bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between house height and mosquito house entry: an experimental study in rural Gambia
Authors: Carrasco-Tenezaca Majo , Jawara Musa , Abdi Mahamed Y. , Bradley John , Brittain Otis Sloan , Ceesay Sainey , D'Alessandro Umberto , Jeffries David , Pinder Margaret , Wood Hannah , Knudsen Jakob B. , Lindsay Steve W.
Published: May 2021

Most malaria infections in sub-Saharan Africa are acquired indoors, thus finding effective ways of preventing mosquito house entry should reduce transmission. Since most malaria mosquitoes fly less than 1 m from the ground, we tested whether raising buildings off the ground would prevent the entry of
Anopheles gambiae
, the principal African malaria vector, in rural Gambia. Nightly collections of mosquitoes were made using light traps from four inhabited experimental huts, each of which could be moved up or down. Mosquito house entry declined with increasing height, with a hut at 3 m reducing
An. gambiae
house entry by 84% when compared with huts on the ground. A propensity for malaria vectors to fly close to the ground and reduced levels of carbon dioxide, a major mosquito attractant, in elevated huts, may explain our findings. Raised buildings may help reduce malaria transmission in Africa.
Coordination of gene expression noise with cell size: analytical results for agent-based models of growing cell populations
Authors: Thomas Philipp , Shahrezaei Vahid
Published: May 2021

The chemical master equation and the Gillespie algorithm are widely used to model the reaction kinetics inside living cells. It is thereby assumed that cell growth and division can be modelled through effective dilution reactions and extrinsic noise sources. We here re-examine these paradigms through developing an analytical agent-based framework of growing and dividing cells accompanied by an exact simulation algorithm, which allows us to quantify the dynamics of virtually any intracellular reaction network affected by stochastic cell size control and division noise. We find that the solution of the chemical master equation—including static extrinsic noise—exactly agrees with the agent-based formulation when the network under study exhibits
stochastic concentration homeostasis
, a novel condition that generalizes concentration homeostasis in deterministic systems to higher order moments and distributions. We illustrate stochastic concentration homeostasis for a range of common gene expression networks. When this condition is not met, we demonstrate by extending the linear noise approximation to agent-based models that the dependence of gene expression noise on cell size can qualitatively deviate from the chemical master equation. Surprisingly, the total noise of the agent-based approach can still be well approximated by extrinsic noise models.
On a class of integrable Hamiltonian equations in 2+1 dimensions
Authors: Gormley Ben , Ferapontov Eugene V. , Novikov Vladimir S.
Published: May 2021

We classify integrable Hamiltonian equations of the form

u
t

=

∂
x

(

δ
H

δ
u

)

,

H
=
∫
h
(
u
,
w
)
 

d

x

d

y
,

where the Hamiltonian density
h
(
u
,
w
) is a function of two variables: dependent variable
u
and the non-locality

w
=

∂
x

−
1

∂
y

u

. Based on the method of hydrodynamic reductions, the integrability conditions are derived (in the form of an involutive PDE system for the Hamiltonian density
h
). We show that the generic integrable density is expressed in terms of the Weierstrass
σ
-function:
h
(
u
,
w
) = 
σ
(
u
) e

w

. Dispersionless Lax pairs, commuting flows and dispersive deformations of the resulting equations are also discussed.
On stretch-limited elastic strings
Authors: Rodriguez Casey
Published: May 2021

Motivated by the increased interest in modelling non-dissipative materials by constitutive relations more general than those from Cauchy elasticity, we initiate the study of a class of
stretch-limited elastic strings
: the string cannot be compressed smaller than a certain length less than its natural length nor elongated larger than a certain length greater than its natural length. In particular, we consider equilibrium states for a string suspended between two points under the force of gravity (catenaries). We study the locations of the supports resulting in tensile states containing both extensible and inextensible segments in two situations: the degenerate case when the string is vertical and the non-degenerate case when the supports are at the same height. We then study the existence and multiplicity of equilibrium states in general with multiplicity differing markedly from strings satisfying classical constitutive relations.
Agri-environment scheme nectar chemistry can suppress the social epidemiology of parasites in an important pollinator
Authors: Folly Arran J. , Koch Hauke , Farrell Iain W. , Stevenson Philip C. , Brown Mark J. F.
Published: May 2021

Emergent infectious diseases are one of the main drivers of species loss. Emergent infection with the microsporidian
Nosema bombi
has been implicated in the population and range declines of a suite of North American bumblebees, a group of important pollinators. Previous work has shown that phytochemicals found in pollen and nectar can negatively impact parasites in individuals, but how this relates to social epidemiology and by extension whether plants can be effectively used as pollinator disease management strategies remains unexplored. Here, we undertook a comprehensive screen of UK agri-environment scheme (AES) plants, a programme designed to benefit pollinators and wider biodiversity in agricultural settings, for phytochemicals in pollen and nectar using liquid chromatography and mass spectrometry. Caffeine, which occurs across a range of plant families, was identified in the nectar of sainfoin (
Onobrychis viciifolia
), a component of UK AES and a major global crop. We showed that caffeine significantly reduces
N. bombi
infection intensity, both prophylactically and therapeutically, in individual bumblebees (
Bombus terrestris
), and, for the first time, that such effects impact social epidemiology, with colonies reared from wild-caught queens having both lower prevalence and intensity of infection. Furthermore, infection prevalence was lower in foraging bumblebees from caffeine-treated colonies, suggesting a likely reduction in population-level transmission. Combined, these results show that
N. bombi
is less likely to be transmitted intracolonially when bumblebees consume naturally available caffeine, and that this may in turn reduce environmental prevalence. Consequently, our results demonstrate that floral phytochemicals at ecologically relevant concentrations can impact pollinator disease epidemiology and that planting strategies that increase floral abundance to support biodiversity could be co-opted as disease management tools.
Landscape complexity promotes resilience of biological pest control to climate change
Authors: Feit Benjamin , Blüthgen Nico , Daouti Eirini , Straub Cory , Traugott Michael , Jonsson Mattias
Published: May 2021

