bluuebunny/crossref_metadata_2025 huggingface dataset:
Which Maturation Indicator is Most Accurate in Predicting Cessation of Facial Growth? A Systematic Review of the Literature
Authors: Reategui Alvaro , Phillips Sarah , Khetpal Sumun , Parsaei Yassmin , Funaro Melissa , Mukherjee Thayer , Lopez Joseph , Steinbacher Derek M.
Published: October 2021

Purpose:

The determination of facial growth maturity is crucial before surgical intervention in pediatric patients. To the author's knowledge, there are several indicators of skeletal maturity, but there remains a lack of consensus regarding their application when determining surgical timing. The purpose of this study was to determine the most accurate skeletal maturity indicator in predicting facial growth maturation.

Materials and Methods:

A systematic review was done to determine the most predictive indicator for facial growth maturity. We hypothesized that menses’ onset was the most predictive of these maturity indicators. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic search of MEDLINE, Cochrane, Embase, Scopus databases, and Google Scholar, was done in October 2020 to identify citations related to maturity indicators assessing craniofacial growth. The quality of evidence was determined using the Joanna Briggs Institute Critical Appraisal Checklist for Cohort Studies.

Results:

Of the 13,289 articles screened, 1 retrospective and 1 prospective study met inclusion criteria. No articles were identified that provided evidence for our hypothesis. Based on the 2 included studies, it was concluded that a handwrist x-ray was more predictive of facial growth cessation (compared to other skeletal maturity indicators).

Conclusions:

Based on the literature, handwrist radiography serves as the most predictive method in determining the facial growth maturity. The paucity of articles within this investigation highlights the need for greater research efforts to investigate the predictability of indicators to evaluate facial growth maturation.

PROSPERO registration number:

CRD42020207388
Comparison of Auricle Reconstruction Using Tissue Expanders With Skin Grafting and Auricle Reconstruction Using Tissue Expanders Without Skin Grafting: A Single-Arm Meta-Analysis
Authors: Sun Pengfei , Zhao Shanbaga , Wang Changchen , Pan Bo
Published: October 2021

Objective:

The authors conducted this meta-analysis to compare the efficacy of auricle reconstruction using tissue expanders with skin grafting and auricle reconstruction using tissue expanders without skin grafting by comparing the 6 major evaluation indicators.

Methods:

The databases such as PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wanfang, and VIP information databases were searched.

Results:

By comparison, the authors found that, the satisfaction rate, the incidence of postoperative hematoma, the incidence of postoperative incision infection, and the incidence of cartilage framework exposure of patients with auricle reconstruction using tissue expanders with skin grafting were all lower than those with auricle reconstruction using tissue expanders without skin grafting. However, the incidence of postoperative skin necrosis, the incidence of leakage or exposure of expanders in patients with auricle reconstruction using tissue expanders with skin grafting were all higher than those with auricle reconstruction using tissue expanders without skin grafting.

Conclusions:

Auricle reconstruction using tissue expanders with skin grafting has advantages in reducing the incidence of postoperative hematoma, the incidence of postoperative incision infection, and the incidence of cartilage framework exposure. Auricle reconstruction using tissue expanders without skin grafting has advantages in improving the satisfaction rate, reducing the incidence of postoperative skin necrosis, and the incidence of leakage or exposure of expanders. From the comparison of specific data, there is no significant difference in the treatment effect between the 2 surgical methods.
Underlying conditions contributing to breathlessness in the population
Authors: Sandberg Jacob , Olsson Max , Ekström Magnus
Published: October 2021

Purpose of review

Assessment of underlying conditions that contribute to breathlessness is fundamental for symptom management. This review aims to summarize the knowledge from the past two years on the most common underlying conditions among individuals with breathlessness in the general population and to identify research gaps.

Recent findings

Nine studies from the last two years were included in the review; two studies systematically assessed underlying conditions among breathless individuals in the general population. The modified Medical Research Council (mMRC) scale was used in eight of nine studies. Respiratory diseases were the main underlying condition (40–57%), of which asthma was the most common (approx. 25%), and chronic obstructive pulmonary disease was particularly strongly associated with breathlessness. Other conditions prevalent among breathless individuals included heart diseases, anxiety, depression, and obesity, and several conditions often co-existed.

Breathlessness in the general population is common and associated with several underlying conditions. Respiratory disease is the most commonly reported underlying condition. Refined methods such as machine learning could be useful to study the complex interplay between multiple underlying causes of breathlessness and impact on outcomes such as quality of life and survival.
Metastasectomy in kidney cancer: current indications and treatment approaches
Authors: Prunty Megan , Bukavina Laura , Psutka Sarah P.
Published: October 2021

Purpose of review

Although systemic agents for the treatment of metastatic renal cell carcinoma (mRCC) have improved survival, remission and cure for mRCC remains rare with systemic therapy alone. However, there is a body of observational evidence supporting a survival benefit in mRCC among patients who undergo complete surgical consolidation including resection of the primary tumor and all metastatic deposits. In this review, we aim to synthesize recent evidence regarding metastasectomy (MTS), with or without concurrent systemic therapy, in mRCC.

Recent findings

MTS is a critical component of mRCC patient care, alongside modern systemic therapy. Presently, there is a robust body of observational data supporting the association between surgical MTS and improved oncologic outcomes, especially when complete MTS is feasible.

