bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of modified-NUTRIC score to assess nutritional risk in surgical intensive care unit
Authors: Lin Pi-Yi , Yen Yu-Tong , Lam Chee-Tat , Li Kuan-Chen , Lu Ming-Jen , Hsu Han-Shui
Published: June 2021

Background:

Modified Nutrition Risk in the Critically Ill (m-NUTRIC) score is used to evaluate the nutritional risk of patients in intensive care units (ICUs). This study aimed to investigate whether m-NUTRIC can be used as a predictive factor related to the outcome of patients in surgical ICU (SICU) and to identify which patients will benefit from aggressive nutritional intervention according to the results of m-NUTRIC score.

Methods:

A total of 205 patients who were admitted to surgical ICU (SICU) with ventilator use for more than 24 hours were enrolled. The m-NUTRIC score data were calculated the day when the patients were admitted to SICU. Patients were divided into two groups according to their m-NUTRIC score: the low-risk group (<5 points, 116 patients) and the high risk group (≥5 points, 89 patients).

Results:

In this study, a total of 205 patients were enrolled for analysis, including patients in the low-risk group (n = 116) and those in the high risk group (n = 89). The mean duration of ventilator use was 3.6 ± 6.5 days, and average SICU stays for all patients was 5.1 ± 7.4 days. The SICU mortality was significantly higher in the high-risk group (10.3% vs 1.7%). Comparison between survivals and nonsurvivals was carried out, and the data showed that the AKI, Vasopressors, SOFA, APACHE-II, m-NUTRIC score, and shock patient were all significantly associated with higher mortality. The multivariate analysis revealed that acute kidney injury (OR = 13.16; 95% confidence intervals = 3.69–46.92; p < 0.0001) and m-NUTRIC score were independent factors of ICU mortality in these patients. A receiver operating characteristic curve was used to calculate the area under the curve, which was 0.801. The data indicated that high m-NUTRIC score were significantly associated with SICU mortality with the cutoff score > 4 (sensitivity = 90.5%, specificity = 62.3%, p < 0.001).

Conclusion:

We found in this study that the high m-NUTRIC score is an independent factor of ICU mortality, and m-NUTRIC score can be used as an initial screening tool for nutritional assessment in patients admitted to surgical ICU. Further investigations to evaluate whether the aggressive nutritional intervention would be beneficial in the SICU patients with higher m-NUTRIC score is mandatory.
Progress in the Use of Platelet-Rich Plasma to Treat Vitiligo and Melasma
Authors: Ding Xian , Liu Sheng-Xiu
Published: June 2021

There have been numerous therapeutic innovations in the field of dermatology during the past decade. Of these, platelet-rich plasma (PRP) has recently aroused significant interest, particularly in treating acne scars and alopecia, and in skin rejuvenation. In contrast, less attention has been paid to the use of PRP as a treatment for other dermatologic conditions, such as vitiligo and melasma. The objective of this literature review was to focus on conditions of pigmented dermatosis and consolidate the available evidence regarding PRP usage for the practicing dermatologist. We reviewed the relevant literature on PRP treatment on vitiligo and melasma, and concluded that PRP has a significant improvement in pigmented dermatosis. Although numerous studies support the use of PRP, more research is needed to standardize the protocols for obtaining, processing, and applying PRP, as well as to determine the biological and molecular bases of its function.
Endoscopic Retrograde Cholangiopancreatography (ERCP) in Patients With Liver Cirrhosis
Authors: Solanki Shantanu , Kichloo Asim , Dahiya Dushyant S. , Solanki Dhanshree , Singh Jagmeet , Wani Farah , Albosta Michael , Ghimire Subash , Haq Khwaja F. , Khan Hafiz M.A. , Jafri Syed-Mohammed , Siddiqui Mohammad Arsalan , Zuchelli Tobias
Published: June 2021

Goals:

We aimed to assess outcomes of patients with liver cirrhosis who underwent therapeutic or diagnostic endoscopic retrograde cholangiopancreatography (ERCP) to determine whether these patients had different outcomes relative to patients without cirrhosis.

Background:

ERCP is an important procedure for treatment of biliary and pancreatic disease. However, ERCP is relatively technically difficult to perform when compared with procedures such as esophagogastroduodenoscopy or colonoscopy. Little is known about how ERCP use affects patients with liver cirrhosis.

Study:

Using patient records from the National Inpatient Sample (NIS) database, we identified adult patients who underwent ERCP between 2009 and 2014 using International Classification of Disease, Ninth Revision coding and stratified data into 2 groups: patients with liver cirrhosis and those without liver cirrhosis. We compared baseline characteristics and multiple outcomes between groups and compared outcomes of diagnostic versus therapeutic ERCP in patients with cirrhosis. A multivariate regression model was used to estimate the association of cirrhosis with ERCP outcomes.

Results:

A total of 1,038,258 hospitalizations of patients who underwent ERCP between 2009 and 2014 were identified, of which 31,294 had cirrhosis and 994,681 did not have cirrhosis. Of the patients with cirrhosis, 21,835 (69.8%) received therapeutic ERCP and 9459 (30.2%) received diagnostic ERCP. Patients with cirrhosis had more ERCP-associated hemorrhages (2.5% vs. 1.2%; P<0.0001) compared with noncirrhosis patients but had lower incidence of perforations (0.1% vs. 0.2%; P<0.0001) and post-ERCP pancreatitis (8.6% vs. 7%; P<0.0001). Cholecystitis was the same between groups (2.3% vs. 2.3%; P<0.0001). In patients with cirrhosis, those who received therapeutic ERCP had higher post-ERCP pancreatitis (7.9% vs. 5.1%; P<0.0001) and ERCP-associated hemorrhage (2.7% vs. 2.1%; P<0.0001) but lower incidences of perforation and cholecystitis (0.1% vs. 0.3%; P<0.0001) and cholecystitis (1.9 vs. 3.1%; P<0.0001) compared with those who received diagnostic ERCP.