Increased climate variability as a result of anthropogenic climate change can threaten the functioning of ecosystem services. However, diverse responses to climate change among species (response diversity) can provide ecosystems with resilience to this growing threat. Measuring and managing response diversity and resilience to global change are key ecological challenges. Here, we develop a novel index of climate resilience of ecosystem services, exemplified by the thermal resilience of predator communities providing biological pest control. Field assays revealed substantial differences in the temperature-dependent activity of predator species and indices of thermal resilience varied among predator communities occupying different fields. Predator assemblages with higher thermal resilience provided more stable pest control in microcosms where the temperature was experimentally varied, confirming that the index of thermal resilience developed here is linked to predator function. Importantly, complex landscapes containing a high number of non-crop habitat patches were more likely to contain predator communities with high thermal resilience. Thus, the conservation and restoration of non-crop habitats in agricultural landscapes—practices known to strengthen natural pest suppression under current conditions—will also confer resilience in ecosystem service provisioning to climate change.
Parasitic wasps do not lack lipogenesis
Authors: Ruther Joachim , Prager Lorena , Pokorny Tamara
Published: May 2021

Fatty acids are crucial primary metabolites for virtually all creatures on earth. Most organisms thus do not rely exclusively on a nutritional supply containing fatty acids, but have the ability to synthesize fatty acids and triacylglycerides de novo from carbohydrates in a process called lipogenesis. The ubiquity of lipogenesis has been questioned by a series of studies reporting that many parasitic wasps (parasitoids) do not accumulate lipid mass despite having unlimited access to sugar. This has been interpreted as an evolutionary metabolic trait loss in parasitoids. Here, we demonstrate de novo biosynthesis of fatty acids from
13
C-labelled α-
d
-glucose in 13 species of parasitoids from seven families. We furthermore show in the model organism
Nasonia vitripennis
that lipogenesis occurs even when lipid reserves are still intact, but relative
13
C-incorporation rates increase in females with widely depleted fat reserves. We therefore conclude that the presumed ‘lack of lipogenesis' in parasitoids needs to be re-evaluated.
Spatio-temporal variation in the wintering associations of an alpine bird
Authors: del Mar Delgado María , Arlettaz Raphaël , Bettega Chiara , Brambilla Mattia , de Gabriel Hernando Miguel , España Antonio , Fernández-González Ángel , Fernández-Martín Ángel , Gil Juan Antonio , Hernández-Gómez Sergio , Laiolo Paola , Resano-Mayor Jaime , Obeso José Ramón , Pedrini Paolo , Roa-Álvarez Isabel , Schano Christian , Scridel Davide , Strinella Eliseo , Toranzo Ignasi , Korner-Nievergelt Fränzi
Published: May 2021

Many animals make behavioural changes to cope with winter conditions, being gregariousness a common strategy. Several factors have been invoked to explain why gregariousness may evolve during winter, with individuals coming together and separating as they trade off the different costs and benefits of living in groups. These trade-offs may, however, change over space and time as a response to varying environmental conditions. Despite its importance, little is known about the factors triggering gregarious behaviour during winter and its change in response to variation in weather conditions is poorly documented. Here, we aimed at quantifying large-scale patterns in wintering associations over 23 years of the white-winged snowfinchMontifringilla nivalis nivalis. We found that individuals gather in larger groups at sites with harsh wintering conditions. Individuals at colder sites reunite later and separate earlier in the season than at warmer sites. However, the magnitude and phenology of wintering associations are ruled by changes in weather conditions. When the temperature increased or the levels of precipitation decreased, group size substantially decreased, and individuals stayed united in groups for a shorter time. These results shed light on factors driving gregariousness and points to shifting winter climate as an important factor influencing this behaviour.
Conventional PCR as a reliable method for diagnosing invasive mucormycosis in resource-limited settings
Authors: Pandey Mragnayani , Xess Immaculata , Singh Gagandeep , Kumar Rakesh , Mahapatra Manoranjan , Jyotsna Viveka P. , Agarwal Reshu , Ghosh Arnab , Iram Azka , Mani Prashant
Published: May 2021

Introduction.Invasive mucormycosis (IM) is a life-threatening infection caused by fungi belonging to the order Mucorales. Histopathology, culture and radiology are the mainstay of diagnosis but lack sensitivity, leading to a delay in timely diagnosis and intervention. Recently, PCR-based approaches have been shown to be a promising method in diagnosing IM.

Hypothesis/Gap Statement.Molecular-based approaches may be a valuable adjunct to standard conventional methods for diagnosing IM, especially among culture negatives and patients on antifungal therapy.

Aim.In the present study we aimed to evaluate the clinical utility of panfungal and Mucorales-specific PCR for diagnosing IM from various clinical specimens.

