bluuebunny/crossref_metadata_2025 huggingface dataset:
Reticulibacter mediterranei gen. nov., sp. nov., within the new family Reticulibacteraceae fam. nov., and Ktedonospora formicarum gen. nov., sp. nov., Ktedonobacter robiniae sp. nov., Dictyobacter formicarum sp. nov. and Dictyobacter arantiisoli sp. nov., belonging to the class Ktedonobacteria
Authors: Yabe Shuhei , Zheng Yu , Wang Chiung-mei , Sakai Yasuteru , Abe Keietsu , Yokota Akira , Donadio Stefano , Cavaletti Linda , Monciardini Paolo
Published: July 2021

The aerobic, Gram-positive, mesophilic

Ktedonobacteria

strains, Uno17T, SOSP1-1T, 1-9T, 1-30T and 150040T, formed mycelia of irregularly branched filaments, produced spores or sporangia, and numerous secondary metabolite biosynthetic gene clusters. The five strains grew at 15–40 °C (optimally at 30 °C) and pH 4.0–8.0 (optimally at pH 6.0–7.0), and had 7.21–12.67 Mb genomes with 49.7–53.7 mol% G+C content. They shared MK9(H2) as the major menaquinone and C16 : 1-2OH and iso-C17 : 0 as the major cellular fatty acids. Phylogenetic and phylogenomic analyses showed that Uno17T and SOSP1-9T were most closely related to members of the genus

Dictyobacter

, with 94.43–96.21 % 16S rRNA gene similarities and 72.16–81.56% genomic average nucleotide identity. The strain most closely related to SOSP1-1T and SOSP1-30T was

Ktedonobacter racemifer

SOSP1-21T, with 91.33 and 98.84 % 16S rRNA similarities, and 75.13 and 92.35% average nucleotide identities, respectively. Strain 150040T formed a distinct clade within the order

Ktedonobacterales

, showing <90.47 % 16S rRNA gene similarity to known species in this order. Based on these results, we propose: strain 150040T as Reticulibacter mediterranei gen. nov., sp. nov. (type strain 150 040T=CGMCC 1.17052T=BCRC 81202T) within the family Reticulibacteraceae fam. nov. in the order

Ktedonobacterales

; strain SOSP1-1T as Ktedonospora formicarum gen. nov., sp. nov. (type strain SOSP1-1T=CGMCC 1.17205T=BCRC 81203T) and strain SOSP1-30T as Ktedonobacter robiniae sp. nov. (type strain SOSP1-30T=CGMCC 1.17733T=BCRC 81205T) within the family

Ktedonobacteraceae

; strain Uno17T as Dictyobacter arantiisoli sp. nov. (type strain Uno17T=NBRC 113155T=BCRC 81116T); and strain SOSP1-9T as Dictyobacter formicarum sp. nov. (type strain SOSP1-9T=CGMCC 1.17206T=BCRC 81204T) within the family

Dictyobacteraceae

.
Surveillance of seasonal respiratory viruses among Chilean patients during the COVID-19 pandemic
Authors: Alonso-Palomares Luis A. , Joaquín Cáceres C. , Tapia Rodrigo , Aguilera-Cortés Paulina , Valenzuela Santiago , Valiente-Echeverría Fernando , Soto-Rifo Ricardo , Gaggero Aldo , Barriga Gonzalo P.
Published: July 2021

The Study

SARS-CoV-2 has generated over 122 million cases worldwide. Non-pharmaceuticals interventions such as confinements and lockdowns started in Chile on March 18th 2020. In Europe, confinements and lockdowns have been accompanied by a decrease in the circulation of other respiratory viruses such as Influenza A virus(IAV), Influenza B virus(IBV) or respiratory syncytial virus(RSV) (1). Although changes in circulation patterns of respiratory viruses have been reported, limited information regarding the southern hemisphere is available where the SARS-CoV-2 pandemic merged with the winter season. We conducted viral surveillance of respiratory viruses and we evaluated their presence and establishing whether they were co-circulating with SARS-CoV-2.
Effects of COVID-19 2021 lockdown on the sleep quality and mental health of undergraduate medical and dental students of Pakistan: A cross-sectional study
Authors: Sheikh Naveen Siddique , Anwar Aiza , Pervaiz Iqra , Arshad Zunaira , Khan Huma Saeed , Hafeez Farida
Published: July 2021

Background and objectives

The COVID-19 pandemic has been recognized as a cause of direct and indirect psychological consequences that impact mental health such as acute stress disorders, anxiety, irritability, poor concentration, and insomnia. This study was planned to evaluate the sleep quality and mental health of undergraduate students amidst the COVID-19 lockdown of 2021.

Materials and Methods

This observational cross-sectional study was conducted in Lahore, Pakistan, where 261 undergraduate medical and dental students enrolled at a private medical and dental school were approached from March to May 2021. The Pittsburg Sleep Quality Index (PSQI) was used to identify the sleep quality along with the Generalized Anxiety Disorder Scale (GAD-7) to establish anxiety symptoms and the Physical Health Questionnaire (PHQ-9) for depression symptoms.

Results

The results show that 212 (81.2%) female and 49 (18.8%) male students participated in the study. Of the participants 75.1% experienced poor sleep quality, 90% had symptoms of depression, and 85.4% had symptoms of anxiety. The mean score on the PSQI scale was 8.59±4.10, on the GAD-7 scale was 11.36±5.94 and on the PHQ-9 scale was 13.70±6.81. Multiple regression analysis showed that anxiety symptoms (β = 0.315, p = 0.000) and depression symptoms (β = 0.398, p = 0.000) were significant predictors of sleep quality amongst the undergraduate medical and dental students.