Conclusions:

Use of therapeutic ERCP in patients with liver cirrhosis may lead to higher risk of complications such as pancreatitis and postprocedure hemorrhage, whereas diagnostic ERCP may increase the risk of pancreatitis and cholecystitis in patients with cirrhosis. Comorbidities in cirrhosis patients may increase the risk of post-ERCP complications and mortality; therefore, use of ERCP in cirrhosis patients should be carefully considered, and further studies on this patient population are needed.
Keys to Success
Authors: Doherty Dennis P. , Coffey Kristin , Weissman Laura , Dwyer Patricia A.
Published: June 2021

Patients with autism spectrum disorder present with an extensive range of communication and social skills that require healthcare workers to have a comprehensive understanding of best practices for providing holistic care. This article presents the planning, curriculum development, implementation, and evaluation of a professional development program aimed at providing interprofessional staff with strategies and resources to use when caring for patients with autism spectrum disorder.
Diversity in orthopaedic trauma: where we are and where we need to be
Authors: Ortega Gil , Benson Emily , Pierrie Sarah N. , McLaurin Toni M. , Tejwani Nirmal C.
Published: June 2021

Diversity has multiple dimensions, and individuals’ interpretation of diversity varies broadly. The Orthopaedic Trauma Association (OTA) leadership recognized the need to address issues of diversity within the organization and appointed the OTA Diversity Committee in 2020. The OTA Diversity Committee has produced a statement that was confirmed by the OTA's board of directors reflecting the organization's position on diversity: “The OTA promotes and values diversity and inclusion at all levels with the goal of creating an environment where every member has the opportunity to excel in leadership, education, and culturally-competent orthopaedic trauma care.” The OTA Diversity Committee surveyed its 1907 OTA members in the United States and Canada to assess its membership's attitudes toward and interpretation of this important topic.

Methods:

Two surveys were distributed. One 15-question survey was sent to 1907 OTA members with different membership categories in the United States and Canada requesting basic demographic information and asking how members felt about the degree to which women and underrepresented minorities (URM) are represented within the OTA and within its leadership. A second 11-question survey was sent to 30 past chairs of 2017–2019 OTA educational courses and meetings evaluating their criteria for choosing faculty for OTA courses. Comments were reviewed and summarized to identify recurring themes.

Results:

Two hundred seven responses from the membership and 14 from course chairs were received from the 1907 surveys that were emailed to OTA members in the United States and Canada. The results reveal awareness of the limited female and URM representation within the OTA. However, there is disagreement in how or even whether this should be addressed at an organizational level. Review of comments from both surveys reveals a number of common themes on these important topics.

Conclusion:

The members and course chairs surveyed recognize that there is limited diversity at the OTA leadership and faculty level. Many members feel that the OTA would benefit from increasing female and URM representation in committees, within the leadership, and as faculty at OTA-sponsored courses. However, survey comments reveal that many members and course chairs feel it is not the organization's role to regulate diversity and that diversity initiatives themselves may introduce an unnecessary form of bias.
Awareness of HIV Preexposure Prophylaxis Among People at Risk for HIV: Results From the 2017–2019 National Survey of Family Growth
Authors: Keddem Shimrit , Dichter Melissa E. , Hamilton Alison B. , Chhatre Sumedha , Sonalkar Sarita
Published: June 2021

Background

Although daily preexposure prophylaxis (PrEP) is now widely accepted as a safe and effective method for reducing the risk of HIV in high-risk groups, uptake has been slow. The goal of this analysis was to identify factors associated with PrEP awareness among individuals at risk for HIV.

Methods

This investigation analyzed data from the Centers for Disease Control and Prevention nationally representative survey, National Survey of Family Growth, for the years 2017 to 2019. Logistic regression was used to explore the relationship between PrEP awareness and demographics, HIV risk factors, and provider HIV risk screening.

Results

Only 37% of survey respondents with an increased risk of HIV were aware of PrEP. Several segments of the at-risk population had lower odds of being aware of PrEP, including heterosexual women, heterosexual men, individuals younger than 20 years, and individuals with lower levels of education. Those who participate in sex in exchange for money or drugs had significantly lower odds of being aware of PrEP. In comparison, PrEP awareness was significantly higher among nonheterosexual men and both men and women whose partners were HIV positive. Lastly, those who had been screened by a provider for HIV risk had significantly higher odds of being aware of PrEP.

Conclusions

This research supports the need for policies and programs to increase awareness of PrEP, especially among certain segments of the population at increased risk for HIV.
Effects of Orthoses on Standing Postural Control and Muscle Activity in Children With Cerebral Palsy
Authors: Leonard Rebecca , Sweeney Jane , Damiano Diane , Bjornson Kristie , Ries Julie
Published: June 2021

Purpose:

This exploratory study assessed postural control and muscle activity in children with cerebral palsy while standing barefoot (BF), in prescribed ankle-foot orthoses (AFOs) and in distal control orthoses (DCOs), which stabilized foot-ankle and deliberately aligned the shank.

Methods:

This within-subject study evaluated 10 participants, Gross Motor Functional Classification System level III, across the 3 ankle-foot conditions in: (1) static standing duration and (2) modified Clinical Test of Sensory Interaction on Balance with electromyography (EMG) on 7 muscles.