Methodology.This was a prospective study in which 239 clinically suspected cases of IM attending our tertiary care hospital from August 2015 to March 2018 were enrolled. All the cases were defined as ‘proven’, ‘probable’ or ‘possible’ based on EORTC/MSGERC guidelines. In addition to conventional diagnostics (KOH-calcofluor stain and culture), panfungal and Mucorales-specific PCR assays were also performed. The amplified products were sequenced for species identification.In vitroantifungal susceptibility was performed on all the culture-positive isolates.

Results.Among 239 clinically suspected cases of IM, only 140 cases were diagnosed by the demonstration of aseptate ribbon-like hyphae on direct microscopy. Culture was positive in 35.7 % (54/140) of direct microscopy-positive samples. Among the proven cases (n=11), the sensitivity for both Mucorales-specific nested PCR and panfungal PCR was 100 %, but specificity was 91.9 and 73.7% respectively. In probable cases (n=129), the sensitivity of both the PCRs was 98.5 % and specificity for panfungal PCR was 73.7 and 91.9 % for Mucorales-specific PCR.

Conclusion.Pan fungal PCR in combination with Mucorales-specific PCR, followed by sequencing, may play a significant role in IM diagnosis especially among those negative for both direct microscopy and culture.
Systematic Review and Meta-Analysis Protocol: Beta adrenoreceptor drugs and risk of Parkinson’s disease
Authors: Singh Ambrish , Hussain Salman , Akkala Sreelatha , Klugarová Jitka , Pokorná Andrea , Klugar Miloslav , Antony Benny
Published: May 2021

Parkinson’s disease (PD) is a progressive nervous system disorder characterised by the loss of dopaminergic neurons leading to motor and non-motor symptoms. Accumulation of α-synuclein protein (SNCA) in the form of Lewy bodies has been observed in dopaminergic neurons of PD patients. Potential relationships between β-adrenergic drugs (agonists and antagonist) and SNCA synthesis in PD have been recently suggested. This study aims to systematically review the evidence from various epidemiological studies that analysed the association between beta-adrenoceptors (agonists and antagonists) and the risk of PD. Biomedical databases such as PubMed and Embase will be searched to identify the individual studies that reported the relationship between beta-adrenoceptors and the risk of PD. JBI critical appraisal tool scale will be used to assess the quality of included studies. The primary outcome will be to compute the pooled risk of PD among beta-agonist and antagonist users. Furthermore, we will consider the pooled risk of PD based on study design, types of beta-agonist or antagonist exposure under secondary outcomes. RevMan 5, STATA 16, and ProMeta 3.0 will be used to conduct the statistical analysis.
Forecasting seizure likelihood with wearable technology
Authors: Stirling Rachel E. , Grayden David B. , D’Souza Wendyl , Cook Mark J. , Nurse Ewan , Freestone Dean R. , Payne Daniel E. , Brinkmann Benjamin H. , Attia Tal Pal , Viana Pedro F. , Richardson Mark P. , Karoly Philippa J.
Published: May 2021

The unpredictability of epileptic seizures exposes people with epilepsy to potential physical harm, restricts day-to-day activities, and impacts mental well-being. Accurate seizure forecasters would reduce the uncertainty associated with seizures but need to be feasible and accessible in the long-term. Wearable devices are perfect candidates to develop non-invasive, accessible forecasts but are yet to be investigated in long-term studies. We hypothesized that machine learning models could utilize heart rate as a biomarker for well-established cycles of seizures and epileptic activity, in addition to other wearable signals, to forecast high and low risk seizure periods.

This feasibility study tracked participants’ (n = 11) heart rates, sleep, and step counts using wearable smartwatches and seizure occurrence using mobile seizure diaries for at least 6 months (mean = 14.6 months, SD = 3.8 months). Eligible participants had a diagnosis of refractory epilepsy and reported at least 20 seizures (mean = 135, SD = 123) during the recording period. An ensembled machine learning and neural network model estimated seizure risk either daily or hourly, with retraining occurring on a weekly basis as additional data was collected. Performance was evaluated retrospectively against a rate-matched random forecast using the area under the receiver operating curve. A pseudo-prospective evaluation was also conducted on a held-out dataset.

Of the 11 participants, seizures were predicted above chance in all (100%) participants using an hourly forecast and in ten (91%) participants using a daily forecast. The average time spent in high risk (prediction time) before a seizure occurred was 37 minutes in the hourly forecast and 3 days in the daily forecast. Cyclic features added the most predictive value to the forecasts, particularly circadian and multiday heart rate cycles.

Wearable devices can be used to produce patient-specific seizure forecasts, particularly when biomarkers of seizure and epileptic activity cycles are utilized.
Reduced Intrinsic Neural Timescales in Schizophrenia along Posterior Parietal and Occipital Areas
Authors: Uscătescu Lavinia Carmen , Said-Yürekli Sarah , Kronbichler Lisa , Stelzig-Schöler Renate , Pearce Brandy-Gale , Reich Luise Antonia , Weber Stefanie , Aichhorn Wolfgang , Kronbichler Martin
Published: May 2021

