bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Bone Buttressing at the Vertical Osteotomy Site on Postoperative Stability After Mandibular Setback Surgery
Authors: Shathi Fatema Farhana , Kim Taeyun , Han Jeong Joon , Kook Min-Suk , Park Hong-Ju , Oh Hee-Kyun
Published: July 2021

This study aimed to assess the effect of bone buttressing at the vertical osteotomy site on postoperative stability after mandibular setback surgery and determine factors contributing to postoperative relapse. This retrospective study was conducted on patients who received mandibular setback surgery using bilateral sagittal split ramus osteotomy. Patients were divided into two groups: group I, intimate bony contact, and group II, bony gap of 2 mm or more. Using lateral cephalograms taken before surgery, 1 week after surgery, and 6 months after surgery, surgical changes, and postoperative relapse were compared between 2 groups. To assess associations between postoperative relapse and other variables, Pearson correlation analysis and multiple linear regression analysis were performed. Twenty-eight patients were evaluated (17 in group I and 11 in group II). Mean relapse was greater in group II (1.8 mm) than in group I (1.2 mm), although there were no significant differences between 2 groups (P = 0.203). Postoperative relapse was significantly associated with intraoperative clockwise rotation of the proximal segment (P < 0.001) and the amount of mandibular setback (P = 0.038). Bony gap was only correlated with postoperative counterclockwise rotation of the proximal segment (P = 0.014). In the regression analysis, intraoperative clockwise rotation of the proximal segment significantly predicted postoperative relapse (P < 0.001, R2 = 0.388). The absence of bone buttressing at the vertical osteotomy site may not significantly affect postoperative stability after mandibular setback surgery, and it is important to minimize intraoperative clockwise rotation of the proximal segment for better postoperative stability.
Effects of Fat Repositioning for Tear Trough Deformity on Eye Movement
Authors: Kokubo Kenichi , Katori Nobutada , Hayashi Kengo , Fujii Akiko , Kitamura Sho , Haga Shoko , Maeda Chie , Kawabata Tomotaka , Maegawa Jiro
Published: July 2021

Fat repositioning is a common surgical technique for treating tear trough deformity. As this technique is mainly performed for cosmetic purposes, its functional outcomes have rarely been evaluated. The purpose of this study was to evaluate the changes in eye movements that occur after fat repositioning for tear trough deformity. The authors performed fat repositioning on 18 eyelids of 9 patients and evaluated their eye movements and binocular vision before surgery and at 1, 3, and 6 months after surgery. Hess screen and Binocular single vision tests were performed during each follow-up examination and the scores were recorded. The authors observed that fat repositioning did not affect binocular vision; however, vertical and horizontal eye movements worsened at 3 months after surgery. Nevertheless, there was no significant difference between the eye movements recorded before surgery and those recorded 6 months after surgery. Regardless of this finding, it should be noted that vertical or horizontal strabismus might occur after fat repositioning for tear trough deformity.
Taxonomic identification bias does not drive patterns of abundance and diversity in theropod dinosaurs
Authors: Cashmore Daniel D. , Butler Richard J. , Maidment Susannah C. R.
Published: July 2021

The ability of palaeontologists to correctly diagnose and classify new fossil species from incomplete morphological data is fundamental to our understanding of evolution. Different parts of the vertebrate skeleton have different likelihoods of fossil preservation and varying amounts of taxonomic information, which could bias our interpretations of fossil material. Substantial previous research has focused on the diversity and macroevolution of non-avian theropod dinosaurs. Theropods provide a rich dataset for analysis of the interactions between taxonomic diagnosability and fossil preservation. We use specimen data and formal taxonomic diagnoses to create a new metric, the Likelihood of Diagnosis, which quantifies the diagnostic likelihood of fossil species in relation to bone preservation potential. We use this to assess whether a taxonomic identification bias impacts the non-avian theropod fossil record. We find that the patterns of differential species abundance and clade diversity are not a consequence of their relative diagnosability. Although there are other factors that bias the theropod fossil record that are not investigated here, our results suggest that patterns of relative abundance and diversity for theropods might be more representative of Mesozoic ecology than often considered.
Sex differences in the cognitive abilities of a sex-changing fish species
Labroides dimidiatus
Authors: Triki Zegni , Bshary Redouan
Published: July 2021

Males and females of the same species are known to differ at least in some cognitive domains, but such differences are not systematic across species. As a consequence, it remains unclear whether reported differences generally reflect adaptive adjustments to diverging selective pressures, or whether differences are mere side products of physiological differences necessary for reproduction. Here, we show that sex differences in cognition occur even in a sex-changing species, a protogynous hermaphroditic species where all males have previously been females. We tested male and female cleaner fish
Labroides dimidiatus
in four cognitive tasks to evaluate their learning and inhibitory control abilities first in an abstract presentation of the tasks, then in more ecologically relevant contexts. The results showed that males were better learners than females in the two learning tasks (i.e. reversal learning as an abstract task and a food quantity assessment task as an ecologically relevant task). Conversely, females showed enhanced abilities compared with males in the abstract inhibitory control task (i.e. detour task); but both sexes performed equally in the ecologically relevant inhibitory control task (i.e. ‘audience effect’ task). Hence, sex-changing species may offer unique opportunities to study proximate and/or ultimate causes underlying sex differences in cognitive abilities.
Quantitative proton nuclear magnetic resonance method for simultaneous analysis of fluticasone propionate and azelastine hydrochloride in nasal spray formulation
Authors: El-Masry Amal A. , El-Wasseef Dalia R. , Eid Manal , Shehata Ihsan A. , Zeid Abdallah M.
Published: July 2021