Conclusion

A high majority of the study participants are experiencing poor sleep quality along with suffering from depression and anxiety amidst the COVID-19 lockdown. It is concluded from the analysis that anxiety and depression symptoms are significant predictors of sleep quality. Relevant authorities need to set up systems that help undergraduate medical students in alleviating and coping with these symptoms midst the COVID-19 pandemic.
Identification and validation of novel candidate risk genes in endocytic vesicular trafficking associated with esophageal atresia and tracheoesophageal fistulas
Authors: Zhong Guojie , Ahimaz Priyanka , Edwards Nicole A. , Hagen Jacob J. , Faure Christophe , Kingma Paul , Middlesworth William , Khlevner Julie , Fiky Mahmoud El , Schindel David , Fialkowski Elizabeth , Kashyap Adhish , Forlenza Sophia , Kenny Alan P. , Zorn Aaron M. , Shen Yufeng , Chung Wendy K.
Published: July 2021

Esophageal atresias/tracheoesophageal fistulas (EA/TEF) are rare congenital anomalies caused by aberrant development of the foregut. Previous studies indicate that rare orde novogenetic variants significantly contribute to EA/TEF risk, and most individuals with EA/TEF do not have pathogenic genetic variants in established risk genes. To identify novel genetic contributions to EA/TEF, we performed whole genome sequencing of 185 trios (probands and parents) with EA/TEF, including 59 isolated and 126 complex cases with additional congenital anomalies and/or neurodevelopmental disorders. There was a significant burden of protein alteringde novocoding variants in complex cases (p=3.3e-4), especially in genes that are intolerant of loss of function variants in the population. We performed simulation analysis of pathway enrichment based on background mutation rate and identified a number of pathways related to endocytosis and intracellular trafficking that as a group have a significant burden of protein alteringde novovariants. We assessed 18 variants for disease causality using CRISPR-Cas9 mutagenesis inXenopusand confirmed 13 with tracheoesophageal phenotypes. Our results implicate disruption of endosome-mediated epithelial remodeling as a potential mechanism of foregut developmental defects. This research may have implications for the mechanisms of other rare congenital anomalies.
Sociodemographic differences in patient experience with virtual care during COVID-19
Authors: Agarwal Payal , Wang Rick , Meaney Christopher , Walji Sakina , Damji Ali , Toor Navsheer Gill , Yip Gina , Elman Debbie , Florindo Tiffiany , Fung Susanna , Witty Melissa , Pham Thuy Nga , Ramji Noor , Kiran Tara
Published: July 2021

Purpose

We sought to understand patients’ care-seeking behaviours during the pandemic, their use and views of different virtual care modalities, and whether these differed by sociodemographic factors.

Methods

We conducted a multi-site cross-sectional patient experience survey at thirteen academic primary care teaching practices between May and June of 2020. An anonymized link to an electronic survey was sent to a subset of patients with a valid email address on file; sampling was based on birth month. For each question, the proportion of respondents who selected each response was calculated, followed by a comparison by sociodemographic characteristics using chi-squared tests.

Results

In total, 7482 participants responded to the survey. Most received care from their primary care clinic during the pandemic (67.7%, 5068/7482), the majority via phone (82.5%, 4195/5086). Among those who received care, 30.53% (1509/4943) stated that they delayed seeking care because of the pandemic. Most participants reported a high degree of comfort with phone (92.4%, 3824/4139), video (95.2%, 238/250) and email or messaging (91.3%, 794/870). However, those reporting difficulty making ends meet, poor or fair health, and arriving in Canada in the last 10 years reported lower levels of comfort with virtual care and fewer wanted their practice to continue offering virtual options after the pandemic.

Conclusions

Our study suggest that newcomers, people living with a lower income, and those reporting poor or fair health have a stronger preference and comfort for in-person primary care. Further research should explore potential barriers to virtual care and how these could be addressed.
Population risk stratification for health systems via accretive predictive modeling
Authors: Bandhakavi Sricharan , Karigowda Sunil , Liu Zhipeng , McCammon Jasmine , Rahmanian Farbod , Lavoie Heather
Published: July 2021

Objective

Health systems rely on multiple approaches for population-level risk stratification/management. However, they can under-represent members with rising risk and complex treatment needs. To address these gaps and broaden the coverage of members at risk, we present an accretive framework of six predictive models across complementary risk measures for population-level stratification/management.

Materials and Methods

Logistic regression models were trained/tested for six outcomes across cost (rising and elevated cost), utilization (rising and elevated utilization), and chronic-disease related (multimorbidities and polypharmacy) risk measures in 2016 using claims-based features from 2015 for ∼8.97 million members in a nation-wide administrative claims database. Model performances were validated against a holdout cohort of ∼2.99 million members. The presence/absence of each outcome prediction for members was summed into an accretive predictive risk index (aPRI) for population-level risk stratification evaluation.

Results

Integrating predictions from the six models enabled member stratification across risk measures including future costs, utilizations, and comorbidities. Each of the risk predictions is represented in aPRI levels 0– 6, and their underlying model probabilities/risk measures increase with increasing aPRI levels. ∼83% of members grouped into a “low risk” (aPRI = 0) or “rising risk” category (aPRI = 1 - 2) and ∼17% into a “high risk” (aPRI = 3 - 6) category. Overlap/correlation analyses of risk predictions and comparison of their drivers further support the complementarity of predictions within aPRI and its enhanced coverage of members at risk.

Discussion

By integrating targeted and complementary risk predictions, aPRI enhances current population-level risk stratification approaches.