We computed intrinsic neural timescales (INT) based on resting state functional magnetic resonance imaging (rsfMRI) data of healthy controls (HC) and patients with schizophrenia spectrum disorder (SZ) from three independently collected samples. Five clusters showed decreased INT in SZ compared to HC in all three samples: Right occipital fusiform gyrus (rOFG), Left superior occipital gyrus (lSOG), Right superior occipital gyrus (rSOG), Left lateral occipital cortex (lLOC), and Right postcentral gyrus (rPG). In other words, it appears that sensory information in visual and posterior parietal areas is stored for reduced lengths of time in SZ compared to HC. We also found some evidence that symptom severity modulates INT of these areas in SZ.
Statistical Analysis Plan for the Stepped-wedge Cluster Randomized Controlled Trial of Electronic Early Notification of Sepsis in Hospitalized Ward Patients (SCREEN) : a study protocol for a stepped-wedge cluster randomized controlled trial
Authors: Arabi Yaseen M , Vishwakarma Ramesh Kumar , Al-Dorzi Hasan M , Qasim Eman Al , Abdukahil Sheryl Ann , Al-Rabeah Fawaz K , Ghamdi Huda Al , Ghamdi Ebtisam Al ,   the SCREEN Trial Group
Published: May 2021

Background

It is unclear whether screening for sepsis using an electronic alert in hospitalized ward patients improves outcomes. The objective of the SCREEN (Stepped-wedge Cluster Randomized Controlled Trial of Electronic Early Notification of Sepsis in Hospitalized Ward Patients) trial is to evaluate whether an electronic screening for sepsis compared to no screening among hospitalized ward patients reduces all-cause 90-day in-hospital mortality.

Methods and design

This study is designed as a stepped-wedge cluster randomized controlled trial in which the unit of randomization or cluster is the hospital ward. An electronic alert for sepsis was developed in the electronic medical record (EMR), with the feature of being active (visible to treating team) or masked (inactive in EMR frontend for the treating team but active in the backend of the EMR). Forty-five clusters in 5 hospitals are randomized into 9 sequences of 5 clusters each to receive the intervention (active alert) over 10 periods, 2-months each, the first being the baseline period. Data are extracted from EMR and are compared between the intervention (active alert) and control group (masked alert). The primary outcome of all-cause hospital mortality by day 90 will be compared using a generalized linear mixed model with a binary distribution and a log-link function to estimate the relative risk as a measure of effect. We will include two levels of random effects to account for nested clustering within wards and periods and two levels of fixed effects; hospitals and COVID-19 ward status. Results will be expressed as relative risk with a 95% confidence interval (CI).

Conclusion

The SCREEN trial provides an opportunity for a novel trial design and analysis of routinely collected and entered data to evaluate the effectiveness of an intervention (alert) for a common medical problem (sepsis in ward patients). In this statistical analysis plan, we outline details of the planned analyses in advance of trial completion. Prior specification of the statistical methods and outcomes analysis will facilitate unbiased analyses of these important clinical data.

Trial registration

ClinicalTrials.govNCT04078594. Registered on September 6, 2019, https://clinicaltrials.gov/ct2/show/NCT04078594
Addressing anti-syncytin antibody levels, and fertility and breastfeeding concerns, following BNT162B2 COVID-19 mRNA vaccination
Authors: Mattar Citra NZ , Koh Winston , Seow Yiqi , Hoon Shawn , Venkatesh Aparna , Dashraath Pradip , Lim Li Min , Ong Judith , Lee Rachel , Johana Nuryanti , Yeo Julie SL , Chong David , Tan Lay-Kok , Chan Jerry , Choolani Mahesh , Tambyah Paul Anantharajah
Published: May 2021

Objective

To determine whether antibodies against the SARS-CoV-2 spike protein following BNT162B2 (Pfizer-BioNTech) COVID-19 mRNA vaccination cross-react with human syncytin-1 protein, and if BNT162B2 mRNA enters breast milk.

Methods

In this observational cohort study of female front-line workers with no history of COVID-19 infection, we amplified BNT162B2 mRNA in plasma and breast milk and assayed anti-SARS-CoV-2 neutralising antibodies and anti-human syncytin-1 binding antibodies in plasma, at early (1-4 days) and late (4-7 weeks) time points following first-dose vaccination.

Results

Fifteen consented participants (mean age 40.4 years, various ethnicities) who received at least one dose of BNT162B2, including five breast-feeding women and two women who were inadvertently vaccinated in early pregnancy, were recruited. BNT162B2 mRNA, detected by amplifying part of the spike-encoding region, was detected in plasma 1-4 days following the first dose (n=13), but not 4-5 weeks later (n=2), nor was the mRNA isolated from aqueous or lipid breast milk fractions collected 0-7 days post-vaccination (n=5). Vaccine recipients demonstrated strong SARS-CoV-2 neutralising activity by at least four weeks after the first dose (n=15), including the two pregnant women. None had placental anti-syncytin-1 binding antibodies at either time-point following vaccination.

Conclusions

BNT162B2-vaccinated women did not transmit vaccine mRNA to breast milk, and did not produce a concurrent humoral response to syncytin-1, suggesting that cross-reactivity to syncytin-1 on the developing trophoblast, or other adverse effects in the breast-fed infant from vaccine mRNA ingestion, are unlikely.

What are the novel findings of this work?

COVID-19 vaccination with BNT162B2 did not elicit a cross-reacting humoral response to human syncytin-1 despite robust neutralising activity to the SARS-CoV2 spike protein, and while vaccine mRNA was isolated from plasma, it was not found in breast milk.

What are the clinical implications of this work?

