impairment and blindness. DR broadly is classified into two stages – non-proliferative (NPDR), where there are almost no symptoms, except a few microaneurysms, and proliferative (PDR) involving a huge number of microaneurysms and hemorrhages, soft and hard exudates, neo-vascularization, macular ischemia or a combination of these, making it easier to detect. More specifically, DR is usually classified into five levels, labeled 0-4, from 0 indicating no DR to 4 which is most severe. This paper firstly presents a discussion on the risk factors of the disease, then surveys the recent literature on the topic followed by examining certain techniques which were found to be highly effective in improving the prognosis accuracy. Finally, a convolutional neural network model is proposed to detect all the stages of DR on a low-memory edge microcontroller. The model has a size of just 5.9 MB, accuracy and F1 score both of 94% and an inference speed of about 20 frames per second.
SARS-CoV-2 introduction and lineage dynamics across three epidemic peaks in Southern Brazil: massive spread of P.1
Authors: Muterle Varela Ana Paula , Prichula Janira , Mayer Fabiana Quoos , Salvato Richard Steiner , Sant’Anna Fernando Hayashi , Gregianini Tatiana Schäffer , Martins Letícia Garay , Seixas Adriana , Veiga Ana B. G.
Published: July 2021

Background

Genomic surveillance of SARS-CoV-2 is paramount for understanding viral dynamics, contributing to disease control. This study analyzed SARS-CoV-2 genomic diversity in Rio Grande do Sul (RS), Brazil, including the first case of each Regional Health Coordination and cases from three epidemic peaks.

Methods

Ninety SARS-CoV-2 genomes from RS were sequenced and analyzed against SARS-CoV-2 datasets available in GISAID for phylogenetic inference and mutation analysis.

Results

SARS-CoV-2 lineages among the first cases in RS were B.1 (33.3%), B.1.1.28 (26.7%), B.1.1 (13.3%), B.1.1.33 (10.0%), and A (6.7%), evidencing SARS-CoV-2 introduction by both international origin and community-driven transmission. We found predominance of B.1.1.33 (50.0%) and B.1.1.28 (35.0%) during the first epidemic peak (July–August, 2020), emergence of P.2 (55.6%) in the second peak (November–December, 2020), and massive spread of P.1 and related sequences (78.4%), such as P.1-like-II, P.1.1 and P.1.2 in the third peak (February–April, 2021). Eighteen novel mutation combinations were found among P.1 genomes, and 22 different spike mutations and/or deletions among P.1 and related sequences.

Conclusions

This study shows the dispersion of SARS-CoV-2 lineages in Southern Brazil, and describes SARS-CoV-2 diversity during three epidemic peaks, highlighting the spread of P.1 and the high genetic diversity of currently circulating lineages. Genomic monitoring of SARS-CoV-2 is essential to guide health authorities’ decisions to control COVID-19 in Brazil.

Ninety SARS-CoV-2 genomes from Rio Grande do Sul, Brazil, were sequenced, including the first cases from 15 State Health Coordination regions and samples from three epidemic peaks. Phylogenomic inferences showed SARS-CoV-2 lineages spread, revealing its genomic diversity.
3D printed cobalt-chromium-molybdenum porous superalloy with superior antiviral activity
Authors: Arjunan Arun , Robinson John , Baroutaji Ahmad , Martí Miguel , Tuñón-Molina Alberto , Serrano-Aroca Ángel
Published: July 2021