Conclusion

We have developed an accretive predictive modeling framework for enhanced population-level risk stratification/management.
Does COVID-19 vaccination improve mental health? A difference-in-difference analysis of the Understanding Coronavirus in America study
Authors: Koltai Jonathan , Raifman Julia , Bor Jacob , McKee Martin , Stuckler David
Published: July 2021

Background

Mental health problems increased during the COVID-19 pandemic. Knowledge that one is less at risk after being vaccinated may alleviate distress, but this hypothesis remains unexplored. Here we test whether psychological distress declined in those vaccinated against COVID-19 in the US and whether changes in perceived risk mediated any association.

Methods

A nationally-representative cohort of U.S. adults (N=5,792) in the Understanding America Study were interviewed every two weeks from March 2020 to June 2021 (28 waves). Difference-in-difference regression tested whether getting vaccinated reduced distress (PHQ-4 scores), with mediation analysis used to identify potential mechanisms, including perceived risks of infection, hospitalization, and death.

Results

Vaccination was associated with a 0.09 decline in distress scores (95% CI:-0.15 to -0.04) (0-12 scale), a 5.7% relative decrease compared to mean scores in the wave prior to vaccination. Vaccination was also associated with an 8.44 percentage point reduction in perceived risk of infection (95% CI:-9.15% to -7.73%), a 7.44-point reduction in perceived risk of hospitalization (95% CI:-8.07% to -6.82%), and a 5.03-point reduction in perceived risk of death (95% CI:-5.57% to -4.49%). Adjusting for risk perceptions decreased the vaccination-distress association by two-thirds. Event study models suggest vaccinated and never vaccinated respondents followed similar PHQ-4 trends pre-vaccination, diverging significantly post-vaccination. Analyses were robust to individual and wave fixed effects, time-varying controls, and several alternative modelling strategies. Results were similar across sociodemographic groups.

Conclusion

Receiving a COVID-19 vaccination was associated with declines in distress and perceived risks of infection, hospitalization, and death. Vaccination campaigns could promote these additional benefits of being vaccinated.
Subgrouping School-Aged Children on the Autism Spectrum Based on Co-Occurring Psychiatric Symptoms
Authors: Piergies Antonia M. H. , Hirota Tomoya , Monden Rei , Zheng Shuting
Published: July 2021

Background

Phenotypic heterogeneity along the autism spectrum is compounded by co-occurring psychiatric conditions. Deriving subgroups of autistic individuals based on symptoms of these conditions could better our understanding of psychiatric symptom patterns existing within this population. This study’s goals were to derive subgroups of school-aged autistic children based on co-occurring psychiatric symptoms while controlling for age and sex and to examine correlates of subgroup membership while controlling for the degree of ASD-related diagnostic features.

Method

Latent class models were estimated in a sample from the Simons Simplex Collection (n = 2,087) using “borderline/clinical” versus “normative” range data from five of the DSM-Oriented Scales from the CBCL/6-18 as indicator variables. We evaluated the predictive value of NVIQ < 70, atypical sleep duration, allergies/autoimmune conditions, gastrointestinal conditions, and neurological conditions on subgroup membership using multinomial logistic regression.

Results

Four subgroups emerged: Low Psychiatric Symptoms (41.02%), Externalizing Symptoms (12.36%), Internalizing Symptoms (31.58%), and High Psychiatric Symptoms (15.05%). Key findings were that NVIQ < 70 was associated with decreased odds of belonging to the Internalizing Symptoms and High Psychiatric Symptoms subgroups over the Low Psychiatric Symptoms subgroup, while atypical sleep duration and gastrointestinal conditions were associated with increased odds of belonging to the Externalizing Symptoms and High Psychiatric Symptoms subgroups. Neurological conditions were also associated with increased odds of belonging to the Externalizing Symptoms subgroup.

Conclusion

Distinct patterns of psychiatric symptoms exist within school-aged autistic children and are correlated with NVIQ < 70, atypical sleep duration, and medical conditions, providing insights for clinical practice and etiology-driven research.
B cell numbers predict humoral and cellular response upon SARS-CoV-2 vaccination among patients treated with rituximab
Authors: Stefanski Ana-Luisa , Rincon-Arevalo Hector , Schrezenmeier Eva , Karberg Kirsten , Szelinski Franziska , Ritter Jacob , Jahrsdörfer Bernd , Schrezenmeier Hubert , Ludwig Carolin , Sattler Arne , Kotsch Katja , Chen Yidan , Claußnitzer Anne , Haibel Hildrun , Proft Fabian , Guerra Gabriella Maria , Durek Pawel , Heinrich Frederik , Gomes Marta Ferreira , Burmester Gerd R. , Radbruch Andreas , Mashreghi Mir-Farzin , Lino Andreia C. , Dörner Thomas
Published: July 2021

Objectives

Patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) therapy show substantially impaired anti-SARS-CoV-2 vaccine humoral but partly inducible cellular immune responses. However, the complex relationship between antigen-specific B and T cells and the level of B cell repopulation necessary to achieve anti-vaccine responses remain largely unknown.

Methods

Antibody responses to SARS-CoV-2 vaccines and induction of antigen-specific B and CD4/CD8 T cell subsets were studied in 19 rheumatoid arthritis (RA) and ANCA-associated vasculitis (AAV) patients receiving RTX, 12 RA patients on other therapies and 30 healthy controls after SARS-CoV-2 vaccination with either mRNA or vector based vaccines.