Among a retrospective, observational body of literature, MTS is associated with improved oncologic outcomes. However, it is impossible to discern to what degree these findings are biased by favorable tumor biology and patient selection, as opposed to being related to surgical MTS itself.
Multivariate Analysis of Immune Reconstitution and Relapse Risk Scoring in Children Receiving Allogeneic Stem Cell Transplantation for Acute Leukemias
Authors: Spadea Manuela , Saglio Francesco , Tripodi Serena I. , Menconi Mariacristina , Zecca Marco , Fagioli Franca
Published: October 2021

Background.

A timely and effective immune reconstitution after hematopoietic stem cell transplantation (HSCT) is of crucial importance to enhance graft-versus-leukemia reaction in hematological malignancies. Several factors can influence the yield of this process, and new mathematical models are needed to describe this complex phenomenon.

Methods.

We retrospectively analyzed immune reconstitution in the early post-HSCT period in a multicenter cohort of 206 pediatric patients affected by acute lymphoblastic leukemia, acute myeloblastic leukemia, and myelodysplastic syndrome who received their first allo-HSCT. All patients were in complete morphological remission at transplantation and were followed-up at least 26 mo post-HSCT. Blood samples for analysis of lymphocyte subset numbers were collected at day 100 (±20 d).

Results.

The 2-y cumulative incidence of relapse was 22.2% (95% confidence interval [CI], 17.3-27). Using principal component analysis, we identified based on 16 input variables a new multivariate model that enables patients’ description in a low-dimensional model, consisting of the first 2 principal components. We found that the numbers of CD3+/CD4+/CD8+ lymphocyte subsets at day 100 post-HSCT and acute graft-versus-host disease had the greatest impact in preventing relapse. We ultimately derived a risk score defining high- or medium-low–risk groups with 2-y cumulative incidence of relapse: 35.3% (95% CI, 25.6-45) and 15.6% (95% CI, 10.1-20.7), respectively (P
 = 0.001*).

Conclusions.

Our model describes immune reconstitution and its main influencing factors in the early posttransplantation period, presenting as a reliable model for relapse risk prediction. If validated, this model could definitely serve as a predictive tool and could be used for clinical trials or for individualized patient counseling.
Safety and Efficacy of Sodium-glucose Cotransporter 2 Inhibitors in Kidney Transplant Recipients With Pretransplant Type 2 Diabetes Mellitus: A Retrospective, Single-center, Inverse Probability of Treatment Weighting Analysis of 85 Transplant Patients
Authors: Hisadome Yu , Mei Takanori , Noguchi Hiroshi , Ohkuma Toshiaki , Sato Yu , Kaku Keizo , Okabe Yasuhiro , Nakamura Masafumi
Published: October 2021

Background.

Whether sodium-glucose cotransporter 2 (SGLT2) inhibitors can be used effectively and safely in kidney transplant (KT) recipients with pretransplant type 2 diabetes as the primary cause of end-stage renal disease (ESRD) remains unclear. In this study, we retrospectively analyzed the efficacy and safety of SGLT2 inhibitors compared with other oral hypoglycemic agents (OHAs) in KT recipients with pretransplant type 2 diabetes as the primary cause of ESRD.

Methods.

In this retrospective, observational, single-center, inverse probability of treatment weighting (IPTW) analysis study, we compared the outcomes of SGLT2 inhibitors (SGLT2 group) and other OHAs (control group) following KT. A total of 85 recipients with type 2 diabetic nephropathy as the major cause of ESRD before KT who were treated at our institute between October 2003 and October 2019 were screened and included. The variables considered for IPTW were recipient age, sex, body mass index, history of cardiovascular disease, ABO incompatibility, insulin therapy, estimated glomerular filtration rate (eGFR), and hemoglobin A1c (HbA1c) at the initiation of additional OHAs. Primary endpoints were changes in HbA1c, body weight, and eGFR 1 y after the initiation of additional OHAs.

Results.

After IPTW analysis, there were 26 patients in the SGLT2 group and 59 patients in the control group (n = 85 overall). The body weights were significantly reduced in the SGLT2 group. There was no statistical difference in changes in HbA1c and eGFR. Similarly, there was no significant difference in the incidence of urinary infection, acute rejection, or other side effects between the groups.

Conclusions.

Our findings suggested that SGLT2 inhibitors reduced the body weight of KT recipients and were used safely without increasing side effects.
Population-level deep sequencing reveals the interplay of clonal and sexual reproduction in the fungal wheat pathogen Zymoseptoria tritici
Authors: Singh Nikhil Kumar , Karisto Petteri , Croll Daniel
Published: October 2021