Results:

Participants had significantly decreased center of gravity (COG) velocity sway in DCO versus BF and AFO, decreased loss of balance (LOB), and increased standing for DCO versus BF. DCO had minimal effect on EMG activity.

Conclusions:

DCO provided significant stabilizing effects on COG sway velocity, standing duration, and LOB. DCO may be effective in balance training. It is unclear whether benefit was derived from stabilization of the ankle joint, the resultant shank alignment, or both.
Police transport of firearm-injured patients—more often and more injured
Authors: Maher Zoё , Beard Jessica H. , Dauer Elizabeth , Carroll Madeleine , Forman Steven , Topper Gena V. , Pathak Abhijit , Santora Thomas A. , Sjoholm Lars Ola , Zhao Huaqing , Goldberg Amy J.
Published: June 2021

BACKGROUND

Police transport (PT) of penetrating trauma patients decreases the time between injury and trauma center arrival. Our study objective was to characterize trends in the rate of PT and its impact on mortality. We hypothesized that PT is increasing and that these patients are more injured.

METHODS

We conducted a single-center, retrospective cohort study of adult (≥18 years) patients presenting with gunshot wounds (GSWs) to a level 1 center from 2012 to 2018. Patients transported by police or ambulance (emergency medical service [EMS]) were included. The association between mode of transport (PT vs. EMS) and mortality was evaluated using χ2, t tests, Mann-Whitney U tests, and logistic regression.

RESULTS

Of 2,007 patients, there were 1,357 PT patients and 650 EMS patients. Overall in-hospital mortality was 23.7%. The rate of GSW patients arriving by PT increased from 48.9% to 78.5% over the study period (p < 0.001). Compared with EMS patients, PT patients were sicker on presentation with lower initial systolic blood pressure (98 vs. 110, p < 0.001), higher Injury Severity Score (median [interquartile range], 10 [2–75] vs. 9 [1–17]; p < 0.001) and more bullet wounds (3.5 vs. 2.9, p < 0.001). Police-transported patients more frequently underwent resuscitative thoracotomy (19.2% vs. 10.0%, p < 0.001) and immediate surgical exploration (31.3% vs. 22.6%, p < 0.001). There was no difference in adjusted in-hospital mortality between transport groups. Of patients surviving to discharge, PT patients had higher Injury Severity Score (9.6 vs. 8.3, p = 0.004) and lower systolic blood pressure on arrival (126 vs. 130, p = 0.013) than EMS patients.

CONCLUSION

Police transport of GSW patients is increasing at our urban level 1 center. Compared with EMS patients, PT patients are more severely injured but have similar in-hospital mortality. Further study is necessary to understand the impact of PT on outcomes in specific subsets in penetrating trauma patients.

LEVEL OF EVIDENCE

Epidemiological, level III.
Prehospital end-tidal carbon dioxide predicts hemorrhagic shock upon emergency department arrival
Authors: Bulger Natalie , Harrington Brenna , Krieger Josh , Latimer Andrew , Arbabi Saman , Counts Catherine R. , Sayre Michael , Maynard Charles , Bulger Eileen M.
Published: June 2021

BACKGROUND

In addition to reflecting gas exchange within the lungs, end-tidal carbon dioxide (ETCO2) also reflects cardiac output based on CO2 delivery to the pulmonary parenchyma. We hypothesized that low prehospital ETCO2 values would be predictive of hemorrhagic shock in intubated trauma patients.

METHODS

A retrospective observational study of adult trauma patients intubated in the prehospital setting and transported to a single Level I trauma center from 2016 to 2019. Continuous prehospital ETCO2 data were linked with patient care registries. We developed a novel analytic approach that allows for reflection of prehospital ETCO2 over the entire prehospital course of care. The primary outcome was hemorrhagic shock on emergency department (ED) presentation, defined as either initial ED systolic blood pressure of 90 mm Hg or less or initial Shock Index (SI) > 0.9, and transfusion of at least one unit of blood product during their ED stay. Prehospital ETCO2 less than 25 mm Hg was evaluated for predictive value of hemorrhagic shock.

RESULTS

Three hundred and seven patients (82% men, 34% penetrating injury, 42% in hemorrhagic shock on ED arrival, 27% mortality) were included in the study. Patients in hemorrhagic shock had lower median ETCO2 values (26.5 mm Hg vs. 32.5 mm Hg; p < 0.001) than those not in hemorrhagic shock. Patients with prehospital ETCO2 less than 25 mm Hg were 3.0 times (adjusted odds ratio = 3.0; 95% confidence interval, 1.1–7.9) more likely to be in hemorrhagic shock upon ED arrival than patients with ETCO2 ≥ 25 mm Hg.

CONCLUSION

Intubated patients with hemorrhagic shock upon ED arrival had significantly lower prehospital ETCO2 values. Incorporating ETCO2 assessment into prehospital care for trauma patients could support decisions regarding prehospital blood transfusion, and triage to higher-level trauma centers, and trauma team activation.

LEVEL OF EVIDENCE

Prognostic, level III.
A Combined microRNA and Chemokine Profile in Urine to Identify Rejection After Kidney Transplantation
Authors: Gielis Els M. , Anholts Jacqueline D.H. , van Beelen Els , Haasnoot Geert W. , De Fijter Hans W. , Bajema Ingeborg , Heidt Sebastiaan , van de Vrie Mathijs , Hilbrands Luuk B. , Mallat Marko J.K. , Ledeganck Kristien J. , Claas Frans H.J. , Eikmans Michael
Published: June 2021

Background.

There is an unmet need for noninvasive tools for diagnosis of rejection after kidney transplantation. The aim of this study was to determine the discriminative value of a combined cellular and molecular biomarker platform in urine for the detection of rejection.