Results

A minimum of 10 B cells/µL in the peripheral circulation was necessary in RTX patients to mount seroconversion to anti-S1 IgG upon SARS-CoV-2 vaccination. RTX patients lacking IgG seroconversion showed reduced antigen-specific B cells, lower frequency of TfH-like cells as well as less activated CD4 and CD8 T cells compared to IgG seroconverted RTX patients. Functionally relevant B cell depletion resulted in impaired IFNγ secretion by spike-specific CD4 T cells. In contrast, antigen-specific CD8 T cells were reduced in patients independently of IgG formation.

Conclusions

Patients receiving rituximab with B cell numbers above 10 B cells/µl were able to mount humoral and more robust cellular responses after SARS-CoV-2 vaccination that may permit optimization of vaccination in these patients. Mechanistically, the data emphasize the crucial role of co-stimulatory B cell functions for the proper induction of CD4 responses propagating vaccine-specific B and plasma cell differentiation.
Impact of real-time assessment on the training of trainers for the introduction of rotavirus vaccine in India
Authors: Kaur Amanjot , Ray Arindam , Koshal Seema Singh , Quadri Syed F , Shersiya Mayank , Haldar Pradeep , Kapur Sanjay , Haseeb Mohammed , Roy Arup Deb
Published: July 2021

Objectives

To assess the effectiveness of training workshops for knowledge enhancement of program managers prior to rotavirus vaccine (RVV) introduction in the routine immunization program.

Method

The study was conducted among the participants attending two training workshops for the introduction of RVV; a state workshop in Pune and a regional workshop in Guwahati. The participants who attended the workshops and participated in both the pre and post-test - 53 for Guwahati and 59 for Pune. Data was collected in real-time via pre-post-test.

Results

In both workshops, a comparison of pre-test and post-test scores of all questions taken together showed a significant increase in the knowledge level of the participants (p<0.05). In Guwahati, the knowledge of the participants regarding doses of RVV, inadequate dosing, Vaccine Vial Monitor (VVM), open vial policy, operationalization of RVV, and monetary incentive increased significantly. In Pune, the knowledge of the participants regarding doses of RVV, bundling approach, schedule and dose, storage temperature for Rotavirus vaccine, VVM, open vial policy, vaccine delivery, and operationalization of RVV increased significantly after the training.

Conclusions

A pre-planned and well-designed knowledge assessment tool can be used to understand the impact of training workshops in enhancing the knowledge and practical skills of the participants prior to the introduction of a new vaccine.
Re-estimating prevalence of hepatitis B virus immunity among adults in the United States: self-reported vaccination, immunologic markers, and bias correction
Authors: Vader Daniel T. , Cohen Chari , Goldstein Neal D. , Lee Brian K. , Quick Harrison , Evans Alison A.
Published: July 2021

Background

Two instruments used to measure adult hepatitis B vaccination coverage in the United States are self-report and antibody to hepatitis B surface antigen (anti-HBs). Estimates based on either of these measures are subject to misclassification when used to determine immunity to hepatitis B. This study presents misclassification-corrected estimates of hepatitis B immune prevalence in the US and compares them to self-report- and antibody-based estimates.

Methods

We used cross-sectional data from the 2015-2016 NHANES cycle on 5,151 adults in the US age 18 and older. Existing literature on long-term immunity after vaccination informed anti-HBs sensitivity as a measure of immunity. Our model incorporated literature-based distributions for sensitivity and specificity using a Bayesian approach to correct for misclassification of true immune status by anti-HBs.

Results

After correcting for misclassification, overall adult immune prevalence was estimated at 31.0% (95% credible interval, 27.9% to 34.1%). Anti-HBs prevalence was 6.4 (3.9 to 8.8) and self-report prevalence 2.6 (−0.6 to 5.8) percentage points lower than overall immune prevalence. Among Asian Americans, anti-HBs and self-report underestimated immune prevalence by 15.8% (11.5% to 20.9%) and 25.1% (17.3% to 33.2%), respectively. Among 19 to 25-year-olds, anti-HBs and self-report underestimated immune prevalence by 26.5% (20.7% to 32.5%) and 21.0% (12.6% to 28.9%).

Conclusions

Both self-reported vaccination and antibody-based measures underestimate hepatitis B immunity among adults. This underestimation was especially large among younger adults and Asian Americans. The consequences of treating these surrogates as unbiased measures of vaccination or immunity may only increase as more vaccinated children age into adulthood.
Intestinal fungal dynamics and linkage to hematopoietic cell transplantation outcomes
Authors: Rolling Thierry , Zhai Bing , Gjonbalaj Mergim , Tosini Nicholas , Yasuma-Mitobe Keiko , Fontana Emily , Amoretti Luigi A , Wright Roberta J , Ponce Doris M , Perales Miguel A , Xavier Joao B , van den Brink Marcel R M , Markey Kate A , Peled Jonathan U , Taur Ying , Hohl Tobias M
Published: July 2021