A facile, rapid, accurate and selective quantitative proton nuclear magnetic resonance (1H-qNMR) method was developed for the simultaneous determination of fluticasone propionate (FLP) and azelastine hydrochloride (AZH) in pharmaceutical nasal spray for the first time. The1H-qNMR analysis of the studied analytes was performed using inositol as the internal standard and dimethyl sulfoxide-d6(DMSO-d6)as the solvent. The quantitative selective proton signal of FLP was doublet of doublet at 6.290, 6.294, 6.316 and 6.319 ppm, while that of AZH was doublet at 8.292 and 8.310 ppm. The internal standard (inositol) produced a doublet signal at 3.70 and 3.71 ppm. The method was rectilinear over the concentration ranges of 0.25–20.0 and 0.2–15.0 mg ml−1for FLP and AZH, respectively. No labelling or pretreatment steps were required for NMR analysis of the studied analytes. The proposed1H-qNMR method was validated efficiently according to the International Council on Harmonisation guidelines in terms of linearity, limit of detection, limit of quantification, accuracy, precision, specificity and stability. Moreover, the method was applied to assay the analytes in their combined nasal spray formulation. The results ensured the linearity (r2> 0.999), precision (% RSD < 1.5), stability, specificity and selectivity of the developed method.
Non-topographic current contrast in scanning field emission microscopy
Authors: Bertolini G. , Gürlü O. , Pröbsting R. , Westholm D. , Wei J. , Ramsperger U. , Zanin D. A. , Cabrera H. , Pescia D. , Xanthakis J. P. , Schnedler M. , Dunin-Borkowski R. E.
Published: July 2021

In scanning field emission microscopy (SFEM), a tip (the source) is approached to few (or a few tens of) nanometres distance from a surface (the collector) and biased to field-emit electrons. In a previous study (Zanin
et al.
2016
Proc. R. Soc. A
472
, 20160475. (
doi:10.1098/rspa.2016.0475
)), the field-emitted current was found to change by approximately 1% at a monatomic surface step (approx. 200 pm thick). Here we prepare surface domains of adjacent different materials that, in some instances, have a topographic contrast smaller than 15 pm. Nevertheless, we observe a contrast in the field-emitted current as high as 10%. This non-topographic collector material dependence is a yet unexplored degree of freedom calling for a new understanding of the quantum mechanical tunnelling barrier at the source site that takes into account the properties of the material at the collector site.
Urban warming and artificial light alter dormancy in the flesh fly
Authors: Mukai Ayumu , Yamaguchi Koki , Goto Shin G.
Published: July 2021

Seasonal changes in temperature and day length are distinct between rural and urban areas due to urban warming and the presence of artificial light at night. Many studies have focused on the impacts of these ubiquitous signatures on daily biological events, but empirical studies on their impacts on insect seasonality are limited. In the present study, we used the flesh flySarcophaga similisas a model insect to determine the impacts of urbanization on the incidence and timing of diapause (dormancy), not only in the laboratory but also in rural and urban conditions. In the laboratory, diapause entry was affected by night-time light levels as low as 0.01 lux. We placed fly cages on outdoor shelves in urban and rural areas to determine the timing of diapause entry; it was retarded by approximately four weeks in urban areas relative to that in rural areas. Moreover, almost all flies in the site facing an urban residential area failed to enter diapause, even by late autumn. Although an autumnal low temperature in the urban area would mitigate the negative effect of artificial light at night, strong light pollution seriously disrupts the flesh fly seasonal adaptation.
8-hydroxyquinoline-5-(N-4-chlorophenyl) sulfonamide and fluconazole combination as a preventive strategy for Candida biofilm in haemodialysis devices
Authors: da Rocha Letícia Fernandes , Pippi Bruna , Joaquim Angélica Rocha , de Andrade Saulo Fernandes , Fuentefria Alexandre Meneghello
Published: July 2021

Introduction. The presence of Candida biofilms in medical devices is a concerning and important clinical issue for haemodialysis patients who require constant use of prosthetic fistulae and catheters.

Hypothesis/Gap Statement. This prolonged use increases the risk of candidaemia due to biofilm formation. PH151 and clioquinol are 8-hydroxyquinoline derivatives that have been studied by our group and showed interesting anti-Candida activity.

Aim. This study evaluated the biofilm formation capacity of Candida species on polytetrafluoroethylene (PTFE) and polyurethane (PUR) and investigated the synergistic effects between the compounds PH151 and clioquinol and fluconazole, amphotericin B and caspofungin against biofilm cells removed from those materials. Further, the synergistic combination was evaluated in terms of preventing biofilm formation on PTFE and PUR discs.

Methodology. Susceptibility testing was performed for planktonic and biofilm cells using the broth microdilution method. The checkerboard method and the time–kill assay were used to evaluate the interactions between antifungal agents. Antibiofilm activity on PTFE and PUR materials was assessed to quantify the prevention of biofilm formation.

Results.
Candida albicans, Candida glabrata and Candida tropicalis showed ability to form biofilms on both materials. By contrast, Candida parapsilosis did not demonstrate this ability. Synergistic interaction was observed when PH151 was combined with fluconazole in 77.8 % of isolates and this treatment was shown to be concentration- and time-dependent. On the other hand, indifferent interactions were predominantly observed with the other combinations. A reduction in biofilm formation on PUR material of more than 50 % was observed when using PH151 combined with fluconazole.