Pathogens cause significant challenges to global food security. On annual crops, pathogens must re-infect from environmental sources in every growing season. Fungal pathogens have evolved mixed reproductive strategies to cope with the distinct challenges of colonizing growing plants. However, how pathogen diversity evolves during growing seasons remains largely unknown. Here, we performed a deep hierarchical sampling in a single experimental wheat field infected by the major fungal pathogen Zymoseptoria tritici. We analysed whole genome sequences of 177 isolates collected from 12 distinct cultivars replicated in space at three time points of the growing season to maximize capture of genetic diversity. The field population was highly diverse with 37 SNPs per kilobase, a linkage disequilibrium decay within 200–700 bp and a high effective population size. Using experimental infections, we tested a subset of the collected isolates on the dominant cultivar planted in the field. However, we found no significant difference in virulence of isolates collected from the same cultivar compared to isolates collected on other cultivars. About 20 % of the isolate genotypes were grouped into 15 clonal groups. Pairs of clones were disproportionally found at short distances (<5 m), consistent with experimental estimates for per-generation dispersal distances performed in the same field. This confirms predominant leaf-to-leaf transmission during the growing season. Surprisingly, levels of clonality did not increase over time in the field although reproduction is thought to be exclusively asexual during the growing season. Our study shows that the pathogen establishes vast and stable gene pools in single fields. Monitoring short-term evolutionary changes in crop pathogens will inform more durable strategies to contain diseases.
Poking COVID-19: insights on genomic constraints among immune-related genes between Qatari and Italian populations
Authors: Mbarek Hamdi , Cocca Massimiliano , Al Sarraj Yasser , Saad Chadi , Mezzavilla Massimo , AlMuftah Wadha , Cocciadiferro Dario , Novelli Antonio , Quinti Isabella , AlTawashi Azza , Salvaggio Salvino , AlThani Asma , Novelli Giuseppe , Ismail Said
Published: October 2021

Host genomic information, specifically genomic variations, may characterize susceptibility to disease and identify people with a higher risk of harm, leading to better targeting of care and vaccination. Italy was the epicentre for the spread of COVID-19 in Europe, the first country to go into a national lockdown and has one of the highest COVID-19 associated mortality rates. Qatar, on the other hand has a very low mortality rate. In this study, we compared whole-genome sequencing data of 14398 adults and Qatari-national to 925 Italian individuals. We also included in the comparison whole-exome sequence data from 189 Italian laboratory confirmed COVID-19 cases. We focused our study on a curated list of 3619 candidate genes involved in innate immunity and host-pathogen interaction. Two population-gene metric scores, the Delta Singleton-Cohort variant score (DSC) and Sum Singleton-Cohort variant score (SSC), were applied to estimate the presence of selective constraints in the Qatari population and in the Italian cohorts. Results based on DSC SSC metrics demonstrated a different selective pressure on three genes (MUC5AC, ABCA7, FLNA) between Qatari and Italian populations. This study highlighted the genetic differences between Qatari and Italian populations and identified a subset of genes involved in innate immunity and host-pathogen interaction.
Multi-Omics Signatures of Alcohol Use Disorder in the Dorsal and Ventral Striatum
Authors: Zillich Lea , Poisel Eric , Frank Josef , Foo Jerome C. , Friske Marion M. , Streit Fabian , Sirignano Lea , Heilmann-Heimbach Stefanie , Heimbach André , Hoffmann Per , Degenhardt Franziska , Hansson Anita C. , Bakalkin Georgy , Nöthen Markus M. , Rietschel Marcella , Spanagel Rainer , Witt Stephanie H.
Published: October 2021

Alcohol Use Disorder (AUD) is a major contributor to global mortality and morbidity. Postmortem human brain tissue enables the investigation of molecular mechanisms of AUD in the neurocircuitry of addiction. We aimed to identify differentially expressed (DE) genes in the ventral and dorsal striatum between individuals with AUD and controls, and to integrate the results with findings from genome- and epigenome-wide association studies (GWAS/EWAS) to identify functionally relevant molecular mechanisms of AUD. DNA-methylation and gene expression (RNA-seq) data was generated from postmortem brain samples of 48 individuals with AUD and 51 controls from the ventral striatum (VS) and the dorsal striatal regions caudate nucleus (CN) and putamen (PUT). We identified DE genes using DESeq2, performed gene-set enrichment analysis (GSEA), and tested enrichment of DE genes in results of GWASs using MAGMA. Weighted correlation network analysis (WGCNA) was performed for DNA-methylation and gene expression data and gene overlap was tested. Differential gene expression was observed in the dorsal (FDR<0.05), but not the ventral striatum of AUD cases. In the VS, DE genes at FDR<0.25 were overrepresented in a recent GWAS of problematic alcohol use. TheARHGEF15gene was upregulated in all three brain regions. GSEA in CN and VS pointed towards cell-structure associated GO-terms and in PUT towards immune pathways. The WGCNA modules most strongly associated with AUD showed strong enrichment for immune response and inflammation pathways. Our integrated analysis of multi-omics data sets provides further evidence for the importance of immune-and inflammation-related processes in AUD.
Procedural time reduction associated with active esophageal cooling during pulmonary vein isolation
Authors: Joseph Chris , Sherman Jacob , Ro Alex , Fisher Wes , Nazari Jose , Metzl Mark
Published: October 2021

Background

Active esophageal cooling is increasingly utilized as an alternative to luminal esophageal temperature (LET) monitoring for protection against thermal injury during pulmonary vein isolation (PVI) when treating atrial fibrillation (AF). Published data demonstrate the efficacy of active cooling in reducing thermal injury, but impacts on procedural efficiency are not as well characterized. LET monitoring compels pauses in ablation due to heat stacking and temperature overheating alarms that in turn delay progress of the PVI procedure, whereas active esophageal cooling allows avoidance of this phenomenon.

Objective

Measure the change in PVI procedure duration after implementation of active esophageal cooling as a protective measure against esophageal injury.

Methods

We performed a retrospective review under IRB approval of patients with AF undergoing PVI between January 2018 to February 2020. For each patient, we recorded age, gender, and total procedure time. We then compared procedure times before and after the implementation of active esophageal cooling as a replacement for LET monitoring.