Allogeneic hematopoietic cell transplantation (allo-HCT) induces profound shifts in the intestinal bacterial microbiota. The dynamics of intestinal fungi and their impact on clinical outcomes have not yet been integrated into a model of microbiota function during allo-HCT. Here, we combined parallel high-throughput fungal ITS1 amplicon sequencing, bacterial 16S amplicon sequencing, and fungal cultures to reveal striking trans-kingdom dynamics and their association with patient outcomes. We saw that the overall density and the biodiversity of intestinal fungi were stable during allo-HCT, but the species composition changed drastically from day to day. We identified a subset of patients with fungal dysbiosis characterized by culture positivity, stable expansion of Candida parapsilosis complex species, and distinct trans-kingdom microbiota profiles. These patients had worse overall survival and higher transplant-related mortality independent of candidemia. Our data expand the clinical significance of the mycobiota and suggest that targeting fungal dysbiosis may help to improve long-term patient survival.
Typically asymptomatic but with robust antibody formation: Children’s unique humoral immune response to SARS-CoV-2
Authors: Renk Hanna , Dulovic Alex , Becker Matthias , Fabricius Dorit , Zernickel Maria , Junker Daniel , Seidel Alina , Groß Rüdiger , Hilger Alexander , Bode Sebastian , Fritsch Linus , Frieh Pauline , Haddad Anneke , Görne Tessa , Remppis Jonathan , Ganzemueller Tina , Dietz Andrea , Huzly Daniela , Hengel Hartmut , Kaier Klaus , Weber Susanne , Jacobsen Eva-Maria , Kaiser Philipp D. , Traenkle Bjoern , Rothbauer Ulrich , Stich Maximilian , Tönshoff Burkhard , Hoffmann Georg F. , Müller Barbara , Ludwig Carolin , Jahrsdörfer Bernd , Schrezenmeier Hubert , Peter Andreas , Hörber Sebastian , Iftner Thomas , Münch Jan , Stamminger Thomas , Groß Hans-Jürgen , Wolkewitz Martin , Engel Corinna , Rizzi Marta , Henneke Philipp , Franz Axel R. , Debatin Klaus-Michael , Schneiderhan-Marra Nicole , Janda Ales , Elling Roland
Published: July 2021

Background

Long-term persistence of antibodies against SARS-CoV-2, particularly the SARS-CoV-2 Spike Trimer, determines individual protection against infection and potentially viral spread. The quality of children’s natural humoral immune response following SARS-CoV-2 infection is yet incompletely understood but crucial to guide pediatric SARS-CoV-2 vaccination programs.

Methods

In this prospective observational multi-center cohort study, we followed 328 households, consisting of 548 children and 717 adults, with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. The serological response was assessed at 3-4 months and 11-12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays.

Results

Overall, 33.76% of SARS-CoV-2 exposed children and 57.88% adults were seropositive. Children were five times more likely to have seroconverted without symptoms compared to adults. Despite the frequently asymptomatic course of infection, children had higher specific antibody levels, and their antibodies persisted longer than in adults (96.22% versus 82.89% still seropositive 11-12 months post infection). Of note, symptomatic and asymptomatic infections induced similar humoral responses in all age groups. In symptomatic children, only dysgeusia was found as diagnostic indicator of COVID-19. SARS-CoV-2 infections occurred independent of HCoV serostatus. Antibody binding responses to VOCs were similar in children and adults, with reduced binding for the Beta variant in both groups.

Conclusions

The long-term humoral immune response to SARS-CoV-2 infection in children is robust and may provide long-term protection even after asymptomatic infection.

(Study ID at German Clinical Trials Register: 00021521)
Sensitivity of excess mortality due to the COVID-19 pandemic to the choice of the mortality index, method, reference period, and the time unit of the death series
Authors: Nepomuceno Marília R. , Klimkin Ilya , Jdanov Dmitry A. , Galarza Ainhoa Alustiza , Shkolnikov Vladimir
Published: July 2021

Estimating excess mortality is challenging. The metric depends on the expected mortality level, which can differ based on given choices, such as the method and the time series length used to estimate the baseline. However, these choices are often arbitrary, and are not subject to any sensitivity analysis. We bring to light the importance of carefully choosing the inputs and methods used to estimate excess mortality. Drawing on data from 26 countries, we investigate how sensitive excess mortality is to the choice of the mortality index, the number of years included in the reference period, the method, and the time unit of the death series. We employ two mortality indices, three reference periods, two data time units, and four methods for estimating the baseline. We show that excess mortality estimates can vary substantially when these factors are changed, and that the largest variations stem from the choice of the mortality index and the method. We also find that the magnitude of the variation in excess mortality can change markedly within countries, resulting in different cross-country rankings. We conclude that the inputs and method used to estimate excess mortality should be chosen carefully based on the specific research question.
Turnover of SARS-CoV-2 lineages shaped the pandemic and enabled the emergence of new variants in the state of Rio de Janeiro, Brazil
Authors: Francisco Junior Ronaldo da Silva , Lamarca Alessandra P , de Almeida Luiz G P , Cavalcante Liliane , Machado Douglas Terra , Martins Yasmmin , Brustolini Otávio , Gerber Alexandra L , Guimarães Ana Paula de C , Gonçalves Reinaldo Bellini , Alves Cassia , Mariani Diana , Cruz Thais Felix , de Souza Isabelle Vasconcellos , de Carvalho Erika Martins , Ribeiro Mario Sergio , Carvalho Silvia , da Silva Flávio Dias , Garcia Marcio Henrique de Oliveira , de Souza Leandro Magalhães , Da Silva Cristiane Gomes , Pereira Ribeiro Caio Luiz , Cavalcanti Andréa Cony , de Mello Claudia Maria Braga , Struchiner Cláudio J. , Tanuri Amilcar , Vasconcelos Ana Tereza R
Published: July 2021