Conclusion. PH151 demonstrated potential as a local treatment for use in a combination therapy approach against Candida biofilm formation on haemodialysis devices.
Investigation into the effect of mannan-rich fraction supplementation on the metagenome of broiler chickens
Authors: Delaney Sarah , Do Thi Thuy , Corrigan Aoife , Murphy Richard , Walsh Fiona
Published: July 2021

Antibiotic resistance is regarded as one of the most serious threats to human health worldwide. The rapid increase in resistance rates has been attributed to the extensive use of antibiotics since they became commercially available. The use of antibiotics as growth promotors has been banned in numerous regions for this reason. Mannan-rich fraction (MRF) has been reported to show similar growth-promoting effects to antibiotics. We investigated the effect of MRF on the microbial community, resistome and metabolic pathways within the caecum of commercial broilers at two different timepoints within the growth of the broiler, day 27 and day 34. The data indicated an overall increase in health and economic gain for the producer with the addition of MRF to the diet of the broilers. The only significant difference across the microbial composition of the samples was in the richness of the microbial communities across all samples. While all samples harboured resistance genes conferring resistance to the same classes of antibiotics, there was significant variation in the antimicrobial resistance gene richness across time and treatment and across combinations of time and treatment. The taxa with positive correlation comprised Bacilli and Clostridia. The negative correlation taxa were also dominated by Bacilli, specifically the Streptococcus genera. The KEGG-pathway analysis identified an age-related change in the metabolism pathway abundances of the caecal microflora. We suggest that the MRF-related increases in health and weight gain in the broilers may be associated with changes in the metabolism of the microbiomes rather than the microbial composition. The resistome variations across samples were correlated with specific genera. These data may be used to further enhance the development of feed supplements to reduce the presence of antibiotic resistance genes (ARGs) within poultry. While the ARGs of greatest concern to human or animal health were not detected in this study, it has identified the potential to reduce the presence of ARGs by the increase in specific genera.
Rare variants in IFFO1, DTNB and NLRC3 associate with Alzheimer’s disease CSF profile of neuronal injury and inflammation
Authors: Neumann Alexander , Küçükali Fahri , Bos Isabelle , Vos Stephanie J.B. , Engelborghs Sebastiaan , De Pooter Tim , Joris Geert , De Rijk Peter , De Roeck Ellen , Tsolaki Magda , Verhey Frans , Martinez-Lage Pablo , Tainta Mikel , Frisoni Giovanni , Blin Oliver , Richardson Jill , Bordet Régis , Scheltens Philip , Popp Julius , Peyratout Gwendoline , Johannsen Peter , Frölich Lutz , Vandenberghe Rik , Freund-Levi Yvonne , Streffer Johannes , Lovestone Simon , Legido-Quigley Cristina , Kate Mara ten , Barkhof Frederik , Strazisar Mojca , Zetterberg Henrik , Bertram Lars , Visser Pieter Jelle , van Broeckhoven Christine , Sleegers Kristel ,   EMIF-AD study group,   Alzheimer’s Disease Neuroimaging Initiative
Published: July 2021

Alzheimer’s disease (AD) biomarkers represent several neurodegenerative processes, such as synaptic dysfunction, neuronal inflammation and injury, as well as amyloid pathology. We performed an exome-wide rare variant analysis of six AD biomarkers (β-amyloid, total/phosphorylated tau, Nfl, YKL-40, and Neurogranin) to discover genes associated with these markers. Genetic and biomarker information was available for 480 participants from two studies: EMIF-AD and ADNI. We applied a principal component (PC) analysis to derive biomarkers combinations, which represent statistically independent biological processes. We then tested whether rare variants in 9,576 protein-coding genes associate with these PCs using a Meta-SKAT test. We also tested whether the PCs are intermediary to gene effects on AD symptoms with a SMUT test. One PC loaded on Nfl and YKL-40, indicators of neuronal injury and inflammation. Three genes were associated with this PC: IFFO1, DTNB and NLRC3. Mediation tests suggest, that these genes also affect dementia symptoms via inflammation/injury. We also observed an association between a PC loading on Neurogranin, a marker for synaptic functioning, with GABBR2 and CASZ1, but no mediation effects. The results suggest that rare variants in IFFO1, DTNB and NLRC3 heighten susceptibility to neuronal injury and inflammation, potentially by altering cytoskeleton structure and immune activity disinhibition, resulting in an elevated dementia risk. GABBR2 and CASZ1 were associated with synaptic functioning, but mediation analyses suggest that the effect of these two genes on synaptic functioning is not consequential for AD development.
Performance evaluation of a multinational data platform for critical care in Asia
Authors: Pisani Luigi , Rashan Thalha , Shamal Maryam , Ghose Aniruddha , Vijayaraghavan Bharath Kumar Tirupakuzhi , Tripathy Swagata , Aryal Diptesh , Hashmi Madiha , Nor Basri , Minh Yen Lam , Dondorp Arjen M. , Haniffa Rashan , Beane Abi
Published: July 2021

Objective

We aimed to evaluate the quality of a multinational intensive care unit (ICU) network of registries of critically ill patients established in seven Asian low and middle income countries (LMICs).

Methods

The Critical Care Asia federated registry platform enables ICUs to collect clinical, outcome and process data for aggregate and unit-level analysis. The evaluation used the standardised criteria of the Directory of Clinical Databases (DoCDat) and a framework for data quality assurance in medical registries. Six reviewers assessed structure, coverage, reliability and validity of the ICU registry data. Case mix and process measures on patient episodes from June to December 2020 were analysed.