Our work directly addresses the fertility and breastfeeding concerns fuelling vaccine hesitancy among reproductive-age women, by suggesting that BNT162B2 vaccination is unlikely to cause adverse effects on the developing trophoblast, via cross-reacting anti-syncytin-1 antibodies, or to the breastfed neonate, via mRNA breast milk transmission.
Comprehensive assessment of Indian variations in the druggable kinome landscape highlights distinct insights at the sequence, structure and pharmacogenomic stratum
Authors: Panda Gayatri , Mishra Neha , Sharma Disha , Kutum Rintu , Bhoyar Rahul C. , Jain Abhinav , Imran Mohamed , Senthilvel Vigneshwar , Divakar Mohit Kumar , Mishra Anushree , Garg Parth , Banerjee Priyanka , Sivasubbu Sridhar , Scaria Vinod , Ray Arjun
Published: May 2021

India confines more than 17% of the world’s population and has a diverse genetic makeup with several clinically relevant rare mutations belonging to many sub-group which are undervalued in global sequencing datasets like the 1000 Genome data (1KG) containing limited samples for Indian ethnicity. Such databases are critical for the pharmaceutical and drug development industry where the diversity plays a crucial role in identifying genetic disposition towards adverse drug reactions. A qualitative and comparative sequence and structural study utilizing variant information present in the recently published, largest curated Indian genome database (IndiGen) and the 1000 Genome data was performed for variants belonging to the kinase coding genes,the second most targeted group of drug targets. The sequence level analysis identified similarities and differences among different populations based on the nsSNVs and amino acid exchange frequencies whereas comparative structural analysis of IndiGen variants was performed with pathogenic variants reported in UniProtKB Humsavar data. The influence of these variations on structural features of the protein, such as structural stability, solvent accessibility, hydrophobicity, and the hydrogen-bond network were investigated. In-silico screening of the known drugs to these Indian variation-containing proteins reveal critical differences imparted in the strength of binding due to the variations present in the Indian population. In conclusion, this study constitutes a comprehensive investigation into the understanding of common variations present in the second largest population in the world, and investigating its implications in the sequence, structural and pharmacogenomic landscape. The preliminary investigation reported in this paper, supporting the screening and detection of ADRs specific to the Indian population could aid in the development of techniques for pre-clinical and post-market screening of drug-related adverse events in the Indian population.
Blood-based epigenome-wide analyses of cognitive abilities
Authors: McCartney Daniel L. , Hillary Robert F. , Conole Eleanor L. S. , Banos Daniel Trejo , Gadd Danni A. , Walker Rosie M. , Nangle Cliff , Flaig Robin , Campbell Archie , Murray Alison D. D. , Maniega Susana Muñoz , Valdés-Hernández María del. C , Harris Mathew A. , Bastin Mark E. , Wardlaw Joanna M. , Harris Sarah E. , Porteous David J. , Tucker-Drob Elliot M. , McIntosh Andrew M. , Evans Kathryn L. , Deary Ian J. , Cox Simon R. , Robinson Matthew R. , Marioni Riccardo E.
Published: May 2021

Using blood-based epigenome-wide analyses of general cognitive function (g; n=9,162) we show that individual differences in DNA methylation (DNAm) explain 35.0% of the variance in g. A DNAm predictor explains ∼4% of the variance in g, independently of a polygenic score, in two external cohorts. It also associates with circulating levels of neurology- and inflammation-related proteins, global brain imaging metrics, and regional cortical volumes. As sample sizes increase, our ability to assess cognitive function from DNAm data may be informative in settings where cognitive testing is unreliable or unavailable.
PUBLIC HOSPITALS PREPAREDNESS IN THE PROVISION OF BREAST AND CERVICAL CANCER SERVICES IN BUSIA AND TRANS-NZOIA COUNTIES IN KENYA
Authors: Itsura Peter , Mwaura Grace W. , Limo Obed K. , Lwande Gerald O. , Too Kenneth , Mugo Richard , Mwangi Ann W. , Kirui Nicholas , Tonui Philip , Gathecha Gladwell , Nyangasi Mary , Kamano Jemimah , Aruasa Wilson
Published: May 2021

Cancer is a major cause of morbidity and mortality globally. This study aimed to determine the preparedness of public health care facilities in the provision of breast and cervical cancer services by assessing healthcare provider’s knowledge on risk factors, screening, symptoms, diagnosis and treatment of the diseases as well as availability of medical equipment required in their management in Western Kenya. This was achieved by using a cross-sectional service provision assessment (SPA) baseline survey technique in Busia and Trans-Nzoia counties of Western Kenya between October and December 2018. Data was collected using an interviewer-assisted questionnaires from healthcare workers, while a structured facility questionnaire was used to assess the level of preparedness of the selected public healthcare facilities. We enrolled 73 healthcare workers 37 (50.6%) of whom were nurses, followed by clinical officers and medical officers. The highest proportion of knowledge on risk factors and screening of breast and cervical cancer was reported among medical officers and consultant physicians while nurses scored highly on the symptoms of breast and cervical cancer. The medical equipment required for breast and cervical cancer screening and diagnosis were found in most healthcare facilities; however, none of them had core-biopsy needles. A single LEEP equipment was found in a health center within Trans Nzoia County while two LEEP equipment were stationed at the Busia county hospital. We report a below average level of knowledge on breast and cervical cancer among the healthcare workers at public healthcare facilities in both Busia and Trans Nzoia counties. There was a disparity in the distribution and quantity of priority medical equipment for the screening, diagnosis and treatment of breast and cervical cancer in the two county hospitals. There is need for capacity building among healthcare workers as well as standardization in the distribution and utilization of these medical equipment.
Ultrafast and Reproducible Proteomics from Small Amounts of Heart Tissue Enabled by Azo and timsTOF Pro
Authors: Aballo Timothy J. , Roberts David S. , Melby Jake A. , Buck Kevin M. , Brown Kyle A. , Ge Ying
Published: May 2021