Methods.

First, microRNA (miR) molecules were screened in transplant biopsies and urine sediments of patients with acute rejection and patients without rejection and stable graft function. Second, the expression of 15 selected miRs was quantified in an independent set of 115 urine sediments of patients with rejection and 55 urine sediments of patients without histological signs of rejection on protocol biopsy. Additionally, CXCL-9 and CXCL-10 protein levels were quantified in the urine supernatant.

Results.

Levels of miR-155-5p (5.7-fold), miR-126-3p (4.2-fold), miR-21-5p (3.7-fold), miR-25-3p (2.5-fold), and miR-615-3p (0.4-fold) were significantly different between rejection and no-rejection urine sediments. CXCL-9 and CXCL-10 levels were significantly elevated in urine from recipients with rejection. In a multivariable model (sensitivity: 89.1%, specificity: 75.6%, area under the curve: 0.94, P < 0.001), miR-155-5p, miR-615-3p, and CXCL-9 levels were independent predictors of rejection. Stratified 10-fold cross validation of the model resulted in an area under the curve of 0.92.

Conclusions.

A combined urinary microRNA and chemokine profile discriminates kidney transplant rejection from stable graft conditions.
Possible future waves of SARS-CoV-2 infection generated by variants of concern with a range of characteristics
Authors: Dyson Louise , Hill Edward M. , Moore Sam , Curran-Sebastian Jacob , Tildesley Michael J. , Lythgoe Katrina A , House Thomas , Pellis Lorenzo , Keeling Matt J.
Published: June 2021

Viral reproduction of SARS-CoV-2 provides opportunities for the acquisition of advantageous mutations, altering viral transmissibility, disease severity, and/or allowing escape from natural or vaccine-derived immunity. We use three mathematical models: a parsimonious deterministic model with homogeneous mixing; an age-structured model; and a stochastic importation model to investigate the effect of potential variants of concern (VOCs). Calibrating to the situation in England in May 2021, we find epidemiological trajectories for putative VOCs are wide-ranging and dependent on their transmissibility, immune escape capability, and the introduction timing of a postulated VOC-targeted vaccine. We demonstrate that a VOC with a substantial transmission advantage over resident variants, or with immune escape properties, can generate a wave of infections and hospitalisations comparable to the winter 2020-2021 wave. Moreover, a variant that is less transmissible, but shows partial immune-escape could provoke a wave of infection that would not be revealed until control measures are further relaxed.
Immunity to SARS-CoV-2 persists 9 months post-symptoms with an altered T cell phenotype compared to influenza A virus-specific memory
Authors: Law Jaclyn C. , Girard Melanie , Chao Gary Y. C. , Ward Lesley A. , Isho Baweleta , Rathod Bhavisha , Colwill Karen , Li Zhijie , Rini James M. , Yue Feng Yun , Mubareka Samira , McGeer Allison J. , Ostrowski Mario A. , Gommerman Jennifer L. , Gingras Anne-Claude , Watts Tania H.
Published: June 2021

SARS-CoV-2 induces T cell, B cell and antibody responses that are detected for several months in recovered individuals. Whether this response resembles a typical respiratory viral infection is a matter of debate. Here we followed T cell and antibody responses in 24 mainly non-hospitalized SARS-CoV-2 recovered subjects at two time points (median of 45- and 145-days post-symptom onset). Antibody responses were detected in 95% of subjects, with a strong correlation between plasma and salivary anti-S and anti-RBD IgG, as well as a correlation between circulating T follicular helper cells and the SARS-CoV-2-specific IgG response. Based on intracellular cytokine production or proliferation, CD4+T cell responses to SARS-CoV-2 were detected in all subjects, decaying with a half-life of 5-6 months for S-specific IL-2-producing cells. CD4+responses were largely of the T helper 1 phenotype, but with a lower ratio of IFN-γ: IL-2 producing cells and a lower frequency of CD8+:CD4+T cells compared to influenza A virus-(IAV)-specific memory responses within the same subjects. Analysis of secreted molecules also revealed a lower ratio of IFN-γ: IL-2 and IFN-γ: IL-6 and an altered cytotoxic profile for S- and N-specific compared to IAV-specific responses. These data suggest that the memory T-cell phenotype after a single infection with SARS-CoV-2 persists over time, with an altered cytokine and cytotoxic profile compared to long term memory to IAV within the same subjects.

One Sentence Summary

Immunity to SARS-CoV-2 in a cohort of patients, mainly with mild COVID-19 disease, persists to 9 months with an altered T cell cytokine and cytotoxicity profile compared to influenza A virus-specific memory T cells from the same subjects.
SARS-CoV-2 B.1.617 Indian variants: are electrostatic potential changes responsible for a higher transmission rate?
Authors: Pascarella Stefano , Ciccozzi Massimo , Zella Davide , Bianchi Martina , Benetti Francesca , Broccolo Francesco , Cauda Roberto , Caruso Arnaldo , Angeletti Silvia , Giovanetti Marta , Cassone Antonio
Published: June 2021