Results

A total of 373 patients received PVI over the study period. LET monitoring using a multi-sensor probe was performed in 198 patients, and active esophageal cooling using a dedicated device was performed in 175 patients. Patient characteristics did not significantly differ between groups (mean age of 67 years, and gender 37.4% female). Mean procedure time was 146 minutes in the LET monitored patients, and 110 minutes in the actively cooled patients, representing a reduction of 36 minutes, or 24.7% (p<.001). Median procedure time was 141 minutes in the LET monitored patients and 100 minutes in the actively cooled patients, for a reduction of 41 minutes, or 29.1% (p<.001).

Conclusions

Implementation of active esophageal cooling for protection against esophageal injury during PVI was associated with a significantly large reduction in procedure duration.
Profiling of mature stage human breastmilk cells identifies host-defense lactocyte sub-populations
Authors: Gleeson John P. , Chaudhary Namit , Doerfler Rose , Fein Katherine C. , Hredzak-Showalter Trish , Whitehead Kathryn A.
Published: October 2021

Breastmilk is chock-full of nutrients, immunological factors, and cells that aid infant development. Maternal cells are the least studied breastmilk component, and their unique properties are difficult to identify using traditional techniques. Here, we characterized the cells in mature stage breastmilk from healthy donors at the protein, gene, and transcriptome levels. Holistic analysis of flow cytometry, qPCR, and single cell RNA sequencing data identified the predominant cell population as epithelial with smaller populations of macrophages and T cells. Two percent of epithelial cells expressed four stem cell markers: SOX2, TRA-1-60, NANOG, and SSEA4. Furthermore, milk contained six distinct epithelial lactocyte sub-populations, including three previously unidentified sub-populations programmed towards host-defense and intestinal development. Pseudotime analysis delineated the differentiation pathways of epithelial progenitors. Together, these data define healthy human maternal breastmilk cells and provide a basis for their application in maternal and infant medicine.
Is the infection of the SARS-CoV-2 Delta variant associated with the outcomes of COVID-19 patients?
Authors: Gunadi  , Hakim Mohamad Saifudin , Wibawa Hendra , Marcellus  , Setiawaty Vivi , Slamet  , Trisnawati Ika , Supriyati Endah , Khair Riat El , Iskandar Kristy , Afiahayati  , Siswanto  , Irene  , Anggorowati Nungki , Daniwijaya Edwin Widyanto , Agung Nugrahaningsih Dwi Aris , Puspadewi Yunika , Puspitarani Dyah Ayu , Tania Irene , Vujira Khanza Adzkia , Ardlyamustaqim Muhammad Buston , Gabriela Gita Christy , Eryvinka Laudria Stella , Nirmala Bunga Citta , Geometri Esensi Tarian , Darutama Abirafdi Amajida , Kuswandani Anisa Adityarini , Lestari  , Irianingsih Sri Handayani , Khoiriyah Siti , Lestari Ina , Ananda Nur Rahmi , Arguni Eggi , Nuryastuti Titik , Wibawa Tri
Published: October 2021

Background

SARS-CoV-2 Delta variant (B.1.617.2) has been responsible for the current increase in COVID-19 infectivity rate worldwide. We compared the impact of the Delta variant and non-Delta variant on the COVID-19 outcomes in patients from Yogyakarta and Central Java provinces, Indonesia.

Methods

We ascertained 161 patients, 69 with the Delta variant and 92 with the non-Delta variant. The Illumina MiSeq next-generation sequencer was used to perform the whole genome sequences of SARS-CoV-2.

Results

The mean age of patients with Delta and the non-Delta variant was 27.3 ± 20.0 and 43.0 ± 20.9 (p=3×10−6). The patients with Delta variant consisted of 23 males and 46 females, while the patients with the non-Delta variant involved 56 males and 36 females (p=0.001). The Ct value of the Delta variant (18.4 ± 2.9) was significantly lower than the non-Delta variant (19.5 ± 3.8) (p=0.043). There was no significant difference in the hospitalization and mortality of patients with Delta and non-Delta variants (p=0.80 and 0.29, respectively). None of the prognostic factors was associated with the hospitalization, except diabetes with an OR of 3.6 (95% CI=1.02-12.5; p=0.036). Moreover, the patients with the following factors have been associated with higher mortality rate than patients without the factors: age ≥65 years, obesity, diabetes, hypertension, and cardiovascular disease with the OR of 11 (95% CI=3.4-36; p=8×10−5), 27 (95% CI=6.1-118; p=1×10−5), 15.6 (95% CI=5.3-46; p=6×10−7), 12 (95% CI=4-35.3; p=1.2×10−5), and 6.8 (95% CI=2.1-22.1; p=0.003), respectively. Multivariate analysis showed that age ≥65 years, obesity, diabetes, and hypertension were the strong prognostic factors for the mortality of COVID-19 patients with the OR of 3.6 (95% CI=0.58-21.9; p=0.028), 16.6 (95% CI=2.5-107.1; p=0.003), 5.5 (95% CI=1.3-23.7; p=0.021), and 5.8 (95% CI=1.02-32.8; p=0.047), respectively.