Results

Data on 20,507 consecutive patient episodes from 97 ICUs in Afghanistan, Bangladesh, India, Malaysia, Nepal, Pakistan and Vietnam were included. The quality level achieved according to the ten prespecified DoCDat criteria was high (average score 3.4 out of 4) as was the structural and organizational performance -- comparable to ICU registries in high-income countries. Identified strengths were types of variables included, reliability of coding, data completeness and validation. Potential improvements include extension of national coverage.

Conclusion

The Critical Care Asia platform evaluates well using standardised frameworks for data quality and equally to registries in resource-rich settings.

Funding

This work was undertaken as part of the existing Wellcome Innovations Flagship award, Collaboration for Research, Improvement and Training in Critical CARE in ASIA (ref. 215522/Z/19/Z). The funder had no role in the decision to publish or in the preparation of this manuscript.
Investigation research on the demand of pre-job training for nursing students in higher vocational colleges
Authors: Liu Li , Qiu Xiaojing , Li Yahui , Yang Junzheng
Published: July 2021

Objectives

To investigate the pre-job training demand of nursing students in higher vocational colleges, lay a foundation for the development of scientific and standardized pre-job training program and help nursing students smoothly transition to clinical practice state from student status.

Methods

A self-designed questionnaire was used to investigate 822 nursing students of grade 2018 in our school from four aspects: the necessity of pre-job training, the demand content of pre-job training, the demand of skill enhancement program, and the stress source of pre-internship.

Results

Demand rate of the pre-job training of nursing students in the college was 99.5%, and main demand of the training content were nursing skill training (96.8%), nursing safety and occupational protection (95.1%), nursing theory training (92.9%); the main demand of nursing skills enhancement program were closed intravenous infusion (90.3%), (intradermal, subcutaneous, intramuscular) injection (87.8%), cardiopulmonary resuscitation (81.8%), and indwelling catheterization (77.5%); the main stress sources of pre-internship was lack of confidence in theory and skills, accounts for 61.1% in total 760 students.

Conclusion

The pre-job training courses in higher vocational colleges should be close to the clinical needs of students, it is necessary to carry out pre-job training courses according to main demand of the training content, the main demand of nursing skills enhancement program and the main stress sources of pre-internship in the college; this article may provide reference for our school and other vocational colleges to develop pre-job training program.
Does trust in government improve Covid-19’s crisis management?
Authors: Apeti Ablam Estel
Published: July 2021

Countries have adopted several measures to control the spread of Covid-19. However, substantial differences remain in terms of performance in controlling the virus, potentially due to heterogeneity in citizen engagement with government measures. Drawing on this observation, this paper seeks to analyze the effect of pre-crisis ties, particularly trust in government, on crisis management, proxied by the number of Covid-19 cases and deaths per million population. We examine this question based on a sample of 41 countries for which data are available. Results reveal that a high level of trust in government predicts better crisis management in terms of relatively low levels of cases and deaths. These results, which successfully pass a series of robustness tests, may vary according to level of contamination and increase with time.

JEL Classification

E71, H12, I12, I18, I38, Z18
A systematic review and meta-analysis of inpatient mortality associated with nosocomial and community COVID-19 exposes the vulnerability of immunosuppressed adults
Authors: Ponsford Mark J. , Ward Tom JC , Stoneham Simon , Dallimore Clare M. , Sham Davina , Osman Khalid , Barry Simon , Jolles Stephen , Humphreys Ian R. , Farewell Daniel
Published: July 2021

Background

Little is known about the mortality of hospital-acquired (nosocomial) COVID-19 infection globally. We investigated the risk of mortality and critical care admission in hospitalised adults with nosocomial COVID-19, relative to adults requiring hospitalisation due to community-acquired infection.

Methods

We systematically reviewed the peer-reviewed and pre-print literature from 1/1/2020 to 9/2/2021 without language restriction for studies reporting outcomes of nosocomial and community-acquired COVID-19. We performed a random effects meta-analysis (MA) to estimate the 1) relative risk of death and 2) critical care admission, stratifying studies by patient cohort characteristics and nosocomial case definition.

Results

21 studies were included in the primary MA, describing 8,246 admissions across 8 countries during the first wave, comprising 1517 probable or definite nosocomial COVID-19, and 6729 community-acquired cases. Across all studies, the risk of mortality was 1.31 times greater in patients with nosocomial infection, compared to community-acquired (95% CI: 1.01 to 1.70). Rates of critical care admission were similar between groups (Relative Risk, RR=0.74, 95% CI: 0.50 to 1.08). Immunosuppressed patients diagnosed with nosocomial COVID-19 were twice as likely to die in hospital as those admitted with community-acquired infection (RR=2.14, 95% CI: 1.76 to 2.61).

Conclusions

Adults who acquire SARS-CoV-2 whilst already hospitalised are at greater risk of mortality compared to patients admitted following community-acquired infection; this finding is largely driven by a substantially increased risk of death in individuals with malignancy or who had undergone transplantation. These findings inform public health and infection control policy, and argue for individualised clinical interventions to combat the threat of nosocomial COVID-19, particularly for immunosuppressed groups.