Lineage B.1.617+, also known as G/452R.V3, is a recently described SARS-CoV-2 variant under investigation (VUI) firstly identified in October 2020 in India. As of May 2021, three sublineages labelled as B.1.617.1, B.1.617.2 and B.1.617.3 have been already identified, and their potential impact on the current pandemic is being studied. This variant has 13 amino acid changes, three in its spike protein, which are currently of particular concern: E484Q, L452R and P681R. Here we report a major effect of the mutations characterizing this lineage, represented by a marked alteration of the surface electrostatic potential (EP) of the Receptor Binding Domain (RBD) of the spike protein. Enhanced RBD-EP is particularly noticeable in the B.1.617.2 sublineage, which shows multiple replacements of neutral or negatively-charged amino acids with positively-charged amino acids. We here hypothesize that this EP change can favor the interaction between the B.1.617+RBD and the negatively-charged ACE2 thus conferring a potential increase in the virus transmission.
Regulation of brain aging by neutral sphingomyelinase 2
Authors: Zhu Zhihui , Quadri Zainuddin , Crivelli Simone M. , Elsherbini Ahmed , Zhang Liping , Tripathi Priyanka , Qin Haiyan , Roush Emily , Spassieva Stefka D. , Nikolova-Karakashian Mariana , McClintock Timothy S. , Bieberich Erhard
Published: June 2021

We have shown that deficiency of neutral sphingomyelinase 2 (nSMase2), an enzyme generating the sphingolipid ceramide, improves memory in adult mice. Here, we performed sphingolipid and RNA-seq analyses on the cortex from 10 month-old nSMase2-deficient (fro/fro) and heterozygous (+/fro) mice. fro/fro cortex showed reduced levels of ceramide, particularly in astrocytes. Differentially abundant transcripts included several functionally related groups, with decreases in mitochondrial oxidative phosphorylation and astrocyte activation transcripts, while axon guidance and synaptic transmission transcripts were increased, indicating a role of nSMase2 in oxidative stress, astrocyte activation, and cognition. Experimentally induced oxidative stress decreased the level of glutathione (GSH), an endogenous inhibitor of nSMase2, and increased immunolabeling for ceramide in primary +/fro astrocytes, but not in fro/fro astrocytes. β-galactosidase activity was lower in 5-weeks old fro/fro astrocytes, indicating delayed senescence due to nSMase2 deficiency. In fro/fro cortex, levels of the senescence markers C3b and p27, and the proinflammatory cytokines interleukin 1β, interleukin 6, and tumor necrosis factor α were reduced, concurrent with 2-fold decreased phosphorylation of their downstream target, protein kinase Stat3. RNA and protein levels of the ionotropic glutamate receptor subunit 2b (Grin2b or NR2B) were increased by 2-fold, an effect known to enhance cognition. This was consistent with 3.5-fold reduced levels of exosomes carrying miR-223-3p, a micro-RNA downregulating Grin2b. In summary, our data show that nSMase2 deficiency prevents oxidative stress-induced elevation of ceramide and secretion of exosomes by astrocytes that suppress neuronal function, indicating a role of nSMase2 in the regulation of neuroinflammation and cognition during brain aging.

Significance statement

Oxidative stress is associated with brain aging and cognitive decline. The underlying mechanism how oxidative stress impairs brain function is still not clear. We provide evidence that oxidative stress increases ceramide in astrocytes, which is prevented by deficiency of nSMase2, an enzyme that is activated by oxidative stress and generates ceramide from sphingomyelin. Mass spectrometric and transciptomic (RNA-seq) analyses show that in middle aged (10-month old) mouse cortex, nSMase2 deficiency reduces ceramide and increases expression of genes important for synaptic transmission and cognition. Therefore, our data show that oxidative stress-induced activation of nSMase2 and generation of ceramide is significant for cognitive decline during aging.
Country-wide genomic surveillance of SARS-CoV-2 strains
Authors: Kalia Kishan , Saberwal Gayatri , Sharma Gaurav
Published: June 2021

Genomic surveillance has enabled the identification of several SARS-CoV-2 variants, allowing the formulation of appropriate public health policies. However, surveillance could be made more effective. We have determined that the time taken from strain collection to genome submission for over 1.7 million SARS-CoV-2 strains available at GISAID. We find that strain-wise, time lag in this process ranges from one day to over a year. Country-wise, the UK has taken a median of 16 days (for 417,287 genomes), India took 57 days (for 15,614 genomes), whereas Qatar spent 289 days (for 2298 genomes). We strongly emphasize that along with increasing the number of genomes of COVID-19 positive cases sequenced, their accelerated submission to GISAID should also be strongly encouraged and facilitated. This will enable researchers across the globe to track the spreading of variants in a timely manner; analyse their biology, epidemiology, and re-emerging infections; and define effective public health policies.
ECCsplorer: a pipeline to detect extrachromosomal circular DNA (eccDNA) from next-generation sequencing data
Authors: Mann Ludwig , Seibt Kathrin M. , Weber Beatrice , Heitkam Tony
Published: June 2021

Motivation

Extrachromosomal circular DNAs (eccDNAs) are ring-like DNA structures physically separated from the chromosomes with 100 bp to several megabasepairs in size. Apart from carrying tandemly repeated DNA, eccDNAs may also harbor extra copies of genes or recently activated transposable elements. As eccDNAs occur in all eukaryotes investigated so far and likely play roles in stress, cancer, and aging, they have been prime targets in recent research – with their investigation limited by the scarcity of computational tools.

Results

Here, we present the ECCsplorer, a bioinformatics pipeline to detect eccDNAs in any kind of organism or tissue using next-generation sequencing techniques. Following Illumina-sequencing of amplified circular DNA (circSeq), the ECCsplorer enables an easy and automated discovery of eccDNA candidates. The data analysis encompasses two major procedures: First, read mapping to the reference genome allows the detection of informative read distributions including high coverage, discordant mapping, and split reads. Second, reference-free comparison of read clusters from amplified eccDNA against control sample data reveals specifically enriched DNA circles. Both software parts can be run separately or jointly, depending on the individual aim or data availability. To illustrate the wide applicability of our approach, we analyzed semiartificial and published circSeq data from the model organisms H. sapiens and A. thaliana, and generated circSeq reads from the non-model crop B. vulgaris. We clearly identified eccDNA candidates from all datasets, with and without reference genomes. The ECCsplorer pipeline specifically detected mitochondrial mini-circles and retrotransposon activation, showcasing the ECCsplorer’s sensitivity and specificity. The derived eccDNA targets are valuable for a wide range of downstream investigations – from analysis of cancer-related eccDNAs over organelle genomics to identification of active transposable elements.