Conclusions

We show that the patients infected by the SARS-CoV-2 Delta variant have a lower Ct value than the patients infected by the non-Delta variant, implying that the Delta variant has a higher viral load, which might cause a more transmissible virus among humans. However, the Delta variant does not affect the COVID-19 outcomes in our patients. Our study also confirms the older age and comorbidity increase the mortality rate of COVID-19 patients.
Internalizing Problems Before and During the COVID-19 Pandemic in Dutch Children and Adolescents with and without Pre-Existing Mental Health Problems
Authors: Fischer Karen , Tieskens Jacintha M. , Luijten Michiel A. J. , Zijlmans Josjan , van Oers Hedy A. , de Groot Rowdy , van der Doelen Daniël , van Ewijk Hanneke , Klip Helen , van der Lans Rikkert M. , De Meyer Ronald , van der Mheen Malindi , van Muilekom Maud M. , Ruisch I. Hyun , Teela Lorynn , van den Berg Germie , Bruining Hilgo , van der Rijken Rachel , Buitelaar Jan , Hoekstra Pieter J. , Lindauer Ramón , Oostrom Kim J. , Staal Wouter , Vermeiren Robert , Cornet Ronald , Haverman Lotte , Bartels Meike , Polderman Tinca J. C. , Popma Arne
Published: October 2021

The aim of the study was to assess internalizing problems before and during the pandemic with data from Dutch consortiumChild and adolescent mental health and wellbeing in times of the COVID-19 pandemic, consisting of two Dutch general population samples (GS) and two clinical samples (CS) referred to youth/psychiatric care. In each sample, measures of internalizing problems were obtained from ongoing data collections pre-pandemic (NGS= 35,357;NCS= 4,487) and twice during the pandemic, in Apr.–May 2020 (NGS= 3,938; clinical:NCS= 1,008) and in Nov.–Dec. 2020 (NGS= 1,489;NCS= 1,536), in children and adolescents (8-18 years) with parent- (Brief Problem Monitor) and/or child reports (Patient-Reported Outcomes Measurement Information System®). Results show significantly greater proportions of worrisome internalizing problems (based on validated cut-offs) and significantly higher internalizing problems mean levels from pre-pandemic to pandemic measurements in the general population. These levels stabilized or decreased over the course of the pandemic. In the clinical sample, we found an increase in child-reported internalizing problems measures over the course of the pandemic, but parents reported no differences in internalizing problems measures over the course of the pandemic, nor from pre-pandemic to during the pandemic. Overall, the findings indicate that children and adolescents of both the general and clinical population were affected negatively by the pandemic in terms of their internalizing problems. Attention is therefore warranted to investigate what long-term effects this may cause and to monitor if internalizing problems return back to pre-pandemic levels or if they remain elevated post-pandemic.
An assessment of a rapid SARS-CoV-2 antigen test in Bangladesh
Authors: Kawser Zannat , Hossain Mohabbat , Suliman Sara , Lockman Shahin , Gitaka Jesse , Bandawe Gama , Rahmat Redwan , Hasan Imrul , Siddik Abu Bakar , Afrad Mokibul Hassan , Rahman Mohammed Ziaur , Miller Glenn , Walt David R. , Ivers Louise C. , LaRocque Regina C. , Harris Jason B. , Qadri Firdausi
Published: October 2021

Early detection of SARS-CoV-2 infection is crucial to prevent the spread of the virus. In this study, we evaluated the performance of a commercial rapid antigen detection test, BD Veritor, and compared this (and another rapid test, Standard Q) against a gold-standard of nasopharyngeal (NP) swab tested by reverse transcription-polymerase chain reaction (RT-PCR) in prospectively-recruited adults in Dhaka, Bangladesh. We compared the sensitivity and specificity of the two rapid antigen tests against RT-PCR results in 130 symptomatic and 130 asymptomatic adults. In addition, we evaluated the suitability and ease-of-use of the BD Veritor test in a subsample of study participants (n=42) and implementers (n=5). The sensitivity of the BD Veritor rapid antigen test was 70% in symptomatic (95% confidence interval [CI]: 51-85%) and 87% (95% CI: 69-96%) in asymptomatic individuals with positive SARSCoV-2 RT-PCR, for overall sensitivity of 78% (95% CI: 66-88%). The sensitivity of the Standard Q rapid antigen test was 63% (95% CI: 44-80%) in symptomatic and 73% (95% CI: 54-87%) in asymptomatic individuals. One false positive in BD Veritor test (specificity 99.5) and no false positive in Standard Q tests were observed (specificity 100%). The BD Veritor rapid antigen test was 78% sensitive when compared with RT-PCR irrespective of the cycle threshold (Ct) levels in this evaluation in Bangladesh. The implementation evaluation data showed good acceptability in the field settings. This warrants large field evaluation as well as use of the rapid antigen test for quick assessment of SARS-CoV-2 for containment of epidemics in the country.
Rotational worker vaccination provides indirect protection to vulnerable groups in regions with low COVID-19 prevalence
Authors: Martignoni Maria M. , Rahman Proton , Hurford Amy
Published: October 2021