In the present study, we provide a retrospective genomic epidemiology analysis of the SARS-CoV-2 pandemic in the state of Rio de Janeiro, Brazil. We gathered publicly available data from GISAD and sequenced more 1,927 new genomes sampled periodically from March 2021 to June 2021 from 91 out of the 92 cities of the state. Our results showed that the pandemic was characterized by three different phases driven by a successive replacement of lineages. All stages occurred in distinct mortality and mobility contexts, with higher evidence of social distancing measures being observed in early pandemic and relaxed in the last two phases. Interestingly, we noticed that viral supercarriers accounted for the overwhelming majority of the circulating virus (> 90%) among symptomatic individuals in the state. Moreover, SARS-CoV-2 genomic surveillance also revealed the emergence and spread of two new variants (P.5 and P.1.2) firstly reported in this study. Altogether, our findings provided important lessons learned from the different epidemiological aspects of the SARS-CoV-2 dynamic in the state of Rio de Janeiro that have a strong potential to shape future decisions aiming to improve public health management and understanding mechanisms underlying virus dispersion.
Variation in SARS-CoV-2 bioaerosol production in exhaled breath
Authors: Verma Renu , Kim Eugene , Degner Nicholas , Walter Katharine S. , Singh Upinder , Andrews Jason R.
Published: July 2021

Using face mask bioaerosol sampling, we found substantial variation between individuals in SARS-CoV-2 copies exhaled over a 15-minute period, which moderately correlated with nasal swab viral load. Talking was associated with a median of 2 log10 greater exhaled viral copies. Exposure varies substantially between individuals but may be risk stratified by nasal swab viral load and whether the exposure involved conversation.
Protocol for systematic review of measurement of fatigue in people with cerebral palsy
Authors: Dutia I. M. , Eres R. , Sawyer S. M. , Johnston L. , Reddihough D. , Cleary S. , Coghill D.
Published: July 2021

Background

Fatigue is a common problem for people with cerebral palsy (CP), which adversely affects health-related outcomes. The emerging body of literature on fatigue in people with CP is characterised by substantial heterogeneity in assessment methods. To date, a systematic analysis of the measurement methods, and appraisal of the tools used to measure fatigue in people with CP has not been carried out. The aim of this review is to use The International Classification of Functioning, Disability and Health (ICF) as a framework to categorise and appraise current methods for measuring fatigue in people with CP.

Methods and Design

Literature searches will be conducted in MEDLINE, PsycInfo, CINAHL, Web of Science and Cochrane databases. Studies will be included in this systematic review if they purport to measure any type of fatigue in people with CP of any age through original research, are written in English and are published in peer-reviewed literature since 1980. From included studies we will extract the assessment methods used to measure fatigue, and demographic and clinical characteristics of the sample of people with CP. We will then provide a narrative synthesis of the type and ICF domain of fatigue purportedly measured and critical appraisal of the assessment methods used.

Discussion

This review will summarise current methods for measuring fatigue in people with CP. Critical appraisal and systematic categorisation of assessment methods will allow us to identify areas for further research on the domains in which fatigue occurs, and the role of fatigue in relation to clustering with other symptoms. Findings are expected to guide future assessment of fatigue in people with CP.
Autosomal recessive SLC30A9 Mutations in a Proband with a Cerebro-Renal Syndrome and No Parental Consanguinity
Authors: Kleyner Robert , Mohammad Arif , Marchi Elaine , Horowitz Naomi , Haworth Andrea , King Brian , Gavin Maureen , Amble Karen , Velinov Milen , Lyon Gholson J.
Published: July 2021

An SLC30A9-associated cerebro-renal syndrome was first reported in consanguineous Bedouin kindred by Perez et al. in 2017. While the function of the gene has not yet been fully elucidated, it may be implicated in Wnt signaling, nuclear regulation, as well as cell and mitochondrial zinc regulation. In this research report, we present a female proband with two distinct, inherited autosomal recessive loss-of-function SLC30A9 variants from unrelated parents. To our knowledge, this is the first reported case of a possible SLC30A9-associated cerebro-renal syndrome in a non-consanguineous family. Furthermore, a limited statistical analysis was conducted to identify possible allele frequency differences between populations. Our findings provide further support for an SLC30A9-associated cerebro-renal syndrome and may help further clarify the gene’s function.
Cultural Adaptation of a Brief Intervention to Reduce Alcohol Use Among Injury Patients in Tanzania
Authors: Zimmerman Armand , Pesambili Msafiri , Phillips Ashley J. , Boshe Judith , Mmbaga Blandina T. , Pantalon Michael H. , Swahn Monica , Hirshon Jon Mark , Vissoci Joao Ricardo Nickenig , Staton Catherine A.
Published: July 2021

Background

Harmful alcohol use is a leading risk factor for injury-related death and disability in low- and middle-income countries (LMICs). Brief negotiational interventions (BNIs) administered in emergency departments (EDs) to injury patients with alcohol use disorders (AUDs) are effective in reducing post-hospital alcohol intake and re-injury rates. However, most BNIs to date have been developed and implemented in high-income countries. The efficacy of BNIs in LMICs is largely unknown as few studies have undertaken the rigorous task of culturally adapting these interventions to new settings. Given the high prevalence of alcohol-related injury in the Kilimanjaro region of Tanzania, we culturally adapted a BNI to reduce post-injury alcohol use for implementation in this patient population.

Methods

We used an iterative, multiphase process to culturally adapt a high-income country standard of care BNI to the Tanzanian setting using the Intervention Mapping ADAPT framework. Our team consisted of local healthcare professionals with extensive experience in counseling patients who use alcohol, as well as an international team of academic and clinical professionals. Focus groups were used to inform culturally appropriate changes to the standard of care BNI protocol. Objective assessment of BNI delivery was performed to ensure adherence to the FRAMES model of motivational interviewing.

Results

We developed the Punguza Pombe Kwa Afya Yako (PPKAY); a one-time, 15-minute nurse-led BNI that encourages safe alcohol use and motivates change in alcohol use behaviors among injury patients in the Kilimanjaro region of Tanzania. Adaptations to the original intervention protocol include changes regarding the interventionist, how a patient is greeted, how the topic of alcohol use is raised, how a patient is informed of their harmful alcohol use, how graphics are visualized within the intervention protocol, how behavior change is motivated, and which behavior changes are encouraged.