Availability and implementation

The ECCsplorer pipeline is available on GitHub at https://github.com/crimBubble/ECCsplorer under the GNU license.

Contact

Tony Heitkam (tony.heitkam@tu-dresden.de)

Supplementary information

Supplementary data are available online.
Genomic Prediction of Strawberry Resistance to Postharvest Fruit Decay Caused by the Fungal PathogenBotrytis cinerea
Authors: Petrasch Stefan , Mesquida-Pesci Saskia D. , Pincot Dominique D.A. , Feldmann Mitchell J. , López Cindy M. , Famula Randi , Hardigan Michael A. , Cole Glenn S. , Knapp Steven J. , Blanco-Ulate Barbara
Published: June 2021

Gray mold, a disease of strawberry (Fragaria×ananassa) caused by the ubiquitous necrotrophBotrytis cinerea, renders fruit unmarketable and causes economic losses in the postharvest supply chain. To explore the feasibility of selecting for increased resistance to gray mold, we undertook genetic and genomic prediction studies in strawberry populations segregating for fruit quality and shelf life traits hypothesized to pleiotropically affect susceptibility. As predicted, resistance to gray mold was heritable but quantitative genetically complex. While every individual was susceptible, the speed of symptom progression and severity differed. Narrow-sense heritability ranged from 0.38-0.71 for lesion diameter (LD) and 0.39-0.44 for speed of emergence of external mycelium (EM). Even though significant additive genetic variation was genome wide observed for LD and EM, the phenotypic ranges were comparatively narrow and genome-wide analyses did not identify any large effect loci. Genomic selection accuracy ranged from 0.28-0.59 for LD and 0.37-0.47 for EM. Additive genetic correlations between fruit quality and gray mold resistance traits were consistent with prevailing hypotheses: LD decreased as titratable acidity increased, whereas EM increased as soluble solid whole genome content decreased and firmness increased. We concluded that phenotypic and genomic selection could be regression effective for reducing LD and increasing EM, especially in long shelf life populations, but that a significant fraction of the genetic variation for resistance to gray mold was caused by the pleiotropic effects of fruit quality traits that differ among market and shelf life classes.
Rapid simultaneous acquisition of macromolecular tissue volume, susceptibility, and relaxometry maps
Authors: Yu Fang Frank , Huang Susie Yi , Witzel Thomas , Kumar Ashwin , Liao Congyu , Duval Tanguy , Cohen-Adad Julien , Bilgic Berkin
Published: June 2021

Purpose

A major obstacle to the clinical implementation of quantitative MR is the lengthy acquisition time required to derive multi-contrast parametric maps. We sought to reduce the acquisition time for quantitative susceptibility mapping (QSM) and macromolecular tissue volume (MTV) by acquiring both contrasts simultaneously by leveraging their redundancies. The Joint Virtual Coil concept with generalized autocalibrating partially parallel acquisitions (JVC-GRAPPA) was applied to reduce acquisition time further.

Methods

Three adult volunteers were imaged on a 3T scanner using a multi-echo 3D GRE sequence acquired at three head orientations. MTV, QSM, R2*, T1, and proton density maps were reconstructed. The same sequence (GRAPPA R=4) was performed in subject #1 with a single head orientation for comparison. Fully sampled data was acquired in subject #2, from which retrospective undersampling was performed (R=6 GRAPPA and R=9 JVC-GRAPPA). Prospective undersampling was performed in subject #3 (R=6 GRAPPA and R=9 JVC-GRAPPA) using gradient blips to shift k-space sampling in later echoes.

Results

Subject #1’s multi-orientation and single-orientation MTV maps were not significantly different based on RMSE. For subject #2, the retrospectively undersampled JVC-GRAPPA and GRAPPA generated similar results as fully sampled data. This approach was validated with the prospectively undersampled images in subject #3. Using QSM, R2*, and MTV, the contributions of myelin and iron content to susceptibility was estimated.

Conclusion

We have developed a novel strategy to simultaneously acquire data for the reconstruction of five intrinsically co-registered 1-mm isotropic resolution multi-parametric maps, with a scan time of 6 minutes using JVC-GRAPPA.
Leveraging host-genetics and gut microbiota to determine immunocompetence in pigs
Authors: Ramayo-Caldas Yuliaxis , Zingaretti Laura M. , Pérez-Pascual David , Alexandre Pamela A. , Reverter Antonio , Dalmau Toni , Quintanilla Raquel , Ballester Maria
Published: June 2021