As COVID-19 vaccines become available, different model-based approach have been developed to evaluate strategic priorities for vaccine allocation to reduce severe illness. One strategy is to directly prioritize groups that are likely to experience medical complications due to COVID-19, such as older adults. A second strategy is to limit community spread by reducing importations, for example by vaccinating members of the mobile labour force, such as rotational workers. This second strategy may be appropriate for regions with low disease prevalence, where importations are a substantial fraction of all cases and reducing the importation rate reduces the risk of community outbreaks, which can provide significant indirect protection for vulnerable individuals. Current studies have focused on comparing vaccination strategies in the absence of importations, and have not considered allocating vaccines to reduce the importation rate. Here, we provide an analytical criteria to compare the reduction in the risk of hospitalization and intensive care unit (ICU) admission over four months when either older adults or rotational workers are prioritized for vaccination. Vaccinating rotational workers (assumed to be 6,000 individuals and about 1% of the Newfoundland and Labrador (NL) population) could reduce the average risk of hospitalization and ICU admission by 42%, if no community spread is observed at the time of vaccination, because epidemic spread is reduced and vulnerable individuals are indirectly protected. In contrast, vaccinating all individuals aged 75 and older (about 43,300 individuals, or 8% of the NL population) would lead to a 24% reduction in the average risk of hospitalization, and to a 45% reduction in the average risk of ICU admission, because a large number of individuals at high risk from COVID-19 are now vaccinated. Therefore, reducing the risk of hospitalization and ICU admission of the susceptible population by reducing case importations would require a significantly lower number of vaccines. Benefits of vaccinating rotational workers decrease with increasing infection prevalence in the community. Prioritizing members of the mobile labour force should be considered as an efficient strategy to indirectly protect vulnerable groups from COVID-19 exposure in regions with low disease prevalence.
Inactivated Poliovirus Vaccine Induces Antibodies that Inhibit RNA Synthesis of SARS-CoV-2: An open-label, pre-post vaccine clinical trial
Authors: Comunale Brittany A. , Jackson-Ward Erin , Jiang Yong , Ward Laura P. , Liu Qianna , Ji Lyuqing , Lai Michelle , Engineer Lilly , Comunale Roderick A. , Xie Qiyi
Published: October 2021

Background

Poliovirus vaccination induces an adaptive humoral immune response; in vitro experiments show polio-immune sera contain antibodies against the poliovirus RNA transcriptase that cross-react with SARS-CoV-2. While structural similarities between poliovirus and SARS-CoV-2 could have major implications for the COVID-19 response worldwide, polio-induced immune responses against SARS-CoV-2 have not been confirmed in prospective clinical trials.

Objective

To evaluate whether immune sera from adults who recently received inactivated poliovirus vaccination (IPV) can block SARS-CoV-2’s ability to synthesize RNA.

Intervention

IPV intramuscular injection.

Measurements

Pre-inoculation and 4-weeks post-inoculation sera were tested for anti-3Dpol (RNA-dependent RNA polymerase, RdRp) antibodies using enzyme-linked immunosorbent assays (ELISA). To assess IPV’s ability to induce antibodies that inhibit SARS-CoV-2 RNA synthesis, immune-based detection assays tested RdRp enzymatic activity in polio-immune sera.

Results

298 of the 300 enrolled participants completed both on-site visits. Comparing pre-inoculation to 4-week samples, 85.2% of participants demonstrated an increase in anti-3Dpolantibodies against RdRp proteins. Among tested post-inoculation samples, 94.4% demonstrated inhibition of SARS-CoV-2 RNA synthesis. Few inoculation-related side effects were reported (2.0%), all were minor.

Limitations

Participants were not systematically tested for COVID-19, though known exposures were reported and positive results (1.7%) were documented.

Conclusion

IPV can induce antibodies that inhibit SARS-CoV-2 RNA synthesis, minimizing the risk of viral replication in infected individuals. This finding has practical implications for resource-deficient areas that may have limited access to newly developed COVID-19 vaccines and/or areas with low COVID-19 vaccination rates due to hesitancy.

Funding Source

Private donors.

Registration

ClinicalTrials.gov: NCT04639375.
Molecular Prognosis of Endometrial Adenocarcinoma by Expression Patterns of the V-ATPase C1 Subunit
Authors: Chacur Abdalla Dib , Couto-Viera Juliana , Façanha Anna Okorokova , Baptista Glenerson , Façanha Arnoldo Rocha
Published: October 2021

Comparative analysis of expression patterns of ATP6V1C1 encoding C1 subunit of V-H+-ATPase revealed that molecular alterations correlated with endometrial cancer of better prognosis were grouped with low ATP6V1C1 expression while those correlated with worse prognosis were clustered with high ATP6V1C1 expression levels.

Expression patterns of C1 subunit in endometrial adenocarcinoma are associated with molecular malignancy signatures shared by histological subtypes of highest mortality rate suggesting that G3 adenocarcinoma exhibits molecular changes resembling endometrial serous carcinoma.

ATP6V1C1 might serve as novel prognostic marker allowing identification of targetable pathways for high-risk endometrial cancer.
In vivo reprogramming of murine host immune response genes following Leishmania major infection
Authors: Venugopal Gopinath , Bird Jordan T. , Washam Charity L. , Roys Hayden , Bowlin Anne , Byrum Stephanie D. , Weinkopff Tiffany
Published: October 2021