Global bottom-up mass spectrometry (MS)-based proteomics is widely used for protein identification and quantification to achieve a comprehensive understanding of the composition, structure, and function of the proteome. However, traditional sample preparation methods are time-consuming, typically including overnight tryptic digestion, extensive sample clean-up to remove MS-incompatible surfactants, and offline sample fractionation to reduce proteome complexity prior to online liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Thus, there is a need for a fast, robust, and reproducible method for protein identification and quantification from complex proteomes. Herein, we developed an ultrafast bottom-up proteomics method enabled by Azo, a photocleavable, MS-compatible surfactant that effectively solubilizes proteins and promotes rapid tryptic digestion, combined with the Bruker timsTOF Pro, which enables deeper proteome coverage through trapped ion mobility spectrometry (TIMS) and parallel accumulation-serial fragmentation (PASEF) of peptides. We applied this method to analyze the complex human cardiac proteome and identified nearly 4,000 protein groups from as little as 1 mg of human heart tissue in a single one-dimensional LC-TIMS-MS/MS run with high reproducibility. Overall, we anticipate this ultrafast, robust, and reproducible bottom-up method empowered by both Azo and the timsTOF Pro will be generally applicable and greatly accelerate the throughput of large-scale quantitative proteomic studies. Raw data are available via the MassIVE repository with identifier MSV000087476.
Tapping into non-English-language science for the conservation of global biodiversity
Authors: Amano Tatsuya , Espinola Violeta Berdejo , Christie Alec P. , Willott Kate , Akasaka Munemitsu , Báldi András , Berthinussen Anna , Bertolino Sandro , Bladon Andrew J. , Chen Min , Choi Chang-Yong , Dagher Kharrat Magda Bou , de Oliveira Luis G. , Farhat Perla , Golivets Marina , Aranzamendi Nataly Hidalgo , Jantke Kerstin , Kajzer-Bonk Joanna , Aytekin M. Çisel Kemahlı , Khorozyan Igor , Kito Kensuke , Konno Ko , Lin Da-Li , Littlewood Nick , Liu Yang , Liu Yifan , Loretto Matthias-Claudio , Marconi Valentina , Martin Philip , Morgan William H. , Narváez-Gómez Juan P. , Negret Pablo Jose , Nourani Elham , Ochoa Quintero Jose M. , Ockendon Nancy , Ying Oh Rachel Rui , Petrovan Silviu , Piovezan-Borges Ana C. , Pollet Ingrid L. , Ramos Danielle L. , Reboredo Segovia Ana L. , Rivera-Villanueva A. Nayelli , Rocha Ricardo , Rouyer Marie-Morgane , Sainsbury Katherine A. , Schuster Richard , Schwab Dominik , Şekercioğlu Çağan H. , Seo Hemin , Shackelford Gorm , Shinoda Yushin , Smith Rebecca K. , Tao Shan-dar , Tsai Ming-shan , Tyler Elizabeth , Vajna Flóra , Valdebenito José Osvaldo , Vozykova Svetlana , Waryszak Paweł , Zamora-Gutierrez Veronica , Zenni Rafael D. , Zhou Wenjun , Sutherland William J.
Published: May 2021

The widely held assumption that any important scientific information would be available in English underlies the underuse of non-English-language science across disciplines. However, non-English-language science is expected to bring unique and valuable scientific information, especially in disciplines where the evidence is patchy, and for emergent issues where synthesising available evidence is an urgent challenge. Yet such contribution of non-English-language science to scientific communities and the application of science is rarely quantified. Here we show that non-English-language studies provide crucial evidence for informing global biodiversity conservation. By screening 419,680 peer-reviewed papers in 16 languages, we identified 1,234 non-English-language studies providing evidence on the effectiveness of biodiversity conservation interventions, compared to 4,412 English-language studies identified with the same criteria. Relevant non-English-language studies are being published at an increasing rate, and can expand the geographical (by 12-25%) and taxonomic (by 5-32%) coverage of English-language evidence, especially in biodiverse regions, albeit often based on less robust study designs. Our results show that synthesising non-English-language studies is key to overcoming the widespread lack of local, context-dependent evidence and facilitating evidence-based conservation globally. We urge wider disciplines to rigorously reassess the untapped potential of non-English-language science in informing decisions to address other global challenges.
Infection of brain pericytes underlying neuropathology of COVID-19 patients
Authors: Bocci Matteo , Oudenaarden Clara , Sàenz-Sardà Xavier , Simrén Joel , Edén Arvid , Sjölund Jonas , Möller Christina , Gisslén Magnus , Zetterberg Henrik , Englund Elisabet , Pietras Kristian
Published: May 2021

A wide range of neurological manifestations have been associated with the development of COVID-19 following SARS-CoV-2 infection. However, the etiology of the neurological symptomatology is still largely unexplored.