Systematic review registration: PROSPERO CRD42021249023
SARS-CoV-2 seroprevalence in asymptomatic or mild symptomatic people and symptomatic patients with negative PCR results: The hidden perspective in epidemiological reports
Authors: Hajiahmadi Nazila , Mojtahedzadeh Faezeh , Yari Atefeh , Tat Mahdi , Soleimanjahi Hoorieh , Jamehdar Saeid Amel , Jafari Mitra , Asli Samira , Dorostkar Rohollah , Nazemipour Maryam , Mansournia Mohammad Ali , Bamdad Taravat
Published: July 2021

Background

SARS-CoV-2 has led to the current pandemic of respiratory disease. The reports of confirmed COVID-19 cases based on molecular tests do not completely cover the total number of infected people. These reports do not include the asymptomatic or mildly symptomatic patients and also the patients with false-negative RT-PCR results, while the infection is contagious in all of these conditions.

Objective

In this study, we tried to improve our conception of the hidden perspective of SARS-CoV-2 in epidemiological reports.

Methods

From May 30 to June 17, 2020, blood samples were collected from two groups of people: asymptomatic or mild symptomatic volunteer participants and severe symptomatic hospitalized patients with negative PCR results. Detection of SARS-CoV-2 antibody was done with ELISA kit targeting N or S proteins.

Results

Totally 716 samples from volunteer participants and 81 samples from symptomatic hospitalized patients with negative PCR were evaluated. The test performance-adjusted seroprevalence (95% CI) of SARS-CoV-2 anti-N IgG was 17.3% (8.8%, 25.8%) for volunteers and 25.5% (12.8%, 39.7%) for anti-N and S IgM in hospitalized group. There was an association between high-risk occupations, high-risk behaviors, or symptomatic diseases with positive SARA-Cov-2 N antibody results. Among anti-N positive infected individuals, 49.2% (21.4%, 78.8%) were anti-S positive.

Conclusion

The results showed that SARS-COV-2 infection occurs in asymptomatic or mildly symptomatic individuals, but in more than half of them, the produced antibody is not protective. Findings of hospitalized patients also showed that the combination of IgM assay with real-time PCR improves the detection of the disease by more than 25% in negative molecular cases.
Vaccine serologic responses among transplant patients associate with COVID-19 infection and T peripheral helper cells
Authors: Lemieux Jacob E. , Li Amy , Gentili Matteo , Perugino Cory A. , Weiss Zoe F. , Bowman Kathryn , Ankomah Pierre , Liu Hang , Lewis Gregory D. , Bitar Natasha , Lipiner Taryn , Hacohen Nir , Pillai Shiv S. , Goldberg Marcia B.
Published: July 2021

Background

Therapeutically immunosuppressed transplant recipients exhibit attenuated responses to COVID-19 vaccines. To better understand the immune alterations that determined poor vaccine response, we correlated quantities of circulating T and B cell subsets at baseline with longitudinal serologic responses to SARS-CoV-2 mRNA vaccination in heart and lung transplant recipients.

Methods

Samples at baseline and at approximately 8 and 30 days after each vaccine dose for 22 heart and lung transplant recipients with no history of COVID-19, four heart and lung transplant recipients with prior COVID-19 infection, and 12 healthy controls undergoing vaccination were analyzed. Anti-spike protein receptor binding domain (RBD) IgG and pseudovirus neutralization activity were measured. Proportions of B and T cell subsets at baseline were comprehensively quantitated.

Results

At 8-30 days post vaccination, healthy controls displayed robust anti-RBD IgG responses, whereas heart and lung transplant recipients showed minimally increased responses. A parallel absence of activity was observed in pseudovirus neutralization. In contrast, three of four (75%) transplant recipients with prior COVID-19 infection displayed robust responses at levels comparable to controls. Baseline levels of activated PD-1+ HLA-DR+ CXCR5- CD4+ T cells (also known as T peripheral helper [TPH] cells) and CD4+ T cells strongly predicted the ability to mount a response.

Conclusions

Immunosuppressed patients have defective vaccine responses but can be induced to generate neutralizing antibodies after SARS-CoV-2 infection. Strong correlations of vaccine responsiveness with baseline TPH and CD4+ T cell numbers highlights a role for T helper activity in B cell differentiation into antibody secreting cells during vaccine response.
The QuantuMDx Q-POC™ SARS-CoV-2 RT-PCR assay for rapid detection of COVID-19 at point-of-care: preliminary evaluation of a novel technology
Authors: Caffry Jessica , Selby Matthew , Barr Katie , Morgan George , McGurk David , Scully Philip , Park Catherine , Caridis Anna-Maria , Southworth Emily , Morrison Jack , Clark David J , Eckersely Nickolas , Groppelli Elisabetta , Kirwan Daniela E. , Monahan Irene , Augustin Yolanda , Toombs Colin , Planche Tim , Staines Henry M , Krishna Sanjeev
Published: July 2021

Background

Accurate, affordable, and rapid point-of-care (PoC) diagnostics are critical to the global control and management of the COVID-19 pandemic. The current standard for accurate diagnosis of SARS-CoV-2 is laboratory-based reverse transcription polymerase chain reaction (RT-PCR). Here, we report a preliminary prospective performance evaluation of the QuantuMDx Q-POC™ SARS CoV-2 RT-PCR assay.

Methods

Between November 2020 and March 2021, we obtained 49 longitudinal nose and throat swabs from 29 individuals hospitalised with RT-PCR confirmed COVID-19 at St George’s NHS Foundation Trust, London (UK). In addition, we obtained 101 mid nasal swabs from healthy volunteers in June 2021. We then used these samples to evaluate the Q-POC™ SARS-CoV-2 RT-PCR assay. The primary analysis was to compare the sensitivity and specificity of the Q-POC™ test against a reference laboratory-based RT-PCR assay.