COVID-19 pandemic and associated supply-chain disruptions emphasise the requirement for antimicrobial materials for on-demand manufacturing. Besides aerosol transmission, SARS-CoV-2 is also propagated through contact with virus-contaminated surfaces. As such, the development of effective biofunctional materials that can inactivate SARS-CoV-2 are critical for pandemic preparedness. Such materials will enable the rational development of antiviral devices with prolonged serviceability reducing the environmental burden of disposable alternatives. This research reveals the novel use of Laser Powder Bed Fusion (LPBF) to 3D print porous Cobalt-Chromium-Molybdenum (Co-Cr-Mo) superalloy with potent antiviral activity (100% viral inactivation in 30 mins). The porous material was rationally conceived using a multi-objective surrogate model featuring track thickness (tt) and pore diameter (ϕd) as responses. The regression analysis found the most significant parameters for Co-Cr-Mo track formation to be the interaction effects of scanning rate (Vs) and laser power (Pl) in the orderPlVs>Vs>Pl. Contrastively, the pore diameter was found to be primarily driven by the hatch spacing (Sh). The study is the first to demonstrate the superior antiviral properties of 3D printed Co-Cr-Mo superalloy against an enveloped virus used as biosafe viral model of SARS-CoV-2. The material significantly outperforms the viral inactivation time of other broadly used antiviral metals such as copper and silver from 5 hours to 30 minutes. As such the study goes beyond the current state-of-the-art in antiviral alloys to provide extra-protection to combat the SARS-COV-2 viral spread. The evolving nature of the COVID-19 pandemic brings new and unpredictable challenges where on-demand 3D printing of antiviral materials can achieve rapid solutions while reducing the environmental impact of disposable devices.

Graphical abstract
Source tracking and global distribution of the mobilized tigecycline resistant gene tet(X)
Authors: Zhang Rong-min , Sun Jian , Sun Ruan-yang , Wang Min-ge , Cui Chao-yue , Fang Liang-xing , Liao Mei-na , Lu Xiao-qing , Liu Yong-xin , Liao Xiao-Ping , Liu Ya-Hong
Published: August 2021

The emergence of tet(X) genes has compromised the clinical use of the last-line antibiotic tigecycline. We identified 322 (1.21%) tet(X) positive samples from 12,829 human microbiome samples distributed in four continents (Asia, Europe, North America and South America) using retrospective data from worldwide. These tet(X) genes were dominated by tet(X2)-like orthologs but we also identified 12 samples carrying novel tet(X) genes, designed tet(X15) and tet(X16), that were resistant to tigecycline. The metagenomic analysis revealed these tet(X) genes distributed in anaerobes dominated by Bacteroidaceae (78.89%) of human-gut origin. The transmission of these tet(X2)-like orthologs between Bacteroidaceae and Riemerella anatipestifer was primarily promoted by the mobile elements ISBf11 and IS4351. tet(X2)-like orthologs was also developed during transmission by mutation to high-level tigecycline resistant determinants tet(X15) and tet(X16). Further tracing these tet(X) in single bacterial isolate from public repository indicated that tet(X) genes were present as early as 1960s in R. anatipestifer that was the primary tet(X) carrier at early stage (before 2000). The tet(X2) and non-tet(X2) orthologs were primarily distributed in humans and food animals respectively, and non-tet(X2) were dominated by tet(X3) and tet(X4). Genomic comparison indicated these tet(X) genes were likely to be generated during tet(X) transmission between Flavobacteriaceae and E. coli/Acinetobacter spp.., and ISCR2 played a key role in the transmission. These results suggest R. anatipestifer was the potential ancestral source of tet(X) gene. Additionally, Bacteroidaceae of human-gut origin was an important hidden reservoir and mutational incubator for the mobile tet(X) genes that enabled spread to facultative anaerobes and aerobes.
Production of human milk fat substitute by engineered strains of Yarrowia lipolytica
Authors: Bhutada Govindprasad , Menard Guillaume , Ledesma-Amaro Rodrigo , Eastmond Peter J
Published: August 2021