Leishmaniaparasites cause cutaneous leishmaniasis (CL), a pathologic disease characterized by disfiguring, ulcerative skin lesions. Both parasite and host gene expression following infection with variousLeishmaniaspecies has been investigated in vitro, but global transcriptional analysis followingL. majorinfection in vivo is lacking. Thus, we conducted a comprehensive transcriptomic profiling study combining bulk RNA sequencing (RNA-Seq) and single-cell RNA sequencing (scRNA-Seq) to identify global changes in gene expression in vivo followingL. majorinfection. Bulk RNA-Seq analysis revealed that host immune response pathways like the antigen processing and presentation pathway were significantly enriched amongst differentially expressed genes (DEGs) upon infection, while ribosomal pathways were significantly downregulated in infected mice compared to naive controls. scRNA-Seq analyses revealed cellular heterogeneity including distinct resident and recruited cell types in the skin following murineL. majorinfection. Within the individual immune cell types, several DEGs indicative of many interferon induced GTPases and antigen presentation molecules were significantly enhanced in the infected ears including macrophages (Gbp2, H2-K1, H2-Aa, H2-Ab1), resident macrophages (H2-K1, H2-D1, Gbp4, Gbp8, Gbp2), and inflammatory monocytes (Gbp2, Gbp5, Gbp7, Gbp3). Ingenuity Pathway Analysis of scRNA-Seq data indicated the antigen presentation pathway was increased with infection, while EIF2 signaling is the top downregulated pathway followed by eIF4/p70S6k and mTOR signaling in multiple cell types including macrophages, BECs, and LECs. Altogether, this transcriptomic profile highlights known recruitment of myeloid cells to lesions and recognizes a previously undefined role for EIF2 signaling in murineL. majorinfection in vivo.

Author summary

Leishmania majorcause cutaneous leishmaniasis, which is characterized by disfiguring, ulcerative skin lesions. Here, we show murineL. major-directed reprogramming of the host transcriptome in vivo. Our bulk RNA-Seq analyses revealed upregulation of antigen processing and presentation pathway, while the host ribosomal pathway was downregulated followingL. majorinfection. Similarly, scRNA-Seq analyses revealed the upregulation of transcripts responsible for antigen presentation and host defense proteins like guanylate binding proteins (GBPs) alongside the downregulation of EIF2 signalling at the site ofL. majorinfection. Overall, our transcriptomic dataset not only provides the comprehensive list of gene expression at the single-cell resolution, and highlights a previously undefined role for EIF2 signalling during murineL. majorinfection in vivo.
Bacteriocinogenic lactic acid bacteria in the traditional cereal-based beverage Boza: a genomic and functional approach
Authors: Queiroz Luciano Lopes , Hoffmann Christian , Lacorte Gustavo Augusto , Franco Bernadette Dora Gombossy de Melo , Todorov Svetoslav Dimitrov
Published: October 2021

Boza is a traditional low-alcohol fermented beverage from the Balkan Peninsula, frequently explored as a functional food product. The product is rich in Lactic Acid Bacteria (LAB) and some of them can produce bacteriocins. In this study, a sample of Boza from Belogratchik, Bulgaria, was analyzed for the presence of bacteriocinogenic LAB, and after analyses by RAPD-PCR, three representative isolates were characterized by genomic analyses, using whole genome sequencing. Isolates identified as Pediococcus pentosaceus ST75BZ and Pediococcus pentosaceus ST87BZ contained operons encoding for bacteriocins pediocin PA-1 and penocin A, while isolate identified as P. acidilactici ST31BZ contained only the operon for pediocin PA-1 and a CRISPR/Cas system for protection against bacteriophage infection. The antimicrobial activity of bacteriocins produced by the three isolates was inhibited by treatment of the cell-free supernatants with proteolytic enzymes. The produced bacteriocins inhibited the growth of Listeria monocytogenes, Enterococcus spp. and some Lactobacillus spp., among other tested species. The levels of bacteriocin production varied from 3200 AU/ml to 12800 AU/ml recorded against L. monocytogenes 104, 637 and 711, measured at 24 h of incubation at 37°C. All bacteriocins remained active after incubation at pH 2.0 to 10.0. The activity mode of the studied bacteriocins was bactericidal, as determined against L. monocytogenes 104, 637 and 711. In addition, bactericidal activity was demonstrated using a cell leakage β-galactosidase assay, indicating a pore formation mechanism as a mode of action. The present study highlights the importance of combining metagenomic analyses and traditional microbiological approaches as way of characterizing microbial interactions in fermented foods.
Ataxia-linked SLC1A3 mutations alter EAAT1 chloride channel activity and glial regulation of CNS function
Authors: Wu Qianyi , Akhter Azman , Pant Shashank , Cho Eunjoo , Zhu Jin Xin , Garner Alastair , Ohyama Tomoko , Tajkhorshid Emad , van Meyel Donald J. , Ryan Renae M.
Published: October 2021

Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system (CNS). Excitatory Amino Acid Transporters (EAATs) regulate extracellular glutamate by transporting it into cells, mostly glia, to terminate neurotransmission and to avoid neurotoxicity. EAATs are also chloride (Cl−) channels, but the physiological role of Cl− conductance through EAATs is poorly understood. Mutations of human EAAT1 (hEAAT1) have been identified in patients with episodic ataxia type 6 (EA6). One mutation showed increased Cl− channel activity and decreased glutamate transport, but the relative contributions of each function of hEAAT1 to mechanisms underlying the pathology of EA6 remain unclear. Here we investigated the effects of five additional EA6-related mutations on hEAAT1 function in Xenopus laevis oocytes, and on CNS function in a Drosophila melanogaster model of locomotor behavior. Our results indicate that mutations with decreased hEAAT1 Cl− channel activity and functional glutamate transport can also contribute to the pathology of EA6, highlighting the importance of Cl− homeostasis in glial cells for proper CNS function. We also identified a novel mechanism involving an ectopic sodium (Na+) leak conductance in glial cells. Together, these results strongly support the idea that EA6 is primarily an ion channelopathy of CNS glia.
Clinically applicable rapid susceptibility testing of multi-drug resistant Staphylococcus aureus by mass spectrometry and extreme gradient boosting machine
Authors: Wang Zhuo , Wang Hsin-Yao , Pang Yuxuan , Chung Chia-Ru , Horng Jorng-Tzong , Lu Jang-Jih , Lee Tzong-Yi
Published: October 2021