Results

The overall sensitivity of the Q-POC™ test compared with the reference test was 96.88% (83.78%-99.92% CI) for a cycle threshold (Ct) cut-off value for the reference test of 35 and 80.00% (64.35% to 90.95% CI) without altering the reference test’s Ct cut-off value of 40.

Conclusions

The Q-POC™ test is a sensitive, specific and rapid point-of-care test for SARS-CoV-2 at a reference Ct cut-off value of 35. The Q-POC™ test provides an accurate and affordable option for RT-PCR at point-of-care without the need for sample pre-processing and laboratory handling. The Q-POC™ test would enable rapid diagnosis and clinical triage in acute care and other settings.
Machine Learning Model for Predicting Number of COVID19 Cases in Countries with Low Number of Tests
Authors: Hashim Samy , Farooq Sally , Syriopoulos Eleni , Cremer Kai de la Lande , Vogt Alexander , de Jong Nol , Aguado Victor L. , Popescu Mihai , Mohamed Ashraf K. , Amin Muhamed
Published: July 2021

The COVID-19 pandemic has presented a series of new challenges to governments and health care systems. Testing is one important method for monitoring and therefore controlling the spread of COVID-19. Yet with a serious discrepancy in the resources available between rich and poor countries not every country is able to employ widespread testing. Here we developed machine learning models for predicting the number of COVID-19 cases in a country based on multilinear regression and neural networks models. The models are trained on data from US states and tested against the reported infections in the European countries. The model is based on four features: Number of tests Population Percentage Urban Population and Gini index. The population and number of tests have the strongest correlation with the number of infections. The model was then tested on data from European countries for which the correlation coefficient between the actual and predicted cases R2 was found to be 0.88 in the multi linear regression and 0.91 for the neural network model. The model predicts that the actual number of infections in countries where the number of tests is less than 10% of their populations is at least 26 times greater than the reported numbers.
A global dataset of seaweed net primary productivity
Authors: Pessarrodona Albert , Filbee-Dexter Karen , Krumhansl Kira A. , Moore Pippa J. , Wernberg Thomas
Published: July 2021

Net primary productivity (NPP) plays a pivotal role in the global carbon balance, but estimating the NPP of underwater habitats remains a challenging task. Seaweeds (marine macroalgae) form the largest and most productive underwater vegetated habitat on Earth. Yet, little is known about the distribution of their NPP at large spatial scales, despite more than 70 years of local-scale studies being scattered throughout the literature. We present a global dataset containing NPP records for 242 seaweed species at 419 individual sites distributed on all continents from the intertidal to 55 m depth. All records are standardized to annual aerial carbon production (g C m-2yr-1) and are accompanied by detailed taxonomical and methodological information. The dataset presented here provides a basis for local, regional and global comparative studies of the NPP of underwater vegetation, and is pivotal for achieving a better understanding of the role seaweeds play in the global coastal carbon cycle.
Single-cell multi-omic analysis of thymocyte development reveals drivers of CD4/CD8 lineage commitment
Authors: Steier Zoë , Aylard Dominik A. , McIntyre Laura L. , Baldwin Isabel , Yoon Kim Esther Jeong , Lutes Lydia K. , Ergen Can , Huang Tse-Shun , Robey Ellen A. , Yosef Nir , Streets Aaron
Published: July 2021

The development of CD4 and CD8 T cells in the thymus is critical to adaptive immunity and is widely studied as a model of lineage commitment. Recognition of self-MHCI/II by the T cell antigen receptor (TCR) determines the lineage choice, but how distinct TCR signals drive transcriptional programs of lineage commitment remains largely unknown. We applied CITE-seq to measure RNA and surface proteins in thymocytes from wild-type and lineage-restricted mice to generate a comprehensive timeline of cell state for each lineage. These analyses revealed a sequential process whereby all thymocytes initiate CD4 lineage differentiation during an initial wave of TCR signaling, followed by a second TCR signaling wave that coincides with CD8 lineage specification. CITE-seq and pharmaceutical inhibition experiments implicate a TCR/calcineurin/NFAT/GATA3 axis in driving the CD4 fate. Overall, our data suggest that multiple redundant mechanisms contribute to the accuracy and efficiency of the lineage choice.
A phage parasite deploys a nicking nuclease effector to inhibit replication of its viral host
Authors: LeGault Kristen N. , Barth Zachary K. , DePaola Peter , Seed Kimberley D.
Published: July 2021

PLEs are phage parasites integrated into the chromosome of epidemicVibrio cholerae. In response to infection by its viral host ICP1, PLE excises, replicates and hijacks ICP1 structural components for transduction. Through an unknown mechanism PLE prevents ICP1 from transitioning to rolling circle replication (RCR), a prerequisite for efficient packaging of the viral genome. Here, we characterize a PLE-encoded nuclease, NixI, that blocks phage development likely by nicking ICP1’s genome as it transitions to RCR. NixI-dependent cleavage sites appear in ICP1’s genome during infection of PLE(+)V. cholerae. Purified NixI demonstratesin vitrospecificity for sites in ICP1’s genome and NixI activity is enhanced by a putative specificity determinant co-expressed with NixI during phage infection. Importantly, NixI is sufficient to limit ICP1 genome replication and eliminate progeny production. We identify distant NixI homologs in an expanded family of putative phage satellites in Vibrios that lack nucleotide homology to PLEs but nonetheless share genomic synteny with PLEs. More generally, our results reveal a previously unknown mechanism deployed by phage parasites to limit packaging of their viral hosts’ genome and highlight the prominent role of nuclease effectors as weapons in the arms race between antagonizing genomes.
2’,3’-cAMP treatment mimics stress molecular response inArabidopsis thaliana
Authors: Chodasiewicz Monika , Kerber Olga , Gorka Michal , Moreno Juan C. , Maruri-Lopez Israel , Minen Romina I. , Sampathkumar Arun , Nelson Andrew D. L. , Skirycz Aleksandra
Published: July 2021