Human milk fat has a distinctive stereoisomeric structure where palmitic acid is esterified to the middle (sn-2) position on the glycerol backbone of the triacylglycerol and unsaturated fatty acids to the outer (sn-1/3) positions. This configuration allows for more efficient nutrient absorption in the infant gut. However, the fat used in most infant formulas originates from plants, which tend only to esterify palmitic acid to the sn-1/3 positions. Oleaginous yeasts provide an alternative source of lipids for human nutrition. However, these yeasts also exclude palmitic acid from the sn-2 position of their triacylglycerol. Here we show that Yarrowia lipolytica can be engineered to produce triacylglycerol with more than 60% of the palmitic acid in the sn-2 position, by expression of a lysophosphatidic acid phosphatase with palmitoyl-Coenzyme A specificity, such as LPAAT2 from Chlamydomonas reinhardtii. The engineered Y. lipolytica strains can be cultured on glycerol, glucose, palm oil or a mixture of substrates, under nitrogen limited condition, to produce triacylglycerol with a fatty acid composition that resembles human milk fat, in terms of the major molecular species; palmitic, oleic and linoleic acids. Culture on palm oil or a mixture of glucose and palm oil produced the highest lipid titre in shake flask culture and a triacylglycerol composition that is most similar with human milk fat. Our data show that an oleaginous yeast can be engineered to produce a human milk fat substitute (β-palmitate), that could potentially be used as an ingredient in infant formulas.
Selective logging shows no impact on the dietary breadth of the fawn leaf-nosed bat (Hipposideros cervinus)
Authors: Hemprich-Bennett David R. , Kemp Victoria A. , Blackman Joshua , Lewis Owen T. , Struebig Matthew J. , Bernard Henry , Rossiter Stephen J. , Clare Elizabeth L.
Published: August 2021

Logging activities degrade forest habitats across large areas of the tropics, but the impacts on trophic interactions that underpin forest ecosystems are poorly understood. DNA metabarcoding provides an invaluable tool to investigate such interactions, allowing analysis at a far greater scale and resolution than has previously been possible. We analysed the diet of the insectivorous fawn leaf-nosed batHipposideros cervinusacross a forest disturbance gradient in Borneo, using a dataset of ecological interactions from an unprecedented number of bat-derived faecal samples. Bats predominantly consumed insects from the orders Lepidoptera, Blattodea, Diptera and Coleoptera, and the taxonomic composition of their diet remained relatively consistent across sites regardless of logging disturbance. There was little difference in the richness of prey consumed in each logging treatment, indicating potential resilience of this species to habitat degradation. In fact, bats consumed a high richness of prey items, and intensive sampling is needed to reliably compare feeding ecology over multiple sites regardless of the bioinformatic procedures used.
Scaffold modelling captures the structure-function-dynamics relationship in brain microcircuits
Authors: Schepper Robin De , Geminiani Alice , Masoli Stefano , Rizza Martina Francesca , Antonietti Alberto , Casellato Claudia , D’Angelo Egidio
Published: August 2021

1

Modelling brain networks with complex configuration and cellular properties requires a set of neuroinformatic tools and an organized staged workflow. We have therefore developed the Brain Scaffold Builder (BSB), a new modeling framework embedding multiple strategies for cell placement and connectivity and a flexible management of cellular and network mechanisms. With BSB, for the first time, the mouse cerebellar cortex was reconstructed and simulated at cellular resolution, using morphologically realistic multi-compartmental single-neuron models. Embedded connection rules allowed BSB to generate the cerebellar connectome, unifying a collection of scattered experimental data into a coherent construct. Naturalistic background and sensory-burst stimulation were used for functional validation against recordings in vivo, monitoring the impact of subcellular mechanisms on signal propagation and spatio-temporal processing and providing a new ground-truth about circuit organization for the prediction of neural dynamics.
Identification and functional characterization of transcriptional activators in human cells
Authors: Alerasool Nader , Lin Zhen-Yuan , Gingras Anne-Claude , Taipale Mikko
Published: July 2021