Conclusions

The PPKAY intervention is the first BNI to be culturally adapted for delivery to injury patients in an LMIC population. Our study demonstrates a unique approach to adapting substance use interventions for use in LMICs, and shows that cultural adaptation of alcohol use interventions is feasible even in settings where community knowledge regarding harmful alcohol use is limited. Our study prompts the need for further research and cultural adaptation of BNIs for other low-income communities at increased risk of alcohol-related harm.
Neuroprotective, antioxidant and antiproliferative activity of grapefruit IntegroPectin on SH-SY5Y cells
Authors: Nuzzo Domenico , Scordino Miriana , Scurria Antonino , Giardina Costanza , Giordano Francesco , Meneguzzo Francesco , Mudò Giuseppa , Pagliaro Mario , Picone Pasquale , Attanzio Alessandro , Raimondo Stefania , Ciriminna Rosaria , Di Liberto Valentina
Published: July 2021

Tested in vitro on SH-SY5Y neuroblastoma cells, grapefruit IntegroPectin is a powerful neuroprotective, antioxidant and antiproliferative agent. The strong antioxidant properties of grapefruit IntegroPectin, and its ability to preserve mitochondrial membrane potential and morphology, severely impaired in neurodegenerative disorders, make this new biopolymer highly soluble in water an attractive therapeutic agent for oxidative stress-associated brain disorders. Similarly, the ability of this new citrus pectin rich in naringin, linalool, linalool oxide and limonene adsorbed at the outer surface to inhibit cell proliferation or even kill, at high doses, neoplastic cells, coupled to its excellent health and safety profile, opens up new therapeutic strategies in cancer research. In order to take full advantage of its vast therapeutic and preventive potential, detailed studies of molecular mechanism involved in the antiproliferative and neuroprotective of IntegroPectin are urgently needed.
Manipulation of RNA Polymerase III by Herpes Simplex Virus-1
Authors: Dremel Sarah E. , Sivrich Frances L. , Tucker Jessica , Glaunsinger Britt A. , DeLuca Neal A.
Published: July 2021

RNA Polymerase III (Pol III) transcribes noncoding RNA, including transfer RNA (tRNA), and acts as a pathogen sensor during the innate immune response. To promote enhanced proliferation, the Pol III machinery is commonly targeted during cancer and viral infection. Herein we employ DM-RNA-Seq, 4SU-Seq, ChIP-Seq, and ATAC-Seq to characterize how Herpes Simplex Virus-1 (HSV-1) perturbs the Pol III landscape. We find that HSV-1 stimulates tRNA expression 10-fold, with mature tRNAs exhibiting a 2-fold increase within 12 hours of infection. Perturbation of host tRNA synthesis requires nuclear viral entry, but not synthesis of specific viral transcripts, nascent viral genomes, or viral progeny. Host tRNA with a specific codon bias were not targeted—rather increased transcription was observed from euchromatic, actively transcribed loci. tRNA upregulation is linked to unique crosstalk between the Pol II and III transcriptional machinery. While viral infection is known to mediate host transcriptional shut off and lead to a depletion of Pol II on host mRNA promoters, we find that Pol II binding to tRNA loci increases. Finally, we report Pol III and associated factors bind the HSV genome, which suggests a previously unrecognized role in HSV-1 gene expression. These data provide insight into novel mechanisms by which HSV-1 alters the host nuclear environment, shifting key processes in favor of the pathogen.
Characterization of early Alzheimer’s-like pathological alterations in non-human primates with aging: a pilot study
Authors: Jester Hannah , Gosrani Saahj , Ding Huiping , Zhou Xueyan , Ko Mei-Chuan , Ma Tao
Published: July 2021

Sporadic or late onset Alzheimer’s disease (LOAD) is a multifactorial neurodegenerative disease with aging the most known risk factor. Non-human primates (NHPs) may serve as an excellent model to study LOAD because of their close similarity to humans in many aspects including neuroanatomy and neurodevelopment. Recent studies reveal AD-like pathology in old NHPs. In this pilot study, we took advantage of brain samples from 6 Cynomolgus macaques that were divided into two groups: middle aged (average age 14.81 years) and older (average age 19.33 years). We found multiple AD-like pathological alteration in the prefrontal cortex (but not in the hippocampus) of the older NHPs including tau hyperphosphorylation, increased activity of AMP-activated protein kinase (AMPK), decreased expression of protein phosphatase 2A (PP2A), impairments in mitochondrial morphology and postsynaptic densities (PSDs) formation. These findings may provide insights into the factors contributing to the development of LOAD, particularly during the early stage transitioning from middle to old age. Future endeavors are warranted to elucidate mechanisms underlying the regional (and perhaps cellular) vulnerability with aging and the functional correlation of such pathological changes in NHPs.
Fast unconscious processing of emotional stimuli in early stages of the visual cortex
Authors: Carretié Luis , Fernández-Folgueiras Uxía , Álvarez Fátima , Cipriani Germán A. , Tapia Manuel , Kessel Dominique
Published: July 2021