The role of the RNA degradation product 2’,3’-cyclic adenosine monophosphate (2’,3’-cAMP) is poorly understood. Recent studies have identified 2’,3’-cAMP in plant material and determined its role in stress signaling. The level of 2’,3’-cAMP increases upon wounding, dark, and heat, and 2’,3’-cAMP by binding to an RNA-binding protein, Rbp47b, promotes stress granule (SG) assembly. To gain further mechanistic insight into 2’,3’-cAMP function, we used a multi-omics approach combining transcriptomics, metabolomics, and proteomics to dissectArabidopsisresponse to 2’,3’-cAMP treatment. We demonstrated that 2’,3’-cAMP is metabolized into adenosine, suggesting that the well-known cyclic nucleotide–adenosine pathway from human cells might also exist in plants. Transcriptomic analysis revealed only minor overlap between 2’,3’-cAMP-and adenosine-treated plants, suggesting that these molecules act through independent mechanisms. Treatment with 2’,3’-cAMP changed the levels of hundreds of transcripts, proteins, and metabolites, many previously associated with plant stress responses including protein and RNA degradation products, glucosinolates, chaperones and SG components. Finally, we demonstrated that 2’,3’-cAMP treatment influences the movement of processing bodies, supporting the role of 2’,3’-cAMP in the formation and motility of membraneless organelles.
VirB4- and VirD4-like ATPases, components of a putative type 4C secretion system in Clostridioides difficile
Authors: Sorokina Julya , Sokolova Irina , Rybolovlev Ivan , Shevlyagina Natalya , Troitskiy Vasiliy , Zhukhovitsky Vladimir , Belyi Yury
Published: July 2021

The type 4 secretion system (T4SS) represents a bacterial nanomachine capable of trans-cell wall transportation of proteins and DNA and which has attracted intense interest due to its roles in the pathogenesis of infectious diseases. During the current investigation we uncovered three distinct gene clusters in Clostridioides difficile strain 630 coding for proteins structurally related to components of the VirB4/D4 type 4C secretion system from Streptococcus suis strain 05ZYH33 and located within sequences of conjugative transposons (CTn). Phylogenic analysis shows that VirB4- and VirD4-like proteins of CTn4 locus, on one hand, and those of CTn2 and CTn5 loci, on the other hand, fit into separate clades, suggesting specific roles of identified secretion system variants in physiology of C. difficile. Our further study on VirB4- and VirD4-like products coded by CTn4 revealed that both proteins possess Mg2+-dependent ATPase activity, form oligomers (most probably, hexamers) in water solutions, and rely on potassium but not sodium ions for the highest catalytic rate. VirD4 binds nonspecifically to DNA and RNA. Its DNA binding activity strongly decreased with the W241A variant. Mutations in the nucleotide sequences coding for presumable Walker A and Walker B motifs decreased stability of the oligomers and significantly but not completely attenuated enzymatic activity of VirB4. In VirD4, substitutions of amino acid residues in the peptides reminiscent of Walker structural motifs resulted neither in attenuation of enzymatic activity of the protein nor influenced the oligomerization state of the ATPase.

Importance

C. difficile is a Gram-positive, anaerobic, spore-forming bacterium that causes life-threatening colitis in humans. Major virulence factors of the microorganism include toxins TcdA, TcdB and CDT. However, other bacterial products, including a type 4C secretion system, have been hypothesized to contribute to the pathogenesis of the infection and are considered as possible virulence factors of C. difficile. In the current paper we describe structural organization of putative T4SS machinery in C. difficile and characterize its VirB4- and VirD4-like components. Our studies, in addition to significance for basic science, can potentially aid development of anti-virulence drugs suitable for treatment of C. difficile infection.
Bacterial microcompartments for isethionate desulfonation in the taurine-degrading human-gut bacteriumBilophila wadsworthia
Authors: Burrichter Anna G. , Dörr Stefanie , Bergmann Paavo , Haiß Sebastian , Keller Anja , Fournier Corentin , Franchini Paolo , Isono Erika , Schleheck David
Published: July 2021

Background

Bilophila wadsworthia, a strictly anaerobic, sulfite-reducing bacterium and common member of the human gut microbiota, has been associated with diseases such as appendicitis and colitis. It is specialized on organosulfonate respiration for energy conservation, i.e., utilization of dietary and host-derived organosulfonates, such as taurine (2-aminoethansulfonate), as sulfite donors for sulfite respiration, producing hydrogen sulfide (H2S), an important intestinal metabolite that may have beneficial as well as detrimental effects on the colonic environment. Its taurine desulfonation pathway involves a glycyl radical enzyme (GRE), isethionate sulfite-lyase (IslAB), which cleaves isethionate (2-hydroxyethane sulfonate) into acetaldehyde and sulfite.