Transcription is orchestrated by thousands of transcription factors and chromatin-associated proteins, but how these are causally connected to transcriptional activation or repression is poorly understood. Here, we conduct an unbiased proteome-scale screen to systematically uncover human proteins that activate transcription in a natural chromatin context. We also identify potent transactivation domains among the hits. By combining interaction proteomics and chemical inhibitors, we delineate the preference of both known and novel transcriptional activators for specific co-activators, highlighting how even closely related TFs can function via distinct co-factors. Finally, we show that many novel activators are partners in fusion events in tumors and functionally characterize a myofibroma-associated fusion between SRF and C3orf62, a potent activator. SRF-C3orf62 activates transcription in a CBP/p300-dependent manner and promotes proliferative and myogenic transcriptional programs. Our work provides a functional catalogue of potent transactivators in the human proteome and a platform for discovering transcriptional regulators at genome scale.
The Pace of Modern Life, Revisited
Authors: Sanderson Sarah , Beausoleil Marc-Olivier , O’Dea Rose E. , Wood Zachary T. , Correa Cristian , Frankel Victor , Gorné Lucas D. , Haines Grant E. , Kinnison Michael T. , Oke Krista B. , Pelletier Fanie , Pérez-Jvostov Felipe , Reyes-Corral Winer Daniel , Ritchot Yanny , Sorbara Freedom , Gotanda Kiyoko M. , Hendry Andrew P.
Published: August 2021

Wild populations must continuously adapt to environmental changes or they risk extinction. Such adaptations can be measured as phenotypic rates of change and can allow us to predict patterns of contemporary evolutionary change. About two decades ago, a dataset of phenotypic rates of change in wild populations was compiled. Since then, researchers have used (and expanded) this dataset to look at microevolutionary processes in relation to specific types of human disturbances. Here, we have updated the dataset adding 5675 estimates of phenotypic changes and used it to revisit established patterns of contemporary evolutionary change. Using this newer version, containing 7338 estimates of phenotypic changes, we revisit the conclusions of four published articles. We then synthesize the expanded dataset to compare rates of change across different types of human disturbance. Analyses of this expanded dataset suggests that: I. a small absolute difference in rates of change exists between human disturbed and natural populations, II. harvesting by humans results in larger rates of change than other types of disturbances, III. introduced populations have increased rates of change, and IV. body size does not increase through time. Overall, findings from earlier analyses have largely held-up in analyses of our new dataset that encompass a much larger breadth of species, traits, and human disturbances. Lastly, we found that types of human disturbances affect rates of phenotypic change, and we call for this database to serve as a steppingstone for further analyses to understand patterns of contemporary evolution.
Neural temporal context reinstatement of event structure during memory recall
Authors: Lohnas Lynn J. , Karl Healey M. , Davachi Lila
Published: August 2021

Although life unfolds continuously, experiences are generally perceived and remembered as discrete events. Accumulating evidence suggests that event boundaries disrupt temporal representations and weaken memory associations. However, less is known about the consequences of event boundaries on temporal representations during retrieval, especially when temporal information is not tested explicitly. Using a neural measure of temporal context extracted from scalp electroencephalography, we found reduced temporal context similarity between studied items separated by an event boundary when compared to items from the same event. Further, while participants free recalled list items, neural activity reflected reinstatement of temporal context representations from study, including temporal disruption. A computational model of episodic memory, the Context Maintenance and Retrieval model (CMR; Polyn, Norman & Kahana, 2009), predicted these results, and made novel predictions regarding the influence of temporal disruption on recall order. These findings implicate the impact of event structure on memory organization via temporal representations.
Directional sensitivity of the cerebral pressure-flow relationship in middle and posterior cerebral arteries using the repeated squat-stand model: within-day reproducibility and impact of diurnal variation in young healthy men and women
Authors: Labrecque Lawrence , Burma Joel S , Roy Marc-Antoine , Smirl Jonathan D , Brassard Patrice
Published: August 2021