The aim of the present work was to identify microbial biomarkers linked to immunity traits and to characterize the contribution of host-genome and gut microbiota to the immunocompetence in healthy pigs. To achieve this goal, we undertook a combination of network, mixed model and microbial-wide association studies (MWAS) for 21 immunity traits and the relative abundance of gut bacterial communities in 389 pigs genotyped for 70K SNPs. The heritability (h2; proportion of phenotypic variance explained by the host genetics) and microbiability (m2; proportion of variance explained by the microbial composition) showed similar values for most of the analyzed immunity traits, except for both IgM and IgG in plasma that were dominated by the host genetics, and the haptoglobin in serum which was the trait with larger m2 (0.275) compared to h2 (0.138). Results from the MWAS suggested a polymicrobial nature of the immunocompetence in pigs and revealed associations between pigs gut microbiota composition and 15 of the analyzed traits. The lymphocytes phagocytic capacity (quantified as mean fluorescence) and the total number of monocytes in blood were the traits associated with the largest number of taxa (6 taxa). Among the associations identified by MWAS, 30% were confirmed by an information theory network approach. The strongest confirmed associations were between Fibrobacter and phagocytic capacity of lymphocytes (r=0.37), followed by correlations between Streptococcus and the percentage of phagocytic lymphocytes (r=-0.34) and between Megasphaera and serum concentration of haptoglobin (r=0.26). In the interaction network, Streptococcus and percentage of phagocytic lymphocytes were the keystone bacterial and immune-trait, respectively. Overall, our findings reveal an important connection between immunity traits and gut microbiota in pigs and highlight the need to consider both sources of information, host genome and microbial levels, to accurately characterize immunocompetence in pigs.
Beyond demographic buffering: Context dependence in demographic strategies across animals
Authors: Lenzi Omar , Ozgul Arpat , Salguero-Gómez Roberto , Paniw Maria
Published: June 2021

Temporal variation in vital rates (e.g., survival, reproduction) can decrease the long-term mean performance of a population. Species are therefore expected to evolve demographic strategies that counteract the negative effects of vital rate variation on the population growth rate. One key strategy, demographic buffering, is reflected in a low temporal variation in vital rates critical to population dynamics. However, comparative studies in plants have found little evidence for demographic buffering, and little is known about the prevalence of buffering in animal populations. Here, we used vital rate estimates from 31 natural populations of 29 animal species to assess the prevalence of demographic buffering. We modeled the degree of demographic buffering using a standard measure of correlation between the standard deviation of vital rates and the sensitivity of the population growth rate to changes in such vital rates across populations. We also accounted for the effects of life-history traits, i.e., age at first reproduction and spread of reproduction across the life cycle, on these correlation measures. We found no strong or consistent evidence of demographic buffering across the study populations. Instead, key vital rates could vary substantially depending on the specific environmental context populations experience. We suggest that it is time to look beyond concepts of demographic buffering when studying natural populations towards a stronger focus on the environmental context-dependence of vital-rate variation.
Saccades and pre-saccadic stimulus repetition alter cortical network topology and dynamics: evidence from EEG and graph theoretical analysis
Authors: Ghaderi Amirhossein , Niemeier Matthias , Crawford John Douglas
Published: June 2021

Parietal and frontal cortex are involved in saccade generation, but their output signals also modify visual signals throughout cortex. These signals produce well-documented behavioral phenomena (saccades, saccadic suppression, various perisaccadic perceptual distortions) but their underlying influence on cortical network dynamics is not known. Here, we combined electroencephalography (EEG) with frequency-dependent source localization and graph theory analysis (GTA) to understand how saccades and pre-saccadic visual stimuli interactively alter cortical network dynamics in humans. 21 participants viewed series of 1-3 vertical or horizontal grids, followed by grid with the opposite orientation just before a horizontal saccade or continued fixation. EEG signals from the presaccadic interval (cue + 200ms, or equivalent fixation period) were used for source localization. Source localization (saccade – fixation) identified bilateral dorsomedial frontoparietal activity across frequency bands, whereas stimulus repetition produced band-specific modulations in left prefrontal, posterior parietal, and central-superior frontal and/or parietal cortex, with significant saccade-repetition interactions in frontal and parietal regions. GTA analysis revealed a saccade-specific functional network with major hubs in inferior parietal cortex (alpha) and the frontal eye fields (beta), and major saccade-repetition interactions in left prefrontal (theta) and supramarginal gyrus (gamma). Overall, quantitative measures of whole-brain network topology and dynamics (segregation, integration, synchronization, complexity) were enhanced during the presaccadic interval, but repetition interactions reduced synchronization and complexity. These results show that presaccadic signals have widespread, coherent influence on cortical network dynamics, likely responsible for both saccade production and the perceptual phenomena associated with saccades.

Highlights

Source localization & graph theory were used to analyze presaccadic EEG signals

Presaccadic signals produced band-specific modulations/hubs in parietofrontal cortex

Frontal/parietal eye fields showed extensive functional connectivity across all lobes

Presaccadic stimulus repetition further modulated functional network connectivity

Saccades and repetition both influenced network clustering, integration, & complexity
High-quality Arabidopsis thaliana Genome Assembly with Nanopore and HiFi Long Reads
Authors: Wang Bo , Yang Xiaofei , Jia Yanyan , Xu Yu , Jia Peng , Dang Ningxin , Wang Songbo , Xu Tun , Zhao Xixi , Gao Shenghan , Dong Quanbin , Ye Kai
Published: June 2021