Results

We demonstrate that taurine metabolism inB. wadsworthia3.1.6 involves bacterial microcompartments (BMCs). First, we confirmed taurine-inducible production of BMCs by proteomic, transcriptomic and ultra-thin sectioning and electron-microscopical analyses. Then, we isolated BMCs from taurine-grown cells by density-gradient ultracentrifugation and analyzed their composition by proteomics as well as by enzyme assays, which suggested that the GRE IslAB and acetaldehyde dehydrogenase are located inside of the BMCs. Finally, we are discussing the recycling of cofactors in the IslAB-BMCs and a potential shuttling of electrons across the BMC shell by a potential ironsulfur (FeS) cluster-containing shell protein identified by sequence analysis.

Conclusions

We characterized a novel subclass of BMCs and broadened the spectrum of reactions known to take place enclosed in BMCs, which is of biotechnological interest. We also provided more details on the energy metabolism of the opportunistic pathobiontB. wadsworthiaand on microbial H2S production in the human gut.
MetaFun: Unveiling Sex-based Differences in Multiple Transcriptomic Studies through Comprehensive Functional Meta-analysis
Authors: Malmierca-Merlo Pablo , Sánchez-Garcia Rubén , Grillo-Risco Rubén , Pérez-Díez Irene , Català-Senent José F. , Leon Santiago , Gómez-Martínez Helena , de la Iglesia-Vayá María , Hidalgo Marta R. , Garcia-Garcia Francisco
Published: July 2021

While sex-based differences in various health scenarios have been thoroughly acknowledged in the literature, we lack a deep analysis of sex as a variable in this context. To fill this knowledge gap, we created MetaFun as an easy-to-use web-based tool to meta-analyze multiple transcriptomic datasets with a sex-based perspective to gain major statistical power and biological soundness. Furthermore, MetaFun can be used to perform case-control meta-analyses, allowing researchers with basic programming skills to access this methodology.

Availability and implementation

MetaFun is freely available athttp://bioinfo.cipf.es/metafunThe back end was implemented in R and Java, and the front end was developed using Angular

Contact

fgarcia@cipf.es,mhidalgo@cipf.es

Supplementary information

R code available athttps://gitlab.com/ubb-cipf/metafunr
Robust Acquisition of High Resolution Spatial Transcriptomes from Preserved Tissues with Immunofluorescence Based Laser Capture Microdissection
Authors: Zhang Xiaodan , Hu Chuansheng , Huang Chen , Wei Ying , Li Xiaowei , Hu Miaomiao , Li Hua , Wu Ji , Czajkowsky Daniel M. , Guo Yan , Shao Zhifeng
Published: July 2021

The functioning of tissues is fundamentally dependent upon not only the phenotypes of the constituent cells but also their spatial organization in the tissue. However, acquisition of comprehensive transcriptomes of spatially- and phenotypically-defined cells in situ remains challenging. Here we present a general and robust method based on immunofluorescence-guided laser capture microdissection (immuno-LCM-RNAseq) to acquire finely resolved spatial transcriptomes including isoforms with as few as tens of cells from snap-frozen or RNAlater-treated clinical tissues, circumventing the problem of significant RNA degradation during this time-consuming process. The efficacy of this approach is exemplified by the characterization of differences at the transcript isoform level between the mouse small intestine lacteal cells at the tip versus the main capillary body. With the extensive repertoire of specific antibodies that are presently available, our method provides a powerful means by which spatially resolved cellular states can now be delineated in situ with preserved tissues. Moreover, such high quality spatial transcriptomes defined by immunomarkers can be used to compare with the phenotypes derived from single-cell RNAseq of dissociated cells as well as applied to bead-based spatial transcriptomic approaches that require such information a priori for cell identification.
Adaptation, spread and transmission of SARS-CoV-2 in farmed minks and related humans in the Netherlands
Authors: Lu Lu , Sikkema Reina S. , Velkers Francisca C. , Nieuwenhuijse David F. , Fischer Egil A.J. , Meijer Paola A. , Bouwmeester-Vincken Noortje , Rietveld Ariene , Wegdam-Blans Marjolijn C.A. , Tolsma Paulien , Koppelman Marco , Smit Lidwien A.M. , Hakze-van der Honing Renate W. , van der Poel Wim H. M. , van der Spek Arco N. , Spierenburg Marcel A. H. , Molenaar Robert Jan , de Rond Jan , Augustijn Marieke , Woolhouse Mark , Stegeman J. Arjan , Lycett Samantha , Oude Munnink Bas B. , Koopmans Marion P. G.
Published: July 2021

In the first wave of the COVID-19 pandemic (April 2020), SARS-CoV-2 was detected in farmed minks and genomic sequencing was performed on mink farms and farm personnel. Here, we describe the outbreak and use sequence data with Bayesian phylodynamic methods to explore SARS-CoV-2 transmission in minks and related humans on farms. High number of farm infections (68/126) in minks and farm related personnel (>50% of farms) were detected, with limited spread to the general human population. Three of five initial introductions of SARS-CoV-2 lead to subsequent spread between mink farms until November 2020. The largest cluster acquired a mutation in the receptor binding domain of the Spike protein (position 486), evolved faster and spread more widely and longer. Movement of people and distance between farms were statistically significant predictors of virus dispersal between farms. Our study provides novel insights into SARS-CoV-2 transmission between mink farms and highlights the importance of combing genetic information with epidemiological information at the animal-human interface.