We recently employed repeated squat-stands (RSS) to quantify directional sensitivity of the cerebral-pressure flow relationship (i.e. hysteresis) using a novel metric. Within-day reproducibility and diurnal variation impacts of this metric are unknown. We evaluated this metric for: 1) within-day reproducibility and the extent diurnal variation has in middle (MCA; ΔMCAvT/ΔMAPT) and posterior cerebral arteries (PCA; ΔPCAvT/ΔMAPT); 2) sex differences. Absolute (ΔMCAvT/ΔMAPT ; ΔPCAvT/ΔMAPT) and relative (%MCAvT/%MAPT, %PCAvT/%MAPT) metrics were calculated at seven time-points (08:00-17:00) in 18 participants (8 women; 24 ± 3 yrs) using the minimum-to-maximum MCAv/PCAv and MAP for each RSS at 0.05 Hz and 0.10 Hz. Reproducibility was evaluated with intraclass correlation coefficient (ICC). For all metrics, reproducibility was good (0.75-0.90) to excellent (>0.90). The metric in both arteries was impacted by MAP direction at 0.10 Hz (all p < 0.024). Time-of-day influenced ΔMCAvT/ΔMAPT (0.05 Hz: p = 0.0028; 0.10 Hz: p = 0.0009), %MCAvT/%MAPT (0.05 Hz: p = 0.035; 0.10 Hz: p = 0.0087), and ΔPCAvT/ΔMAPT (0.05 Hz: p = 0.0236). Sex differences in the MCA (p = 0.0028) vanished in relative terms and was absent in the PCA. These findings demonstrate within-day reproducibility of this metric in both arteries. Moreover, hysteresis is not impacted by sex.
Mitotic Chromosome Condensation Driven by a Volume Phase Transition
Authors: Beel Andrew J. , Matteï Pierre-Jean , Kornberg Roger D.
Published: July 2021

Procedures were devised for the reversible decondensation and recondensation of purified mitotic chromosomes. Computational methods were developed for the quantitative analysis of chromosome morphology in high throughput, enabling the recording of condensation behavior of thousands of individual chromosomes. Established physico-chemical theory for ionic hydrogels was modified for application to chromosomal material and shown to accurately predict the observed condensation behavior. The theory predicts a change of state (a “volume phase transition”) in the course of condensation, and such a transition was shown to occur. These findings, together with classical cytology showing loops of chromatin, lead to the description of mitotic chromosome structure in terms of two simple principles: contraction of length of chromatin fibers by the formation of loops, radiating from a central axis; and condensation of the chromosomal material against the central axis through a volume phase transition.

One sentence summary

The mitotic chromosome is an axially scaffolded ionic hydrogel, undergoing a volume phase transition to achieve a condensed state.
Classification of the plant-associated phenotype of Pseudomonas strains using genome properties and machine learning
Authors: Poncheewin Wasin , van Diepeningen Anne D. , van der Lee Theo AJ , Suarez-Diez Maria , Schaap Peter J.
Published: July 2021

The rhizosphere, the region of soil surrounding roots of plants, is colonized by a unique population of Plant Growth Promoting Rhizobacteria (PGPR). By enhancing nutrient uptake from the soil and through modulation of plant phytohormone status and metabolism, PGPR can increase the stress tolerance, growth and yield of crop plants. Many important PGPR as well as plant pathogens belong to the genus Pseudomonas. There is, however, uncertainty on the divide between phytobeneficial and phytopathogenic strains as previously thought to be signifying genomic features have limited power to separate these strains. Here the Genome properties (GP) common biological pathways annotation system was applied to establish the relationship between the genome wide GP composition and the plant-associated phenotype of 91 Pseudomonas strains representing both phenotypes. GP enrichment analysis, Random Forest model fitting and feature selection revealed 28 discriminating features. A validation dataset of 67 new strains confirmed the importance of the selected features for classification. A number of unexpected discriminating features were found, suggesting involvement of novel molecular mechanisms. The results suggest that GP annotations provide a promising computational tool to better classify the plant-associated phenotype.

Author summary

With a growing population the need to double the agricultural food production is specified. Simultaneously, there is an urgent need to implement sustainable and climate change resilient agricultural practices that preserve natural ecosystems. Cooperative microbiomes play important positive roles in plant growth development and fitness. Properly tuned, these microbiomes can significantly reduce the need for synthetic fertilizers and can replace chemicals in crop pest control. To select beneficial candidates, their traits need to be described and likewise, potential detrimental traits should be avoided. Here we applied GP-based comparative functional genomics, enrichment analysis and Random Forest model fitting to compare known phytobeneficial and phytopathogenic Pseudomonas strains. A number of unexpected discriminating features were found suggesting the involvement of novel molecular mechanisms.