Here, we used state-of-the-art multiplexed immunostaining of human brains (n = 6 COVID-19, median age = 69,5 years; and n = 7 control, median age = 68 years), and demonstrated that expression of the SARS-CoV-2 receptor ACE2 is restricted to a subset of neurovascular pericytes. Strikingly, neurological symptoms were exclusive to, and ubiquitous in, patients that exhibited moderate to high ACE2 expression in peri-vascular cells. Viral particles were identified in the vascular wall and paralleled by peri-vascular inflammation, as signified by T cell and macrophage infiltration. Furthermore, fibrinogen leakage indicated compromised integrity of the blood-brain barrier. Notably, cerebrospinal fluid from an additional 16 individuals (n = 8 COVID-19, median age = 67 years; and n = 8 control, median age = 69,5 years) exhibited significantly lower levels of the pericyte marker PDGFRβ in SARS-CoV-2-infected cases, indicative of disrupted pericyte homeostasis.

We conclude that pericyte infection by SARS-CoV-2 underlies virus entry into the privileged central nervous system space, as well as neurological symptomatology due to peri-vascular inflammation and a locally compromised blood-brain barrier.
SARS-CoV-2 surveillance in Italy through phylogenomic inferences based on Hamming distances derived from functional annotations of SNPs, MNPs and InDels
Authors: Pasquale Adriano Di , Radomski Nicolas , Mangone Iolanda , Calistri Paolo , Lorusso Alessio , Cammà Cesare
Published: May 2021

Background

Faced to the ongoing global pandemic of coronavirus disease, the ‘National Reference Centre for Whole Genome Sequencing of microbial pathogens: database and bioinformatic analysis’ (GENPAT) formally established at the ‘Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise’ (IZSAM) in Teramo (Italy) supports the genomic surveillance of the SARS-CoV-2. In a context of SARS-CoV-2 surveillance needed proper and fast assessment of epidemiological clusters from large amount of samples, the present manuscript proposes a workflow for identifying accurately the PANGOLIN lineages of SARS-CoV-2 samples and building of discriminant minimum spanning trees (MST) bypassing the usual time consuming phylogenomic inferences based on multiple sequence alignment (MSA) and substitution model.

Results

GENPAT constituted two collections of SARS-CoV-2 samples. The samples of the first collection were isolated by IZSAM in the Abruzzo region (Italy), then shotgun sequenced and analyzed in GENPAT (n = 1 592), while those of the second collection were isolated from several Italian provinces and retrieved from the reference Global Initiative on Sharing All Influenza Data (GISAID) (n = 17 201). The main outcomes of the present study showed that (i) GENPAT and GISAID identified identical PANGOLIN lineages, (ii) the PANGOLIN lineages B.1.177 (i.e. historical in Italy) and B.1.1.7 (i.e. ‘UK variant’) are major concerns today in several Italian provinces, and the new MST-based method (iii) clusters most of the PANGOLIN lineages together, (iv) with a higher dicriminatory power than PANGOLIN, (v) and faster that the usual phylogenomic methods based on MSA and substitution model.

Conclusions

The shotgun sequencing efforts of Italian provinces, combined to a structured national system of metagenomics data management, provided support for surveillance SARS-CoV-2 in Italy. We recommend to infer phylogenomic relationships of SARS-CoV-2 variants through an accurate, discriminant and fast MST-based method bypassing the usual time consuming steps related to MSA and substitution model-based phylogenomic inference.
Outpatient Portal Use in Prenatal Care: Differential Use by Race, Risk, and Area Social Determinants of Health Factors
Authors: Singh Priti , Jonnalagadda Pallavi , Morgan Evan , Fareed Naleef
Published: May 2021

Objective

To report the relationship of Outpatient Patient Portal (OPP) use with clinical risk, area social determinants of health (SDoH), and race/ethnicity among pregnant women.

Methods

Regression models predicting overall and individual portal feature use (main effects and interactions) based on key variables were specified using logfiles and clinical data.

Results

Overall OPP use among non-Hispanic Black women or patients who lived in lower SDoH neighborhoods were significantly less. High-risk pregnancy patients were likely to use the OPP more than those with normal-risk pregnancy. We found similar associations with individual OPP features, like the Visit (scheduling) and My Record (test results). We also found significant interactive associations between race, clinical risk, and SDoH. Non-Hispanic Black women living in lower SDoH areas used OPP less than non-Hispanic White women from similar or affluent areas.

Conclusion

More research must be conducted to learn of OPP implications for pregnant women with specific clinical diagnoses.
SARS-CoV-2 Antibody Testing in Healthcare Workers: a comparison of the clinical performance of three commercially available antibody assays
Authors: Allen Niamh , Brady Melissa , Martin Antonio Isidro Carrion , Domegan Lisa , Walsh Cathal , Houlihan Elaine , Kerr Colm , Doherty Lorraine , King Joanne , Doheny Martina , Griffin Damian , Molloy Maria , Dunne Jean , Crowley Vivion , Holmes Philip , Keogh Evan , Naughton Sean , Kelly Martina , O’Rourke Fiona , Lynagh Yvonne , Crowley Brendan , de Gascun Cillian , Holder Paul ,   PRECISE Study Steering Group, Bergin Colm , Fleming Catherine , Ni Riain Una , Conlon Niall
Published: May 2021

SARS-CoV-2 antibodies are an excellent indicator of past COVID-19 infection. As the COVID-19 pandemic progresses, retained sensitivity over time is an important quality in an antibody assay that is to be used for the purpose of population seroprevalence studies.