Multi-drug resistant Staphylococcus aureus is one of the major causes of severe infections. Due to the delays of conventional antibiotic susceptibility test (AST), most cases were prescribed by experience with a lower recovery rate. Linking a 7-year study of over 20,000 Staphylococcus aureus infected patients, we incorporated mass spectrometry and machine learning technology to predict the susceptibilities of patients for 4 different antibiotics that can enable early antibiotic decisions. The predictive models were externally validated in an independent patient cohort, resulting in an area under the receiver operating characteristic curve of 0.94, 0.90, 0.86, 0.91 and an area under the precision-recall curve of 0.93, 0.87, 0.87, 0.81 for oxacillin (OXA), clindamycin (CLI), erythromycin (ERY) and trimethoprim-sulfamethoxazole (SXT), respectively. Moreover, our pipeline provides AST 24–36 h faster than standard workflows, reduction of inappropriate antibiotic usage with preclinical prediction, and demonstrates the potential of combining mass spectrometry with machine learning (ML) to assist early and accurate prescription. Therapies to individual patients could be tailored in the process of precision medicine.
A spiking neural network model of the Superior Colliculus that is robust to changes in the spatial-temporal input
Authors: Alizadeh Arezoo , Van Opstal A. John
Published: October 2021

Previous studies have indicated that the location of a large neural population in the Superior Colliculus (SC) motor map specifies the amplitude and direction of the saccadic eye-movement vector, while the saccade trajectory and velocity profile are encoded by the population firing rates. We recently proposed a simple spiking neural network model of the SC motor map, based on linear summation of individual spike effects of each recruited neuron, which accounts for many of the observed properties of SC cells in relation to the ensuing eye movement. However, in the model, the cortical input was kept invariant across different saccades. Electrical microstimulation and reversible lesion studies have demonstrated that the saccade properties are quite robust against large changes in supra-threshold SC activation, but that saccade amplitude and peak eye-velocity systematically decrease at low input strengths. These features are not accounted for by the linear spike-vector summation model. Here we show that the model’s input projection strengths and intra-collicular lateral connections can be tuned to generate saccades that follow the experimental results.

Author statement

The midbrain SC generates fast saccadic eye movements through a large population of cells within a topographically organized motor map, in which the location, spike count and temporal firing patterns of recruited cells determine saccade metrics and kinematics. According to the dynamic ensemble-coding model, each recruited SC cell contributes to the saccade by linear vector summation of all its spike contributions. Our previous spiking neural network model used invariant cortical inputs to the SC cells for all saccades. We here improved the robustness of the model to large spatial-temporal variations in the input patterns, by tuning its top-down and lateral synaptic connections, to generate saccades with properties observed in electrophysiological experiments.
Seed banks alter the molecular evolutionary dynamics ofBacillus subtilis
Authors: Shoemaker William R. , Polezhaeva Evgeniya , Givens Kenzie B. , Lennon Jay T.
Published: October 2021

Fluctuations in the availability of resources constrains the growth and reproduction of individuals, which subsequently effects the evolution of their respective populations. Many organisms contend with such fluctuations by entering a reversible state of reduced metabolic activity, a phenomenon known as dormancy. This pool of dormant individuals (i.e., a seed bank) does not reproduce and is expected to act as an evolutionary buffer, though it is difficult to observe this effect directly over an extended evolutionary timescale. Through genetic manipulation, we analyze the molecular evolutionary dynamics ofBacillus subtilispopulations in the presence and absence of a seed bank over 700 days. The ability of these bacteria to enter a dormant state increased the accumulation of genetic diversity over time and altered the trajectory of mutations, findings that were recapitulated using simulations based on a mathematical model of evolutionary dynamics. While the ability to form a seed bank did not alter the degree of negative selection, we found that it consistently altered the direction of molecular evolution across genes. Together, these results show that the ability to form a seed bank can affect the direction and rate of molecular evolution over an extended evolutionary timescale.
RAxML Grove: An empirical Phylogenetic Tree Database
Authors: Höhler Dimitri , Pfeiffer Wayne , Ioannidis Vassilios , Stockinger Heinz , Stamatakis Alexandros
Published: October 2021

The assessment of novel phylogenetic models and inference methods is routinely being conducted via experiments on simulated as well as empirical data. When generating synthetic data it is often unclear how to set simulation parameters for the models and generate trees that appropriately reflect empirical model parameter distributions and tree shapes. As a solution, we present and make available a new database called ‘RAxML Grove’ currently comprising more than 60,000 inferred trees and respective model parameter estimates from fully anonymized empirical data sets that were analyzed using RAxML (1) and RAxML-NG (2) on two web servers. We also describe and make available two simple applications of RAxML Grove to exemplify its usage and highlight its utility for designing realistic simulation studies and analyzing empirical model parameter and tree shape distributions.

RAxML Grove is freely available at https://github.com/angtft/RAxMLGrove.