Several cortical and subcortical brain areas have been reported to be sensitive to the emotional content of subliminal stimuli. However, the timing of these activations remains unclear. Our scope was to detect the earliest cortical traces of visual unconscious processing by recording event-related potentials (ERPs) from 43 participants. Subliminal spiders (emotional) and wheels (neutral), sharing similar low-level visual parameters, were presented at two different locations (fixation and periphery). The differential (peak to peak) amplitude from CP1 (77 milliseconds from stimulus onset) to C2 (100 milliseconds), two early visual ERP components originated in V1/V2 according to source localization analyses, was analyzed via Bayesian and traditional analyses. Spiders elicited greater CP1-C2 amplitudes than wheels when presented at fixation. This fast effect of subliminal stimulation -not reported previously to the best of our knowledge-has implications in several debates: i) the amygdala cannot be mediating these effects, ii) latency of other evaluative structures recently proposed, such as the visual thalamus, is compatible with these results, iii) the absence of peripheral stimuli effects points to a relevant role of the parvocellular visual system in unconscious processing.
Panx1b modulates the luminance response and direction of motion in the zebrafish
Authors: Safarian Nickie , Houshangi-Tabrizi Sarah , Zoidl Christiane , Zoidl Georg R.
Published: July 2021

Pannexin1 (Panx1) can form ATP-permeable integral membrane channels that play roles in the physiology of the visual system. Two independent gene copies of Panx1, panx1a and panx1b, have been identified in the zebrafish with unique and shared properties and tissue expression patterns. Panx1a channels, located in horizontal cells of the outer retina, modulate light decrement detection through an ATP/pH-dependent mechanisms and adenosine/dopamine signaling. Here, we decipher how the strategic localization of Panx1b channels in the inner retina and ganglion cell layer modulates visually evoked motor behavior. We describe a panx1b knockout model generated by TALEN technology. The RNA-seq analysis of 6 days post-fertilization larvae is confirmed by Real-Time PCR and paired with testing of visual-motor behaviors. The Panx1b protein emerges as a modulator of the circadian clock system. The loss of panx1b also disrupts the retinal response to the abrupt loss of illumination and decreases the larval ability to follow leftward direction of motion in the dark. The evidence suggests that in the retina Panx1b contributes to the OFF pathways function, like Panx1a, though through different signaling mechanisms. In this process, the loss of Panx1b channels compromises the final output of luminance as well as direction of motion detector RGCs. In addition, the disruption of the circadian clock system in mutants suggests that Panx1b could participate in non-image forming processes in the inner retina.
Chronic release of tailless phage particles from Lactococcus lactis
Authors: Liu Yue , Alexeeva Svetlana , Bachmann Herwig , Martínez Jesús Adrián Guerra , Yeremenko Nataliya , Abee Tjakko , Smid Eddy J.
Published: July 2021

Lactococcus lactis strains residing in the microbial community of a complex dairy starter culture named “Ur” are hosts to prophages belonging to the family Siphoviridae. L. lactis strains (TIFN1 to TIFN7) showed detectable spontaneous phage production and release (109-1010 phage particles/mL) and up to 10-fold increases upon prophage induction, while in both cases we observed no obvious cell lysis, typically described for the lytic life cycle of Siphoviridae phages. Intrigued by this phenomenon, we investigated the host-phage interaction using strain TIFN1 (harboring prophage proPhi1) as a representative. We confirmed that during the massive phage release, all bacterial cells remain viable. Further, by monitoring phage replication in vivo, using a green fluorescence protein reporter combined with flow cytometry, we demonstrated that the majority of the bacterial population (over 80%) is actively producing phage particles when induced with mitomycin C. The released tailless phage particles were found to be engulfed in lipid membranes, as evidenced by electron microscopy and lipid staining combined with chemical lipid analysis. Based on the collective observations, we propose a model of phage-host interaction in L. lactis TIFN1, where the phage particles are engulfed in membranes upon release, thereby leaving the producing host intact. Moreover, we discuss possible mechanisms of chronic, or non-lytic release of LAB Siphoviridae phages and its impact on the bacterial host.
Dietary Patterns Among 13-17-Years Old School Adolescents: A National Comparison of the Three Geographical Regions in Bolivia
Authors: Villalta Noelia , Arauco Nattalia , Mamani Marisol , Illanes Daniel E , Singh Pramil , Moura Lenildo De , Sabaté Joan
Published: July 2021

Introduction

Bolivia is considered one to the most biodiverse countries in the world. It has three ecological floors or geographical regions (highlands, plains and valleys) with very different climatic and cultural characteristics. Traditionally dietary patterns varied in each region. Because two-thirds of premature deaths are associated with behaviors that begin in adolescence, understanding dietary patterns among adolescents is important to improving health. The aim of this study was to identify dietary patterns of adolescents in the different geographical regions of Bolivia.

Methodology

Data were obtained from the World Health Organization’s Global School-based Student Health Survey 2018 that assesses risky behaviors and protective factors in students aged 13 to 17 years old. It uses an observational cross-sectional method and included 7945 adolescents in schools that were representative of all students in this age group in each of the three geographical regions in Bolivia.

Results

3.9% of students in Bolivia are food insecure, with the highest percentage in the highlands (4.6%) and the lowest in the plains (3.1%). Adolescents in the highlands consume vegetables and fruits more frequently than adolescents in the plains and valleys. Water consumption in the valleys was 19.6% students who drink 1-3 glasses/d. Dairy consumption ≥2 in 7 days is higher in the highlands and lower in the valleys. Consumption of soft drinks at ≥1 glass per day is 34.3% in the plains and 30.1% in the valleys. Junk food consumption ≥1 in 7 days was 62.0% with a greater presence on the plains at 65.7%.

Conclusion

The highlands revealed a greater presence of protective factors than the other regions. The valley, despite having greater access to fruits and vegetables, has a greater presence of risky behaviors. Teenagers in the plains have greater exposure to advertising and access to junk food at school.