We compared 5788 healthcare worker (HCW) serum samples on two serological assays (Abbott SARS-CoV-2 anti-nucleocapsid IgG and Roche Anti-SARS-CoV-2 anti-nucleocapsid Total Antibody) and a subset of samples (all Abbott assay positive or grayzone, n=485) on Wantai SARS-CoV-2 anti-spike Antibody ELISA. For 367 samples from HCW with previous PCR-confirmed SARS-CoV-2 infection we correlated the timing of infection with assay results.

Overall seroprevalence was 4.2% on Abbott, 9.5% on Roche. Of those with previously confirmed infection, 41% (150/367) and 95% (348/367) tested positive on Abbott and Roche respectively. At 21 weeks (150 days) after confirmed infection, positivity on Abbott started to decline. Roche positivity was retained for the entire study period (33 weeks). Factors associated (P≤ 0.050) with Abbott seronegativity in those with previous PCR-confirmed infection included sex (male OR0.30;95%CI0.15-0.60), symptom severity (OR0.19 severe symptoms;95%CI0.05-0.61), ethnicity (OR0.28 Asian ethnicity;95%CI0.12-0.60) and time since PCR diagnosis (OR2.06 for infection 6 months previously;95%CI1.01-4.30. Wantai detected all previously confirmed infections.

In our population, Roche detected antibodies up to at least seven months after natural infection with SARS-CoV-2. This may indicate that Roche is better suited than Abbott to population-based studies. Wantai demonstrated high sensitivity but sample selection was biased. The relationship between serological response and functional immunity to SARS-CoV-2 infection needs to be delineated.
Probing DNA-protein interactions using single-molecule diffusivity contrast
Authors: Wilson Hugh , Lee Miles , Wang Quan
Published: May 2021

Single-molecule fluorescence investigations of protein-nucleic acid interactions require robust means to identify the binding state of individual substrate molecules in real time. Here we show that diffusivity contrast, widely used in fluorescence correlation spectroscopy at the ensemble level and in single-particle tracking on individual (but slowly diffusing) species, can be used as a general readout to determine the binding state of single DNA molecules with unlabeled proteins in solution. We first describe the technical basis of drift-free single-molecule diffusivity measurements in an Anti-Brownian ELetrokinetic (ABEL) trap. We then cross-validate our method with protein-induced fluorescence enhancement (PIFE), a popular technique to detect protein binding on nucleic acid substrates with single-molecule sensitivity. We extend an existing hydrodynamic modeling framework to link measured diffusivity to particular DNA-protein structures and obtain good agreement between the measured and predicted diffusivity values. Finally, we show that combining diffusivity contrast with PIFE allows simultaneous mapping of binding stoichiometry and location on individual DNA-protein complexes, potentially enhancing single-molecule views of relevant biophysical processes.
Subcellular micropatterning for visual immunoprecipitation reveals differences in cytosolic protein complexes downstream the EGFR
Authors: Hager Roland , Müller Ulrike , Ollinger Nicole , Weghuber Julian , Lanzerstorfer Peter
Published: May 2021

Analysis of protein-protein interactions in living cells by protein micropatterning is currently limited to the spatial arrangement of transmembrane proteins and their corresponding downstream molecules. Here we present a robust method for visual immunoprecipitation of cytosolic protein complexes by use of an artificial transmembrane bait construct in combination with micropatterned antibody arrays on cyclic olefin polymer (COP) substrates. The method was used to characterize Grb2-mediated signalling pathways downstream the epidermal growth factor receptor (EGFR). Ternary protein complexes (Shc1:Grb2:SOS1 and Grb2:Gab1:PI3K) were identified and we found that EGFR downstream signalling is based on constitutively bound (Grb2:SOS1 and Grb2:Gab1) as well as on agonist-dependent protein associations with transient interaction properties (Grb2:Shc1 and Grb2:PI3K). Spatiotemporal analysis further revealed significant differences in stability and exchange kinetics of protein interactions. Furthermore, we could show that this approach is well suited to study the efficacy and specificity of SH2 and SH3 protein domain inhibitors in a live cell context. Altogether, this method represents a significant enhancement of quantitative subcellular micropatterning approaches as an alternative to standard biochemical analyses.
Purification of functional Plasmodium falciparum tubulin allows for the identification of parasite-specific microtubule inhibitors
Authors: Hirst William Graham , Fachet Dominik , Kuropka Benno , Weise Christoph , Saliba Kevin , Reber Simone
Published: May 2021

Cytoskeletal proteins are essential for parasite proliferation, growth, and transmission, and therefore represent promising drug targets. While αβ-tubulin, the molecular building block of microtubules, is an established drug target in a variety of cancers, we still lack substantial knowledge of the biochemistry of parasite tubulins, which would allow us to exploit the structural divergence between parasite and human tubulins. Indeed, mechanistic insights have been limited by the lack of purified, functional parasite tubulin. In this study, we isolated Plasmodium falciparum tubulin that is assembly-competent and shows specific microtubule dynamics in vitro. We further present mechanistic evidence that two compounds selectively interact with parasite over host microtubules and inhibit Plasmodium microtubule polymerization at substoichiometric compound concentrations. The ability of compounds to selectively disrupt protozoan microtubule growth without affecting human microtubules provides the exciting possibility for the targeted development of novel antimalarials.