Arabidopsis thaliana is an important and long-established model species for plant molecular biology, genetics, epigenetics, and genomics. However, the latest version of reference genome still contains significant number of missing segments. Here, we report a high-quality and almost complete Col-0 genome assembly with two gaps (Col-XJTU) using combination of Oxford Nanopore Technology ultra-long reads, PacBio high-fidelity long reads, and Hi-C data. The total genome assembly size is 133,725,193 bp, introducing 14.6 Mb of novel sequences compared to the TAIR10.1 reference genome. All five chromosomes of Col-XJTU assembly are highly accurate with consensus quality (QV) scores > 60 (ranging from 62 to 68), which are higher than those of TAIR10.1 reference (QV scores ranging from 45 to 52). We have completely resolved chromosome (Chr) 3 and Chr5 in a telomere-to-telomere manner. Chr4 has been completely resolved except the nucleolar organizing regions, which comprise long repetitive DNA fragments. The Chr1 centromere (CEN1), reportedly around 9 Mb in length, is particularly challenging to assemble due to the presence of tens of thousands of CEN180 satellite repeats. Using the cutting-edge sequencing data and novel computational approaches, we assembled about 4 Mb of sequence for CEN1 and a 3.5-Mb-long CEN2. We investigated the structure and epigenetics of centromeres. We detected four clusters of CEN180 monomers, and found that the centromere-specific histone H3-like protein (CENH3) exhibits a strong preference for CEN180 cluster 3. Moreover, we observed hypomethylation patterns in CENH3-enriched regions. We believe that this high-quality genome assembly, Col-XJTU, would serve as a valuable reference to better understand the global pattern of centromeric polymorphisms, as well as genetic and epigenetic features in plants.
Typical resting state activity of the brain requires visual input during an early sensitive period
Authors: Rączy Katarzyna , Hölig Cordula , Guerreiro Maria J. S. , Lingareddy Sunitha , Kekunnaya Ramesh , Röder Brigitte
Published: June 2021

Sensory deprivation, following a total loss of one sensory modality e.g. vision, has been demonstrated to result in intra- and cross-modal plasticity. It is yet not known to which extent intra- and cross-modal plasticity as a consequence of blindness reverse if sight is restored.

Here, we used functional magnetic resonance imaging to acquire blood oxygen level dependent (BOLD) resting state activity during an eyes open and an eyes closed state in congenital cataract-reversal individuals, developmental cataract-reversal individuals, congenitally permanently blind individuals and sighted controls. The amplitude of low frequency fluctuations (ALFF) of the BOLD signal - a neural marker of spontaneous brain activity during rest - was analyzed.

As has been shown before, in normally sighted controls we observed an increase in ALFF during rest with the eyes open compared to rest with eyes closed in visual association areas and in parietal cortex but a decrease in auditory and sensorimotor regions. In congenital cataract-reversal individuals, we found an increase of the amplitude of slow BOLD fluctuations in visual cortex during rest with eyes open compared to rest with eyes closed too but this increase was larger in amplitude than in normally sighted controls. At the same time, congenital cataract-reversal individuals lagged a similar increase in parietal regions and did not show the typical decrease of ALFF in auditory and sensorimotor cortex. Congenitally blind individuals displayed an overall higher amplitude in slow BOLD fluctuations in visual cortex compared to sighted individuals and compared to congenital cataract-reversal individuals in the eyes closed condition.

Higher ALFF in visual cortex of congenital cataract-reversal individuals than in normally sighted controls during eyes open might indicate an altered excitatory-inhibitory balance of visual neural circuits. By contrast, the lower parietal increase and the missing downregulation in auditory and sensorimotor regions suggest a reduced influence of the visual system on multisensory and the remaining sensory systems after restoring sight in congenitally blind individuals. These results demonstrate a crucial dependence of multisensory neural networks on visual experience during a sensitive phase in human brain development.
Cross-species comparative hippocampal transcriptomics in Alzheimer’s disease
Authors: De Bastiani Marco Antônio , Bellaver Bruna , Carello-Collar Giovanna , Zimmermann Maria , Kunach Peter , Lima-Filho Ricardo A. S. , Forner Stefania , Martini Alessandra Cadete , Pascoal Tharick A. , Lourenco Mychael V. , Rosa-Neto Pedro , Zimmer Eduardo R.
Published: June 2021

Alzheimer’s disease (AD) is a multifactorial pathology, with most cases having a sporadic origin. Recently, knock-in (KI) models have been developed with the promise of resembling better sporadic human AD, such as the novel hAβ-KI mouse. Here, we compared hippocampal publicly available transcriptomic profiles of transgenic (5xFAD and APP/PS1) and KI (hAβ-KI) mouse models with early- (EOAD) and late- (LOAD) onset AD patients. Experimental validation of consistently dysregulated genes revealed four altered in mice (SLC11A1, S100A6, CD14, CD33, C1QB) and three in humans (S100A6, SLC11A1, KCNK). Additionally, the three mouse models presented more Gene Ontology biological processes terms and enriched signaling pathways in common with LOAD than with EOAD individuals. Finally, we identified 17 transcription factors potentially acting as master regulators of AD. Our cross-species analyses revealed that the three mouse models presented a remarkable similarity to LOAD, with the hAβ-KI being the more specific one.
DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging
Authors: Sepe Sara , Rossiello Francesca , Cancila Valeria , Iannelli Fabio , Matti Valentina , Cicio Giada , Cabrini Matteo , Marinelli Eugenia , Alabi Busola , di Lillo Alessia , Di Napoli Arianna , Shay Jerry W. , Tripodo Claudio , d’Adda di Fagagna Fabrizio
Published: June 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is known to be more common in the elderly, who show also more severe symptoms and a higher risk of hospitalization and death. Here we show that the expression of the Angiotensin Converting Enzyme 2 (ACE2), the SARS-CoV2 cell receptor, increases during aging in mouse and human lungs, and following telomere shortening or dysfunction in mammalian cells and in mouse models. This increase is regulated at the transcription level, and Ace2 promoter activity is DNA damage response (DDR)-dependent. Indeed, ATM inhibition or the selective inhibition of telomeric DDR, through the use of antisense oligonucleotides, prevents Ace2 upregulation following telomere damage, in cultured cells and in mice.

We propose that during aging telomeric shortening, by triggering DDR activation, causes the upregulation of ACE2, the SARS-CoV2 cell receptor, thus making the elderly likely more susceptible to the infection.